The efficacy of concurrent cisplatin and 5-flurouracil chemotherapy and radiation therapy for locally advanced cancer of the uterine cervix

PubMed Central

Choi, Il Jung; Park, Eunku Seul; Han, Myung Seok; Choi, Youngmin; Je, Goo Hwa; Kim, Hyun Ho

2008-01-01

Objective To evaluate the efficacy of concurrent chemoradiation (CCRT) using 5-flurouracil (5-FU) and cisplatin for locally advanced cervical cancer. Methods We reviewed the medical records of 57 patients with locally advanced cervical cancer (stage IIB-IVA and bulky IB2-IIA tumor) who underwent the CCRT at Dong-A University Hospital from January 1997 to June 2007. The CCRT consisted of 5-FU, cisplatin and pelvic radiation. Every three weeks, 75 mg/m2 cisplatin was administered on the first day of each cycle and 5-FU was infused at the dose of 1,000 mg/m2/d from the second day to the fifth day of each cycle. Radiation was administered to the pelvis at a daily dose of 1.8 Gy for five days per week until a medium accumulated dose reached to 50.4 Gy. If necessary, the radiation field was extended to include paraaortic lymph nodes. Consolidation chemotherapy was performed using 5-FU and cisplatin. Results Fifty-seven patients were enrolled and the median follow-up duration was 53 months (range 7-120 months). The overall response rate was 91.5% (74% complete response and 17.5% partial response). The 5-year overall survival and 3-year progression free survival rates were 69.4% and 74.9%, respectively. During the follow-up period (median 23 months, range 7-60 months), fourteen patients were diagnosed as recurrent disease. Conclusion CCRT with 5-FU and cisplatin which is the primary treatment for patients with locally advanced cervical cancer was effective and well tolerated. PMID:19471554

Retrospective Analysis of Outcome Differences in Preoperative Concurrent Chemoradiation With or Without Elective Nodal Irradiation for Esophageal Squamous Cell Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hsu, Feng-Ming; Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan; Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan

2011-11-15

Purpose: To evaluate the efficacy and patterns of failure of elective nodal irradiation (ENI) in patients with esophageal squamous cell carcinoma (SCC) undergoing preoperative concurrent chemoradiation (CCRT) followed by radical surgery. Methods and Materials: We retrospectively studied 118 patients with AJCC Stage II to III esophageal SCC undergoing preoperative CCRT (median, 36 Gy), followed by radical esophagectomy. Of them, 73 patients (62%) had ENI and 45 patients (38%) had no ENI. Patients with ENI received radiotherapy to either supraclavicular (n = 54) or celiac (n = 19) lymphatics. Fifty-six patients (57%) received chemotherapy with paclitaxel plus cisplatin. The 3-year progression-freemore » survival, overall survival, and patterns of failure were analyzed. Distant nodal recurrence was classified into M1a and M1b regions. A separate analysis using matched cases was conducted. Results: The median follow-up was 38 months. There were no differences in pathological complete response rate (p = 0.12), perioperative mortality rate (p = 0.48), or delayed Grade 3 or greater cardiopulmonary toxicities (p = 0.44), between the groups. More patients in the non-ENI group had M1a failure than in the ENI group, with 3-year rates of 11% and 3%, respectively (p = 0.05). However, the 3-year isolated distant nodal (M1a + M1b) failure rates were not different (ENI, 10%; non-ENI, 14%; p = 0.29). In multivariate analysis, pathological nodal status was the only independent prognostic factor associated with overall survival (hazard ratio = 1.78, p = 0.045). The 3-year overall survival and progression-free survival were 45% and 45%, respectively, in the ENI group, and 52% and 43%, respectively, in the non-ENI group (p = 0.31 and 0.89, respectively). Matched cases analysis did not show a statistical difference in outcomes between the groups. Conclusions: ENI reduced the M1a failure rate but was not associated with improved outcomes in patients undergoing preoperative CCRT for esophageal SCC. Pathological nodal metastasis predicted poor outcome.« less

Retrospective analysis of outcome differences in preoperative concurrent chemoradiation with or without elective nodal irradiation for esophageal squamous cell carcinoma.

PubMed

Hsu, Feng-Ming; Lee, Jang-Ming; Huang, Pei-Ming; Lin, Chia-Chi; Hsu, Chih-Hung; Tsai, Yu-Chieh; Lee, Yung-Chie; Chia-Hsien Cheng, Jason

2011-11-15

To evaluate the efficacy and patterns of failure of elective nodal irradiation (ENI) in patients with esophageal squamous cell carcinoma (SCC) undergoing preoperative concurrent chemoradiation (CCRT) followed by radical surgery. We retrospectively studied 118 patients with AJCC Stage II to III esophageal SCC undergoing preoperative CCRT (median, 36 Gy), followed by radical esophagectomy. Of them, 73 patients (62%) had ENI and 45 patients (38%) had no ENI. Patients with ENI received radiotherapy to either supraclavicular (n = 54) or celiac (n = 19) lymphatics. Fifty-six patients (57%) received chemotherapy with paclitaxel plus cisplatin. The 3-year progression-free survival, overall survival, and patterns of failure were analyzed. Distant nodal recurrence was classified into M1a and M1b regions. A separate analysis using matched cases was conducted. The median follow-up was 38 months. There were no differences in pathological complete response rate (p = 0.12), perioperative mortality rate (p = 0.48), or delayed Grade 3 or greater cardiopulmonary toxicities (p = 0.44), between the groups. More patients in the non-ENI group had M1a failure than in the ENI group, with 3-year rates of 11% and 3%, respectively (p = 0.05). However, the 3-year isolated distant nodal (M1a + M1b) failure rates were not different (ENI, 10%; non-ENI, 14%; p = 0.29). In multivariate analysis, pathological nodal status was the only independent prognostic factor associated with overall survival (hazard ratio = 1.78, p = 0.045). The 3-year overall survival and progression-free survival were 45% and 45%, respectively, in the ENI group, and 52% and 43%, respectively, in the non-ENI group (p = 0.31 and 0.89, respectively). Matched cases analysis did not show a statistical difference in outcomes between the groups. ENI reduced the M1a failure rate but was not associated with improved outcomes in patients undergoing preoperative CCRT for esophageal SCC. Pathological nodal metastasis predicted poor outcome. Copyright © 2011 Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oh, Dongryul; Ahn, Yong Chan, E-mail: ycahn.ahn@samsung.com; Kim, Seok Jin

Purpose: To evaluate the effectiveness of concurrent chemoradiation therapy (CCRT) with 40 Gy followed by consolidation chemotherapy for localized extranodal natural killer (NK)/T-cell lymphoma (ENKTL), nasal type. Methods and Materials: From August 2004 to August 2012, 62 patients with newly diagnosed stage IE to IIE ENKTL underwent CCRT followed by consolidation chemotherapy. The median RT dose was 40 Gy. Cisplatin, 30 mg/m{sup 2}, was administered weekly during the RT course. Responders to CCRT were encouraged to undergo consolidation chemotherapy. Three different consolidation chemotherapy regimens were used consecutively: VIPD (etoposide, ifosfamide, cisplatin, and dexamethasone); VIDL (etoposide, ifosfamide, and dexamethasone followed by intramuscular injection ofmore » L-asparaginase); and MIDLE (methotrexate, etoposide, ifosfamide, mesna, and L-asparaginase). Results: The median follow-up period was 49 months (range 8-112). After completion of CCRT, 56 patients (90.3%) had a complete response, 4 (6.4%) had a partial response, 1 (1.6%) had stable disease, and 1 patient (1.6%) had progressive disease (PD). Consolidation chemotherapy was recommended to 61 patients, after excluding the patient with PD, but was actually delivered to 58. Of these 58 patients, 56 (96.5%) had a complete response and 2 (3.5%) had PD. During the follow-up period, 17 patients (including 3 with PD) experienced progression. The median interval to progression was 11 months (range 1-61). Local failure developed in 6 patients, of whom, 2 had developed progression outside the RT field. For all patients, the 3-year overall survival, progression-free survival, and local control rates were 83.1%, 77.1%, and 92.4%, respectively. Grade ≥3 nonhematologic toxicity developed in only 3 patients (4.8%). Conclusions: Excellent clinical outcomes were achieved using CCRT with 40 Gy followed by consolidation chemotherapy. Additional investigation, however, is warranted to confirm our findings.« less

Treatment outcomes regarding the addition of targeted agents in the therapeutic portfolio for stage II-III rectal cancer undergoing neoadjuvant chemoradiation.

PubMed

Liang, Jin-Tung; Chen, Tzu-Chun; Huang, John; Jeng, Yung-Ming; Cheng, Jason Chia-Hsien

2017-11-24

To evaluate the impact of targeted agents in stage II-III rectal cancer undergoing neoadjuvant concurrent chemoradiation therapy (CCRT). A retrospective study was performed in 124 consecutive patients with clinically T 3 N 0-2 M 0 -staged rectal cancer incorporating targeted agents in CCRT. Pathologic complete response was detected in 34.2% (n=26) of bevacizumab+FOLFOX-treated patients (n=76), which was significantly higher (p=0.019, post-hoc statistical power =35.87%) than that (n=10, 20.8%) of the cetuximab+FOLFOX-treated patients (n=48). Patients receiving cetuximab+FOLFOX therapy tended to develop severe liver toxicity (91.7%, n=44 versus 17.1%, n=13, p<0.0001), as evaluated by morphologic grading of hepatic steatosis and sinusoidal dilatation in laparoscopy. In the 57 patients with morphologically severe liver toxicity, 36 (63.2%) retained a normal liver function; for the remaining 21 patients with an abnormal liver function, the abnormality was self-limited in 19 patients, whereas 2 cetuximab-treated patients progressed to hepatic failure and mortality. A subset analysis within bevacizumab+FOLFOX-treated patients with either wild-type (n=36) or mutant (n=40) K-ras status indicated K-ras status did not significantly influence the treatment outcomes. The addition of bevacizumab instead of cetuximab to FOLFOX in the neoadjuvant settings for T 3 N 0-2 M 0 -staged rectal cancer could induce a promising rate of pathologic complete response and lesser hepatotoxicity.

Three-dimensional conformal radiotherapy with concurrent chemotherapy for postoperative recurrence of esophageal squamous cell carcinoma: clinical efficacy and failure pattern

PubMed Central

2013-01-01

Background To assess the therapeutic outcome and failure pattern of three-dimensional conformal radiotherapy (3D-CRT)-based concurrent chemoradiotherapy (CCRT) for recurrence of esophageal squamous cell carcinoma (SCC) after radical surgery. Methods Treatment outcome and failure pattern were retrospectively evaluated in 83 patients with localized cervical and thoracic recurrences after radical surgery for thoracic esophageal SCC. All patients were treated with 3DCRT-based CCRT (median radiation dose 60 Gy), in which 39 received concurrent cisplatin plus 5-fluorouracil (PF), and 44 received concurrent docetaxel plus cisplatin (TP). Treatment response was evaluated at 1–3 months after CCRT. Results With a median follow-up of 34 months (range, 2–116 months), the 3-year overall survival (OS) of all the patients was 51.8% and the median OS time was 43.0 months. The overall tumor response rate was 75.9% (63/83), with a complete remission (CR) rate of 44.6% (37/83). In univariate analysis, tumor response after CCRT (p = 0.000), recurrence site (p = 0.028) and concurrent chemotherapy (p = 0.090) showed a trend favoring better OS. Multivariate analysis revealed that tumor response after CCRT (p = 0.000) and concurrent chemotherapy (p = 0.010) were independent predictors of OS. Forty-seven patients had progressive diseases after CCRT, 27 had local failure (27/47, 57.4%), 18 had distant metastasis (18/47, 38.3%) and 2 had both local and distant failures (2/47, 4.3%). Conclusions 3DCRT-based CCRT is effective in postoperatively recurrent esophageal SCC. Patients that obtained complete remission after CCRT appeared to achieve long-term OS and might benefit from concurrent TP regimen. Local and distant failures remained high and prospective studies are needed to validate these factors. PMID:24139225

Three-dimensional conformal radiotherapy with concurrent chemotherapy for postoperative recurrence of esophageal squamous cell carcinoma: clinical efficacy and failure pattern.

PubMed

Bao, Yong; Liu, ShiLiang; Zhou, QiChao; Cai, PeiQiang; Anfossi, Simone; Li, QiaoQiao; Hu, YongHong; Liu, MengZhong; Fu, JianHua; Rong, TieHua; Li, Qun; Liu, Hui

2013-10-18

To assess the therapeutic outcome and failure pattern of three-dimensional conformal radiotherapy (3D-CRT)-based concurrent chemoradiotherapy (CCRT) for recurrence of esophageal squamous cell carcinoma (SCC) after radical surgery. Treatment outcome and failure pattern were retrospectively evaluated in 83 patients with localized cervical and thoracic recurrences after radical surgery for thoracic esophageal SCC. All patients were treated with 3DCRT-based CCRT (median radiation dose 60 Gy), in which 39 received concurrent cisplatin plus 5-fluorouracil (PF), and 44 received concurrent docetaxel plus cisplatin (TP). Treatment response was evaluated at 1-3 months after CCRT. With a median follow-up of 34 months (range, 2-116 months), the 3-year overall survival (OS) of all the patients was 51.8% and the median OS time was 43.0 months. The overall tumor response rate was 75.9% (63/83), with a complete remission (CR) rate of 44.6% (37/83). In univariate analysis, tumor response after CCRT (p = 0.000), recurrence site (p = 0.028) and concurrent chemotherapy (p = 0.090) showed a trend favoring better OS. Multivariate analysis revealed that tumor response after CCRT (p = 0.000) and concurrent chemotherapy (p = 0.010) were independent predictors of OS. Forty-seven patients had progressive diseases after CCRT, 27 had local failure (27/47, 57.4%), 18 had distant metastasis (18/47, 38.3%) and 2 had both local and distant failures (2/47, 4.3%). 3DCRT-based CCRT is effective in postoperatively recurrent esophageal SCC. Patients that obtained complete remission after CCRT appeared to achieve long-term OS and might benefit from concurrent TP regimen. Local and distant failures remained high and prospective studies are needed to validate these factors.

Concurrent chemoradiotherapy degrades the quality of life of patients with stage II nasopharyngeal carcinoma as compared to radiotherapy

PubMed Central

Pan, Xin-Bin; Huang, Shi-Ting; Chen, Kai-Hua; Jiang, Yan-Ming; Ma, Jia-Lin; Qu, Song; Li, Ling; Chen, Long; Zhu, Xiao-Dong

2017-01-01

The purpose of this study was to compare the quality of life (QoL) of stage II nasopharyngeal carcinoma (NPC) patients treated with radiotherapy (RT) versus concurrent chemoradiotherapy (CCRT). In a cross-sectional study, these patients were treated with RT (n = 55) or CCRT (n = 51) between June 2008 and June 2013. For all subjects, disease-free survival was more than 3 years. QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) questions and the Head and Neck 35 (EORTC QLQ-H&N35) questions. RT had better outcomes than CCRT for global QoL, functional scales, symptom scales of fatigue and insomnia, financial problems, and weight gain. Survivors receiving 1 cycle of concurrent chemotherapy had worse QoL outcomes than survivors receiving 2 cycles of concurrent chemotherapy. Patients receiving 3 cycles of concurrent chemotherapy had the best QoL outcomes. Thus, CCRT adversely affects the QoL of patients with stage II NPC as compared to radiotherapy. PMID:28152511

Beneficial effects of anti-EGFR agents, Cetuximab or Nimotuzumab, in combination with concurrent chemoradiotherapy in advanced nasopharyngeal carcinoma.

PubMed

Lin, Mei; You, Rui; Liu, You-Ping; Zhang, Yi-Nuan; Zhang, Hao-Jiong; Zou, Xiong; Yang, Qi; Li, Chao-Feng; Hua, Yi-Jun; Yu, Tao; Cao, Jing-Yu; Li, Ji-Bin; Mo, Hao-Yuan; Guo, Ling; Lin, Ai-Hua; Sun, Ying; Qian, Chao-Nan; Ma, Jun; Mai, Hai-Qiang; Chen, Ming-Yuan

2018-05-01

This study aimed to evaluate the efficacy and safety in locoregionally advanced nasopharyngeal carcinoma (NPC) patients receiving concurrent chemoradiotherapy (CCRT) plus Cetuximab (CTX) or Nimotuzumab (NTZ) compared to those receiving induction chemotherapy (IC) plus CCRT. From January 2008 to December 2013, 715 eligible patients were enrolled in the study. Using propensity scores to adjust for gender, age, Karnofsky performance status (KPS), tumor stage, node stage, and clinical stage, a well-balanced cohort was created by matching each patient who received CTX/NTZ plus CCRT (137 patients) with two patients who underwent IC plus CCRT (274 patients). The primary endpoint was overall survival (OS), and other outcome variables included disease-free survival (DFS), distant metastasis-free survival (DMFS) and loco-regional relapse-free survival (LRRFS). The median follow-up was 57.0 months and 55.0 months for the CTX/NTZ plus CCRT group and IC plus CCRT group, respectively. No significant differences were found between the CTX/NTZ plus CCRT group and the IC plus CCRT group in 3-year OS (95.5% vs. 94.7%, P = 0.083), 3-year DFS (93.3% vs. 86.1%, P = 0.104), 3-year DMFS (96.2% vs. 92.5%, P = 0.243) and 3-year LRRFS (97.0% vs. 95.1%, P = 0.297). Patients undergoing IC plus CCRT suffered from severe hematologic toxicity and diarrhea compared with those treated with CTX/NTZ plus CCRT. The combination of CTX/NTZ with CCRT is comparable to IC plus CCRT treatment in survival outcomes for locoregionally advanced NPC patients but has a better safety profile than IC plus CCRT treatment. Copyright © 2018 Elsevier Ltd. All rights reserved.

Histogram analysis of apparent diffusion coefficient for monitoring early response in patients with advanced cervical cancers undergoing concurrent chemo-radiotherapy.

PubMed

Meng, Jie; Zhu, Lijing; Zhu, Li; Ge, Yun; He, Jian; Zhou, Zhengyang; Yang, Xiaofeng

2017-11-01

Background Apparent diffusion coefficient (ADC) histogram analysis has been widely used in determining tumor prognosis. Purpose To investigate the dynamic changes of ADC histogram parameters during concurrent chemo-radiotherapy (CCRT) in patients with advanced cervical cancers. Material and Methods This prospective study enrolled 32 patients with advanced cervical cancers undergoing CCRT who received diffusion-weighted (DW) magnetic resonance imaging (MRI) before CCRT, at the end of the second and fourth week during CCRT and one month after CCRT completion. The ADC histogram for the entire tumor volume was generated, and a series of histogram parameters was obtained. Dynamic changes of those parameters in cervical cancers were investigated as early biomarkers for treatment response. Results All histogram parameters except AUC low showed significant changes during CCRT (all P < 0.05). There were three variable trends involving different parameters. The mode, 5th, 10th, and 25th percentiles showed similar early increase rates (33.33%, 33.99%, 34.12%, and 30.49%, respectively) at the end of the second week of CCRT. The pre-CCRT 5th and 25th percentiles of the complete response (CR) group were significantly lower than those of the partial response (PR) group. Conclusion A series of ADC histogram parameters of cervical cancers changed significantly at the early stage of CCRT, indicating their potential in monitoring early tumor response to therapy.

Apparent diffusion coefficient histogram shape analysis for monitoring early response in patients with advanced cervical cancers undergoing concurrent chemo-radiotherapy.

PubMed

Meng, Jie; Zhu, Lijing; Zhu, Li; Wang, Huanhuan; Liu, Song; Yan, Jing; Liu, Baorui; Guan, Yue; Ge, Yun; He, Jian; Zhou, Zhengyang; Yang, Xiaofeng

2016-10-22

To explore the role of apparent diffusion coefficient (ADC) histogram shape related parameters in early assessment of treatment response during the concurrent chemo-radiotherapy (CCRT) course of advanced cervical cancers. This prospective study was approved by the local ethics committee and informed consent was obtained from all patients. Thirty-two patients with advanced cervical squamous cell carcinomas underwent diffusion weighted magnetic resonance imaging (b values, 0 and 800 s/mm 2 ) before CCRT, at the end of 2nd and 4th week during CCRT and immediately after CCRT completion. Whole lesion ADC histogram analysis generated several histogram shape related parameters including skewness, kurtosis, s-sD av , width, standard deviation, as well as first-order entropy and second-order entropies. The averaged ADC histograms of 32 patients were generated to visually observe dynamic changes of the histogram shape following CCRT. All parameters except width and standard deviation showed significant changes during CCRT (all P < 0.05), and their variation trends fell into four different patterns. Skewness and kurtosis both showed high early decline rate (43.10 %, 48.29 %) at the end of 2nd week of CCRT. All entropies kept decreasing significantly since 2 weeks after CCRT initiated. The shape of averaged ADC histogram also changed obviously following CCRT. ADC histogram shape analysis held the potential in monitoring early tumor response in patients with advanced cervical cancers undergoing CCRT.

Predicting Esophagitis After Chemoradiation Therapy for Non-Small Cell Lung Cancer: An Individual Patient Data Meta-Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Palma, David A., E-mail: david.palma@uwo.ca; Senan, Suresh; Oberije, Cary

Purpose: Concurrent chemoradiation therapy (CCRT) improves survival compared with sequential treatment for locally advanced non-small cell lung cancer, but it increases toxicity, particularly radiation esophagitis (RE). Validated predictors of RE for clinical use are lacking. We performed an individual-patient-data meta-analysis to determine factors predictive of clinically significant RE. Methods and Materials: After a systematic review of the literature, data were obtained on 1082 patients who underwent CCRT, including patients from Europe, North America, Asia, and Australia. Patients were randomly divided into training and validation sets (2/3 vs 1/3 of patients). Factors predictive of RE (grade ≥2 and grade ≥3) weremore » assessed using logistic modeling, with the concordance statistic (c statistic) used to evaluate the performance of each model. Results: The median radiation therapy dose delivered was 65 Gy, and the median follow-up time was 2.1 years. Most patients (91%) received platinum-containing CCRT regimens. The development of RE was common, scored as grade 2 in 348 patients (32.2%), grade 3 in 185 (17.1%), and grade 4 in 10 (0.9%). There were no RE-related deaths. On univariable analysis using the training set, several baseline factors were statistically predictive of RE (P<.05), but only dosimetric factors had good discrimination scores (c > .60). On multivariable analysis, the esophageal volume receiving ≥60 Gy (V60) alone emerged as the best predictor of grade ≥2 and grade ≥3 RE, with good calibration and discrimination. Recursive partitioning identified 3 risk groups: low (V60 <0.07%), intermediate (V60 0.07% to 16.99%), and high (V60 ≥17%). With use of the validation set, the predictive model performed inferiorly for the grade ≥2 endpoint (c = .58) but performed well for the grade ≥3 endpoint (c = .66). Conclusions: Clinically significant RE is common, but life-threatening complications occur in <1% of patients. Although several factors are statistically predictive of RE, the V60 alone provides the best predictive ability. Efforts to reduce the V60 should be prioritized, with further research needed to identify and validate new predictive factors.« less

Correlation between location of transposed ovary and function in cervical cancer patients who underwent radical hysterectomy.

PubMed

Yoon, Aera; Lee, Yoo-Young; Park, Won; Huh, Seung Jae; Choi, Chel Hun; Kim, Tae-Joong; Lee, Jeong-Won; Kim, Byoung-Gie; Bae, Duk-Soo

2015-05-01

The study investigated the association between the location of transposed ovaries and posttreatment ovarian function in patients with early cervical cancer (IB1-IIA) who underwent radical hysterectomy and ovarian transposition with or without adjuvant therapies. Retrospective medical records were reviewed to enroll the patients with early cervical cancer who underwent ovarian transposition during radical hysterectomy at Samsung Medical Center between July 1995 and July 2012. Serum follicle-stimulating hormone (FSH) level was used as a surrogate marker for ovarian function. Twenty-one patients were enrolled. The median age and body mass index (BMI) were 31 years (range, 24-39 years) and 21.3 kg/m² (range, 17.7-31.2 kg/m²), respectively. The median serum FSH level after treatment was 7.9 mIU/mL (range, 2.4-143.4 mIU/mL). The median distance from the iliac crest to transposed ovaries on erect plain abdominal x-ray was 0.5 cm (range, -2.7 to 5.2 cm). In multivariate analysis, posttreatment serum FSH levels were significantly associated with the location of transposed ovaries (β = -8.1, P = 0.032), concurrent chemoradiation (CCRT) as an adjuvant therapy (β = 71.08, P = 0.006), and BMI before treatment (underweight: β = -59.93, P = 0.05; overweight: β = -40.62, P = 0.041). Location of transposed ovaries, adjuvant CCRT, and BMI before treatment may be associated with ovarian function after treatment. We suggest that ovaries should be transposed as highly as possible during radical hysterectomy to preserve ovarian function in young patients with early cervical cancer who might be a candidate for adjuvant CCRT and who have low BMI before treatment.

Effectiveness of Cetuximab in Combination with Concurrent Chemoradiotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma: A 1:2 Propensity Score-matched Analysis.

PubMed

Wu, Li-Rong; Zhu, Huan-Feng; Xu, Jianhua; Jiang, Xue-Song; Yin, Li; Jiang, Ning; Zong, Dan; Wang, Fei-Jiang; Huang, Sheng-Fu; Bian, Xiu-Hua; Wu, Jian-Feng; Song, Dan; Guo, Wen-Jie; Liu, Ju-Ying; He, Xia

2018-01-01

Background : This study aimed to compare concurrent chemoradiotherapy (CCRT) plus cetuximab (C) with CCRT alone in locoregionally advanced nasopharyngeal carcinoma(NPC). Methods : A total of 682 locoregionally advanced NPC patients who had undergone chemoradiotherapy with or without cetuximab were included. Propensity score-matching method was used to match patients. Progression-free survival (PFS), overall survival (OS), locoregional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) were compared between the two treatment arms. Results : After matching, 225 patients were identified for the analysis. Compared to CCRT, CCRT plus C was associated with significantly improved 3-year PFS (83.7% vs 71.9%, P = 0.036), LRFS (98.6% vs 90.2%, P = 0.034) but not OS (91.4% vs 85.4%, P = 0.117). Among patients with T4 and/or N3 category, CCRT plus C significantly prolonged 3-year PFS (81.0% vs 61.4%, P = 0.022) and increased 3-year OS (88.0% vs 77.9%, P = 0.086). No significant differences were observed between CCRT plus C and CCRT alone groups with regard to 3-year PFS, OS, LRFS and DMFS rates in stage III patients. Acute oral and oropharyngeal mucositis during radiotherapy were more common in the CCRT plus C than that in CCRT, but late toxicities were comparable. Conclusions: This study reveals that patients with locoregionally advanced NPC could benefit from the addition of cetuximab to CCRT, and this therapeutic gain mainly originated from T4 and/or N3 subgroup although suffering more acute moderate to severe toxicities.

Should helical tomotherapy replace brachytherapy for cervical cancer? Case report.

PubMed

Hsieh, Chen-Hsi; Wei, Ming-Chow; Hsu, Yao-Peng; Chong, Ngot-Swan; Chen, Yu-Jen; Hsiao, Sheng-Mou; Hsieh, Yen-Ping; Wang, Li-Ying; Shueng, Pei-Wei

2010-11-23

Stereotactic body radiation therapy (SBRT) administered via a helical tomotherapy (HT) system is an effective modality for treating lung cancer and metastatic liver tumors. Whether SBRT delivered via HT is a feasible alternative to brachytherapy in treatment of locally advanced cervical cancer in patients with unusual anatomic configurations of the uterus has never been studied. A 46-year-old woman presented with an 8-month history of abnormal vaginal bleeding. Biopsy revealed squamous cell carcinoma of the cervix. Magnetic resonance imaging (MRI) showed a cervical tumor with direct invasion of the right parametrium, bilateral hydronephrosis, and multiple uterine myomas. International Federation of Gynecology and Obstetrics (FIGO) stage IIIB cervical cancer was diagnosed. Concurrent chemoradiation therapy (CCRT) followed by SBRT delivered via HT was administered instead of brachytherapy because of the presence of multiple uterine myomas with bleeding tendency. Total abdominal hysterectomy was performed after 6 weeks of treatment because of the presence of multiple uterine myomas. Neither pelvic MRI nor results of histopathologic examination at X-month follow-up showed evidence of tumor recurrence. Only grade 1 nausea and vomiting during treatment were noted. Lower gastrointestinal bleeding was noted at 14-month follow-up. No fistula formation and no evidence of haematological, gastrointestinal or genitourinary toxicities were noted on the most recent follow-up. CCRT followed by SBRT appears to be an effective and safe modality for treatment of cervical cancer. Larger-scale studies are warranted.

Acute Cardiac Impairment Associated With Concurrent Chemoradiotherapy for Esophageal Cancer: Magnetic Resonance Evaluation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hatakenaka, Masamitsu, E-mail: mhatakenaka@sapmed.ac.jp; Department of Diagnostic Radiology, School of Medicine, Sapporo Medical University, Sapporo; Yonezawa, Masato

2012-05-01

Purpose: To evaluate acute cardiac effects of concurrent chemoradiotherapy (CCRT) for esophageal cancer. Methods and Materials: This prospective study was approved by the institutional review board, and written informed consent was obtained from all participants. The left ventricular function (LVF) of 31 patients with esophageal cancer who received cisplatin and 5-fluorouracil-based CCRT was evaluated using cardiac cine magnetic resonance imaging. The patients were classified into two groups according to mean LV dose. The parameters related to LVF were compared between before and during (40 Gy) or between before and after CCRT using a Wilcoxon matched-pairs single rank test, and parametermore » ratios (during/before CCRT, after/before CCRT) were also compared between the groups with a t test. Data were expressed as mean {+-} SE. Results: In the low LV-dose group (n = 10; mean LV dose <0.6 Gy), LV ejection fraction decreased significantly (before vs. during vs. after CCRT; 62.7% {+-} 2.98% vs. 59.8% {+-} 2.56% vs. 60.6% {+-} 3.89%; p < 0.05). In the high LV-dose group (n = 21; mean LV dose of 3.6-41.2 Gy), LV end-diastolic volume index (before vs. after CCRT; 69.1 {+-} 2.93 vs. 57.0 {+-} 3.23 mL/m{sup 2}), LV stroke volume index (38.6 {+-} 1.56 vs. 29.9 {+-} 1.60 mL/m{sup 2}), and LV ejection fraction (56.9% {+-} 1.79% vs. 52.8% {+-} 1.15%) decreased significantly (p < 0.05) after CCRT. Heart rate increased significantly (before vs. during vs. after CCRT; 66.8 {+-} 3.05 vs. 72.4 {+-} 4.04 vs. 85.4 {+-} 3.75 beats per minute, p < 0.01). Left ventricle wall motion decreased significantly (p < 0.05) in segments 8 (before vs. during vs. after CCRT; 6.64 {+-} 0.54 vs. 4.78 {+-} 0.43 vs. 4.79 {+-} 0.50 mm), 9 (6.88 {+-} 0.45 vs. 5.04 {+-} 0.38 vs. 5.27 {+-} 0.47 mm), and 10 (9.22 {+-} 0.48 vs. 8.08 {+-} 0.34 vs. 8.19 {+-} 0.56 mm). The parameter ratios of LV end-diastolic volume index, stroke volume index, wall motion in segment 9, and heart rate showed significant difference (p < 0.05) after CCRT between the groups. Conclusions: Concurrent chemoradiotherapy for esophageal cancer impairs LVF from an early treatment stage. This impairment is prominent in patients with high LV dose.« less

The management of patients with esophageal cancer and coronary artery stenosis undergoing radiotherapy or concurrent chemoradiotherapy: a single-center experience.

PubMed

Luo, Hui; Chen, Xiaojian; Zhang, Qiugui; Wang, Lanhua; Qiao, Lili; Liang, Ning; Xie, Jian; Yu, Xinshuang; Song, Meijuan; Liu, Zhen; Lv, Yajuan; Liu, Fengjun; Tian, Yuan; Cheng, Jian; Deng, Guodong; Zhang, Jingxin; Li, X Allen; Zhang, Jiandong

2016-01-01

The incidence of esophageal cancer (EC) patients with coronary artery stenosis presents particular challenges. The aim of this retrospective study was to evaluate the efficiency of management on patients with both diseases treated by radiotherapy (RT) or concurrent chemoradiotherapy (CCRT). Fifty-three patients with both EC and coronary artery stenosis from June 2009 to August 2012 were retrospectively analyzed. The patients received RT or CCRT with coronary artery stenosis management. Cardiac treatments often prescribed included aspirin, β-blockers, statins etc. The adverse effects, overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) were analyzed. Most of the patients were 40-70 years old. There were 25 patients in the CCRT group and 28 patients in the RT group. The complete response (CR) rate was higher in the patients in the CCRT group than in those in the RT group (48.0 vs 21.4%; p=0.041). The median PFS was 15.9 months in the CCRT group and 11.6 months in the RT group (p=0.025). OS was 22.4 months in the CCRT group and 15.8 months in the RT group (p=0.013). Though adverse effects were less in the RT group, no significance differences in grade 3-4 toxicity were observed. With the appropriate of coronary artery stenosis management, RT and CCRT were both tolerable and effective in EC patients with coronary artery stenosis.

Ultrasonic histogram assessment of early response to concurrent chemo-radiotherapy in patients with locally advanced cervical cancer: a feasibility study.

PubMed

Xu, Yan; Ru, Tong; Zhu, Lijing; Liu, Baorui; Wang, Huanhuan; Zhu, Li; He, Jian; Liu, Song; Zhou, Zhengyang; Yang, Xiaofeng

To monitor early response for locally advanced cervical cancers undergoing concurrent chemo-radiotherapy (CCRT) by ultrasonic histogram. B-mode ultrasound examinations were performed at 4 time points in thirty-four patients during CCRT. Six ultrasonic histogram parameters were used to assess the echogenicity, homogeneity and heterogeneity of tumors. I peak increased rapidly since the first week after therapy initiation, whereas W low , W high and A high changed significantly at the second week. The average ultrasonic histogram progressively moved toward the right and converted into more symmetrical shape. Ultrasonic histogram could be served as a potential marker to monitor early response during CCRT. Copyright © 2018 Elsevier Inc. All rights reserved.

Prospective Pilot Study of Consolidation Chemotherapy With Docetaxel and Cisplatin After Concurrent Chemoradiotherapy for Advanced Head and Neck Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Kyun Chan; Lee, Seok Ho; Lee, Yuna

Purpose: With the improvement concurrent chemoradiotherapy (CCRT) in the management of patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC), distant failures have become a more relevant problem in terms of survival. The primary objective of this Phase II study is to assess the feasibility of docetaxel and cisplatin consolidation after primary CCRT for patients with HNSCC. Methods and Materials: Patients with locoregionally advanced HNSCC received chemotherapy with three cycles of cisplatin, 100 mg/m{sup 2}, on Days 1, 22, and 43. Concurrent radiotherapy to the primary tumor and neck was given in a daily dose of 2 Gymore » to a total dose of 70-70.2 Gy over 7 weeks. After completion of CCRT, patients without evidence of disease progression received an additional four cycles of consolidation chemotherapy with docetaxel, 75 mg/m{sup 2}, and cisplatin, 75 mg/m{sup 2}, every 3 weeks. Results: Of 33 patients, 27 (81%) completed CCRT. After CCRT, three complete and 19 partial responses were recorded, giving an overall response rate of 67%. Of 19 patients who went to the consolidation phase, only 4 (21%) received all four cycles of docetaxel and cisplatin. Causes of failure of consolidation chemotherapy were toxicity in 11 patients, including three treatment-related deaths, and progression in 4 patients. Three patients died of sepsis during the consolidation phase. Median survival was 11 months for all patients and 8 months for those treated with consolidation chemotherapy. Conclusion: The poor compliance and high incidence of severe toxicities prompted no further evaluation of this consolidation chemotherapy after CCRT.« less

[Concurrent chemoradiation in lung cancer].

PubMed

Girard, Nicolas; Mornex, Françoise

2005-12-01

Concurrent chemoradiation has become for the 15 last years the standard treatment for locally advanced non-small cell lung cancer, either as a definite therapy in non resectable tumors, or in a neoadjuvant setting in potentially resectable tumors. Associating sequential and concurrent schedules, by administering chemotherapy before or after concurrent chemoradiation, has been recently investigated, but the best sequence remains a matter of controversy. Increasing local control and survival after definite chemoradiation seems possible not only by using optimized radiation fractionation schedules and escalated total doses, but also by associating more convenient and less toxic chemotherapy agents at the right cytotoxic or radio-sensitizing dose. Moreover, recent data have suggested that surgery following induction chemoradiation is feasible and effective in selected patients without mediastinal nodes involvement, if a complete resection can be performed. In patients with localized small cell lung cancer, early concurrent chemoradiation with platinium and etoposide has been recognized as the state-of-the-art treatment. The increasing number of ongoing trials including modern radiation schedules combined with newer chemotherapy agents shows that chemoradiation is one of the most promising therapeutic strategies in thoracic oncology.

Randomized phase III trial of concurrent chemoradiotherapy vs accelerated hyperfractionation radiotherapy in locally advanced head and neck cancer

PubMed Central

Chitapanarux, Imjai; Tharavichitkul, Ekkasit; Kamnerdsupaphon, Pimkhuan; Pukanhapan, Nantaka; Vongtama, Roy

2013-01-01

The aim of this study was to compare the efficacy and safety of concurrent chemoradiotherapy (CCRT) vs accelerated hyperfractionation with concomitant boost (CCB) as a primary treatment for patients with Stage III–IV squamous cell carcinoma of head and neck (SCCHN). A total of 85 non-metastatic advanced SCCHN patients were accrued from January 2003 to December 2007. Of these, 48 and 37 patients received CCRT and CCB, respectively. The patients were randomized to receive either three cycles of carboplatin and 5-fluorouracil plus conventional radiotherapy (CCRT, 66 Gy in 6.5 weeks) or hybrid accelerated radiotherapy (CCB, 70 Gy in 6 weeks). The primary endpoint was determined by locoregional control rate. The secondary endpoints were overall survival and toxicity. With a median follow-up of 43 months (range, 3–102), the 5-year locoregional control rate was 69.6% in the CCRT arm vs 55.0% in the CCB arm (P = 0.184). The 5-year overall survival rate was marginally significantly different (P = 0.05): 76.1% in the CCRT arm vs 63.5% in the CCB arm. Radiotherapy treatment interruptions of more than three days were 60.4% and 40.5% in the CCRT arm and CCB arm, respectively. The median total treatment time was 55.5 days in the CCRT arm and 49 days in the CCB arm. The rate of Grade 3–4 acute mucositis was significantly higher in the CCB arm (67.6% vs 41.7%, P = 0.01), but no high grade hematologic toxicities were found in the CCB arm (27.2% vs 0%). CCRT has shown a trend of improving outcome over CCB irradiation in locoregionally advanced head and neck cancer. PMID:23740894

Induction Chemotherapy plus Concurrent Chemoradiotherapy in Endemic Nasopharyngeal Carcinoma: Individual Patient Data Pooled Analysis of Four Randomized Trials.

PubMed

Chen, Yu-Pei; Tang, Ling-Long; Yang, Qi; Poh, Sharon-Shuxian; Hui, Edwin P; Chan, Anthony T C; Ong, Whee-Sze; Tan, Terence; Wee, Joseph; Li, Wen-Fei; Chen, Lei; Ma, Brigette B Y; Tong, Macy; Tan, Sze-Huey; Cheah, Shie-Lee; Fong, Kam-Weng; Sommat, Kiattisa; Soong, Yoke Lim; Guo, Ying; Lin, Ai-Hua; Sun, Ying; Hong, Ming-Huang; Cao, Su-Mei; Chen, Ming-Yuan; Ma, Jun

2018-04-15

Purpose: Because of the uneven geographic distribution and small number of randomized trials available, the value of additional induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma (NPC) remains controversial. This study performed an individual patient data (IPD) pooled analysis to better assess the precise role of IC + CCRT in locoregionally advanced NPC. Experimental Design: Four randomized trials in endemic areas were identified, representing 1,193 patients; updated IPD were obtained. Progression-free survival (PFS) and overall survival (OS) were the primary and secondary endpoints, respectively. Results: Median follow-up was 5.0 years. The HR for PFS was 0.70 [95% confidence interval (CI), 0.56-0.86; P = 0.0009; 9.3% absolute benefit at 5 years] in favor of IC + CCRT versus CCRT alone. IC + CCRT also improved OS (HR = 0.75; 95% CI, 0.57-0.99; P = 0.04) and reduced distant failure (HR = 0.68; 95% CI, 0.51-0.90; P = 0.008). IC + CCRT had a tendency to improve locoregional control compared with CCRT alone (HR = 0.70; 95% CI, 0.48-1.01; P = 0.06). There was no heterogeneity between trials in any analysis. No interactions between patient characteristics and treatment effects on PFS or OS were found. After adding two supplementary trials to provide a more comprehensive overview, the conclusions remained valid and were strengthened. In a supplementary Bayesian network analysis, no statistically significant differences in survival between different IC regimens were detected. Conclusions: This IPD pooled analysis demonstrates the superiority of additional IC over CCRT alone in locoregionally advanced NPC, with the survival benefit mainly associated with improved distant control. Clin Cancer Res; 24(8); 1824-33. ©2018 AACR . ©2018 American Association for Cancer Research.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Machtay, Mitchell, E-mail: mitchell.machtay@uhhospitals.org; Moughan, Jennifer; Farach, Andrew

Purpose: Concurrent chemoradiation therapy (CCRT) for squamous cell carcinoma of the head and neck (SCCHN) increases local tumor control but at the expense of increased toxicity. We recently showed that several clinical/pretreatment factors were associated with the occurrence of severe late toxicity. This study evaluated the potential relationship between radiation dose delivered to the pharyngeal wall and toxicity. Methods and Materials: This was an analysis of long-term survivors from 3 previously reported Radiation Therapy Oncology Group (RTOG) trials of CCRT for locally advanced SCCHN (RTOG trials 91-11, 97-03, and 99-14). Severe late toxicity was defined in this secondary analysis asmore » chronic grade 3-4 pharyngeal/laryngeal toxicity and/or requirement for a feeding tube {>=}2 years after registration and/or potential treatment-related death (eg, pneumonia) within 3 years. Radiation dosimetry (2-dimensional) analysis was performed centrally at RTOG headquarters to estimate doses to 4 regions of interest along the pharyngeal wall (superior oropharynx, inferior oropharynx, superior hypopharynx, and inferior hypopharynx). Case-control analysis was performed with a multivariate logistic regression model that included pretreatment and treatment potential factors. Results: A total of 154 patients were evaluable for this analysis, 71 cases (patients with severe late toxicities) and 83 controls; thus, 46% of evaluable patients had a severe late toxicity. On multivariate analysis, significant variables correlated with the development of severe late toxicity, including older age (odds ratio, 1.062 per year; P=.0021) and radiation dose received by the inferior hypopharynx (odds ratio, 1.023 per Gy; P=.016). The subgroup of patients receiving {<=}60 Gy to the inferior hypopharynx had a 40% rate of severe late toxicity compared with 56% for patients receiving >60 Gy. Oropharyngeal dose was not associated with this outcome. Conclusions: Severe late toxicity following CCRT is common in long-term survivors. Age is the most significant factor, but hypopharyngeal dose also was associated.« less

Trajectories of Symptom Clusters, Performance Status, and Quality of Life During Concurrent Chemoradiotherapy in Patients With High-Grade Brain Cancers.

PubMed

Kim, Sang-Hee; Byun, Youngsoon

Symptom clusters must be identified in patients with high-grade brain cancers for effective symptom management during cancer-related therapy. The aims of this study were to identify symptom clusters in patients with high-grade brain cancers and to determine the relationship of each cluster with the performance status and quality of life (QOL) during concurrent chemoradiotherapy (CCRT). Symptoms were assessed using the Memorial Symptom Assessment Scale, and the performance status was evaluated using the Karnofsky Performance Scale. Quality of life was assessed using the Functional Assessment of Cancer Therapy-General. This prospective longitudinal survey was conducted before CCRT and at 2 to 3 weeks and 4 to 6 weeks after the initiation of CCRT. A total of 51 patients with newly diagnosed primary malignant brain cancer were included. Six symptom clusters were identified, and 2 symptom clusters were present at each time point (ie, "negative emotion" and "neurocognitive" clusters before CCRT, "negative emotion and decreased vitality" and "gastrointestinal and decreased sensory" clusters at 2-3 weeks, and "body image and decreased vitality" and "gastrointestinal" clusters at 4-6 weeks). The symptom clusters at each time point demonstrated a significant relationship with the performance status or QOL. Differences were observed in symptom clusters in patients with high-grade brain cancers during CCRT. In addition, the symptom clusters were correlated with the performance status and QOL of patients, and these effects could change during CCRT. The results of this study will provide suggestions for interventions to treat or prevent symptom clusters in patients with high-grade brain cancer during CCRT.

Concurrent chemoradiotherapy versus radiotherapy alone for locoregionally advanced nasopharyngeal carcinoma in the era of intensity-modulated radiotherapy: a meta-analysis.

PubMed

He, Yan; Guo, Tao; Guan, Hui; Wang, Jingjing; Sun, Yu; Peng, Xingchen

2018-01-01

In this study, we attempted to compare the efficacy and toxicity of concurrent chemoradiotherapy (CCRT) with radiotherapy alone (RT) for locoregionally advanced nasopharyngeal carcinoma (LANPC) in the era of intensity-modulated radiotherapy (IMRT) by meta-analysis. We searched databases, and all randomized controlled trials meeting the inclusion criteria were utilized for a meta-analysis with RevMan 5.3 based on the Cochrane methodology. Fifteen studies were found suitable based on the inclusion criteria. CCRT not only significantly improved the overall response rate (risk ratio [RR]=0.53, 95% CI 0.43-0.66) and the complete response rate (RR=0.60, 95% CI 0.51-0.71) but also contributed to longer overall survival. The incidence of grade 3-4 adverse events from CCRT group increased in hematologic toxicity (RR 2.25, 95% CI 1.54-3.29), radiation-induced oral mucositis (RR 1.64, 95% CI 1.14-2.35), and radiodermatitis (RR 1.80, 95% CI 1.13-2.88). Compared with IMRT alone, CCRT provided survival benefit with acceptable toxicity in patients with LANPC. However, we need multicenter randomized controlled trials and long-term follow-up to evaluate the eventual efficacy and toxicity of concurrent chemotherapy plus IMRT.

Whole-lesion ADC histogram and texture analysis in predicting recurrence of cervical cancer treated with CCRT.

PubMed

Meng, Jie; Zhu, Lijing; Zhu, Li; Xie, Li; Wang, Huanhuan; Liu, Song; Yan, Jing; Liu, Baorui; Guan, Yue; He, Jian; Ge, Yun; Zhou, Zhengyang; Yang, Xiaofeng

2017-11-03

To explore the value of whole-lesion apparent diffusion coefficient (ADC) histogram and texture analysis in predicting tumor recurrence of advanced cervical cancer treated with concurrent chemo-radiotherapy (CCRT). 36 women with pathologically confirmed advanced cervical squamous carcinomas were enrolled in this prospective study. 3.0 T pelvic MR examinations including diffusion weighted imaging (b = 0, 800 s/mm 2 ) were performed before CCRT (pre-CCRT) and at the end of 2nd week of CCRT (mid-CCRT). ADC histogram and texture features were derived from the whole volume of cervical cancers. With a mean follow-up of 25 months (range, 11 ∼ 43), 10/36 (27.8%) patients ended with recurrence. Pre-CCRT 75th, 90th, correlation, autocorrelation and mid-CCRT ADC mean , 10th, 25th, 50th, 75th, 90th, autocorrelation can effectively differentiate the recurrence from nonrecurrence group with area under the curve ranging from 0.742 to 0.850 (P values range, 0.001 ∼ 0.038). Pre- and mid-treatment whole-lesion ADC histogram and texture analysis hold great potential in predicting tumor recurrence of advanced cervical cancer treated with CCRT.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gunderson, Leonard L., E-mail: gunderson.leonard@mayo.edu; Moughan, Jennifer; Ajani, Jaffer A.

Purpose: The long-term update of US GI Intergroup RTOG 98-11 anal cancer trial found that concurrent chemoradiation (CCRT) with fluorouracil (5-FU) plus mitomycin had a significant impact on disease-free survival (DFS) and overall survival (OS) compared with induction plus concurrent 5-FU plus cisplatin. The intent of the current analysis was to determine the impact of tumor node (TN) category of disease on survival (DFS and OS), colostomy failure (CF), and relapse (local-regional failure [LRF] and distant metastases [DM]) in this patient group. Methods and Materials: DFS and OS were estimated univariately by using the Kaplan-Meier method, and 6 TN categoriesmore » were compared by the log–rank test (T2N0, T3N0, T4N0, T2N1-3, T3N1-3, and T4N1-3). Time to relapse and colostomy were estimated by the cumulative incidence method, and TN categories were compared using Gray's test. Results: Of 682 patients, 620 were analyzable for outcomes by TN category. All endpoints showed statistically significant differences among the TN categories of disease (OS, P<.0001; DFS, P<.0001; LRF, P<.0001; DM, P=.0011; CF, P=.01). Patients with the poorest OS, DFS, and LRF outcomes were those with T3-4N-positive (+) disease. CF was lowest for T2N0 and T2N+ (11%, 11%, respectively) and worst for the T4N0, T3N+, and T4N+ categories (26%, 27%, 24%, respectively). Conclusions: TN category of disease has a statistically significant impact on OS, DFS, LRF, DM, and CF in patients treated with CCRT and provides excellent prognostic information for outcomes in patients with anal carcinoma. Significant challenges remain for patients with T4N0 and T3-4N+ categories of disease with regard to survival, relapse, and CF and lesser challenges for T2-3N0/T2N+ categories.« less

Outcomes of Preoperative Chemoradiotherapy and Combined Chemotherapy with Radiotherapy Without Surgery for Locally Advanced Rectal Cancer.

PubMed

Supaadirek, Chunsri; Pesee, Montien; Thamronganantasakul, Komsan; Thalangsri, Pimsiree; Krusun, Srichai; Supakalin, Narudom

2016-01-01

To evaluate the treatment outcomes of patients with locally advanced rectal cancer treated with preoperative concurrent chemoradiotherapy (CCRT) or combined chemotherapy together with radiotherapy (CMTRT) without surgery. A total of 84 patients with locally advanced rectal adenocarcinoma (stage II or III) between January 1st, 2003 and December 31st, 2013 were enrolled, 48 treated with preoperative CCRT (Gr.I) and 36 with combined chemotherapy and radiotherapy (CMTRT) without surgery (Gr.II). The chemotherapeutic agents used concurrent with radiotherapy were either 5fluorouracil short infusion plus leucovorin and/or capecitabine or 5fluorouracil infusion alone. All patients received pelvic irradiation. There were 5 patients (10.4%) with a complete pathological response. The 3 yearoverall survival rates were 83.2% in Gr.I and 24.8 % in Gr.II (p<0.01). The respective 5 yearoverall survival rates were 70.3% and 0% (p<0.01). The 5 yearoverall survival rates in Gr.I for patients who received surgery within 56 days after complete CCRT as compared to more than 56 days were 69.5% and 65.1% (p=0.91). Preoperative CCRT used for 12 of 30 patients in Gr.I (40%) with lower rectal cancer demonstrated that in preoperative CCRT a sphincter sparing procedure can be performed. The results of treatment with preoperative CCRT for locally advanced rectal cancer showed comparable rates of overall survival and sphincter sparing procedures as compared to previous studies.

Modified Weekly Cisplatin-Based Chemotherapy Is Acceptable in Postoperative Concurrent Chemoradiotherapy for Locally Advanced Head and Neck Cancer

PubMed Central

Lu, Hsueh-Ju; Yang, Chao-Chun; Wang, Ling-Wei; Chu, Pen-Yuan; Tai, Shyh-Kuan; Chen, Ming-Huang; Yang, Muh-Hwa; Chang, Peter Mu-Hsin

2015-01-01

Background. Triweekly cisplatin-based postoperative concurrent chemoradiotherapy (CCRT) has high intolerance and toxicities in locally advanced head and neck cancer (LAHNC). We evaluated the effect of a modified weekly cisplatin-based chemotherapy in postoperative CCRT. Methods. A total of 117 patients with LAHNC were enrolled between December 2007 and December 2012. Survival, compliance/adverse events, and independent prognostic factors were analyzed. Results. Median follow-up time was 30.0 (3.1–73.0) months. Most patients completed the entire course of postoperative CCRT (radiotherapy ≥ 60 Gy, 94.9%; ≥6 times weekly chemotherapy, 75.2%). Only 17.1% patients required hospital admission. The most common adverse effect was grade 3/4 mucositis (28.2%). No patient died due to protocol-related adverse effects. Multivariate analysis revealed the following independent prognostic factors: oropharyngeal cancer, extracapsular spread, and total radiation dose. Two-year progression-free survival and overall survival rates were 70.9% and 79.5%, respectively. Conclusion. Modified weekly cisplatin-based chemotherapy is an acceptable regimen in postoperative CCRT for LAHNC. PMID:25793192

Can concurrent chemoradiotherapy replace surgery and postoperative radiation for locally advanced stage III/IV tonsillar squamous cell carcinoma?

PubMed

Park, Geumju; Lee, Sang-Wook; Kim, Sang Yoon; Nam, Soon Yuhl; Choi, Seung-Ho; Kim, Sung-Bae; Roh, Jong-Lyel; Yoon, Dok Hyun; Kim, Su Ssan; Park, Jin-Hong; Kim, Young Seok; Yoon, Sang Min; Song, Si Yeol; Kim, Jong Hoon; Choi, Eun Kyung; DO Ahn, Seung

2013-03-01

To compare surgery and postoperative radiotherapy (PORT) with the non-surgical combination of chemotherapy and radiation therapy (CCRT) for locally advanced squamous cell carcinoma (SCC) of the tonsil by measuring treatment outcomes and treatment-related complications. The records of 114 patients with non-metastatic stage III/IV tonsillar SCC treated between July, 1998 and December, 2010 were reviewed retrospectively. Among the 114 patients, 65 received PORT and 49 received CCRT. In the PORT group, treatment included wide surgical resection of the tumor with neck dissection and administration of PORT to the primary tumor bed with a median dose of 60 Gy. In the CCRT group, a median dose of 70 Gy was delivered to the gross tumor, and 46 patients received concurrent chemotherapy with i.v. cisplatin. The median follow-up time was 58 months in the PORT group and 44 months in the CCRT group. There was no significant difference between PORT and CCRT in terms of 5-year locoregional recurrence-free survival (88.4% vs. 91.4%, p=0.68), distant metastasis-free survival (88.9% vs. 92.3%, p=0.60), disease-free survival (79.5% vs. 84.2%, p=0.63) or overall survival (78.9% vs. 88.9%, p=0.45). More CCRT patients than PORT patients experienced grade 3 (or higher) hematological toxicities and grade 2 pharyngitis during treatment. Chronic toxicity, manifested as swallowing difficulty, dry mouth and trismus, was similar between the two treatment groups. CCRT provides similar levels of local and distant control in patients with locally advanced tonsillar SCC as PORT, yet fails to show any superiority in preserving functions such as swallowing, saliva production, and mastication.

Concurrent IMRT and weekly cisplatin followed by GDP chemotherapy in newly diagnosed, stage IE to IIE, nasal, extranodal NK/T-Cell lymphoma.

PubMed

Ke, Q-H; Zhou, S-Q; Du, W; Liang, G; Lei, Y; Luo, F

2014-12-12

On the basis of the benefits of frontline radiation in early-stage, extranodal natural killer (NK)/T-cell lymphoma (ENKTL), we conducted the trial of concurrent chemoradiotherapy (CCRT) followed by three cycles of gemcitabine, dexamethasone and cisplatin (GDP). Thirty-two patients with newly diagnosed, stage IE to IIE, nasal ENKTL received CCRT (that is, all patients received intensity-modulated radiotherapy 56 Gy and cisplatin 30 mg/m(2) weekly, 3-5 weeks). Three cycles of GDP (gemcitabine 1000 mg/m(2) intravenously (i.v.) on days 1 and 8, dexamethasone 40 mg orally on days 1-4 and cisplatin 75 mg/m(2) i.v. on day 1 (GDP), every 21 days as an outpatient were scheduled after CCRT. All patients completed CCRT, which resulted in 100% response that included 24 complete responses (CRs) and eight partial responses. The CR rate after CCRT was 75.0% (that is, 24 of 32 responses). Twenty-eight of the 32 patients completed the planned three cycles of GDP, whereas four patients did not because they withdrew (n = 1) or because they had an infection (n = 3). The overall response rate and the CR rate were 90.6% (that is, 29 of 32 responses) and 84.4% (that is, 27 of 32 responses), respectively. Only two patient experienced grade 3 toxicity during CCRT (nausea), whereas 13 of the 30 patients experienced grade 4 neutropenia. The estimated 3-year overall survival and progression-free rates were 87.50% and 84.38%, respectively. In conclusion, CCRT followed by GDP chemotherapy can be a feasible and effective treatment strategy for stage IE to IIE nasal ENKTL.

Impact of Concomitant Chemotherapy on Outcomes of Radiation Therapy for Head-and-Neck Cancer: A Population-Based Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gupta, Shlok; Kong, Weidong; Booth, Christopher M.

2014-01-01

Purpose: Clinical trials have shown that the addition of chemotherapy to radiation therapy (RT) improves survival in advanced head-and-neck cancer. The objective of this study was to describe the effectiveness of concomitant chemoradiation therapy (C-CRT) in routine practice. Methods and Materials: This was a population-based cohort study. Electronic records of treatment from all provincial cancer centers were linked to a population--based cancer registry to describe the adoption of C-CRT for head-and-neck cancer patients in Ontario, Canada. The study population was then divided into pre- and postadoption cohorts, and their outcomes were compared. Results: Between 1992 and 2008, 18,867 patients hadmore » diagnoses of head-and-neck cancer in Ontario, of whom 7866 (41.7%) were treated with primary RT. The proportion of primary RT cases that received C-CRT increased from 2.2% in the preadoption cohort (1992-1998) to 39.3% in the postadoption cohort (2003-2008). Five-year survival among all primary RT cases increased from 43.6% in the preadoption cohort to 51.8% in the postadoption cohort (P<.001). Over the same period, treatment-related hospital admissions increased significantly, but there was no significant increase in treatment-related deaths. Conclusions: C-CRT was widely adopted in Ontario after 2003, and its adoption was temporally associated with an improvement in survival.« less

Prognostic significance of DSG3 in rectal adenocarcinoma treated with preoperative chemoradiotherapy.

PubMed

Chao, Tung-Bo; Li, Chien-Feng; Lin, Ching-Yih; Tian, Yu-Feng; Chang, I-Wei; Sheu, Ming-Jen; Lee, Ying-En; Chan, Ti-Chun; He, Hong-Lin

2016-06-01

This study aimed to investigate the prognostic significance of DSG3 and its association with response to neoadjuvant concurrent chemoradiotherapy (CCRT) in rectal cancer. Data mining of a publicly available dataset was performed to find genes associated with CCRT response. Immunohistochemistry was applied to evaluate DSG3 expression. The relationships between DSG3 expression and various clinicopathological parameters and survival were analyzed. The DSG3 gene was significantly associated with CCRT response. The expression of DSG3 negatively correlated with poorer tumor regression (p < 0.001) and had an independent negative impact on disease-specific survival (p = 0.011), local recurrence-free survival (p = 0.031) and metastasis-free survival (p = 0.029). DSG3 was a key prognostic factor and predictor for CCRT response in rectal cancer patients.

Impacts of treatments on the quality of life among esophageal squamous cell carcinoma patients.

PubMed

Chen, C-Y; Hsieh, V C-R; Chang, C-H; Chen, P-R; Liang, W-M; Pan, S-C; Shieh, S-H

2017-10-01

This study aims to investigate the effects of treatments on the quality of life for patients with esophageal squamous cell carcinoma patients diagnosed at early and late stages. From a medical center in central Taiwan, patients who had been diagnosed with esophageal squamous cell carcinoma from February 2007 and March 2011 were recruited. Using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and the Quality of Life Questionnaire Oesophageal 18 (QLQ-OES18), quality of life scores for 105 esophageal squamous cell carcinoma patients were obtained and assessed. Multivariate analysis was performed on the quality of life scores after stratification by cancer stage. Among early-stage esophageal squamous cell carcinoma patients, those received only surgery (S-only) performed better in physical and social functioning compared with patients who underwent surgery and concurrent chemoradiotherapy (S+CCRT) (β = 9.0, P = 0.03; β = 12.1, P = 0.04, respectively). For those that received only concurrent chemoradiotherapy (CCRT-only), they performed worse in role and emotional functioning relative to S+CCRT patients (β = -17.2, P = 0.02; β = -15.7, P = 0.05, respectively). Among late-stage patients, CCRT-only treatment gave insignificantly better global health status and functional scale scores and less severe symptoms compared to the S+CCRT option. Better functional scores and less aggravated symptoms are observed in early-stage esophageal squamous cell carcinoma patients who received surgery-only treatment relative to those that underwent both surgery and chemoradiotherapy. For late-stage esophageal cancer patients, the measured difference of quality of life is not significant between CCRT-only and S+CCRT treatments. © The Authors 2017. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Overexpression of Transcobalamin 1 is an Independent Negative Prognosticator in Rectal Cancers Receiving Concurrent Chemoradiotherapy.

PubMed

Lee, Yi-Ying; Wei, Yu-Ching; Tian, Yu-Feng; Sun, Ding-Ping; Sheu, Ming-Jen; Yang, Ching-Chieh; Lin, Li-Ching; Lin, Chen-Yi; Hsing, Chung-Hsi; Li, Wan-Shan; Li, Chien-Feng; Hsieh, Pei-Ling; Lin, Ching-Yih

2017-01-01

Objective: Neoadjuvant concurrent chemoradiotherapy (CCRT) is an increasingly common therapeutic strategy for locally advanced rectal cancer, but stratification of risk and final outcomes remain a major challenge. Transcobalamin 1 (TCN1), a vitamin B12 (cobalamin)-binding protein, regulates cobalamin homeostasis. High expression of TCN1 have been reported in neoplasms such as breast cancer and hepatocellular carcinoma. However, little is known about the relevance of TCN1 to rectal cancer receiving CCRT. This study examined the predictive and prognostic impact of TCN1 expression in patients with rectal cancer following neoadjuvant CCRT. Methods: Through data mining from a published transcriptome of rectal cancers (GSE35452), we identified upregulation of TCN1 gene as the most significantly predicted poor response to CCRT among ion transport-related genes (GO:0006811). We evaluated TCN1 immunohistochemistry and performed an H-score analysis on endoscopic biopsy specimens from 172 rectal cancer patients receiving neoadjuvant CCRT followed by curative surgery. Expression levels of TCN1 were further correlated with clinicopathologic features, therapeutic response, tumor regression grade (TRG) and survivals including metastasis-free survival (MeFS), disease-specific survival (DSS) and recurrent-free survival (LRFS). Results: TCN1 overexpression was significantly related to advanced post-treatment tumor (T3, T4; p <0.001) and nodal status (N1, N2; p <0.001), vascular invasion ( p =0.003) and inferior tumor regression grade ( p < 0.001). In survival analyses, TCN1 overexpression was significantly associated with shorter DSS ( p <0.0001), MeFS ( p =0.0002) and LRFS ( p =0.0001). Furthermore, it remained an independent prognosticator of worse DSS ( p =0.002, hazard ratio=3.344), MeFS ( p =0.021, hazard ratio=3.015) and LRFS ( p =0.037, hazard ratio=3.037) in the multivariate comparison. Conclusion: Overexpression of TCN1 is associated with poor therapeutic response and adverse outcomes in rectal cancer patients receiving CCRT, justifying the potential prognostic value of TCN1 in rectal cancer receiving CCRT.

Prognostic role of initial pan-endoscopic tumor length at diagnosis in operable esophageal squamous cell carcinoma undergoing esophagectomy with or without neoadjuvant concurrent chemoradiotherapy

PubMed Central

Lin, Chen-Sung; Liu, Chao-Yu; Cheng, Chih-Tao; Tsai, Yu-Chen; Chiou, Lun-Wei; Lee, Ming-Yuan

2017-01-01

Background The objective of this study was to appraise the prognostic role of initial pan-endoscopic tumor length at diagnosis within or between operable esophageal squamous cell carcinoma (ESCC) undergoing upfront esophagectomy or neoadjuvant concurrent chemoradiotherapy (nCCRT) followed by esophagectomy. Methods Between Jan 2001 and Dec 2013 in Koo-Foundation Sun Yat-sen Cancer Center in Taiwan, 101 ESCC patients who underwent upfront esophagectomy (surgery group) and 128 nCCRT followed by esophagectomy (nCCRT-surgery group) were retrospectively collected. Prognostic variables, including initial pan-endoscopic tumor length at diagnosis (sub-grouped ≤3, 3–5 and >5 cm), status of circumferential resection margin (CRM), and pathological T/N/M-status and cancer stage, were appraised within or between surgery and nCCRT-surgery groups. Results Within surgery group, longer initial pan-endoscopic tumor length at diagnosis (≤3, 3–5 and >5 cm; HR =1.000, 1.688 and 4.165; P=0.007) was an independent prognostic factor that correlated with advanced T/N/M-status, late cancer stage, and CRM invasion (all’s P<0.001). Based on the initial pan-endoscopic tumor length at diagnosis ≤3, 3–5 and >5 cm, nCCRT-surgery group had a poorer (P=0.039), similar (P=0.447) and better (P<0.001) survivals than did surgery group, respectively. For those with initial pan-endoscopic tumor length at diagnosis >5 cm, nCCRT-surgery group had more percentage of T0/N0-status and stage 0 (all’s P<0.05), and fewer rate of CRM invasion (P=0.036) than did surgery group. Conclusions Initial pan-endoscopic tumor length at diagnosis could be a criterion to select proper ESCC cases for nCCRT followed by esophagectomy to improve survival and reduce CRM invasion. PMID:29221296

Optimizing Survival of Patients With Marginally Operable Stage IIIA Non-Small-Cell Lung Cancer Receiving Chemoradiotherapy With or Without Surgery.

PubMed

Yang, Kai-Lin; Chang, Yih-Chen; Ko, Hui-Ling; Chi, Mau-Shin; Wang, Hsin-Ell; Hsu, Pei-Sung; Lin, Chen-Chun; Yeh, Diana Yu-Wung; Kao, Shang-Jyh; Jiang, Jiunn-Song; Chi, Kwan-Hwa

2016-11-01

For marginally operable stage IIIA non-small-cell lung cancer (NSCLC), surgery might not be done as planned after neoadjuvant concurrent chemoradiotherapy (CCRT) for reasons (unresectable or medically inoperable conditions, or patient refusal). This study aims to investigate the outcomes of a phased CCRT protocol established to maximize the operability of marginally operable stage IIIA NSCLC and to care for reassessed inoperable patients, in comparison with continuous-course definitive CCRT. Forty-seven patients with marginally operable stage IIIA NSCLC receiving CCRT were included. Twenty-eight patients were treated with our phased CCRT protocol, including neoadjuvant CCRT followed by surgery (group A, n = 16) or, for reassessed inoperable patients, maintenance chemotherapy and split-course CCRT boost (group B, n = 12). The other 19 were treated with continuous-course definitive CCRT (group C). Overall survival (OS) and progression-free survival (PFS) were analyzed. Among all, median OS and PFS were 35.6 and 12.8 months, respectively (median follow-up, 22.3 months). The median OS of group A (not reached) was better than that of group B (34.4 months) and group C (15.2 months) (P = .009). On multivariate analysis, performance status 0 to 1 (hazard ratio [HR], 0.026; P < .001), adenocarcinoma (HR, 0.156; P = .003), and group A (HR, 0.199; P = .033) were independent prognostic factors. The OS of group B (HR, 0.450; 95% confidence interval, 0.118-1.717; P = .243) was not statistically different from that of group C. For marginally operable stage IIIA NSCLC, our phased CCRT strategy may optimize survival by maximizing operability and maintain an acceptable survival for reassessed inoperable patients by split-course CCRT boost following maintenance chemotherapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Neoadjuvant chemotherapy followed by surgery has no therapeutic advantages over concurrent chemoradiotherapy in International Federation of Gynecology and Obstetrics stage IB-IIB cervical cancer.

PubMed

Lee, Jeongshim; Kim, Tae Hyung; Kim, Gwi Eon; Keum, Ki Chang; Kim, Yong Bae

2016-09-01

We aimed to assess the efficacy of neoadjuvant chemotherapy followed by surgery (NACT+S), and compared the clinical outcome with that of concurrent chemoradiotherapy (CCRT) in patients with International Federation of Gynecology and Obstetrics (FIGO) IB-IIB cervical cancer. We reviewed 85 patients with FIGO IB-IIB cervical cancer who received NACT+S between 1989 and 2012, and compared them to 358 control patients who received CCRT. The clinical application of NACT was classified based on the following possible therapeutic benefits: increasing resectability after NACT by reducing tumor size or negative conversion of node metastasis; downstaging adenocarcinoma regarded as relatively radioresistant; and preservation of fertility through limited surgery after NACT. Of 85 patients in the NACT+S group, the pathologic downstaging and complete response rates were 68.2% and 22.6%, respectively. Only two young patients underwent limited surgery for preservation of fertility. Patients of the NACT+S group were younger, less likely to have node metastasis, and demonstrated a higher proportion of FIGO IB cases than those of the CCRT group (p≤0.001). The 5-year locoregional control, progression-free survival, and overall survival rates in the NACT+S group were 89.7%, 75.6%, and 92.1%, respectively, which were not significantly different from the rates of 92.5%, 74%, and 84.9% observed in the CCRT group, respectively (p>0.05). NACT+S has no therapeutic advantages over CCRT, the standard treatment. Therefore, NACT+S should be considered only in selected patients through multidisciplinary discussion or clinical trial setting.

Anal Carcinoma: Impact of TN Category of Disease on Survival, Disease Relapse, and Colostomy Failure in US Gastrointestinal Intergroup RTOG 98-11 Phase 3 Trial

PubMed Central

Gunderson, Leonard L.; Moughan, Jennifer; Ajani, Jaffer A.; Pedersen, John E.; Winter, Kathryn A.; Benson, Al B.; Thomas, Charles R.; Mayer, Robert J.; Haddock, Michael G.; Rich, Tyvin A.; Willett, Christopher G.

2013-01-01

Purpose The long-term update of US GI Intergroup RTOG 98-11 anal cancer trial found that concurrent chemoradiation (CCRT) with fluorouracil (5-FU) plus mitomycin had a significant impact on disease-free survival (DFS) and overall survival (OS) compared with induction plus concurrent 5-FU plus cisplatin. The intent of the current analysis was to determine the impact of tumor node (TN) category of disease on survival (DFS and OS), colostomy failure (CF), and relapse (local-regional failure [LRF] and distant metastases [DM]) in this patient group. Methods and Materials DFS and OS were estimated univariately by using the Kaplan-Meier method, and 6 TN categories were compared by the log–rank test (T2N0, T3N0, T4N0, T2N1-3, T3N1-3, and T4N1-3). Time to relapse and colostomy were estimated by the cumulative incidence method, and TN categories were compared using Gray’s test. Results Of 682 patients, 620 were analyzable for outcomes by TN category. All endpoints showed statistically significant differences among the TN categories of disease (OS, P<.0001; DFS, P<.0001; LRF, P<.0001; DM, P=.0011; CF, P=.01). Patients with the poorest OS, DFS, and LRF outcomes were those with T3-4N-positive (+) disease. CF was lowest for T2N0 and T2N+ (11%, 11%, respectively) and worst for the T4N0, T3N+, and T4N+ categories (26%, 27%, 24%, respectively). Conclusions TN category of disease has a statistically significant impact on OS, DFS, LRF, DM, and CF in patients treated with CCRT and provides excellent prognostic information for outcomes in patients with anal carcinoma. Significant challenges remain for patients with T4N0 and T3-4N+ categories of disease with regard to survival, relapse, and CF and lesser challenges for T2-3N0/T2N+ categories. PMID:24035327

Acute Esophagus Toxicity in Lung Cancer Patients After Intensity Modulated Radiation Therapy and Concurrent Chemotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kwint, Margriet; Uyterlinde, Wilma; Nijkamp, Jasper

2012-10-01

Purpose: The purpose of this study was to investigate the dose-effect relation between acute esophageal toxicity (AET) and the dose-volume parameters of the esophagus after intensity modulated radiation therapy (IMRT) and concurrent chemotherapy for patients with non-small cell lung cancer (NSCLC). Patients and Methods: One hundred thirty-nine patients with inoperable NSCLC treated with IMRT and concurrent chemotherapy were prospectively analyzed. The fractionation scheme was 66 Gy in 24 fractions. All patients received concurrently a daily dose of cisplatin (6 mg/m Superscript-Two ). Maximum AET was scored according to Common Toxicity Criteria 3.0. Dose-volume parameters V5 to V70, D{sub mean} andmore » D{sub max} of the esophagus were calculated. A logistic regression analysis was performed to analyze the dose-effect relation between these parameters and grade {>=}2 and grade {>=}3 AET. The outcome was compared with the clinically used esophagus V35 prediction model for grade {>=}2 after radical 3-dimensional conformal radiation therapy (3DCRT) treatment. Results: In our patient group, 9% did not experience AET, and 31% experienced grade 1 AET, 38% grade 2 AET, and 22% grade 3 AET. The incidence of grade 2 and grade 3 AET was not different from that in patients treated with CCRT using 3DCRT. The V50 turned out to be the most significant dosimetric predictor for grade {>=}3 AET (P=.012). The derived V50 model was shown to predict grade {>=}2 AET significantly better than the clinical V35 model (P<.001). Conclusions: For NSCLC patients treated with IMRT and concurrent chemotherapy, the V50 was identified as most accurate predictor of grade {>=}3 AET. There was no difference in the incidence of grade {>=}2 AET between 3DCRT and IMRT in patients treated with concurrent chemoradiation therapy.« less

Overexpression of Transcobalamin 1 is an Independent Negative Prognosticator in Rectal Cancers Receiving Concurrent Chemoradiotherapy

PubMed Central

Lee, Yi-Ying; Wei, Yu-Ching; Tian, Yu-Feng; Sun, Ding-Ping; Sheu, Ming-Jen; Yang, Ching-Chieh; Lin, Li-Ching; Lin, Chen-Yi; Hsing, Chung-Hsi; Li, Wan-Shan; Li, Chien-Feng; Hsieh, Pei-Ling; Lin, Ching-Yih

2017-01-01

Objective: Neoadjuvant concurrent chemoradiotherapy (CCRT) is an increasingly common therapeutic strategy for locally advanced rectal cancer, but stratification of risk and final outcomes remain a major challenge. Transcobalamin 1 (TCN1), a vitamin B12 (cobalamin)-binding protein, regulates cobalamin homeostasis. High expression of TCN1 have been reported in neoplasms such as breast cancer and hepatocellular carcinoma. However, little is known about the relevance of TCN1 to rectal cancer receiving CCRT. This study examined the predictive and prognostic impact of TCN1 expression in patients with rectal cancer following neoadjuvant CCRT. Methods: Through data mining from a published transcriptome of rectal cancers (GSE35452), we identified upregulation of TCN1 gene as the most significantly predicted poor response to CCRT among ion transport-related genes (GO:0006811). We evaluated TCN1 immunohistochemistry and performed an H-score analysis on endoscopic biopsy specimens from 172 rectal cancer patients receiving neoadjuvant CCRT followed by curative surgery. Expression levels of TCN1 were further correlated with clinicopathologic features, therapeutic response, tumor regression grade (TRG) and survivals including metastasis-free survival (MeFS), disease-specific survival (DSS) and recurrent-free survival (LRFS). Results: TCN1 overexpression was significantly related to advanced post-treatment tumor (T3, T4; p<0.001) and nodal status (N1, N2; p<0.001), vascular invasion (p=0.003) and inferior tumor regression grade (p < 0.001). In survival analyses, TCN1 overexpression was significantly associated with shorter DSS (p<0.0001), MeFS (p=0.0002) and LRFS (p=0.0001). Furthermore, it remained an independent prognosticator of worse DSS (p=0.002, hazard ratio=3.344), MeFS (p=0.021, hazard ratio=3.015) and LRFS (p=0.037, hazard ratio=3.037) in the multivariate comparison. Conclusion: Overexpression of TCN1 is associated with poor therapeutic response and adverse outcomes in rectal cancer patients receiving CCRT, justifying the potential prognostic value of TCN1 in rectal cancer receiving CCRT. PMID:28638446

Concurrent Etoposide, Steroid, High-dose Ara-C and Platinum chemotherapy with radiation therapy in localised extranodal natural killer (NK)/T-cell lymphoma, nasal type.

PubMed

Michot, Jean-Marie; Mazeron, Renaud; Danu, Alina; Lazarovici, Julien; Ghez, David; Antosikova, Anna; Willekens, Christophe; Chamseddine, Ali N; Minard, Veronique; Dartigues, Peggy; Bosq, Jacques; Carde, Patrice; Koscielny, Serge; De Botton, Stéphane; Ferme, Christophe; Girinsky, Theodore; Ribrag, Vincent

2015-11-01

Radiation combined with chemotherapy has recently been proposed to treat patients with localised extranodal natural killer (NK)/T lymphoma (ENKTL), nasal type. However, the modalities of the chemoradiotherapy combination and drug choices remain a matter of debate. We conducted a concurrent chemoradiotherapy (CCRT) study with the ESHAP (Etoposide, Steroid, High-dose Ara-C and Platinum) regimen. An induction phase with two upfront courses of CCRT delivering a 40Gy dose of radiation concurrently with two cycles of the ESHAP chemotherapy regimen, followed by a consolidation phase with 2-3 cycles of ESHAP chemotherapy alone. Thirteen patients with localised ENKTL nasal type were enrolled between January 2005 and December 2014. The median age was 62years. Ten and three patients had Ann Arbor stage IE and IIE disease, respectively. They all completed the induction CCRT phase. A median of two consolidation ESHAP cycles were delivered. During consolidation, 8/13 (62%) patients had a reduction in the number of chemotherapy cycles or reduced chemotherapy doses, due to haematologically adverse events. The other five patients (38%) received the full number of ESHAP cycles of chemotherapy scheduled without a dose reduction. All but one patient (92%) experienced grade 3-4 haematological toxicity. The main non-haematological grade 3-4 toxicity was mucositis in 6/13 (46%) patients. All but one patient (92%) achieved a complete remission. Two-year overall survival was 72%. With optimal management of the specific toxicities induced by this treatment modality, CCRT with the ESHAP regimen yielded high efficacy against localised ENKTL, nasal type. Copyright © 2015 Elsevier Ltd. All rights reserved.

Efficacy and safety of concurrent chemoradiation with weekly cisplatin ± low-dose celecoxib in locally advanced undifferentiated nasopharyngeal carcinoma: a phase II-III clinical trial.

PubMed

Mohammadianpanah, Mohammad; Razmjou-Ghalaei, Sasan; Shafizad, Amin; Ashouri-Taziani, Yaghoub; Khademi, Bijan; Ahmadloo, Niloofar; Ansari, Mansour; Omidvari, Shapour; Mosalaei, Ahmad; Mosleh-Shirazi, Mohammad Amin

2011-01-01

This is the first study that aimed to determine the efficacy and safety of concurrent chemoradiation with weekly cisplatin ± celecoxib 100 mg twice daily in locally advanced undifferentiated nasopharyngeal carcinoma. Eligible patients had newly diagnosed locally advanced (T3-T4, and/or N2-N3, M0) undifferentiated nasopharyngeal carcinoma, no prior therapy, Karnofsky performance status ≥ 70, and normal organ function. The patients were assigned to receive 7 weeks concurrent chemoradiation (70 Gy) with weekly cisplatin 30 mg/m 2 with either celecoxib 100 mg twice daily, (study group, n = 26) or placebo (control group, n = 27) followed by adjuvant combined chemotherapy with cisplatin 70 mg/m 2 on day 1 plus 5-fluorouracil 750 mg/m 2 /d with 8-h infusion on days 1-3, 3-weekly for 3 cycles. Overall clinical response rate was 100% in both groups. Complete and partial clinical response rates were 64% and 36% in the study group and 44% and 56% in the control group, respectively (P > 0.25). The addition of celecoxib to concurrent chemoradiation was associated with improved 2-year locoregional control rate from 84% to 100% (P = 0.039). The addition of celecoxib 100 mg twice daily to concurrent chemoradiation improved 2-year locoregional control rate.

Tumor cavitation in patients with stage III non-small-cell lung cancer undergoing concurrent chemoradiotherapy: incidence and outcomes.

PubMed

Phernambucq, Erik C J; Hartemink, Koen J; Smit, Egbert F; Paul, Marinus A; Postmus, Pieter E; Comans, Emile F I; Senan, Suresh

2012-08-01

Commonly reported complications after concurrent chemoradiotherapy (CCRT) in patients with stage III non-small-cell lung cancer (NSCLC) include febrile neutropenia, radiation esophagitis, and pneumonitis. We studied the incidence of tumor cavitation and/or "tumor abscess" after CCRT in a single-institutional cohort. Between 2003 and 2010, 87 patients with stage III NSCLC underwent cisplatin-based CCRT and all subsequent follow-up at the VU University Medical Center. Diagnostic and radiotherapy planning computed tomography scans were reviewed for tumor cavitation, which was defined as a nonbronchial air-containing cavity located within the primary tumor. Pulmonary toxicities scored as Common Toxicity Criteria v3.0 of grade III or more, occurring within 90 days after end of radiotherapy, were analyzed. In the entire cohort, tumor cavitation was observed on computed tomography scans of 16 patients (18%). The histology in cavitated tumors was squamous cell (n = 14), large cell (n = 1), or adenocarcinoma (n = 1). Twenty patients (23%) experienced pulmonary toxicity of grade III or more, other than radiation pneumonitis. Eight patients with a tumor cavitation (seven squamous cell carcinoma) developed severe pulmonary complications; tumor abscess (n = 5), fatal hemorrhage (n = 2), and fatal embolism (n = 1). Two patients with a tumor abscess required open-window thoracostomy post-CCRT. The median overall survival for patients with or without tumor cavitation were 9.9 and 16.3 months, respectively (p = 0.09). With CCRT, acute pulmonary toxicity of grade III or more developed in 50% of patients with stage III NSCLC, who also had radiological features of tumor cavitation. The optimal treatment of patients with this presentation is unclear given the high risk of a tumor abscess.

Treatment Variation of Sequential versus Concurrent Chemoradiotherapy in Stage III Non-Small Cell Lung Cancer Patients in the Netherlands and Belgium.

PubMed

Walraven, I; Damhuis, R A; Ten Berge, M G; Rosskamp, M; van Eycken, L; de Ruysscher, D; Belderbos, J S A

2017-11-01

Concurrent chemoradiotherapy (CCRT) is considered the standard treatment regimen in non-surgical locally advanced non-small cell lung cancer (NSCLC) patients and sequential chemoradiotherapy (SCRT) is recommended in patients who are unfit to receive CCRT or when the treatment volume is considered too large. In this study, we investigated the proportion of CCRT/SCRT in the Netherlands and Belgium. Furthermore, patient and disease characteristics associated with SCRT were assessed. An observational study was carried out with data from three independent national registries: the Belgian Cancer Registry (BCR), the Netherlands Cancer Registry (NCR) and the Dutch Lung Cancer Audit-Radiotherapy (DLCA-R). Differences in patient and disease characteristics between CCRT and SCRT were tested with unpaired t-tests (for continuous variables) and with chi-square tests (for categorical variables). A prognostic model was constructed to determine patient and disease parameters predictive for the choice of SCRT. This study included 350 patients from the BCR, 780 patients from the NCR and 428 patients from the DLCA-R. More than half of the stage III NSCLC patients in the Netherlands (55%) and in Belgium more than a third (35%) were treated with CCRT. In both the Dutch and Belgian population, higher age and more advanced N-stage were significantly associated with SCRT. Performance score, pulmonary function, comorbidities and tumour volume were not associated with SCRT. In this observational population-based study, a large treatment variation in non-surgical stage III NSCLC patients was observed between and within the Netherlands and Belgium. Higher age and N-stage were significantly associated with the choice for SCRT. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Identification of surrogate endpoints in patients with locoregionally advanced nasopharyngeal carcinoma receiving neoadjuvant chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone.

PubMed

Chen, Yu-Pei; Zhang, Wen-Na; Tang, Ling-Long; Mao, Yan-Ping; Liu, Xu; Chen, Lei; Zhou, Guan-Qun; Mai, Hai-Qiang; Shao, Jian-Yong; Jia, Wei-Hua; Kang, Tie-Bang; Zeng, Mu-Sheng; Sun, Ying; Ma, Jun

2015-11-24

In the era of intensity-modulated radiotherapy (IMRT), the efficacy of additional neoadjuvant chemotherapy (NACT) to concurrent chemoradiotherapy (CCRT) in locoregionally advanced nasopharyngeal carcinoma (NPC) is currently being investigated in ongoing trials. Overall survival (OS) is the gold standard endpoint in NPC trials. We performed this analysis to identify surrogate endpoints for OS, which could shorten follow-up duration and speed up assessment of treatment effects. We retrospectively analysed 208 matched-pair patients with locoregionally advanced NPC receiving NACT+CCRT or CCRT. Progression-free survival (PFS), failure-free survival (FFS), distant failure-free survival (D-FFS) and locoregional failure-free survival (LR-FFS) at 2 and 3 years were assessed as surrogates for 5-year OS according to Prentice's criteria. The strength of the associations were assessed using Spearman's rank correlation coefficient. No significant differences were observed between treatment arms for any surrogate endpoint at 2 years, which rejected Prentice's second criterion. In contrast, 3-year LR-FFS, PFS, FFS and D-FFS were consistent with all four of Prentice's criteria; the rank correlation coefficient (0.730) between 3-year PFS and 5-year OS was highest. 3-year PFS, FFS and D-FFS could be valid surrogate endpoints for 5-year OS; 3-year PFS may be the most accurate.

Usefulness of Interim FDG-PET After Induction Chemotherapy in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck Receiving Sequential Induction Chemotherapy Followed by Concurrent Chemoradiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoon, Dok Hyun; Cho, Yoojin; Kim, Sang Yoon

2011-09-01

Purpose: Induction chemotherapy (ICT) has been used to select patients for organ preservation and determine subsequent treatments in patients with locally advanced squamous cell carcinoma of the head and neck (LASCCHN). Still, the clinical outcomes of LASCCHN patients who showed response to ICT are heterogeneous. We evaluated the efficacy of interim 18-fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) after ICT in this specific subgroup of LASCCHN patients who achieved partial response (PR) after ICT to predict clinical outcomes after concurrent chemoradiotherapy (CCRT). Methods and Materials: Twenty-one patients with LASCCHN who showed PR to ICT by Response Evaluation Criteria In Solid Tumors beforemore » definitive CCRT were chosen in this retrospective analysis. FDG-PET was performed before and 2-4 weeks after ICT to assess the extent of disease at baseline and the metabolic response to ICT, respectively. We examined the correlation of the metabolic response by the percentage decrease of maximum standardized uptake value (SUVmax) on the primary tumor or lymph node after ICT or a specific threshold of SUVmax on interim FDG-PET with clinical outcomes including complete response (CR) rate to CCRT, progression-free survival (PFS), and overall survival (OS). Results: A SUVmax of 4.8 on interim FDG-PET could predict clinical CR after CCRT (100% vs. 20%, p = 0.001), PFS (median, not reached vs. 8.5 mo, p < 0.001), and OS (median, not reached vs. 12.0 months, p = 0.001) with a median follow-up of 20.3 months in surviving patients. A 65% decrease in SUVmax after ICT from baseline also could predict clinical CR after CCRT (100% vs. 33.3%, p = 0.003), PFS (median, not reached vs. 8.9 months, p < 0.001) and OS (median, not reached vs. 24.4 months, p = 0.001) of the patients. Conclusion: These data suggest that interim FDG-PET after ICT might be a useful determinant to predict clinical outcomes in patients with LASCCHN receiving sequential ICT followed by CCRT.« less

Efficacy and Factors Affecting Outcome of Gemcitabine Concurrent Chemoradiotherapy in Patients With Locally Advanced Pancreatic Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, P.-I.; National Yang-Ming University School of Medicine, Taipei, Taiwan; Chao, Yee

Purpose: To evaluate the efficacy and prognostic factors of gemcitabine (GEM) concurrent chemoradiotherapy (CCRT) in patients with locally advanced pancreatic cancer. Methods and Materials: Between January 2002 and December 2005, 55 patients with locally advanced pancreatic cancer treated with GEM (400 mg/m{sup 2}/wk) concurrently with radiotherapy (median dose, 50.4 Gy; range, 26-61.2) at Taipei Veterans General Hospital were enrolled. GEM (1,000 mg/m{sup 2}) was continued after CCRT as maintenance therapy once weekly for 3 weeks and repeated every 4 weeks. The response, survival, toxicity, and prognostic factors were evaluated. Results: With a median follow-up of 10.8 months, the 1- andmore » 2-year survival rate was 52% and 19%, respectively. The median overall survival (OS) and median time to progression (TTP) was 12.4 and 5.9 months, respectively. The response rate was 42% (2 complete responses and 21 partial responses). The major Grade 3-4 toxicities were neutropenia (22%) and anorexia (19%). The median OS and TTP was 15.8 and 9.5 months in the GEM CCRT responders compared with 7.5 and 3.5 months in the nonresponders, respectively (both p < 0.001). The responders had a better Karnofsky performance status (KPS) (86 {+-} 2 vs. 77 {+-} 2, p = 0.002) and had received a greater GEM dose intensity (347 {+-} 13 mg/m{sup 2}/wk vs. 296 {+-} 15 mg/m{sup 2}/wk, p = 0.02) than the nonresponders. KPS and serum carbohydrate antigen 19-9 were the most significant prognostic factors of OS and TTP. Conclusion: The results of our study have shown that GEM CCRT is effective and tolerable for patients with locally advanced pancreatic cancer. The KPS and GEM dose correlated with response. Also, the KPS and CA 19-9 level were the most important factors affecting OS and TTP.« less

A randomized study to compare sequential chemoradiotherapy with concurrent chemoradiotherapy for unresectable locally advanced esophageal cancer.

PubMed

Gupta, Arunima; Roy, Somnath; Majumdar, Anup; Hazra, Avijit; Mallik, Chandrani

2014-01-01

Chemotherapy combined with radiotherapy can improve outcome in locally advanced esophageal cancer. This study aimed to compare efficacy and toxicity between concurrent chemoradiotherapy (CCRT) and sequential chemoradiotherapy (SCRT) in unresectable, locally advanced, esophageal squamous cell carcinoma (ESSC). Forty-one patients with unresectable, locally advanced ESCC were randomized into two arms. In the CCRT arm (Arm A), 17 patients received 50.4 Gy at 1.8 Gy per fraction over 5.6 weeks along with concurrent cisplatin (75 mg m(-2) intravenously on day 1 and 5-fluorouracil (1000 mg m(-2) continuous intravenous infusion on days 1-4 starting on the first day of irradiation and given after 28 days. In the SCRT arm (Arm B), 20 patients received two cycles of chemotherapy, using the same schedule, followed by radiotherapy fractionated in a similar manner. The endpoints were tumor response, acute and late toxicities, and disease-free survival. With a median follow up of 12.5 months, the complete response rate was 82.4% in Arm A and 35% in Arm B (P = 0.003). Statistically significant differences in frequencies of acute skin toxicity (P = 0.016), gastrointestinal toxicity (P = 0.005) and late radiation pneumonitis (P = 0.002) were found, with greater in the CCRT arm. A modest but non-significant difference was observed in median time to recurrence among complete responders in the two arms (Arm A 13 months and Arm B 15.5 months, P = 0.167) and there was also no significant difference between the Kaplan Meier survival plots (P = 0.641) of disease-free survival. Compared to sequential chemoradiotherapy, concurrent chemoradiotherapy can significantly improve local control rate but with greater risk of adverse reactions.

The Prognostic Value of Plasma Epstein-Barr Viral DNA and Tumor Response to Neoadjuvant Chemotherapy in Advanced-Stage Nasopharyngeal Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Li-Ting; Tang, Lin-Quan; Chen, Qiu-Yan

Purpose: To explore the prognostic value of the plasma load of Epstein-Barr viral (EBV) DNA and the tumor response to neoadjuvant chemotherapy (NACT) in advanced-stage nasopharyngeal carcinoma (NPC). Patients and Methods: In all, 185 consecutive patients with stage III to IVb NPC treated with NACT followed by concurrent chemoradiation therapy (CCRT) were prospectively enrolled. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included locoregional relapse–free survival (LRFS) and distant metastasis–free survival (DMFS). Results: EBV DNA was detected in 165 (89%) patients before treatment but was undetectable in 127 (69%) patients after NACT. Detectable EBV DNA levels aftermore » NACT were correlated with poor prognosis (3-year PFS 71.8% vs 85.2%, P=.008 and 3-year DMFS 82.5% vs 92.3%, P=.013). An unsatisfactory tumor response (stable disease or disease progression) after NACT was also correlated with poor clinical outcome (3-year PFS 71.1% vs 85.9%, P=.005 and 3-year LRFS 82.7% vs 93.5%, P=.012). Multivariate analysis showed that the EBV DNA level after NACT (hazard ratio [HR] 2.31, 95% CI 1.18-4.54, P=.015) and the tumor response to NACT (HR 2.84, 95% CI 1.42-5.67, P=.003) were both significant prognostic factors for PFS. Multivariate analysis also showed that EBV DNA after NACT was the only significant predictor of DMFS (HR 2.99, 95% CI 1.25-7.15, P=.014) and that tumor response to NACT was the only significant predictor of LRFS (HR 3.31, 95% CI 1.21-9.07, P=.020). Conclusion: Detectable EBV DNA levels and an unsatisfactory tumor response (stable disease or disease progression) after NACT serve as predictors of poor prognosis for patients with advanced-stage NPC. These findings will facilitate further risk stratification, early treatment modification, or both before CCRT.« less

Predictive factors of head and neck squamous cell carcinoma patient tolerance to high-dose cisplatin in concurrent chemoradiotherapy

PubMed Central

NAKANO, KENJI; SATO, YASUYOSHI; TOSHIYASU, TAKASHI; SATO, YUKIKO; INAGAKI, LINA; TOMOMATSU, JUNICHI; SASAKI, TORU; SHIMBASHI, WATARU; FUKUSHIMA, HIROFUMI; YONEKAWA, HIROYUKI; MITANI, HIROKI; KAWABATA, KAZUYOSHI; TAKAHASHI, SHUNJI

2016-01-01

Although high-dose cisplatin is the standard regimen of concurrent chemoradiotherapy (CCRT) for locally advanced head and neck squamous cell carcinoma (HNSCC), varying levels of patient tolerance towards cisplatin have been reported, and the predictive factors of cisplatin tolerance remain to be elucidated. The present study retrospectively reviewed newly diagnosed HNSCC patients who received CCRT. Cisplatin (80 mg/m2) was administered every 3 weeks. The proportion of high-dose cisplatin-tolerant patients (cumulative cisplatin dose, ≥200 mg/m2) was determined, and the predictive factors of cisplatin tolerance were analyzed in a logistic regression analysis. Between June 2006 and March 2013, a total of 159 patients were treated with CCRT. The median follow-up time was 36.7 months. A total of 73 patients (46%) tolerated a cumulative cisplatin dose ≥200 mg/m2; male gender [odds ratio (OR), 25.00; P=0.005] and high body surface area (BSA) (>1.80 m2; OR, 2.21; P=0.032) were significantly predictive of high-dose cisplatin tolerance. The high-dose cisplatin-tolerant patients had a significantly higher complete response (CR) rate (82 vs. 67%, P=0.045); however, there were no significant between-group differences in the 3-year OS (79.5 vs. 81.2%, P=0.59) or PFS (70.4 vs. 44.6%, P=0.076) by cisplatin tolerance. In clinical practice, approximately one-half of the patients tolerated high-dose cisplatin in CCRT. Male gender and high BSA could be predictive of cisplatin tolerance. PMID:26893880

Is heterogeneity in stage 3 non-small cell lung cancer obscuring the potential benefits of dose-escalated concurrent chemo-radiotherapy in clinical trials?

PubMed

Hudson, Andrew; Chan, Clara; Woolf, David; McWilliam, Alan; Hiley, Crispin; O'Connor, James; Bayman, Neil; Blackhall, Fiona; Faivre-Finn, Corinne

2018-04-01

The current standard of care for the management of inoperable stage 3 non-small cell lung cancer (NSCLC) is concurrent chemoradiotherapy (cCRT) using radiotherapy dose-fractionation and chemotherapy regimens that were established 3 decades ago. In an attempt to improve the chances of long-term control from cCRT, dose-escalation of the radiotherapy dose was assessed in the RTOG 0617 randomised control study comparing the standard 60 Gy in 30 fractions with a high-dose arm receiving 74 Gy in 37 fractions. Following the publication of this trial the thoracic oncology community were surprised to learn that there was worse survival in the dose-escalated arm and that for now the standard of care must remain with the lower dose. In this article we review the RTOG 0617 paper with subsequent analyses and studies to explore why the use of dose-escalated cCRT in stage 3 NSCLC has not shown the benefits that were expected. The overarching theme of this opinion piece is how heterogeneity between stage 3 NSCLC cases in terms of patient, tumour, and clinical factors may obscure the potential benefits of dose-escalation by causing imbalances in the arms of studies such as RTOG 0617. We also examine recent advances in the staging, management, and technological delivery of radiotherapy in NSCLC and how these may be employed to optimise cCRT trials in the future and ensure that any potential benefits of dose-escalation can be detected. Copyright © 2018 Elsevier B.V. All rights reserved.

Anemia During Sequential Induction Chemotherapy and Chemoradiation for Head and Neck Cancer: The Impact of Blood Transfusion on Treatment Outcome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhide, Shreerang A.; Ahmed, Merina; Head and Neck Unit, Royal Marsden National Health Service Foundation Trust Hospital, London

2009-02-01

Purpose: Sequential treatment (chemotherapy followed by concomitant chemoradiation; CCRT) is increasingly being used for radical treatment of squamous cell cancer of the head and neck (SCCHN), which results in increased myelosuppression. In this study, we review the incidence of anemia and the effect of a policy of hemoglobin (Hb) maintenance by blood transfusion on disease outcomes in these patients. Methods and Materials: Retrospective review of the records of patients with SCCHN treated with sequential CCRT formed the basis of this study. The incidence of anemia and statistics on blood transfusion were documented. For the purpose of outcome analyses, patients weremore » divided into four categories by (1) transfusion status, (2) nadir Hb concentration, (3) number of transfusion episodes, and (4) number of units of blood transfused (NOUT). Data on 3-year locoregional control (LRC), relapse-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) were analyzed. Results: One hundred and sixty-nine patients were identified. The median follow-up was 23.6 months. The RFS (52% vs. 41%, p = 0.03), DSS (71% vs. 66%, p = 0.02), and OS (58% vs. 42% p = 0.005) were significantly better for patients who did not have a transfusion vs. those who did. The LRC, RFS, DSS, and OS were also significantly better for patients with nadir Hb level >12 vs. <12 g/dL and NOUT 1-4 vs. >4. Conclusion: Our study seems to suggest that blood transfusion during radical treatment for SCCHN might be detrimental. Further research should be undertaken into the complex interactions among tumor hypoxia, anemia, and the treatment of anemia before making treatment recommendations.« less

Effects of intensity-modulated radiotherapy and chemoradiotherapy on attention in patients with nasopharyngeal cancer

PubMed Central

Wei, Qing; Li, Ling; Zhu, Xiao-Dong; Qin, Ling; Mo, Yan-Lin; Liang, Zheng-You; Deng, Jia-Li; Tao, Su-Ping

2017-01-01

This study evaluated the short-term effects of intensity-modulated radiotherapy (IMRT) and cisplatin concurrent chemo-radiotherapy (CCRT) on attention in patients with nasopharyngeal cancer (NPC). Timely detection and early prevention of cognitive decline are important in cancer patients, because long-term cognitive effects may be permanent and irreversible. Thirty-eight NPC patients treated with IMRT (17/38) or CCRT (21/38) and 38 healthy controls were recruited for the study. Neuropsychological tests were administered to each patient before treatment initiation and within a week after treatment completion. Changes in attention performance over time were evaluated using difference values (D-values). Decreased attention was already observable in patients with NPC prior to treatment. Baseline quotient scores for auditory attention, auditory and visual vigilance, and auditory speed were lower in patients treated with CCRT than in healthy controls (P=0.037, P=0.001, P=0.007, P=0.032, respectively). Auditory stamina D-values were higher in patients treated with IMRT alone (P=0.042), while full-scale response control quotient D-values were lower in patients treated with CCRT (P=0.030) than in healthy controls. Gender, depression, education, and sleep quality were each related to decreased attention and response control. Our results showed that IMRT had no negative acute effects on attention in NPC patients, while CCRT decreased response control. PMID:28947979

The effectiveness of a saline mouth rinse regimen and education programme on radiation-induced oral mucositis and quality of life in oral cavity cancer patients: A randomised controlled trial.

PubMed

Huang, B-S; Wu, S-C; Lin, C-Y; Fan, K-H; Chang, J T-C; Chen, S-C

2018-03-01

Radiation therapy (RT) and concurrent chemotherapy RT (CCRT) generate radiation-induced oral mucositis (OM) and lower quality of life (QOL). This study assessed the impact of a saline mouth rinse regimen and education programme on radiation-induced OM symptoms, and QOL in oral cavity cancer (OCC) patients receiving RT or CCRT. Ninety-one OCC patients were randomly divided into a group that received saline mouth rinses and an education programme and a control group that received standard care. OM symptoms and QOL were assessed with the WHO Oral Toxicity Scale, MSS-moo and UW-QOL. Data were collected at the first postoperative visit to the radiation department (T0) and at 4 weeks and 8 weeks after beginning RT or CCRT. Patients in both groups had significantly higher levels of physical and social-emotional QOL at 8 weeks after beginning RT or CCRT compared to the first visit. Patients in the saline rinse group had significantly better physical and social-emotional QOL as compared to the standard care group at 8 weeks. Radiation-induced OM symptoms and overall QOL were not different between the groups. We thus conclude the saline rinse and education programme promote better physical and social-emotional QOL in OCC patients receiving RT/CCRT. © 2018 John Wiley & Sons Ltd.

Three-dimensional power Doppler ultrasound in the early assessment of response to concurrent chemo-radiotherapy for advanced cervical cancer.

PubMed

Xu, Yan; Zhu, Lijing; Ru, Tong; Wang, Huanhuan; He, Jian; Zhou, Zhengyang; Yang, Xiaofeng

2017-09-01

Background Three-dimensional power Doppler ultrasound (3D-PDU) imaging has been widely applied to the differentiation of benign and malignant cervical lesions; however, its potential value for predicting response to chemo-radiotherapy has not been fully explored. Purpose To investigate the feasibility of 3D-PDU imaging in predicting treatment response in patients receiving concurrent chemo-radiotherapy (CCRT) for advanced cervical cancer. Material and Methods Fifty-two patients with advanced cervical cancer who received CCRT underwent 3D-PDU examinations at four timepoints: pre-therapy (baseline), 1 week and 2 weeks during, as well as immediately post CCRT. Final tumor response was determined by change in tumor size using magnetic resonance imaging (MRI). Cervical tumor volumes and vascular indices were calculated and compared with the clinical outcome. Results Of the 52 patients, 32 patients who completed all four examinations were included in the analyses: 21 were classified as complete response (CR) and 11 as partial response (PR). During the treatment, the CR group showed that 3D vascular indices (VI and VFI) significantly increased at 1 week ( P = 0.028, P = 0.017, respectively) then decreased at 2 weeks and obviously decreased at therapy completion (both P < 0.001), whereas tumors significantly decreased in volume at 2 weeks after therapy initiation ( P < 0.05). However, no significant differences in 3D vascular indices values were seen in the PR group during the treatment course (all P > 0.05). Conclusion Prospective longitudinal 3D-PDU imaging may have potentials in monitoring early therapeutic response to CCRT in patients with cervical cancer.

Concurrent Chemoradiotherapy With Paclitaxel and Nedaplatin Followed by Consolidation Chemotherapy in Locally Advanced Squamous Cell Carcinoma of the Uterine Cervix: Preliminary Results of a Phase II Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang Meiqin, E-mail: pianozmq@hotmail.co; Liu Suping; Wang, Xiang-E.

Purpose: To evaluate the efficacy and toxicities of concurrent chemoradiotherapy (CCRT) and consolidation chemotherapy in patients with locally advanced squamous cell cervical carcinoma. Methods and Materials: Patients with LASCC (FIGO Stage IIB-IIIB) were treated with pelvic external beam radiotherapy (45 Gy for Stage IIB and 50 Gy for Stage III) and high-dose-rate intracavitary brachytherapy (50 Gy for Stage IIB and 35 Gy for Stage III). The cumulative dose at point A was 50 Gy for Stage IIB and 65 Gy for Stage III. Concurrent chemotherapy with paclitaxel (35 mg/m{sup 2}) and nedaplatin (20 mg/m{sup 2}) was given every week formore » 6 weeks. Consolidation chemotherapy with paclitaxel (135 mg/m{sup 2}) and nedaplatin (60 mg/m{sup 2}) was administered every 3 weeks for 4 cycles. Results: All patients completed CCRT, and 28 of 34 patients completed consolidation chemotherapy. The complete response rate was 88% (95% CI, 73-96%). The most common Grade 3 or higher toxicities were leukopenia/neutropenia (10.9% of the cycles). During a median follow up of 23 months (range, 14-30 months), 5 patients had locoregional failure and 1 patient had distant metastasis. The estimated 2-year progression-free survival and overall survival were 82% (95% CI, 68-95%) and 93% (95% CI, 83-100%), respectively. Grade 3 late complications occurred in 3 patients (9%). Conclusions: CCRT with paclitaxel and nedaplatin followed by consolidation chemotherapy is well tolerated and effective in patients with locally advanced squamous cell cervical carcinoma. Further randomized trials of comparing this regimen with the standard treatment are worth while.« less

DPYD, TYMS, TYMP, TK1, and TK2 Genetic Expressions as Response Markers in Locally Advanced Rectal Cancer Patients Treated with Fluoropyrimidine-Based Chemoradiotherapy

PubMed Central

Wu, Chan-Han; Huang, Chun-Ming; Chung, Fu-Yen; Huang, Ching-Wen; Tsai, Hsiang-Lin; Chen, Chin-Fan; Wang, Jaw-Yuan

2013-01-01

This study is to investigate multiple chemotherapeutic agent- and radiation-related genetic biomarkers in locally advanced rectal cancer (LARC) patients following fluoropyrimidine-based concurrent chemoradiotherapy (CCRT) for response prediction. We initially selected 6 fluoropyrimidine metabolism-related genes (DPYD, ORPT, TYMS, TYMP, TK1, and TK2) and 3 radiotherapy response-related genes (GLUT1, HIF-1 α, and HIF-2 α) as targets for gene expression identification in 60 LARC cancer specimens. Subsequently, a high-sensitivity weighted enzymatic chip array was designed and constructed to predict responses following CCRT. After CCRT, 39 of 60 (65%) LARC patients were classified as responders (pathological tumor regression grade 2 ~ 4). Using a panel of multiple genetic biomarkers (chip), including DPYD, TYMS, TYMP, TK1, and TK2, at a cutoff value for 3 positive genes, a sensitivity of 89.7% and a specificity of 81% were obtained (AUC: 0.915; 95% CI: 0.840–0.991). Negative chip results were significantly correlated to poor CCRT responses (TRG 0-1) (P = 0.014, hazard ratio: 22.704, 95% CI: 3.055–235.448 in multivariate analysis). Disease-free survival analysis showed significantly better survival rate in patients with positive chip results (P = 0.0001). We suggest that a chip including DPYD, TYMS, TYMP, TK1, and TK2 genes is a potential tool to predict response in LARC following fluoropyrimidine-based CCRT. PMID:24455740

Neoadjuvant irinotecan, cisplatin, and concurrent radiation therapy with celecoxib for patients with locally advanced esophageal cancer.

PubMed

Cleary, James M; Mamon, Harvey J; Szymonifka, Jackie; Bueno, Raphael; Choi, Noah; Donahue, Dean M; Fidias, Panos M; Gaissert, Henning A; Jaklitsch, Michael T; Kulke, Matthew H; Lynch, Thomas P; Mentzer, Steven J; Meyerhardt, Jeffrey A; Swanson, Richard S; Wain, John; Fuchs, Charles S; Enzinger, Peter C

2016-07-13

Patients with locally advanced esophageal cancer who are treated with trimodality therapy have a high recurrence rate. Preclinical evidence suggests that inhibition of cyclooxygenase 2 (COX2) increases the effectiveness of chemoradiation, and observational studies in humans suggest that COX-2 inhibition may reduce esophageal cancer risk. This trial tested the safety and efficacy of combining a COX2 inhibitor, celecoxib, with neoadjuvant irinotecan/cisplatin chemoradiation. This single arm phase 2 trial combined irinotecan, cisplatin, and celecoxib with concurrent radiation therapy. Patients with stage IIA-IVA esophageal cancer received weekly cisplatin 30 mg/m(2) plus irinotecan 65 mg/m(2) on weeks 1, 2, 4, and 5 concurrently with 5040 cGy of radiation therapy. Celecoxib 400 mg was taken orally twice daily during chemoradiation, up to 1 week before surgery, and for 6 months following surgery. Forty patients were enrolled with stage IIa (30 %), stage IIb (20 %), stage III (22.5 %), and stage IVA (27.5 %) esophageal or gastroesophageal junction cancer (AJCC, 5th Edition). During chemoradiation, grade 3-4 treatment-related toxicity included dysphagia (20 %), anorexia (17.5 %), dehydration (17.5 %), nausea (15 %), neutropenia (12.5 %), diarrhea (10 %), fatigue (7.5 %), and febrile neutropenia (7.5 %). The pathological complete response rate was 32.5 %. The median progression free survival was 15.7 months and the median overall survival was 34.7 months. 15 % (n = 6) of patients treated on this study developed brain metastases. The addition of celecoxib to neoadjuvant cisplatin-irinotecan chemoradiation was tolerable; however, overall survival appeared comparable to prior studies using neoadjuvant cisplatin-irinotecan chemoradiation alone. Further studies adding celecoxib to neoadjuvant chemoradiation in esophageal cancer are not warranted. Clinicaltrials.gov: NCT00137852 , registered August 29, 2005.

Nanomedicine in chemoradiation

PubMed Central

Miller, Seth M; Wang, Andrew Z

2013-01-01

Chemoradiotherapy, the concurrent administration of chemotherapy and radiotherapy, is a treatment paradigm in oncology. It is part of the standard of care and curative treatment of many cancers. Given its importance, one of the primary goals of cancer research has been to identify agents and/or strategies that can improve the therapeutic index of chemoradiation. Recent advances in nanomedicine have provided a unique and unprecedented opportunity for improving chemoradiotherapy. Nanoparticles possess properties that are ideally suited for delivering chemotherapy in the chemoradiation setting. The goal of this review is to examine the role of incorporating nanomedicine into chemoradiation and the potential impact of nanomedicine to chemoradiotherapy. PMID:23343162

Short-course versus long-course chemoradiation in rectal cancer--time to change strategies?

PubMed

Palta, Manisha; Willett, Christopher G; Czito, Brian G

2014-09-01

There is significant debate regarding the optimal neoadjuvant regimen for resectable rectal cancer patients. Short-course radiotherapy, a standard approach throughout most of northern Europe, is generally defined as 25 Gy in 5 fractions over the course of 1 week without the concurrent administration of chemotherapy. Long-course radiotherapy is typically defined as 45 to 50.4 Gy in 25-28 fractions with the administration of concurrent 5-fluoropyrimidine-based chemotherapy and is the standard approach in other parts of Europe and the United States. At present, two randomized trials have compared outcomes for short course radiotherapy with long-course chemoradiation showing no difference in respective study endpoints. Late toxicity data are lacking given limited follow-up. Although the ideal neoadjuvant regimen is controversial, our current bias is long-course chemoradiation to treat patients with locally advanced, resectable rectal cancer.

Incorporating Erlotinib or Irinotecan Plus Cisplatin into Chemoradiotherapy for Stage III Non-small Cell Lung Cancer According to EGFR Mutation Status.

PubMed

Lee, Youngjoo; Han, Ji-Youn; Moon, Sung Ho; Nam, Byung-Ho; Lim, Kun Young; Lee, Geon Kook; Kim, Heung Tae; Yun, Tak; An, Hye Jin; Lee, Jin Soo

2017-10-01

Concurrent chemoradiotherapy (CCRT) is the standard care for stage III non-small cell lung cancer (NSCLC) patients; however, a more effective regimen is needed to improve the outcome by better controlling occult metastases. We conducted two parallel randomized phase II studies to incorporate erlotinib or irinotecan-cisplatin (IP) into CCRT for stage III NSCLC depending on epidermal growth factor receptor (EGFR) mutation status. Patients with EGFR-mutant tumors were randomized to receive three cycles of erlotinib first and then either CCRT with erlotinib followed by erlotinib (arm A) or CCRT with IP only (arm B). Patients with EGFR unknown or wild-type tumors were randomized to receive either three cycles of IP before (arm C) or after CCRT with IP (arm D). Seventy-three patients were screened and the study was closed early because of slow accrual after 59 patients were randomized. Overall, there were seven patients in arm A, five in arm B, 22 in arm C, and 25 in arm D. The response rate was 71.4% and 80.0% for arm A and B, and 70.0% and 73.9% for arm C and D. The median overall survival (OS) was 39.3 months versus 31.2 months for arm A and B (p=0.442), and 16.3 months versus 25.3 months for arm C and D (p=0.050). Patients with sensitive EGFR mutations had significantly longer OS than EGFR-wild patients (74.8 months vs. 25.3 months, p=0.034). There were no unexpected toxicities. Combined-modality treatment by molecular diagnostics is feasible in stage III NSCLC. EGFR-mutant patients appear to be a distinct subset with longer survival.

Risk factors for pericardial effusion after chemoradiotherapy for thoracic esophageal cancer—comparison of four-field technique and traditional two opposed fields technique

PubMed Central

Takata, Noriko; Kataoka, Masaaki; Hamamoto, Yasushi; Tsuruoka, Shintaro; Kanzaki, Hiromitsu; Uwatsu, Kotaro; Nagasaki, Kei; Mochizuki, Teruhito

2018-01-01

Abstract Pericardial effusion is an important late toxicity after concurrent chemoradiotherapy (CCRT) for locally advanced esophageal cancer. We investigated the clinical and dosimetric factors that were related to pericardial effusion among patients with thoracic esophageal cancer who were treated with definitive CCRT using the two opposed fields technique (TFT) or the four-field technique (FFT), as well as the effectiveness of FFT. During 2007–2015, 169 patients with middle and/or lower thoracic esophageal cancer received definitive CCRT, and 94 patients were evaluable (51 FFT cases and 43 TFT cases). Pericardial effusion was observed in 74 patients (79%) and appeared at 1–18.5 months (median: 5.25 months) after CCRT. The 1-year incidences of pericardial effusions were 73.2% and 76.7% in the FFT and TFT groups, respectively (P = 0.6395). The mean doses to the pericardium were 28.6 Gy and 31.8 Gy in the FFT and TFT groups, respectively (P = 0.0259), and the V40 Gy proportions were 33.5% and 48.2% in the FFT and TFT groups, respectively (P < 0.0001). Grade 3 pericardial effusion was not observed in patients with a pericardial V40 Gy of <40%, or in patients who were treated using the FFT. Although the mean pericardial dose and V40 Gy in the FFT group were smaller than those in the TFT group, the incidences of pericardial effusion after CCRT were similar in both groups. As symptomatic pericardial effusion was not observed in patients with a pericardial V40 Gy of <40% or in the FFT group, it appears that FFT with a V40 Gy of <40% could help minimize symptomatic pericardial effusion. PMID:29659940

Risk factors for pericardial effusion after chemoradiotherapy for thoracic esophageal cancer-comparison of four-field technique and traditional two opposed fields technique.

PubMed

Takata, Noriko; Kataoka, Masaaki; Hamamoto, Yasushi; Tsuruoka, Shintaro; Kanzaki, Hiromitsu; Uwatsu, Kotaro; Nagasaki, Kei; Mochizuki, Teruhito

2018-05-01

Pericardial effusion is an important late toxicity after concurrent chemoradiotherapy (CCRT) for locally advanced esophageal cancer. We investigated the clinical and dosimetric factors that were related to pericardial effusion among patients with thoracic esophageal cancer who were treated with definitive CCRT using the two opposed fields technique (TFT) or the four-field technique (FFT), as well as the effectiveness of FFT. During 2007-2015, 169 patients with middle and/or lower thoracic esophageal cancer received definitive CCRT, and 94 patients were evaluable (51 FFT cases and 43 TFT cases). Pericardial effusion was observed in 74 patients (79%) and appeared at 1-18.5 months (median: 5.25 months) after CCRT. The 1-year incidences of pericardial effusions were 73.2% and 76.7% in the FFT and TFT groups, respectively (P = 0.6395). The mean doses to the pericardium were 28.6 Gy and 31.8 Gy in the FFT and TFT groups, respectively (P = 0.0259), and the V40 Gy proportions were 33.5% and 48.2% in the FFT and TFT groups, respectively (P < 0.0001). Grade 3 pericardial effusion was not observed in patients with a pericardial V40 Gy of <40%, or in patients who were treated using the FFT. Although the mean pericardial dose and V40 Gy in the FFT group were smaller than those in the TFT group, the incidences of pericardial effusion after CCRT were similar in both groups. As symptomatic pericardial effusion was not observed in patients with a pericardial V40 Gy of <40% or in the FFT group, it appears that FFT with a V40 Gy of <40% could help minimize symptomatic pericardial effusion.

Low thrombospondin 2 expression is predictive of low tumor regression after neoadjuvant chemoradiotherapy in rectal cancer.

PubMed

Lin, Cheng-Yi; Lin, Ching-Yih; Chang, I-Wei; Sheu, Ming-Jen; Li, Chien-Feng; Lee, Sung-Wei; Lin, Li-Ching; Lee, Ying-En; He, Hong-Lin

2015-01-01

Neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery is the mainstay of treatment for locally advanced rectal cancer. Several heparin-binding associated proteins have been reported to play a critical role in cancer progression. However, the clinical relevancies of such proteins and their associations with CCRT response in rectal cancer have not yet to be fully elucidated. The analysis of a public transcriptome of rectal cancer indicated that thrombospondin 2 (THBS2) is a predictive factor for CCRT response. Immunohistochemical analyses were conducted to evaluate the expression of THBS2 in pretreatment biopsy specimens from rectal cancer patients without distant metastasis. Furthermore, the relationships between THBS2 expression and various clinicopathological factors or survival were analyzed. Low expression of THBS2 was significantly associated with advanced pretreatment tumor (P<0.001) and nodal status (P=0.004), post-treatment tumor (P<0.001) and nodal status (P<0.001), increased vascular invasion (P=0.003), increased perineural invasion (P=0.023) and inferior tumor regression grade (P=0.015). In univariate analysis, low THBS2 expression predicted worse outcomes for disease-free survival, local recurrence-free survival and metastasis-free survival (all P<0.001). In multivariate analysis, low expression of THBS2 still served as a negative prognostic factor for disease-free survival (Hazard ratio=3.057, P=0.002) and metastasis-free survival (Hazard ratio=3.362, P=0.012). Low THBS2 expression was correlated with advanced disease status and low tumor regression after preoperative CCRT and that it acted as an independent negative prognostic factor in rectal cancer. THBS2 may represent a predictive biomarker for CCRT response in rectal cancer.

[Planned neck dissection in the treatment of locally advanced head and neck squamous cell carcinoma].

PubMed

Jiang, L; Lou, J L; Wang, K J; Fang, M Y; Fu, Z F

2018-02-07

Objective: To investigate the value of planned neck dissection combined with induction chemotherapy and concurrent chemoradiotherapy in regional control and the outcome of locally advanced head and neck squamous cell carcinoma. Methods: A prospective randomized controlled study totally enrolled sixty-four patients of head and neck squamous cell carcinomas(include oropharynx, hypopharynx, and larynx) in stages Ⅳa-Ⅳb with lymph node metastase was were N2-N3. All patients firstly received 2-3 cycles of induction chemotherapy(ICT), then divided into two groups randomly, according to the efficacy of ICT. Group A(the study group) received planned neck dissection(PND) and concurrent chemoradiotherapy(CCRT). Group B(the control group) received concurrent chemoradiotherapy(CCRT). The differences in clinicopathologic features, local recurrence(LR), regional recurrence(RR), disease-free survival(DFS), and overall survival(OS) between the two groups were estimated. SPSS 19.0 software was used to analyze the data. Results: Group A enrolled twenty-one patients, and group B enrolled forty-three patients.The follow-up of all patients were 4-55 months, median follow-up time was 22 months. In study group, two-year OS and DFS were 80.9% and 68.3%, respectively. In control group, two-year OS and DFS were 90.7% and 67.1%, respectively. There was no significant difference in gender( P =0.215), age( P =0.828), primary tumor site( P =0.927), LR( P =0.126), DFS( P =0.710), and OS( P =0.402) between the two groups, while the RR(χ(2)=5.640, P <0.05) and distant metastasis(χ(2)=10.363, P <0.01) showed significant differences between the two groups. Conclusion: The ICT+ PND+ CCRT treatment model has benefit on regional control of locally advanced head and neck squamous cell carcinoma.

Early tumor shrinkage served as a prognostic factor for patients with stage III non-small cell lung cancer treated with concurrent chemoradiotherapy.

PubMed

Wei, Min; Ye, Qingqing; Wang, Xuan; Wang, Men; Hu, Yan; Yang, Yonghua; Yang, Jiyuan; Cai, Jun

2018-05-01

Lung cancer is the most common cause of cancer death. About 80% of patients are diagnosed at stage III in the non-small cell lung cancer (NSCLC). It is extremely important to understand the progression of this disease which has low survival times despite the advancing treatment modalities. We aimed to investigate the relationship between early tumor shrinkage (ETS) after initial concurrent chemoradiotherapy (C-CRT) and survival outcome in patients with stage III (NSCLC). A retrospective review of 103 patients with stage III NSCLC who had received C-CRT from January 2006 to October 2011 was performed. Patients were treated with systemic chemotherapy regimen of Cisplatin/Vp-16 and concurrent thoracic radiotherapy at a median dose of 66 Gy (range 60-70 Gy). All patients received a computed tomography (CT) examination before treatment. Also subsequently, chest CT scans were performed with the same imaging parameters at approximately 5 weeks after the initiation of treatment. ETS is here stratified by a decrease in tumor size ≥30% and <30% in the longest dimension of the target lesion within 5 weeks. Of the 103 patients, 59 ones showed a 30% decrease in tumor size, and the rest displayed a decrease of <30%. ETS showed no significant correlation with age, T classification, N classification, histological classification, smoking status, G classification, EGFR status, or acute pulmonary toxicity. In the current retrospective clinical study, Kaplan-Meier curves showed that patients with ETS ≥ 30% had a better progression-free survival and overall survival. The univariate and multivariate Cox regression analyses indicated that ETS < 30% was associated with a significantly increased risk of cancer-related death (P < .05) in stage IIINSCLC. ETS may be served as a useful prognostic factor to predict the outcome of stage III NSCLC patients treated with CCRT.

Concurrent chemoradiotherapy with S-1 in patients with stage III-IV oral squamous cell carcinoma: A retrospective analysis of nodal classification based on the neck node level.

PubMed

Murakami, Ryuji; Semba, Akiko; Kawahara, Kenta; Matsuyama, Keiya; Hiraki, Akimitsu; Nagata, Masashi; Toya, Ryo; Yamashita, Yasuyuki; Oya, Natsuo; Nakayama, Hideki

2017-07-01

The aim of the present study was to retrospectively evaluate the treatment outcomes of concurrent chemoradiotherapy (CCRT) with S-1, an oral fluoropyrimidine anticancer agent, for advanced oral squamous cell carcinoma (SCC). The study population consisted of 47 patients with clinical stage III or IV oral SCC, who underwent CCRT with S-1. Pretreatment variables, including patient age, clinical stage, T classification, midline involvement of the primary tumor and nodal status, were analyzed as predictors of survival. In addition to the N classification (node-positive, multiple and contralateral), the prognostic impact of the level of nodal involvement was assessed. Nodal involvement was mainly observed at levels Ib and II; involvement at levels Ia and III-V was considered to be anterior and inferior extension, respectively, and was recorded as extensive nodal involvement (ENI). The 3-year overall survival (OS) and progression-free survival (PFS) rates were 37 and 27%, respectively. A finding of ENI was a significant factor for OS [hazard ratio (HR)=2.16; 95% confidence interval (CI): 1.03-4.55; P=0.038] and PFS (HR=2.65; 95% CI: 1.32-5.33; P=0.005); the 3-year OS and PFS rates in patients with vs. those without ENI were 23 vs. 50% and 9 vs. 43%, respectively. The other variables were not significant. Therefore, CCRT with S-1 may be an alternative treatment for advanced oral SCC; favorable outcomes are expected in patients without ENI.

Radiation therapy in the management of head-and-neck cancer of unknown primary origin: how does the addition of concurrent chemotherapy affect the therapeutic ratio?

PubMed

Chen, Allen M; Farwell, D Gregory; Lau, Derick H; Li, Bao-Qing; Luu, Quang; Donald, Paul J

2011-10-01

To determine how the addition of cisplatin-based concurrent chemotherapy to radiation therapy influences outcomes among a cohort of patients treated for head-and-neck cancer of unknown primary origin. The medical records of 60 consecutive patients treated by radiation therapy for squamous cell carcinoma of the head and neck presenting as cervical lymph node metastasis of occult primary origin were reviewed. Thirty-two patients (53%) were treated by concurrent chemoradiation, and 28 patients (47%) were treated by radiation therapy alone. Forty-five patients (75%) received radiation therapy after surgical resection, and 15 patients (25%) received primary radiation therapy. Thirty-five patients (58%) were treated by intensity-modulated radiotherapy. The 2-year estimates of overall survival, local-regional control, and progression-free survival were 89%, 89%, and 79%, respectively, among patients treated by chemoradiation, compared to 90%, 92%, and 83%, respectively, among patients treated by radiation therapy alone (p > 0.05, for all). Exploratory analysis failed to identify any subset of patients who benefited from the addition of concurrent chemotherapy to radiation therapy. The use of concurrent chemotherapy was associated with a significantly increased incidence of Grade 3+ acute and late toxicity (p < 0.001, for both). Concurrent chemoradiation is associated with significant toxicity without a clear advantage to overall survival, local-regional control, and progression-free survival in the treatment of head-and-neck cancer of unknown primary origin. Although selection bias cannot be ignored, prospective data are needed to further address this question. Copyright © 2011 Elsevier Inc. All rights reserved.

Beneficial Effects of Adjuvant Melatonin in Minimizing Oral Mucositis Complications in Head and Neck Cancer Patients Receiving Concurrent Chemoradiation.

PubMed

Onseng, Kittipong; Johns, Nutjaree Pratheepawanit; Khuayjarernpanishk, Thanut; Subongkot, Suphat; Priprem, Aroonsri; Hurst, Cameron; Johns, Jeffrey

2017-12-01

Oral mucositis is a major cause of pain and delayed cancer treatment leading to poor survival in head and neck cancer patients receiving concurrent chemoradiation. The study evaluated the effect of adjuvant melatonin on minimizing oral mucositis complications to reduce these treatment delays and interruptions. A randomized, double-blind, double dummy, placebo-controlled clinical trial. Ubon Ratchathani Cancer Hospital, Thailand. Thirty-nine head and neck cancer patients receiving concurrent chemoradiation (5 days/week of radiation plus chemotherapy three or six cycles). Patients were randomized to receive 20 mg melatonin gargle (or matched placebo) before each irradiation, and 20 mg melatonin capsules (or matched placebo) taken nightly during 7 weeks of concurrent chemoradiation. Endpoints were oral mucositis events (incidence and time to grade 3 mucositis or grade 2 xerostomia), pain medication consumption and quality of life (QOL). Melatonin group reported lower incidence of grade 3 oral mucositis (42% vs. 55%) and grade 2 xerostomia (20% vs. 21%); no statistical significance was detected. Melatonin regimen delayed onset of grade 3 mucositis (median 34 days vs. 50 days; p = 0.0318), allowing median time of 16 more patient visits before its onset and fewer interrupted treatments due to oral mucositis were reported (n = 1 vs. n = 5). There was no difference of grade 2 xerostomia (median 32 days vs. 50 days; p = 0.624). Morphine consumption was also reduced (median 57 mg vs. 0 mg; p = 0.0342), while QOL was comparable during the study period. Adjuvant melatonin delayed the onset of oral mucositis, which enables uninterrupted cancer treatment and reduced the amount of morphine used for pain treatment.

Development of symptomatic brain metastases after chemoradiotherapy for stage III non-small cell lung cancer: Does the type of chemotherapy regimen matter?

PubMed

Hendriks, Lizza E L; Brouns, Anita J W M; Amini, Mohammad; Uyterlinde, Wilma; Wijsman, Robin; Bussink, Jan; Biesma, Bonne; Oei, S Bing; Stigt, Jos A; Bootsma, Gerben P; Belderbos, José S A; De Ruysscher, Dirk K M; Van den Heuvel, Michel M; Dingemans, Anne-Marie C

2016-11-01

Symptomatic brain metastases (BM) occur frequently after chemoradiotherapy (CRT) for stage III NSCLC. Aim of the current study was to determine whether the specific chemotherapy used in a CRT regimen influences BM development. Retrospective multicenter study including all consecutive stage III NSCLC who completed CRT. Primary endpoints: symptomatic BM development, whether this was the only site of first relapse. Differences between regimens were assessed with a logistic regression model including known BM risk factors and the specific chemotherapy: concurrent versus sequential (cCRT/sCRT), within cCRT: daily low dose cisplatin (LDC)-cyclic dose polychemotherapy; LDC-(non-)taxane cyclic dose; LDC-polychemotherapy subgroups of ≥50 patients. Between January 2006 and June 2014, 838 patients were eligible (737 cCRT, 101 sCRT). 18.2% developed symptomatic BM, 8.0% had BM as only site of first relapse. BM patients were significantly younger, female, had more advanced N-stage and had adenocarcinoma histology. In both cCRT and sCRT BM were found in 18% (p=0.904). In cyclic dose cCRT (N=346) and LDC (N=391) BM were found in 18.8% and 17.9%, respectively (p=0.757). In 7.2% and 8.7%, respectively, BM were the only site of first relapse (p=0.463). The chemotherapy used (cCRT versus sCRT) had no influence on BM development, not for all brain relapses nor as only site of first relapse (OR 0.88 (p=0.669), OR 0.93 (p=0.855), respectively). LDC versus cyclic dose cCRT was not significantly different: neither for all brain relapses nor as only site of first relapse (OR 0.96 (p=0.819), OR 1.21 (p=0.498), respectively). Comparable results were found for LDC versus cyclic dose non-taxane (N=277) and cyclic dose taxane regimens (N=69) and for cCRT regimens with ≥50 patients (LDC versus cisplatin/etoposide (N=188), cisplatin/vinorelbin (N=65), weekly cisplatin/docetaxel (N=60)). approximately 18% developed symptomatic BM after stage III diagnosis, not dependent on type of chemotherapy regimen used within a CRT treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effectiveness of esophagectomy in patients with thoracic esophageal squamous cell carcinoma receiving definitive radiotherapy or concurrent chemoradiotherapy through intensity-modulated radiation therapy techniques.

PubMed

Yen, Yu-Chun; Chang, Jer-Hwa; Lin, Wei-Cheng; Chiou, Jeng-Fong; Chang, Yin-Chun; Chang, Chia-Lun; Hsu, Han-Lin; Chow, Jyh-Ming; Yuan, Kevin Sheng-Po; Wu, Alexander T H; Wu, Szu-Yuan

2017-06-01

Few large, prospective, randomized studies have investigated the effectiveness of esophagectomy in patients with thoracic esophageal squamous cell carcinoma (TESCC) who receive definitive radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) through modern, intensity modulated-RT (IMRT) techniques. The therapeutic effects of esophagectomy in patients with TESCC were evaluated using modern clinical staging and RT techniques and suitable RT doses. The authors analyzed data from patients with TESCC from the Taiwan Cancer Registry database. Patients were categorized into the following groups on the basis of treatment modality to compare their outcomes: group 1 received definitive CCRT, group 2 received neoadjuvant RT followed by esophagectomy (total IMRT dose, ≥50 grays [Gy]), and group 3 receiving neoadjuvant CCRT followed by esophagectomy (total IMRT dose, ≥ 50 Gy). The median total RT dose and fraction size were 50.4 Gy and 1.8 Gy per fraction, respectively. Group 1 was used as the control arm for investigating the risk of mortality after treatment. In total, 3123 patients who had TESCC without distant metastasis were enrolled. Patient ages 65 years and older, Charlson comorbidity index scores ≥3, advanced clinical stages (IIA-IIIC), alcohol consumption, and cigarette smoking were identified as significant, independent poor prognostic risk factors for overall survival in multivariate Cox regression analyses. In group 3, after adjustment for confounders, the adjusted hazard ratios (95% confidence intervals [CIs]) for overall mortality were 0.62 (95% CI, 0.41-0.93) for patients with clinical stage IIA disease, 0.61 (95% CI, 0.41-0.91) for those with clinical stage IIB disease, 0.47 (95% CI, 0.38-0.55) for those with clinical stage IIIA disease, 0.47 (95% CI, 0.39-0.56) for those with clinical stage IIIB disease, and 0.46 (95% CI, 0.37-0.57) for those with clinical stage IIIC disease. Esophagectomy can be beneficial in patients with TESCC after definitive CCRT, especially in those who have advanced-stage disease. Cancer 2017;123:2043-2053. © 2017 American Cancer Society. © 2017 American Cancer Society.

A Contralateral Esophagus-Sparing Technique to Limit Severe Esophagitis Associated With Concurrent High-Dose Radiation and Chemotherapy in Patients With Thoracic Malignancies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Al-Halabi, Hani; Paetzold, Peter; Sharp, Gregory C.

2015-07-15

Purpose: Severe (Radiation Therapy Oncology Group [RTOG] grade 3 or greater) esophagitis generally occurs in 15% to 25% of non–small cell lung cancer (NSCLC) patients undergoing concurrent chemotherapy and radiation therapy (CCRT), which may result in treatment breaks that compromise local tumor control and pose a barrier to dose escalation. Here, we report a novel contralateral esophagus-sparing technique (CEST) that uses intensity modulated radiation therapy (IMRT) to reduce the incidence of severe esophagitis. Methods and Materials: We reviewed consecutive patients with thoracic malignancies undergoing curative CCRT in whom CEST was used. The esophageal wall contralateral (CE) to the tumor wasmore » contoured as an avoidance structure, and IMRT was used to guide a rapid dose falloff gradient beyond the target volume in close proximity to the esophagus. Esophagitis was recorded based on the RTOG acute toxicity grading system. Results: We identified 20 consecutive patients treated with CCRT of at least 63 Gy in whom there was gross tumor within 1 cm of the esophagus. The median radiation dose was 70.2 Gy (range, 63-72.15 Gy). In all patients, ≥99% of the planning and internal target volumes was covered by ≥90% and 100% of prescription dose, respectively. Strikingly, no patient experienced grade ≥3 esophagitis (95% confidence limits, 0%-16%) despite the high total doses delivered. The median maximum dose, V45, and V55 of the CE were 60.7 Gy, 2.1 cc, and 0.4 cc, respectively, indicating effective esophagus cross-section sparing by CEST. Conclusion: We report a simple yet effective method to avoid exposing the entire esophagus cross-section to high doses. By using proposed CE dose constraints of V45 <2.5 cc and V55 <0.5 cc, CEST may improve the esophagus toxicity profile in thoracic cancer patients receiving CCRT even at doses above the standard 60- to 63-Gy levels. Prospective testing of CEST is warranted.« less

Radiation Therapy in the Management of Head-and-Neck Cancer of Unknown Primary Origin: How Does the Addition of Concurrent Chemotherapy Affect the Therapeutic Ratio?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Allen M., E-mail: allen.chen@ucdmc.ucdavis.edu; Farwell, D. Gregory; Lau, Derick H.

2011-10-01

Purpose: To determine how the addition of cisplatin-based concurrent chemotherapy to radiation therapy influences outcomes among a cohort of patients treated for head-and-neck cancer of unknown primary origin. Methods and Materials: The medical records of 60 consecutive patients treated by radiation therapy for squamous cell carcinoma of the head and neck presenting as cervical lymph node metastasis of occult primary origin were reviewed. Thirty-two patients (53%) were treated by concurrent chemoradiation, and 28 patients (47%) were treated by radiation therapy alone. Forty-five patients (75%) received radiation therapy after surgical resection, and 15 patients (25%) received primary radiation therapy. Thirty-five patientsmore » (58%) were treated by intensity-modulated radiotherapy. Results: The 2-year estimates of overall survival, local-regional control, and progression-free survival were 89%, 89%, and 79%, respectively, among patients treated by chemoradiation, compared to 90%, 92%, and 83%, respectively, among patients treated by radiation therapy alone (p > 0.05, for all). Exploratory analysis failed to identify any subset of patients who benefited from the addition of concurrent chemotherapy to radiation therapy. The use of concurrent chemotherapy was associated with a significantly increased incidence of Grade 3+ acute and late toxicity (p < 0.001, for both). Conclusions: Concurrent chemoradiation is associated with significant toxicity without a clear advantage to overall survival, local-regional control, and progression-free survival in the treatment of head-and-neck cancer of unknown primary origin. Although selection bias cannot be ignored, prospective data are needed to further address this question.« less

Impact of the early detection of esophageal neoplasms in hypopharyngeal cancer patients treated with concurrent chemoradiotherapy.

PubMed

Watanabe, Shigenobu; Ogino, Ichiro; Inayama, Yoshiaki; Sugiura, Madoka; Sakuma, Yasunori; Kokawa, Atsushi; Kunisaki, Chikara; Inoue, Tomio

2017-04-01

We examined the risk factors and prognostic factors for synchronous esophageal neoplasia (SEN) by comparing the characteristics of hypopharyngeal cancer (HPC) patients with and without SEN. We examined 183 patients who were treated with definitive radiotherapy for HPC. Lugol chromoendoscopy screening of the esophagus was performed in all patients before chemoradiotherapy. Thirty-six patients had SEN, 49 patients died of HPC and two died of esophageal cancer. The patients with SEN exhibited significantly higher alcohol consumption than those without SEN (P = 0.018). The 5-year overall survival (OS) rate of the 36 patients with SEN was lower than that of the other patients (36.2% vs 63.4%, P = 0.006). The SEN patients exhibited significantly shorter HPC cause-specific survival than the other patients (P = 0.039). Both the OS (P = 0.005) and the HPC cause-specific survival (P = 0.026) of the patients with SEN were significantly shorter than those of the patients without SEN in multivariate analysis. Category 4/T1 stage esophageal cancer was treated with concurrent chemoradiotherapy (CCRT), endoscopic treatment or chemotherapy. The 5-year survival rates for esophageal cancer recurrence for CCRT, endoscopic treatment and chemotherapy were 71.5, 43.7 and 0%, respectively. The median (range) survival time (months) of CCRT, endoscopic treatment and chemotherapy was 22.7 (7.5-90.6), 46.44 (17.3-136.7) and 7.98 (3.72-22.8), respectively. Advanced HPC patients with SEN might have a poorer prognosis than those without SEN even when the esophageal cancer is detected early and managed appropriately. © 2014 Wiley Publishing Asia Pty Ltd.

Phase I trial of adoptively transferred tumor-infiltrating lymphocyte immunotherapy following concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma

PubMed Central

Li, Jiang; Chen, Qiu-Yan; He, Jia; Li, Ze-Lei; Tang, Xiao-Feng; Chen, Shi-Ping; Xie, Chuan-Miao; Li, Yong-Qiang; Huang, Li-Xi; Ye, Shu-bio; Ke, Miao-La; Tang, Lin-Quan; Liu, Huai; Zhang, Lu; Guo, Shan-Shan; Xia, Jian-Chuan; Zhang, Xiao-Shi; Zheng, Li-Min; Guo, Xiang; Qian, Chao-Nan; Mai, Hai-Qiang; Zeng, Yi-Xin

2015-01-01

Adoptive cell therapy (ACT) for cancers using autologous tumor-infiltrating lymphocytes (TILs) can induce immune responses and antitumor activity in metastatic melanoma patients. Here, we aimed to assess the safety and antitumor activity of ACT using expanded TILs following concurrent chemoradiotherapy (CCRT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC). Twenty-three newly diagnosed, locoregionally advanced NPC patients were enrolled, of whom 20 received a single-dose of TIL infusion following CCRT. All treated patients were assessed for toxicity, survival and clinical and immunologic responses. Correlations between immunological responses and treatment effectiveness were further studied. Only mild adverse events (AEs), including Grade 3 neutropenia (1/23, 5%) consistent with immune-related causes, were observed. Nineteen of 20 patients exhibited an objective antitumor response, and 18 patients displayed disease-free survival longer than 12 mo after ACT. A measurable plasma Epstein–Barr virus (EBV) load was detected in 14 patients at diagnosis, but a measurable EBV load was not found in patients after one week of ACT, and the plasma EBV load remained undetectable in 17 patients at 6 mo after ACT. Expansion and persistence of T cells specific for EBV antigens in peripheral blood following TIL therapy were observed in 13 patients. The apparent positive correlation between tumor regression and the expansion of T cells specific for EBV was further investigated in four patients. This study shows that NPC patients can tolerate ACT with TILs following CCRT and that this treatment results in sustained antitumor activity and anti-EBV immune responses. A larger phase II trial is in progress. PMID:25949875

Predictive relevance of PD-L1 expression combined with CD8+ TIL density in stage III non-small cell lung cancer patients receiving concurrent chemoradiotherapy.

PubMed

Tokito, Takaaki; Azuma, Koichi; Kawahara, Akihiko; Ishii, Hidenobu; Yamada, Kazuhiko; Matsuo, Norikazu; Kinoshita, Takashi; Mizukami, Naohisa; Ono, Hirofumi; Kage, Masayoshi; Hoshino, Tomoaki

2016-03-01

Expression of programmed cell death-ligand 1 (PD-L1) is known to be a mechanism whereby cancer can escape immune surveillance, but little is known about factors predictive of efficacy in patients with locally advanced non-small cell lung cancer (NSCLC). We investigated the predictive relevance of PD-L1 expression and CD8+ tumour-infiltrating lymphocytes (TILs) density in patients with locally advanced NSCLC receiving concurrent chemoradiotherapy (CCRT). We retrospectively reviewed 74 consecutive patients with stage III NSCLC who had received CCRT. PD-L1 expression and CD8+ TIL density were evaluated by immunohistochemical analysis. Univariate and multivariate analyses demonstrated that CD8+ TIL density was an independent and significant predictive factor for progression-free survival (PFS) and OS, whereas PD-L1 expression was not correlated with PFS and OS. Sub-analysis revealed that the PD-L1+/CD8 low group had the shortest PFS (8.6 months, p = 0.02) and OS (13.9 months, p = 0.11), and that the PD-L1-/CD8 high group had the longest prognosis (median PFS and OS were not reached) by Kaplan-Meier curves of the four sub-groups. Among stage III NSCLC patients who received CCRT, there was a trend for poor survival in those who expressed PD-L1. Our analysis indicated that a combination of lack of PD-L1 expression and CD8+ TIL density was significantly associated with favourable survival in these patients. It is proposed that PD-L1 expression in combination with CD8+ TIL density could be a useful predictive biomarker in patients with stage III NSCLC. Copyright © 2015 Elsevier Ltd. All rights reserved.

Early disease progression in patients with localized natural killer/T-cell lymphoma treated with concurrent chemoradiotherapy.

PubMed

Yamaguchi, Motoko; Suzuki, Ritsuro; Kim, Seok Jin; Ko, Young Hyeh; Oguchi, Masahiko; Asano, Naoko; Miyazaki, Kana; Terui, Yasuhiko; Kubota, Nobuko; Maeda, Takeshi; Kobayashi, Yukio; Amaki, Jun; Soejima, Toshinori; Saito, Bungo; Shimoda, Emiko; Fukuhara, Noriko; Tsukamoto, Norifumi; Shimada, Kazuyuki; Choi, Ilseung; Utsumi, Takahiko; Ejima, Yasuo; Kim, Won Seog; Katayama, Naoyuki

2018-03-30

Prognosis of patients with localized nasal extranodal natural killer/T-cell lymphoma, nasal type (ENKL) has been improved by non-anthracycline-containing treatments such as concurrent chemoradiotherapy (CCRT). However, some patients experience early disease progression. To clarify the clinical features and outcomes of these patients, data from 165 patients with localized nasal ENKL who were diagnosed between 2000 and 2013 at 31 institutes in Japan and who received radiotherapy with dexamethasone, etoposide, ifosfamide, and carboplatin (RT-DeVIC) were retrospectively analyzed. Progression of disease within 2 years after diagnosis (POD24) was used as the definition of early progression. An independent dataset of 60 patients with localized nasal ENKL who received CCRT at Samsung Medical Center was used in the validation analysis. POD24 was documented in 23% of patients who received RT-DeVIC and in 25% of patients in the validation cohort. Overall survival (OS) from risk-defining events of the POD24 group was inferior to that of the reference group in both cohorts (P < .00001). In the RT-DeVIC cohort, pretreatment elevated levels of serum soluble interleukin-2 receptor (sIL-2R), lactate dehydrogenase, C-reactive protein, and detectable Epstein-Barr virus DNA in peripheral blood were associated with POD24. In the validation cohort, no pretreatment clinical factor associated with POD24 was identified. Our study indicates that POD24 is a strong indicator of survival in localized ENKL, despite the different CCRT regimens adopted. In the treatment of localized nasal ENKL, POD24 is useful for identifying patients who have unmet medical needs. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

A Phase II Study of a Paclitaxel-Based Chemoradiation Regimen With Selective Surgical Salvage for Resectable Locoregionally Advanced Esophageal Cancer: Initial Reporting of RTOG 0246

DOE Office of Scientific and Technical Information (OSTI.GOV)

Swisher, Stephen G., E-mail: sswisher@mdanderson.org; Winter, Kathryn A.; Komaki, Ritsuko U.

2012-04-01

Purpose: The strategy of definitive chemoradiation with selective surgical salvage in locoregionally advanced esophageal cancer was evaluated in a Phase II trial in Radiation Therapy Oncology Group (RTOG)-affiliated sites. Methods and Materials: The study was designed to detect an improvement in 1-year survival from 60% to 77.5% ({alpha} = 0.05; power = 80%). Definitive chemoradiation involved induction chemotherapy with 5-fluorouracil (5-FU) (650 mg/mg{sup 2}/day), cisplatin (15 mg/mg{sup 2}/day), and paclitaxel (200 mg/mg{sup 2}/day) for two cycles, followed by concurrent chemoradiation with 50.4 Gy (1.8 Gy/fraction) and daily 5-FU (300 mg/mg{sup 2}/day) with cisplatin (15 mg/mg{sup 2}/day) over the first 5more » days. Salvage surgical resection was considered for patients with residual or recurrent esophageal cancer who did not have systemic disease. Results: Forty-three patients with nonmetastatic resectable esophageal cancer were entered from Sept 2003 to March 2006. Forty-one patients were eligible for analysis. Clinical stage was {>=}T3 in 31 patients (76%) and N1 in 29 patients (71%), with adenocarcinoma histology in 30 patients (73%). Thirty-seven patients (90%) completed induction chemotherapy followed by concurrent chemoradiation. Twenty-eight patients (68%) experienced Grade 3+ nonhematologic toxicity. Four treatment-related deaths were noted. Twenty-one patients underwent surgery following definitive chemoradiation because of residual (17 patients) or recurrent (3 patients) esophageal cancer,and 1 patient because of choice. Median follow-up of live patients was 22 months, with an estimated 1-year survival of 71%. Conclusions: In this Phase II trial (RTOG 0246) evaluating selective surgical salvage after definitive chemoradiation in locoregionally advanced esophageal cancer, the hypothesized 1-year RTOG survival rate (77.5%) was not achieved (1 year, 71%; 95% confidence interval< 54%-82%).« less

High Expression of Aldolase B Confers a Poor Prognosis for Rectal Cancer Patients Receiving Neoadjuvant Chemoradiotherapy.

PubMed

Tian, Yu-Feng; Hsieh, Pei-Ling; Lin, Ching-Yih; Sun, Ding-Ping; Sheu, Ming-Jen; Yang, Ching-Chieh; Lin, Li-Ching; He, Hong-Lin; Solórzano, Julia; Li, Chien-Feng; Chang, I-Wei

2017-01-01

Background : Colorectal cancer is the third most common cancer in both sex worldwide and it is also the fourth most common cause of cancer mortality. For rectal cancer, neoadjuvant concurrent chemoradiotherapy (CCRT) followed by radical proctectomy is gold standard treatment for patients with stage II/III rectal cancer. By data mining a documented database of rectal cancer transcriptome (GSE35452) from Gene Expression Omnibus, National Center of Biotechnology Information, we recognized that ALDOB was the most significantly up-regulated transcript among those related to glycolysis (GO: 0006096). Hence, we analyzed the clinicopathological correlation and prognostic effect of ALDOB protein (Aldolase B), which encoded by ALDOB gene. Methods : ALDOB immunostain was performed in 172 rectal adenocarcinomas treated with preoperative chemoradiotherapy followed by radical surgery, which were divided into high- and low-expression groups. Furthermore, statistical analyses were examined to correlate the relationship between ALDOB immunoreactivity and important clinical and pathological characteristics, as well as three survival indices: disease-specific survival (DSS), local recurrence-free survival (LRFS) and metastasis-free survival (MeFS). Results : ALDOB (Aldolase B) over-expression was significantly associated with pre-CCRT and post-CCRT tumor advancement, lymphovascular invasion, perineural invasion and poor response to CCRT (all P ≤ .023). In addition, ALDOB high expression was linked to adverse DSS, LRFS and MeFS in univariate analysis ( P ≤ .0075) and also served as an independent prognosticator indicating dismal DSS and MeFS in multivariate analysis (hazard ratio (HR) = 3.462, 95% confidence interval (CI): 1.263-9.495; HR = 2.846, 95% CI: 1.190-6.808, respectively). Conclusion : ALDOB (Aldolase B) may play an imperative role in rectal cancer progression and responsiveness to neoadjuvant CCRT, and serve as a novel prognostic biomarker. Additional researches to clarify the molecular and biochemical pathways are essential for developing promising ALDOB-targeted therapies for patients with rectal cancers.

Long-term follow-up and salvage surgery in patients with T2N0M0 squamous cell carcinoma of the glottic larynx who received concurrent chemoradiation therapy with carboplatin (CBDCA) - AUC 1.5 vs AUC 2.0.

PubMed

Furusaka, Tohru; Matsuda, Hiroshi; Saito, Tsutomu; Katsura, Yoshihisa; Ikeda, Minoru

2012-11-01

Patients who received concurrent chemoradiation therapy with carboplatin were followed up on a long-term basis. In 25 patients treated with carboplatin at an AUC of 2.0 mg/ml, the complete response (CR), 10-year survival, and 10-year larynx preservation rates were 96.0%, 91.1%, and 75.2%, respectively, and the safety margin for partial laryngectomy was 4 mm from the gross tumor. To perform long-term follow-up of the therapeutic outcomes of concurrent chemoradiation therapy and salvage surgery to determine the additive and synergistic effects of anticancer drugs combined with chemoradiotherapy. Fifty male patients (aged 33-76 years) with untreated T2N0M0 squamous cell carcinoma of the glottic larynx were included. Carboplatin was intravenously administered once a week for 4 weeks. Radiotherapy was delivered by an external beam of 4 MV linac X-ray (total = 66 Gy). The AUC 1.5 combination group showed overall response, CR, 5-year survival, 10-year survival, 5-year larynx preservation, and 10-year larynx preservation rates of 100.0%, 68.0%, 83.4%, 77.0%, 75.2%, and 75.2%, respectively. The AUC 2.0 combination group showed corresponding rates of 100%, 96.0%, 95.7%, 91.1%, 82.9%, and 72.7%, respectively. The most common side effects of grade 3 or more were leukopenia, neutropenia, and mucositis (stomatitis), and all were reversible. Thirteen patients (52.0%) in the AUC 1.5 combination group and nine patients (36.0%) in the AUC 2.0 combination group required salvage surgery. Histologically, concurrent chemoradiation therapy with carboplatin caused more severe cancer tissue degeneration. Pathological examinations indicated that the safety margin for partial laryngectomy was 4 mm from the gross tumor.

Treating Locally Advanced Cervical Cancer With Concurrent Chemoradiation Without Brachytherapy in Low-resource Countries.

PubMed

Chuang, Linus; Kanis, Margaux J; Miller, Brigitte; Wright, Jason; Small, William; Creasman, William

2016-02-01

To summarize the literature on options of management of patients treated for locally advanced cervical cancers with a specific focus on resource-constrained settings where brachytherapy is not available. A Medline search was performed to summarize studies about treatment approaches including neoadjuvant chemotherapy, primary surgery for bulky cervical cancer, and chemoradiation followed by surgery. Summaries are by treatment approaches that are relevant to resource-constrained settings. There are a lack of studies performed on neoadjuvant chemotherapy in low-resource settings. Primary surgery followed by chemoradiation therapy for selected patients with bulky cervical cancer is a feasible option. The disadvantage is the potential increase in treatment complications. Chemoradiation without brachytherapy followed by surgery has been found to have equivalent outcomes and is associated with acceptable morbidity. In resource-constrained settings where brachytherapy is not available, performing radical hysterectomy after chemoradiation therapy without brachytherapy has been shown to produce equivalent outcomes. It seems reasonable to adopt a modified therapeutic protocol of chemoradiation followed by extrafascial hysterectomy as an alternative treatment option in low-resource countries where brachytherapy is not readily available.

Weekly Cisplatin-Based Concurrent Chemoradiotherapy for Treatment of Locally Advanced Head and Neck Cancer: a Single Institution Study.

PubMed

Ghosh, Saptarshi; Rao, Pamidimukkala Brahmananda; Kumar, P Ravindra; Manam, Surendra

2015-01-01

The organ preservation approach of choice for the treatment of locally advanced head and neck cancers is concurrent chemoradiation with three weekly high doses of cisplatin. Although this is an efficacious treatment policy, it has high acute systemic and mucosal toxicities, which lead to frequent treatment breaks and increased overall treatment time. Hence, the current study was undertaken to evaluate the efficacy of concurrent chemoradiation using 40 mg/m2 weekly cisplatin. This is a single institutional retrospective study including the data of 266 locally advanced head and neck cancer patients who were treated with concurrent chemoradiation using 40 mg/m2 weekly cisplatin from January 2012 to January 2014. A p-value of < 0.05 was taken to be significant statistically for all purposes in the study. The mean age of the study patients was 48.8 years. Some 36.1% of the patients had oral cavity primary tumors. The mean overall treatment time was 57.2 days. With a mean follow up of 15.2 months for all study patients and 17.5 months for survivors, 3 year local control, locoregional control and disease free survival were seen in 62.8%, 42.8% and 42.1% of the study patients. Primary tumor site, nodal stage of disease, AJCC stage of the disease and number of cycles of weekly cisplatin demonstrated statistically significant correlations with 3 year local control, locoregional control and disease free survival. Concurrent chemoradiotherapy with moderate dose weekly cisplatin is an efficacious treatment regime for locally advanced head and neck cancers with tolerable toxicity which can be used in developing countries with limited resources.

Neoadjuvant Bevacizumab, Oxaliplatin, 5-Fluorouracil, and Radiation for Rectal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dipetrillo, Tom; Pricolo, Victor; Lagares-Garcia, Jorge

Purpose: To evaluate the feasibility and pathologic complete response rate of induction bevacizumab + modified infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) 6 regimen followed by concurrent bevacizumab, oxaliplatin, continuous infusion 5-fluorouracil (5-FU), and radiation for patients with rectal cancer. Methods and Materials: Eligible patients received 1 month of induction bevacizumab and mFOLFOX6. Patients then received 50.4 Gy of radiation and concurrent bevacizumab (5 mg/kg on Days 1, 15, and 29), oxaliplatin (50 mg/m{sup 2}/week for 6 weeks), and continuous infusion 5-FU (200 mg/m{sup 2}/day). Because of gastrointestinal toxicity, the oxaliplatin dose was reduced to 40 mg/m{sup 2}/week. Resection was performedmore » 4-8 weeks after the completion of chemoradiation. Results: The trial was terminated early because of toxicity after 26 eligible patients were treated. Only 1 patient had significant toxicity (arrhythmia) during induction treatment and was removed from the study. During chemoradiation, Grade 3/4 toxicity was experienced by 19 of 25 patients (76%). The most common Grade 3/4 toxicities were diarrhea, neutropenia, and pain. Five of 25 patients (20%) had a complete pathologic response. Nine of 25 patients (36%) developed postoperative complications including infection (n = 4), delayed healing (n = 3), leak/abscess (n = 2), sterile fluid collection (n = 2), ischemic colonic reservoir (n = 1), and fistula (n = 1). Conclusions: Concurrent oxaliplatin, bevacizumab, continuous infusion 5-FU, and radiation causes significant gastrointestinal toxicity. The pathologic complete response rate of this regimen was similar to other fluorouracil chemoradiation regimens. The high incidence of postoperative wound complications is concerning and consistent with other reports utilizing bevacizumab with chemoradiation before major surgical resections.« less

Concurrent chemoradiotherapy with elective lymph node irradiation for esophageal cancer: a systemic review and pooled analysis of the literature.

PubMed

Du, Dexi; Song, Tao; Liang, Xiaodong; Fang, Min; Wu, Shixiu

2017-02-01

Concurrent chemoradiotherapy (CCRT) has been accepted as the standard non-surgical treatment for esophageal cancer. However, no consistent conclusions have been reached whether elective lymph node irradiation (ENI) should be delivered. Therefore, we performed a systematic review and pooled analysis to evaluate the value of CCRT with ENI. A literature search based on PubMed, Embase and Google Scholar was carried out and all of the studies were evaluated carefully regarding with survival outcomes, response rates, patterns of failure rates and acute/late toxicities. Twenty-two studies were identified based on the criteria: median overall survival time was 21.0 months; pooled response rates were 56.8% (CR) and 85.8% (CR+PR), respectively; residual disease rate, local-regional recurrence rate, distant failure rate and both (local-regional recurrence plus distant failure) rate was 28%, 21%, 11%, and 7%, respectively; hematologic toxicities were the most sever acute toxicities and esophagus-related toxicity was the most common radiation-related toxicity both in acute (15.7%) and late (6.2%) phase. In conclusion, ENI is feasible with acceptable toxicities in esophageal carcinoma and the efficacy should be verified in randomized trials. © 2016 International Society for Diseases of the Esophagus.

Phase II study of preoperative concurrent chemoradiotherapy with oxaliplatin for locally advanced esophageal cancer.

PubMed

Huang, Jing-Wen; Yeh, Hui-Ling; Hsu, Chung-Ping; Chuang, Cheng-Yen; Lin, Jin-Ching; Lin, Jai-Fu; Chang, Chen-Fa

2017-07-01

We investigated preoperative concurrent chemoradiotherapy (CCRT) with oxaliplatin for locally advanced, potentially operative esophageal cancer in this Phase II study. Between October 2009 and October 2011, 35 consecutive patients with newly diagnosed esophageal cancer clinical stage T3-4, N0-1, M0 were enrolled into this study. One dose of chemotherapy with oxaliplatin (35 mg/m 2 ) on Day 1 and Day 2, leucovorin (200 mg/m 2 ) on Day 1, and 5-fluorouracil [5-FU; 2400 mg/m 2 intravenously (i.v.) administered continuously for 48 hours] on Day 1 was administered 2 weeks before preoperative CCRT. During preoperative CCRT, radiation dose of 4500 cGy in 25 fractions was administered to the clinical target volume and 5000 cGy to 5040 cGy in 25 fractions was administered to the gross tumor volume; chemotherapy is administered concomitantly with oxaliplatin (45 mg/m 2 ) on Day 1 of radiation therapy (R/T) every 14 days; 5-FU (400 mg/m 2 i.v. bolus for 1 hour) for 5 days on Weeks 1 and 5 of R/T. Operation was performed 4-6 weeks after preoperative CCRT. Acute toxicity profile, overall survival rate, disease-free survival rate, distant metastasis failure-free survival rate, and local recurrence rate were evaluated. Four patients withdrew from the study. The total number of patients in this analysis was 31. The resection rate was 64.5%. The pathologic complete response rate was 15%. The overall median survival was 19.3 months. The 5-year overall survival rate was 37.8%. The 5-year disease-free survival rate was 31.1%. The 5-year distant metastasis failure-free survival rate was 40.7% (50.56% for patients with operation; 27.2% for patients without operation, p=0.0298). The acute toxicities were mild, and no Grade 3 or above hematologic toxicity was noted. There was only one patient with Grade 3 esophagus toxicity. Grade 3 lung toxicity occurred in only three patients. Preoperative chemoradiotherapy with oxaliplatin in the treatment of locally advanced, potentially resectable esophageal cancer is feasible and safe. Copyright © 2017. Published by Elsevier Taiwan LLC.

1 H MR spectroscopy in cervical carcinoma using external phase array body coil at 3.0 Tesla: Prediction of poor prognostic human papillomavirus genotypes.

PubMed

Lin, Gigin; Lai, Chyong-Huey; Tsai, Shang-Yueh; Lin, Yu-Chun; Huang, Yu-Ting; Wu, Ren-Chin; Yang, Lan-Yan; Lu, Hsin-Ying; Chao, Angel; Wang, Chiun-Chieh; Ng, Koon-Kwan; Ng, Shu-Hang; Chou, Hung-Hsueh; Yen, Tzu-Chen; Hung, Ji-Hong

2017-03-01

To assess the clinical value of proton ( 1 H) MR spectroscopy in cervical carcinomas, in the prediction of poor prognostic human papillomavirus (HPV) genotypes as well as persistent disease following concurrent chemoradiotherapy (CCRT). 1 H MR spectroscopy using external phase array coil was performed in 52 consecutive cervical cancer patients at 3 Tesla (T). Poor prognostic HPV genotypes (alpha-7 species or absence of HPV infection) and persistent cervical carcinoma after CCRT were recorded. Statistical significance was calculated with the Mann-Whitney two-sided nonparametric test and areas under the receiver operating characteristics curve (AUC) analysis. A 4.3-fold (P = 0.032) increased level of methyl resonance at 0.9 ppm was found in the poor prognostic HPV genotypes, mainly attributed to the presence of HPV18, with a sensitivity of 75%, a specificity of 81%, and an AUC of 0.76. Poor prognostic HPV genotypes were more frequently observed in patients with adeno-/adenosquamous carcinoma (Chi-square, P < 0.0001). In prediction of the four patients with persistent disease after CCRT, elevated methyl resonance demonstrated a sensitivity of 100%, a specificity of 74%, and an AUC of 0.82. 1 H MR spectroscopy at 3T can be used to depict the elevated lipid resonance levels in cervical carcinomas, as well as help to predict the poor prognostic HPV genotypes and persistent disease following CCRT. Further large studies with longer follow up times are warranted to validate our initial findings. 1 J. Magn. Reson. Imaging 2017;45:899-907. © 2016 International Society for Magnetic Resonance in Medicine.

18F-fluorodeoxyglucose uptake on positron emission tomography as a prognostic predictor in locally advanced hepatocellular carcinoma.

PubMed

Kim, Beom Kyung; Kang, Won Jun; Kim, Ja Kyung; Seong, Jinsil; Park, Jun Yong; Kim, Do Young; Ahn, Sang Hoon; Lee, Do Youn; Lee, Kwang Hoon; Lee, Jong Doo; Han, Kwang-Hyub

2011-10-15

Metabolic activity assessed by (18)F-fluorodeoxyglocuse-positron emission tomography ((18)F-FDG-PET) reflects biological aggressiveness and prognoses in various tumors. The authors present a correlation between tumor metabolic activity and clinical outcomes in patients with hepatocellular carcinoma (HCC). Over a 3-year period (2005-2008), 135 locally advanced HCC patients were treated with localized concurrent chemoradiotherapy (CCRT; external beam radiotherapy at 45 grays for 5 weeks plus concurrent hepatic arterial infusion of 5-fluorouracil during the first and fifth week) followed by repetitive hepatic arterial infusional chemotherapy with 5-fluorouracil and cisplatin. Among them, the authors studied 107 who received (18)F-FDG-PET before CCRT. Maximal standardized uptake values (SUVs) of tumors were calculated. The median maximal tumor SUV was 6.1 (range, 2.4-∼19.2). Patients with low maximal tumor SUVs (<6.1) had a higher disease control rate than those with high maximal tumor SUVs (≥6.1) (86.8% vs 68.5%, respectively, P = .023). Both median progression-free survival (PFS; 8.4 vs 5.2 months; P = .003) and overall survival (OS; 17.9 vs 11.3 months; P = .013) were significantly longer in the low maximal tumor SUV group than in the high maximal tumor SUV group, respectively. In multivariate analysis, low maximal tumor SUV and objective responses to CCRT remained significant for PFS and OS. The high maximal tumor SUV group was more likely to have extrahepatic metastasis within 6 months than the low maximal tumor SUV group (58.1% vs 26.8%, respectively; P < .001). Similar results were obtained for the maximal tumor SUV/normal liver maximal SUV ratio (<2 vs ≥2) concerning progression, death, and extrahepatic metastasis. Metabolic activity may be useful not only in predicting prognosis and treatment responses, but also in establishing optimal treatment plans in locally advanced HCC. Copyright © 2011 American Cancer Society.

125I Brachytherapy in Locally Advanced Nonsmall Cell Lung Cancer After Progression of Concurrent Radiochemotherapy

PubMed Central

Xiang, Zhanwang; Li, Guohong; Liu, Zhenyin; Huang, Jinhua; Zhong, Zhihui; Sun, Lin; Li, Chuanxing; Zhang, Funjun

2015-01-01

Abstract To investigate the safety and effectiveness of computed tomography (CT)-guided 125I seed implantation for locally advanced nonsmall cell lung cancer (NSCLC) after progression of concurrent radiochemotherapy (CCRT). We reviewed 78 locally advanced NSCLC patients who had each one cycle of first-line CCRT but had progressive disease identified from January 2006 to February 2015 at our institution. A total of 37 patients with 44 lesions received CT-guided percutaneous 125I seed implantation and second-line chemotherapy (group A), while 41 with 41 lesions received second-line chemotherapy (group B). Patients in group A and B received a total of 37 and 41 first cycle of CCRT treatment. The median follow-up was 19 (range 3–36) months. After the second treatment, the total response rate (RR) in tumor response accounted for 63.6% in group A, which was significantly higher than that of group B (41.5%) (P = 0.033). The median progression-free survival time (PFST) was 8.00 ± 1.09 months and 5.00 ± 0.64 months in groups A and B (P = 0.011). The 1-, 2-, and 3-year overall survival (OS) rates for group A were 56.8%, 16.2%, and 2.7%, respectively. For group B, OS rates were 36.6%, 9.8%, and 2.4%, respectively. The median OS time was 14.00 ± 1.82 months and 10.00 ± 1.37 months for groups A and B, respectively (P = 0.059). Similar toxicity reactions were found in both groups. Tumor-related clinical symptoms were significantly reduced and the patients’ quality of life was obviously improved. CT-guided 125I seed implantation proved to be potentially beneficial in treating localized advanced NSCLC; it achieved good local control rates and relieved clinical symptoms without increasing side effects. PMID:26656370

Concurrent Chemoradiotherapy with Temozolomide Followed by Adjuvant Temozolomide for Newly Diagnosed Glioblastoma Patients: A Retrospective Multicenter Observation Study in Korea.

PubMed

Kim, Byung Sup; Seol, Ho Jun; Nam, Do-Hyun; Park, Chul-Kee; Kim, Il Han; Kim, Tae Min; Kim, Jeong Hoon; Cho, Young Hyun; Yoon, Sang Min; Chang, Jong Hee; Kang, Seok-Gu; Kim, Eui Hyun; Suh, Chang-Ok; Jung, Tae-Young; Lee, Kyung-Hwa; Kim, Chae-Yong; Kim, In Ah; Hong, Chang-Ki; Yoo, Heon; Kim, Jin Hee; Kang, Shin-Hyuk; Kang, Min Kyu; Kim, Eun-Young; Kim, Sun-Hwan; Chung, Dong-Sup; Hwang, Sun-Chul; Song, Joon-Ho; Cho, Sung Jin; Lee, Sun-Il; Lee, Youn-Soo; Ahn, Kook-Jin; Kim, Se Hoon; Lim, Do Hun; Gwak, Ho-Shin; Lee, Se-Hoon; Hong, Yong-Kil

2017-01-01

The purpose of this study was to investigate the feasibility and survival benefits of combined treatment with radiotherapy and adjuvant temozolomide (TMZ) in a Korean sample. A total of 750 Korean patients with histologically confirmed glioblastoma multiforme, who received concurrent chemoradiotherapy with TMZ (CCRT) and adjuvant TMZ from January 2006 until June 2011, were analyzed retrospectively. After the first operation, a gross total resection (GTR), subtotal resection (STR), partial resection (PR), biopsy alone were achieved in 388 (51.7%), 159 (21.2%), 96 (12.8%), and 107 (14.3%) patients, respectively. The methylation status of O 6 -methylguanine-DNA methyltransferase (MGMT) was reviewed retrospectively in 217 patients. The median follow-up period was 16.3 months and the median overall survival (OS) was 17.5 months. The actuarial survival rates at the 1-, 3-, and 5-year OS were 72.1%, 21.0%, and 9.0%, respectively. The median progression-free survival (PFS) was 10.1 months, and the actuarial PFS at 1-, 3-, and 5-year PFS were 42.2%, 13.0%, and 7.8%, respectively. The patients who received GTR showed a significantly longer OS and PFS than those who received STR, PR, or biopsy alone, regardless of the methylation status of the MGMT promoter. Patients with a methylated MGMT promoter also showed a significantly longer OS and PFS than those with an unmethylated MGMT promoter. Patients who received more than six cycles of adjuvant TMZ had a longer OS and PFS than those who received six or fewer cycles. Hematologic toxicity of grade 3 or 4 was observed in 8.4% of patients during the CCRT period and in 10.2% during the adjuvant TMZ period. Patients treated with CCRT followed by adjuvant TMZ had more favorable survival rates and tolerable toxicity than those who did not undergo this treatment.

Dose-Volume Histogram Predictors of Chronic Gastrointestinal Complications After Radical Hysterectomy and Postoperative Concurrent Nedaplatin-Based Chemoradiation Therapy for Early-Stage Cervical Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Isohashi, Fumiaki, E-mail: isohashi@radonc.med.osaka-u.ac.jp; Yoshioka, Yasuo; Mabuchi, Seiji

2013-03-01

Purpose: The purpose of this study was to evaluate dose-volume histogram (DVH) predictors for the development of chronic gastrointestinal (GI) complications in cervical cancer patients who underwent radical hysterectomy and postoperative concurrent nedaplatin-based chemoradiation therapy. Methods and Materials: This study analyzed 97 patients who underwent postoperative concurrent chemoradiation therapy. The organs at risk that were contoured were the small bowel loops, large bowel loop, and peritoneal cavity. DVH parameters subjected to analysis included the volumes of these organs receiving more than 15, 30, 40, and 45 Gy (V15-V45) and their mean dose. Associations between DVH parameters or clinical factors andmore » the incidence of grade 2 or higher chronic GI complications were evaluated. Results: Of the clinical factors, smoking and low body mass index (BMI) (<22) were significantly associated with grade 2 or higher chronic GI complications. Also, patients with chronic GI complications had significantly greater V15-V45 volumes and higher mean dose of the small bowel loops compared with those without GI complications. In contrast, no parameters for the large bowel loop or peritoneal cavity were significantly associated with GI complications. Results of the receiver operating characteristics (ROC) curve analysis led to the conclusion that V15-V45 of the small bowel loops has high accuracy for prediction of GI complications. Among these parameters, V40 gave the highest area under the ROC curve. Finally, multivariate analysis was performed with V40 of the small bowel loops and 2 other clinical parameters that were judged to be potential risk factors for chronic GI complications: BMI and smoking. Of these 3 parameters, V40 of the small bowel loops and smoking emerged as independent predictors of chronic GI complications. Conclusions: DVH parameters of the small bowel loops may serve as predictors of grade 2 or higher chronic GI complications after postoperative concurrent nedaplatin-based chemoradiation therapy for early-stage cervical cancer.« less

Chemoradiation in nasopharyngeal carcinoma: a 6-year experience in Tehran cancer institute.

PubMed

Kalaghchi, Bita; Kazemian, Ali; Hashem, Farnaz Amouzegar; Aghili, Mehdi; Farhan, Farshid; Haddad, Peiman

2011-01-01

To determine the addition of value of neoadjuvant, concurrent and adjuvant chemotherapy to radiation in the treatment of nasopharyngeal carcinoma with regard to the overall survival (OS) and disease free survival (DFS) within a six year period in Tehran cancer institute. Files of all patients with nasopharyngeal carcinoma treated by radiotherapy with or without concurrent chemotherapy in a curative setting in Tehran cancer institute during the period of 1999-2005 were retrospectively reviewed.. A total of 103 patients with nasopharyngeal carcinoma had been treated during the study period with radiotherapy or chemoradiotherapy in our institute. There were 29 (28.2%) females and 74 (71.8%) males. The median age at the time of radiotherapy was 47 years old (range 9-75 years). The patients were followed 2 to 76 months with a median follow-up of 14 months. Time of first recurrence after treatment was 3-44 months with a median of 10 months.. Survival in 2 groups of patients treated with radiotherapy alone or chemoradiation did not have a significant difference (P>0.1). Two-year survival in patients treated with or without adjuvant chemotherapy and had local recurrence after treatment did not have significant difference (P>0.1). Two-year survival in patients with or without local recurrence after treatment did not have significant difference (P>0.1). A beneficial affect or a survival benefit of adjuvant/neoadjuvant chemotherapy and concurrent chemoradiation was not observed in Iranian patients.

Benefit of neoadjuvant concurrent chemoradiotherapy for locally advanced perihilar cholangiocarcinoma

PubMed Central

Jung, Jang Han; Lee, Hyun Jik; Lee, Hee Seung; Jo, Jung Hyun; Cho, In Rae; Chung, Moon Jae; Park, Jeong Youp; Park, Seung Woo; Song, Si Young; Bang, Seungmin

2017-01-01

AIM To clarify the role of neoadjuvant concurrent chemoradiotherapy (NACCRT) followed by surgical resection for localized or locally advanced perihilar cholangiocarcinoma (CCA). METHODS We retrospectively reviewed 57 patients who underwent surgical resection with or without NACCRT for perihilar CCA; 12 patients received NACCRT and 45 patients did not received NACCRT. Patients with locally advanced perihilar CCA requiring NACCRT were defined as follows: (1) a mass involving unilateral branches of the portal vein or hepatic artery with insufficient volume of the anticipated remnant lobe; or (2) an infiltrating mass in the main portal vein that was too long for reconstruction, identified at preoperative staging. RESULTS The median disease-free survival (DFS) durations of the neoadjuvant and non-neoadjuvant CCRT groups were 26.0 and 15.1 mo, respectively (P = 0.91). The median overall survival (OS) durations of the neoadjuvant and non-neoadjuvant CCRT groups were 32.9 and 27.1 mo, respectively (P = 0.26). The NACCRT group showed a downstaging tendency compared to the non-NACCRT group as compared with the tumor stage confirmed by histological examination after surgery and the tumor stage confirmed by imaging test at the time of diagnosis (P = 0.01). CONCLUSION NACCRT does not prolong DFS and OS in localized or locally advanced perihilar CCA. However, NACCRT may allow tumor downstaging and improve tumor resectability. PMID:28566890

A phase III concurrent chemoradiotherapy trial with cisplatin and paclitaxel or docetaxel or gemcitabine in unresectable non-small cell lung cancer: KASLC 0401.

PubMed

Oh, In-Jae; Kim, Kyu-Sik; Kim, Young-Chul; Ban, Hee-Jung; Kwon, Yong-Soo; Kim, Yu-Il; Lim, Sung-Chul; Chung, Woong-Ki; Nam, Taek-Keun; Song, Joo-Young; Yoon, Mee-Sun; Ahn, Sung-Ja

2013-12-01

Concurrent chemoradiotherapy (CCRT) is recommended for the management of patients with unresectable non-small cell lung cancer (NSCLC). This prospective study aimed to compare the efficacy of concurrently delivered cisplatin doublets with paclitaxel, or docetaxel, or gemcitabine. The main eligibility criteria consisted of previously untreated stage IIIB NSCLC. The subjects were randomized into three arms: paclitaxel 45 mg/m(2)/week (TP), docetaxel 20 mg/m(2)/week (DP), and gemcitabine 350 mg/m(2)/week (GP) in addition to cisplatin 20 mg/m(2)/week. Three-dimensional conformal radiotherapy was given once daily, weekly 5 fractions and the total prescription dose was 60-66 Gy. The primary endpoint was response rate, and the secondary endpoints were survival and toxicity. A total of 101 patients were recruited into this trial of whom 93 (TP: 33, DP: 29, GP: 31) patients were treated with CCRT from March 2005 to July 2007. Similar response rates were observed across arms: TP: 63.6 %, DP: 72.4 %, GP: 61.3 % (p = 0.679). There was no statistically significant difference of median survival (TP: 27.3, DP: 27.6, GP: 16.5 months, p = 0.771). In subgroup analysis, a survival benefit of consolidation chemotherapy was not seen, but leucopenia (63.2 %) and neutropenia (68.4 %) more than grade 3 were significantly high in DP arm. The grade ≥3 radiation esophagitis was more frequent in the GP arm (22.6 %, p = 0.163). Among the three arms, no statistically significant difference in response rate, survival, and toxicity was observed. However, clinically significant radiation toxicity was more frequent in the GP arm.

Recombine Endostatin With Neoadjuvant Chemotherapy Followed by Concurrent Chemoradiation in Advanced Nasopharynx Cancer

ClinicalTrials.gov

2013-03-11

1、Enough Cases; 2、Elekta Precise 1343 Digital Control Electron Linear Accelerator; Can Undertake Nasopharyngeal Carcinoma Specimens in the Materia，; Image Department of Nose Pharynx Ministry MRI Dynamic Testing,

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morota, Madoka; Gomi, Kotaro; Kozuka, Takuyo

Purpose: To evaluate late cardiopulmonary toxicities after concurrent chemoradiotherapy (CCRT) for esophageal carcinomas. Methods and Materials: From February 2002 through April 2005, 74 patients with clinical Stage I-IVB carcinoma of the esophagus were treated with CCRT. Sixty-nine patients with thoracic squamous cell carcinoma were the core of this analysis. Patients received 60 Gy of radiation therapy in 30 fractions over 8 weeks, including a 2-week break, and received 2 cycles of fluorouracil/cisplatin chemotherapy concomitantly. Initial radiation fields included primary tumors, metastatic lymph nodes, and supraclavicular, mediastinal, and celiac nodes areas. Late toxicities were assessed with the late radiation morbidity scoringmore » scheme of the Radiation Therapy Oncology Group/European Organiation for Research and Treatment of Cancer. Results: The median age was 67 years (range, 45-83 years). The median follow-up time was 26.1 months for all patients and 51.4 months for patients still alive at the time of analysis. Five cardiopulmonary toxic events of Grade 3 or greater were observed in 4 patients, Grade 5 heart failure and Grade 3 pericarditis in 1 patient, and Grade 3 myocardial infarction, Grade 3 radiation pneumonitis, and Grade 3 pleural effusion. The 2-year cumulative incidence of late cardiopulmonary toxicities of Grade 3 or greater for patients 75 years or older was 29% compared with 3% for younger patients (p = 0.005). Conclusion: The CCRT used in this study with an extensive radiation field is acceptable for younger patients but is not tolerated by patients older than 75 years.« less

High Expression of EphA4 Predicted Lesser Degree of Tumor Regression after Neoadjuvant Chemoradiotherapy in Rectal Cancer.

PubMed

Lin, Ching-Yih; Lee, Ying-En; Tian, Yu-Feng; Sun, Ding-Ping; Sheu, Ming-Jen; Lin, Chen-Yi; Li, Chien-Feng; Lee, Sung-Wei; Lin, Li-Ching; Chang, I-Wei; Wang, Chieh-Tien; He, Hong-Lin

2017-01-01

Background: Numerous transmembrane receptor tyrosine kinase pathways have been found to play an important role in tumor progression in some cancers. This study was aimed to evaluate the clinical impact of Eph receptor A4 (EphA4) in patients with rectal cancer treated with neoadjuvant concurrent chemoradiotherapy (CCRT) combined with mesorectal excision, with special emphasis on tumor regression. Methods: Analysis of the publicly available expression profiling dataset of rectal cancer disclosed that EphA4 was the top-ranking, significantly upregulated, transmembrane receptor tyrosine kinase pathway-associated gene in the non-responders to CCRT, compared with the responders. Immunohistochemical study was conducted to assess the EphA4 expression in pre-treatment biopsy specimens from 172 rectal cancer patients without distant metastasis. The relationships between EphA4 expression and various clinicopathological factors or survival were statistically analyzed. Results: EphA4 expression was significantly associated with vascular invasion ( P =0.015), post-treatment depth of tumor invasion ( P =0.006), pre-treatment and post-treatment lymph node metastasis ( P =0.004 and P =0.011, respectively). More importantly, high EphA4 expression was significantly predictive for lesser degree of tumor regression after CCRT ( P =0.031). At univariate analysis, high EphA4 expression was a negative prognosticator for disease-specific survival ( P =0.0009) and metastasis-free survival ( P =0.0001). At multivariate analysis, high expression of EphA4 still served as an independent adverse prognostic factor for disease-specific survival (HR, 2.528; 95% CI, 1.131-5.651; P =0.024) and metastasis-free survival (HR, 3.908; 95% CI, 1.590-9.601; P =0.003). Conclusion: High expression of EphA4 predicted lesser degree of tumor regression after CCRT and served as an independent negative prognostic factor in patients with rectal cancer.

Alterations in Hormone Levels After Adjuvant Chemoradiation in Male Rectal Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoon, Frederick H.; Perera, Francisco; Fisher, Barbara

Purpose: To evaluate follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels after postoperative chemoradiation in men with rectal cancer. Methods and Materials: Forty-three men with rectal cancer had baseline and postchemoradiation FSH, LH, and testosterone measured. Adjuvant chemoradiation consisted of two 5-day cycles of bolus 5-fluorouracil (5-FU) every 4 weeks at a dose of 500 mg/m{sup 2}/d followed by concurrent chemoradiation followed by two additional 5-day cycles of 5-FU at a dose of 450 mg/m{sup 2}/d. Continuous-infusion 5-FU at 225 mg/m{sup 2}/d was given during radiation. Pelvic radiation consisted of a three- or four-field technique with a median dosemore » of 54.0 Gy in 30 fractions. Results: Median follow-up was 6.1 years. Mean baseline FSH levels increased from 5.3 to a peak of 23.9 IU/L (p < 0.001) 13-24 months after chemoradiation. Mean baseline LH levels increased from 4.3 to a peak of 8.5 IU/L (p < 0.001) within 6 months after chemoradiation. Mean testosterone levels decreased from 15.4 nmol/L at baseline to 8.0 nmol/L more than 4 years after chemoradiation. Mean testosterone to mean LH ratio decreased from 4.4 at baseline to 1.1 after 48 months posttreatment, suggesting a continued decrease in Leydig cell function with time. Testicular dose was measured in 5 patients. Median dose was 4 Gy (range, 1.5-8.9 Gy). Conclusions: Chemoradiation in men with rectal cancer causes persistent increases in FSH and LH levels and decreases in testosterone levels.« less

CAPIRI-IMRT: a phase II study of concurrent capecitabine and irinotecan with intensity-modulated radiation therapy for the treatment of recurrent rectal cancer.

PubMed

Cai, Gang; Zhu, Ji; Palmer, Joshua D; Xu, Ye; Hu, Weigang; Gu, Weilie; Cai, Sanjun; Zhang, Zhen

2015-02-28

This study investigated the local effect and acute toxicity of irinotecan and capecitabine with concurrent intensity-modulated radiation therapy (IMRT) for the treatment of recurrent rectal cancer without prior pelvic irradiation. Seventy-one patients diagnosed with recurrent rectal cancer who did not previously receive pelvic irradiation were treated in our hospital from October 2009 to July 2012. Radiotherapy was delivered to the pelvis, and IMRT of 45 Gy (1.8 Gy per fraction), followed by a boost of 10 Gy to 16 Gy (2 Gy per fraction), was delivered to the recurrent sites. The concurrent chemotherapy regimen was 50 mg/m(2) irinotecan weekly and 625 mg/m(2) capecitabine twice daily (Mon-Fri). Radical surgery was recommended for medically fit patients without extra-pelvic metastases. The patients were followed up every 3 months. Tumor response was evaluated using CT/MRIs according to the RECIST criteria or postoperative pathological findings. NCI-CTC 3.0 was used to score the toxicities. Forty-eight patients (67.6%) had confirmed recurrent rectal cancer without extra pelvic metastases, and 23 patients (32.4%) had extra pelvic metastases. Fourteen patients (19.7%) underwent radical resections (R0) post-chemoradiation. A pathologic complete response was observed in 7 of 14 patients. A clinical complete response was observed in 4 patients (5.6%), and a partial response was observed in 22 patients (31.0%). Only 5 patients (7.0%) showed progressive disease during or shortly after treatment. Of 53 symptomatic patients, clinical complete and partial symptom relief with chemoradiation was achieved in 56.6% and 32.1% of patients, respectively. Only 2 patients (2.8%) experienced grade 4 leukopenia. The most common grade 3 toxicity was diarrhea (16 [22.5%] patients). The median follow-up was 31 months. The cumulative local progression-free survival rate was 74.2% and 33.9% at 1 and 3 years after chemoradiation, respectively. The cumulative total survival rate was 80.1% and 36.5% at 1 and 3 years after chemoradiation, respectively. This study revealed that concurrent irinotecan and capecitabine with IMRT significantly relieves local symptoms and exhibits promising efficacy with manageable toxicities in recurrent rectal cancer without prior pelvic irradiation. Improving the rate of R0 resections will be investigated in a future study.

[Late adverse events after concurrent chemoradiation therapy in long-term survivors with non-small cell lung cancer].

PubMed

Hasegawa, Takaaki; Sawa, Toshiyuki; Futamura, Yohei; Horiba, Akane; Ishiguro, Takashi; Yoshida, Tsutomu; Iida, Takayoshi; Marui, Tsutomu

2013-11-01

Long-term survival in patients with non-small cell lung cancer( NSCLC) can be achieved more frequently with combined modality therapy. However, an increased risk of late treatment-related toxicities has been reported for this treatment strategy. We retrospectively evaluated NSCLC patients treated with chemoradiation therapy from January 1988 to January 2007. Patients who had survived for more than 5 years after treatment were included in an analysis of late adverse events (excluding radiation pneumonitis and pulmonary fibrosis). A total of 188 NSCLC patients treated with chemoradiation therapy were evaluated, with 25 patients having survived for more than 5 years. Of these patients, 4 had stage I disease, 4 had stage IIB disease, 1 had stage IIIA disease, 14 had stage IIIB disease, 1 had stage IV disease, and 1 had disease of unknown stage. The following grade 3 late adverse events were noted: skin ulceration( n=1), skin induration( n=1), brachial plexopathy( n=1), malignant neoplasm( n=1). Adequate management of late adverse events due to chemoradiation therapy is needed for long-term NSCLC survivors.

Long-Term Prognostic Effects of Plasma Epstein-Barr Virus DNA by Minor Groove Binder-Probe Real-Time Quantitative PCR on Nasopharyngeal Carcinoma Patients Receiving Concurrent Chemoradiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, J.-C.; Wang, W.-Y.; Liang, W.-M.

Purpose: To evaluate the long-term prognostic impact of plasma Epstein-Barr virus (EBV) DNA concentration measured by real-time quantitative polymerase chain reaction (RTQ-PCR) in nasopharyngeal carcinoma (NPC) patients receiving concurrent chemoradiotherapy (CCRT). Methods and Materials: Epstein-Barr virus DNA was retrospectively measured from stock plasma of 152 biopsy-proven NPC patients with Stage II-IV (M0) disease with a RTQ-PCR using the minor groove binder-probe. All patients received CCRT with a median follow-up of 78 months. We divided patients into three subgroups: (1) low pretreatment EBV DNA (<1,500 copies/mL) and undetectable posttreatment EBV DNA (pre-L/post-U) (2) high pretreatment EBV DNA ({>=}1,500 copies/mL) and undetectablemore » posttreatment EBV DNA (pre-H/post-U), and (3) low or high pretreatment EBV DNA and detectable posttreatment EBV DNA (pre-L or H/post-D) for prognostic analyses. Results: Epstein-Barr virus DNA (median concentration, 573 copies/mL; interquartile range, 197-3,074) was detected in the pretreatment plasma of 94.1% (143/152) of patients. After treatment, plasma EBV DNA decreased or remained 0 for all patients and was detectable in 31 patients (20.4%) with a median concentration 0 copy/mL (interquartile range, 0-0). The 5-year overall survival rates of the pre-L/post-U, pre-H/post-U, and pre-L or H/post-D subgroups were 87.2%, 71.0%, and 38.7%, respectively (p < 0.0001). The relapse-free survival showed similar results with corresponding rates of 85.6%, 75.9%, and 26.9%, respectively (p < 0.0001). Multivariate Cox analysis confirmed the superior effects of plasma EBV DNA compared to other clinical parameters in prognosis prediction. Conclusion: Plasma EBV DNA is the most valuable prognostic factor for NPC. More chemotherapy should be considered for patients with persistently detectable EBV DNA after CCRT.« less

Nimotuzumab combined with concurrent chemoradiotherapy in Japanese patients with esophageal cancer: A phase I study.

PubMed

Kato, Ken; Ura, Takashi; Koizumi, Wasaburo; Iwasa, Satoru; Katada, Chikatoshi; Azuma, Mizutomo; Ishikura, Satoshi; Nakao, Yoshinori; Onuma, Hiroshi; Muro, Kei

2018-03-01

Nimotuzumab is a humanized anti-epidermal growth factor receptor IgG1 monoclonal antibody. This phase I study assessed the tolerability, safety, efficacy, and pharmacokinetics of nimotuzumab in combination with chemoradiotherapy in Japanese patients with esophageal cancer. Patients with stage II, III, and IV esophageal cancer were enrolled. Patients were planned to receive nimotuzumab (level 1: 200 mg/wk for 25 weeks; or level 2: 400 mg/wk in the chemoradiation period, 400 mg biweekly in an additional chemotherapy period [8 weeks after the chemoradiation period] and a maintenance therapy period [after chemotherapy to 25 weeks]) combined with cisplatin (75 mg/m 2 on day 1) and fluorouracil (1000 mg/m 2 on days 1-4) in the chemoradiation and additional chemotherapy periods. Radiotherapy was given concurrently at 50.4 Gy. A total of 10 patients were enrolled in level 1. Dose-limiting toxicities were observed in 2 patients (grade 3 infection and renal disorder). Maximum-tolerated dose was estimated to be at least 200 mg/wk and the dose was not escalated to level 2. The most common grade ≥3 toxicities were lymphopenia (90%), leukopenia (60%), neutropenia (50%), and febrile neutropenia, decreased appetite, hyponatremia, and radiation esophagitis (30% each). Neither treatment-related death nor grade ≥3 skin toxicity was observed in any patient. Complete response rate was 50%. Progression-free survival was 13.9 months. One- and 3-year survival rates were 75% and 37.5%, respectively. Immunogenicity was not reported in any patient. Nimotuzumab in combination with concurrent chemoradiotherapy was tolerable and effective for Japanese patients with esophageal cancer. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Radiotherapy for locally advanced resectable T3–T4 laryngeal cancer—does laryngeal preservation strategy compromise survival?

PubMed Central

Suzuki, Gen; Nakamura, Satoaki; Hirano, Shigeru; Yoshida, Ken; Konishi, Koji; Teshima, Teruki; Ogawa, Kazuhiko

2018-01-01

Abstract With the advancement of chemotherapy, a laryngeal preservation (LP) strategy was explored with the aim of improving maintenance of quality of life. Induction chemotherapy (ICT) following radiotherapy (RT) was considered a viable option because of its high initial response rate without hampering of overall survival (OS). Subsequently, concurrent chemoradiotherapy (CCRT) using CDDP became the standard of care for LP, showing the best LP ratio. For enhancing treatment intensity, ICT with taxan + CDDP + 5-FU (TPF-ICT) followed by RT showed superiority over ICT with CDDP + 5-FU (PF-ICT) followed by RT. Given that almost all randomized controlled trials investigating ICT include not only operable (endpoint, LP) but also inoperable (endpoint, OS) cases, physicians are faced with a dilemma regarding application in daily practice. In addition, increased treatment intensity causes augmentation of adverse events, which might reduce compliance. Thereafter, cetuximab, an effective drug with fewer adverse effects [bioradiotherapy (BRT)], emerged as another option. However, little evidence has confirmed its superiority over RT (or CCRT) in laryngeal cancer subpopulations. In spite of these developments, the OS of patients with laryngeal cancer has not improved for several decades. In fact, several studies indicated a decrease in OS during the 1990s, probably due to overuse of CCRT. Fortunately, the latter was not the case in most institutions. Currently, no other treatment has better OS than surgery. The eligibility criteria for LP and/or surgery largely depend upon the available expertise and experience, which differ from one institution to another. Therefore, a multidisciplinary team is required for the treatment of LP. PMID:29190391

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miyamoto, David T.; Mamon, Harvey J.; Ryan, David P.

Purpose: To review the outcomes and tolerability of full-dose chemoradiation in elderly patients aged 75 years or older with localized pancreatic cancer. Methods and Materials: We retrospectively reviewed patients aged 75 years or older with nonmetastatic pancreatic cancer treated with chemoradiation therapy at two institutions from 2002 to 2007. Patients were analyzed for treatment toxicity, local recurrences, distant metastases, and survival. Results: A total of 42 patients with a median age of 78 years (range, 75-90 years) who received chemoradiation therapy for pancreatic cancer were identified. Of the patients, 24 had locally advanced disease treated with definitive chemoradiation, and 18more » had disease treated with surgery and chemoradiation. Before chemoradiotherapy, the mean Eastern Cooperative Oncology Group performance status was 1.0 {+-} 0.8, and the mean 6-month weight loss was 5.3 {+-} 3.8 kg. The mean radiation dose delivered was 48.1 {+-} 9.2 Gy. All patients received fluoropyrimidine-based chemotherapy concurrently with radiotherapy. In all, 8 patients (19%) were hospitalized, 7 (17%) had an emergency room visit, 15 (36%) required a radiation treatment break, 3 (7%) required a chemotherapy break, 9 (21%) did not complete therapy, and 22 (49%) had at least one of these adverse events. The most common toxicities were nausea, pain, and failure to thrive. Median overall survival was 8.6 months (95% confidence interval, 7.2-13.1) in patients who received definitive chemoradiation therapy and 20.6 months (95% confidence interval, 9.5-{infinity}) in patients who underwent resection and chemoradiation therapy. Conclusions: In this dataset of very elderly patients with pancreatic cancer and good Eastern Cooperative Oncology Group performance status, outcomes after chemoradiotherapy were similar to those among historic controls for patients with locally advanced and resected pancreatic cancer, although many patients experienced substantial treatment-related toxicity.« less

Phase 2 Sequential and Concurrent Chemoradiation for Advanced Nasopharyngeal Carcinoma (NPC)

ClinicalTrials.gov

2016-12-09

Stage II Lymphoepithelioma of the Nasopharynx; Stage II Squamous Cell Carcinoma of the Nasopharynx; Stage III Lymphoepithelioma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage IV Lymphoepithelioma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx

Phase 1 Trial of Bevacizumab With Concurrent Chemoradiation Therapy for Squamous Cell Carcinoma of the Head and Neck With Exploratory Functional Imaging of Tumor Hypoxia, Proliferation, and Perfusion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nyflot, Matthew J., E-mail: nyflot@uw.edu; Kruser, Tim J.; Traynor, Anne M.

2015-04-01

Purpose: A phase 1 trial was completed to examine the safety and feasibility of combining bevacizumab with radiation and cisplatin in patients with locoregionally advanced squamous cell carcinoma of the head and neck (HNSCC) treated with curative intent. Additionally, we assessed the capacity of bevacizumab to induce an early tumor response as measured by a series of biological imaging studies. Methods and Materials: All patients received a single induction dose of bevacizumab (15 mg/kg) delivered 3 weeks (±3 days) before the initiation of chemoradiation therapy. After the initial dose of bevacizumab, comprehensive head and neck chemoradiation therapy was delivered with curativemore » intent to 70 Gy in 33 fractions with concurrent weekly cisplatin at 30 mg/m{sup 2} and bevacizumab every 3 weeks (weeks 1, 4, 7) with dose escalation from 5 to 10 to 15 mg/kg. All patients underwent experimental imaging with [{sup 18}F]fluorothymidine positron emission tomography (FLT-PET) (proliferation), [{sup 61}Cu]Cu-diacetyl-bis(N4-methylthiosemicarbazone) PET (Cu-ATSM-PET) (hypoxia), and dynamic contrast-enhanced computed tomography (DCE-CT) (perfusion) at 3 time points: before bevacizumab monotherapy, after bevacizumab monotherapy, and during the combined therapy course. Results: Ten patients were enrolled. All had stage IV HNSCC, all achieved a complete response to treatment, and 9 of 10 remain alive, with a mean survival time of 61.3 months. All patients experienced grade 3 toxicity, but no dose-limiting toxicities or significant bleeding episodes were observed. Significant reductions were noted in tumor proliferation (FLT-PET), tumor hypoxia (Cu-ATSM-PET), and DCE-CT contrast enhancement after bevacizumab monotherapy, with further decreases in FLT-PET and Cu-ATSM-PET during the combined therapy course. Conclusions: The incorporation of bevacizumab into comprehensive chemoradiation therapy regimens for patients with HNSCC appears safe and feasible. Experimental imaging demonstrates measureable changes in tumor proliferation, hypoxia, and perfusion after bevacizumab monotherapy and during chemoradiation therapy. These findings suggest opportunities to preview the clinical outcomes for individual patients and thereby design personalized therapy approaches in future trials.« less

Does Response to Induction Chemotherapy Predict Survival for Locally Advanced Non-Small-Cell Lung Cancer? Secondary Analysis of RTOG 8804/8808

DOE Office of Scientific and Technical Information (OSTI.GOV)

McAleer, Mary Frances, E-mail: mfmcalee@mdanderson.or; Moughan, Jennifer M.S.; Byhardt, Roger W.

2010-03-01

Purpose: Induction chemotherapy (ICT) improves survival compared with radiotherapy (RT) alone in locally advanced non-small-cell lung cancer (LANSCLC) patients with good prognostic factors. Concurrent chemoradiotherapy (CCRT) is superior to ICT followed by RT. The question arises whether ICT response predicts the outcome of patients subsequently treated with CCRT or RT. Methods and Materials: Between 1988 and 1992, 194 LANSCLC patients were treated prospectively with ICT (two cycles of vinblastine and cisplatin) and then CCRT (cisplatin plus 63 Gy for 7 weeks) in the Radiation Therapy Oncology Group 8804 trial (n = 30) or ICT and then RT (60 Gy/6 wk)more » on Radiation Therapy Oncology Group 8808 trial (n = 164). Of the 194 patients, 183 were evaluable and 141 had undergone a postinduction assessment. The overall survival (OS) of those with complete remission (CR) or partial remission (PR) was compared with that of patients with stable disease (SD) or progressive disease (PD) after ICT. Results: Of the 141 patients, 6, 30, 99, and 6 had CR, PR, SD, and PD, respectively. The log-rank test showed a significant difference (p <0.0001) in OS when the response groups were compared (CR/PR vs. SD/PD). On univariate and multivariate analyses, a trend was seen toward a response to ICT with OS (p = 0.097 and p = 0.06, respectively). A squamous histologic type was associated with worse OS on univariate and multivariate analyses (p = 0.031 and p = 0.018, respectively). SD/PD plus a squamous histologic type had a hazard ratio of 2.25 vs. CR/PR plus a nonsquamous histologic type (p = 0.007) on covariate analysis. Conclusion: The response to ICT was associated with a significant survival difference when the response groups were compared. A response to ICT showed a trend toward, but was not predictive of, improved OS in LANSCLC patients. Patients with SD/PD after ICT and a squamous histologic type had the poorest OS. These data suggest that patients with squamous LANSCLC might benefit from immediate RT or CCRT.« less

A Randomized Controlled Trial to Evaluate if Computerized Cognitive Rehabilitation Improves Neurocognition in Ugandan Children with HIV.

PubMed

Boivin, Michael J; Nakasujja, Noeline; Sikorskii, Alla; Opoka, Robert O; Giordani, Bruno

2016-08-01

Clinically stable children with HIV can have neuromotor, attention, memory, visual-spatial, and executive function impairments. We evaluated neuropsychological and behavioral benefits of computerized cognitive rehabilitation training (CCRT) in Ugandan HIV children. One hundred fifty-nine rural Ugandan children with WHO Stage I or II HIV disease (6 to 12 years; 77 boys, 82 girls; M = 8.9, SD = 1.86 years) were randomized to one of three treatment arms over a 2-month period. The CCRT arm received 24 one-hour sessions over 2 months, using Captain's Log (BrainTrain Corporation) programmed for games targeting working memory, attention, and visual-spatial analysis. These games progressed in difficulty as the child's performance improved. The second arm was a "limited CCRT" with the same games rotated randomly from simple to moderate levels of training. The third arm was a passive control group receiving no training. All children were assessed at enrollment, 2 months (immediately following CCRT), and 3 months after CCRT completion. The CCRT group had significantly greater gains through 3 months of follow-up compared to passive controls on overall Kaufman Assessment Battery for Children-second edition (KABC-II) mental processing index (p < .01), planning (p = .04), and knowledge (p = .03). The limited CCRT group performed better than controls on learning (p = .05). Both CCRT arms had significant improvements on CogState Groton maze learning (p < .01); although not on CogState attention/memory, TOVA/impulsivity, or behavior rating inventory for executive function and child behavior checklist (psychiatric behavior/symptom problems) ratings by caregiver. CCRT intervention can be effective for neurocognitive rehabilitation in children with HIV in low-resource settings, especially in children who are clinically stable on ARV treatment.

Surgical resection after TNFerade therapy for locally advanced pancreatic cancer.

PubMed

Chadha, Manpreet K; Litwin, Alan; Levea, Charles; Iyer, Renuka; Yang, Gary; Javle, Milind; Gibbs, John F

2009-09-04

Treatment of pancreatic cancer remains a major oncological challenge and survival is dismal. Most patients, present with advanced disease at diagnosis and are not candidates for curative resection. Preoperative chemoradiation may downstage and improve survival in locally advanced pancreatic cancer. This has prompted investigators to look for novel neoadjuvant therapies. Gene therapy for pancreatic cancer is a novel investigational approach that may have promise. TNFerade is a replication deficient adenovirus vector carrying the human tumor necrosis factor (TNF)-alpha gene regulated under control of a radiation-inducible gene promoter. Transfection of tumor cells with TNFerade maximizes the antitumor effect of TNF-alpha under influence of radiation leading to synergistic effects in preclinical studies. We describe a case of locally advanced unresectable pancreatic cancer treated with a novel multimodal approach utilizing gene therapy with TNFerade and concurrent chemoradiation that was followed by successful surgical resection. Neoadjuvant TNFerade based chemoradiation therapy may be a useful adjunct to treatment of locally advanced pancreatic cancer.

Radiotherapy for locally advanced resectable T3-T4 laryngeal cancer-does laryngeal preservation strategy compromise survival?

PubMed

Yamazaki, Hideya; Suzuki, Gen; Nakamura, Satoaki; Hirano, Shigeru; Yoshida, Ken; Konishi, Koji; Teshima, Teruki; Ogawa, Kazuhiko

2018-01-01

With the advancement of chemotherapy, a laryngeal preservation (LP) strategy was explored with the aim of improving maintenance of quality of life. Induction chemotherapy (ICT) following radiotherapy (RT) was considered a viable option because of its high initial response rate without hampering of overall survival (OS). Subsequently, concurrent chemoradiotherapy (CCRT) using CDDP became the standard of care for LP, showing the best LP ratio. For enhancing treatment intensity, ICT with taxan + CDDP + 5-FU (TPF-ICT) followed by RT showed superiority over ICT with CDDP + 5-FU (PF-ICT) followed by RT. Given that almost all randomized controlled trials investigating ICT include not only operable (endpoint, LP) but also inoperable (endpoint, OS) cases, physicians are faced with a dilemma regarding application in daily practice. In addition, increased treatment intensity causes augmentation of adverse events, which might reduce compliance. Thereafter, cetuximab, an effective drug with fewer adverse effects [bioradiotherapy (BRT)], emerged as another option. However, little evidence has confirmed its superiority over RT (or CCRT) in laryngeal cancer subpopulations. In spite of these developments, the OS of patients with laryngeal cancer has not improved for several decades. In fact, several studies indicated a decrease in OS during the 1990s, probably due to overuse of CCRT. Fortunately, the latter was not the case in most institutions. Currently, no other treatment has better OS than surgery. The eligibility criteria for LP and/or surgery largely depend upon the available expertise and experience, which differ from one institution to another. Therefore, a multidisciplinary team is required for the treatment of LP. © The Author 2017. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Locally advanced squamous cell carcinoma of the head and neck: A systematic review and Bayesian network meta-analysis of the currently available treatment options.

PubMed

Iocca, Oreste; Farcomeni, Alessio; Di Rocco, Arianna; Di Maio, Pasquale; Golusinski, Paweł; Pardiñas López, Simón; Savo, Alfredo; Pellini, Raul; Spriano, Giuseppe

2018-05-01

There are still many unresolved questions in the management of locally advanced Head and Neck Cancer (HNC). Many chemotherapeutic drugs and radiotherapy fractionation schemes are available and not all have been evaluated in head-to-head clinical trials. This systematic review and Bayesian network meta-analysis aims to compare the available treatment strategies and chemotherapeutic options for locally advanced HNC. We performed a search on bibliography databases, trials registries and meetings proceedings for published and unpublished randomized trials from January 1st 2000 to December 1st 2017. Trials had to compare systemic interventions and radiotherapy (RT) approaches for locally advanced, non-metastatic HNC. Trials recruiting patients whose surgery was the first treatment option, sample size less than 20 per arm or that did not use randomization for treatment allocation were excluded from the analysis. Summary estimates on Overall survival (OS), Progression-free survival (PFS) and toxicity outcomes (grade 3-4 mucositis and neutropenia) were extracted from the included studies on a predefined database sheet. Bias was assessed through the Chocrane risk of bias assessment tool. We performed a set of pair-wise meta-analyses using a random effect model. We also performed a random effect network meta-analysis under a Bayesian framework. From the 57 included trials, including 15,723 patients, was possible to conduct analysis on 26 treatments for OS, 22 treatments for PFS and 10 treatments for toxicity. In terms of OS Concurrent chemoradiotherapy (CCRT) with cisplatin (HR 0.70, 95% CrI [credible interval] 0.62-0.78) and cetuximab on top of CCRT (HR 0.7, 95% CrI 0.5-0.97) are clearly superior to conventional RT alone. Induction chemotherapy (IC) with cisplatin and fluorouracil (HR 0.74, 95% CrI 0.52-0.95), IC with docetaxel, cisplatin, fluorouracil (HR 0.55, 95% CrI 0.54-0.89) and IC with paclitaxel, cisplatin, fluorouracil (HR 0.55, 95% CrI 0.34-0.89) before CCRT are all superior to conventional RT. CCRT with cisplatin is also superior to altered fractionation RT (HR 0.74, 95% CrI 0.64-0.84). Altered fractionation RT is not superior to conventional RT (HR 0.95, 95% CrI 0.85-1.06). Regarding PFS, CCRT with cisplatin (HR 0.72, 95% CrI 0.63-0.83), cisplatin and fluorouracil (HR 0.67, 95% CrI 0.5-0.88), carboplatin (HR 0.63, 95% CrI 0.46-0.87), carboplatin and fluorouracil (HR 0.75, 95% CrI 0.56-1), IC with cisplatin and fluorouracil (HR 0.59, 95% CrI 0.45-0.78), IC with docetaxel, cisplatin and fluorouracil (HR 0.53, 95% CrI 0.41-0.68) and IC with paclitaxel, cisplatin and fluorouracil (HR 0.59, 95% CrI 0.35-0.99) are superior to conventional RT and altered fractionation RT. IC with docetaxel, cisplatin and fluorouracil shows a significant superiority against CCRT with cisplatin (HR 0.73 95% CrI 0.58-0.92). Altered fractionation RT is not superior to conventional RT (HR 0.91, 95% CrI 0.81-1.02). Altered fractionation increases the risk of developing grade 3-4 mucositis compared to conventional RT (OR 3.74 95% 1.64-8.67) INTERPRETATION: CCRT with cisplatin remains the gold standard of treatment. Taxane based IC regimens may have a impact on locally advanced disease. Altered fractionation RT is inferior to CCRT and also does not seem to be meaningfully better than conventionally fractionated RT alone. Its role in locally advanced disease should be reevaluated. Copyright © 2018 Elsevier Ltd. All rights reserved.

Adjuvant chemoradiotherapy instead of revision radical resection after local excision for high-risk early rectal cancer.

PubMed

Jeong, Jae-Uk; Nam, Taek-Keun; Kim, Hyeong-Rok; Shim, Hyun-Jeong; Kim, Yong-Hyub; Yoon, Mee Sun; Song, Ju-Young; Ahn, Sung-Ja; Chung, Woong-Ki

2016-09-05

After local excision of early rectal cancer, revision radical resection is recommended for patients with high-risk pathologic stage T1 (pT1) or pT2 cancer, but the revision procedure has high morbidity rates. We evaluated the efficacy of adjuvant concurrent chemoradiotherapy (CCRT) for reducing recurrence after local excision in these patients. Eighty-three patients with high-risk pT1 or pT2 rectal cancer underwent postoperative adjuvant CCRT after local excision. We defined high-risk features as pT1 having tumor size ≤3 cm, and/or resection margin (RM) ≤3 mm, and/or lymphovascular invasion (LVI), and/or non-full thickness excision such as endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD), or unknown records regarding those features, or pT2 cancer. Radiotherapy was administered with a median dose of 50.4 Gy in 1.8 Gy fraction size over 5-7 weeks. Concurrent 5-fluorouracil and leucovorin were administered for 4 days in the first and fifth weeks of radiotherapy. The median interval between local excision and radiotherapy was 34 (range, 11-104) days. Fifteen patients (18.1 %) had stage pT2 tumors, 22 (26.5 %) had RM of ≥3 mm, and 21 (25.3 %) had tumors of ≥3 cm in size. Thirteen patients (15.7 %) had LVI. Transanal excision was performed in 58 patients (69.9 %) and 25 patients (30.1 %) underwent EMR or ESD. The median follow-up was 61 months. The 5-year overall survival (OS), locoregional relapse-free survival (LRFS), and disease-free survival (DFS) rates for all patients were 94.9, 91.0, and 89.8 %, respectively. Multivariate analysis did not identify any significant factors for OS or LRFS, but the only significant factor affecting DFS was the pT stage (p = 0.027). In patients with high-risk pT1 rectal cancer, adjuvant CCRT after local excision could be an effective alternative treatment instead of revision radical resection. However, patients with pT2 stage showed inferior DFS compared to pT1.

Phase 3 Trial of Postoperative Chemotherapy Alone Versus Chemoradiation Therapy in Stage III-IV Gastric Cancer Treated With R0 Gastrectomy and D2 Lymph Node Dissection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Tae Hyun; Park, Sook Ryun; Ryu, Keun Won

2012-12-01

Purpose: To compare chemotherapy alone with chemoradiation therapy in stage III-IV(M0) gastric cancer treated with R0 gastrectomy and D2 lymph node dissection. Methods and Materials: The chemotherapy arm received 5 cycles of fluorouracil and leucovorin (FL), and the chemoradiation therapy arm received 1 cycle of FL, then radiation therapy of 45 Gy concurrently with 2 cycles of FL, followed by 2 cycles of FL. Intent-to-treat analysis and per-protocol analyses were performed. Results: Between May 6, 2002 and June 29, 2006, a total of 90 patients were enrolled. Forty-four were randomly assigned to the chemotherapy arm and 46 to the chemoradiationmore » therapy arm. Treatment was completed as planned by 93.2% of patients in the chemotherapy arm and 87.0% in the chemoradiation therapy arm. Overall intent-to-treat analysis showed that addition of radiation therapy to chemotherapy significantly improved locoregional recurrence-free survival (LRRFS) but not disease-free survival. In subgroup analysis for stage III, chemoradiation therapy significantly prolonged the 5-year LRRFS and disease-free survival rates compared with chemotherapy (93.2% vs 66.8%, P=.014; 73.5% vs 54.6%, P=.056, respectively). Conclusions: Addition of radiation therapy to chemotherapy could improve the LRRFS in stage III gastric cancer treated with R0 gastrectomy and D2 lymph node dissection.« less

An Intergroup Randomized Phase II Study of Bevacizumab or Cetuximab in Combination with Gemcitabine and in Combination with Chemoradiation in Patients with Resected Pancreatic Carcinoma: A Trial of the ECOG-ACRIN Cancer Research Group (E2204).

PubMed

Berlin, Jordan D; Feng, Yang; Catalano, Paul; Abbruzzese, James L; Philip, Philip A; McWilliams, Robert R; Lowy, Andrew M; Benson, Al B; Blackstock, A William

2018-01-01

Evaluate toxicity of two treatment arms, A (cetuximab) and B (bevacizumab), when combined with gemcitabine, and chemoradiation in patients with completely resected pancreatic carcinoma. Secondary objectives included overall survival (OS) and disease-free survival (DFS). Patients with R0/R1 resection were randomized 1:1 to cetuximab or bevacizumab administered in combination with gemcitabine for two treatment cycles. Next three cycles included concurrent cetuximab/bevacizumab plus chemoradiation, followed by one cycle of cetuximab/bevacizumab. Cycles 7-12 included cetuximab/bevacizumab with gemcitabine. Cycles were 2 weeks. Frequency of specific toxicities was summarized for each treatment arm at two times during the study, after chemotherapy but prior to chemoradiation and after all therapy. A total of 127 patients were randomized (A, n = 65; B, n = 62). Prior to chemoradiation, the overall rate for toxicities of interest was 10% for arm A and 2% for arm B. After all therapy, the overall rates for toxicities of interest were 30 and 25% for arms A and B, respectively. Overall median OS and DFS were 17 and 11 months, respectively, which is not a significant improvement over expected survival rates for historical controls. Both treatments were tolerable with manageable toxicities, and were safe enough for a phase III trial had this been indicated. © 2017 S. Karger AG, Basel.

Management of acute skin toxicity with Hypericum perforatum and neem oil during platinum-based concurrent chemo-radiation in head and neck cancer patients.

PubMed

Franco, Pierfrancesco; Rampino, Monica; Ostellino, Oliviero; Schena, Marina; Pecorari, Giancarlo; Garzino Demo, Paolo; Fasolis, Massimo; Arcadipane, Francesca; Martini, Stefania; Cavallin, Chiara; Airoldi, Mario; Ricardi, Umberto

2017-02-01

Acute skin toxicity is a frequent finding during combined radiotherapy and chemotherapy in head and neck cancer patients. Its timely and appropriate management is crucial for both oncological results and patient's global quality of life. We herein report clinical data on the use of Hypericum perforatum and neem oil in the treatment of acute skin toxicity during concurrent chemo-radiation for head and neck cancer. A consecutive series of 50 head and neck cancer patients undergoing concomitant radio-chemotherapy with weekly cisplatin was analyzed. Treatment with Hypericum perforatum and neem oil was started in case of G2 acute skin toxicity according to the RTOG/EORTC scoring scale and continued during the whole treatment course and thereafter until complete recovery. The maximum detected acute skin toxicity included Grade 2 events in 62% of cases and G3 in 32% during treatment and G2 and G3 scores in 52 and 8%, respectively, at the end of chemo-radiation. Grade 2 toxicity was mainly observed during weeks 4-5, while G3 during weeks 5-6. Median times spent with G2 or G3 toxicity were 23.5 and 14 days. Patients with G3 toxicity were reconverted to a G2 profile in 80% of cases, while those with a G2 score had a decrease to G1 in 58% of cases. Time between maximum acute skin toxicity and complete skin recovery was 30 days. Mean worst pain score evaluated with the Numerical Rating Scale-11 was 6.9 during treatment and 4.5 at the end of chemo-radiotherapy. Hypericum perforatum and neem oil proved to be a safe and effective option in the management of acute skin toxicity in head and neck cancer patients submitted to chemo-radiation with weekly cisplatin. Further studies with a control group and patient-reported outcomes are needed to confirm this hypothesis.

Adjuvant Chemoradiation for Gastric Cancer Using Epirubicin, Cisplatin, and 5-Fluorouracil Before and After Three-Dimensional Conformal Radiotherapy With Concurrent Infusional 5-Fluorouracil: A Multicenter Study of the Trans-Tasman Radiation Oncology Group

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leong, Trevor, E-mail: trevor.leong@petermac.or; Joon, Daryl Lim; Willis, David

Purpose: The INT0116 study has established postoperative chemoradiotherapy as the standard of care for completely resected gastric adenocarcinoma. However, the optimal chemoradiation regimen remains to be defined. We conducted a prospective, multicenter study to evaluate an alternative chemoradiation regimen that combines more current systemic treatment with modern techniques of radiotherapy delivery. Methods and Materials: Patients with adenocarcinoma of the stomach who had undergone an R0 resection were eligible. Adjuvant therapy consisted of one cycle of epirubicin, cisplatin, and 5-FU (ECF), followed by radiotherapy with concurrent infusional 5-FU, and then two additional cycles of ECF. Radiotherapy was delivered using precisely defined,more » multiple-field, three-dimensional conformal techniques. Results: A total of 54 assessable patients were enrolled from 19 institutions. The proportion of patients commencing Cycles 1, 2, and 3 of ECF chemotherapy were 100%, 81%, and 67% respectively. In all, 94% of patients who received radiotherapy completed treatment as planned. Grade 3/4 neutropenia occurred in 66% of patients with 7.4% developing febrile neutropenia. Most neutropenic episodes (83%) occurred in the post-radiotherapy period during cycles 2 and 3 of ECF. Grade 3/4 gastrointestinal toxicity occurred in 28% of patients. In all, 35% of radiotherapy treatment plans contained protocol deviations that were satisfactorily amended before commencement of treatment. At median follow-up of 36 months, the 3-year overall survival rate was estimated at 61.6%. Conclusions: This adjuvant regimen using ECF before and after three-dimensional conformal chemoradiation is feasible and can be safely delivered in a cooperative group setting. A regimen similar to this is currently being compared with the INT0116 regimen in a National Cancer Institute-sponsored, randomized Phase III trial.« less

A preliminary investigation into textural features of intratumoral metabolic heterogeneity in 18F-FDG PET for overall survival prognosis in patients with bulky cervical cancer treated with definitive concurrent chemoradiotherapy

PubMed Central

Ho, Kung-Chu; Fang, Yu-Hua Dean; Chung, Hsiao-Wen; Yen, Tzu-Chen; Ho, Tsung-Ying; Chou, Hung-Hsueh; Hong, Ji-Hong; Huang, Yi-Ting; Wang, Chun-Chieh; Lai, Chyong-Huey

2016-01-01

We examined the role of intratumoral metabolic heterogeneity on 18F-FDG PET during concurrent chemoradiotherapy (CCRT) in predicting survival outcomes for patients with cervical cancer. This prospective study consisted of 44 patients with bulky (≥ 4 cm) cervical cancer treated with CCRT. All patients underwent serial 18F-FDG PET studies. Primary cervical tumor standardized uptake values, metabolic tumor volume, and total lesion glycolysis (TLG) were measured in pretreatment and intra-treatment (2 weeks) PET scans. Regional textural features were analyzed using the grey level run length encoding method (GLRLM) and grey-level size zone matrix. Associations between PET parameters and overall survival (OS) were tested by Kaplan-Meier analysis and Cox regression model. In univariate analysis, pretreatment grey-level nonuniformity (GLNU) > 48 by GLRLM textural analysis and intra-treatment decline of run length nonuniformity < 55% and the decline of TLG (∆TLG) < 60% were associated with significantly worse OS. In multivariate analysis, only ∆TLG was significant (P = 0.009). Combining pretreatment with intra-treatment factors, we defined the patients with a initial GLNU > 48 and a ∆TLG ≤ 60% as the high-risk group and the other patients as the low-risk. The 5-year OS rate for the high-risk group was significantly worse than that for the low-risk group (42% vs. 81%, respectively, P = 0.001). The heterogeneity of intratumoral FDG distribution and the early temporal change in TLG may be an important predictor for OS in patients with bulky cervical cancer. This gives the opportunity to adjust individualized regimens early in the treatment course. PMID:27508103

Prospective clinical study on long-term swallowing function and voice quality in advanced head and neck cancer patients treated with concurrent chemoradiotherapy and preventive swallowing exercises.

PubMed

Kraaijenga, Sophie A C; van der Molen, Lisette; Jacobi, Irene; Hamming-Vrieze, Olga; Hilgers, Frans J M; van den Brekel, Michiel W M

2015-11-01

Concurrent chemoradiotherapy (CCRT) for advanced head and neck cancer (HNC) is associated with substantial early and late side effects, most notably regarding swallowing function, but also regarding voice quality and quality of life (QoL). Despite increased awareness/knowledge on acute dysphagia in HNC survivors, long-term (i.e., beyond 5 years) prospectively collected data on objective and subjective treatment-induced functional outcomes (and their impact on QoL) still are scarce. The objective of this study was the assessment of long-term CCRT-induced results on swallowing function and voice quality in advanced HNC patients. The study was conducted as a randomized controlled trial on preventive swallowing rehabilitation (2006-2008) in a tertiary comprehensive HNC center with twenty-two disease-free and evaluable HNC patients as participants. Multidimensional assessment of functional sequels was performed with videofluoroscopy, mouth opening measurements, Functional Oral Intake Scale, acoustic voice parameters, and (study specific, SWAL-QoL, and VHI) questionnaires. Outcome measures at 6 years post-treatment were compared with results at baseline and at 2 years post-treatment. At a mean follow-up of 6.1 years most initial tumor-, and treatment-related problems remained similarly low to those observed after 2 years follow-up, except increased xerostomia (68%) and increased (mild) pain (32%). Acoustic voice analysis showed less voicedness, increased fundamental frequency, and more vocal effort for the tumors located below the hyoid bone (n = 12), without recovery to baseline values. Patients' subjective vocal function (VHI score) was good. Functional swallowing and voice problems at 6 years post-treatment are minimal in this patient cohort, originating from preventive and continued post-treatment rehabilitation programs.

A preliminary investigation into textural features of intratumoral metabolic heterogeneity in (18)F-FDG PET for overall survival prognosis in patients with bulky cervical cancer treated with definitive concurrent chemoradiotherapy.

PubMed

Ho, Kung-Chu; Fang, Yu-Hua Dean; Chung, Hsiao-Wen; Yen, Tzu-Chen; Ho, Tsung-Ying; Chou, Hung-Hsueh; Hong, Ji-Hong; Huang, Yi-Ting; Wang, Chun-Chieh; Lai, Chyong-Huey

2016-01-01

We examined the role of intratumoral metabolic heterogeneity on (18)F-FDG PET during concurrent chemoradiotherapy (CCRT) in predicting survival outcomes for patients with cervical cancer. This prospective study consisted of 44 patients with bulky (≥ 4 cm) cervical cancer treated with CCRT. All patients underwent serial (18)F-FDG PET studies. Primary cervical tumor standardized uptake values, metabolic tumor volume, and total lesion glycolysis (TLG) were measured in pretreatment and intra-treatment (2 weeks) PET scans. Regional textural features were analyzed using the grey level run length encoding method (GLRLM) and grey-level size zone matrix. Associations between PET parameters and overall survival (OS) were tested by Kaplan-Meier analysis and Cox regression model. In univariate analysis, pretreatment grey-level nonuniformity (GLNU) > 48 by GLRLM textural analysis and intra-treatment decline of run length nonuniformity < 55% and the decline of TLG (∆TLG) < 60% were associated with significantly worse OS. In multivariate analysis, only ∆TLG was significant (P = 0.009). Combining pretreatment with intra-treatment factors, we defined the patients with a initial GLNU > 48 and a ∆TLG ≤ 60% as the high-risk group and the other patients as the low-risk. The 5-year OS rate for the high-risk group was significantly worse than that for the low-risk group (42% vs. 81%, respectively, P = 0.001). The heterogeneity of intratumoral FDG distribution and the early temporal change in TLG may be an important predictor for OS in patients with bulky cervical cancer. This gives the opportunity to adjust individualized regimens early in the treatment course.

Combined-modality treatment for advanced oral tongue squamous cell carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fan, K.-H.; Lin, C.-Y.; Kang, C.-J.

Purpose: The aim of this study was to investigate prognostic factors in advanced-stage oral tongue cancer treated with postoperative adjuvant therapy and to identify indications for adjuvant concomitant chemoradiotherapy (CCRT). Methods and Materials: We retrospectively reviewed the records of 201 patients with advanced squamous cell carcinoma of the oral tongue managed between January 1995 and November 2002. All had undergone wide excision and neck dissection plus adjuvant radiotherapy or CCRT. Based on postoperative staging, 123 (61.2%) patients had Stage IV and 78 (38.8%) had Stage III disease. All patients were followed for at least 18 months after completion of radiotherapymore » or until death. The median follow-up was 40.4 months for surviving patients. The median dose of radiotherapy was 64.8 Gy (range, 58.8-72.8 Gy). Cisplatin-based regimens were used for chemotherapy. Results: The 3-year overall survival (OS) and recurrence-free survival (RFS) rates were 48% and 50.8%, respectively. Stage, multiple nodal metastases, differentiation, and extracapsular spread (ECS) significantly affected disease-specific survival on univariate analysis. On multivariate analysis, multiple nodal metastases, differentiation, ECS, and CCRT were independent prognostic factors. If ECS was present, only CCRT significantly improved survival (3-year RFS with ECS and with CCRT = 48.2% vs. without CCRT = 15%, p = 0.038). In the presence of other poor prognostic factors, results of the two treatment strategies did not significantly differ. Conclusions: Based on this study, ECS appears to be an absolute indication for adjuvant CCRT. CCRT can not be shown to be statistically better than radiotherapy alone in this retrospective series when ECS is not present.« less

Preoperative Short-Course Concurrent Chemoradiation Therapy Followed by Delayed Surgery for Locally Advanced Rectal Cancer: A Phase 2 Multicenter Study (KROG 10-01)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yeo, Seung-Gu; Department of Radiation Oncology, Soonchunhyang University College of Medicine, Cheonan; Oh, Jae Hwan

Purpose: A prospective phase 2 multicenter trial was performed to investigate the efficacy and safety of preoperative short-course concurrent chemoradiation therapy (CRT) followed by delayed surgery for patients with locally advanced rectal cancer. Methods and Materials: Seventy-three patients with cT3-4 rectal cancer were enrolled. Radiation therapy of 25 Gy in 5 fractions was delivered over 5 consecutive days using helical tomotherapy. Concurrent chemotherapy was administered on the same 5 days with intravenous bolus injection of 5-fluorouracil (400 mg/m{sup 2}/day) and leucovorin (20 mg/m{sup 2}/day). After 4 to 8 weeks, total mesorectal excision was performed. The primary endpoint was the pathologicmore » downstaging (ypStage 0-I) rate, and secondary endpoints included tumor regression grade, tumor volume reduction rate, and toxicity. Results: Seventy-one patients completed the planned preoperative CRT and surgery. Downstaging occurred in 20 (28.2%) patients, including 1 (1.4%) with a pathologic complete response. Favorable tumor regression (grade 4-3) was observed in 4 (5.6%) patients, and the mean tumor volume reduction rate was 62.5 ± 21.3%. Severe (grade ≥3) treatment toxicities were reported in 27 (38%) patients from CRT until 3 months after surgery. Conclusions: Preoperative short-course concurrent CRT followed by delayed surgery for patients with locally advanced rectal cancer demonstrated poor pathologic responses compared with conventional long-course CRT, and it yielded considerable toxicities despite the use of an advanced radiation therapy technique.« less

Neuroendocrine small cell carcinoma of the uterine cervix.

PubMed

Reig Castillejo, Anna; Membrive Conejo, Ismael; Foro Arnalot, Palmira; Rodríguez de Dios, Nuria; Algara López, Manuel

2010-07-01

Neuroendocrine small cell carcinoma of the uterine cervix (SCC) is a rare disease that mixes clinical and biological characteristics of both cervical neoplasms and neuroendocrine small cell cancer. The prognosis is poor and the optimal treatment has not yet been clarified. Multimodality treatment, with surgery and concurrent chemoradiation has recently been shown to improve local control and survival rates.

Analysis of a novel protocol of combined induction chemotherapy and concurrent chemoradiation in unresected non-small-cell lung cancer: a ten-year experience with vinblastine, Cisplatin, and radiation therapy.

PubMed

Waters, Eugenie; Dingle, Brian; Rodrigues, George; Vincent, Mark; Ash, Robert; Dar, Rashid; Inculet, Richard; Kocha, Walter; Malthaner, Richard; Sanatani, Michael; Stitt, Larry; Yaremko, Brian; Younus, Jawaid; Yu, Edward

2010-07-01

The London Regional Cancer Program (LRCP) uses a unique schedule of induction plus concurrent chemoradiation, termed VCRT (vinblastine, cisplatin, and radiation therapy), for the treatment of a subset of unresectable stage IIIA and IIIB non-small-cell lung cancer (NSCLC). This analysis was conducted to better understand the outcomes in VCRT-treated patients. We report a retrospective analysis of a large cohort of patients who underwent VCRT at the LRCP over a 10-year period, from 1996 to 2006. The analysis focused on OS, toxicities, and the outcomes from completion surgery in a small subset of patients. A total of 294 patients were included and 5-year OS, determined using Kaplan-Meier methodology, was 19.8% with a MST of 18.2 months. Reported grade 3-4 toxicities included neutropenia (39%), anemia (10%), pneumonitis (1%), and esophagitis (3%). Significant differences in survival between groups of patients were demonstrated with log-rank tests for completion surgery, use of radiation therapy, and cisplatin dose. Similarly, Univariate Cox regression showed that completion surgery, use of radiation therapy, cisplatin dose, and vinblastine dose were associated with increased survival. This retrospective analysis of a large cohort of patients reveals an OS for VCRT comparable to that reported in the literature for other current combined chemoradiation protocols. The success of this protocol seems to be dose dependent and the outcomes in those who underwent completion surgery suggests that pathologic complete remission is possible for IIIA and IIIB NSCLC.

Chemoradiation With Paclitaxel and Carboplatin in High-Risk Cervical Cancer Patients After Radical Hysterectomy: A Korean Gynecologic Oncology Group Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Taek Sang; Kang, Soon Beom, E-mail: tslee70@gmail.com; Kim, Young Tak

Purpose: To evaluate the efficacy and toxicity of concurrent chemoradiation with paclitaxel and carboplatin in patients with high-risk cervical cancer. Methods and Materials: Patients after radical hysterectomy for cervical cancer, with at least 1 high-risk characteristic, were administered paclitaxel 135 mg/m{sup 2}, carboplatin area under the curve = 5 every 3 weeks for 3 cycles concomitant with radiation therapy as adjuvant treatment. Results: This prospective study enrolled 71 consecutive patients. Sixty-six patients (93%) completed the planned treatment. The majority of grade 3/4 neutropenia or nonhematologic toxicities were usually self-limited. Diarrhea grades 3/4 were observed in 4 patients (5.6%). One patientmore » developed anaphylactic shock after infusion of paclitaxel. With a median follow-up of 57 months, recurrences occurred in 16 patients. Multivariable analysis indicated that common iliac lymph node involvement is an independent risk factor for disease recurrence (odds ratio 13.48; 95% confidence interval 2.93-62.03). In the intent-to-treat population (n=71), the estimated 5-year disease-free survival and overall survival rates were 77.3% and 80.3% respectively. In the per-protocol population (n=62), disease-free survival was 78.9% and overall survival was 83.9%. Conclusions: Concurrent chemoradiation with paclitaxel/carboplatin is well tolerated and seems to be effective for patients who undergo radical hysterectomy. Therefore, a prospective, randomized controlled study should be designed to evaluate efficacy of this approach for patients with high-risk cervical cancer.« less

Adjuvant chemoradiation for resected gallbladder cancer: Treatment strategies for one of the leading causes of cancer death in Chilean women.

PubMed

Müller, Bettina; Sola, José A; Carcamo, Marcela; Ciudad, Ana M; Trujillo, Cristian; Cerda, Berta

2013-01-01

Gallbladder cancer (GBC) is the second leading cause of cancer death in women in Chile. Even after curative surgery, prognosis is grim. To evaluate acute and late toxicity and efficacy of adjuvant chemoradiation (CRT) after curatively resected GBC. We retrospectively analyzed the cohort of patients diagnosed between January 1999 and December 2009, treated with adjuvant CRT at our institution. Treatment protocol considered external beam radiation (RT) (45-54 Gy) to tumor bed and regional lymph nodes with or without concurrent 5-fluorouracil (5-FU) (500 mg/m2/day by 120-hours continuous infusion on days 1-5 and 29-33). Data was obtained from medical records, mortality from death certificates. Survival was estimated by Kaplan- Meier curves. 46 patients with curatively resected GBC received adjuvant CRT. Median age was 57 years (range 33-76); 39 patients were female. After diagnosis, a second surgery was performed in 42 patients. Cholecystectomy with hepatic segmentectomy and lymphadenectomy was the curative surgery in 41 patients. All patients received RT with a planned dose of 45 Gy in 25 fractions, 11 patients received a boost to the tumor bed up to 54 Gy and 34 patients had concurrent 5-FU. Therapy was well tolerated. Five patients experienced grade 3 toxicities. No grade 4 or 5 toxicity was observed. No grade >2 late toxicity was observed. Three- and 5-year overall survival (OS) were 57% and 51%, respectively. Adjuvant chemoradiation is well tolerated and might impact favorably on survival in patients with curatively resected GBC.

Robot-Assisted Mckeown Esophagectomy is Feasible After Neoadjuvant Chemoradiation. Our Initial Experience.

PubMed

Goel, Ashish; Shah, Swati H; Selvakumar, Veda Padma Priya; Garg, Shubha; Kumar, Kapil

2018-02-01

Neoadjuvant chemoradiation has become the standard of care for esophageal cancer, especially for middle third esophageal lesions and those with squamous histology. Although more and more thoracic surgeons and surgical oncologists have now shifted to video-assisted and robot-assisted thoracoscopic esophagectomy; there is still limited experience for the use of minimal-assisted approaches in patients undergoing surgery after neoadjuvant chemoradiation. Most surgeons have concerns of feasibility, safety, and oncological outcomes as well as issues related to difficult learning curve in adopting robotic esophagectomy in patients after chemoradiation. We present our initial experience of Robot-Assisted Mckeown Esophagectomy in 27 patients after neoadjuvant chemoradiation, from May 2013 to October 2014. All patients underwent neoadjuvant chemoradiation to a dose of 50.4 Gy/25Fr with concurrent weekly cisplatin, followed by reassessment with clinical examination and repeat FDG PET/CT 6 weeks after completion of chemoradiation. Patients with progressive disease underwent palliative chemotherapy while patients with either partial or significant response to chemoradiation underwent Robot-Assisted Mckeown Esophagectomy with esophageal replacement by gastric conduit and esophagogastric anastomosis in the left neck. Out of 27 patients, 92.5 % patients had stage cT3/T4 tumours and node-positive disease in 48.1 % on imaging. Most patients were middle thoracic esophageal cancers (23/27), with squamous histology in all except for one. All patients received neoadjuvant chemoradiation and subsequently underwent Robot Assisted Mckeown Esophagectomy. The average time for robot docking, thoracic mobilization and total surgical procedure was 13.2, 108.4 and 342.7 min, respectively. The procedure was well tolerated by all patients with only one case of peri-operative mortality. Average ICU stay was 6.35 days (range 3-9 days). R0 resection rate of 96.3 % and average lymph node yield of 18 could be achieved. Pathological node negativity rate (pN0) and complete response (pCR) were 66.6 and 44.4 %, respectively. In the initial cases, four patients had to be converted to open due technical reasons or intraoperative complications. The present study, with shorter operative times, similar ICU stay, overall low morbidity, and mortality and optimal oncological outcomes suggest that robot-assisted thoracic mobilization of esophagus in patients with prior chemoradiation is feasible and safe with acceptable oncological outcomes. It has a shorter learning curve and hence allows for a transthoracic minimally invasive transthoracic esophagectomy to more and more patients, otherwise unfit for conventional approach.

Pilot study of postoperative adjuvant chemoradiation for advanced gastric cancer: Adjuvant 5-FU/cisplatin and chemoradiation with capecitabine

PubMed Central

Lee, Hyung-Sik; Choi, Youngmin; Hur, Won-Joo; Kim, Hyo-Jin; Kwon, Hyuk-Chan; Kim, Sung-Hyun; Kim, Jae-Seok; Lee, Jong-Hoon; Jung, Ghap-Joong; Kim, Min-Chan

2006-01-01

AIM: To evaluate the efficacy and toxicity of postoperative chemoradiation using FP chemotherapy and oral capecitabine during radiation for advanced gastric cancer following curative resection. METHODS: Thirty-one patients who had underwent a potentially curative resection for Stage III and IV (M0) gastric cancer were enrolled. Therapy consists of one cycle of FP (continuous infusion of 5-FU 1000 mg/m2 on d 1 to 5 and cisplatin 60 mg/m2 on d 1) followed by 4500 cGy (180 cGy/d) with capecitabine (1650 mg/m2 daily throughout radiotherapy). Four wk after completion of the radiotherapy, patients received three additional cycles of FP every three wk. The median follow-up duration was 22.2 mo. RESULTS: The 3-year disease free and overall survival in this study were 82.7% and 83.4%, respectively. Four patients (12.9%) showed relapse during follow-up. Eight patients did not complete all planned adjuvant therapy. Grade 3/4 toxicities included neutropenia in 50.2%, anemia in 12.9%, thrombocytopenia in 3.2% and nausea/vomiting in 3.2%. Neither grade 3/4 hand foot syndrome nor treatment related febrile neutropenia or death were observed. CONCLUSION: These preliminary results suggest that this postoperative adjuvant chemoradiation regimen of FP before and after capecitabine and concurrent radiotherapy appears well tolerated and offers a comparable toxicity profile to the chemoradiation regimen utilized in INT-0116. This treatment modality allowed successful loco-regional control rate and 3-year overall survival. PMID:16489675

True progression versus pseudoprogression in the treatment of glioblastomas: a comparison study of normalized cerebral blood volume and apparent diffusion coefficient by histogram analysis.

PubMed

Song, Yong Sub; Choi, Seung Hong; Park, Chul-Kee; Yi, Kyung Sik; Lee, Woong Jae; Yun, Tae Jin; Kim, Tae Min; Lee, Se-Hoon; Kim, Ji-Hoon; Sohn, Chul-Ho; Park, Sung-Hye; Kim, Il Han; Jahng, Geon-Ho; Chang, Kee-Hyun

2013-01-01

The purpose of this study was to differentiate true progression from pseudoprogression of glioblastomas treated with concurrent chemoradiotherapy (CCRT) with temozolomide (TMZ) by using histogram analysis of apparent diffusion coefficient (ADC) and normalized cerebral blood volume (nCBV) maps. Twenty patients with histopathologically proven glioblastoma who had received CCRT with TMZ underwent perfusion-weighted imaging and diffusion-weighted imaging (b = 0, 1000 sec/mm(2)). The corresponding nCBV and ADC maps for the newly visible, entirely enhancing lesions were calculated after the completion of CCRT with TMZ. Two observers independently measured the histogram parameters of the nCBV and ADC maps. The histogram parameters between the true progression group (n = 10) and the pseudoprogression group (n = 10) were compared by use of an unpaired Student's t test and subsequent multivariable stepwise logistic regression analysis to determine the best predictors for the differential diagnosis between the two groups. Receiver operating characteristic analysis was employed to determine the best cutoff values for the histogram parameters that proved to be significant predictors for differentiating true progression from pseudoprogression. Intraclass correlation coefficient was used to determine the level of inter-observer reliability for the histogram parameters. The 5th percentile value (C5) of the cumulative ADC histograms was a significant predictor for the differential diagnosis between true progression and pseudoprogression (p = 0.044 for observer 1; p = 0.011 for observer 2). Optimal cutoff values of 892 × 10(-6) mm(2)/sec for observer 1 and 907 × 10(-6) mm(2)/sec for observer 2 could help differentiate between the two groups with a sensitivity of 90% and 80%, respectively, a specificity of 90% and 80%, respectively, and an area under the curve of 0.880 and 0.840, respectively. There was no other significant differentiating parameter on the nCBV histograms. Inter-observer reliability was excellent or good for all histogram parameters (intraclass correlation coefficient range: 0.70-0.99). The C5 of the cumulative ADC histogram can be a promising parameter for the differentiation of true progression from pseudoprogression of newly visible, entirely enhancing lesions after CCRT with TMZ for glioblastomas.

True Progression versus Pseudoprogression in the Treatment of Glioblastomas: A Comparison Study of Normalized Cerebral Blood Volume and Apparent Diffusion Coefficient by Histogram Analysis

PubMed Central

Song, Yong Sub; Park, Chul-Kee; Yi, Kyung Sik; Lee, Woong Jae; Yun, Tae Jin; Kim, Tae Min; Lee, Se-Hoon; Kim, Ji-Hoon; Sohn, Chul-Ho; Park, Sung-Hye; Kim, Il Han; Jahng, Geon-Ho; Chang, Kee-Hyun

2013-01-01

Objective The purpose of this study was to differentiate true progression from pseudoprogression of glioblastomas treated with concurrent chemoradiotherapy (CCRT) with temozolomide (TMZ) by using histogram analysis of apparent diffusion coefficient (ADC) and normalized cerebral blood volume (nCBV) maps. Materials and Methods Twenty patients with histopathologically proven glioblastoma who had received CCRT with TMZ underwent perfusion-weighted imaging and diffusion-weighted imaging (b = 0, 1000 sec/mm2). The corresponding nCBV and ADC maps for the newly visible, entirely enhancing lesions were calculated after the completion of CCRT with TMZ. Two observers independently measured the histogram parameters of the nCBV and ADC maps. The histogram parameters between the true progression group (n = 10) and the pseudoprogression group (n = 10) were compared by use of an unpaired Student's t test and subsequent multivariable stepwise logistic regression analysis to determine the best predictors for the differential diagnosis between the two groups. Receiver operating characteristic analysis was employed to determine the best cutoff values for the histogram parameters that proved to be significant predictors for differentiating true progression from pseudoprogression. Intraclass correlation coefficient was used to determine the level of inter-observer reliability for the histogram parameters. Results The 5th percentile value (C5) of the cumulative ADC histograms was a significant predictor for the differential diagnosis between true progression and pseudoprogression (p = 0.044 for observer 1; p = 0.011 for observer 2). Optimal cutoff values of 892 × 10-6 mm2/sec for observer 1 and 907 × 10-6 mm2/sec for observer 2 could help differentiate between the two groups with a sensitivity of 90% and 80%, respectively, a specificity of 90% and 80%, respectively, and an area under the curve of 0.880 and 0.840, respectively. There was no other significant differentiating parameter on the nCBV histograms. Inter-observer reliability was excellent or good for all histogram parameters (intraclass correlation coefficient range: 0.70-0.99). Conclusion The C5 of the cumulative ADC histogram can be a promising parameter for the differentiation of true progression from pseudoprogression of newly visible, entirely enhancing lesions after CCRT with TMZ for glioblastomas. PMID:23901325

Randomized Phase 2 Trial of S1 and Oxaliplatin-Based Chemoradiotherapy With or Without Induction Chemotherapy for Esophageal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoon, Dok Hyun; Jang, Geundoo; Department of Internal Medicine, Hallym Medical Center, Hallym University College of Medicine, Seoul

2015-03-01

Purpose: To assess, in a randomized, phase 2 trial, the efficacy and safety of chemoradiotherapy with or without induction chemotherapy (ICT) of S1 and oxaliplatin for esophageal cancer. Patients and Methods: Patients with stage II, III, or IVA esophageal cancer were randomly allocated to either 2 cycles of ICT (oxaliplatin 130 mg/m{sup 2} on day 1 and S1 at 40 mg/m{sup 2} twice daily on days 1-14, every 3 weeks) followed by concurrent chemoradiotherapy (CCRT) (46 Gy, 2 Gy/d with oxaliplatin 130 mg/m{sup 2} on days 1 and 21 and S1 30 mg/m{sup 2} twice daily, 5 days per week during radiation therapy) and esophagectomy (arm A), ormore » the same CCRT followed by esophagectomy without ICT (arm B). The primary endpoint was the pathologic complete response (pCR) rate. Results: A total of 97 patients were randomized (arm A/B, 47/50), 70 of whom underwent esophagectomy (arm A/B, 34/36). The intention-to-treat pCR rate was 23.4% (95% confidence interval [CI] 11.2-35.6%) in arm A and 38% (95% CI 24.5% to 51.5%) in arm B. With a median follow-up duration of 30.3 months, the 2-year progression-free survival rate was 58.4% in arm A and 58.6% in arm B, whereas the 2-year overall survival rate was 60.7% and 63.7%, respectively. Grade 3 or 4 thrombocytopenia during CCRT was more common in arm A than in arm B (35.4% vs 4.1%). The relative dose intensity of S1 (89.5% ± 20.6% vs 98.3% ± 5.2%, P=.005) and oxaliplatin (91.4% ± 16.8% vs 99.0% ± 4.2%, P=.007) during CCRT was lower in arm A compared with arm B. Three patients in arm A, compared with none in arm B, died within 90 days after surgery. Conclusions: Combination chemotherapy of S1 and oxaliplatin is an effective chemoradiotherapy regimen to treat esophageal cancer. However, we failed to show that the addition of ICT to the regimen can improve the pCR rate.« less

Randomized phase 2 trial of S1 and oxaliplatin-based chemoradiotherapy with or without induction chemotherapy for esophageal cancer.

PubMed

Yoon, Dok Hyun; Jang, Geundoo; Kim, Jong Hoon; Kim, Yong-Hee; Kim, Ji Youn; Kim, Hyeong Ryul; Jung, Hwoon-Yong; Lee, Gin-Hyug; Song, Ho Young; Cho, Kyung-Ja; Ryu, Jin-Sook; Kim, Sung-Bae

2015-03-01

To assess, in a randomized, phase 2 trial, the efficacy and safety of chemoradiotherapy with or without induction chemotherapy (ICT) of S1 and oxaliplatin for esophageal cancer. Patients with stage II, III, or IVA esophageal cancer were randomly allocated to either 2 cycles of ICT (oxaliplatin 130 mg/m(2) on day 1 and S1 at 40 mg/m(2) twice daily on days 1-14, every 3 weeks) followed by concurrent chemoradiotherapy (CCRT) (46 Gy, 2 Gy/d with oxaliplatin 130 mg/m(2) on days 1 and 21 and S1 30 mg/m(2) twice daily, 5 days per week during radiation therapy) and esophagectomy (arm A), or the same CCRT followed by esophagectomy without ICT (arm B). The primary endpoint was the pathologic complete response (pCR) rate. A total of 97 patients were randomized (arm A/B, 47/50), 70 of whom underwent esophagectomy (arm A/B, 34/36). The intention-to-treat pCR rate was 23.4% (95% confidence interval [CI] 11.2-35.6%) in arm A and 38% (95% CI 24.5% to 51.5%) in arm B. With a median follow-up duration of 30.3 months, the 2-year progression-free survival rate was 58.4% in arm A and 58.6% in arm B, whereas the 2-year overall survival rate was 60.7% and 63.7%, respectively. Grade 3 or 4 thrombocytopenia during CCRT was more common in arm A than in arm B (35.4% vs 4.1%). The relative dose intensity of S1 (89.5% ± 20.6% vs 98.3% ± 5.2%, P=.005) and oxaliplatin (91.4% ± 16.8% vs 99.0% ± 4.2%, P=.007) during CCRT was lower in arm A compared with arm B. Three patients in arm A, compared with none in arm B, died within 90 days after surgery. Combination chemotherapy of S1 and oxaliplatin is an effective chemoradiotherapy regimen to treat esophageal cancer. However, we failed to show that the addition of ICT to the regimen can improve the pCR rate. Copyright © 2015 Elsevier Inc. All rights reserved.

External validation of leukocytosis and neutrophilia as a prognostic marker in anal carcinoma treated with definitive chemoradiation.

PubMed

Schernberg, Antoine; Huguet, Florence; Moureau-Zabotto, Laurence; Chargari, Cyrus; Rivin Del Campo, Eleonor; Schlienger, Michel; Escande, Alexandre; Touboul, Emmanuel; Deutsch, Eric

2017-07-01

To validate the prognostic value of leukocyte disorders in anal squamous cell carcinoma (SCC) patients receiving definitive concurrent chemoradiation. Bi-institutional clinical records from consecutive patients treated between 2001 and 2015 with definitive chemoradiation for anal SCC were retrospectively reviewed. Prognostic value of pretreatment leukocyte disorders was examined, with focus on patterns of relapse and survival. Leukocytosis and neutrophilia were defined as leukocyte or neutrophil count exceeding 10G/L and 7G/L, respectively. We identified 133 patients, treated in two institutions. Eight% and 7% displayed baseline leukocytosis and neutrophilia, respectively. Estimated 3-year overall survival (OS) and progression-free survival (PFS) were 88% and 77%, respectively. In univariate analysis, both leukocytosis and neutrophilia were associated with worse OS, PFS (p<0.01), locoregional control (LRC) and Distant Metastasis Control (DMC) (p<0.05), also after stratification by each institution. In multivariate analysis, leukocytosis and neutrophilia remained as independent risk factors associated with poorer OS, PFS, LRC and DMC (p<0.05). This study validates leukocytosis and neutrophilia as independent prognostic factors in anal SCC patients treated with definitive chemoradiation. Although prospective confirmation is warranted, it is suggested that the leukocyte and neutrophil count parameters are clinically relevant biomarkers to be considered for further clinical investigations. Copyright © 2017 Elsevier B.V. All rights reserved.

Concurrent Chemoradiation with Concomitant Boost in Locally Advanced Rectal Cancer: A Phase II Study.

PubMed

Picardi, Vincenzo; Deodato, Francesco; Guido, Alessandra; Giaccherini, Lucia; Macchia, Gabriella; Gambacorta, Maria A; Arcelli, Alessandra; Farioli, Andrea; Cellini, Francesco; Cuicchi, Dajana; DI Fabio, Francesca; Poggioli, Gilberto; Ardizzoni, Andrea; Frezza, Giovanni; Cilla, Savino; Caravatta, Luciana; Valentini, Vincenzo; Fuccio, Lorenzo; Morganti, Alessio G

2016-08-01

The aim of this study was to evaluate the pathological response of locally advanced rectal cancer after preoperative concurrent two-drug chemotherapy and intensified radiation therapy (RT) with concomitant boost. Patients with T4 tumor or local recurrence were included. A trial based on two-stage Simon's design was planned. RT was performed with 3D-conformal technique. The dose to the mesorectum and pelvic lymph nodes was 45 Gy (1.8 Gy/fraction). A concomitant boost was delivered to Gross Tumor Volume (GTV) 2 cm margin to a total dose of 55 Gy (2.2 Gy/fraction). The following concurrent chemotherapy was administered: Raltitrexed (3 mg/m(2)) and oxaliplatin (130 mg/m(2)) on days 1, 17, and 35 of RT. Pathological response was evaluated according to the Mandard classification. Toxicities were scored according to the Common Terminology Criteria for Adverse Events v3.0 scale. Eighteen patients (median age=64.5 years) were enrolled. The median follow-up was 22 months (range=2-36 months). After chemoradiation treatment, 16 patients underwent surgical resection (seven anterior resections and nine abdominal-perineal amputation); two patients did not undergo surgery due to early metastatic progression or refusal. R0 resection was achieved in all patients who underwent surgery. Five patients had pathological complete response [27.7%; 95% confidence interval (CI)=9.7-53.5%] and two patients showed only microscopic residual disease (11.1%; 95% CI=0.1-34.7%). Mandard grades 1 and 2 were detected in seven patients (38.9%; 95% CI=17.3-64.3%). Acute grade 3 or more toxicity was found in eight patients (44.4%; 95% CI=21.5-69.2%): one leucopenia-neutropenia, one liver, one skin and five cases of gastrointestinal toxicities. No patient had local tumor recurrence. One-, 2- and 3-year cumulative disease-free survival were 93.8%. One-, 2- and 3-year cumulative overall survival were 92.3%. Concurrent chemoradiation with concomitant boost in patients with advanced rectal cancer allows complete or near-complete pathological response in more than 38% of patients. However, severe acute toxicity was reported in more than one-third of patients. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Late post-treatment radiographic changes 3 years following chemoradiation for glioma: the importance of histopathology.

PubMed

Galante, Joao R; Rodriguez, Fausto; Grossman, Stuart A; Strowd, Roy E

2017-07-18

Treatment-related changes can mimic brain tumor progression both clinically and radiographically. Distinguishing these two entities represents a major challenge in neuro-oncology. No single imaging modality is capable of reliably achieving such distinction. While histopathology remains the gold standard, definitive pathological criteria are also lacking which can further complicate such cases. We report a patient with high-grade glioma who, after initially presenting with histopathologically confirmed pseudoprogression 10 months following treatment, re-presented 3 years following concurrent chemoradiation with clinical and radiographic changes that were most consistent with progressive disease but for which histopathology revealed treatment effects without active glioma. This case highlights the potential late onset of treatment-related changes and underscores the importance of histopathologic assessment even years following initial therapy.

A Randomized Controlled Trial to Evaluate if Computerized Cognitive Rehabilitation Improves Neurocognition in Ugandan Children with HIV

PubMed Central

Nakasujja, Noeline; Sikorskii, Alla; Opoka, Robert O.; Giordani, Bruno

2016-01-01

Abstract Objectives: Clinically stable children with HIV can have neuromotor, attention, memory, visual–spatial, and executive function impairments. We evaluated neuropsychological and behavioral benefits of computerized cognitive rehabilitation training (CCRT) in Ugandan HIV children. Design: One hundred fifty-nine rural Ugandan children with WHO Stage I or II HIV disease (6 to 12 years; 77 boys, 82 girls; M = 8.9, SD = 1.86 years) were randomized to one of three treatment arms over a 2-month period. Methods: The CCRT arm received 24 one-hour sessions over 2 months, using Captain's Log (BrainTrain Corporation) programmed for games targeting working memory, attention, and visual–spatial analysis. These games progressed in difficulty as the child's performance improved. The second arm was a “limited CCRT” with the same games rotated randomly from simple to moderate levels of training. The third arm was a passive control group receiving no training. All children were assessed at enrollment, 2 months (immediately following CCRT), and 3 months after CCRT completion. Results: The CCRT group had significantly greater gains through 3 months of follow-up compared to passive controls on overall Kaufman Assessment Battery for Children–second edition (KABC-II) mental processing index (p < .01), planning (p = .04), and knowledge (p = .03). The limited CCRT group performed better than controls on learning (p = .05). Both CCRT arms had significant improvements on CogState Groton maze learning (p < .01); although not on CogState attention/memory, TOVA/impulsivity, or behavior rating inventory for executive function and child behavior checklist (psychiatric behavior/symptom problems) ratings by caregiver. Conclusions: CCRT intervention can be effective for neurocognitive rehabilitation in children with HIV in low-resource settings, especially in children who are clinically stable on ARV treatment. PMID:27045714

Neoadjuvant Chemoradiation Therapy Using Concurrent S-1 and Irinotecan in Rectal Cancer: Impact on Long-Term Clinical Outcomes and Prognostic Factors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakamura, Takatoshi; Yamashita, Keishi; Sato, Takeo

2014-07-01

Purpose: To assess the long-term outcomes of patients with rectal cancer who received neoadjuvant chemoradiation therapy (NCRT) with concurrent S-1 and irinotecan (S-1/irinotecan) therapy. Methods and Materials: The study group consisted of 115 patients with clinical stage T3 or T4 rectal cancer. Patients received pelvic radiation therapy (45 Gy) plus concurrent oral S-1/irinotecan. The median follow-up was 60 months. Results: Grade 3 adverse effects occurred in 7 patients (6%), and the completion rate of NCRT was 87%. All 115 patients (100%) were able to undergo R0 surgical resection. Twenty-eight patients (24%) had a pathological complete response (ypCR). At 60 months,more » the local recurrence-free survival was 93%, disease-free survival (DFS) was 79%, and overall survival (OS) was 80%. On multivariate analysis with a proportional hazards model, ypN2 was the only independent prognostic factor for DFS (P=.0019) and OS (P=.0064) in the study group as a whole. Multivariate analysis was additionally performed for the subgroup of 106 patients with ypN0/1 disease, who had a DFS rate of 85.3%. Both ypT (P=.0065) and tumor location (P=.003) were independent predictors of DFS. A combination of these factors was very strongly related to high risk of recurrence (P<.0001), which occurred most commonly in the lung. Conclusions: NCRT with concurrent S-1/irinotecan produced high response rates and excellent long-term survival, with acceptable adverse effects in patients with rectal cancer. ypN2 is a strong predictor of dismal outcomes, and a combination of ypT and tumor location can identify high-risk patients among those with ypN0/1 disease.« less

Concurrent cetuximab versus platinum-based chemoradiation for the definitive treatment of locoregionally advanced head and neck cancer.

PubMed

Tang, Chad; Chan, Cato; Jiang, Wen; Murphy, James D; von Eyben, Rie; Colevas, A Dimitrios; Pinto, Harlan; Lee-Enriquez, Nancy; Kong, Christina; Le, Quynh-Thu

2015-03-01

The purpose of this study was to present our experience utilizing cetuximab and platinum-based concurrent chemoradiotherapy for the definitive treatment of head and neck squamous cell carcinoma (HNSCC). Patients (n = 177) who received definitive concurrent chemoradiotherapy for HNSCC were stratified into 3 groups: receiving cetuximab monotherapy (n = 24), cetuximab and chemotherapy combination (n = 33), or platinum-based chemotherapy without cetuximab (n = 120). Primary endpoints were freedom from relapse, event-free survival, and overall survival (OS). Patients receiving cetuximab monotherapy were older with lower Karnofsky performance status (KPS) and higher Charlson comorbidity scores compared with those treated with combination cetuximab and chemotherapy or platinum-based concurrent chemoradiotherapy. Patients treated with platinum-based concurrent chemoradiotherapy exhibited significantly better freedom from relapse, event-free survival, and OS compared with those receiving cetuximab monotherapy or cetuximab and chemotherapy combination therapies (all p < .05). Differences between patients receiving cetuximab monotherapy and platinum-based concurrent chemoradiotherapy held on multivariate Cox regression. This study suggests that platinum-based concurrent chemoradiotherapy is superior to cetuximab-based monotherapy for the definitive treatment of HNSCC. © 2014 Wiley Periodicals, Inc.

A Phase 2 Trial of Radiation Therapy With Concurrent Paclitaxel Chemotherapy After Surgery in Patients With High-Risk Endometrial Cancer: A Korean Gynecologic Oncologic Group Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cho, Hanbyoul; Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul; Nam, Byung-Ho

2014-09-01

Purpose: A phase 2 study was completed by the Korean Gynecologic Oncologic Group to evaluate the efficacy and toxicity of concurrent chemoradiation with weekly paclitaxel in patients with high-risk endometrial cancer. Methods and Materials: Pathologic requirements included endometrial endometrioid adenocarcinoma stages III and IV. Radiation therapy consisted of a total dose of 4500 to 5040 cGy in 5 fractions per week for 6 weeks. Paclitaxel 60 mg/m{sup 2} was administered once weekly for 5 weeks during radiation therapy. Results: Fifty-seven patients were enrolled between January 2006 and March 2008. The median follow-up time was 60.0 months (95% confidence interval [CI], 51.0-58.2). All grade 3/4 toxicitiesmore » were hematologic and usually self-limited. There was no life-threatening toxicity. The cumulative incidence of intrapelvic recurrence sites was 1.9% (1/52), and the cumulative incidence of extrapelvic recurrence sites was 34.6% (18/52). The estimated 5-year disease-free and overall survival rates were 63.5% (95% CI, 50.4-76.5) and 82.7% (95% CI, 72.4-92.9), respectively. Conclusions: Concurrent chemoradiation with weekly paclitaxel is well tolerated and seems to be effective for high-risk endometrioid endometrial cancers. This approach appears reasonable to be tested for efficacy in a prospective, randomized controlled study.« less

Duodenal Toxicity After Fractionated Chemoradiation for Unresectable Pancreatic Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kelly, Patrick; Das, Prajnan; Pinnix, Chelsea C.

2013-03-01

Purpose: Improving local control is critical to improving survival and quality of life for patients with locally advanced unresectable pancreatic cancer (LAPC). However, previous attempts at radiation dose escalation have been limited by duodenal toxicity. In order to guide future studies, we analyzed the clinical and dosimetric factors associated with duodenal toxicity in patients undergoing fractionated chemoradiation for LAPC. Methods and Materials: Medical records and treatment plans of 106 patients with LAPC who were treated with chemoradiation between July 2005 and June 2010 at our institution were reviewed. All patients received neoadjuvant and concurrent chemotherapy. Seventy-eight patients were treated withmore » conventional radiation to 50.4 Gy in 28 fractions; 28 patients received dose-escalated radiation therapy (range, 57.5-75.4 Gy in 28-39 fractions). Treatment-related toxicity was graded according to Common Terminology Criteria for Adverse Events, version 4.0. Univariate and multivariate analyses were performed to assess prognostic influence of clinical, pathologic, and treatment-related factors by using Kaplan-Meier and Cox regression methods. Results: Twenty patients had treatment-related duodenal toxicity events, such as duodenal inflammation, ulceration, and bleeding. Four patients had grade 1 events, 8 had grade 2, 6 had grade 3, 1 had grade 4, and 1 had grade 5. On univariate analysis, a toxicity grade ≥2 was associated with tumor location, low platelet count, an absolute volume (cm{sup 3}) receiving a dose of at least 55 Gy (V{sub 55} {sub Gy} > 1 cm{sup 3}), and a maximum point dose >60 Gy. Of these factors, only V{sub 55} {sub Gy} ≥1 cm{sup 3} was associated with duodenal toxicity on multivariate analysis (hazard ratio, 6.7; range, 2.0-18.8; P=.002). Conclusions: This study demonstrates that a duodenal V{sub 55} {sub Gy} >1 cm{sup 3} is an important dosimetric predictor of grade 2 or greater duodenal toxicity and establishes it as a dosimetric constraint when treating patients with unresectable pancreatic cancer with concurrent chemoradiation.« less

Induction Chemotherapy With Gemcitabine, Oxaliplatin, and 5-Fluorouracil/Leucovorin Followed by Concomitant Chemoradiotherapy in Patients With Locally Advanced Pancreatic Cancer: A Taiwan Cooperative Oncology Group Phase II Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ch'ang, Hui-Ju; Department of Radiation Oncology, National Cheng Kung University Hospital, Tainan, Taiwan; Lin, Yu-Lin

Purpose: To evaluate the therapeutic efficacy of 3-month triplet induction chemotherapy (ICT) followed by concomitant chemoradiotherapy (CCRT) in patients with locally advanced pancreatic cancer (LAPC). Patients and Methods: Chemonaieve patients with measurable, histologically confirmed LAPC were eligible. The ICT consisted of biweekly gemcitabine (800 mg/m{sup 2}) infusion at a fixed dose rate (10 mg/m{sup 2}/min), followed by 85 mg/m{sup 2} oxaliplatin and 48-h infusion of 5-fluorouracil/leucovorin (3000/150 mg/m{sup 2}) for 6 cycles. Patients without disease progression 4 weeks after ICT would receive weekly 400 mg/m{sup 2} gemcitabine and 5040 cGy radiation in 28 fractions. After CCRT, patients were subjected formore » surgical intervention and/or maintenance chemotherapy until progression or intolerable toxicity. Results: Between December 2004 and August 2008, 50 patients were enrolled. The best responses after ICT were partial response (PR) in 9, stable disease in 26, and progressive disease or not evaluable in 15. Among the former 35 patients, 2 had disease progression before CCRT, and 3 declined to have CCRT. Of the 30 patients receiving CCRT, an additional 4 and 1 patient(s) achieved PR at the end of CCRT and during maintenance chemotherapy, respectively. On intent-to-treat analysis, the overall best response was PR in 14 patients and stable disease in 21. The overall response rate and disease control rate were 28% (95% confidence interval [CI], 16.2-42.5%) and 70% (95% CI, 44.4-99.2%), respectively. The median time to progression and overall survival of the intent-to-treat population was 9.3 (95% CI, 5.8-12.8) months and 14.5 (95% CI, 11.9-17.1) months, respectively. One- and two-year survival rates were 68% (95% CI, 55.1-80.9%) and 20.6% (95% CI, 8.7-32.5%), respectively. Neutropenia was the most common Grade 3-4 toxicity of both ICT and CCRT, with a frequency of 28% and 26.7%, respectively. Significant sensory neuropathy occurred in 9 patients (18%). Conclusion: Three months of triplet ICT followed by gemcitabine-based CCRT is feasible, moderately active, and associated with encouraging survival in patients with LAPC.« less

Cumulative cisplatin dose in concurrent chemoradiotherapy for head and neck cancer: A systematic review.

PubMed

Strojan, Primož; Vermorken, Jan B; Beitler, Jonathan J; Saba, Nabil F; Haigentz, Missak; Bossi, Paolo; Worden, Francis P; Langendijk, Johannes A; Eisbruch, Avraham; Mendenhall, William M; Lee, Anne W M; Harrison, Louis B; Bradford, Carol R; Smee, Robert; Silver, Carl E; Rinaldo, Alessandra; Ferlito, Alfio

2016-04-01

The optimal cumulative dose and timing of cisplatin administration in various concurrent chemoradiotherapy protocols for nonmetastatic head and neck squamous cell carcinoma (HNSCC) has not been determined. The absolute survival benefit at 5 years of concurrent chemoradiotherapy protocols versus radiotherapy alone observed in prospective randomized trials reporting on the use of cisplatin monochemotherapy for nonnasopharyngeal HNSCC was extracted. In the case of nonrandomized studies, the outcome results at 2 years were compared between groups of patients receiving different cumulative cisplatin doses. Eleven randomized trials and 7 nonrandomized studies were identified. In 6 definitive radiotherapy phase III trials, a statistically significant association (p = .027) between cumulative cisplatin dose, independent of the schedule, and overall survival benefit was observed for higher doses. Results support the conclusion that the cumulative dose of cisplatin in concurrent chemoradiation protocols for HNSCC has a significant positive correlation with survival. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2151-E2158, 2016. © 2015 Wiley Periodicals, Inc.

Long-Term Survival and Local Relapse Following Surgery Without Radiotherapy for Locally Advanced Upper Rectal Cancer

PubMed Central

Park, Jun Seok; Sakai, Yoshiharu; Simon, NG Siu Man; Law, Wai Lun; Kim, Hyeong Rok; Oh, Jae Hwan; Shan, Hester Cheung Yui; Kwak, Sang Gyu; Choi, Gyu-Seog

2016-01-01

Abstract Controversy remains regarding whether preoperative chemoradiation protocol should be applied uniformly to all rectal cancer patients regardless of tumor height. This pooled analysis was designed to evaluate whether preoperative chemoradiation can be safely omitted in higher rectal cancer. An international consortium of 7 institutions was established. A review of the database that was collected from January 2004 to May 2008 identified a series of 2102 patients with stage II/III rectal or sigmoid cancer (control arm) without concurrent chemoradiation. Data regarding patient demographics, recurrence pattern, and oncological outcomes were analyzed. The primary end point was the 5-year local recurrence rate. The local relapse rate of the sigmoid colon cancer (SC) and upper rectal cancer (UR) cohorts was significantly lower than that of the mid/low rectal cancer group (M-LR), with 5-year estimates of 2.5% for the SC group, 3.5% for the UR group, and 11.1% for the M-LR group, respectively. A multivariate analysis showed that tumor depth, nodal metastasis, venous invasion, and lower tumor level were strongly associated with local recurrence. The cumulative incidence rate of local failure was 90.6%, 92.5%, and 94.4% for tumors located within 5, 7, and 9 cm from the anal verge, respectively. Routine use of preoperative chemoradiation for stage II/III rectal tumors located more than 8 to 9 cm above the anal verge would be excessive. The integration of a more individualized approach focused on systemic control is warranted to improve survival in patients with upper rectal cancer. PMID:27258487

Complete Neoadjuvant Treatment for Rectal Cancer: The Brown University Oncology Group CONTRE Study.

PubMed

Perez, Kimberly; Safran, Howard; Sikov, William; Vrees, Matthew; Klipfel, Adam; Shah, Nishit; Schechter, Steven; Oldenburg, Nicklas; Pricolo, Victor; Rosati, Kayla; Dipetrillo, Thomas

2017-06-01

Following preoperative chemoradiation and surgery, many patients with stage II to III rectal cancer are unable to tolerate full-dose adjuvant chemotherapy. BrUOG R-224 was designed to assess the impact of COmplete Neoadjuvant Treatment for REctal cancer (CONTRE), primary chemotherapy followed by chemoradiation and surgery, on treatment delivery, toxicities, and pathologic response at surgery. Patients with clinical stage II to III (T3 to T4 and/or N1 to N2) rectal cancer received 8 cycles of modified FOLFOX6 followed by capecitabine 825 mg/m bid concurrent with 50.4 Gy intensity-modulated radiation therapy. Surgery was performed 6 to 10 weeks after chemoradiation. Thirty-nine patients were enrolled between August 2010 and June 2013. Median age was 61 years (30 to 79 y); 7 patients (18%) were clinical stage II and 32 (82%) stage III. Thirty-six patients (92%) received all 8 cycles of mFOLFOX6, of whom 35 completed subsequent chemoradiation; thus 89% of patients received CONTRE as planned. No unexpected toxicities were reported. All patients had resolution of bleeding and improvement of obstructive symptoms, with no complications requiring surgical intervention. Pathologic complete response (ypT0N0) was demonstrated in 13 patients (33%; 95% CI, 18.24%-47.76%). CONTRE seems to be a well-tolerated alternative to the current standard treatment sequence. Evaluating its impact on long-term outcomes would require a large randomized trial, but using pathologic response as an endpoint, it could serve as a platform for assessing the addition of novel agents to preoperative treatment in stage II to III rectal cancer.

Is the progression free survival advantage of concurrent gemcitabine plus cisplatin and radiation followed by adjuvant gemcitabine and cisplatin in patients with advanced cervical cancer worth the additional cost? A cost-effectiveness analysis.

PubMed

Smith, B; Cohn, D E; Clements, A; Tierney, B J; Straughn, J M

2013-09-01

The objective of this study is to determine whether concurrent and adjuvant chemoradiation with gemcitabine/cisplatin is cost-effective in patients with stage IIB to IVA cervical cancer. A cost-effectiveness model compared two arms of the trial performed by Duenas-Gonzalez et al. [1]: concurrent and adjuvant chemoradiation with gemcitabine/cisplatin (RT/GC+GC) versus concurrent radiation with cisplatin (RT/C). Major adverse events (AEs) and progression free survival (PFS) rates of each arm were incorporated in the model. AEs were defined as any hospitalization including grade 4 anemia, grade 4 neutropenia, and death. Medicare data and literature review were used to estimate costs. Incremental cost-effectiveness ratios (ICERs) per progression-free life-year saved (PF-LYS) were calculated. Sensitivity analyses were performed for pertinent uncertainties. For 10,000 women with locally advanced cervical cancer, the cost of therapy and AEs was $173.9 million (M) for RT/C versus $259.8M for RT/GC+GC. There were 879 additional 3-year progression-free survivors in the RT/GC+GC arm. The ICER for RT/GC+GC was $97,799 per PF-LYS. When the rate of hospitalization was equalized to 4.3%, the ICER for RT/GC+GC exceeded $80,000. The resultant ICER when increasing PFS in the RT/GC+GC arm by 5% was $62,605 per PF-LYS. When the cost of chemotherapy was decreased by 50%, the ICER was below $50,000 at $41,774 per PF-LYS. Radiation and gemcitabine/cisplatin for patients with stage IIB to IVA cervical cancer are not cost-effective. The increased financial burden of radiation with gemcitabine/cisplatin and associated toxicities appears to outweigh the benefit of increased 3-year PFS and is primarily dependent on chemotherapy drug costs. Copyright © 2013 Elsevier Inc. All rights reserved.

Preoperative downstaging chemoradiation with concurrent irinotecan and capecitabine in MRI-defined locally advanced rectal cancer: a phase I trial (NWCOG-2).

PubMed

Gollins, S W; Myint, S; Susnerwala, S; Haylock, B; Wise, M; Topham, C; Samuel, L; Swindell, R; Morris, J; Mason, L; Levine, E

2009-09-15

The aim of this study was to investigate the safety of neoadjuvant chemoradiation using radiotherapy (RT) combined with concurrent capecitabine and irinotecan for locally advanced rectal cancer before surgery. Forty-six patients were recruited and treated on the basis that MRI scanning had shown poor-risk tumours with threatening (< or =1 mm) or involvement of the mesorectal fascia. Conformal RT was given using 3 or 4 fields at daily fractions of 1.8 Gy on 5 days per week to a total dose of 45 Gy. Concurrently oral capecitabine was given twice daily throughout radiotherapy continuously from days 1 to 35 and intravenous irinotecan was given once per week during weeks 1 to 4 of RT. Dose levels were gradually escalated as follows. Dose level 1: capecitabine 650 mg m(-2) b.i.d. and irinotecan 50 mg m(-2); Dose level 2: capecitabine 650 mg m(-2) b.i.d. and irinotecan 60 mg m(-2); Dose level 3: capecitabine 825 mg m(-2) b.i.d. and irinotecan 60 mg m(2); Dose level 4: capecitabine 825 mg m(-2) b.i.d. and irinotecan 70 mg m(-2). Diarrhoea (grade 3, no grade 4) was the main serious acute toxicity with lesser degrees of fatigue, neutropenia, anorexia and palmar-plantar erythrodysesthesia. The recommended dose for future study was dose level 2 at which 3 of 14 patients (21%) developed grade 3 diarrhoea. Postoperative complications included seven pelvic or wound infections and two anastomotic and two perineal wound dehiscences. There were no deaths in the first 30 days postoperatively. Of 41 resected specimens, 11 (27%) showed a pathological complete response (pCR) and five (12%) showed an involved circumferential resection margin (defined as < or =1 mm). The 3-year disease-free survival (intent-to-treat) was 53.2%. In patients with poor-risk MRI-defined locally advanced rectal cancer threatening or involving the mesorectal fascia, preoperative chemoradiation based on RT at 45 Gy in 25 daily fractions over 5 weeks with continuous daily oral capecitabine at 650 mg m(-2) b.i.d. days 1-35 and weekly IV irinotecan at 60 mg m(-2) weeks 1-4, provides acceptable acute toxicity and postoperative morbidity with encouraging response and curative resection rates.

Efficacy and Safety of Low-Dose-Rate Endorectal Brachytherapy as a Boost to Neoadjuvant Chemoradiation in the Treatment of Locally Advanced Distal Rectal Cancer: A Phase-II Clinical Trial

PubMed Central

Omidvari, Shapour; Zohourinia, Shadi; Ansari, Mansour; Ghahramani, Leila; Zare-Bandamiri, Mohammad; Mosalaei, Ahmad; Ahmadloo, Niloofar; Pourahmad, Saeedeh; Nasrolahi, Hamid; Hamedi, Sayed Hasan

2015-01-01

Purpose Despite advances in rectal cancer treatment over the last decade, local control and risk of late side effects due to external beam radiation therapy (EBRT) remain as concerns. The present study aimed to investigate the efficacy and the safety of low-dose-rate endorectal brachytherapy (LDRBT) as a boost to neoadjuvant chemoradiation for use in treating locally advanced distal rectal adenocarcinomas. Methods This phase-II clinical trial included 34 patients (as the study arm) with newly diagnosed, locally advanced (clinical T3-T4 and/or N1/N2, M0) lower rectal cancer. For comparative analysis, 102 matched patients (as the historical control arm) with rectal cancer were also selected. All the patients were treated with LDRBT (15 Gy in 3 fractions) and concurrent chemoradiation (45-50.4 Gy). Concurrent chemotherapy consisted of oxaliplatin 130 mg/m2 intravenously on day 1 plus oral capecitabine 825 mg/m2 twice daily during LDRBT and EBRT. Results The study results revealed a significant differences between the study arm and the control arm in terms in the pathologic tumor size (2.1 cm vs. 3.6 cm, P = 0.001), the pathologic tumor stage (35% T3-4 vs. 65% T3-4, P = 0.003), and the pathologic complete response (29.4% vs. 11.7%, P < 0.028). Moreover, a significantly higher dose of EBRT (P = 0.041) was found in the control arm, and a longer time to surgery was observed in the study arm (P < 0.001). The higher rate of treatment-related toxicities, such as mild proctitis and anemia, in the study arm was tolerable and easily manageable. Conclusion A boost of LDRBT can optimize the pathologic complete response, with acceptable toxicities, in patients with distal rectal cancer. PMID:26361613

Efficacy and Safety of Low-Dose-Rate Endorectal Brachytherapy as a Boost to Neoadjuvant Chemoradiation in the Treatment of Locally Advanced Distal Rectal Cancer: A Phase-II Clinical Trial.

PubMed

Omidvari, Shapour; Zohourinia, Shadi; Ansari, Mansour; Ghahramani, Leila; Zare-Bandamiri, Mohammad; Mosalaei, Ahmad; Ahmadloo, Niloofar; Pourahmad, Saeedeh; Nasrolahi, Hamid; Hamedi, Sayed Hasan; Mohammadianpanah, Mohammad

2015-08-01

Despite advances in rectal cancer treatment over the last decade, local control and risk of late side effects due to external beam radiation therapy (EBRT) remain as concerns. The present study aimed to investigate the efficacy and the safety of low-dose-rate endorectal brachytherapy (LDRBT) as a boost to neoadjuvant chemoradiation for use in treating locally advanced distal rectal adenocarcinomas. This phase-II clinical trial included 34 patients (as the study arm) with newly diagnosed, locally advanced (clinical T3-T4 and/or N1/N2, M0) lower rectal cancer. For comparative analysis, 102 matched patients (as the historical control arm) with rectal cancer were also selected. All the patients were treated with LDRBT (15 Gy in 3 fractions) and concurrent chemoradiation (45-50.4 Gy). Concurrent chemotherapy consisted of oxaliplatin 130 mg/m(2) intravenously on day 1 plus oral capecitabine 825 mg/m(2) twice daily during LDRBT and EBRT. The study results revealed a significant differences between the study arm and the control arm in terms in the pathologic tumor size (2.1 cm vs. 3.6 cm, P = 0.001), the pathologic tumor stage (35% T3-4 vs. 65% T3-4, P = 0.003), and the pathologic complete response (29.4% vs. 11.7%, P < 0.028). Moreover, a significantly higher dose of EBRT (P = 0.041) was found in the control arm, and a longer time to surgery was observed in the study arm (P < 0.001). The higher rate of treatment-related toxicities, such as mild proctitis and anemia, in the study arm was tolerable and easily manageable. A boost of LDRBT can optimize the pathologic complete response, with acceptable toxicities, in patients with distal rectal cancer.

Symptomatic pericardial effusion after chemoradiation therapy in esophageal cancer patients.

PubMed

Fukada, Junichi; Shigematsu, Naoyuki; Takeuchi, Hiroya; Ohashi, Toshio; Saikawa, Yoshiro; Takaishi, Hiromasa; Hanada, Takashi; Shiraishi, Yutaka; Kitagawa, Yuko; Fukuda, Keiichi

2013-11-01

We investigated clinical and treatment-related factors as predictors of symptomatic pericardial effusion in esophageal cancer patients after concurrent chemoradiation therapy. We reviewed 214 consecutive primary esophageal cancer patients treated with concurrent chemoradiation therapy between 2001 and 2010 in our institute. Pericardial effusion was detected on follow-up computed tomography. Symptomatic effusion was defined as effusion ≥grade 3 according to Common Terminology Criteria for Adverse Events v4.0 criteria. Percent volume irradiated with 5 to 65 Gy (V5-V65) and mean dose to the pericardium were evaluated employing dose-volume histograms. To evaluate dosimetry for patients treated with two-dimensional planning in the earlier period (2001-2005), computed tomography data at diagnosis were transferred to a treatment planning system to reconstruct three-dimensional plans without modification. Optimal dosimetric thresholds for symptomatic pericardial effusion were calculated by receiver operating characteristic curves. Associating clinical and treatment-related risk factors for symptomatic pericardial effusion were detected by univariate and multivariate analyses. The median follow-up was 29 (range, 6-121) months for eligible 167 patients. Symptomatic pericardial effusion was observed in 14 (8.4%) patients. Dosimetric analyses revealed average values of V30 to V45 for the pericardium and mean pericardial doses were significantly higher in patients with symptomatic pericardial effusion than in those with asymptomatic pericardial effusion (P<.05). Pericardial V5 to V55 and mean pericardial doses were significantly higher in patients with symptomatic pericardial effusion than in those without pericardial effusion (P<.001). Mean pericardial doses of 36.5 Gy and V45 of 58% were selected as optimal cutoff values for predicting symptomatic pericardial effusion. Multivariate analysis identified mean pericardial dose as the strongest risk factor for symptomatic pericardial effusion. Dose-volume thresholds for the pericardium facilitate predicting symptomatic pericardial effusion. Mean pericardial dose was selected based not only on the optimal dose-volume threshold but also on the most significant risk factor for symptomatic pericardial effusion. Copyright © 2013 Elsevier Inc. All rights reserved.

Impact of Prophylactic Cranial Irradiation Timing on Brain Relapse Rates in Patients With Stage IIIB Non-Small-Cell Lung Carcinoma Treated With Two Different Chemoradiotherapy Regimens

DOE Office of Scientific and Technical Information (OSTI.GOV)

Topkan, Erkan, E-mail: docdretopkan@gmail.com; Parlak, Cem; Kotek, Ayse

2012-07-15

Purpose: To retrospectively assess the influence of prophylactic cranial irradiation (PCI) timing on brain relapse rates in patients treated with two different chemoradiotherapy (CRT) regimens for Stage IIIB non-small-cell lung cancer (NSCLC). Methods and Materials: A cohort of 134 patients, with Stage IIIB NSCLC in recursive partitioning analysis Group 1, was treated with PCI (30 Gy at 2 Gy/fr) following one of two CRT regimens. Regimen 1 (n = 58) consisted of three cycles of induction chemotherapy (ICT) followed by concurrent CRT (C-CRT). Regimen 2 (n = 76) consisted of immediate C-CRT during thoracic radiotherapy. Results: At a median follow-upmore » of 27.6 months (range, 7.2-40.4), 65 patients were alive. Median, progression-free, and brain metastasis-free survival (BMFS) times for the whole study cohort were 23.4, 15.4, and 23.0 months, respectively. Median survival time and the 3-year survival rate for regimens 1 and 2 were 19.3 vs. 26.1 months (p = 0.001) and 14.4% vs. 34.4% (p < .001), respectively. Median time from the initiation of primary treatment to PCI was 123.2 (range, 97-161) and 63.4 (range, 55-74) days for regimens 1 and 2, respectively (p < 0.001). Overall, 11 (8.2%) patients developed brain metastasis (BM) during the follow-up period: 8 (13.8%) in regimen 1 and 3 (3.9%) in regimen 2 (p = 0.03). Only 3 (2.2%) patients developed BM at the site of first failure, and for 2 of them, it was also the sole site of recurrence. Median BMFS for regimens 1 and 2 were 17.4 (13.5-21.3) vs. 26.0 (22.9-29.1 months), respectively (p < 0.001). Conclusion: These results suggest that in Stage IIIB NSCLC patients treated with PCI, lower BM incidence and longer survival rates result from immediate C-CRT rather than ITC-first regimens. This indicates the benefit of earlier PCI use without delay because of induction protocols.« less

Lymphoepithelioma-Like Carcinoma of the Skin Treated with Wide Local Excision and Chemoradiation Therapy: A Case Report and Review of the Literature

DTIC Science & Technology

2012-01-01

oral cavity mucositis . He received concurrent cisplatin (20 milligram per meter squared) weekly for five weeks. He was also referred to an outside...carcinoma, melanoma , lymphoma, and cutaneous lymphadenoma. It can generally be differentiated from undifferentiated nasopharyngeal carcinoma by the...overlying epidermis. Melanoma is positive for S100 and lymphoma cells will be positive for lymphoid markers. Cutaneous lymphadenoma is benign and does not

Preoperative Chemoradiation With Cetuximab, Irinotecan, and Capecitabine in Patients With Locally Advanced Resectable Rectal Cancer: A Multicenter Phase II Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Sun Young; Hong, Yong Sang; Kim, Dae Yong

Purpose: To evaluate the efficacy and safety of preoperative chemoradiation with cetuximab, irinotecan, and capecitabine in patients with rectal cancer. Methods and Materials: Forty patients with locally advanced, nonmetastatic, and mid- to lower rectal cancer were enrolled. Radiotherapy was delivered at a dose of 50.4 Gy/28 fractions. Concurrent chemotherapy consisted of an initial dose of cetuximab of 400 mg/m{sup 2} 1 week before radiotherapy, and then cetuximab 250 mg/m{sup 2}/week, irinotecan 40 mg/m{sup 2}/week for 5 consecutive weeks and capecitabine 1,650 mg/m{sup 2}/day for 5 days a week (weekdays only) from the first day during radiotherapy. Total mesorectal excision wasmore » performed within 6 {+-} 2 weeks. The pathologic responses and survival outcomes were evaluated as study endpoints, and an additional KRAS mutation analysis was performed. Results: In total, 39 patients completed their planned preoperative chemoradiation and underwent R0 resection. The pathologic complete response rate was 23.1% (9/39), and 3 patients (7.7%) showed near total regression of tumor. The 3-year disease-free and overall survival rates were 80.0% and 94.7%, respectively. Grade 3/4 toxicities included leukopenia (4, 10.3%), neutropenia (2, 5.1%), anemia (1, 2.6%), diarrhea (2, 5.1%), fatigue (1, 2.6%), skin rash (1, 2.6%), and ileus (1, 2.6%). KRAS mutations were found in 5 (13.2%) of 38 patients who had available tissue for testing. Clinical outcomes were not significantly correlated with KRAS mutation status. Conclusions: Preoperative chemoradiation with cetuximab, irinotecan, and capecitabine was active and well tolerated. KRAS mutation status was not a predictive factor for pathologic response in this study.« less

A Phase II Study of Fixed-Dose Rate Gemcitabine Plus Low-Dose Cisplatin Followed by Consolidative Chemoradiation for Locally Advanced Pancreatic Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ko, Andrew H.; Quivey, Jeanne M.; Venook, Alan P.

Purpose: The optimal strategy for treating locally advanced pancreatic cancer remains controversial, including the respective roles and timing of chemotherapy and radiation. We conducted a Phase II nonrandomized trial to evaluate sequential chemotherapy followed by chemoradiation in this patient population. Methods and Materials: Chemotherapy naive patients with locally advanced pancreatic adenocarcinoma were treated with fixed-dose rate gemcitabine (1,000 mg/m{sup 2} at 10 mg/m{sup 2}/min) plus cisplatin 20 mg/m{sup 2} on Days 1 and 15 of a 28-day cycle. Those without evidence of extrapancreatic metastases after six cycles of chemotherapy received radiation (5,040 cGy over 28 fractions) with concurrent capecitabine (800more » mg/m{sup 2} orally twice daily on the day of radiation) as a radiosensitizer. Results: A total of 25 patients were enrolled with a median follow-up time of 656 days. Twelve patients (48%) successfully received all six cycles of chemotherapy plus chemoradiation. Eight patients (32%) progressed during chemotherapy, including 7 with extrapancreatic metastases. Grade 3/4 hematologic toxicities were uncommon. Two patients sustained myocardial infarctions during chemotherapy, and 4 were hospitalized for infectious complications, although none in the setting of neutropenia. Median time to progression was 10.5 months and median survival was 13.5 months, with an estimated 1-year survival rate of 62%. Patients receiving all components of therapy had a median survival of 17.0 months. Conclusions: A strategy of initial fixed-dose rate gemcitabine-based chemotherapy, followed by chemoradiation, shows promising efficacy for treatment of locally advanced disease. A substantial proportion of patients will be identified early on as having extrapancreatic disease and spared the potential toxicities associated with radiation.« less

Poor oral intake causes enteral nutrition dependency after concomitant chemoradiotherapy for pharyngeal cancers.

PubMed

Ishii, Ryo; Kato, Kengo; Ogawa, Takenori; Sato, Takeshi; Nakanome, Ayako; Ohkoshi, Akira; Kawamoto-Hirano, Ai; Shirakura, Masayuki; Hidaka, Hiroshi; Katori, Yukio

2018-06-01

To identify precipitating factors responsible for enteral nutrition (EN) dependency after concomitant chemoradiotherapy (CCRT) of head and neck cancers and to examine their statistical correlations. Factors related to feeding condition, nutritional status, disease, and treatment of 26 oropharyngeal and hypopharyngeal cancer patients who received definitive CCRT were retrospectively investigated by examining their medical records. The days of no oral intake (NOI) during hospitalization and the months using enteral nutrition after CCRT were counted as representing the feeding condition, and the changes in body weight (BW) were examined as reflecting nutritional status. The factors related to EN dependency after CCRT were analyzed. Long duration of total NOI (≥ 30 days) and maximum NOI ≥ 14 days were significant predictors of EN dependency. Decreased BW (≥ 7.5 kg) was the next predictor identified, but it was not significant. Multivariate analysis showed that the total duration of NOI was more correlated with EN dependency than changes in BW. A long duration of NOI was more strongly related to EN dependency than nutritional factors.

Leukocytosis and neutrophilia predicts outcome in anal cancer.

PubMed

Schernberg, Antoine; Escande, Alexandre; Rivin Del Campo, Eleonor; Ducreux, Michel; Nguyen, France; Goere, Diane; Chargari, Cyrus; Deutsch, Eric

2017-01-01

Leukocytosis and neutrophilia could be the tip of the iceberg in the inflammatory tumor microenvironment. We aimed to validate their prognostic significance in a cohort of patients treated with definitive chemoradiation for anal squamous cell carcinoma (SCC). Clinical records from all consecutive patients treated in a single institution between 2006 and 2016 with curative-intent radiotherapy were retrospectively analyzed. Leukocytosis and neutrophilia, defined as leukocyte or neutrophil count over 10,000 and 7500/mm 3 , respectively, were studied in terms of overall survival (OS), progression (PFS), locoregional (LFS) and distant (DFS)-free survival. We identified 103 non-metastatic HIV-negative patients, with concurrent chemotherapy use in 78%. Twelve and 8% displayed baseline leukocytosis and neutrophilia, respectively. Estimated 3-year OS and PFS were 88% and 67%, respectively. In univariate analysis, both leukocytosis and neutrophilia were strongly associated with inferior OS, PFS, LFS and DFS (p<0.01). In multivariate analysis, leukocytosis and neutrophilia remained strongly associated with patient outcome (p<0.01), independently from tumor T and N-stage. Anemia was an independent predictor of worse OS and PFS, while chemoradiation overall treatment time below 50days improved PFS. Leukocytosis and neutrophilia are strong prognostic factors for OS, PFS, LFS and DFS in anal cancer treated with chemoradiation. These biomarkers could help identify patients with higher risk of tumor relapse that require treatment intensification. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Combined chemo-radiotherapy in locally advanced nasopharyngeal carcinomas.

PubMed

Perri, Francesco; Della Vittoria Scarpati, Giuseppina; Buonerba, Carlo; Di Lorenzo, Giuseppe; Longo, Francesco; Muto, Paolo; Schiavone, Concetta; Sandomenico, Fabio; Caponigro, Francesco

2013-05-10

To provide efficacy and safety data about the combined use of radiotherapy and chemo-radiotherapy in nasopharyngeal carcinoma (NPC). We reviewed data of 40 patients with locally advanced NPC treated with induction chemotherapy followed by concomitant chemo-radiotherapy (CCRT) (22/40 patients) or CCRT alone (18/40) from March 2006 to March 2012. Patients underwent fiberoscopy with biopsy of the primitive tumor, and computed tomography scan of head, neck, chest and abdomen with and without contrast. Cisplatin was used both as induction and as concomitant chemotherapy, while 3D conformal radiation therapy was delivered to the nasopharynx and relevant anatomic regions (total dose, 70 Gy). The treatment was performed using 6 MV photons of the linear accelerator administered in 2 Gy daily fraction for five days weekly. This retrospective analysis was approved by the review boards of the participating institutions. Patients gave their consent to treatment and to anonymous analysis of clinical data. Thirty-three patients were males and 7 were females. Median follow-up time was 58 mo (range, 1-92 mo). In the sub-group of twenty patients with a follow-up time longer than 36 mo, the 3-year survival and disease free survival rates were 85% and 75%, respectively. Overall response rate both in patients treated with induction chemotherapy followed by CCRT and in those treated with CCRT alone was 100%. Grade 3 neutropenia was the most frequent acute side-effect and it occurred in 20 patients. Grade 2 mucositis was seen in 29 patients, while grade 2 xerostomia was seen in 30 patients. Overall toxicity was manageable and it did not cause any significant treatment delay. In the whole sample population, long term toxicity included grade 2 xerostomia in 22 patients, grade 1 dysgeusia in 17 patients and grade 1 subcutaneous fibrosis in 30 patients. Both CCRT and induction chemotherapy followed by CCRT showed excellent activity in locally advanced NPC. The role of adjuvant chemotherapy remains to be defined.

Effect of p16 Status on the Quality-of-Life Experience During Chemoradiation for Locally Advanced Oropharyngeal Cancer: A Substudy of Randomized Trial Trans-Tasman Radiation Oncology Group (TROG) 02.02 (HeadSTART).

PubMed

Ringash, Jolie; Fisher, Richard; Peters, Lester; Trotti, Andy; O'Sullivan, Brian; Corry, June; Kenny, Lizbeth; Nuyts, Sandra; Wratten, Chris; Rischin, Danny

2017-03-15

Human papillomavirus-associated oropharyngeal cancer (OPC) has a favorable prognosis. Current research de-escalates treatment, aiming to improve quality of life (QOL). Understanding the QOL experience with current standard treatment (chemoradiation therapy) provides context for emerging data. We report the impact of p16 status on QOL for patients with stage III or IV OPC undergoing chemoradiation therapy in an international phase 3 trial (TROG 02.02 [HeadSTART]). A subgroup analysis by p16 status was conducted in patients with OPC treated in a phase 3 randomized trial. The study subset with OPC and known p16 status was mainly from Australasia, Western Europe, and North America. Of 861 participants, 200 had OPC, known p16 status, and baseline QOL data; 82 were p16 negative and 118 were p16 positive. Radiation therapy (70 Gy over a period of 7 weeks) was given concurrently with 3 cycles of either cisplatin (100 mg/m 2 ) or cisplatin (75 mg/m 2 ) plus tirapazamine. QOL was measured with the Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N) questionnaire at baseline and 2, 6, 12, 23, and 38 months. Because no significant difference in QOL score was observed between arms, results by p16 status are reported with arms combined. The p16-positive patients were younger, had a better Eastern Cooperative Oncology Group performance status, and were less often current smokers. Our primary hypothesis that the change in FACT-H&N score from baseline to 6 months would be more favorable in the p16-positive cohort was not met (p16 positive, -6.3; p16 negative, -1.8; P=.14). The mean baseline FACT-H&N score was statistically and clinically significantly better in p16-positive patients (111 vs 102, P<.001); at 2 months, scores declined in both groups but more dramatically for p16-positive patients. By 12 months, p16-positive patients again had superior scores. A higher baseline FACT-H&N score and p16-positive status were independent predictors of overall survival. Patients with p16-positive OPC exhibited better baseline QOL but showed a more dramatic QOL drop with concurrent chemoradiation. Given the favorable prognosis of p16-positive OPC, efforts to reduce the QOL burden of treatment are warranted. Copyright © 2016 Elsevier Inc. All rights reserved.

Final Results of NRG Oncology RTOG 0246: An Organ-Preserving Selective Resection Strategy in Esophageal Cancer Patients Treated with Definitive Chemoradiation.

PubMed

Swisher, Stephen G; Moughan, Jennifer; Komaki, Ritsuko U; Ajani, Jaffer A; Wu, Tsung T; Hofstetter, Wayne L; Konski, Andre A; Willett, Christopher G

2017-02-01

The impact of selective surgical resection for patients with esophageal cancer treated with definitive chemoradiation has not been clearly evaluated long-term. NRG (National Surgical Adjuvant Breast and Bowel Project, Radiation Therapy Oncology Group, Gynecologic Oncology Group) Oncology Radiation Therapy Oncology Group 0246 was a multi-institutional, single-arm, open-label, nonrandomized phase II study that enrolled 43 patients from September 2003 to March 2008 with clinical stage T1-4N0-1M0 squamous cell or adenocarcinoma of the esophagus or gastroesophageal junction from 19 sites. Patients received induction chemotherapy with fluorouracil (650 mg/m 2 /d), cisplatin (15 mg/m 2 /d), and paclitaxel (200 mg/m 2 /d) for two cycles followed by concurrent chemoradiation consisting of 50.4 Gy of radiation (1.8 Gy per fraction) and daily fluorouracil (300 mg/m 2 /d) with cisplatin (15 mg/m 2 /d) over the first 5 days. After definitive chemoradiation, patients were evaluated for residual disease. Selective esophagectomy was considered only for patients with residual disease after chemoradiation (clinical incomplete response) or recurrent disease on surveillance. This report looks at the long-term outcome of this selective surgical strategy. With a median follow-up of 8.1 years (minimum to maximum for 12 alive patients 7.2-9.8 years), the estimated 5- and 7-year survival rates are 36.6% (95% confidence interval [CI]: 22.3-51.0) and 31.7% (95% CI: 18.3-46.0). Clinical complete response was achieved in 15 patients (37%), with 5- and 7-yearr survival rates of 53.3% (95% CI: 26.3-74.4) and 46.7% (95% CI: 21.2-68.7). Esophageal resection was not required in 20 of 41 patients (49%) on this trial. The long-term results of NRG Oncology Radiation Therapy Oncology Group 0246 demonstrate promising efficacy of a selective surgical resection strategy and suggest the need for larger randomized studies to further evaluate this organ-preserving approach. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Epidermal Growth Factor Receptor Expression As Prognostic Marker in Patients With Anal Carcinoma Treated With Concurrent Chemoradiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fraunholz, Ingeborg, E-mail: inge.fraunholz@kgu.de; Rödel, Franz; Kohler, Daniela

Purpose: To investigate the prognostic value of epidermal growth factor receptor (EGFR) expression in pretreatment tumor biopsy specimens of patients with anal cancer treated with concurrent 5-fluorouracil and mitomycin C-based chemoradiation therapy (CRT). Methods and Materials: Immunohistochemical staining for EGFR was performed in pretreatment biopsy specimens of 103 patients with anal carcinoma. EGFR expression was correlated with clinical and histopathologic characteristics and with clinical endpoints, including local failure-free survival (LFFS), colostomy-free survival (CFS), distant metastases-free survival (DMFS), cancer-specific survival (CSS), and overall survival (OS). Results: EGFR staining intensity was absent in 3%, weak in 23%, intermediate in 36% and intensemore » in 38% of the patients. In univariate analysis, the level of EGFR staining was significantly correlated with CSS (absent/weak vs intermediate/intense expression: 5-year CSS, 70% vs 86%, P=.03). As a trend, this was also observed for DMFS (70% vs 86%, P=.06) and LFFS (70% vs 87%, P=.16). In multivariate analysis, N stage, tumor differentiation, and patients’ sex were independent prognostic factors for CSS, whereas EGFR expression only reached borderline significance (hazard ratio 2.75; P=.08). Conclusion: Our results suggest that elevated levels of pretreatment EGFR expression could be correlated with favorable clinical outcome in anal cancer patients treated with CRT. Further studies are warranted to elucidate how EGFR is involved in the response to CRT.« less

Comparison of peripheral and central capillary refill time in febrile children presenting to a paediatric emergency department and its utility in identifying children with serious bacterial infection.

PubMed

de Vos-Kerkhof, Evelien; Krecinic, Tarik; Vergouwe, Yvonne; Moll, Henriëtte A; Nijman, Ruud G; Oostenbrink, Rianne

2017-01-01

To determine the agreement between peripheral and central capillary refill time (pCRT/cCRT) and their diagnostic values for detecting serious bacterial infection (SBI) in febrile children attending the paediatric emergency department (ED). Prospective observational study. Paediatric ED, Erasmus Medium Care-Sophia Children's hospital, the Netherlands. 1193 consecutively included, previously healthy, febrile children (1 month-16 years) with both pCRT measurements and cCRT measurements available. SBI diagnosis was based on abnormal radiographic findings and/or positive cultures from normally sterile locations in addition to clinical criteria. Agreement between pCRT and cCRT (Cohen's κ), overall and stratified for age and body temperature. The diagnostic value of pCRT and cCRT for SBI was assessed with logistic regression. Overall agreement was 0.35 (95% CI 0.27 to 0.43; considered 'fair'). Although not significant, agreement was lower in children aged 1-<5 years (κ: 0.15 (95% CI 0.04 to 0.27)) and decreased with higher body temperatures with κ ranging from 0.55 (95% CI 0.32 to 0.79) for temperature <37.5°C to 0.21 (95% CI 0.07 to 0.34) for temperature >39.5°C. Abnormal pCRT (>2 s) was observed in 153 (12.8%; 95% CI 10.9% to 14.7%) and abnormal cCRT in 55 (4.6%; 95% CI 3.4% to 5.8%) children. The OR of abnormal pCRT (>2 s) for predicting SBI was 1.10 (95% CI 0.65 to 1.84). For abnormal cCRT (>2 s), the OR was 0.43 (95% CI 0.13 to 1.39). The pCRT and cCRT values showed only fair agreement in a general population of febrile children at the ED, and no significant association with age or body temperature was found. Only a small part of febrile children at risk for serious infections at the ED show abnormal CRT values. Both abnormal pCRT and cCRT (defined as >2 s) performed poorly and were non-significant in this study detecting SBI in a general population of febrile children. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Emerging Therapies for Stage III Non-Small Cell Lung Cancer: Stereotactic Body Radiation Therapy and Immunotherapy.

PubMed

Kumar, Sameera S; Higgins, Kristin A; McGarry, Ronald C

2017-01-01

The current standard of care for locally advanced non-small cell lung cancer (NSCLC) includes radiation, chemotherapy, and surgery in certain individualized cases. In unresectable NSCLC, chemoradiation has been the standard of care for the past three decades. Local and distant failure remains high in this group of patients, so dose escalation has been studied in both single institution and national clinical trials. Though initial studies showed a benefit to dose escalation, phase III studies examining dose escalation using standard fractionation or hyperfractionation have failed to show a benefit. Over the last 17 years, stereotactic body radiation therapy (SBRT) has shown a high degree of safety and local control for stage I lung cancers and other localized malignancies. More recently, phase I/II studies using SBRT for dose escalation after conventional chemoradiation in locally advanced NSCLC have been promising with good apparent safety. Immunotherapy also offers opportunities to address distant disease and preclinical data suggest immunotherapy in tandem with SBRT may be a rational way to induce an "abscopal effect" although there are little clinical data as yet. By building on the proven concept of conventional chemoradiation for patients with locally advanced NSCLC with a subsequent radiation dose intensification to residual disease with SBRT concurrent with immunotherapy, we hope address the issues of metastatic and local failures. This "quadmodality" approach is still in its infancy but appears to be a safe and rational approach to the improving the outcome of NSCLC therapy.

Voice outcomes after concurrent chemoradiotherapy for advanced nonlaryngeal head and neck cancer: a prospective study.

PubMed

Paleri, Vinidh; Carding, Paul; Chatterjee, Sanjoy; Kelly, Charles; Wilson, Janet Ann; Welch, Andrew; Drinnan, Michael

2012-12-01

The voice impact of treatment for nonlaryngeal head and neck primary sites remains unknown. We conducted a prospective study of a consecutive sample of patients undergoing chemoradiation for nonlaryngeal head and neck cancer. The Voice Symptom Scale (VoiSS) was completed, and voice recordings were made at 3 time-points. Of 42 recruited patients, 34 completed the measures before and in the early posttreatment phase (mean 16.5 weeks), while 21 patients were assessed at the final time-point (mean, 20.4 months). VoiSS scores showed statistically significant progressive deterioration in the total score (p = .02) and impairment subscale (p < .0001) through to the final assessment. Acoustic measures and perceptual ratings deteriorated significantly (p < .001) in the early posttreatment weeks and improved at the final assessment, but not to the baseline. Interrater agreement was excellent for expert measures. To the best of our knowledge, this is the first prospective study to show that chemoradiation therapy for nonlaryngeal head and neck cancer has a significant effect on the patients' self-reported voice quality, even in the long term. Copyright © 2012 Wiley Periodicals, Inc.

Focal Radiation Therapy Dose Escalation Improves Overall Survival in Locally Advanced Pancreatic Cancer Patients Receiving Induction Chemotherapy and Consolidative Chemoradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krishnan, Sunil, E-mail: skrishnan@mdanderson.org; Chadha, Awalpreet S.; Suh, Yelin

2016-03-15

Purpose: To review outcomes of locally advanced pancreatic cancer (LAPC) patients treated with dose-escalated intensity modulated radiation therapy (IMRT) with curative intent. Methods and Materials: A total of 200 patients with LAPC were treated with induction chemotherapy followed by chemoradiation between 2006 and 2014. Of these, 47 (24%) having tumors >1 cm from the luminal organs were selected for dose-escalated IMRT (biologically effective dose [BED] >70 Gy) using a simultaneous integrated boost technique, inspiration breath hold, and computed tomographic image guidance. Fractionation was optimized for coverage of gross tumor and luminal organ sparing. A 2- to 5-mm margin around the gross tumor volume wasmore » treated using a simultaneous integrated boost with a microscopic dose. Overall survival (OS), recurrence-free survival (RFS), local-regional and distant RFS, and time to local-regional and distant recurrence, calculated from start of chemoradiation, were the outcomes of interest. Results: Median radiation dose was 50.4 Gy (BED = 59.47 Gy) with a concurrent capecitabine-based (86%) regimen. Patients who received BED >70 Gy had a superior OS (17.8 vs 15.0 months, P=.03), which was preserved throughout the follow-up period, with estimated OS rates at 2 years of 36% versus 19% and at 3 years of 31% versus 9% along with improved local-regional RFS (10.2 vs 6.2 months, P=.05) as compared with those receiving BED ≤70 Gy. Degree of gross tumor volume coverage did not seem to affect outcomes. No additional toxicity was observed in the high-dose group. Higher dose (BED) was the only predictor of improved OS on multivariate analysis. Conclusion: Radiation dose escalation during consolidative chemoradiation therapy after induction chemotherapy for LAPC patients improves OS and local-regional RFS.« less

Cost-effectiveness of low-level laser therapy (LLLT) in head and neck cancer patients receiving concurrent chemoradiation.

PubMed

Antunes, Héliton S; Schluckebier, Luciene Fontes; Herchenhorn, Daniel; Small, Isabele A; Araújo, Carlos M M; Viégas, Celia Maria Pais; Rampini, Mariana P; Ferreira, Elza M S; Dias, Fernando L; Teich, Vanessa; Teich, Nelson; Ferreira, Carlos G

2016-01-01

Oral mucositis is a major event increasing treatment costs of head and neck squamous cell carcinoma (HNSCC) patients treated with chemoradiation (CRT). This study was designed to estimate the cost-effectiveness of low-level laser therapy (LLLT) to prevent oral mucositis in HNSCC patients receiving CRT. From June 2007 to December 2010, 94 patients with HNSCC of nasopharynx, oropharynx, and hypopharynx entered a prospective, randomized, double blind, placebo-controlled, phase III trial. CRT consisted of conventional radiotherapy (RT: 70.2 Gy, 1.8 Gy/d, 5 times/wk)+concurrent cisplatin (100mg/m2) every 3 weeks. An InGaAlP (660 nm-100 mW-4J/cm2) laser diode was used for LLLT. From the perspective of Brazil's public health care system (SUS), total costs were higher in Placebo Group (PG) than Laser Group (LG) for opioid use (LG=US$ 9.08, PG=US$ 44.28), gastrostomy feeding (LG=US$ 50.50, PG=US$ 129.86), and hospitalization (PG=US$ 77.03). In LG, the cost was higher for laser therapy only (US$ 1880.57). The total incremental cost associated with the use of LLLT was US$ 1689.00 per patient. The incremental cost-effectiveness ratio (ICER) was US$ 4961.37 per grade 3-4 OM case prevented compared to no treatment. Our results indicate that morbidity was lower in the Laser Group and that LLLT was more cost-effective than placebo up to a threshold of at least US$ 5000 per mucositis case prevented. NCT01439724. Copyright © 2015 Elsevier Ltd. All rights reserved.

Curative Chemoradiotherapy in Patients With Stage IVB Cervical Cancer Presenting With Paraortic and Left Supraclavicular Lymph Node Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Ji-Yoon; Kim, Joo-Young; Kim, Jin Hee

2012-11-01

Purpose: To evaluate the efficacy and toxicity of concurrent chemoradiotherapy (CCRT) with curative intent in patients with stage IVB cervical cancer initially presenting with paraortic and left supraclavicular lymph node metastases. Methods and Materials: The medical records of 25 patients with both paraortic and left supraclavicular lymph nodal metastases (group I) were reviewed and compared with those of 101 women with paraortic lymph node metastases alone (group II). Group I received a mean 59.4 Gy to the paraortic and left supraclavicular areas and 50.4 Gy to the pelvis, followed by 30 Gy of high-dose-rate brachytherapy in 6 fractions. Group IImore » received the same dose to the paraortic area and pelvis followed by intracavitary brachytherapy. All patients received platinum-based chemotherapy simultaneously. Results: Of the 25 patients in group I, 16 (64%) experienced acute grade 3-4 hematologic toxicities, and 1 had a late grade 3 genitourinary toxicity. Complete responses, including the primary mass and pelvic, paraortic, and left supraclavicular lymph nodes, were observed in 13 patients (52%). At a median follow-up of 32 months for surviving patients, 3 experienced in-field failure, 6 showed distant failure, and 9 showed both. The 3-year overall and disease-free survival rates were 49% and 33%, respectively. In comparison, of the 101 patients in group II, 16 showed in-field failure, 14 experienced distant failure, and 11 showed both. The 3-year overall and disease-free survival rates were 69% and 57%, respectively. Conclusions: Curative CCRT is feasible in patients with stage IVB cervical cancer presenting with paraortic and left supraclavicular lymph nodal metastases, with acceptable late toxicity and high response rates, despite high rates of acute hematologic toxicity.« less

Comparison of adverse effects of proton and X-ray chemoradiotherapy for esophageal cancer using an adaptive dose–volume histogram analysis

PubMed Central

Makishima, Hirokazu; Ishikawa, Hitoshi; Terunuma, Toshiyuki; Hashimoto, Takayuki; Yamanashi, Koichi; Sekiguchi, Takao; Mizumoto, Masashi; Okumura, Toshiyuki; Sakae, Takeji; Sakurai, Hideyuki

2015-01-01

Cardiopulmonary late toxicity is of concern in concurrent chemoradiotherapy (CCRT) for esophageal cancer. The aim of this study was to examine the benefit of proton beam therapy (PBT) using clinical data and adaptive dose–volume histogram (DVH) analysis. The subjects were 44 patients with esophageal cancer who underwent definitive CCRT using X-rays (n = 19) or protons (n = 25). Experimental recalculation using protons was performed for the patient actually treated with X-rays, and vice versa. Target coverage and dose constraints of normal tissues were conserved. Lung V5–V20, mean lung dose (MLD), and heart V30–V50 were compared for risk organ doses between experimental plans and actual treatment plans. Potential toxicity was estimated using protons in patients actually treated with X-rays, and vice versa. Pulmonary events of Grade ≥2 occurred in 8/44 cases (18%), and cardiac events were seen in 11 cases (25%). Risk organ doses in patients with events of Grade ≥2 were significantly higher than for those with events of Grade ≤1. Risk organ doses were lower in proton plans compared with X-ray plans. All patients suffering toxicity who were treated with X-rays (n = 13) had reduced predicted doses in lung and heart using protons, while doses in all patients treated with protons (n = 24) with toxicity of Grade ≤1 had worsened predicted toxicity with X-rays. Analysis of normal tissue complication probability showed a potential reduction in toxicity by using proton beams. Irradiation dose, volume and adverse effects on the heart and lung can be reduced using protons. Thus, PBT is a promising treatment modality for the management of esophageal cancer. PMID:25755255

Stereotactic Body Radiation Therapy Boost After Concurrent Chemoradiation for Locally Advanced Non-Small Cell Lung Cancer: A Phase 1 Dose Escalation Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hepel, Jaroslaw T., E-mail: jhepel@lifespan.org; Department of Radiation Oncology, Tufts Medical Center, Tufts University, Boston, Massachusetts; Leonard, Kara Lynne

Purpose: Stereotactic body radiation therapy (SBRT) boost to primary and nodal disease after chemoradiation has potential to improve outcomes for advanced non-small cell lung cancer (NSCLC). A dose escalation study was initiated to evaluate the maximum tolerated dose (MTD). Methods and Materials: Eligible patients received chemoradiation to a dose of 50.4 Gy in 28 fractions and had primary and nodal volumes appropriate for SBRT boost (<120 cc and <60 cc, respectively). SBRT was delivered in 2 fractions after chemoradiation. Dose was escalated from 16 to 28 Gy in 2 Gy/fraction increments, resulting in 4 dose cohorts. MTD was defined when ≥2 of 6 patients permore » cohort experienced any treatment-related grade 3 to 5 toxicity within 4 weeks of treatment or the maximum dose was reached. Late toxicity, disease control, and survival were also evaluated. Results: Twelve patients (3 per dose level) underwent treatment. All treatment plans met predetermined dose-volume constraints. The mean age was 64 years. Most patients had stage III disease (92%) and were medically inoperable (92%). The maximum dose level was reached with no grade 3 to 5 acute toxicities. At a median follow-up time of 16 months, 1-year local-regional control (LRC) was 78%. LRC was 50% at <24 Gy and 100% at ≥24 Gy (P=.02). Overall survival at 1 year was 67%. Late toxicity (grade 3-5) was seen in only 1 patient who experienced fatal bronchopulmonary hemorrhage (grade 5). There were no predetermined dose constraints for the proximal bronchial-vascular tree (PBV) in this study. This patient's 4-cc PBV dose was substantially higher than that received by other patients in all 4 cohorts and was associated with the toxicity observed: 20.3 Gy (P<.05) and 73.5 Gy (P=.07) for SBRT boost and total treatment, respectively. Conclusions: SBRT boost to both primary and nodal disease after chemoradiation is feasible and well tolerated. Local control rates are encouraging, especially at doses ≥24 Gy in 2 fractions. Toxicity at the PBV is a concern but potentially can be avoided with strict dose-volume constraints.« less

Hypofractionated Palliative Radiotherapy with Concurrent Radiosensitizing Chemotherapy for Advanced Head and Neck Cancer Using the "QUAD-SHOT Regimen".

PubMed

Gamez, Mauricio E; Agarwal, Manuj; Hu, Kenneth S; Lukens, John N; Harrison, Louis B

2017-02-01

To analyze the outcomes using the hypofractionated palliative radiotherapy regimen "QUAD-Shot" with concurrent radiosensitizing chemotherapy for advanced head and neck cancer. We analyzed twenty-one patients with newly-diagnosed or recurrent head and neck cancer treated with palliative hypofractionated concurrent chemoradiation using the QUAD-Shot regimen. All patients received at least one cycle of RT, with sixteen patients (76%) completing all three cycles. 85.7 % of patients had objective response to therapy with five patients (23.8%) demonstrating complete response (CR) and thirteen patients (61.9%) demonstrating partial response (PR). Palliation of symptoms was achieved in all (100%) of the sixteen patients that completed the three cycles. Median overall survival and median progression-free survival were 7 and 4 months, respectively. QUAD-Shot palliative radiation therapy coupled with radiosensitizing chemotherapy is efficacious and well-tolerated in patients with newly-diagnosed or recurrent head and neck cancer not amenable to curative therapy. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Predictors and Patterns of Recurrence After Definitive Chemoradiation for Anal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Das, Prajnan; Bhatia, Sumita; Eng, Cathy

2007-07-01

Purpose: To evaluate patterns of locoregional failure, and predictors of recurrence and survival in patients treated with chemoradiation for anal cancer. Methods and Materials: Between September 1992 and August 2004, 167 patients with nonmetastatic squamous cell anal carcinoma were treated with definitive chemoradiation. The median dose of radiotherapy was 5500 cGy. Concurrent chemotherapy was given with 5-fluorouracil and cisplatin in 117 patients, 5-fluorouracil and mitomycin C in 24 patients, and other regimens in 26 patients. Results: The estimated 3-year rates of locoregional control, distant control, disease-free survival, and overall survival were 81%, 88%, 67%, and 84%, respectively. Multivariate analysis showedmore » that higher T stage and N stage independently predicted for a higher rate of locoregional failure; higher N stage and basaloid subtype independently predicted for a higher rate of distant metastasis; and higher N stage and positive human immunodeficiency virus status independently predicted for a lower rate of overall survival. Among the patients who had locoregional failure, 18 (75%) had failure involving the anus or rectum, 5 (21%) had other pelvic recurrences, and 1 (4%) had inguinal recurrence. The 5 pelvic recurrences all occurred in patients with the superior border of the radiotherapy field at the bottom of the sacroiliac joint. Conclusions: Trials of more aggressive and innovative locoregional and systemic therapies are warranted in high-risk patients, based on their T and N stages. The majority of locoregional failures involve the anus and rectum, whereas inguinal recurrences occur rarely. Placing the superior border of the radiotherapy field at L5/S1 could potentially reduce pelvic recurrences.« less

A cost-effectiveness analysis of a preventive exercise program for patients with advanced head and neck cancer treated with concomitant chemo-radiotherapy

PubMed Central

2011-01-01

Background Concomitant chemo-radiotherapy (CCRT) has become an indispensable organ, but not always function preserving treatment modality for advanced head and neck cancer. To prevent/limit the functional side effects of CCRT, special exercise programs are increasingly explored. This study presents cost-effectiveness analyses of a preventive (swallowing) exercise program (PREP) compared to usual care (UC) from a health care perspective. Methods A Markov decision model of PREP versus UC was developed for CCRT in advanced head and neck cancer. Main outcome variables were tube dependency at one-year and number of post-CCRT hospital admission days. Primary outcome was costs per quality adjusted life years (cost/QALY), with an incremental cost-effectiveness ratio (ICER) as outcome parameter. The Expected Value of Perfect Information (EVPI) was calculated to obtain the value of further research. Results PREP resulted in less tube dependency (3% and 25%, respectively), and in fewer hospital admission days than UC (3.2 and 4.5 days respectively). Total costs for UC amounted to €41,986 and for PREP to €42,271. Quality adjusted life years for UC amounted to 0.68 and for PREP to 0.77. Based on costs per QALY, PREP has a higher probability of being cost-effective as long as the willingness to pay threshold for 1 additional QALY is at least €3,200/QALY. At the prevailing threshold of €20,000/QALY the probability for PREP being cost-effective compared to UC was 83%. The EVPI demonstrated potential value in undertaking additional research to reduce the existing decision uncertainty. Conclusions Based on current evidence, PREP for CCRT in advanced head and neck cancer has the higher probability of being cost-effective when compared to UC. Moreover, the majority of sensitivity analyses produced ICERs that are well below the prevailing willingness to pay threshold for an additional QALY (range from dominance till €45,906/QALY). PMID:22051143

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li Gang; Hu Wei; Wang Jianhua

Purpose: To investigate the feasibility and efficacy of concurrent chemoradiation in combination with erlotinib for locally advanced esophageal carcinoma. Methods and Materials: Twenty-four patients with locally advanced esophageal carcinoma were treated with concurrent chemoradiotherapy. A daily fraction of 2.0 Gy was prescribed to a total dose of 60 Gy over 6 weeks. Concurrent paclitaxel (135 mg/m{sup 2}, d{sub 1}) and cisplatin (20 mg/m{sup 2}, d{sub 1-3}) were administered on Day 1 and Day 29 of the radiotherapy. Erlotinib, an oral epidermal growth factor receptor-tyrosine kinase inhibitor, was taken by every patient at the dose of 150 mg daily during themore » chemoradiotherapy. Results: The median follow-up of the 24 patients was 18.6 months (range, 7.1-29.6 months). The 2-year overall survival, local-regional control, and relapse-free survival were 70.1% (95% CI, 50.4-90%), 87.5% (95% CI, 73.5-100%), and 57.4% (95% CI, 36.3-78.7%), respectively. During the chemoradiotheapy, the incidences of acute toxicities of Grade 3 or greater, such as leucopenia and thrombocytopenia, were 16.7 % (4/24) and 8.3% (2/24). Conclusions: Application of concurrent chemoradiotherapy in combination with erlotinib for locally advanced esophageal carcinoma yielded satisfactory 2-year overall survival and local-regional control. The toxicities were well tolerated.« less

Fine-Mapping and Selective Sweep Analysis of QTL for Cold Tolerance in Drosophila melanogaster

PubMed Central

Wilches, Ricardo; Voigt, Susanne; Duchen, Pablo; Laurent, Stefan; Stephan, Wolfgang

2014-01-01

There is a growing interest in investigating the relationship between genes with signatures of natural selection and genes identified in QTL mapping studies using combined population and quantitative genetics approaches. We dissected an X-linked interval of 6.2 Mb, which contains two QTL underlying variation in chill coma recovery time (CCRT) in Drosophila melanogaster from temperate (European) and tropical (African) regions. This resulted in two relatively small regions of 131 kb and 124 kb. The latter one co-localizes with a very strong selective sweep in the European population. We examined the genes within and near the sweep region individually using gene expression analysis and P-element insertion lines. Of the genes overlapping with the sweep, none appears to be related to CCRT. However, we have identified a new candidate gene of CCRT, brinker, which is located just outside the sweep region and is inducible by cold stress. We discuss these results in light of recent population genetics theories on quantitative traits. PMID:24970882

NRG Oncology Radiation Therapy Oncology Group 0822: A Phase 2 Study of Preoperative Chemoradiation Therapy Using Intensity Modulated Radiation Therapy in Combination With Capecitabine and Oxaliplatin for Patients With Locally Advanced Rectal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hong, Theodore S., E-mail: tshong1@mgh.harvard.edu; Moughan, Jennifer; Garofalo, Michael C.

Purpose: To evaluate the rate of gastrointestinal (GI) toxicity of neoadjuvant chemoradiation with capecitabine, oxaliplatin, and intensity modulated radiation therapy (IMRT) in cT3-4 rectal cancer. Methods and Materials: Patients with localized, nonmetastatic T3 or T4 rectal cancer <12 cm from the anal verge were enrolled in a prospective, multi-institutional, single-arm study of preoperative chemoradiation. Patients received 45 Gy with IMRT in 25 fractions, followed by a 3-dimensional conformal boost of 5.4 Gy in 3 fractions with concurrent capecitabine/oxaliplatin (CAPOX). Surgery was performed 4 to 8 weeks after the completion of therapy. Patients were recommended to receive FOLFOX chemotherapy after surgery. The primary endpoint ofmore » the study was acute grade 2 to 5 GI toxicity. Seventy-one patients provided 80% probability to detect at least a 12% reduction in the specified GI toxicity with the treatment of CAPOX and IMRT, at a significance level of .10 (1-sided). Results: Seventy-nine patients were accrued, of whom 68 were evaluable. Sixty-one patients (89.7%) had cT3 disease, and 37 (54.4%) had cN (+) disease. Postoperative chemotherapy was given to 42 of 68 patients. Fifty-eight patients had target contours drawn per protocol, 5 patients with acceptable variation, and 5 patients with unacceptable variations. Thirty-five patients (51.5%) experienced grade ≥2 GI toxicity, 12 patients (17.6%) experienced grade 3 or 4 diarrhea, and pCR was achieved in 10 patients (14.7%). With a median follow-up time of 3.98 years, the 4-year rate of locoregional failure was 7.4% (95% confidence interval [CI]: 1.0%-13.7%). The 4-year rates of OS and DFS were 82.9% (95% CI: 70.1%-90.6%) and 60.6% (95% CI: 47.5%-71.4%), respectively. Conclusion: The use of IMRT in neoadjuvant chemoradiation for rectal cancer did not reduce the rate of GI toxicity.« less

Phase 2 Trial of Induction Gemcitabine, Oxaliplatin, and Cetuximab Followed by Selective Capecitabine-Based Chemoradiation in Patients With Borderline Resectable or Unresectable Locally Advanced Pancreatic Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Esnaola, Nestor F.; Chaudhary, Uzair B.; O'Brien, Paul

Purpose: To evaluate, in a phase 2 study, the safety and efficacy of induction gemcitabine, oxaliplatin, and cetuximab followed by selective capecitabine-based chemoradiation in patients with borderline resectable or unresectable locally advanced pancreatic cancer (BRPC or LAPC, respectively). Methods and Materials: Patients received gemcitabine and oxaliplatin chemotherapy repeated every 14 days for 6 cycles, combined with weekly cetuximab. Patients were then restaged; “downstaged” patients with resectable disease underwent attempted resection. Remaining patients were treated with chemoradiation consisting of intensity modulated radiation therapy (54 Gy) and concurrent capecitabine; patients with borderline resectable disease or better at restaging underwent attempted resection. Results:more » A total of 39 patients were enrolled, of whom 37 were evaluable. Protocol treatment was generally well tolerated. Median follow-up for all patients was 11.9 months. Overall, 29.7% of patients underwent R0 surgical resection (69.2% of patients with BRPC; 8.3% of patients with LAPC). Overall 6-month progression-free survival (PFS) was 62%, and median PFS was 10.4 months. Median overall survival (OS) was 11.8 months. In patients with LAPC, median OS was 9.3 months; in patients with BRPC, median OS was 24.1 months. In the group of patients who underwent R0 resection (all of which were R0 resections), median survival had not yet been reached at the time of analysis. Conclusions: This regimen was well tolerated in patients with BRPC or LAPC, and almost one-third of patients underwent R0 resection. Although OS for the entire cohort was comparable to that in historical controls, PFS and OS in patients with BRPC and/or who underwent R0 resection was markedly improved.« less

Dose-Painted Intensity-Modulated Radiation Therapy for Anal Cancer: A Multi-Institutional Report of Acute Toxicity and Response to Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kachnic, Lisa A., E-mail: lisa.kachnic@bmc.org; Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA; Tsai, Henry K.

2012-01-01

Purpose: Chemoradiation for anal cancer yields effective tumor control, but is associated with significant acute toxicity. We report our multi-institutional experience using dose-painted IMRT (DP-IMRT). Patients and Methods: Between August 2005 and May 2009, 43 patients were treated with DP-IMRT and concurrent chemotherapy for biopsy-proven, squamous cell carcinoma of the anal canal at two academic medical centers. DP-IMRT was prescribed as follows: T2N0: 42 Gy, 1.5 Gy/fraction (fx) to elective nodal planning target volume (PTV) and 50.4 Gy, 1.8 Gy/fx to anal tumor PTV; T3-4N0-3: 45 Gy, 1.5 Gy/fx to elective nodal PTV, and 54 Gy, 1.8 Gy/fx to themore » anal tumor and metastatic nodal PTV >3 cm with 50.4 Gy, 1.68 Gy/fx to nodal PTVs {<=}3 cm in size. Acute and late toxicity was reported by the treating physician. Actuarial analysis was performed using the Kaplan-Meier method. Results: Median age was 58 years; 67% female; 16% Stage I, 37% II; 42% III; 5% IV. Fourteen patients were immunocompromised: 21% HIV-positive and 12% on chronic immunosuppression. Median follow-up was 24 months (range, 0.6-43.5 months). Sixty percent completed chemoradiation without treatment interruption; median duration of treatment interruption was 2 days (range, 2-24 days). Acute Grade 3+ toxicity included: hematologic 51%, dermatologic 10%, gastrointestinal 7%, and genitourinary 7%. Two-year local control, overall survival, colostomy-free survival, and metastasis-free survival were 95%, 94%, 90%, and 92%, respectively. Conclusions: Dose-painted IMRT appears effective and well-tolerated as part of a chemoradiation therapy regimen for the treatment of anal canal cancer.« less

Phase 2 Trial of Induction Gemcitabine, Oxaliplatin, and Cetuximab Followed by Selective Capecitabine Based Chemoradiation in Patients With Borderline Resectable or Unresectable Locally Advanced Pancreatic Cancer

PubMed Central

Esnaola, Nestor F.; Chaudhary, Uzair B.; O'Brien, Paul; Garrett-Mayer, Elizabeth; Camp, E. Ramsay; Thomas, Melanie B.; Cole, David J.; Montero, Alberto J.; Hoffman, Brenda J.; Romagnuolo, Joseph; Orwat, Kelly P.; Marshall, David T.

2014-01-01

Purpose To evaluate, in a phase 2 study, the safety and efficacy of induction gemcitabine, oxaliplatin, and cetuximab followed by selective capecitabine-based chemoradiation in patients with borderline resectable or unresectable locally advanced pancreatic cancer (BRPC or LAPC, respectively). Methods and Materials Patients received gemcitabine and oxaliplatin chemotherapy repeated every 14 days for 6 cycles, combined with weekly cetuximab. Patients were then restaged; “downstaged” patients with resectable disease underwent attempted resection. Remaining patients were treated with chemoradiation consisting of intensity modulated radiation therapy (54 Gy) and concurrent capecitabine; patients with borderline resectable disease or better at restaging underwent attempted resection. Results A total of 39 patients were enrolled, of whom 37 were evaluable. Protocol treatment was generally well tolerated. Median follow-up for all patients was 11.9 months. Overall, 29.7% of patients underwent R0 surgical resection (69.2% of patients with BRPC; 8.3% of patients with LAPC). Overall 6-month progression-free survival (PFS) was 62%, and median PFS was 10.4 months. Median overall survival (OS) was 11.8 months. In patients with LAPC, median OS was 9.3 months; in patients with BRPC, median OS was 24.1 months. In the group of patients who underwent R0 resection (all of which were R0 resections), median survival had not yet been reached at the time of analysis. Conclusions This regimen was well tolerated in patients with BRPC or LAPC, and almost one-third of patients underwent R0 resection. Although OS for the entire cohort was comparable to that in historical controls, PFS and OS in patients with BRPC and/or who underwent R0 resection was markedly improved. PMID:24606850

Clinically Meaningful Differences in Patient-Reported Outcomes With Amifostine in Combination With Chemoradiation for Locally Advanced Non-Small-Cell Lung Cancer: An Analysis of RTOG 9801

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sarna, Linda; Swann, Suzanne; Langer, Corey

2008-12-01

Purpose: The purpose of this study is to analyze changes in quality of life (QOL) and symptoms from pretreatment to 6 weeks posttreatment in a Phase III randomized study (Radiation Therapy Oncology Group 9801) of amifostine (AM) vs. no AM in patients with Stages II-III non-small-cell lung cancer receiving paclitaxel and carboplatin as induction and then concurrently with hyperfractionated radiation therapy (RT). Methods and Materials: One hundred thirty-eight patients with baseline and 6-week posttreatment QOL data were analyzed. There were no significant differences in baseline demographics between those who did and did not have QOL data. The QOL and symptomsmore » were assessed by using the European Organization for Research and Treatment of Cancer (EORTC) Global QOL and Pain subscales and the EORTC-Lung Cancer-13 symptom tool. Clinically relevant changes in QOL were characterized by 10-point differences in individual scores pre/post treatment. A daily diary of patient-rated difficulty swallowing and a weekly physician-rated dysphagia log (using National Cancer Institute Common Toxicity Criteria) were completed during treatment. Weight loss was monitored. Differences in outcomes were examined according to smoking status, alcohol use, and sex. Results: Patients receiving AM reported significantly greater pain reduction after chemoradiation (34% vs. no AM, 21%), less difficulty swallowing during chemoradiation, and less weight loss than patients not receiving AM. However, physician-rated assessments of dysphagia were not significantly different by treatment arm. There were no other significant changes in QOL or symptoms according to treatment arm, smoking status, alcohol use, or sex. Conclusions: Patient evaluations of difficulty swallowing and pain suggest benefits from AM use that are distinct from clinician-rated assessments.« less

Asian Versus Non-Asian Outcomes in Nasopharyngeal Carcinoma: A North American Population-based Analysis.

PubMed

Hamilton, Sarah N; Ho, Cheryl; Laskin, Janessa; Zhai, Yongliang; Mak, Paul; Wu, Jonn

2016-12-01

The effect of ethnicity on nasopharyngeal cancer (NPC) outcomes is unclear. This retrospective analysis examines survival and the impact of concurrent chemoradiation (chemoRT) among Asian and non-Asian patients. Subjects included 380 consecutive patients with NPC treated at a Canadian institution from 2000 to 2009. Five-year Kaplan-Meier progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS) were compared between Asian (n=279) and non-Asian (n=101) subjects. Multivariable analysis was performed using Cox regression modeling. Two-variable interaction terms with concurrent chemoRT were used to examine whether concurrent chemoRT conferred different effects among subgroups. Asian subjects presented with earlier stage (P=0.005), were younger, had better performance status, and were less likely smokers (all P<0.001). Survival among Asian versus non-Asian subjects with stage I/II NPC were: PFS 68% versus 59% (P=0.04), DSS 87% versus 77% (P=0.08), and OS 84% versus 74% (P=0.003). Corresponding rates with stage III/IVA/IVB disease were PFS 49% versus 42% (P=0.12), DSS 72% versus 46% (P=0.001), and OS 70% versus 44% (P<0.001). On multivariable analysis, Asian ethnicity, age below 65 years, ECOG performance status 0-1, early stage, staging MRI use, and concurrent chemoRT were associated with improved DSS and OS (P<0.05). On testing interactions with concurrent chemoRT, Asian versus non-Asian ethnicity was significant (hazard ratio 3.9), suggesting that concurrent chemoRT conferred more benefit among non-Asian compared with Asian subjects. In this population-based study, Asian ethnicity was associated with improved DSS and OS. Concurrent chemoRT conferred more benefit among non-Asian compared with Asian subjects.

Effect of the Addition of Cetuximab to Paclitaxel, Cisplatin, and Radiation Therapy for Patients With Esophageal Cancer: The NRG Oncology RTOG 0436 Phase 3 Randomized Clinical Trial.

PubMed

Suntharalingam, Mohan; Winter, Kathryn; Ilson, David; Dicker, Adam P; Kachnic, Lisa; Konski, André; Chakravarthy, A Bapsi; Anker, Christopher J; Thakrar, Harish; Horiba, Naomi; Dubey, Ajay; Greenberger, Joel S; Raben, Adam; Giguere, Jeffrey; Roof, Kevin; Videtic, Gregory; Pollock, Jondavid; Safran, Howard; Crane, Christopher H

2017-11-01

The role of epidermal growth factor receptor (EGFR) inhibition in chemoradiation strategies in the nonoperative treatment of patients with esophageal cancer remains uncertain. To evaluate the benefit of cetuximab added to concurrent chemoradiation therapy for patients undergoing nonoperative treatment of esophageal carcinoma. A National Cancer Institute (NCI) sponsored, multicenter, phase 3, randomized clinical trial open to patients with biopsy-proven carcinoma of the esophagus. The study accrued 344 patients from 2008 to 2013. Patients were randomized to weekly concurrent cisplatin (50 mg/m2), paclitaxel (25 mg/m2), and daily radiation of 50.4 Gy/1.8 Gy fractions with or without weekly cetuximab (400 mg/m2 on day 1 then 250 mg/m2 weekly). Overall survival (OS) was the primary endpoint, with a study designed to detect an increase in 2-year OS from 41% to 53%; 80% power and 1-sided α = .025. Between June 30, 2008, and February 8, 2013, 344 patients were enrolled. This analysis used all data received at NRG Oncology through April 12, 2015. Sixteen patients were ineligible, resulting in 328 evaluable patients, 159 in the experimental arm and 169 in the control arm. Patients were well matched between the treatment arms for patient and tumor characteristics: 263 (80%) with T3 or T4 disease, 215 (66%) N1, and 62 (19%) with celiac nodal involvement. Incidence of grade 3, 4, or 5 treatment-related adverse events at any time was 71 (46%), 35 (23%), or 6 (4%) in the experimental arm and 83 (50%), 28 (17%), or 2 (1%) in the control arm, respectively. A clinical complete response (cCR) rate of 81 (56%) was observed in the experimental arm vs 92 (58%) in the control arm (Fisher exact test, P = .66). No differences were seen in cCR between treatment arms for either histology (adenocarcinoma or squamous cell). Median follow-up for all patients was 18.6 months. The 24- and 36-month local failure for the experimental arm was 47% (95% CI, 38%-57%) and 49% (95% CI, 40%-59%) vs 49% (95% CI, 41%-58%) and 49% (95% CI, 41%-58%) for the control arm (HR, 0.92; 95% CI, 0.66-1.28; P = .65). The 24- and 36-month OS rates for the experimental arm were 45% (95% CI, 37%-53%) and 34% (95% CI, 26%-41%) vs 44% (95% CI, 36%-51%) and 28% (95% CI, 21%-35%) for the control arm (HR, 0.90; 95% CI, 0.70-1.16; P = .47). The addition of cetuximab to concurrent chemoradiation did not improve OS. These phase 3 trial results point to little benefit to current EGFR-targeted agents in an unselected patient population, and highlight the need for predictive biomarkers in the treatment of esophageal cancer. clinicaltrials.gov Identifier: NCT00655876.

Pre- and posttreatment voice and speech outcomes in patients with advanced head and neck cancer treated with chemoradiotherapy: expert listeners' and patient's perception.

PubMed

van der Molen, Lisette; van Rossum, Maya A; Jacobi, Irene; van Son, Rob J J H; Smeele, Ludi E; Rasch, Coen R N; Hilgers, Frans J M

2012-09-01

Perceptual judgments and patients' perception of voice and speech after concurrent chemoradiotherapy (CCRT) for advanced head and neck cancer. Prospective clinical trial. A standard Dutch text and a diadochokinetic task were recorded. Expert listeners rated voice and speech quality (based on Grade, Roughness, Breathiness, Asthenia, and Strain), articulation (overall, [p], [t], [k]), and comparative mean opinion scores of voice and speech at three assessment points calculated. A structured study-specific questionnaire evaluated patients' perception pretreatment (N=55), at 10-week (N=49) and 1-year posttreatment (N=37). At 10 weeks, perceptual voice quality is significantly affected. The parameters overall voice quality (mean, -0.24; P=0.008), strain (mean, -0.12; P=0.012), nasality (mean, -0.08; P=0.009), roughness (mean, -0.22; P=0.001), and pitch (mean, -0.03; P=0.041) improved over time but not beyond baseline levels, except for asthenia at 1-year posttreatment (voice is less asthenic than at baseline; mean, +0.20; P=0.03). Perceptual analyses of articulation showed no significant differences. Patients judge their voice quality as good (score, 18/20) at all assessment points, but at 1-year posttreatment, most of them (70%) judge their "voice not as it used to be." In the 1-year versus 10-week posttreatment comparison, the larynx-hypopharynx tumor group was more strained, whereas nonlarynx tumor voices were judged less strained (mean, -0.33 and +0.07, respectively; P=0.031). Patients' perceived changes in voice and speech quality at 10-week post- versus pretreatment correlate weakly with expert judgments. Overall, perceptual CCRT effects on voice and speech seem to peak at 10-week posttreatment but level off at 1-year posttreatment. However, at that assessment point, most patients still perceive their voice as different from baseline. Copyright © 2012 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

Comparison of adverse effects of proton and X-ray chemoradiotherapy for esophageal cancer using an adaptive dose-volume histogram analysis.

PubMed

Makishima, Hirokazu; Ishikawa, Hitoshi; Terunuma, Toshiyuki; Hashimoto, Takayuki; Yamanashi, Koichi; Sekiguchi, Takao; Mizumoto, Masashi; Okumura, Toshiyuki; Sakae, Takeji; Sakurai, Hideyuki

2015-05-01

Cardiopulmonary late toxicity is of concern in concurrent chemoradiotherapy (CCRT) for esophageal cancer. The aim of this study was to examine the benefit of proton beam therapy (PBT) using clinical data and adaptive dose-volume histogram (DVH) analysis. The subjects were 44 patients with esophageal cancer who underwent definitive CCRT using X-rays (n = 19) or protons (n = 25). Experimental recalculation using protons was performed for the patient actually treated with X-rays, and vice versa. Target coverage and dose constraints of normal tissues were conserved. Lung V5-V20, mean lung dose (MLD), and heart V30-V50 were compared for risk organ doses between experimental plans and actual treatment plans. Potential toxicity was estimated using protons in patients actually treated with X-rays, and vice versa. Pulmonary events of Grade ≥2 occurred in 8/44 cases (18%), and cardiac events were seen in 11 cases (25%). Risk organ doses in patients with events of Grade ≥2 were significantly higher than for those with events of Grade ≤1. Risk organ doses were lower in proton plans compared with X-ray plans. All patients suffering toxicity who were treated with X-rays (n = 13) had reduced predicted doses in lung and heart using protons, while doses in all patients treated with protons (n = 24) with toxicity of Grade ≤1 had worsened predicted toxicity with X-rays. Analysis of normal tissue complication probability showed a potential reduction in toxicity by using proton beams. Irradiation dose, volume and adverse effects on the heart and lung can be reduced using protons. Thus, PBT is a promising treatment modality for the management of esophageal cancer. © The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

External radiotherapy and brachytherapy in the management of extrahepatic and intrahepatic cholangiocarcinoma: available evidence.

PubMed

Sahai, Puja; Kumar, Senthil

2017-08-01

This review aims to summarize the currently available evidence for the role of external radiotherapy and brachytherapy in the management of cholangiocarcinoma. High locoregional disease recurrence rates after surgical resection alone for both the extrahepatic cholangiocarcinoma (EHCC) and intrahepatic cholangiocarcinoma (IHCC) provide a rationale for using adjuvant radiotherapy with chemotherapy. We performed a literature search related to radiotherapy in cholangiocarcinoma published between 2000 and 2016. The role of radiation is discussed in the adjuvant, neoadjuvant, definitive and the palliative setting. Evidence from Phase II trials have demonstrated efficacy of adjuvant chemoradiation in combination with chemotherapy in EHCC. Locally advanced cholangiocarcinoma may be treated with neoadjuvant chemoradiotherapy. In the case of downsizing, assessment for resection may be considered. Brachytherapy offers dose escalation after external radiotherapy. Selected unresectable cases of cholangiocarcinoma may be considered for stereotactic body radiation therapy with neoadjuvant and/or concurrent chemotherapy. Liver transplantation is a treatment option in selected patients with EHCC and IHCC after neoadjuvant chemoradiation. Stenting in combination with palliative external radiotherapy and/or brachytherapy provides improved stent patency and survival. Newer advanced radiation techniques provide a scope for achieving better disease control with reduced morbidity. Effective multimodality treatment incorporating radiotherapy is the way forward for improving survival in patients with cholangiocarcinoma.

Gemcitabine-induced gouty arthritis attacks.

PubMed

Bottiglieri, Sal; Tierson, Neil; Patel, Raina; Mo, Jae-Hyun; Mehdi, Syed

2013-09-01

In this case report, we review the experience of a patient who presented with early stage pancreatic cancer (Stage IIb) who underwent a Whipple procedure and adjuvant chemoradiation. The patient's past medical history included early stage colon cancer in remission, post-traumatic-stress-disorder, hypertension, hyperlipidemia, osteoarthritis, gout, and pre-diabetes. Chemotherapy initially consisted of weekly gemcitabine. The patient developed acute gouty attacks after his second dose of gemcitabine, which brought him to the emergency room for emergent treatment on several occasions. Gemcitabine was held and treatment began with fluorouracil and concurrent radiation. After completion of his chemoradiation with fluorouracil, he was again treated with weekly gemcitabine alone. As soon as the patient started gemcitabine chemotherapy the patient developed gouty arthritis again, requiring discontinuation of chemotherapy. The patient received no additional treatment until his recent recurrence 8 months later where gemcitabine chemotherapy was again introduced with prophylactic medications consisting of allopurinol 100 mg by mouth daily and colchicine 0.6 mg by mouth daily throughout gemcitabine chemotherapy, and no signs of gouty arthritis occurred. To our knowledge, this is the first case report describing gout attacks associated with gemcitabine therapy. There is limited data available describing the mechanism that gouty arthritis may be precipitated from gemcitabine chemotherapy. Further monitoring and management may be required in patients receiving gemcitabine chemotherapy with underlying gout.

Progressive resistance training in head and neck cancer patients undergoing concomitant chemoradiotherapy

PubMed Central

Lonkvist, Camilla K.; Vinther, Anders; Zerahn, Bo; Rosenbom, Eva; Deshmukh, Atul S.; Hojman, Pernille

2017-01-01

Objectives Patients with head and neck squamous cell carcinoma undergoing concomitant chemoradiotherapy (CCRT) frequently experience weight loss, especially loss of lean body mass (LBM), and reduced functional performance. This study investigated whether a 12‐week hospital‐based progressive resistance training (PRT) program during CCRT is feasible in the clinical setting before planning initiation of a larger randomized study which is the long‐term goal. Study design Prospective pilot study. Methods Twelve patients receiving CCRT were planned to attend a 12‐week PRT program. Primary endpoint was feasibility measured as attendance to training sessions. Secondary endpoints included changes in functional performance, muscle strength, and body composition measured by Dual‐energy X‐ray Absorptiometry (DXA) scans. Furthermore, sarcomeric protein content, pentose phosphate pathway (PPP) activity, and glycolysis were determined in muscle biopsies. Results Twelve patients with p16 positive oropharyngeal cancer were enrolled. The primary endpoint was met with 9 of the 12 patients completing at least 25 of 36 planned training sessions. The mean attendance rate was 77%. Functional performance was maintained during the treatment period and increased during follow‐up (p < 0.01). Strength was regained after an initial dip during treatment, paralleling responses in LBM and sarcomeric protein content. LBM began to increase immediately after treatment. The PPP was upregulated after the treatment period, whilst glycolysis remained unchanged. No adverse events were related to PRT and in questionnaires, patients emphasized the social and psychological benefits of attendance. Conclusion Progressive resistance training is feasible and safe during CCRT for head and neck cancer, and is associated with high patient satisfaction. Level of Evidence 2C. PMID:29094074

The effect of neck dissection on quality of life after chemoradiation.

PubMed

Donatelli-Lassig, Amy Anne; Duffy, Sonia A; Fowler, Karen E; Ronis, David L; Chepeha, Douglas B; Terrell, Jeffrey E

2008-10-01

To determine differences in quality of life (QOL) between patients with head and neck cancer who receive chemoradiation versus chemoradiation and neck dissection. A prospective cohort study was conducted at two tertiary otolaryngology clinics and a Veterans Administration hospital. 103 oropharyngeal patients with Stage IV squamous cell carcinoma treated via chemoradiation +/- neck dissection. self-administered health survey to collect health, demographic, and QOL information pretreatment and 1 year later. QOL via SF-36 and HNQoL. Descriptive statistics were calculated for health/clinical characteristics, demographics, and QOL scores. t tests evaluated changes in QOL over time. Sixty-five patients underwent chemoradiation and 38 patients underwent chemoradiation and neck dissection. Only the pain index of the SF-36 showed a significant difference between groups (P < 0.05) with the neck dissection group reporting greater pain. After post-treatment neck dissection, patients experience statistically significant decrement in bodily pain domain scores, but other QOL scores are similar to those of patients who underwent chemoradiation alone.

The effect of neck dissection on quality of life after chemoradiation

PubMed Central

Lassig, Amy Anne Donatelli; Duffy, Sonia A.; Fowler, Karen E.; Ronis, David L.; Chepeha, Douglas B.; Terrell, Jeffrey E.

2010-01-01

Objective To determine differences in QOL between head and neck cancer patients receiving chemoradiation versus chemoradiation and neck dissection. Methods A prospective cohort study was conducted at 2 tertiary otolaryngology clinics and a VA. Sample: 103 oropharyngeal Stage IV SCCA patients treated via chemoradiation +/− neck dissection. Intervention: self-administered health survey collecting health, demographic, and QOL information pretreatment and 1 year later. Main outcome measures: QOL via SF-36 and HNQoL. Descriptive statistics were calculated for health / clinical characteristics, demographics, and QOL scores. T-tests evaluated changes in QOL over time. Results 65 patients received chemoradiation and 38 chemoradiation + neck dissection. Only the pain index of the SF-36 showed a significant difference between groups (p<.05) with the neck dissection group reporting greater pain. Conclusions After post-treatment neck dissection, patients experience statistically significant decrement in bodily pain domain scores, but other QOL scores are similar to those of patients undergoing chemoradiation alone. PMID:18922336

Final Results of a Randomized Phase 2 Trial Investigating the Addition of Cetuximab to Induction Chemotherapy and Accelerated or Hyperfractionated Chemoradiation for Locoregionally Advanced Head and Neck Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seiwert, Tanguy Y., E-mail: tseiwert@medicine.bsd.uchicago.edu; Melotek, James M.; Blair, Elizabeth A.

Purpose: The role of cetuximab in the treatment of locoregionally advanced head and neck squamous cell cancer (LA-HNSCC) remains poorly defined. In this phase 2 randomized study, we investigated the addition of cetuximab to both induction chemotherapy (IC) and hyperfractionated or accelerated chemoradiation. Methods and Materials: Patients with LA-HNSCC were randomized to receive 2 cycles of weekly IC (cetuximab, paclitaxel, carboplatin) and either Cetux-FHX (concurrent cetuximab, 5-fluorouracil, hydroxyurea, and 1.5 Gy twice-daily radiation therapy every other week to 75 Gy) or Cetux-PX (cetuximab, cisplatin, and accelerated radiation therapy with delayed concomitant boost to 72 Gy in 42 fractions). The primary endpoint was progression-freemore » survival (PFS), with superiority compared with historical control achieved if either arm had 2-year PFS ≥70%. Results: 110 patients were randomly assigned to either Cetux-FHX (n=57) or Cetux-PX (n=53). The overall response rate to IC was 91%. Severe toxicity on IC was limited to rash (23% grade ≥3) and myelosuppression (38% grade ≥3 neutropenia). The 2-year rates of PFS for both Cetux-FHX (82.5%) and Cetux-PX (84.9%) were significantly higher than for historical control (P<.001). The 2-year overall survival (OS) was 91.2% for Cetux-FHX and 94.3% for Cetux-PX. With a median follow-up time of 72 months, there were no significant differences in PFS (P=.35) or OS (P=.15) between the treatment arms. The late outcomes for the entire cohort included 5-year PFS, OS, locoregional failure, and distant metastasis rates of 74.1%, 80.3%, 15.7%, and 7.4%, respectively. The 5-year PFS and OS were 84.4% and 91.3%, respectively, among human papillomavirus (HPV)-positive patients and 65.9% and 72.5%, respectively, among HPV-negative patients. Conclusions: The addition of cetuximab to IC and chemoradiation was tolerable and produced long-term control of LA-HNSCC, particularly among poor-prognosis HPV-negative patients. Further investigation of cetuximab may be warranted in the neoadjuvant setting and with non–platinum-based chemoradiation.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fukada, Junichi, E-mail: fukada@rad.med.keio.ac.jp; Shigematsu, Naoyuki; Takeuchi, Hiroya

Purpose: We investigated clinical and treatment-related factors as predictors of symptomatic pericardial effusion in esophageal cancer patients after concurrent chemoradiation therapy. Methods and Materials: We reviewed 214 consecutive primary esophageal cancer patients treated with concurrent chemoradiation therapy between 2001 and 2010 in our institute. Pericardial effusion was detected on follow-up computed tomography. Symptomatic effusion was defined as effusion ≥grade 3 according to Common Terminology Criteria for Adverse Events v4.0 criteria. Percent volume irradiated with 5 to 65 Gy (V5-V65) and mean dose to the pericardium were evaluated employing dose-volume histograms. To evaluate dosimetry for patients treated with two-dimensional planning inmore » the earlier period (2001-2005), computed tomography data at diagnosis were transferred to a treatment planning system to reconstruct three-dimensional plans without modification. Optimal dosimetric thresholds for symptomatic pericardial effusion were calculated by receiver operating characteristic curves. Associating clinical and treatment-related risk factors for symptomatic pericardial effusion were detected by univariate and multivariate analyses. Results: The median follow-up was 29 (range, 6-121) months for eligible 167 patients. Symptomatic pericardial effusion was observed in 14 (8.4%) patients. Dosimetric analyses revealed average values of V30 to V45 for the pericardium and mean pericardial doses were significantly higher in patients with symptomatic pericardial effusion than in those with asymptomatic pericardial effusion (P<.05). Pericardial V5 to V55 and mean pericardial doses were significantly higher in patients with symptomatic pericardial effusion than in those without pericardial effusion (P<.001). Mean pericardial doses of 36.5 Gy and V45 of 58% were selected as optimal cutoff values for predicting symptomatic pericardial effusion. Multivariate analysis identified mean pericardial dose as the strongest risk factor for symptomatic pericardial effusion. Conclusions: Dose-volume thresholds for the pericardium facilitate predicting symptomatic pericardial effusion. Mean pericardial dose was selected based not only on the optimal dose-volume threshold but also on the most significant risk factor for symptomatic pericardial effusion.« less

Induction chemotherapy selects patients with locally advanced, unresectable pancreatic cancer for optimal benefit from consolidative chemoradiation therapy.

PubMed

Krishnan, Sunil; Rana, Vishal; Janjan, Nora A; Varadhachary, Gauri R; Abbruzzese, James L; Das, Prajnan; Delclos, Marc E; Gould, Morris S; Evans, Douglas B; Wolff, Robert A; Crane, Christopher H

2007-07-01

The current study was conducted to determine whether there were differences in outcome for patients with unresectable locally advanced pancreatic cancer (LAPC) who received treatment with chemoradiation therapy (CR) versus induction chemotherapy followed by CR (CCR). Between December 1993 and July 2005, 323 consecutive patients with LAPC were treated at the authors' institution with radiotherapy and concurrent gemcitabine or fluoropyrimidine chemotherapy. Two hundred forty-seven patients received CR as initial treatment, and 76 patients received a median of 2.5 months of gemcitabine-based induction chemotherapy prior to CR. Most patients received a radiation dose of 30 grays in 10 fractions (85%) concurrently with infusional 5-fluorouracil (41%), gemcitabine (39%), or capecitabine (20%). The median follow-up was 5.5 months (range, 1-63 months). For all patients, the median overall survival (OS) and progression-free survival (PFS) were 9 months and 5 months, respectively, and the 2-year estimated OS and PFS rates were 9% and 5%, respectively. The median OS and PFS were 8.5 months and 4.2 months, respectively, in the CR group and 11.9 months and 6.4 months, respectively, in the CCR group (both P < .001). The median times to local and distant progression were 6.0 months and 5.6 months, respectively, in the CR group and 8.9 and 9.5 months, respectively, in the CCR group (P = .003 and P = .007, respectively). There was no significant difference in the patterns of failure with the use of induction chemotherapy. The results from this analysis indicated that, by excluding patients with rapid distant progression, induction chemotherapy may select patients with LAPC for optimal benefit from consolidative CR. The authors believe that this strategy of enriching the population of patients who receive a locoregional treatment modality merits prospective randomized evaluation. Copyright (c) 2007 American Cancer Society.

Clear Cell Carcinoma of the Uterine Cervix: A Clinical and Pathological Analysis of 47 Patients Without Intrauterine Diethylstilbestrol Exposure.

PubMed

Yang, Li; Zheng, Aiwen; Zhang, Xiang; Fang, Xianhua; Sun, Wenyong; Chen, Yaqing

2017-06-01

The aim of this study was to summarize the clinical and pathological characteristics and to conduct prognosis analysis of patients who were diagnosed with clear cell carcinoma of the uterine cervix (CCCUC) and without a history of exposure to diethylstilbestrol. We performed a retrospective review of all the patients with CCCUC who were diagnosed and treated at Zhejiang Cancer Hospital between 1998 and 2014. Charts were reviewed for clinical and pathological characteristics, and prognosis analysis was conducted. A total of 47 patients were included. Median age was 52 years. No patient had a history of exposure to diethylstilbestrol. The International Federation of Gynecology and Obstetrics stage distribution was 55.3% (n = 26) stage I, 40.4% (n = 19) stage II, 2.1% (n = 1) stage III, and 2.1% (n = 1) stage IV. Forty-two patients (89.4%) underwent radical hysterectomy and pelvic lymphadenectomy. Pathological examination revealed deep cervical stromal invasion (greater than two thirds) in 20 patients (48.4%), pelvic lymph node (PLN) metastasis in 10 patients (23.8%), lymphovascular space involvement in 9 patients (21.4%), and ovarian metastasis in 1 patient (2.4%). Advanced tumor stage (IIB-IV), larger tumor size (>4 cm), and PLN metastasis had negative effects on progression-free survival (PFS) and overall survival (OS) (P < 0.05). Adjuvant radiation therapy alone or concurrent chemoradiation therapy after radical surgery did not affect PFS or OS in patients with risk factors (P > 0.05). International Federation of Gynecology and Obstetrics stage, tumor size, and PLN status were prognostic factors for both PFS and OS in patients with CCCUC. The long-term effects of adjuvant radiation therapy or concurrent chemoradiation therapy may be limited for CCCUC patients with risk factors. Future larger case series or clinical trials are required to confirm these findings.

Patterns of Care for Elderly Patients With Locally Advanced Head and Neck Cancer.

PubMed

Juarez, Jesus E; Choi, Jehee; St John, Maie; Abemayor, Elliot; TenNapel, Mindi; Chen, Allen M

2017-07-15

To compare patterns of care for elderly patients aged ≥70 years with locally advanced head and neck cancer versus those of younger patients treated for the same disease. The medical records of 421 consecutive patients over the age of 50 years treated at a single institution between April 2011 and June 2016 for stage III/IV squamous cell carcinoma of the head and neck were reviewed. The primary treatment approach was compared using a t test statistic among 3 age cohorts: 50 to 59 years (118 patients); 60 to 69 years (152 patients); and 70 years and older (151 patients). Logistical regression was used to determine variables that influenced the likelihood of receiving surgery versus nonsurgical treatment, as well as radiation alone versus chemoradiation. There was no difference in sex, T stage, N stage, Karnofsky performance status, or the number of chronic comorbid conditions among the 3 age cohorts (P>.05 for all). A greater proportion of elderly patients aged ≥70 years were treated by radiation alone compared with those aged 50 to 59 and 60 to 69 years (44% vs 16% and 24%, P=.01). Increasing age was associated with a greater likelihood of receiving primary nonsurgical versus surgical treatment (odds ratio 1.023, 95% confidence interval 1.004-1.042) and radiation alone compared with chemoradiation (odds ratio 1.054; 95% confidence interval 1.034-1.075). Ten chemotherapy regimens were used concurrently with radiation for patients aged ≥70 years, including carboplatin/paclitaxel (19%), carboplatin/cetuximab (19%), cisplatin (17%), and cetuximab (17%). Despite similar performance status and comorbidity burden compared with their younger counterparts, patients aged ≥70 years were more commonly treated with less-aggressive strategies, including radiation alone. The variability of concurrent chemotherapy regimens used further suggests that the standard of care remains to be defined for this population. Copyright © 2017 Elsevier Inc. All rights reserved.

Phase 2 Trial of De-intensified Chemoradiation Therapy for Favorable-Risk Human Papillomavirus–Associated Oropharyngeal Squamous Cell Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chera, Bhishamjit S., E-mail: bchera@med.unc.edu; Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina; Amdur, Robert J.

Purpose: To perform a prospective, multi-institutional, phase 2 study of a substantial decrease in concurrent chemoradiation therapy (CRT) intensity as primary treatment for favorable-risk, human papillomavirus–associated oropharyngeal squamous cell carcinoma. Methods and Materials: The major inclusion criteria were: (1) T0 to T3, N0 to N2c, M0; (2) human papillomavirus or p16 positive; and (3) minimal/remote smoking history. Treatment was limited to 60 Gy intensity modulated radiation therapy with concurrent weekly intravenous cisplatinum (30 mg/m{sup 2}). The primary study endpoint was pathologic complete response (pCR) rate based on required biopsy of the primary site and dissection of pretreatment positive lymph node regions, regardless ofmore » radiographic response. Power computations were performed for the null hypothesis that the pCR rate is 87% and n=40, resulting in a type 1 error of 14.2%. Secondary endpoint measures included physician-reported toxicity (Common Toxicity Terminology for Adverse Events, CTCAE), patient-reported symptoms (PRO-CTCAE), and modified barium swallow studies. Results: The study population was 43 patients. The pCR rate was 86% (37 of 43). The incidence of CTCAE grade 3/4 toxicity and PRO-CTCAE severe/very severe symptoms was as follows: mucositis 34%/45%, general pain 5%/48%, nausea 18%/52%, vomiting 5%/34%, dysphagia 39%/55%, and xerostomia 2%/75%. Grade 3/4 hematologic toxicities were 11%. Thirty-nine percent of patients required a feeding tube for a median of 15 weeks (range, 5-22 weeks). There were no significant differences in modified barium swallow studies before and after CRT. Conclusions: The pCR rate with decreased intensity of therapy with 60 Gy of IMRT and weekly low-dose cisplatinum is very high in favorable-risk oropharyngeal squamous cell carcinoma, with evidence of decreased toxicity compared with standard therapies. (ClinicalTrials.gov) ID: (NCT01530997).« less

Change in chemotherapy during concurrent radiation followed by surgery after a suboptimal positron emission tomography response to induction chemotherapy improves outcomes for locally advanced esophageal adenocarcinoma.

PubMed

Ku, Geoffrey Y; Kriplani, Anuja; Janjigian, Yelena Y; Kelsen, David P; Rusch, Valerie W; Bains, Manjit; Chou, Joanne; Capanu, Marinela; Wu, Abraham J; Goodman, Karyn A; Ilson, David H

2016-07-01

A positron emission tomography (PET) scan after induction chemotherapy before preoperative chemoradiation and surgery for esophageal adenocarcinoma predicts outcomes. Some patients with progression on PET after induction chemotherapy had long-term overall survival (OS) when they were changed to alternative chemotherapy during radiation. This study retrospectively reviewed esophageal adenocarcinoma patients who received induction chemotherapy and chemoradiation before planned surgery; all had undergone a PET scan before and after induction chemotherapy. There were 201 patients, and 113 (56%) were PET responders (≥35% decrease in the maximum standardized uptake value of the tumor). All PET responders received the same chemotherapy during radiation, whereas 38 of the 88 PET nonresponders (43%) changed chemotherapy. Among the 152 patients who underwent surgery, the pathologic complete response rate was 15% for PET responders and 3% for PET nonresponders who did not change chemotherapy (P = .046). The median progression-free survival (PFS; 18.9 vs 10.0 months, P < 0.01) and OS (37 vs 25.3 months, P = .02) were significantly better for PET responders versus PET nonresponders who did not change chemotherapy. The median PFS for PET nonresponders who changed chemotherapy was 17.9 months, and it was superior to the median PFS for PET nonresponders who did not change chemotherapy (P = .01). For PET nonresponders, the 5-year OS rates were 37% for those who changed chemotherapy and 25% for those who did not change chemotherapy (P = .18). A PET scan after induction chemotherapy predicts outcomes for locally advanced esophageal adenocarcinoma patients who undergo chemoradiation and surgery. The median PFS is improved, and trends toward improved OS appear possible in PET nonresponders who change chemotherapy during radiation. The fully accrued Cancer and Leukemia Group B 80803 study (NCT01333033) is evaluating this strategy. Cancer 2016;122:2083-90. © 2016 American Cancer Society. © 2016 American Cancer Society.

Promising outcomes of definitive chemoradiation and cetuximab for patients with esophageal squamous cell carcinoma.

PubMed

Chen, Yongshun; Wu, Xiaoyuan; Bu, Shanshan; He, Chunyu; Wang, Wen; Liu, Jinsong; Guo, Wei; Tan, Bo; Wang, Yanxia; Wang, Jianhua

2012-11-01

This study investigated cetuximab added to definitive concurrent chemoradiation for esophageal squamous cell carcinoma (ESCC). Previously untreated patients with stage II-IVa ESCC received cetuximab (400 mg/m(2) per week in week 1, then 250 mg/m(2) per week during weeks 2-8), paclitaxel (45 mg/m(2) per week) and cisplatin (20 mg/m(2) per week) in weeks 2-8 with 59.4 Gy radiotherapy. Epidermal growth factor receptor (EGFR) status in tumor specimens was assessed. Thirty-one patients were enrolled and evaluated for toxicity. Of the 29 patients assessable for a response, 20 (69.0%) had a clinical complete response (CR). Over a median follow up of 23.6 months, disease progression was observed in seven patients. The 1- and 2-year progression-free survival (PFS) rates were 85.5% and 75.1%, respectively. The PFS was shorter for patients with lymphatic metastatic disease than for those with locally confined tumor; the 1-year PFS rates were 78.7% and 92.3%, respectively (P = 0.038). Sixteen (55.2%) patients were immunohistochemically positive for EGFR. The patients with EGFR-expressing tumor had a CR rate of 75.0% compared with 61.5% in those with negative EGFR expression (P = 0.024). The PFS for patients with EGFR-expressing tumor was longer compared with the PFS of patients with negative EGFR (P = 0.133). The patients with prominent cetuximab-induced rash (≥grade 2) had a better CR rate and PFS than those with no or grade 1 rash (P < 0.05). The rates of grades 3/4 esophagitis, hematological and dermatological toxicities were 9.7%, 29.0% and 16.1%, respectively. The regimen of definitive chemoradiation plus cetuximab achieved good clinical response and has an acceptable safety profile in Chinese ESCC patients. © 2012 Japanese Cancer Association.

Role of Adjuvant Treatment in Esophageal Cancer With Incidental Pathologic Node Positivity.

PubMed

Gao, Sarah J; Park, Henry S; Corso, Christopher D; Rutter, Charles E; Kim, Anthony W; Johung, Kimberly L

2017-07-01

The optimal adjuvant treatment for cT1-2 N0 esophageal cancer patients found to have pathologic nodal involvement after an upfront operation is unclear. This study investigated the effects of postoperative chemotherapy and chemoradiation therapy on overall survival in cT1-2 N0 patients with incidental pN + disease stratified by margin status. We identified cT1-2 N0 M0 esophageal carcinoma patients from 2004 to 2012 from the National Cancer Data Base. Patients were categorized as having received surgical resection alone, surgical resection followed by chemotherapy (S+CT), and surgical resection followed by concurrent chemoradiation therapy (S+CRT). Subset analyses were conducted on margin-negative and margin-positive patients. Overall survival was compared by Kaplan-Meier estimation, the log-rank test, and multivariable Cox regression analysis. Among 443 patients, 52.6% received surgical resection alone, 18.7% received S+CT, and 28.6% received S+CRT. Significantly more adenocarcinoma patients received adjuvant treatment (50.8%) than squamous cell carcinoma patients (27.7%, p = 0.001). On multivariable analysis, S+CT (hazard ratio, 0.64; 95% confidence interval, 0.45 to 0.91; p = 0.014) and S+CRT (hazard ratio, 0.73; 95% confidence interval,. 0.55 to 0.98; p = 0.038) both were associated with significantly increased overall survival. These findings persisted among margin-negative patients. However, in margin-positive patients, S+CRT (hazard ratio, 0.29; p = 0.002) was the only treatment arm that was associated with significantly improved survival compared with surgical resection alone. Among cT1-2 N0 pN + esophageal cancer patients, adjuvant chemotherapy may be sufficient for margin-negative patients, whereas adjuvant chemoradiation therapy appears necessary for margin-positive patients. Further prospective studies are needed to confirm the results. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Cytomegalovirus-targeted immunotherapy and glioblastoma: hype or hope?

PubMed

Ferguson, Sherise D; Srinivasan, Visish M; Ghali, Michael Gz; Heimberger, Amy B

2016-01-01

Malignant gliomas, including glioblastoma (GBM), are the most common primary brain tumors. Despite extensive research only modest gains have been made in long-term survival. Standard of care involves maximizing safe surgical resection followed by concurrent chemoradiation with temozolomide. Immunotherapy for GBM is an area of intense research in recent years. New immunotherapies, although promising, have not been integrated into standard practice. Human cytomegalovirus (HCMV) is a DNA virus of the family Herpesviridae. Human seroprevalence is approximately 80%, and in most cases, is associated with asymptomatic infection. HCMV may be an important agent in the initiation, promotion and/or progression of tumorigenesis. Regardless of a possible etiologic role in GBM, interest has centered on exploiting this association for development of immunomodulatory therapies.

Nasopharyngeal carcinoma.

PubMed

Kamran, Sophia C; Riaz, Nadeem; Lee, Nancy

2015-07-01

Nasopharyngeal carcinoma is uncommon in the United States, with only 0.2 to 0.5 cases per 100,00 people; this is in contrast to southern China and Hong Kong, where the incidence is 25 to 50 per 100,000 people. There is a potential link between Epstein-Barr virus and the development of nasopharyngeal carcinoma. Radiotherapy alone as a single modality leads to similar 10-year survival rates in United States, Denmark, and Hong Kong (34%, 37%, and 43%, respectively). Multiple studies have shown an advantage to concurrent chemoradiation in the treatment of advanced disease. Radiation therapy remains the mainstay of salvage therapy, and modern techniques have allowed clinicians to achieve adequate local control without excessive toxicity. Copyright © 2015 Elsevier Inc. All rights reserved.

Stereotactic body radiation therapy with concurrent full-dose gemcitabine for locally advanced pancreatic cancer: a pilot trial demonstrating safety

PubMed Central

2013-01-01

Background Concurrent chemoradiation is a standard option for locally advanced pancreatic cancer (LAPC). Concurrent conventional radiation with full-dose gemcitabine has significant toxicity. Stereotactic body radiation therapy (SBRT) may provide the opportunity to administer radiation in a shorter time frame with similar efficacy and reduced toxicity. This Pilot study assessed the safety of concurrent full-dose gemcitabine with SBRT for LAPC. Methods Patients received gemcitabine, 1000 mg/m2 for 6 cycles. During week 4 of cycle 1, patients received SBRT (25 Gy delivered in five consecutive daily fractions of 5 Gy prescribed to the 75-83% isodose line). Acute and late toxicities were assessed using NIH CTCAE v3. Tumor response was assessed by RECIST. Patients underwent an esophagogastroduodenoscopy at baseline, 2, and 6 months to assess the duodenal mucosa. Quality of life (QoL) data was collected before and after treatment using the QLQ-C30 and QLQ-PAN26 questionnaires. Results Between September 2009 and February 2011, 11 patients enrolled with one withdrawal during radiation therapy. Patients had grade 1 to 2 gastrointestinal toxicity from the start of SBRT to 2 weeks after treatment. There were no grade 3 or greater radiation-related toxicities or delays for cycle 2 of gemcitabine. On endoscopy, there were no grade 2 or higher mucosal toxicities. Two patients had a partial response. The median progression free and overall survival were 6.8 and 12.2 months, respectively. Global QoL did not change between baseline and immediately after radiation treatment. Conclusions SBRT with concurrent full dose gemcitabine is safe when administered to patients with LAPC. There is no delay in administration of radiation or chemotherapy, and radiation is completed with minimal toxicity. PMID:23452509

Premalignant Lesions of the Anal Canal and Squamous Cell Carcinoma of the Anal Canal

PubMed Central

Poggio, Juan Lucas

2011-01-01

Squamous cell carcinoma of the anus (SCCA) is a rare tumor. However, its incidence has been increasing in men and women over the past 25 years worldwide. Risk factors associated with this cancer are those behaviors that predispose individuals to human papillomavirus (HPV) infection and immunosuppression. Anal cancer is generally preceded by high-grade anal intraepithelial neoplasia (HGAIN), which is most prevalent in human immunodeficiency virus-positive men who have sex with men. High-risk patients may benefit from screening. The most common presentation is rectal bleeding, which is present in nearly 50% of patients. Twenty percent of patients have no symptoms at the time of presentation. Clinical staging of anal cancer requires a digital rectal exam and a positron emission tomography/computed tomography scan of the chest, abdomen, and pelvis. Endorectal/endoanal ultrasound appears to add more-specific staging information when compared with digital rectal examination alone. Treatment of anal cancer prior to the 1970s involved an abdominoperineal resection. However, the current standard of care for localized anal cancer is concurrent chemoradiation therapy, primarily because of its sphincter-saving and colostomy-sparing potential. Studies have addressed alternative chemoradiation regimens to improve the standard protocol of fluorouracil, misogynic, and radiation, but no alternative regimen has proven superior. Surgery is reserved for those patients with residual disease or recurrence. PMID:22942800

Salvage radiation therapy and chemoradiation therapy for postoperative locoregional recurrence of esophageal cancer.

PubMed

Kobayashi, R; Yamashita, H; Okuma, K; Shiraishi, K; Ohtomo, K; Nakagawa, K

2014-01-01

The purpose of this retrospective study was to assess the efficacy of salvage radiation therapy (RT) or chemoradiation therapy (CRT) for locoregional recurrence (LR) of esophageal cancer after curative surgery. Forty-two patients who received salvage RT or CRT for LR of esophageal cancer after curative surgery between November 2000 and May 2012 were reviewed. The intended RT regimen was 60 Gy in 30 fractions combined with concurrent platinum-based chemotherapy. Median follow-up periods were 17.9 months for all evaluable patients and 28.2 months for patients still alive (19 patients) at analysis time. The 1-, 2-, and 3-year survival rates were 81.2 ± 6.4%, 51.3 ± 8.6%, and 41.1 ± 8.7%, respectively, with a median survival time of 24.3 ± 4.1 months. Out of 41 evaluable patients, 16 patients (39%) were alive beyond 2 years from salvage therapy. However, univariate analyses for overall survival showed no significant prognostic factor. Grade 3 or higher leukocytopenia was observed in 46% of the patients. Salvage RT or CRT for LR after surgery for esophageal cancer was safe and effective. These therapies may offer long-term survival to some patients. RT or CRT should be considered for LR. © 2013 Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

Divided attention enhances explicit but not implicit conceptual memory: an item-specific account of the attentional boost effect.

PubMed

Spataro, Pietro; Mulligan, Neil W; Bechi Gabrielli, Giulia; Rossi-Arnaud, Clelia

2017-02-01

The Attentional Boost Effect (ABE) refers to the counterintuitive finding that words encoded with to-be-responded targets in a divided-attention condition are remembered better than words encoded with distractors. Previous studies suggested that the ABE-related enhancement of verbal memory depends upon the activation of abstract lexical representations. In the present study, we extend this hypothesis by embedding it in the context of a broader perspective, which proposes that divided attention in the ABE paradigm affects item-specific, but not relational, processing. To this purpose, we examined the ABE in the matched tasks of category-cued recall (CCRT: explicit memory) and category exemplar generation (CEGT: implicit memory). In addition, study time was varied (500, 1500 or 4000 ms), to further determine whether the attentional boost manipulation could influence late-phase elaborative processing. In agreement with the predictions of the item-specific account, the results showed that exemplars encoded with targets were recalled better than exemplars encoded with distractors in the CCRT, but not in the CEGT. Moreover, performance in the CCRT increased with study time, whereas the size of the ABE-related enhancement tended to decrease, further confirming that this effect hinges upon early phase encoding processes.

Epigenetic Alteration by DNA Methylation of ESR1, MYOD1 and hTERT Gene Promoters is Useful for Prediction of Response in Patients of Locally Advanced Invasive Cervical Carcinoma Treated by Chemoradiation.

PubMed

Sood, S; Patel, F D; Ghosh, S; Arora, A; Dhaliwal, L K; Srinivasan, R

2015-12-01

Locally advanced invasive cervical cancer [International Federation of Gynecology and Obstetrics (FIGO) IIB/III] is treated by chemoradiation. The response to treatment is variable within a given FIGO stage. Therefore, the aim of the present study was to evaluate the gene promoter methylation profile and corresponding transcript expression of a panel of six genes to identify genes which could predict the response of patients treated by chemoradiation. In total, 100 patients with invasive cervical cancer in FIGO stage IIB/III who underwent chemoradiation treatment were evaluated. Ten patients developed systemic metastases during therapy and were excluded. On the basis of patient follow-up, 69 patients were chemoradiation-sensitive, whereas 21 were chemoradiation-resistant. Gene promoter methylation and gene expression was determined by TaqMan assay and quantitative real-time PCR, respectively, in tissue samples. The methylation frequency of ESR1, BRCA1, RASSF1A, MLH1, MYOD1 and hTERT genes ranged from 40 to 70%. Univariate and hierarchical cluster analysis revealed that gene promoter methylation of MYOD1, ESR1 and hTERT could predict for chemoradiation response. A pattern of unmethylated MYOD1, unmethylated ESR1 and methylated hTERT promoter as well as lower ESR1 transcript levels predicted for chemoradiation resistance. Methylation profiling of a panel of three genes that includes MYOD1, ESR1 and hTERT may be useful to predict the response of invasive cervical carcinoma patients treated with standard chemoradiation therapy. Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Evaluating Mesorectal Lymph Nodes in Rectal Cancer Before and After Neoadjuvant Chemoradiation Using Thin-Section T2-Weighted Magnetic Resonance Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koh, Dow-Mu; Chau, Ian; Tait, Diana

2008-06-01

Purpose: To apply thin-section T2-weighted magnetic resoance imaging (MRI) to evaluate the number, size, distribution, and morphology of benign and malignant mesorectal lymph nodes before and after chemoradiation treatment compared with histopathologic findings. Methods and Materials: Twenty-five patients with poor-risk adenocarcinoma of the rectum treated with neoadjuvant chemoradiation were evaluated prospectively. Thin-section T2-weighted MR images obtained before and after chemoradiation treatment were independently reviewed in consensus by 2 expert radiologists to determine the tumor stage, nodal size, nodal distribution, and nodal stage. Total mesorectal excision surgery after chemoradiation allowed MR nodal stage to be compared with histopathology using {kappa} statistics.more » Nodal downstaging was compared using the Chi-square test. Results: Before chemoradiation, 152 mesorectal nodes were visible (mean, 6.2 mm; 100 benign, 52 malignant) and 4 of 52 malignant nodes were in contact with the mesorectal fascia. The nodal staging was 7/25 N0, 10/25 N1, and 7/25 N2. After chemoradiation, only 29 nodes (mean, 4.1 mm; 24 benign, 5 malignant) were visible, and none were in contact with the mesorectal fascia. Nodal downstaging was observed: 20/25 N0 and 5/25 N1 (p < 0.01, Chi-square test). There was good agreement between MRI and pathologic T-staging ({kappa} = 0.64) and N-staging ({kappa} = 0.65) after chemoradiation. Conclusions: Neoadjuvant chemoradiation treatment resulted in a decrease in size and number of malignant- and benign-appearing mesorectal nodes on MRI. Nodal downstaging and nodal regression from the mesorectal fascia were observed after treatment. MRI is a useful tool for assessing nodal response to neoadjuvant treatment.« less

Chemoradiation for ductal pancreatic carcinoma: principles of combining chemotherapy with radiation, definition of target volume and radiation dose.

PubMed

Wilkowski, Ralf; Thoma, Martin; Weingandt, Helmut; Dühmke, Eckhart; Heinemann, Volker

2005-05-10

Review of the role of chemoradiotherapy in the treatment of locally advanced pancreatic cancer with a specific focus on the technical feasibility and the integration of chemoradiotherapy into multimodal treatment concepts. Combined chemoradiotherapy of pancreatic cancer is a safe treatment with an acceptable profile of side effects when applied with modern planning and radiation techniques as well as considering tissue tolerance. Conventionally fractionated radiation regimens with total doses of 45-50 Gy and small-volume boost radiation with 5.4 Gy have found the greatest acceptance. Locoregional lymphatic drainage should be included in the planning of target volumes because the risk of tumor involvement and local or loco-regional recurrence is high. Up to now, 5-fluorouracil has been considered the "standard" agent for concurrent chemoradiotherapy. The role of gemcitabine given concurrently with radiation has not yet been defined, since high local efficacy may also be accompanied by enhanced toxicities. In addition, no dose or administration form has been determined to be "standard" up to now. The focus of presently ongoing research is to define an effective and feasible regimen of concurrent chemoradiotherapy. While preliminary results indicate promising results using gemcitabine-based chemoradiotherapy, reliable data derived from mature phase III trials are greatly needed. Intensity-modulated radiotherapy has been developed to improve target-specific radiation and to reduce organ toxicity. Its clinical relevance still needs to be defined.

Preoperative chemoradiation of locally advanced T3 rectal cancer combined with an endorectal boost

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jakobsen, Anders; Mortensen, John P.; Bisgaard, Claus

2006-02-01

Purpose: To investigate the effect and feasibility of concurrent radiation and chemotherapy combined with endorectal brachytherapy in T3 rectal cancer with complete pathologic remission as end point. Methods and Materials: The study included 50 patients with rectal adenocarcinoma. All patients had T3 tumor with a circumferential margin 0-5 mm on a magnetic resonance imaging scan. The radiotherapy was delivered by a technique including two planning target volumes. Clinical target volume 1 (CTV1) received 60 Gy/30 fractions, and CTV2 received 48.6 Gy/27 fractions. The tumor dose was raised to 65 Gy with endorectal brachytherapy 5 Gy/1 fraction to the tumor bed.more » On treatment days, the patients received uracil and tegafur 300 mg/m2 concurrently with radiotherapy. Results: Forty-eight patients underwent operation. Histopathologic tumor regression was assessed by the Tumor Regression Grade (TRG) system. TRG1 was recorded in 27% of the patients, and a further 27% were classified as TRG2. TRG3 was found in 40%, and 6% had TRG4. The toxicity was low. Conclusion: The results indicate that high-dose radiation with concurrent chemotherapy and endorectal brachytherapy is feasible with a high rate of complete response, but further trials are needed to define its possible role as treatment option.« less

Preservation of Immune Function in Cervical Cancer Patients during Chemoradiation using a Novel Integrative Approach

PubMed Central

Lutgendorf, Susan K.; Mullen-Houser, Elizabeth; Russell, Daniel; DeGeest, Koen; Jacobson, Geraldine; Hart, Laura; Bender, David; Anderson, Barrie; Buekers, Thomas E.; Goodheart, Michael J.; Antoni, Michael H.; Sood, Anil K.; Lubaroff, David M.

2010-01-01

Patients receiving chemoradiation for cervical cancer are at risk for distress, chemoradiation-related side-effects, and immunosuppression. This prospective randomized clinical trial examined effects of a complementary therapy, Healing Touch (HT), versus relaxation training (RT) and usual care (UC) for 1) supporting cellular immunity, 2) improving mood and quality of life (QOL), and 3) reducing treatment-associated toxicities and treatment delay in cervical cancer patients receiving chemoradiation. Sixty women with stages IB1 to IVA cervical cancer were randomly assigned to receive UC or 4×/weekly individual sessions of either HT or RT immediately following radiation during their 6-week chemoradiation treatment. Patients completed psychosocial assessments and blood sampling before chemoradiation at baseline, weeks 4 and 6. Multilevel regression analyses using orthogonal contrasts tested for differences between treatment conditions over time. HT patients had a minimal decrease in natural killer cell cytotoxicity (NKCC) over the course of treatment whereas NKCC of RT and UC patients declined sharply during chemoradiation (group by time interaction: p=0.018). HT patients showed greater decreases in 2 different indicators of depressed mood (CESD depressed mood subscale and POMS depression scale) compared to RT and UC (group by time interactions: p < 0.05). No between group differences were observed in QOL, treatment delay, or clinically-rated toxicities. HT may benefit cervical cancer patients by moderating effects of chemoradiation on depressed mood and cellular immunity. Effects of HT on toxicities, treatment delay, QOL, and fatigue were not observed. Long-term clinical implications of findings are not known. PMID:20600809

Rectal adenocarcinoma infiltrating the bulbar urethra and metastasising to the penis

PubMed Central

James, Mathews; Amaranathan, Anandhi; Nelamangala Ramakrishnaiah, Vishnu Prasad; Toi, Pampa Chakrabarty

2016-01-01

Secondary penile tumours from rectal carcinoma is a known clinical entity but can be missed unless carefully evaluated. We report a case of rectal adenocarcinoma with synchronous painless penile nodules. A patient presented with constipation and rectal bleeding. He had an anorectal growth as well as palpable nodules on his penis. Rectal biopsy yielded adenocarcinoma. Imaging revealed direct infiltration of tumour into the bulb of the penis as well as distal shaft lesions. Fine-needle aspiration cytology of the penile nodule showed metastatic adenocarcinoma. Diversion colostomy was performed and the patient referred for chemoradiation. Since he did not have any urinary symptoms, the penile lesions were left unaltered. Repeat imaging after concurrent chemoradiotherapy showed no response. The prognosis was explained and the patient was given palliative clinic care. PMID:27312852

Longitudinal Changes in Active Bone Marrow for Cervical Cancer Patients Treated With Concurrent Chemoradiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Noticewala, Sonal S.; Li, Nan; Williamson, Casey W.

Purpose: To quantify longitudinal changes in active bone marrow (ABM) distributions within unirradiated (extrapelvic) and irradiated (pelvic) bone marrow (BM) in cervical cancer patients treated with concurrent chemoradiation therapy (CRT). Methods and Materials: We sampled 39 cervical cancer patients treated with CRT, of whom 25 were treated with concurrent cisplatin (40 mg/m{sup 2}) and 14 were treated with cisplatin (40 mg/m{sup 2}) plus gemcitabine (50-125 mg/m{sup 2}) (C/G). Patients underwent {sup 18}F-fluorodeoxyglucose positron emission tomographic/computed tomographic imaging at baseline and 1.5 to 6.0 months after treatment. ABM was defined as the subvolume of bone with standardized uptake value (SUV) above the mean SUV ofmore » the total bone. The primary aim was to measure the compensatory response, defined as the change in the log of the ratio of extrapelvic versus pelvic ABM percentage from baseline to after treatment. We also quantified the change in the proportion of ABM and mean SUV in pelvic and extrapelvic BM using a 2-sided paired t test. Results: We observed a significant increase in the overall extrapelvic compensatory response after CRT (0.381; 95% confidence interval [CI]: 0.312, 0.449) and separately in patients treated with cisplatin (0.429; 95% CI: 0.340, 0.517) and C/G (0.294; 95% CI: 0.186, 0.402). We observed a trend toward higher compensatory response in patients treated with cisplatin compared with C/G (P=.057). Pelvic ABM percentage was reduced after CRT both in patients receiving cisplatin (P<.001) and in those receiving C/G (P<.001), whereas extrapelvic ABM percentage was increased in patients receiving cisplatin (P<.001) and C/G (P<.001). The mean SUV in pelvic structures was lower after CRT with both cisplatin (P<.001) and C/G (P<.001). The mean SUV appeared lower in extrapelvic structures after CRT in patients treated with C/G (P=.076) but not with cisplatin (P=.942). We also observed that older age and more intense chemotherapy regimens were correlated with a decreased compensatory response on multivariable analysis. In patients treated with C/G, mean pelvic bone marrow dose was found to be negatively correlated with the compensatory response. Conclusion: Patients have differing subacute compensatory responses after CRT, owing to variable recovery in unirradiated marrow. Intensive chemotherapy regimens appear to decrease the extrapelvic compensatory response, which may lead to increased hematologic toxicity.« less

Roles of posttherapy 18F-FDG PET/CT in patients with advanced squamous cell carcinoma of the uterine cervix receiving concurrent chemoradiotherapy.

PubMed

Liu, Feng-Yuan; Su, Tzu-Pei; Wang, Chun-Chieh; Chao, Angel; Chou, Hung-Hsueh; Chang, Yu-Chen; Yen, Tzu-Chen; Lai, Chyong-Huey

2018-07-01

To assess the clinical roles of [ 18 F]fluorodeoxyglucose ( 18 F-FDG) positron emission tomography/computed tomography (PET/CT) performed 2-3 months after completion of concurrent chemoradiotherapy (CCRT), along with pretherapy characteristics, in patients with advanced squamous cell carcinoma of the uterine cervix enrolled in a prospective randomized clinical trial. Posttherapy PET/CT in patients with advanced FIGO stage or positive pelvic or para-aortic lymph node (PALN) defined on pretherapy PET/CT was classified as positive, equivocal, or negative. Overall survival (OS) rates between patients with different PET/CT results are compared. Pretherapy characteristics are examined for association with posttherapy PET/CT results and for prognostic significance in patients with equivocal or negative PET/CT. PET/CT scans (n = 55) were positive, equivocal and negative in 9, 13 and 33 patients, respectively. All patients with positive scans were confirmed to have residual or metastatic disease and died despite salvage therapies. There is a significant OS difference between patients with positive and equivocal scans (P < .001) but not between patients with equivocal and negative scans (P = .411). Positive pretherapy PALN is associated with positive posttherapy PET/CT (P = .033) and predicts a poorer survival in patients with equivocal or negative posttherapy PET/CT (P < .001). Positive PET/CT 2-3 months posttherapy implies treatment failure and novel therapy is necessary to improve outcomes for such patients. A more intense posttherapy surveillance may be warranted in patients with positive pretherapy PALN.

Sheltered women's perceptions of their abusive marital relationship: Conflictual themes of dominance and submissiveness.

PubMed

Sommerfeld, Eliane; Shechory Bitton, Mally

2016-07-01

The Core Conflictual Relationship Themes (CCRT) approach was applied in order to examine the conflictual nature of sheltered women's perceptions of their marital relationship following domestic violence in Israel. Thirty-six sheltered women and 89 community-based women were compared. The CCRT method was useful in revealing that battered women, when thinking retrospectively about their relationships with their abusive partners, are concerned with conflictual themes of dominance and submissiveness. The sheltered women reported a desire to be more dominant and less submissive in their relationships with their abusive spouse, despite being less dominant than they wished in practice. These findings help clarify the emotional conflicts that battered women may be dealing with after leaving an abusive relationship and imply that interventions should promote their empowerment.

Predicting severe hematologic toxicity from extended-field chemoradiation of para-aortic nodal metastases from cervical cancer.

PubMed

Yan, Kevin; Ramirez, Ezequiel; Xie, Xian-Jin; Gu, Xuejun; Xi, Yin; Albuquerque, Kevin

The purpose of this study was to determine factors predictive for severe hematologic toxicity (HT) in cervical cancer patients with para-aortic lymph node metastasis treated with concurrent cisplatin chemoradiation to an extended field (EFCRT). Thirty-eight patients with cervical cancer and para-aortic lymph node metastasis who underwent EFCRT were analyzed. Active bone marrow was defined as the region within irradiated total bone marrow (BM TOT ) with a standard uptake value on 18 F-fluorodeoxyglucose positron emission tomography/computed tomography greater than the mean standard uptake value for BM TOT . Serial weekly blood counts from the beginning to the end of radiation treatment were evaluated for HT using Common Terminology Criteria for Adverse Events, version 4.0. Nineteen patients had grade 3 or higher hematologic toxicity (HT3+), not including lymphocyte toxicity. Obese patients (n = 12) were less likely to get HT3+ (P = .03) despite getting equivalent doses of chemotherapy. Volumes of BM TOT and active bone marrow receiving doses of 20, 30, and 45 Gy and body mass index significantly predicted HT3+. Patients who had HT3+ had prolonged treatment time (62 vs 53 days, P < .001). For patients receiving EFCRT, bone marrow irradiation parameters and patient body mass index were associated with HT3+. A simplified nomogram has been created to predict HT3+ in these patients, allowing the potential to explore bone marrow-sparing delivery techniques. Copyright © 2017 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

The prognostic role of hemoglobin levels in patients undergoing concurrent chemo-radiation for anal cancer.

PubMed

Franco, Pierfrancesco; Montagnani, Francesco; Arcadipane, Francesca; Casadei, Chiara; Andrikou, Kalliopi; Martini, Stefania; Iorio, Giuseppe Carlo; Scartozzi, Mario; Mistrangelo, Massimiliano; Fornaro, Lorenzo; Cassoni, Paola; Cascinu, Stefano; Ricardi, Umberto; Casadei Gardini, Andrea

2018-05-02

Concurrent chemo-radiation (CT-RT) is a standard therapy for squamous cell carcinoma of anal canal. Different clinical and biological factors may potentially affect outcome. We investigated the prognostic role of baseline hemoglobin (Hb) in a cohort of anal cancer patients submitted to CT-RT with 5-fluorouracil and mitomycin C. Up to 161 patients with clinical stage T1-T4/N0-N3/M0 were treated. Response was assessed at 6 weeks and thereafter at 3, 6 and 12 months. Two different approaches were used:a)simultaneous integrated boost following RTOG 05-29 indications;b)first sequence of 45Gy/25 fractions to the pelvis followed by 9-14.4 Gy/5-8 fractions to the macroscopic disease. Primary endpoints were progression-free survival (PFS) and overall survival (OS). On multivariate analysis, pre-treatment Hb level had a significant correlation to OS (HR:0.53;95% CI:0.33-0.87; p = 0.001), but not to PFS (HR:0.78;95% CI:0.53-1.15; p = 0.12) Patients with pre-treatment Hb ≥ 12 g/dl had 5-year PFS and OS of 82.2%, compared to 29.3% and 32.8% for those below the threshold. The likelihood to achieve a complete remission increased by 5.6% for every single-unit (g/dl) increase in baseline Hb level over 11 g/dl. On multivariate analysis, response to treatment had a significant correlation to PFS (incomplete vs complete response - HR:5.43;95% CI:2.75-10.7; p < 0.0001) and OS (HR: 6.96;95% CI:2.96-16.5; p < 0.0001). We showed that baseline Hb level is a strong indicator for poor response to RT-CT in anal cancer patients. A close clinical monitoring for incomplete response to treatment should be advised in patients with low pre-treatment Hb. The hypothesis that the preservation of adequate Hb level during treatment may lead to a better outcome needs prospective evaluation.

Long-Term Follow-Up of a Phase II Trial of High-Dose Radiation With Concurrent 5-Fluorouracil and Cisplatin in Patients With Anal Cancer (ECOG E4292)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chakravarthy, A. Bapsi, E-mail: bapsi.chak@vanderbilt.edu; Catalano, Paul J.; Martenson, James A.

Purpose: Although chemoradiation using 5-fluorouracil (5-FU) and mitomycin-C (MMC) is the standard of care in the treatment of anal cancer, many patients are unable to tolerate MMC. This Phase II clinical trial was performed to determine whether cisplatin could replace MMC in the treatment of anal cancer. Methods and Materials: Thirty-three patients with localized anal cancer were enrolled. One patient registered but never received any assigned therapy and was excluded from all analyses. Between February 1, 1993, and July 21, 1993, 19 patients were accrued to Cohort 1. Radiation consisted of 45 Gy to the primary tumor and pelvic nodes,more » followed by a boost to the primary and involved nodes to 59.4 Gy. A planned 2-week treatment break was used after 36 Gy. Concurrent chemotherapy consisted of 5-FU 1,000 mg/m{sup 2}/day on Days 1 to 4 and cisplatin 75 mg/m{sup 2} on Day 1. A second course of 5-FU and cisplatin was given after 36 Gy, when the patient resumed radiation therapy. Between April 4, 1996, and September 23, 1996, an additional 13 patients (Cohort 2) were accrued to the study and received the same treatment except without the planned treatment break. Results: Complete response was seen in 78% (90% CI, 63-89) of patients and was higher in patients who did not get a planned treatment break (92% vs. 68%). The overall Grade 4 toxicity rate was 31%. One treatment-related death (Grade 5) occurred in a patient who developed sepsis. The 5-year overall survival was 69%. Conclusions: Radiation therapy, cisplatin, and 5-FU resulted in an overall objective response (complete response + partial response) of 97%. Although the 5-year progression-free survival was only 55%, the overall 5-year survival was 69%. Given the excellent salvage provided by surgery, this study affirms that cisplatin-based regimens may be an alternative for patients who cannot tolerate the severe hematologic toxicities associated with mitomycin-based chemoradiation regimens.« less

{sup 18}F-Fluorodeoxyglucose/Positron Emission Tomography Predicts Patterns of Failure After Definitive Chemoradiation Therapy for Locally Advanced Non-Small Cell Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ohri, Nitin, E-mail: ohri.nitin@gmail.com; Bodner, William R.; Halmos, Balazs

Background: We previously reported that pretreatment positron emission tomography (PET) identifies lesions at high risk for progression after concurrent chemoradiation therapy (CRT) for locally advanced non-small cell lung cancer (NSCLC). Here we validate those findings and generate tumor control probability (TCP) models. Methods: We identified patients treated with definitive, concurrent CRT for locally advanced NSCLC who underwent staging {sup 18}F-fluorodeoxyglucose/PET/computed tomography. Visible hypermetabolic lesions (primary tumors and lymph nodes) were delineated on each patient's pretreatment PET scan. Posttreatment imaging was reviewed to identify locations of disease progression. Competing risks analyses were performed to examine metabolic tumor volume (MTV) and radiation therapymore » dose as predictors of local disease progression. TCP modeling was performed to describe the likelihood of local disease control as a function of lesion size. Results: Eighty-nine patients with 259 hypermetabolic lesions (83 primary tumors and 176 regional lymph nodes) met the inclusion criteria. Twenty-eight patients were included in our previous report, and the remaining 61 constituted our validation cohort. The median follow-up time was 22.7 months for living patients. In 20 patients, the first site of progression was a primary tumor or lymph node treated with radiation therapy. The median time to progression for those patients was 11.5 months. Data from our validation cohort confirmed that lesion MTV predicts local progression, with a 30-month cumulative incidence rate of 23% for lesions above 25 cc compared with 4% for lesions below 25 cc (P=.008). We found no evidence that radiation therapy dose was associated with local progression risk. TCP modeling yielded predicted 30-month local control rates of 98% for a 1-cc lesion, 94% for a 10-cc lesion, and 74% for a 50-cc lesion. Conclusion: Pretreatment FDG-PET identifies lesions at risk for progression after CRT for locally advanced NSCLC. Strategies to improve local control should be tested on high-risk lesions, and treatment deintensification for low-risk lesions should be explored.« less

Neoadjuvant Sandwich Treatment With Oxaliplatin and Capecitabine Administered Prior to, Concurrently With, and Following Radiation Therapy in Locally Advanced Rectal Cancer: A Prospective Phase 2 Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gao, Yuan-Hong; Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou; Lin, Jun-Zhong

Purpose: Systemic failure remains the major challenge in management of locally advanced rectal cancer (LARC). To optimize the timing of neoadjuvant treatment and enhance systemic control, we initiated a phase 2 trial to evaluate a new strategy of neoadjuvant sandwich treatment, integrating induction chemotherapy, concurrent chemoradiation therapy, and consolidation chemotherapy. Here, we present preliminary results of this trial, reporting the tumor response, toxicities, and surgical complications. Methods and Materials: Fifty-one patients with LARC were enrolled, among which were two patients who were ineligible because of distant metastases before treatment. Patients were treated first with one cycle of induction chemotherapy consistingmore » of oxaliplatin, 130 mg/m² on day 1, with capecitabine, 1000 mg/m² twice daily for 14 days every 3 weeks (the XELOX regimen), followed by chemoradiation therapy, 50 Gy over 5 weeks, with the modified XELOX regimen (oxaliplatin 100 mg/m²), and then with another cycle of consolidation chemotherapy with the XELOX regimen. Surgery was performed 6 to 8 weeks after completion of radiation therapy. Tumor responses, toxicities, and surgical complications were recorded. Results: All but one patent completed the planned schedule of neoadjuvant sandwich treatment. Neither life-threatening blood count decrease nor febrile neutropenia were observed. Forty-five patents underwent optimal surgery with total mesorectal excision (TME). Four patients refused surgery because of clinically complete response. There was no perioperative mortality in this cohort. Five patients (11.1%) developed postoperative complications. Among the 45 patients who underwent TME, pathologic complete response (pCR), pCR or major regression, and at least moderate regression were achieved in 19 (42.2%), 37 (82.2%), and 44 patients (97.8%), respectively. Conclusions: Preliminary results suggest that the strategy of neoadjuvant sandwich treatment using XELOX regimen as induction, concomitant, and consolidation chemotherapy to the conventional radiation is well tolerated. The strategy is highly effective in terms of pCR and major regression, which warrants further investigation.« less

Thoracic Vertebral Body Irradiation Contributes to Acute Hematologic Toxicity During Chemoradiation Therapy for Non-Small Cell Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deek, Matthew P.; Benenati, Brian; Kim, Sinae

Purpose: To determine the relationships between radiation doses to the thoracic bone marrow and declines in blood cell counts in non-small cell lung cancer (NSCLC) patients treated with chemoradiation therapy (CRT). Methods and Materials: We included 52 patients with NSCLC treated with definitive concurrent carboplatin–paclitaxel and RT. Dose-volume histogram (DVH) parameters for the thoracic vertebrae (TV), sternum, scapulae, clavicles, and ribs were assessed for associations with changes in blood counts during the course of CRT. Linear and logistic regression analyses were performed to identify associations between hematologic nadirs and DVH parameters. A DVH parameter of Vx was the percentage ofmore » the total organ volume exceeding x radiation dose. Results: Grade ≥3 hematologic toxicity including neutropenia developed in 21% (n=11), leukopenia in 42% (n=22), anemia in 6% (n=3), and throbocytopenia in 2% (n=1) of patients. Greater RT dose to the TV was associated with higher risk of grade ≥3 leukopenia across multiple DVH parameters, including TV V{sub 20} (TVV) (odds ratio [OR] 1.06; P=.025), TVV{sub 30} (OR 1.07; P=.013), and mean vertebral dose (MVD) (OR 1.13; P=.026). On multiple regression analysis, TVV{sub 30} (β = −0.004; P=.018) and TVV{sub 20} (β = −0.003; P=.048) were associated with white blood cell nadir. Additional bone marrow sites (scapulae, clavicles, and ribs) did not affect hematologic toxicity. A 20% chance of grade ≥3 leukopenia was associated with a MVD of 13.5 Gy and a TTV{sub 30} of 28%. Cutoff values to avoid grade ≥3 leukopenia were MVD ≤23.9 Gy, TVV{sub 20} ≤56.0%, and TVV{sub 30} ≤52.1%. Conclusions: Hematologic toxicity is associated with greater RT doses to the TV during CRT for NSCLC. Sparing of the TV using advanced radiation techniques may improve tolerance of CRT and result in improved tolerance of concurrent chemotherapy.« less

Comparison of Toxicity and Treatment Outcomes in HIV-positive Versus HIV-negative Patients With Squamous Cell Carcinoma of the Anal Canal.

PubMed

White, Evan C; Khodayari, Behnood; Erickson, Kelly T; Lien, Winston W; Hwang-Graziano, Julie; Rao, Aroor R

2017-08-01

To compare the toxicity and treatment outcomes in human immunodeficiency virus (HIV)-positive versus HIV-negative patients with squamous cell carcinoma of the anal canal who underwent definitive concurrent chemoradiation at a single institution. Fifty-three consecutive HIV-positive patients treated between 1987 and 2013 were compared with 205 consecutive HIV-negative patients treated between 2003 and 2013. All patients received radiotherapy at a single regional facility. The median radiation dose was 54 Gy (range, 28 to 60 Gy). Concurrent chemotherapy consisted of 2 cycles 5-FU with mitomycin-C given on day 1±day 29). After treatment, patients were closely followed with imaging studies, clinical examinations, and rigid proctoscopies. Outcomes assessed were toxicity rates, progression-free survival, colostomy-free survival, cancer-specific survival, and overall survival. Median follow-up was 34 months. Compared with HIV-negative patients, HIV-positive patients were younger (median age, 48 vs. 62 y) and predominantly male sex (98% of HIV-positive patients were male vs. 22% of HIV-negative patients). Of the HIV-positive patients, 37 (70%) were on highly active antiretroviral therapy, 26 (65%) had an undetectable viral load at the time of treatment, and 36 (72%) had a CD4 count>200 (mean CD4 count, 455). There were no significant differences in acute or late nonhematologic or hematologic toxicity rates between the 2 groups. At 3 years, there was no significant difference between HIV-positive and HIV-negative patients in regards to progression-free survival (75% vs. 76%), colostomy-free survival (85% vs. 85%), or cancer-specific survival (79% vs. 88%, P=0.36), respectively. On univariate analysis, there was a trend toward worse overall survival in HIV-positive patients (72% vs. 84% at 3 y, P=0.06). For the entire cohort, on multivariate analysis only male sex and stage were predictive of worse survival outcomes. HIV status was not associated with worse outcomes in Cox models. In the highly active antiretroviral therapy era, HIV-positive patients with anal cancer treated with standard definitive chemoradiation have equivalent toxicity and cancer-specific survival compared with HIV-negative patients.

Long-term follow-up of a Phase II trial of high-dose radiation with concurrent 5-fluorouracil and cisplatin in patients with anal cancer (ECOG E4292).

PubMed

Chakravarthy, A Bapsi; Catalano, Paul J; Martenson, James A; Mondschein, Joshua K; Wagner, Henry; Mansour, Edward G; Talamonti, Mark S; Benson, Al Bowen

2011-11-15

Although chemoradiation using 5-fluorouracil (5-FU) and mitomycin-C (MMC) is the standard of care in the treatment of anal cancer, many patients are unable to tolerate MMC. This Phase II clinical trial was performed to determine whether cisplatin could replace MMC in the treatment of anal cancer. Thirty-three patients with localized anal cancer were enrolled. One patient registered but never received any assigned therapy and was excluded from all analyses. Between February 1, 1993, and July 21, 1993, 19 patients were accrued to Cohort 1. Radiation consisted of 45 Gy to the primary tumor and pelvic nodes, followed by a boost to the primary and involved nodes to 59.4 Gy. A planned 2-week treatment break was used after 36 Gy. Concurrent chemotherapy consisted of 5-FU 1,000 mg/m(2)/day on Days 1 to 4 and cisplatin 75 mg/m(2) on Day 1. A second course of 5-FU and cisplatin was given after 36 Gy, when the patient resumed radiation therapy. Between April 4, 1996, and September 23, 1996, an additional 13 patients (Cohort 2) were accrued to the study and received the same treatment except without the planned treatment break. Complete response was seen in 78% (90% CI, 63-89) of patients and was higher in patients who did not get a planned treatment break (92% vs. 68%). The overall Grade 4 toxicity rate was 31%. One treatment-related death (Grade 5) occurred in a patient who developed sepsis. The 5-year overall survival was 69%. Radiation therapy, cisplatin, and 5-FU resulted in an overall objective response (complete response + partial response) of 97%. Although the 5-year progression-free survival was only 55%, the overall 5-year survival was 69%. Given the excellent salvage provided by surgery, this study affirms that cisplatin-based regimens may be an alternative for patients who cannot tolerate the severe hematologic toxicities associated with mitomycin-based chemoradiation regimens. Copyright © 2011 Elsevier Inc. All rights reserved.

Phase 2 study of high-dose proton therapy with concurrent chemotherapy for unresectable stage III nonsmall cell lung cancer.

PubMed

Chang, Joe Y; Komaki, Ritsuko; Lu, Charles; Wen, Hong Y; Allen, Pamela K; Tsao, Anne; Gillin, Michael; Mohan, Radhe; Cox, James D

2011-10-15

The authors sought to improve the toxicity of conventional concurrent chemoradiation therapy for stage III nonsmall cell lung cancer (NSCLC) by using proton-beam therapy to escalate the radiation dose to the tumor. They report early results of a phase 2 study of high-dose proton therapy and concurrent chemotherapy in terms of toxicity, failure patterns, and survival. Forty-four patients with stage III NSCLC were treated with 74 grays (radiobiologic equivalent) proton therapy with weekly carboplatin (area under the curve, 2 U) and paclitaxel (50 mg/m(2)). Disease was staged with positron emission tomography/computed tomography (CT), and treatments were simulated with 4-dimensional (4D) CT to account for tumor motion. Protons were delivered as passively scattered beams, and treatment simulation was repeated during the treatment process to determine the need for adaptive replanning. Median follow-up time was 19.7 months (range, 6.1-44.4 months), and median overall survival time was 29.4 months. No patient experienced grade 4 or 5 proton-related adverse events. The most common nonhematologic grade 3 toxicities were dermatitis (n = 5), esophagitis (n = 5), and pneumonitis (n = 1). Nine (20.5%) patients experienced local disease recurrence, but only 4 (9.1%) had isolated local failure. Four (9.1%) patients had regional lymph node recurrence, but only 1 (2.3%) had isolated regional recurrence. Nineteen (43.2%) patients developed distant metastasis. The overall survival and progression-free survival rates were 86% and 63% at 1 year. Concurrent high-dose proton therapy and chemotherapy are well tolerated, and the median survival time of 29.4 months is encouraging for unresectable stage III NSCLC. Copyright © 2011 American Cancer Society.

The Impact of Radiation Treatment Time on Survival in Patients With Head and Neck Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shaikh, Talha; Handorf, Elizabeth A.; Murphy, Colin T.

Purpose: To assess the impact of radiation treatment time (RTT) in head and neck cancers on overall survival (OS) in the era of chemoradiation. Methods and Materials: Patients with diagnoses of tongue, hypopharynx, larynx, oropharynx, or tonsil cancer were identified by use of the National Cancer Database. RTT was defined as date of first radiation treatment to date of last radiation treatment. In the definitive setting, prolonged RTT was defined as >56 days, accelerated RTT was defined as <47 days, and standard RTT was defined as 47 to 56 days. In the postoperative setting, prolonged RTT was defined as >49 days, accelerated RTT wasmore » defined as <40 days, and standard RTT was defined as 40 to 49 days. We used χ{sup 2} tests to identify predictors of RTT. The Kaplan-Meier method was used to compare OS among groups. Cox proportional hazards model was used for OS analysis in patients with known comorbidity status. Results: 19,531 patients were included; 12,987 (67%) had a standard RTT, 4,369 (34%) had an accelerated RTT, and 2,165 (11%) had a prolonged RTT. On multivariable analysis, accelerated RTT (hazard ratio [HR] 0.84; 95% confidence interval [CI] 0.73-0.97) was associated with an improved OS, and prolonged RTT (HR 1.25; 95% CI 1.14-1.37) was associated with a worse OS relative to standard RTT. When the 9,200 (47%) patients receiving definitive concurrent chemoradiation were examined, prolonged RTT (HR 1.29; 95% CI 1.11-1.50) was associated with a worse OS relative to standard RTT, whereas there was no significant association between accelerated RTT and OS (HR 0.76; 95% CI 0.57-1.01). Conclusion: Prolonged RTT is associated with worse OS in patients receiving radiation therapy for head and neck cancer, even in the setting of chemoradiation. Expeditious completion of radiation should continue to be a quality metric for the management of head and neck malignancies.« less

Definitive chemoradiation for locoregional recurrences of esophageal cancer after primary curative treatment.

PubMed

Jeene, P M; Versteijne, E; van Berge Henegouwen, M I; Bergmann, J J G H M; Geijsen, E D; Muller, K; van Laarhoven, H W M; Hulshof, M C C M

2017-02-01

The aim of this study was to determine the outcome of salvage definitive chemoradiation (dCRT) for a locoregional recurrence after any prior curative treatment outside previously irradiated areas. Thirty-nine patients treated between January 2005 and December 2014 were reviewed for locoregional recurrent esophageal cancer outside previously irradiated areas. All patients received salvage treatment with external beam radiotherapy (50.4 Gy in 28 fractions) combined with weekly concurrent paclitaxel and carboplatin. The median follow-up period was 15 months (range 1.7-120). The median overall survival (OS) for all patients after salvage dCRT was 22 months (95% CI 6.2-37.6). The 1-, 3-, and 5-year OS was 72%, 31%, and 28%, respectively. Median survival after salvage dCRT for a regional lymph node recurrence was 33 months (95% CI 5.8-60.3) versus 14 months (95% CI 6.8-21.6) for a recurrence at the anastomosis (P = 0.022, logrank). Median OS was 35 months for the squamous cell carcinoma group and 19 months for the adenocarcinoma group (P = 0.67). Sixteen of 39 patients developed a locoregional recurrence after salvaged dCRT. The median locoregional recurrence-free survival (LRFS) was 24 months. The 1-, 3-, and 5-year LRFS was 79%, 36%, and 36%, respectively. Median disease-free survival (DFS) was 15 months. The 1-, 3-, and 5-year DFS was 66%, 27%, and 27%, respectively. Of 16 patients, 8 (50%) with a primary failure at the site of the anastomosis developed a local recurrence after salvaged dCRT compared to 7 of 22 patients (32%) with a primary recurrence in a lymph node. Definitive chemoradiation is a feasible and effective treatment for locoregional recurrent esophageal cancer outside a previously irradiated area, and should be given with a curative intent. This holds true for recurrence of both squamous cell carcinoma and adenocarcinoma. Lymph node recurrences have a markedly better prognosis than recurrences at the site of the anastomosis. © 2016 International Society for Diseases of the Esophagus.

Predictors of Locoregional Failure and Impact on Overall Survival in Patients With Resected Exocrine Pancreatic Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Merrell, Kenneth W.; Haddock, Michael G.; Quevedo, J. Fernando

Purpose: Resection of exocrine pancreatic cancer is necessary for cure, but locoregional and distant relapse is common. We evaluated our institutional experience to better understand risk factors for locoregional failure (LRF) and its impact on overall survival (OS). Methods and Materials: We reviewed 1051 consecutive patients with nonmetastatic exocrine pancreatic cancer who underwent resection at our institution between March 1987 and January 2011. Among them, 458 had adequate follow-up and evaluation for study inclusion. All patients received adjuvant chemotherapy (n=80 [17.5%]) or chemoradiation therapy (n=378 [82.5%]). Chemotherapy and chemoradiation therapy most frequently consisted of 6 cycles of gemcitabine and 50.4 Gymore » in 28 fractions with concurrent 5-fluorouracil, respectively. Locoregional control (LRC) and OS were estimated with the Kaplan-Meier method. Univariate and multivariate analyses were performed with Cox proportional hazards regression models incorporating propensity score. Results: Median patient age was 64.5 years (range: 29-88 years). Median follow-up for living patients was 84 months (range: 6-300 months). Extent of resection was R0 (83.8%) or R1 (16.2%). Overall crude incidence of LRF was 17% (n=79). The 5-year LRC for patients with and without radiation therapy was 80% and 68%, respectively (P=.003; hazard ratio [HR]: 0.45; 95% confidence interval [CI]: 0.28-0.76). Multivariate analysis, incorporating propensity score, indicated radiation therapy (P<.0001; HR: 0.23; 95% CI: 0.12-0.42) and positive lymph node ratio of ≥0.2 (P=.02; HR: 1.78; 95% CI: 1.10-2.9) were associated with LRC. In addition, LRF was associated with worse OS (P<.0001; HR: 5.0; 95% CI: 3.9-6.3). Conclusions: In our analysis of 458 patients with resected pancreatic cancer, positive lymph node ratio of ≥0.2 and no adjuvant chemoradiation therapy were associated with increased LRF risk. LRF was associated with poor OS. Radiation therapy should be considered as adjuvant locoregional treatment following pancreatic cancer resection.« less

Radiation or chemoradiation: initial utility study of selected therapy for local advanced stadium cervical cancer

NASA Astrophysics Data System (ADS)

Pramitasari, D. A.; Gondhowiardjo, S.; Nuranna, L.

2017-08-01

This study aimed to compare radiation only or chemo radiation treatment of local advanced cervical cancers by examining the initial response of tumors and acute side effects. An initial assessment employed value based medicine (VBM) by obtaining utility values for both types of therapy. The incidences of acute lower gastrointestinal, genitourinary, and hematology side effects in patients undergoing chemoradiation did not differ significantly from those undergoing radiation alone. Utility values for patients who underwent radiation alone were higher compared to those who underwent chemoradiation. It was concluded that the complete response of patients who underwent chemoradiation did not differ significantly from those who underwent radiation alone.

Immunocompetent syngeneic cotton rat tumor models for the assessment of replication-competent oncolytic adenovirus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steel, Jason C.; Morrison, Brian J.; Mannan, Poonam

Oncolytic adenoviruses as a treatment for cancer have demonstrated limited clinical activity. Contributing to this may be the relevance of preclinical animal models used to study these agents. Syngeneic mouse tumor models are generally non-permissive for adenoviral replication, whereas human tumor xenograft models exhibit attenuated immune responses to the vector. The cotton rat (Sigmodon hispidus) is susceptible to human adenovirus infection, permissive for viral replication and exhibits similar inflammatory pathology to humans with adenovirus replicating in the lungs, respiratory passages and cornea. We evaluated three transplantable tumorigenic cotton rat cell lines, CCRT, LCRT and VCRT as models for the studymore » of oncolytic adenoviruses. All three cells lines were readily infected with adenovirus type-5-based vectors and exhibited high levels of transgene expression. The cell lines supported viral replication demonstrated by the induction of cytopathogenic effect (CPE) in tissue culture, increase in virus particle numbers and assembly of virions seen on transmission electron microscopy. In vivo, LCRT and VCRT tumors demonstrated delayed growth after injection with replicating adenovirus. No in vivo antitumor activity was seen in CCRT tumors despite in vitro oncolysis. Adenovirus was also rapidly cleared from the CCRT tumors compared to LCRT and VCRT tumors. The effect observed with the different cotton rat tumor cell lines mimics the variable results of human clinical trials highlighting the potential relevance of this model for assessing the activity and toxicity of oncolytic adenoviruses.« less

Comparative effectiveness of upfront esophagectomy versus induction chemoradiation in clinical stage T2N0 esophageal cancer: A decision analysis.

PubMed

Semenkovich, Tara R; Panni, Roheena Z; Hudson, Jessica L; Thomas, Theodore; Elmore, Leisha C; Chang, Su-Hsin; Meyers, Bryan F; Kozower, Benjamin D; Puri, Varun

2018-05-01

We compared the effectiveness of upfront esophagectomy versus induction chemoradiation followed by esophagectomy for overall survival in patients with clinical T2N0 (cT2N0) esophageal cancer. We also assessed the influence of the diagnostic uncertainty of endoscopic ultrasound on the expected benefit of chemoradiation. We created a decision analysis model representing 2 treatment strategies for cT2N0 esophageal cancer: upfront esophagectomy that may be followed by adjuvant therapy for upstaged patients and induction chemoradiation for all patients with cT2N0 esophageal cancer followed by esophagectomy. Parameter values within the model were obtained from published data, and median survival for pathologic subgroups was derived from the National Cancer Database. In sensitivity analyses, staging uncertainty of endoscopic ultrasound was introduced by varying the probability of pathologic upstaging. The baseline model showed comparable median survival for both strategies: 48.3 months for upfront esophagectomy versus 45.9 months for induction chemoradiation and surgery. The sensitivity analysis demonstrated induction chemoradiation was beneficial, with probability of upstaging > 48.1%, which is within the published range of 32% to 65% probability of pathologic upstaging after cT2N0 diagnosis. The presence of any of 3 key variables (size larger than 3 cm, high grade, or lymphovascular invasion) was associated with > 48.1% risk of upstaging, thus conferring a survival advantage to induction chemoradiation. The optimal treatment strategy for cT2N0 esophageal cancer depends on the accuracy of endoscopic ultrasound staging. High-risk features that confer increased probability of upstaging can inform clinical decision making to recommend induction chemoradiation for select cT2N0 patients. Copyright © 2018 The American Association for Thoracic Surgery. All rights reserved.

Application of low-level laser radiation in children's oncology with complications caused by chemoradiation

NASA Astrophysics Data System (ADS)

Balakirev, S. A.; Gusev, L. I.; Grabovschiner, A. A.; Khristoforov, V. N.; Ivanova, J. V.; Shyshkova, E. I.

1999-12-01

The present work is based on a 12 month clinical observation period of 155 patients aged from 6 months to 15 years with multiple complications after chemoradiant treatment of hemoblastos and solid tumors. The application of Magnetic Infrared Laser therapy for different complications caused by chemoradiation treatment of children's malignant tumors is an entirely new method and for the first time has been tried in children's oncology.

Conventional radiotherapy with concurrent weekly Cisplatin in locally advanced head and neck cancers of squamous cell origin - a single institution experience.

PubMed

Dimri, Kislay; Pandey, Awadhesh Kumar; Trehan, Romeeta; Rai, Bhavana; Kumar, Anup

2013-01-01

Platinum based concurrent chemo-radiation is the de-facto standard of care in the non-surgical management of locally-advanced head and neck cancer of squamous origin. Three-weekly single agent cisplatin at 100 mg/m2 concurrent with radical radiotherapy has demonstrated consistent improvement in loco-regional control and survival. This improvement is however at the cost of considerable hematologic toxicity and poor overall compliance. The routine use of this regime is improbable in developing countries with limited resources. We therefore aimed to determine the safety and efficacy of an alternative regime of weekly cisplatin and concurrent radiotherapy in such patients. January-05 and April-12, 188 patients of locally-advanced head and neck cancer of squamous origin were treated with concurrent weekly-cisplatin at 35 mg/m2 and conventional radiotherapy 60-66Gy/30-33 fractions/5 days per week. Overall, 95% patients received planned doses of RT while 74% completed within the stipulated overall treatment time of <50 days. Eighty-two percent received at-least 5 weekly cycles. Grade-III/IV mucositis was seen in 58%/9% respectively, which resulted in mean weight loss of 9.2% from a pre-treatment mean of 54.5 kg. Grade-III hematologic toxicity-0.5%; grade II nephrotoxicity-2.5% and grade III emesis-3% were also seen. Grade-III/IV subcutaneous toxicity-10%/1% and grade-III/IV xerostomia-10%/0% were observed. Complete responses at the primary site, regional nodes and overall disease were seen in 86%, 89% and 83% patients respectively. The median and 5-years disease-free survival were 26 months and 39.4% respectively, while the median and overall survival were 27 months and 41.8% respectively. Weekly-cisplatin at 35 mg /m2 when delivered concurrently with conventional radical RT (at-least 66y/33 fractions) in locally-advanced head and neck cancer is well tolerated with minimal hematologic and neprologic toxicity and can be routinely delivered on an out-patient basis. It is an effective alternative to the standard 3-weekly cisplatin especially in the context of developing countries.

A phase I study of gefitinib with concurrent dose-escalated weekly docetaxel and conformal three-dimensional thoracic radiation followed by consolidative docetaxel and maintenance gefitinib for patients with stage III non-small cell lung cancer.

PubMed

Center, Brian; Petty, William Jeffrey; Ayala, Diandra; Hinson, William H; Lovato, James; Capellari, James; Oaks, Timothy; Miller, Antonius A; Blackstock, Arthur William

2010-01-01

Concurrent radiation and chemotherapy is the standard of care for good performance status patients with stage III non-small cell lung cancer. Locoregional control remains a significant factor relating to poor outcome. Preclinical and early clinical data suggest that docetaxel and gefitinib have radiosensitizing activity. This study sought to define the maximum tolerated dose of weekly docetaxel that could be given with daily gefitinib and concurrent thoracic radiation therapy. Patients with histologically confirmed, inoperable stage III non-small cell lung cancer and good performance status (Eastern Cooperative Oncology Group 0-1) were eligible for this study. Patients received three-dimensional conformal thoracic radiation to a dose of 70 Gy concurrently with oral gefitinib at a dose of 250 mg daily and intravenous, weekly docetaxel at escalating doses from 15 to 30 mg/m2 in cohorts of patients. Patients were given a 2-week rest period after the concurrent therapy, during which they received only gefitinib. After the 2-week rest period, patients received consolidation chemotherapy with docetaxel 75 mg/m2 given every 21 days for two cycles. Maintenance gefitinib was continued until disease progression or study completion. Sixteen patients were enrolled on the study between December 2003 and April 2007 with the following characteristics: median age, 64 years (range 43-79 years); M/F: 9/7; and performance status 0/1, 1/15. Dose-limiting pulmonary toxicity and esophagitis were encountered at a weekly docetaxel dose of 25 mg/m2, resulting in a maximum tolerated dose of 20 mg/m2/wk. Overall, grade 3/4 hematologic toxicity was observed in 27% of patients. Grade 3/4 esophageal and pulmonary toxicities were reported in 27% and 20% of patients, respectively. The overall response rate was 46%, and the median survival for all patients was 21 months. Concurrent thoracic radiation with weekly docetaxel and daily gefitinib is feasible but results in moderate toxicity. For further studies, the recommended weekly docetaxel dose for this chemoradiation regimen is 20 mg/m2.

Role of concomitant chemoradiation in locally advanced head and neck cancers.

PubMed

Lasrado, Savita; Moras, Kuldeep; Pinto, George Jawahar Oliver; Bhat, Mahesh; Hegde, Sanath; Sathian, Brijesh; Luis, Neil Aaron

2014-01-01

Standard therapy for advanced head and neck cancer consists of a combination of surgery and radiation. However, survival of this patient population has not improved during the past 20 years. Many different multimodality treatment schedules have been proposed, and chemotherapy is often used with the intent of organ preservation. The present study was intended to establish the efficacy of concomitant chemoradiation with a single agent carboplatin in advanced head and neck cancers.The objectives were to investigate the feasibility of concomitant administration of carboplatin, monitor acute toxicity during radiotherapy, and determine subacute side effects, such as wound healing following surgery after chemoradiotherapy. A prospective study was conducted wherein a total of 40 patients with stage III and IV squamous cell carcinomas of oral cavity, oropharynx, hypopharynx and larynx were enrolled. All patients were treated with external beam radiotherapy and weekly carboplatin area under curve (AUC of 5). Radiotherapy was given in single daily fractions of 1.8-2 grays (Gy) to a total dose of 66-72 Gy. Salvage surgery was performed for any residual or recurrent locoregional disease. Neck dissection was recommended for all patients with neck disease showing less than a complete response after chemoradiation. A total of 40 patients were enrolled of whom 32 were males and 8 were females. Highest incidence of cancer was seen in the 5th-6th decades of life with a median age of 47.7 years. Oropharyngeal tumours constituted a maximum of 21 patients followed by hypopharynx in 10, larynx in 7 and oral cavity in 2. 80% of the patients had a neck node on presentation of which 40% had N2-N3 nodal status. TNM staging revealed that 58% of patients were in stage III and 43% in stage IV. Evaluation of acute toxicity revealed that 50% had grade II mucositis, 25% grade III mucositis, 2.5% grade IV mucositis. 50% of patients had grade I skin reactions, 65% of patients had grade I thrombocytopenia, and 24% of patients had grade I anaemia. After completion of treatment 65% of patients had complete response at the primary and regional sites, and 35% of patients had a partial response of whom 23% underwent neck dissection and 5% of them underwent salvage surgery at the primary site. At the end of one year there were six deaths and four recurrences and 70% were free of disease. Concurrent chemoradiation with carboplatin provided good locoregional control for locally advanced head and neck cancers. This regimen, although toxic, is tolerable with appropriate supportive intervention. Primary site conservation is possible in many patients. Chemoradiotherapy appears to have an emerging role in the primary management of head and neck cancers.

Investigation of clinical and dosimetric factors associated with postoperative pulmonary complications in esophageal cancer patients treated with concurrent chemoradiotherapy followed by surgery.

PubMed

Wang, Shu-lian; Liao, Zhongxing; Vaporciyan, Ara A; Tucker, Susan L; Liu, Helen; Wei, Xiong; Swisher, Stephen; Ajani, Jaffer A; Cox, James D; Komaki, Ritsuko

2006-03-01

To assess the association of clinical and especially dosimetric factors with the incidence of postoperative pulmonary complications among esophageal cancer patients treated with concurrent chemoradiation therapy followed by surgery. Data from 110 esophageal cancer patients treated between January 1998 and December 2003 were analyzed retrospectively. All patients received concurrent chemoradiotherapy followed by surgery; 72 patients also received irinotecan-based induction chemotherapy. Concurrent chemotherapy was 5-fluorouracil-based and in 97 cases included taxanes. Radiotherapy was delivered to a total dose of 41.4-50.4 Gy at 1.8-2.0 Gy per fraction with a three-dimensional conformal technique. Surgery (three-field, Ivor-Lewis, or transhiatal esophagectomy) was performed 27-123 days (median, 45 days) after completion of radiotherapy. The following dosimetric parameters were generated from the dose-volume histogram (DVH) for total lung: lung volume, mean dose to lung, relative and absolute volumes of lung receiving more than a threshold dose (relative V(dose) and absolute V(dose)), and absolute volume of lung receiving less than a threshold dose (volume spared, or VS(dose)). Occurrence of postoperative pulmonary complications, defined as pneumonia or acute respiratory distress syndrome (ARDS) within 30 days after surgery, was the endpoint for all analyses. Fisher's exact test was used to investigate the relationship between categorical factors and incidence of postoperative pulmonary complications. Logistic analysis was used to analyze the relationship between continuous factors (e.g., V(dose) or VS(dose)) and complication rate. Logistic regression with forward stepwise inclusion of factors was used to perform multivariate analysis of those factors having univariate significance (p < 0.05). The Mann-Whitney test was used to compare length of hospital stay in patients with and without lung complications and to compare lung volumes, VS5 values, and absolute and relative V5 values in male vs. female patients. Pearson correlation analysis was used to determine correlations between dosimetric factors. Eighteen (16.4%) of the 110 patients developed postoperative pulmonary complications. Two of these died of progressive pneumonia. Hospitalizations were significantly longer for patients with postoperative pulmonary complications than for those without (median, 15 days vs. 11 days, p = 0.003). On univariate analysis, female gender (p = 0.017), higher mean lung dose (p = 0.036), higher relative volume of lung receiving > or = 5 Gy (V5) (p = 0.023), and smaller volumes of lung spared from doses > or = 5-35 Gy (VS5-VS35) (p < 0.05) were all significantly associated with an increased incidence of postoperative pulmonary complications. No other clinical factors were significantly associated with the incidence of postoperative pulmonary complications in this cohort. On multivariate analysis, the volume of lung spared from doses > or = 5 Gy (VS5) was the only significant independent factor associated with postoperative pulmonary complications (p = 0.005). Dosimetric factors but not clinical factors were found to be strongly associated with the incidence of postoperative pulmonary complications in this cohort of esophageal cancer patients treated with concurrent chemoradiation plus surgery. The volume of the lung spared from doses of > or = 5 Gy was the only independent dosimetric factor in multivariate analysis. This suggests that ensuring an adequate volume of lung unexposed to radiation might reduce the incidence of postoperative pulmonary complications.

Long-term survival based on pathologic response to neoadjuvant therapy in esophageal cancer.

PubMed

Tiesi, Gregory; Park, Wungki; Gunder, Meredith; Rubio, Gustavo; Berger, Michael; Ardalan, Bach; Livingstone, Alan; Franceschi, Dido

2017-08-01

Neoadjuvant treatment is standard for locally advanced esophageal cancer. However, whether the addition of radiation to neoadjuvant regimen improves survival remains unclear. The aim of this study was to compare survival in locally advanced esophageal cancer treated with neoadjuvant chemotherapy versus chemoradiation. A prospectively maintained database of esophagectomies (1999-2012) was analyzed. We identified 297 patients with locally advanced esophageal cancer that underwent either neoadjuvant chemotherapy (n = 231) or chemoradiation (n = 66) followed by esophagectomy. Pretreatment and pathologic staging were compared to assess response. Overall survival was recorded. Most patients in the chemotherapy and chemoradiation groups had pretreatment stage III disease (66.7% versus 65.2%; P = 0.44). Median follow-up was 79.3 and 64.9 mo for chemotherapy and chemoradiation cohorts, respectively. Complete response rate was higher in chemoradiation than chemotherapy groups (30.3% versus 13.8%; P < 0.001). Overall survival was similar between complete responders in both groups (median not reached versus 121.1 mo; chemotherapy versus chemoradiation). However, partial responders in the chemotherapy cohort had improved median survival (147.2 mo) versus those in the chemoradiation cohort (83.7 mo, P < 0.03). Within the chemotherapy-only group, partial responders had improved survival compared with nonresponders (P = 0.041); however, there was no difference in survival between partial and complete responders (P = 0.36). In patients undergoing esophagectomy for locally advanced esophageal cancer, neoadjuvant chemotherapy was associated with an equivalent overall survival, when compared with neoadjuvant chemoradiotherapy. Adding neoadjuvant radiation may enhance complete response rates but does not appear to be associated with improved survival. Copyright © 2017 Elsevier Inc. All rights reserved.

Phase 1 Study of Preoperative Chemoradiation Therapy With Temozolomide and Capecitabine in Patients With Locally Advanced Rectal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jeong, Jae Ho; Hong, Yong Sang; Park, Yangsoon

Purpose: Preoperative chemoradiation therapy (CRT) with capecitabine is a standard treatment strategy in patients with locally advanced rectal cancer (LARC). Temozolomide improves the survival of patients with glioblastoma with hypermethylated O{sup 6}-methylguanine DNA methyltransferase (MGMT); MGMT hypermethylation is one of the colorectal carcinogenesis pathways. We aimed to determine the dose-limiting toxicity (DLT) and recommended dose (RD) of temolozomide in combination with capecitabine-based preoperative CRT for LARC. Methods and Materials: Radiation therapy was delivered with 45 Gy/25 daily fractions with coned-down boost of 5.4 Gy/3 fractions. Concurrent chemotherapy comprised fixed and escalated doses of capecitabine and temozolomide, respectively. The MGMT hypermethylation was evaluatedmore » in pretreatment tumor samples. This trial is registered with (ClinicalTrials.gov) with the number (NCT01781403). Results: Twenty-two patients with LARC of cT3-4N0 or cT{sub any}N1-2 were accrued. Dose level 3 was chosen as the RD because DLT was noticeably absent in 10 patients treated up to dose level 3. An additional 12 patients were recruited in this group. Grade III adverse events were noted, and pathologic complete response (pCR) was observed in 7 patients (31.8%); MGMT hypermethylation was detected in 16. The pCR rate was 37.5% and 16.7% in the hypermethylated and unmethylated MGMT groups, respectively (P=.616). Conclusions: There was a tendency toward higher pCR rates in patients with hypermethylated MGMT. Future randomized studies are therefore warranted.« less

Long-term survival of a randomized phase III trial of head and neck cancer patients receiving concurrent chemoradiation therapy with or without low-level laser therapy (LLLT) to prevent oral mucositis.

PubMed

Antunes, Héliton S; Herchenhorn, Daniel; Small, Isabele A; Araújo, Carlos M M; Viégas, Celia Maria Pais; de Assis Ramos, Gabriela; Dias, Fernando L; Ferreira, Carlos G

2017-08-01

The impact of low-level laser therapy (LLLT) to prevent oral mucositis in patients treated with exclusive chemoradiation therapy remains unknown. This study evaluated the overall, disease-free and progression-free survival of these patients. Overall, disease-free and progression-free survival of 94 patients diagnosed with oropharynx, nasopharynx, and hypopharynx cancer, who participated on a phase III study, was evaluated from 2007 to 2015. The patients were subjected to conventional radiotherapy plus cisplatin every 3weeks. LLLT was applied with an InGaAlP diode (660nm-100mW-1J-4J/cm 2 ). With a median follow-up of 41.3months (range 0.7-101.9), patients receiving LLLT had a statistically significant better complete response to treatment than those in the placebo group (LG=89.1%; PG=67.4%; p=0.013). Patients subjected to LLLT also displayed increase in progression-free survival than those in the placebo group (61.7% vs. 40.4%; p=0.030; HR:1:93; CI 95%: 1.07-3.5) and had a tendency for better overall survival (57.4% vs. 40.4%; p=0.90; HR:1.64; CI 95%: 0.92-2.91). This is the first study to suggest that LLLT may improve survival of head and neck cancer patients treated with chemoradiotherapy. Further studies, with a larger sample, are necessary to confirm our findings. Copyright © 2017 Elsevier Ltd. All rights reserved.

Neoadjuvant Chemotherapy versus Chemoradiation Prior to Esophagectomy: Impact on Rate of Complete Pathologic Response and Survival in Esophageal Cancer Patients.

PubMed

Samson, Pamela; Robinson, Clifford; Bradley, Jeffrey; Lockhart, A Craig; Puri, Varun; Broderick, Stephen; Kreisel, Daniel; Krupnick, A Sasha; Patterson, G Alexander; Meyers, Bryan; Crabtree, Traves

2016-12-01

The aim of this study was to evaluate differences in pathologic complete response (pCR) rates and overall survival among patients receiving either neoadjuvant chemotherapy or chemoradiation before esophagectomy for locally advanced esophageal cancer. Patients with esophageal cancer receiving either neoadjuvant chemotherapy or chemoradiation before esophagectomy were identified using the National Cancer Database. Univariate analysis compared patient, tumor, and postoperative outcome characteristics. Logistic regression was performed to identify variables associated with achieving pCR. Kaplan-Meier analysis was performed to compare overall median survival by neoadjuvant therapy type and pCR status. Finally, a Cox proportional hazards model was fitted to identify variables associated with increased mortality hazard. From 2006 to 2012, a total of 916 of 7338 of patients (12.5%) received neoadjuvant chemotherapy whereas 6422 (87.5%) received neoadjuvant chemoradiation. Patients who received neoadjuvant chemoradiation were more likely to achieve a pCR (17.2% versus 6.4%, p < 0.001) and less likely to have positive margins (5.6% versus 11.5%, p < 0.001) than were patients who received neoadjuvant chemotherapy, with no difference in 30- or 90-day mortality. Achieving a pCR was associated with improved overall median survival (59.5 ± 4.0 months versus 30.1 ± 0.76 months for those with persistent disease, p < 0.001). On logistic regression, neoadjuvant chemoradiation therapy was independently associated with achieving a pCR (OR = 2.75, 95% confidence interval: 2.01-3.77, p < 0.001). Despite improvement in the pCR rate with neoadjuvant chemoradiation, neoadjuvant therapy type was not independently associated with long-term survival (hazard ratio = 1.12; 95% confidence interval: 0.97-1.30, p = 0.12). Although neoadjuvant chemoradiation is more successful in downstaging esophageal cancer before esophagectomy, it was not independently prognostic for improved long-term survival. Other factors affecting long-term survival among pathologic complete responders and among patients with persistent disease should be investigated to clarify this association. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

KRAS Mutation Status and Clinical Outcome of Preoperative Chemoradiation With Cetuximab in Locally Advanced Rectal Cancer: A Pooled Analysis of 2 Phase II Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Sun Young; Shim, Eun Kyung; Yeo, Hyun Yang

2013-01-01

Purpose: Cetuximab-containing chemotherapy is known to be effective for KRAS wild-type metastatic colorectal cancer; however, it is not clear whether cetuximab-based preoperative chemoradiation confers an additional benefit compared with chemoradiation without cetuximab in patients with locally advanced rectal cancer. Methods and Materials: We analyzed EGFR, KRAS, BRAF, and PIK3CA mutation status with direct sequencing and epidermal growth factor receptor (EGFR) and Phosphatase and tensin homolog (PTEN) expression status with immunohistochemistry in tumor samples of 82 patients with locally advanced rectal cancer who were enrolled in the IRIX trial (preoperative chemoradiation with irinotecan and capecitabine; n=44) or the ERBIRIX trial (preoperativemore » chemoradiation with irinotecan and capecitabine plus cetuximab; n=38). Both trials were similarly designed except for the administration of cetuximab; radiation therapy was administered at a dose of 50.4 Gy/28 fractions and irinotecan and capecitabine were given at doses of 40 mg/m{sup 2} weekly and 1650 mg/m{sup 2}/day, respectively, for 5 days per week. In the ERBIRIX trial, cetuximab was additionally given with a loading dose of 400 mg/m{sup 2} on 1 week before radiation, and 250 mg/m{sup 2} weekly thereafter. Results: Baseline characteristics before chemoradiation were similar between the 2 trial cohorts. A KRAS mutation in codon 12, 13, and 61 was noted in 15 (34%) patients in the IRIX cohort and 5 (13%) in the ERBIRIX cohort (P=.028). Among 62 KRAS wild-type cancer patients, major pathologic response rate, disease-free survival and pathologic stage did not differ significantly between the 2 cohorts. No mutations were detected in BRAF exon 11 and 15, PIK3CA exon 9 and 20, or EGFR exon 18-24 in any of the 82 patients, and PTEN and EGFR expression were not predictive of clinical outcome. Conclusions: In patients with KRAS wild-type locally advanced rectal cancer, the addition of cetuximab to the chemoradiation with irinotecan plus capecitabine regimen was not associated with improved clinical outcome compared with chemoradiation without cetuximab.« less

Thermal acclimation is not induced by habitat-of-origin, maintenance temperature, or acute exposure to low or high temperatures in a pit-building wormlion (Vermileo sp.).

PubMed

Bar-Ziv, Michael A; Scharf, Inon

2018-05-01

Wormlions are sit-and-wait insect predators that construct pit-traps to capture arthropod prey. They require loose soil and shelter from direct sun, both common in Mediterranean cities, and explaining their high abundance in urban habitats. We studied different aspects of thermal acclimation in wormlions. We compared chill-coma recovery time (CCRT) and heat-shock recovery time (HSRT) of wormlions from urban, semi-urban and natural habitats, expecting those originating from the urban habitat to be more heat tolerant and less cold tolerant. However, no differences were detected among the three habitats. We then examined whether maintenance temperature affects CCRT and HSRT, and expected beneficial acclimation. However, CCRT was unaffected by maintenance temperature, while temperature affected HSRT in an opposite direction to our prediction: wormlions maintained under the higher temperatures took longer to recover. When testing with two successive thermal shocks, wormlions took longer to recover from both cold and heat shock after applying an initial cold shock. We therefore conclude that cold shock inflicts some damage rather than induces acclimation. Finally, both cold- and heat-shocked wormlions constructed smaller pits than wormlions of a control group. Smaller pits probably translate to a lower likelihood of capturing prey and also limit the size of the prey, indicating a concrete cost of thermal shock. In summary, we found no evidence for thermal acclimation related either to the habitat-of-origin or to maintenance temperatures, but, rather, negative effects of unfavorable temperatures. Copyright © 2018 Elsevier Ltd. All rights reserved.

Refining Preoperative Therapy for Locally Advanced Rectal Cancer

Cancer.gov

In the PROSPECT trial, patients with locally advanced, resectable rectal cancer will be randomly assigned to receive either standard neoadjuvant chemoradiation therapy or neoadjuvant FOLFOX chemotherapy, with chemoradiation reserved for nonresponders.

Cancer cervix: Establishing an evidence-based strategy, an experience of a tertiary care centre in India.

PubMed

Shrivastava, Shyam Kishore; Lewis, Shirley; Sastri, Supriya Chopra; Lavanya, G; Mahantshetty, Umesh; Engineer, Reena

2018-01-12

Carcinoma cervix is a common cancer among Indian women. Evidence based management is essential for best practice in treatment of carcinoma cervix for its effective control. The current imaging system like CT, MRI and PET CT scans have contributed in identifying the patients for optimal treatment and delivering treatment accurately. For stages IB2 to IV, concurrent chemoradiation is advocated with improvement in overall survival proven with randomized trials. Brachytherapy is an integral part in the radiation treatment. Imaged-guided brachytherapy using MRI is desirable, however less expensive imaging modalities such as CT and ultrasonography has been evaluated. In special situation such as for HIV positive patients and patients with neuroendocrine tumors have role of radiotherapy. For further improvement in control of cancer, it is required to integrate basic research to answer clinically relevant questions. Copyright © 2018 Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumar, Bhavna; Cordell, Kitrina G.; Department of Pathology, University of Michigan, Ann Arbor, MI

Induction chemotherapy and concurrent chemoradiation for responders or immediate surgery for non-responders is an effective treatment strategy head and neck squamous cell carcinoma (HNSCC) of the larynx and oropharynx. Biomarkers that predict outcome would be valuable in selecting patients for therapy. In this study, the presence and titer of high risk human papilloma virus (HPV) and expression of epidermal growth factor receptor (EGFR) in pre-treatment biopsies, as well as smoking and gender were examined in oropharynx cancer patients enrolled in an organ sparing trial. HPV16 copy number was positively associated with response to therapy and with overall and disease specificmore » survival, whereas EGFR expression, current or former smoking behavior, and female gender (in this cohort) were associated with poor response and poor survival in multivariate analysis. Smoking cessation and strategies to target EGFR may be useful adjuncts for therapy to improve outcome in the cases with the poorest biomarker profile.« less

Weekly Versus Triweekly Cisplatin-Based Chemotherapy Concurrent With Radiotherapy in the Treatment of Cervical Cancer: A Meta-Analysis.

PubMed

Chen, Xingxing; Zou, Haizhou; Li, Huifang; Lin, Ruifang; Su, Meng; Zhang, Wenyi; Zhou, Yongqiang; Zhang, Ping; Hou, Meng; Deng, Xia; Zou, Changlin

2017-02-01

The aim of this study was to evaluate toxicity, compliance, recurrence and the survival of weekly and triweekly cisplatin-based concomitant chemoradiation in treatment of cervical cancer. The databases were searched from 1995 until 2015 to identify eligible studies on weekly versus triweekly cisplatin chemoradiotherapy. The data were analyzed by RevMan 5.3 software. A total of 5 randomized controlled trials were included in this review. Weekly cisplatin regimen significantly reduced the incidence of Hematologic toxicity. However, there was no significantly different between the 2 arms in compliance, recurrence and the survival rate (all P >0.05). Weekly cisplatin regimen had the similar therapeutic effect as the triweekly cisplatin regimen but with less hematologic toxicity. Therefore, we recommend the weekly cisplatin 30 to 40 mg/m chemoradiotherapy as the strong candidate for the optimal cisplatin dose and dosing schedule in the treatment of locally advanced cervical cancer.

Intensity-Modulated Radiation Therapy for the Treatment of Squamous Cell Anal Cancer With Para-aortic Nodal Involvement

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hodges, Joseph C.; Das, Prajnan, E-mail: PrajDas@mdanderson.or; Eng, Cathy

2009-11-01

Purpose: To determine the rates of toxicity, locoregional control, distant control, and survival in anal cancer patients with para-aortic nodal involvement, treated with intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy at a single institution. Methods and Materials: Between 2001 and 2007, 6 patients with squamous cell anal cancer and para-aortic nodal involvement were treated with IMRT and concurrent infusional 5-fluorouracil and cisplatin. The primary tumor was treated with a median dose of 57.5 Gy (range, 54-60 Gy), involved para-aortic, pelvic, and inguinal lymph nodes were treated with a median dose of 55 Gy (range, 50.5-55 Gy), and noninvolved nodal regions weremore » treated with a median dose of 45 Gy (range, 43.5-45 Gy). Results: After a median follow-up of 25 months, none of the patients had a recurrence at the primary tumor, pelvic/inguinal nodes, or para-aortic nodes, whereas 2 patients developed distant metastases to the liver. Four of the 6 patients are alive. The 3-year actuarial locoregional control, distant control, and overall survival rates were 100%, 56%, and 63%, respectively. Four of the 6 patients developed Grade 3 acute gastrointestinal toxicity during chemoradiation. Conclusions: Intensity-modulated radiotherapy and concurrent chemotherapy could potentially serve as definitive therapy in anal cancer patients with para-aortic nodal involvement. Adjuvant chemotherapy may be indicated in these patients, as demonstrated by the distant failure rates. These patients need to be followed carefully because of the potential for treatment-related toxicities.« less

Prognostic Cell Biological Markers in Cervical Cancer Patients Primarily Treated With (Chemo)radiation: A Systematic Review

DOE Office of Scientific and Technical Information (OSTI.GOV)

Noordhuis, Maartje G.; Eijsink, Jasper J.H.; Roossink, Frank

2011-02-01

The aim of this study was to systematically review the prognostic and predictive significance of cell biological markers in cervical cancer patients primarily treated with (chemo)radiation. A PubMed, Embase, and Cochrane literature search was performed. Studies describing a relation between a cell biological marker and survival in {>=}50 cervical cancer patients primarily treated with (chemo)radiation were selected. Study quality was assessed, and studies with a quality score of 4 or lower were excluded. Cell biological markers were clustered on biological function, and the prognostic and predictive significance of these markers was described. In total, 42 studies concerning 82 cell biologicalmore » markers were included in this systematic review. In addition to cyclooxygenase-2 (COX-2) and serum squamous cell carcinoma antigen (SCC-ag) levels, markers associated with poor prognosis were involved in epidermal growth factor receptor (EGFR) signaling (EGFR and C-erbB-2) and in angiogenesis and hypoxia (carbonic anhydrase 9 and hypoxia-inducible factor-1{alpha}). Epidermal growth factor receptor and C-erbB-2 were also associated with poor response to (chemo)radiation. In conclusion, EGFR signaling is associated with poor prognosis and response to therapy in cervical cancer patients primarily treated with (chemo)radiation, whereas markers involved in angiogenesis and hypoxia, COX-2, and serum SCC-ag levels are associated with a poor prognosis. Therefore, targeting these pathways in combination with chemoradiation may improve survival in advanced-stage cervical cancer patients.« less

[A recent trial of chemo-radiation with S-1 against gastric cancer].

PubMed

Saikawa, Yoshiro; Kiyota, Tsuyoshi; Nakamura, Rieko; Wada, Norihito; Yoshida, Masashi; Kubota, Tetsuro; Kumai, Koichiro; Shigematsu, Naoyuki; Kubo, Atsushi; Kitajima, Masaki

2006-06-01

A recent development of novel anticancer agents like S-1, CPT-11 or taxanes has improved a therapeutic outcome for advanced gastric cancer, while conventional anticancer agents showed less anticancer effect against gastric cancer. The present main drug in Japan is S-1, which is easily used for outpatient with a high efficacy rate and low toxicity, also shows better effect in combination with other anticancer drugs than S-1 alone. In the present article, we demonstrated significant meaning of additional radiation therapy with anticancer drugs like S-1. With novel anticancer drugs like S-1, we will expose a clinical advantage and appropriateness for chemo-radiation therapy against gastric cancer discussed in the present references according to chemo-radiation therapy. Although chemo-radiation therapy has been recognized as one of the standard therapies for gastric cancer in Western countries, radiation therapy was selected in Japan for palliation therapy of recurrent disease or a terminal cancer to improve patients' QOL. On the other hand, we demonstrated in our trial of chemo-radiation therapy with S-1/low-dose CDDP/radiation (TSLDR), which was applied to initial treatment against highly advanced Stage IV gastric cancer and revealed the usefulness of the regimen in anticancer effect and toxicity. In addition, chemo-radiation therapy including novel anticancer agents like S-1 will be discussed based on various kinds of view points, expecting a better clinical outcome of multimodal therapies against advanced gastric cancer.

Predictive value of MRI-detected extramural vascular invasion in stage T3 rectal cancer patients before neoadjuvant chemoradiation.

PubMed

Sun, Yiqun; Li, Jianwen; Shen, Lijun; Wang, Xiaolin; Tong, Tong; Gu, Yajia

2018-01-01

We set out to explore the probability of MRI-detected extramural vascular invasion (mr-EMVI) before chemoradiation to predict responses to chemoradiation and survival in stage T3 rectal cancer patients. A total of 100 patients with T3 rectal cancer who underwent MRI examination and received neoadjuvant chemoradiation and surgery were enrolled. The correlation between mr-EMVI and other clinical factors were analyzed by chi-square. Logistic regression model was performed to select the potential factors influencing tumor responses to neoadjuvant chemoradiation. A Cox proportional hazards regression model was performed to explore potential predictors of survival. The positive mr-EMVI result was more likely to be present in patients with a higher T3 subgroup (T3a+b = 7.1% vs. T3c+d = 90.1%, P < 0.001) and more likely in patients with mesorectal fascia involvement than in those without MRF (65% vs. 38.8%, P = 0.034). Compared with mr-EMVI (+) patients, more mr-EMVI (-) patients showed a good response (staged ≤ ypT2N0) (odds ratio [OR], 3.020; 95% confidence interval [CI], 1.071-8.517; P = 0.037). In univariate analysis, mr-EMVI (+) (hazard ratio [HR], 5.374; 95% CI, 1.210-23.872; P = 0.027) and lower rectal cancers (HR, 3.326; 95% CI, 1.135-9.743; P = 0.028) were significantly associated with decreased disease-free survival. A positive mr-EMVI status (HR, 5.727; 95% CI, 1.286-25.594; P = 0.022) and lower rectal cancers (HR, 3.137; 95% CI, 1.127-8.729; P = 0.029) also served as prognostic factors related to decreased disease-free survival in multivariate analysis. The mr-EMVI status before chemoradiation is a significant prognostic factor and could be used for identifying T3 rectal cancer patients who might benefit from neoadjuvant chemoradiation.

Appropriate customization of radiation therapy for stage II and III rectal cancer: Executive summary of an ASTRO Clinical Practice Statement using the RAND/UCLA Appropriateness Method.

PubMed

Goodman, Karyn A; Patton, Caroline E; Fisher, George A; Hoffe, Sarah E; Haddock, Michael G; Parikh, Parag J; Kim, John; Baxter, Nancy N; Czito, Brian G; Hong, Theodore S; Herman, Joseph M; Crane, Christopher H; Hoffman, Karen E

2016-01-01

To summarize results of a Clinical Practice Statement on radiation therapy for stage II-III rectal cancer, which addressed appropriate customization of (neo)adjuvant radiation therapy and use of non-surgical therapy for patients who are inoperable or refuse abdominoperineal resection. The RAND/University of California, Los Angeles, Appropriateness Method was applied to combine current evidence with multidisciplinary expert opinion. A systematic literature review was conducted and used by the expert panel to rate appropriateness of radiation therapy options for different clinical scenarios. Treatments were categorized by median rating as Appropriate, May Be Appropriate, or Rarely Appropriate. In the neoadjuvant setting, chemoradiation was rated Appropriate and the ratings indicated short-course radiation therapy, chemotherapy alone, and no neoadjuvant therapy are potential options in selected patients. However, neoadjuvant endorectal brachytherapy was rated Rarely Appropriate. For adjuvant therapy, chemoradiation (plus ≥4 months of chemotherapy) was rated Appropriate and chemotherapy alone May Be Appropriate for most scenarios. For medically inoperable patients, definitive external beam radiation therapy and chemotherapy alone were rated May Be Appropriate, whereas endorectal brachytherapy and chemoradiation plus endorectal brachytherapy were possible approaches for some scenarios. The last option, definitive chemoradiation, was rated Appropriate to May Be Appropriate based on performance status. Finally, for patients with low-lying tumors refusing abdominoperineal resection, definitive chemoradiation alone, chemoradiation plus endorectal brachytherapy, and chemoradiation plus external beam radiation therapy were all rated Appropriate. This Clinical Practice Statement demonstrated the central role of radiation therapy in stage II-III rectal cancer management and evaluated ways to better individualize its use in the neoadjuvant, adjuvant, and definitive settings. Ongoing trials may clarify areas of continuing uncertainty and allow further customization. Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Long-term complications of definitive chemoradiotherapy for esophageal cancer using the classical method

PubMed Central

Ito, Hitoshi; Itasaka, Satoshi; Sakanaka, Katsuyuki; Araki, Norio; Mizowaki, Takashi; Hiraoka, Masahiro

2017-01-01

Chemoradiation therapy is widely used to treat both inoperable and operable patients, and is less invasive than surgery. Although the number of long-term survivors who have received chemoradiation therapy is increasing, the long-term toxicity pattern and cumulative incidence of toxicity regarding this modality are poorly understood. Classically, chemoradiation therapy for esophageal cancer consists of an anterior–posterior field and a subsequent oblique boost field. We retrospectively analyzed patients who were treated with definitive chemoradiation therapy for esophageal cancer using this classical method from 1999 to 2008. For the assessment of toxicity, the National Cancer Institute Common Toxicity Criteria Version 3.0 was adopted. A total of 101 patients were analyzed. The median follow-up time was 16 months for all patients and 62 months for the surviving patients. Eleven patients experienced late toxicities of ≥Grade 3. Two patients died of late toxicities. The 3- and 5-year cumulative incidences for the first late cardiopulmonary toxicities of ≥Grade 3 were 17.4% and 20.8%, respectively. Cardiopulmonary effusions were observed within the first 3 years of completion of the initial treatment in seven out of eight patients. Sudden death and cardiac ischemia were observed over a 10-year period. Older age was found to be a risk factor for late toxicity after definitive chemoradiation therapy for esophageal cancer. Substantial toxicities were observed in patients who had received chemoradiation therapy for esophageal cancer using the classical method. To minimize the incidence of late toxicity, more sophisticated radiation techniques may be useful. PMID:27475126

c-Met Expression Is a Marker of Poor Prognosis in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma Treated With Chemoradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baschnagel, Andrew M.; Williams, Lindsay; Hanna, Alaa

2014-03-01

Purpose: To examine the prognostic significance of c-Met expression in relation to p16 and epidermal growth factor receptor (EGFR) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated with definitive concurrent chemoradiation. Methods and Materials: Archival tissue from 107 HNSCC patients treated with chemoradiation was retrieved, and a tissue microarray was assembled. Immunohistochemical staining of c-Met, p16, and EGFR was performed. c-Met expression was correlated with p16, EGFR, clinical characteristics, and clinical endpoints including locoregional control (LRC), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS). Results: Fifty-one percent of patients were positive for p16,more » and 53% were positive for EGFR. Both p16-negative (P≤.001) and EGFR-positive (P=.019) status predicted for worse DFS. Ninety-three percent of patients stained positive for c-Met. Patients were divided into low (0, 1, or 2+ intensity) or high (3+ intensity) c-Met expression. On univariate analysis, high c-Met expression predicted for worse LRC (hazard ratio [HR] 2.27; 95% CI, 1.08-4.77; P=.031), DM (HR 4.41; 95% CI, 1.56-12.45; P=.005), DFS (HR 3.00; 95% CI, 1.68-5.38; P<.001), and OS (HR 4.35; 95% CI, 2.13-8.88; P<.001). On multivariate analysis, after adjustment for site, T stage, smoking history, and EGFR status, only high c-Met expression (P=.011) and negative p16 status (P=.003) predicted for worse DFS. High c-Met expression was predictive of worse DFS in both EGFR-positive (P=.032) and -negative (P=.008) patients. In the p16-negative patients, those with high c-Met expression had worse DFS (P=.036) than did those with low c-Met expression. c-Met expression was not associated with any outcome in the p16-positive patients. Conclusions: c-Met is expressed in the majority of locally advanced HNSCC cases, and high c-Met expression predicts for worse clinical outcomes. High c-Met expression predicted for worse DFS in p16-negative patients but not in p16-positive patients. c-Met predicted for worse outcome regardless of EGFR status.« less

Correlation Between the Severity of Cetuximab-Induced Skin Rash and Clinical Outcome for Head and Neck Cancer Patients: The RTOG Experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bar-Ad, Voichita, E-mail: voichita.bar-ad@jefferson.edu; Zhang, Qiang; Harari, Paul M.

Purpose: To evaluate the severity of cetuximab-induced skin rash and its correlation with clinical outcome and late skin toxicity in patients with head and neck squamous cell carcinoma treated with chemoradiation therapy and cetuximab. Methods and Materials: Analysis included patients who received loading dose and ≥1 cetuximab dose concurrent with definitive chemoradiation therapy (70 Gy + cisplatin) or postoperative chemoradiation therapy (60-66 Gy + docetaxel or cisplatin). Results: Six hundred two patients were analyzed; 383 (63.6%) developed grade 2 to 4 cetuximab rash. Patients manifesting grade 2 to 4 rash had younger age (P<.001), fewer pack-years smoking history (P<.001), were more likely to be males (P=.04), and hadmore » p16-negative (P=.04) oropharyngeal tumors (P=.003). In univariate analysis, grade 2 to 4 rash was associated with better overall survival (hazard ratio [HR] 0.58, P<.001) and progression-free survival (HR 0.75, P=.02), and reduced distant metastasis rate (HR 0.61, P=.03), but not local-regional failure (HR 0.79, P=.16) relative to grade 0 to 1 rash. In multivariable analysis, HRs for overall survival, progression-free survival, distant metastasis, and local-regional failure were, respectively, 0.68 (P=.008), 0.85 (P=.21), 0.64 (P=.06), and 0.89 (P=.48). Grade ≥2 rash was associated with improved survival in p16-negative patients (HR 0.28 [95% confidence interval 0.11-0.74]) but not in p16-positive patients (HR 1.10 [0.42-2.89]) (P=.05 for interaction). Twenty-five percent of patients with grade 2 to 4 acute in-field radiation dermatitis experienced grade 2 to 4 late skin fibrosis, versus 14% of patients with grade 0 to 1 acute in-field radiation dermatitis (P=.002). Conclusion: Grade 2 to 4 cetuximab rash was associated with better survival, possibly due to reduction of distant metastasis. This observation was noted mainly in p16-negative patients. Grade 2 to 4 acute in-field radiation dermatitis was associated with higher rate of late grade 2 to 4 skin fibrosis.« less

Predictive factors for survival and correlation to toxicity in advanced Stage III non-small cell lung cancer patients with concurrent chemoradiation.

PubMed

Kim, Yong-Hyub; Ahn, Sung-Ja; Kim, Young-Chul; Kim, Kyu-Sik; Oh, In-Jae; Ban, Hee-Jung; Chung, Woong-Ki; Nam, Taek-Keun; Yoon, Mee Sun; Jeong, Jae-Uk; Song, Ju-Young

2016-02-01

Concurrent chemoradiotherapy is the standard treatment for locally advanced Stage III non-small cell lung cancer in patients with a good performance status and minimal weight loss. This study aimed to define subgroups with different survival outcomes and identify correlations with the radiation-related toxicities. We retrospectively reviewed 381 locally advanced Stage III non-small cell lung cancer patients with a good performance status or weight loss of <10% who received concurrent chemoradiotherapy between 2004 and 2011. Three-dimensional conformal radiotherapy was administered once daily, combined with weekly chemotherapy. The Kaplan-Meier method was used for survival comparison and Cox regression for multivariate analysis. Multivariate analysis was performed using all variables with P values <0.1 from the univariate analysis. Median survival of all patients was 24 months. Age > 75 years, the diffusion lung capacity for carbon monoxide ≤80%, gross tumor volume ≥100 cm(3) and subcarinal nodal involvement were the statistically significant predictive factors for poor overall survival both in univariate and multivariate analyses. Patients were classified into four groups according to these four predictive factors. The median survival times were 36, 29, 18 and 14 months in Groups I, II, III and IV, respectively (P < 0.001). Rates of esophageal or lung toxicity ≥Grade 3 were 5.9, 14.1, 12.5 and 22.2%, respectively. The radiotherapy interruption rate differed significantly between the prognostic subgroups; 8.8, 15.4, 22.7 and 30.6%, respectively (P = 0.017). Severe toxicity and interruption of radiotherapy were more frequent in patients with multiple adverse predictive factors. To maintain the survival benefit in patients with concurrent chemoradiotherapy, strategies to reduce treatment-related toxicities need to be deeply considered. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Climate variability differentially impacts thermal fitness traits in three coprophagic beetle species.

PubMed

Nyamukondiwa, Casper; Chidawanyika, Frank; Machekano, Honest; Mutamiswa, Reyard; Sands, Bryony; Mgidiswa, Neludo; Wall, Richard

2018-01-01

While the impacts of extreme and rising mean temperatures are well documented, increased thermal variability associated with climate change may also threaten ectotherm fitness and survival, but remains poorly explored. Using three wild collected coprophagic species Copris elphenor, Metacatharsius opacus and Scarabaeus zambezianus, we explored the effects of thermal amplitude around the mean on thermal tolerance. Using standardized protocols, we measured traits of high- (critical thermal maxima [CTmax] and heat knockdown time [HKDT]) and -low temperature tolerance (critical thermal minima [CTmin], chill coma recovery time [CCRT] and supercooling points [SCPs]) following variable temperature pulses (δ0, δ3, δ6 and δ9°C) around the mean (27°C). Our results show that increased temperature variability may offset basal and plastic responses to temperature and differs across species and metrics tested. Furthermore, we also show differential effects of body mass, body water content (BWC) and body lipid content (BLC) on traits of thermal tolerance. For example, body mass significantly influenced C. elphenor and S. zambezianus CTmax and S. zambezianus HKDT but not CTmin and CCRT. BWC significantly affected M. opacus and C. elphenor CTmax and in only M. opacus HKDT, CTmin and CCRT. Similarly, BLC only had a significant effect for M opacus CTmin. These results suggest differential and species dependent effects of climate variability of thermal fitness traits. It is therefore likely that the ecological services provided by these species may be constrained in the face of climate change. This implies that, to develop more realistic predictions for the effects of climate change on insect biodiversity and ecosystem function, thermal variability is a significant determinant.

Physical properties of particulate matter (PM) from late model heavy-duty diesel vehicles operating with advanced PM and NO x emission control technologies

NASA Astrophysics Data System (ADS)

Biswas, Subhasis; Hu, Shaohua; Verma, Vishal; Herner, Jorn D.; Robertson, William H.; Ayala, Alberto; Sioutas, Constantinos

Emission control technologies designed to meet the 2007 and 2010 emission standards for heavy-duty diesel vehicles (HDDV) remove effectively the non-volatile fraction of particles, but are comparatively less efficient at controlling the semi-volatile components. A collaborative study between the California Air Resources Board (CARB) and the University of Southern California was initiated to investigate the physicochemical and toxicological characteristics of the semi-volatile and non-volatile particulate matter (PM) fractions from HDDV emissions. This paper reports the physical properties, including size distribution, volatility (in terms of number and mass), surface diameter, and agglomeration of particles emitted from HDDV retrofitted with advanced emission control devices. Four vehicles in combination with six after-treatment devices (V-SCRT ®, Z-SCRT ®, CRT ®, DPX, Hybrid-CCRT ®, EPF) were tested under three driving cycles: steady state (cruise), transient (urban dynamometer driving schedule, UDDS), and idle. An HDDV without any control device is served as the baseline vehicle. Substantial reduction of PM mass emissions (>90%) was accomplished for the HDDV operating with advanced emission control technologies. This reduction was not observed for particle number concentrations under cruise conditions, with the exceptions of the Hybrid-CCRT ® and EPF vehicles, which were efficient in controlling both—mass and number emissions. In general, significant nucleation mode particles (<50 nm) were formed during cruise cycles in comparison with the UDDS cycles, which emit higher PM mass in the accumulation mode. The nucleation mode particles (<50 nm) were mainly internally mixed, and evaporated considerably between 150 and 230 °C. Compared to the baseline vehicle, particles from vehicles with controls (except of the Hybrid-CCRT ®) had a higher mass specific surface area.

Radiation dose does not influence anastomotic complications in patients with esophageal cancer treated with neoadjuvant chemoradiation and transhiatal esophagectomy.

PubMed

Koëter, Marijn; van der Sangen, Maurice J C; Hurkmans, Coen W; Luyer, Misha D P; Rutten, Harm J T; Nieuwenhuijzen, Grard A P

2015-03-06

Neoadjuvant chemoradiation might increase anastomotic leakage and stenosis in patients with esophageal cancer treated with neoadjuvant chemoradiation and esophagectomy. The aim of this study was to determine the influence of radiation dose on the incidence of leakage and stenosis. Fifty-three patients with esophageal cancer received neoadjuvant chemoradiation (23 × 1.8 Gy) (combined with Paclitaxel and Carboplatin) followed by a transhiatal esophagectomy between 2009 and 2011. On planning CT, the future anastomotic region was determined and the mean radiation dose, V20, V25, V30, V35 and V40 were calculated. Logistic regression analysis was conducted to examine determinants of anastomotic leakage and stenosis. Anastomotic leaks occurred in 13 of 53 patients (25.5%) and anastomotic stenosis occurred in 24 of 53 patients (45.3%). Median follow-up was 20 months. Logistic regression analysis showed that mean dose, V20-V40, age, co-morbidity, method of anastomosis, operating time and interval between last radiotherapy treatment and surgery were not predictors of anastomotic leakage and stenosis. A radiation dose of 23 × 1.8 Gy on the future anastomotic region has no influence on the occurrence of anastomotic leakage and stenosis in patients with esophageal cancer treated with neoadjuvant chemoradiation followed by transhiatal esophagectomy.

The Benefit of Chemotherapy in Esophageal Cancer Patients With Residual Disease After Trimodality Therapy.

PubMed

Kim, Grace J; Koshy, Matthew; Hanlon, Alexandra L; Horiba, M Naomi; Edelman, Martin J; Burrows, Whitney M; Battafarano, Richard J; Suntharalingam, Mohan

2016-04-01

The objective of this retrospective study was to determine the potential benefits of chemotherapy in esophageal cancer patients treated with chemoradiation followed by surgery. At our institution, 145 patients completed trimodality therapy from 1993 to 2009. Neoadjuvant treatment predominantly consisted of 5-fluorouracil and cisplatin with a concurrent median radiation dose of 50.4 Gy. Sixty-two patients received chemotherapy postoperatively. The majority (49/62) received 3 cycles of docetaxel. Within the entire cohort, a 5-year overall survival (OS) benefit was found in those who received postoperative chemotherapy, OS 37.1% versus 18.0% (P=0.024). The response after neoadjuvant chemoradiation was as follows: 33.8% had a pathologic complete response and 62.8% with residual disease. A 5-year OS and cause-specific survival (CSS) advantage were associated with postoperative chemotherapy among those with macroscopic residual disease after neoadjuvant therapy: OS 38.7% versus 13.9% (P=0.016), CSS 42.8% versus 18.8% (P=0.048). This benefit was not seen in those with a pathologic complete response or those with microscopic residual. A stepwise multivariate Cox regression model evaluating the partial response group revealed that postoperative chemotherapy and M stage were independent predictors of overall and CSS. This analysis revealed that patients with gross residual disease after trimodality therapy for esophageal cancer who received postoperative chemotherapy had an improved overall and CSS. These data suggest that patients with residual disease after trimodality therapy and a reasonable performance status may benefit from postoperative chemotherapy. Prospective trials are needed to confirm these results to define the role of postoperative treatment after trimodality therapy.

Clinical Usefulness of {sup 18}F-Fluorodeoxyglucose-Positron Emission Tomography in Patients With Locally Advanced Pancreatic Cancer Planned to Undergo Concurrent Chemoradiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang, Jee Suk; Choi, Seo Hee; Lee, Youngin

2014-09-01

Purpose: To assess the role of coregistered {sup 18}F-fluorodeoxyglucose positron emission tomography (FDG-PET) in detecting radiographically occult distant metastasis (DM) at staging in patients with locally advanced pancreatic cancer (LAPC) and to study whether FDG-PET parameters can predict relatively long-term survival in patients who are more likely to benefit from chemoradiation therapy (CRT). Methods and Materials: From our institutional database, we identified 388 LAPC patients with M0 on conventional computed tomography (CT) who were planned to undergo CRT. Coregistered FDG-PET staging was offered to all patients, and follow-up FDG-PET was used at the clinical discretion of the physician. Results: FDG-PET detectedmore » unsuspected CT-occult DM in 33% of all 388 patients and allowed them to receive systemic therapy immediately. The remaining 260 patients (PET-M0) underwent CRT selectively as an initial treatment. Early DM arose in 13.1% of 260 patients, and the 1-year estimated locoregional recurrence rate was 5.4%. Median overall survival (OS) and progression-free survival (PFS) were 14.6 and 9.3 months, respectively, at a median follow-up time of 32.3 months (range, 10-99.1 months). Patients with a baseline standardized uptake value (SUV) <3.5 and/or SUV decline ≥60% had significantly better OS and PFS than those having none, even after adjustment for all potential confounding variables (all P<.001). Conclusions: FDG-PET can detect radiographically occult DM at staging in one-third of patients and spare them from the potentially toxic therapy. Additionally, FDG-PET parameters including baseline SUV and SUV changes may serve as useful clinical markers for predicting the prognosis in LAPC patients.« less

Radiobiological Determination of Dose Escalation and Normal Tissue Toxicity in Definitive Chemoradiation Therapy for Esophageal Cancer☆

PubMed Central

Warren, Samantha; Partridge, Mike; Carrington, Rhys; Hurt, Chris; Crosby, Thomas; Hawkins, Maria A.

2014-01-01

Purpose This study investigated the trade-off in tumor coverage and organ-at-risk sparing when applying dose escalation for concurrent chemoradiation therapy (CRT) of mid-esophageal cancer, using radiobiological modeling to estimate local control and normal tissue toxicity. Methods and Materials Twenty-one patients with mid-esophageal cancer were selected from the SCOPE1 database (International Standard Randomised Controlled Trials number 47718479), with a mean planning target volume (PTV) of 327 cm3. A boost volume, PTV2 (GTV + 0.5 cm margin), was created. Radiobiological modeling of tumor control probability (TCP) estimated the dose required for a clinically significant (+20%) increase in local control as 62.5 Gy/25 fractions. A RapidArc (RA) plan with a simultaneously integrated boost (SIB) to PTV2 (RA62.5) was compared to a standard dose plan of 50 Gy/25 fractions (RA50). Dose-volume metrics and estimates of normal tissue complication probability (NTCP) for heart and lungs were compared. Results Clinically acceptable dose escalation was feasible for 16 of 21 patients, with significant gains (>18%) in tumor control from 38.2% (RA50) to 56.3% (RA62.5), and only a small increase in predicted toxicity: median heart NTCP 4.4% (RA50) versus 5.6% (RA62.5) P<.001 and median lung NTCP 6.5% (RA50) versus 7.5% (RA62.5) P<.001. Conclusions Dose escalation to the GTV to improve local control is possible when overlap between PTV and organ-at-risk (<8% heart volume and <2.5% lung volume overlap for this study) generates only negligible increase in lung or heart toxicity. These predictions from radiobiological modeling should be tested in future clinical trials. PMID:25304796

Phase I Study of Preoperative Chemoradiation With S-1 and Oxaliplatin in Patients With Locally Advanced Resectable Rectal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hong, Yong Sang; Lee, Jae-Lyun; Park, Jin Hong

Purpose: To perform a Phase I study of preoperative chemoradiation (CRT) with S-1, a novel oral fluoropyrimidine, plus oxaliplatin in patients with locally advanced rectal cancer, to determine the maximum tolerated dose and the recommended dose. Methods and Materials: Radiotherapy was delivered to a total of 45 Gy in 25 fractions and followed by a coned-down boost of 5.4 Gy in 3 fractions. Concurrent chemotherapy consisted of a fixed dose of oxaliplatin (50 mg/m{sup 2}/week) on Days 1, 8, 22, and 29 and escalated doses of S-1 on Days 1-14 and 22-35. The initial dose of S-1 was 50 mg/m{supmore » 2}/day, gradually increasing to 60, 70, and 80 mg/m{sup 2}/day. Surgery was performed within 6 {+-} 2 weeks. Results: Twelve patients were enrolled and tolerated up to Dose Level 4 (3 patients at each dose level) without dose-limiting toxicity. An additional 3 patients were enrolled at Dose Level 4, with 1 experiencing a dose-limiting toxicity of Grade 3 diarrhea. Although maximum tolerated dose was not attained, Dose Level 4 (S-1 80 mg/m{sup 2}/day) was chosen as the recommended dose for further Phase II studies. No Grade 4 toxicity was observed, and Grade 3 toxicities of leukopenia and diarrhea occurred in the same patient (1 of 15, 6.7%). Pathologic complete responses were observed in 2 of 15 patients (13.3%). Conclusions: The recommended dose of S-1 was determined to be 80 mg/m{sup 2}/day when combined with oxaliplatin in preoperative CRT, and a Phase II trial is now ongoing.« less

Cetuximab Combined With Induction Oxaliplatin and Capecitabine, Followed by Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer: SWOG 0713.

PubMed

Leichman, Cynthia Gail; McDonough, Shannon L; Smalley, Stephen R; Billingsley, Kevin G; Lenz, Heinz-Josef; Beldner, Matthew A; Hezel, Aram F; Velasco, Mario R; Guthrie, Katherine A; Blanke, Charles D; Hochster, Howard S

2018-03-01

Neoadjuvant chemoradiation (NCRT) is standard treatment for locally advanced rectal cancer. Pathologic complete response (pCR) has associated with improved survival. In modern phase III trials of NCRT, pCR ranges from 10% to 20%. Cetuximab improves response in KRAS (KRAS proto-oncogene) wild type (wt) metastatic colorectal cancer. S0713 was designed to assess improvement in pCR with additional use of cetuximab with induction chemotherapy and NCRT for locally advanced, KRAS-wt rectal cancer. Patient eligibility: stage II to III biopsy-proven, KRAS-wt rectal adenocarcinoma; no bowel obstruction; adequate hematologic, hepatic and renal function; performance status of 0 to 2. Target enrollment: 80 patients. induction chemotherapy with wCAPOX (weekly capecitabine and oxaliplatin) and cetuximab followed by the same regimen concurrent with radiation (omitting day 15 oxaliplatin). If fewer than 7 pCRs were observed at planned interim analysis after 40 patients received all therapy, the study would close. Eighty eligible patients would provide 90% power given a true pCR rate > 35% at a significance of 0.04. The regimen would lack future interest if pCR probability was ≤ 20%. Between February 2009 and April 2013, 83 patients registered. Four were ineligible and 4 not treated, leaving 75 evaluable for clinical outcomes and toxicity, of whom 65 had surgery. Of 75 patients, 20 had pCR (27%; 95% confidence interval [CI], 17%-38%); 19 (25%) had microscopic cancer; 36 (48%) had minor/no response (including 10 without surgery). Three-year disease-free survival was 73% (95% CI, 63%-83%). Our trial did not meet the pCR target of 35%. Toxicity was generally acceptable. This regimen cannot be recommended outside the clinical trial setting. Copyright © 2017 Elsevier Inc. All rights reserved.

Supraclavicular node disease is not an independent prognostic factor for survival of esophageal cancer patients treated with definitive chemoradiation.

PubMed

Jeene, Paul M; Versteijne, Eva; van Berge Henegouwen, Mark I; Bergmann, Jacques J G H M; Geijsen, Elisabeth D; van Laarhoven, Hanneke W M; Hulshof, Maarten C C M

2017-01-01

The prognostic value of supraclavicular lymph node (SCN) metastases in esophageal cancer is not well established. We analyzed the prognostic value of SCN disease in patients after definitive chemoradiation (dCRT) for esophageal cancer. We retrospectively analyzed 207 patients treated between 2003 and 2013 to identify the prognostic value of metastasis in the SCN on treatment failure and survival. All patients were treated with external beam radiotherapy (50.4 Gy in 28 fractions) combined with weekly concurrent paclitaxel 50 mg/m 2 and carboplatin AUC2. Median follow-up for patients alive was 43.3 months. The median overall survival (OS) for all patients was 17.5 months. OS at one, three and five years was 67%, 36% and 21%, respectively. For patients with metastasis in a SCN, OS was 23.6 months compared to 17.1 months for patients without metastasis in the SCN (p = .51). In multivariate analyses, higher cT status, cN status and adenocarcinoma were found to be prognostically unfavorable, but a positive SCN was not (p = .67). Median OS and median disease-free survival for tumors with SCN involvement and N0/1 disease was 49.0 months and 51.6 months, respectively, compared to 14.2 months and 8.2 months, respectively, in patients with N2/3 disease. In esophageal cancer treated with dCRT, the number of affected lymph nodes is an important independent prognostic factor, whereas involvement of a SCN is not. Supraclavicular lymph nodes should be considered as regional lymph nodes and treated with curative intent if the total number of involved lymph nodes is limited.

Role of Adjuvant Chemoradiation Therapy in Adenocarcinomas of the Ampulla of Vater

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krishnan, Sunil; Rana, Vishal; Evans, Douglas B.

2008-03-01

Purpose: The role of adjuvant chemoradiation therapy (CRT) in the treatment of ampullary cancers remains undefined. We retrospectively compared treatment outcomes in patients treated with pancreaticoduodenectomy alone versus those who received additional adjuvant CRT. Methods and Materials: Between May 1990 and January 2006, 54 of 96 patients with ampullary adenocarcinoma who underwent potentially curative pancreaticoduodenectomy also received adjuvant CRT. The median preoperative radiation dose was 45 Gy (range, 30-50.4 Gy) and median postoperative dose was 50.4 Gy (range, 45-55.8 Gy). Concurrent chemotherapy included primarily 5-fluorouracil (52%) and capecitabine (43%). Median follow-up was 31 months. Univariate and multivariate statistical methodologies weremore » used to determine significant prognostic factors for local control (LC), distant control (DC), and overall survival (OS). Results: Actuarial 5-year LC, DC, and OS were 77%, 69%, and 64%, respectively. On univariate analysis, age, gender, race/ethnicity, tumor grade, use of adjuvant treatment, and sequencing of adjuvant therapy were not significantly associated with LC, DC, or OS. However, on univariate analysis, T3/T4 tumor stage was prognostic for poorer LC and OS (p = 0.02 and p < 0.001, respectively); node-positive disease was prognostic for poorer LC (p = 0.03). On multivariate analysis, T3/T4 tumor stage was independently prognostic for decreased OS (p = 0.002). Among these patients (n = 34), those who received adjuvant CRT had a trend toward improved OS (median, 35.2 vs. 16.5 months; p = 0.06). Conclusions: Ampullary cancers have a distinctly better treatment outcome than pancreatic adenocarcinomas. Higher primary tumor stage (T3/T4), an independent adverse risk factor for poorer treatment outcomes, may warrant the addition of adjuvant CRT to pancreaticoduodenectomy.« less

Cetuximab Plus Chemoradiotherapy in Immunocompetent Patients With Anal Carcinoma: A Phase II Eastern Cooperative Oncology Group–American College of Radiology Imaging Network Cancer Research Group Trial (E3205)

PubMed Central

Garg, Madhur K.; Zhao, Fengmin; Palefsky, Joel; Whittington, Richard; Mitchell, Edith P.; Mulcahy, Mary F.; Armstrong, Karin I.; Nabbout, Nassim H.; Kalnicki, Shalom; El-Rayes, Bassel F.; Onitilo, Adedayo A.; Moriarty, Daniel J.; Fitzgerald, Thomas J.; Benson, Al B.

2017-01-01

Purpose Squamous cell carcinoma of the anal canal (SCCAC) is characterized by high locoregional failure (LRF) rates after sphincter-preserving definitive chemoradiation (CRT) and is typically associated with anogenital human papilloma virus infection. Because cetuximab enhances the effect of radiation therapy in human papilloma virus–associated oropharyngeal squamous cell carcinoma, we hypothesized that adding cetuximab to CRT would reduce LRF in SCCAC. Methods Sixty-one patients with stage I to III SCCAC received CRT including cisplatin, fluorouracil, and radiation therapy to the primary tumor and regional lymph nodes (45 to 54 Gy) plus eight once-weekly doses of concurrent cetuximab. The study was designed to detect at least a 50% reduction in 3-year LRF rate (one-sided α, 0.10; power 90%), assuming a 35% LRF rate from historical data. Results Poor risk features included stage III disease in 64% and male sex in 20%. The 3-year LRF rate was 23% (95% CI, 13% to 36%; one-sided P = .03) by binomial proportional estimate using the prespecified end point and 21% (95% CI, 7% to 26%) by Kaplan-Meier estimate in a post hoc analysis using methods consistent with historical data. Three-year rates were 68% (95% CI, 55% to 79%) for progression-free survival and 83% (95% CI, 71% to 91%) for overall survival. Grade 4 toxicity occurred in 32%, and 5% had treatment-associated deaths. Conclusion Although the addition of cetuximab to chemoradiation for SCCAC was associated with lower LRF rates than historical data with CRT alone, toxicity was substantial, and LRF still occurs in approximately 20%, indicating the continued need for more effective and less toxic therapies. PMID:28068178

Individualized Radiation Dose Escalation Based on the Decrease in Tumor FDG Uptake and Normal Tissue Constraints Improve Survival in Patients With Esophageal Carcinoma.

PubMed

Ma, Jinbo; Wang, Zhaoyang; Wang, Chengde; Chen, Ercheng; Dong, Yaozong; Song, Yipeng; Wang, Wei; You, Dong; Jiang, Wei; Zang, Rukun

2017-02-01

To determine whether individualized radiation dose escalation after planned chemoradiation based on the decrease in tumor and normal tissue constraints can improve survival in patients with esophageal carcinoma. From August 2005 to December 2010, 112 patients with squamous esophageal carcinoma were treated with radical concurrent chemoradiation. Patients received positron emission tomography-computer tomography scan twice, before radiation and after radiation dose of 50.4 Gy. All patients were noncomplete metabolic response groups according to the Response Evaluation Criteria in solid tumors. Only 52 patients with noncomplete metabolic response received individualized dose escalation based on tumor and normal tissue constraints. Survival and treatment failure were observed and analyzed using SPSS (13.0). The rate of complete metabolic response for patients with noncomplete metabolic response after dose escalation reached 17.3% (9 of 52). The 2-year overall survival rates for patients with noncomplete metabolic response in the conventional and dose-escalation groups were 20.5% and 42.8%, respectively( P = .001). The 2-year local control rates for patients were 35.7% and 76.2%, respectively ( P = .002). When patients were classified into partial metabolic response and no metabolic response, 2-year overall survival rates for patients with partial metabolic response were significantly different in conventional and dose-escalation groups (33.8% vs 78.4%; P = .000). The 2-year overall survival rates for patients with no metabolic response in two groups (8.6% vs 15.1%) did not significantly differ ( P = .917). Individualized radiation dose escalation has the potential to improve survival in patients with esophageal carcinoma according to increased rate of complete metabolic response. However, further trials are needed to confirm this and to identify patients who may benefit from dose escalation.

A Phase 1/2 Study of Definitive Chemoradiation Therapy Using Docetaxel, Nedaplatin, and 5-Fluorouracil (DNF-R) for Esophageal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ohnuma, Hiroyuki; Sato, Yasushi; Hirakawa, Masahiro

Purpose: Patient survival in esophageal cancer (EC) remains poor. The purpose of this study was to investigate a regimen of definitive chemoradiation therapy (CRT) that exerts good local control of EC. We performed a phase 1/2 study to assess the safety and efficacy of CRT with docetaxel, nedaplatin, and 5-fluorouracil (DNF-R). Methods and Materials: Eligible patients presented with stage IB to IV EC. Patients received 2 cycles of docetaxel (20, 30, or 40 mg/m{sup 2}) and nedaplatin (50 mg/m{sup 2}) on days 1 and 8 and a continuous infusion of 5-fluorouracil (400 mg/m{sup 2}/day) on days 1 to 5 and 8 to 12,more » every 5 weeks, with concurrent radiation therapy (59.4 Gy/33 fractions). The recommended dose (RD) was determined using a 3 + 3 design. Results: In the phase 1 study, the dose-limiting toxicities were neutropenia and thrombocytopenia. The RD of docetaxel was determined to be 20 mg/m{sup 2}. In the phase 2 study, grade 3 to 4 acute toxicities included neutropenia (42.8%), febrile neutropenia (7.14%), thrombocytopenia (17.9%), and esophagitis (21.4%). Grade 3 to 4 late radiation toxicity included esophagostenosis (10.7%). The complete response rate was 82.1% (95% confidence interval: 67.9-96.3%). Both the median progression-free survival and overall survival were 41.2 months. Conclusions: DNF-R showed good tolerability and strong antitumor activity, suggesting that it is a potentially effective therapeutic regimen for EC.« less

Dosimetric Predictors of Symptomatic Cardiac Events after Conventional-Dose Chemoradiation Therapy for Inoperable Non-Small Cell Lung Cancer.

PubMed

Yegya-Raman, Nikhil; Wang, Kyle; Kim, Sinae; Reyhan, Meral; Deek, Matthew P; Sayan, Mutlay; Li, Diana; Patel, Malini; Malhotra, Jyoti; Aisner, Joseph; Marks, Lawrence B; Jabbour, Salma K

2018-06-05

We hypothesized that higher cardiac doses correlates with clinically significant cardiotoxicity after standard-dose chemoradiation therapy (CRT) (∼60 Gy) for inoperable non-small cell lung cancer (NSCLC). We retrospectively reviewed the records of 140 patients with inoperable NSCLC treated with concurrent CRT from 2007-2015. Extracted data included baseline cardiac status, dosimetric parameters to the whole heart (WH) and cardiac substructures, and the development of post-CRT symptomatic cardiac events (acute coronary syndrome [ACS], arrhythmia, pericardial effusion, pericarditis, and congestive heart failure [CHF]). Competing risks analysis was used to estimate time to cardiac events. Median follow-up was 47.4 months. Median radiation therapy dose was 61.2 Gy (interquartile range, 60-66 Gy). Forty patients (28.6%) developed 47 symptomatic cardiac events at a median of 15.3 months to first event. On multivariate analysis, higher WH doses and baseline cardiac status were associated with an increased risk of symptomatic cardiac events. The 4-year cumulative incidence of symptomatic cardiac events was 48.6% versus 18.5% for mean WH dose ≥ 20 Gy versus < 20 Gy, respectively (p = 0.0002). Doses to the WH, ventricles, and left anterior descending artery were associated with ACS/CHF, whereas doses to the WH and atria were not associated with supraventricular arrhythmias. Symptomatic cardiac events (p = 0.0001) were independently associated with death. Incidental cardiac irradiation was associated with subsequent symptomatic cardiac events, particularly ACS/CHF, and symptomatic cardiac events were associated with inferior survival. These results support the minimization of cardiac doses among patients with inoperable NSCLC receiving standard-dose CRT. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Preoperative chemoradiation with capecitabine, irinotecan and cetuximab in rectal cancer: significance of pre-treatment and post-resection RAS mutations.

PubMed

Gollins, Simon; West, Nick; Sebag-Montefiore, David; Myint, Arthur Sun; Saunders, Mark; Susnerwala, Shabbir; Quirke, Phil; Essapen, Sharadah; Samuel, Leslie; Sizer, Bruce; Worlding, Jane; Southward, Katie; Hemmings, Gemma; Tinkler-Hundal, Emma; Taylor, Morag; Bottomley, Daniel; Chambers, Philip; Lawrie, Emma; Lopes, Andre; Beare, Sandy

2017-10-24

The influence of EGFR pathway mutations on cetuximab-containing rectal cancer preoperative chemoradiation (CRT) is uncertain. In a prospective phase II trial (EXCITE), patients with magnetic resonance imaging (MRI)-defined non-metastatic rectal adenocarinoma threatening/involving the surgical resection plane received pelvic radiotherapy with concurrent capecitabine, irinotecan and cetuximab. Resection was recommended 8 weeks later. The primary endpoint was histopathologically clear (R0) resection margin. Pre-planned retrospective DNA pyrosequencing (PS) and next generation sequencing (NGS) of KRAS, NRAS, PIK3CA and BRAF was performed on the pre-treatment biopsy and resected specimen. Eighty-two patients were recruited and 76 underwent surgery, with R0 resection in 67 (82%, 90%CI: 73-88%) (four patients with clinical complete response declined surgery). Twenty-four patients (30%) had an excellent clinical or pathological response (ECPR). Using NGS 24 (46%) of 52 matched biopsies/resections were discrepant: ten patients (19%) gained 13 new resection mutations compared to biopsy (12 KRAS, one PIK3CA) and 18 (35%) lost 22 mutations (15 KRAS, 7 PIK3CA). Tumours only ever testing RAS wild-type had significantly greater ECPR than tumours with either biopsy or resection RAS mutations (14/29 [48%] vs 10/51 [20%], P=0.008), with a trend towards increased overall survival (HR 0.23, 95% CI 0.05-1.03, P=0.055). This regimen was feasible and the primary study endpoint was met. For the first time using pre-operative rectal CRT, emergence of clinically important new resection mutations is described, likely reflecting intratumoural heterogeneity manifesting either as treatment-driven selective clonal expansion or a geographical biopsy sampling miss.

The Impact of Adjuvant Postoperative Radiation Therapy and Chemotherapy on Survival After Esophagectomy for Esophageal Carcinoma.

PubMed

Wong, Andrew T; Shao, Meng; Rineer, Justin; Lee, Anna; Schwartz, David; Schreiber, David

2017-06-01

The objective of this study was to analyze the impact on overall survival (OS) from the addition of postoperative radiation with or without chemotherapy after esophagectomy, using a large, hospital-based dataset. Previous retrospective studies have suggested an OS advantage for postoperative chemoradiation over surgery alone, although prospective data are lacking. The National Cancer Data Base was queried to select patients diagnosed with stage pT3-4Nx-0M0 or pT1-4N1-3M0 esophageal carcinoma (squamous cell or adenocarcinoma) from 1998 to 2011 treated with definitive esophagectomy ± postoperative radiation and/or chemotherapy. OS was analyzed using the Kaplan-Meier method and compared using the log-rank test. Multivariate Cox regression analysis was used to identify covariates associated with OS. There were 4893 patients selected, of whom 1153 (23.6%) received postoperative radiation. Most patients receiving radiation also received sequential/concomitant chemotherapy (89.9%). For the entire cohort, postoperative radiation was associated with a statistically significant but modest absolute improvement in survival (hazard ratio 0.77; 95% CI, 0.71-0.83; P < 0.001). On subgroup analysis, postoperative radiation was associated with improved OS for patients with node-positive disease (3-yr OS 34.3 % vs 27.8%, P < 0.001) or positive margins (3-yr OS 36.4% vs 18.0%, P < 0.001). When chemotherapy usage was incorporated, sequential chemotherapy was associated with the best survival (P < 0.001). Multivariate analysis revealed that the addition of chemotherapy to radiation therapy, whether sequentially or concurrently, was a strong prognostic factor for OS. In this hospital-based study, the addition of postoperative chemoradiation (either sequentially or concomitantly) after esophagectomy was associated with improved OS for patients with node-positive disease or positive margins.

Short-term psychodynamic therapy for obsessive-compulsive disorder: A manual-guided approach to treating the "inhibited rebel".

PubMed

Leichsenring, Falk; Steinert, Christiane

2017-01-01

Obsessive-compulsive disorder (OCD) is a chronic disabling disorder characterized by recurrent obsessions and uncontrolled compulsions. Recent research on anxiety disorders suggests that manual-guided short-term psychodynamic therapy (STPP) may be a promising approach. Building on this, a model of STPP for OCD was developed based on Luborsky's supportive-expressive (SE) therapy. Treatment consists of 12 modules, which include the characteristic elements of SE therapy, that is, a focus on the Core Conflictual Relationship Theme (CCRT) associated with OCD symptoms and on establishing a secure alliance. Disorder-specific treatment elements were integrated, including addressing ambivalence, differentiating between thinking and acting, mitigating the superego, addressing existential issues, and, last but not least, implementing Freud's original recommendation to induce OCD patients to face the feared situation and to use the aroused experiences to work on the underlying conflict (i.e., CCRT). There are reasons to assume that the empirically derived model of STPP described here may be beneficial in OCD.

Gene Expression Changes in Cervical Squamous Cell Carcinoma After Initiation of Chemoradiation and Correlation With Clinical Outcome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Klopp, Ann H.; Jhingran, Anuja; Ramdas, Latha

2008-05-01

Purpose: The purpose of this study was to investigate early gene expression changes after chemoradiation in a human solid tumor, allowing identification of chemoradiation-induced gene expression changes in the tumor as well as the tumor microenvironment. In addition we aimed to identify a gene expression profile that was associated with clinical outcome. Methods and Materials: Microarray experiments were performed on cervical cancer specimens obtained before and 48 h after chemoradiation from 12 patients with Stage IB2 to IIIB squamous cell carcinoma of the cervix treated between April 2001 and August 2002. Results: A total of 262 genes were identified thatmore » were significantly changed after chemoradiation. Genes involved in DNA repair were identified including DDB2, ERCC4, GADD45A, and XPC. In addition, significantly regulated cell-to-cell signaling pathways included insulin-like growth factor-1 (IGF-1), interferon, and vascular endothelial growth factor signaling. At a median follow-up of 41 months, 5 of 12 patients had experienced either local or distant failure. Supervised clustering analysis identified a 58-gene set from the pretreatment samples that were differentially expressed between patients with and without recurrence. Genes involved in integrin signaling and apoptosis pathways were identified in this gene set. Immortalization-upregulated protein (IMUP), IGF-2, and ARHD had particularly marked differences in expression between patients with and without recurrence. Conclusions: Genetic profiling identified genes regulated by chemoradiation including DNA damage and cell-to-cell signaling pathways. Genes associated with recurrence were identified that will require validation in an independent patient data set to determine whether the 58-gene set associated with clinical outcome could be useful as a prognostic assay.« less

Effects of Change in Tongue Pressure and Salivary Flow Rate on Swallow Efficiency Following Chemoradiation Treatment for Head and Neck Cancer

PubMed Central

Rogus-Pulia, Nicole M.; Larson, Charles; Mittal, Bharat B; Pierce, Marge; Zecker, Steven; Kennelty, Korey; Kind, Amy; Connor, Nadine P.

2016-01-01

Purpose Patients treated with chemoradiation for head and neck cancer frequently develop dysphagia. Tissue damage to the oral tongue causing weakness and decreases in saliva production may contribute to dysphagia. Yet, effects of these variables on swallowing-related measures are unclear. The purpose of this study was (1) to determine effects of chemoradiation on tongue pressures, as a surrogate for strength, and salivary flow rates and (2) to elucidate relationships among tongue pressures, saliva production, and swallowing efficiency by bolus type. Methods and Materials 21 patients with head and neck cancer treated with chemoradiation were assessed before and after treatment and matched with 21 healthy control participants who did not receive chemoradiation. Each participant was given a questionnaire to rate dysphagia symptoms. Videofluoroscopic evaluation of swallowing was used to determine swallowing efficiency; the Saxon test measured salivary flow rate; and the Iowa Oral Performance Instrument (IOPI) was used for oral tongue maximum and endurance measures. Results Results revealed significantly lower tongue endurance measures for patients post-treatment as compared to controls (p=.012). Salivary flow rates also were lower compared to pre-treatment (p=.000) and controls (p=.000). Simple linear regression analyses showed that change in salivary flow rate was predictive of change in swallow efficiency measures from pre- to post-treatment for 1mL thin liquid (p=.017), 3mL nectar-thick liquid (p=.026), and 3mL standard barium pudding (p=.011) boluses. Conclusions Based on these findings, it appears that chemoradiation treatment affects tongue endurance and salivary flow rate and these changes may impact swallow efficiency. These factors should be considered when planning treatment for dysphagia. PMID:27492408

Utility of Adjuvant Chemotherapy After Neoadjuvant Chemoradiation and Esophagectomy for Esophageal Cancer.

PubMed

Burt, Bryan M; Groth, Shawn S; Sada, Yvonne H; Farjah, Farhood; Cornwell, Lorraine; Sugarbaker, David J; Massarweh, Nader N

2017-08-01

To determine whether adjuvant chemotherapy (AC) after neoadjuvant chemoradiation and esophagectomy is associated with improved overall survival for patients with locally advanced esophageal cancer, and to evaluate how pathologic disease response to neoadjuvant treatment impacts this effect. Neoadjuvant chemoradiation is currently the preferred management approach for locoregional esophageal cancer. Although there is interest in the use of AC, the benefit of systemic therapy after neoadjuvant chemoradiation and esophagectomy is unclear. Retrospective cohort study of patients with esophageal cancer treated with neoadjuvant chemoradiation and esophagectomy in the National Cancer Data Base (2006-2012). Among 3592 patients with esophageal cancer (84.7% adenocarcinoma, 15.2% squamous cell carcinoma), 335 (9.3%) were treated with AC. AC was not associated with a significantly lower risk of death among patients with no residual disease (ypT0N0) or residual non-nodal disease (ypT+N0). Among patients with residual nodal disease (ypTanyN+), AC was associated with a 30% lower risk of death in the overall cohort [hazard ratio (HR) 0.70, (0.57-0.85)] and among those with adenocarcinoma [HR 0.69 (0.57-0.85)]. Using a 90-day postoperative landmark, findings were similar. Among patients with postoperative length of stay ≤10 days and no unplanned readmission, AC was associated with approximately 40% lower risk of death among patients with residual nodal disease [overall cohort, HR 0.63 (0.48-0.84); adenocarcinoma, HR 0.66 (0.49-0.88)]. AC after neoadjuvant chemoradiation and esophagectomy is associated with improved survival in patients with residual nodal disease. Our findings suggest AC may provide additional benefit for esophageal cancer patients, and merits further investigation.

Esophageal Cancer: New Insights into a Heterogenous Disease.

PubMed

Krug, Sebastian; Michl, Patrick

2017-01-01

Esophageal cancer represents a heterogeneous malignancy mostly diagnosed in advanced stages. Worldwide, squamous cell carcinomas (SCCs) continue to be the most prevalent subtype; however, in the Western countries, the incidence of adenocarcinomas is increasing and will exceed that of SCC in the near future. During the last decade, several landmark trials contributed to a better understanding of the disease and emphasized the importance of multimodal treatment protocols. With the introduction of perioperative or neoadjuvant approaches, the survival of both subtypes of esophageal cancer has significantly improved. Several trials confirmed a survival benefit for perioperative chemotherapy or neoadjuvant chemoradiation, respectively, for patients with resectable locally advanced adenocarcinomas. However, the question of whether perioperative chemotherapy or neoadjuvant chemoradiation is more effective for the long-term survival in this population has yet to be fully elucidated. In SCCs, neoadjuvant chemoradiation followed by surgery or definitive chemoradiation in case of functional inoperability represent the preferred treatment options. Compared to neoadjuvant protocols, adjuvant chemotherapy or chemoradiation have only minor effects and are associated with enhanced toxicities. Current preclinical and clinical trials investigate efficacy and tolerability of novel drugs aiming to modulate immune check-points and dual inhibition of HER2. In this "to-the-point" article, we review the current standard and summarize the most recent and encouraging therapeutic advances in esophageal cancer. Multimodal treatment approaches for esophageal cancer should be discussed in a multidisciplinary team based on histology, tumor localization, and patient performance status. Neoadjuvant chemoradiation is beneficial for patients with locally advanced SCC and adenocarcinomas of the esophagus and the gastroesophageal junction (GEJ), with perioperative chemotherapy representing a valid alternative for GEJ adenocarcinomas. Combination therapies are indicated for metastatic adenocarcinomas, while the benefit of palliative chemotherapy in SCC remains controversial. Trastuzumab is indicated in HER2+ metastatic adenocarcinomas. © 2017 S. Karger AG, Basel.

Long-term complications of definitive chemoradiotherapy for esophageal cancer using the classical method.

PubMed

Ito, Hitoshi; Itasaka, Satoshi; Sakanaka, Katsuyuki; Araki, Norio; Mizowaki, Takashi; Hiraoka, Masahiro

2017-01-01

Chemoradiation therapy is widely used to treat both inoperable and operable patients, and is less invasive than surgery. Although the number of long-term survivors who have received chemoradiation therapy is increasing, the long-term toxicity pattern and cumulative incidence of toxicity regarding this modality are poorly understood. Classically, chemoradiation therapy for esophageal cancer consists of an anterior-posterior field and a subsequent oblique boost field. We retrospectively analyzed patients who were treated with definitive chemoradiation therapy for esophageal cancer using this classical method from 1999 to 2008. For the assessment of toxicity, the National Cancer Institute Common Toxicity Criteria Version 3.0 was adopted. A total of 101 patients were analyzed. The median follow-up time was 16 months for all patients and 62 months for the surviving patients. Eleven patients experienced late toxicities of ≥Grade 3. Two patients died of late toxicities. The 3- and 5-year cumulative incidences for the first late cardiopulmonary toxicities of ≥Grade 3 were 17.4% and 20.8%, respectively. Cardiopulmonary effusions were observed within the first 3 years of completion of the initial treatment in seven out of eight patients. Sudden death and cardiac ischemia were observed over a 10-year period. Older age was found to be a risk factor for late toxicity after definitive chemoradiation therapy for esophageal cancer. Substantial toxicities were observed in patients who had received chemoradiation therapy for esophageal cancer using the classical method. To minimize the incidence of late toxicity, more sophisticated radiation techniques may be useful. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

A phase I study evaluating the role of the anti-epidermal growth factor receptor (EGFR) antibody cetuximab as a radiosensitizer with chemoradiation for locally advanced pancreatic cancer

PubMed Central

Arnoletti, J. P.; Frolov, A.; Eloubeidi, M.; Keene, K.; Posey, J.; Wood, T.; Greeno, Edward; Jhala, N.; Varadarajulu, S.; Russo, S.; Christein, J.; Oster, R.; Buchsbaum, D. J.; Vickers, S. M.

2012-01-01

Purpose (1) To determine the safety of the epidermal growth factor receptor (EGFR) antibody cetuximab with concurrent gemcitabine and abdominal radiation in the treatment of patients with locally advanced adenocarcinoma of the pancreas. (2) To evaluate the feasibility of pancreatic cancer cell epithelial–mesenchymal transition (EMT) molecular profiling as a potential predictor of response to anti-EGFR treatment. Methods Patients with non-metastatic, locally advanced pancreatic cancer were treated in this dose escalation study with gemcitabine (0–300 mg/m2/week) given concurrently with cetuximab (400 mg/m2 loading dose, 250 mg/m2 weekly maintenance dose) and abdominal irradiation (50.4 Gy). Expression of E-cadherin and vimentin was assessed by immunohistochemistry in diagnostic endoscopic ultrasound fine-needle aspiration (EUS-FNA) specimens. Results Sixteen patients were enrolled in 4 treatment cohorts with escalating doses of gemcitabine. Incidence of grade 1–2 adverse events was 96%, and incidence of 3–4 adverse events was 9%. There were no treatment-related mortalities. Two patients who exhibited favorable treatment response underwent surgical exploration and were intraoperatively confirmed to have unresectable tumors. Median overall survival was 10.5 months. Pancreatic cancer cell expression of E-cadherin and vimentin was successfully determined in EUS-FNA specimens from 4 patients. Conclusions Cetuximab can be safely administered with abdominal radiation and concurrent gemcitabine (up to 300 mg/m2/week) in patients with locally advanced adenocarcinoma of the pancreas. This combined therapy modality exhibited limited activity. Diagnostic EUS-FNA specimens could be analyzed for molecular markers of EMT in a minority of patients with pancreatic cancer. PMID:20589377

Concurrent Chemoradiotherapy With Helical Tomotherapy for Oropharyngeal Cancer: A Preliminary Result

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shueng, Pei-Wei; Department of Radiation Oncology, National Defense Medical Center, Taipei, Taiwan; General Education Center, Oriental Technology Institute, Taipei, Taiwan

Purpose: To review the experience with and evaluate the treatment plan for helical tomotherapy for the treatment of oropharyngeal cancer. Methods and Materials: Between November 1, 2006 and January 31, 2009, 10 histologically confirmed oropharyngeal cancer patients were enrolled. All patients received definitive concurrent chemoradiation with helical tomotherapy. The prescription dose to the gross tumor planning target volume, the high-risk subclinical area, and the low-risk subclinical area was 70Gy, 63Gy, and 56Gy, respectively. During radiotherapy, all patients were treated with cisplatin, 30mg/m{sup 2}, plus 5-fluorouracil (425mg/m{sup 2})/leucovorin (30mg/m{sup 2}) intravenously weekly. Toxicity of treatment was scored according to the Commonmore » Terminology Criteria for Adverse Events, version 3.0. Several parameters, including maximal or median dose to critical organs, uniformity index, and conformal index, were evaluated from dose-volume histograms. Results: The mean survival was 18 months (range, 7-22 months). The actuarial overall survival, disease-free survival, locoregional control, and distant metastasis-free rates at 18 months were 67%, 70%, 80%, and 100%, respectively. The average for uniformity index and conformal index was 1.05 and 1.26, respectively. The mean of median dose for right side and left side parotid glands was 23.5 and 23.9Gy, respectively. No Grade 3 toxicity for dermatitis and body weight loss and only one instance of Grade 3 mucositis were noted. Conclusion: Helical tomotherapy achieved encouraging clinical outcomes in patients with oropharyngeal carcinoma. Treatment toxicity was acceptable, even in the setting of concurrent chemotherapy. Long-term follow-up is needed to confirm these preliminary findings.« less

Organ Preservation With Concurrent Chemoradiation for Advanced Laryngeal Cancer: Are We Succeeding?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lambert, Louise, E-mail: louise.lambert@gmail.co; Fortin, Bernard; Soulieres, Denis

2010-02-01

Purpose: To determine the rates of organ preservation and function in patients with advanced laryngeal and hypopharyngeal carcinomas treated with concurrent chemoradiotherapy (CRT). Methods and Materials: Between April 1999 and September 2005, 82 patients with advanced laryngeal (67%) and hypopharyngeal carcinomas (33%) underwent conventional radiotherapy and concurrent platinum-based chemotherapy with curative intent. Sixty-two patients were male (75.6%). The median age was 59 years. Eighteen patients (22%) were in Stage III and 64 (78%) were in Stage IV. The median radiation dose was 70 Gy. The median potential follow-up was 3.9 years. Results: Overall survival and disease-free survival were respectively 63%more » and 73% at 3 years. Complete response rate from CRT was 75%. Nineteen patients (23%) experienced significant long-term toxicity after CRT: 6 (7.3%) required a percutaneous endoscopic gastrostomy, 5 (6%) had persistent Grade 2 or 3 dysphagia, 2 (2.4%) had pharyngoesophageal stenosis requiring multiple dilations, 2 (2.4%) had chronic lung aspiration, and 7 (8.5%) required a permanent tracheostomy. Four patients (4.9%) underwent laryngectomy without pathologic evidence of disease. At last follow-up, 5 (6%) patients were still dependent on a gastrostomy. Overall, 42 patients (52%) were alive, in complete response, with a functional larynx and no other major complications. Conclusions: In our institution, CRT for advanced hypopharyngeal and laryngeal carcinoma has provided good overall survival and locoregional control in the majority of patients, but a significant proportion did not benefit from this approach because of either locoregional failure or late complications. Better organ preservation approaches are necessary to improve locoregional control and to reduce long-term toxicities.« less

Community Cohesion: A Report of the Independent Review Team.

ERIC Educational Resources Information Center

Home Office, London (England).

This study examined the views of English citizens and community leaders regarding problems related to disaffected, disadvantaged, culturally diverse groups. The Community Cohesion Review Team (CCRT) investigated issues needing to be addressed to bring about social cohesion. Communities were deeply polarized, with separate educational systems,…

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang Shulian; Liao Zhongxing; Vaporciyan, Ara A.

Purpose: To assess the association of clinical and especially dosimetric factors with the incidence of postoperative pulmonary complications among esophageal cancer patients treated with concurrent chemoradiation therapy followed by surgery. Method and Materials: Data from 110 esophageal cancer patients treated between January 1998 and December 2003 were analyzed retrospectively. All patients received concurrent chemoradiotherapy followed by surgery; 72 patients also received irinotecan-based induction chemotherapy. Concurrent chemotherapy was 5-fluorouracil-based and in 97 cases included taxanes. Radiotherapy was delivered to a total dose of 41.4-50.4 Gy at 1.8-2.0 Gy per fraction with a three-dimensional conformal technique. Surgery (three-field, Ivor-Lewis, or transhiatal esophagectomy)more » was performed 27-123 days (median, 45 days) after completion of radiotherapy. The following dosimetric parameters were generated from the dose-volume histogram (DVH) for total lung: lung volume, mean dose to lung, relative and absolute volumes of lung receiving more than a threshold dose (relative V{sub dose} and absolute V{sub dose}), and absolute volume of lung receiving less than a threshold dose (volume spared, or VS{sub dose}). Occurrence of postoperative pulmonary complications, defined as pneumonia or acute respiratory distress syndrome (ARDS) within 30 days after surgery, was the endpoint for all analyses. Fisher's exact test was used to investigate the relationship between categorical factors and incidence of postoperative pulmonary complications. Logistic analysis was used to analyze the relationship between continuous factors (e.g., V{sub dose} or VS{sub dose}) and complication rate. Logistic regression with forward stepwise inclusion of factors was used to perform multivariate analysis of those factors having univariate significance (p < 0.05). The Mann-Whitney test was used to compare length of hospital stay in patients with and without lung complications and to compare lung volumes, VS5 values, and absolute and relative V5 values in male vs. female patients. Pearson correlation analysis was used to determine correlations between dosimetric factors. Results: Eighteen (16.4%) of the 110 patients developed postoperative pulmonary complications. Two of these died of progressive pneumonia. Hospitalizations were significantly longer for patients with postoperative pulmonary complications than for those without (median, 15 days vs. 11 days, p = 0.003). On univariate analysis, female gender (p = 0.017), higher mean lung dose (p = 0.036), higher relative volume of lung receiving {>=}5 Gy (V5) (p = 0.023), and smaller volumes of lung spared from doses {>=}5-35 Gy (VS5-VS35) (p < 0.05) were all significantly associated with an increased incidence of postoperative pulmonary complications. No other clinical factors were significantly associated with the incidence of postoperative pulmonary complications in this cohort. On multivariate analysis, the volume of lung spared from doses {>=}5 Gy (VS5) was the only significant independent factor associated with postoperative pulmonary complications (p = 0.005). Conclusions: Dosimetric factors but not clinical factors were found to be strongly associated with the incidence of postoperative pulmonary complications in this cohort of esophageal cancer patients treated with concurrent chemoradiation plus surgery. The volume of the lung spared from doses of {>=}5 Gy was the only independent dosimetric factor in multivariate analysis. This suggests that ensuring an adequate volume of lung unexposed to radiation might reduce the incidence of postoperative pulmonary complications.« less

Role of secondary low energy electrons in radiobiology and chemoradiation therapy of cancer

NASA Astrophysics Data System (ADS)

Sanche, Léon

2009-05-01

With the chemotherapeutic agent cisplatin bound to DNA, damage to the molecule by electrons of low and high energies increases by factors varying from 1.3 to 4.4. The enhancement in bond dissociation is triggered by modifications of the interaction of low energy electrons with DNA. From our understanding of the latter, the present Letter attempts to explain the basic radiation-damage mechanism responsible for the efficiency of the concomitant chemoradiation treatment of cancer. Such a basic comprehension of the direct effects of radiation may have implications in the design of new chemotherapeutic and radiosensitizing drugs, as well as in the development of more efficient protocols in chemoradiation therapy.

Mortality following single-fraction stereotactic body radiation therapy for central pulmonary oligometastasis

PubMed Central

Ma, Sung Jun; Mix, Michael; Rivers, Charlotte; Hennon, Mark; Gomez, Jorge

2017-01-01

The case of a 56-year-old male who developed bronchopulmonary hemorrhage after a course of stereotactic body radiation therapy (SBRT) for centrally located squamous cell lung carcinoma is presented. The patient was previously treated with concurrent chemoradiation for stage IVA squamous cell carcinoma of the base of tongue. He showed no evidence of disease for 4 years until he developed a solitary metastasis of squamous cell carcinoma in the right hilum. He underwent a single fraction of 26 Gy with heterogeneity correction. He showed no evidence of disease for 13 months until he developed a sudden grade 4 bronchopulmonary hemorrhage. He underwent an urgent right pneumonectomy and later died of a post-operative complication. Pathologic analysis of the specimen revealed no evidence of tumor. Single-fraction SBRT of 26 Gy was sufficient to achieve complete response of his large central lung tumor. However, when treating patients with central lung tumors, some risk of mortality may be unavoidable with either SBRT or pneumonectomy. PMID:29296456

[Nasopharyngeal adenoid cystic carcinoma, a rare but highly challenging disease with unmet therapeutic needs: A case-report and review of the literature].

PubMed

Afani, L; Errihani, H; Benchafai, I; Lalami, Y

2016-07-01

Nasopharyngeal adenoid cystic carcinoma is a rare tumour. Compared with others nasopharyngeal tumours, it is characterised by slow evolution but it is locally aggressive and has a high tendency to recurrences. Due to the rarity of cases, no consensus exists about treatment approaches. We report the case of 45-year-old-man with a locally advanced adenoid cystic carcinoma. The patient received concurrent chemoradiation and had a good objective response. After one year, he developed a paucisymptomatic lung metastasis. The follow-up showed local recurrence after 3 years. One cycle of chemotherapy was given but poorly supported. Carbon ion radiotherapy was proposed. The aim of this work is to review the literature concerning this rare malignancy and discusses treatment approaches in initial situations and during recurrences. Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

On-demand intracellular amplification of chemoradiation with cancer-specific plasmonic nanobubbles.

PubMed

Lukianova-Hleb, Ekaterina Y; Ren, Xiaoyang; Sawant, Rupa R; Wu, Xiangwei; Torchilin, Vladimir P; Lapotko, Dmitri O

2014-07-01

Chemoradiation-resistant cancers limit treatment efficacy and safety. We show here the cancer cell-specific, on-demand intracellular amplification of chemotherapy and chemoradiation therapy via gold nanoparticle- and laser pulse-induced mechanical intracellular impact. Cancer aggressiveness promotes the clustering of drug nanocarriers and gold nanoparticles in cancer cells. This cluster, upon exposure to a laser pulse, generates a plasmonic nanobubble, the mechanical explosion that destroys the host cancer cell or ejects the drug into its cytoplasm by disrupting the liposome and endosome. The same cluster locally amplifies external X-rays. Intracellular synergy of the mechanical impact of plasmonic nanobubble, ejected drug and amplified X-rays improves the efficacy of standard chemoradiation in resistant and aggressive head and neck cancer by 100-fold in vitro and 17-fold in vivo, reduces the effective entry doses of drugs and X-rays to 2-6% of their clinical doses and efficiently spares normal cells. The developed quadrapeutics technology combines four clinically validated components and transforms a standard macrotherapy into an intracellular on-demand theranostic microtreatment with radically amplified therapeutic efficacy and specificity.

On-demand intracellular amplification of chemoradiation with cancer-specific plasmonic nanobubbles

PubMed Central

Lukianova-Hleb, Ekaterina Y; Wu, Xiangwei; Torchilin, Vladimir P; Lapotko, Dmitri O

2014-01-01

Chemoradiation-resistant cancers limit treatment efficacy and safety. We show here the cancer cell–specific, on-demand intracellular amplification of chemotherapy and chemoradiation therapy via gold nanoparticle– and laser pulse–induced mechanical intracellular impact. Cancer aggressiveness promotes the clustering of drug nanocarriers and gold nanoparticles in cancer cells. This cluster, upon exposure to a laser pulse, generates a plasmonic nanobubble, the mechanical explosion that destroys the host cancer cell or ejects the drug into its cytoplasm by disrupting the liposome and endosome. The same cluster locally amplifies external X-rays. Intracellular synergy of the mechanical impact of plasmonic nanobubble, ejected drug and amplified X-rays improves the efficacy of standard chemoradiation in resistant and aggressive head and neck cancer by 100-fold in vitro and 17-fold in vivo, reduces the effective entry doses of drugs and X-rays to 2–6% of their clinical doses and efficiently spares normal cells. The developed quadrapeutics technology combines four clinically validated components and transforms a standard macrotherapy into an intracellular on-demand theranostic microtreatment with radically amplified therapeutic efficacy and specificity. PMID:24880615

Leukocytosis and neutrophilia predict outcome in locally advanced esophageal cancer treated with definitive chemoradiation

PubMed Central

Schernberg, Antoine; Moureau-Zabotto, Laurence; Del Campo, Eleonor Rivin; Escande, Alexandre; Ducreux, Michel; Nguyen, France; Goere, Diane; Chargari, Cyrus; Deutsch, Eric

2017-01-01

Purpose To investigate the prognostic value of leukocyte and neutrophil count as biomarkers in patients with locally advanced esophageal squamous cell carcinoma (SCC) undergoing exclusive chemoradiation. Results A total of 126 patients were identified. Respectively, 33% and 35% displayed baseline leukocytosis and neutrophilia. Estimated 3-year OS and PFS from chemoradiation completion were 31% and 25%, respectively. In univariate analysis, both leukocytosis and neutrophilia were associated with worse OS, PFS, and LRC (p < 0.01). In multivariate analysis, leukocytosis remained an independent risk factor associated with poorer OS, PFS and LRC (p < 0.05), independently from tumor stage and length, with higher prognostic value for OS compared with patients’ performance status (PS). Materials and Methods Bi-institutional clinical records from consecutive non-operable patients treated between 2003 and 2015 with definitive chemoradiation for locally advanced esophageal carcinoma were reviewed. Leukocytosis and neutrophilia were defined as a leukocyte or neutrophil count over 10 G/L and 7 G/L, respectively. These parameters were studied for their potential correlation with overall survival (OS), progression free survival (PFS), locoregional control (LRC) and distant metastases control (DMC). Conclusions Leukocytosis and neutrophilia were independent prognostic factors of poor OS, PFS, and LRC in this bi-institutional series of locally advanced esophageal SCC treated with definitive chemoradiation. Although prospective confirmation is warranted, it is suggested that the leukocyte and neutrophil count parameters might be clinically relevant biomarkers to be considered for further clinical investigations. PMID:28086222

[Detection and prognostic significance of micrometastasis in peripheral blood of patients with non-small cell lung cancer treated by chemo-radiation therapy].

PubMed

Chen, Ting-feng; Jiang, Guo-liang; Zhang, Yi-qin; Wang, Li-juan; Fu, Xiao-long; Qian, Hao; Wu, Kai-liang; Zhao, Sen

2007-05-01

To investigate the prognostic significance of micrometastasis (MM) in peripheral blood of patients with non-small cell lung cancer (NSCLC) treated by chemo-radiation therapy. Peripheral blood was taken from 67 NSCLC patients before and after definitive chemo-radiation therapy. CK19 mRNA of the peripheral blood was measured by nested RT-PCR and both their relationship with clinicopathological features and prognostic significance were further investigated. The micrometastasis-positive rates were 65.7% (44/67) and 32.8% (22/67), respectively, before and after the treatment. The micrometastasis-positive rate before treatment was closely in correlation with N-stage (P = 0.014). In contrast, it turned out to be more closely related with histological types (P = 0.019), weight loss (P = 0.01), KPS status (P = 0.027) as well as N-stage (P = 0.032) after chemo-radiation therapy. 4-yr distant metastasis rates (DMR) for micrometastasis-positive and -negative patients were 78.3% and 70.4%, respectively, before the treatment (P = 0.544) while they were 100% and 62.9%, respectively, after the chemoradiation (P < 0.001). The median survival time (MST) and 4-yr overall survival rate (OSR) for pretreatment micrometastasis-positive and -negative patients were 13.8 months and 17.6 months, and 18.2% and 17.4%, respectively (P = 0.619), while for post-treatment micrometastasis-positive and -negative patients they were 7.8 months and 27.6 months and 0 and 26.4%, respectively (P < 0.001). Multivariate analysis showed that the post-treatment positive micrometastasis was an independent unfavorable prognostic factor (P = 0.000). Detection of micrometastasis in peripheral blood may possess a prognostic significance after definitive chemo-radiation therapy. Micrometastasis-negative patients have better prognosis compared to those with positive micrometastasis.

The effect of a supersaturated calcium phosphate mouth rinse on the development of oral mucositis in head and neck cancer patients treated with (chemo)radiation: a single-center, randomized, prospective study of a calcium phosphate mouth rinse + standard of care versus standard of care.

PubMed

Lambrecht, Maarten; Mercier, Carole; Geussens, Yasmyne; Nuyts, Sandra

2013-10-01

Mucosal damage is an important and debilitating side effect when treating head and neck cancer patients with (chemo-)radiation. The aim of this randomized clinical trial was to investigate whether the addition of a neutral, supersaturated, calcium phosphate (CP) mouth rinse benefits the severity and duration of acute mucositis in head and neck cancer patients treated with (chemo)radiation. A total of 60 patients with malignant neoplasms of the head and neck receiving (chemo)radiation were included in this study. Fifty-eight patients were randomized into two treatment arms: a control group receiving standard of care (n = 31) and a study group receiving standard of care + daily CP mouth rinses (n = 27) starting on the first day of (chemo-)radiation. Oral mucositis and dysphagia were assessed twice a week using the National Cancer Institute common toxicity criteria scale version 3, oral pain was scored with a visual analogue scale. No significant difference in grade III mucositis (59 vs. 71 %; p = 0.25) and dysphagia (33 vs. 42 %, p = 0.39) was observed between the study group compared to the control group. Also no significant difference in time until development of peak mucositis (28.6 vs. 28.7 days; p = 0.48), duration of peak mucositis (22.7 vs. 24.6 days; p = 0.31), recuperation of peak dysphagia (20.5 vs 24.2 days; p = 0.13) and occurrence of severe pain (56 vs. 52 %, p = 0.5). In this randomized study, the addition of CP mouth rinse to standard of care did not improve the frequency, duration or severity of the most common acute toxicities during and early after (chemo)radiation. There is currently no evidence supporting its standard use in daily practice.

Anti-EGFR targeted therapy delivered before versus during radiotherapy in locoregionally advanced nasopharyngeal carcinoma: a big-data, intelligence platform-based analysis.

PubMed

Peng, Hao; Tang, Ling-Long; Liu, Xu; Chen, Lei; Li, Wen-Fei; Mao, Yan-Ping; Zhang, Yuan; Liu, Li-Zhi; Tian, Li; Guo, Ying; Sun, Ying; Ma, Jun

2018-03-27

Little is known about the prognostic difference of anti-EGFR therapy, cetuximab (CTX) or nimotuzumab (NTZ), concurrently with induction chemotherapy (IC, investigational arm) or RT (control arm) for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). We conducted this retrospective study to address this. We identified 296 patients with newly diagnosed LA-NPC at Sun Yat-Sen University Cancer Center between January 2012 and May 2015. Patients were treated by IC with CCRT or RT and CTX/NTZ was delivered during IC or radiotherapy. Survival outcomes and toxicities between different arms were compared. In total, there were 149 patients in the investigational arm and 147 in control arm. The 3-year disease-free survival, overall survival, distant metastasis-free survival and locoregional relapse-free survival rates for investigational arm vs. control arm were 84.3% vs. 74.3% (P = 0.027), 94.0% vs. 92.1% (P = 0.673), 88.0% vs. 81.8% (P = 0.147) and 93.3% vs. 88.0% (P = 0.093). Multivariate analysis revealed patients in the control arm achieved significantly worse disease-free survival (HR, 1.497; 95% CI, 1.016-2.206; P = 0.026) compared with those in the investigational arm; however, no significant difference was identified for other endpoints. Patients in the investigational arm experienced more grade 3-4 skin reaction (15.4% vs. 2.0%, P <  0.001) and mucositis (10.1% vs. 3.4%, P = 0.022) during induction phase, but less skin reaction (5.4% vs. 25.9%, P <  0.001) and mucositis (24.8% vs. 36.7%, P = 0.026) during RT. Our findings suggested that CTX/NTZ concurrently with IC may be a more effective and promising strategy for patients with LA-NPC receiving intensity-modulated radiotherapy.

Factors Associated With Early Mortality in Patients Treated With Concurrent Chemoradiation Therapy for Locally Advanced Non-Small Cell Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Warner, Andrew; Dahele, Max; Hu, Bo

Purpose: Concurrent chemoradiation therapy (con-CRT) is recommended for fit patients with locally advanced non-small cell lung cancer (LA-NSCLC) but is associated with toxicity, and observed survival continues to be limited. Identifying factors associated with early mortality could improve patient selection and identify strategies to improve prognosis. Methods and Materials: Analysis of a multi-institutional LA-NSCLC database consisting of 1245 patients treated with con-CRT in 13 institutions was performed to identify factors predictive of 180-day survival. Recursive partitioning analysis (RPA) was performed to identify prognostic groups for 180-day survival. Multivariate logistic regression analysis was used to create a clinical nomogram predicting 180-daymore » survival based on important predictors from RPA. Results: Median follow-up was 43.5 months (95% confidence interval [CI]: 40.3-48.8) and 127 patients (10%) died within 180 days of treatment. Median, 180-day, and 1- to 5-year (by yearly increments) actuarial survival rates were 20.9 months, 90%, 71%, 45%, 32%, 27%, and 22% respectively. Multivariate analysis adjusted by region identified gross tumor volume (GTV) (odds ratio [OR] ≥100 cm{sup 3}: 2.61; 95% CI: 1.10-6.20; P=.029) and pulmonary function (forced expiratory volume in 1 second [FEV{sub 1}], defined as the ratio of FEV{sub 1} to forced vital capacity [FVC]) (OR <80%: 2.53; 95% CI: 1.09-5.88; P=.030) as significant predictors of 180-day survival. RPA resulted in a 2-class risk stratification system: low-risk (GTV <100 cm{sup 3} or GTV ≥100 cm{sup 3} and FEV{sub 1} ≥80%) and high-risk (GTV ≥100 cm{sup 3} and FEV{sub 1} <80%). The 180-day survival rates were 93% for low risk and 79% for high risk, with an OR of 4.43 (95% CI: 2.07-9.51; P<.001), adjusted by region. A clinical nomogram predictive of 180-day survival, incorporating FEV{sub 1}, GTV, N stage, and maximum esophagus dose yielded favorable calibration (R{sup 2} = 0.947). Conclusions: This analysis identified several risk factors associated with early mortality and suggests that future research in the optimization of pretreatment pulmonary function and/or functional lung avoidance treatment may alter the therapeutic ratio in this patient population.« less

Nutrition therapy in esophageal cancer-Consensus statement of the Gastroenterological Society of Taiwan.

PubMed

Chen, M-J; Wu, I-C; Chen, Y-J; Wang, T-E; Chang, Y-F; Yang, C-L; Huang, W-C; Chang, W-K; Sheu, B-S; Wu, M-S; Lin, J-T; Chu, C-H

2018-05-31

A number of clinical guidelines on nutrition therapy in cancer patients have been published by national and international societies; however, most of the reviewed data focused on gastrointestinal cancer or non-cancerous abdominal surgery. To collate the corresponding data for esophageal cancer (EC), a consensus panel was convened to aid specialists from different disciplines, who are involved in the clinical nutrition care of EC patients. The literature was searched using MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and the ISI Web of Knowledge. We searched for the best evidence pertaining to nutrition therapy in the case of EC. The panel summarized the findings in 3 sections of this consensus statement, based on which, after the diagnosis of EC, an initial distinction is made between the patients, as follows: (1) Assessment; (2) Therapy in patients with resectable disease; patients receiving chemotherapy or chemoradiotherapy prior to resection, and patients with unresectable disease, requiring chemoradiotherapy or palliative therapy; and (3) Formula. The resulting consensus statement reflects the opinions of a multidisciplinary group of experts, and a review of the current literature, and outlines the essential aspects of nutrition therapy in the case of EC. The statements are: Patients with EC are among one of the highest risk to have malnutrition. Patient generated suggestive global assessment is correlated with performance status and prognosis. Nutrition assessment for patients with EC at the diagnosis, prior to definitive therapy and change of treatment strategy are suggested and the timing interval can be two weeks during the treatment period, and one month while the patient is stable. Patients identified as high risk of malnutrition should be considered for preoperative nutritional support (tube feeding) for at least 7-10 days. Various routes for tube feedings are available after esophagectomy with similar nutrition support benefits. Limited intrathoracic anastomotic leakage postesophagectomy can be managed with intravenous antibiotics and self-expanding metal stent (SEMS) or jejunal tube. Enteral nutrition in patients receiving preoperative chemotherapy or chemoradiation provides benefits of maintaining weight, decreasing toxicity, and preventing treatment interruption. Tube feeding or SEMS can offer nutrition support in patients with unresectable esophageal cancer, but SEMS is not recommended for those with neoadjuvant chemoradiation before surgery. Enteral immunonutrition may preserve lean body mass and attenuates stress response after esophagectomy. Administration of glutamine may decrease the severity of chemotherapy induced mucositis. Enteral immunonutrition achieves greater nutrition status or maintains immune functions during concurrent chemoradiation.

Does adjuvant therapy improve overall survival for stage IA/B pancreatic adenocarcinoma?

PubMed

Ostapoff, Katherine T; Gabriel, Emmanuel; Attwood, Kristopher; Kuvshinoff, Boris W; Nurkin, Steven J; Hochwald, Steven N

2017-07-01

Current guidelines recommend adjuvant chemotherapy for resected pancreatic adenocarcinoma (PDAC). However, no studies have addressed its survival benefit for stage I patients as they comprise <10% of PDAC. Using the NCDB 2006-2012, resected PDAC patients with stage I disease who received adjuvant therapy (chemotherapy or chemoradiation) were analyzed. Factors associated with overall survival (OS) were identified. 3909 patients with resected stage IA or IB PDAC were identified. Median OS was 60.3 months (mo) for stage IA and 36.9 mo for IB. 45.5% received adjuvant chemotherapy; 19.9% received adjuvant chemoradiation. There was OS benefit for both stage IA/IB patients with adjuvant chemotherapy (HR = 0.73 and 0.76 for IA and IB, respectively, p = 0.002 and <0.001). For patients with Stage IA disease (n = 1,477, 37.8%), age ≥70 (p < 0.001), higher grade (p < 0.001), ≤10 lymph nodes examined (p = 0.008), positive margins (p < 0.001), and receipt of adjuvant chemoradiation (p = 0.002) were associated with worse OS. For stage IB patients (n = 2,432, 62.2%), similar associations were observed with the exception of adjuvant chemoradiation whereby there was no significant association (p = 0.35). Adjuvant chemotherapy was associated with an OS benefit for patients with stage I PDAC; adjuvant chemoradiation was either of no benefit or associated with worse OS. Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

Validation of post-operative residual contrast enhancing tumor volume as an independent prognostic factor for overall survival in newly diagnosed glioblastoma.

PubMed

Ellingson, Benjamin M; Abrey, Lauren E; Nelson, Sarah J; Kaufmann, Timothy J; Garcia, Josep; Chinot, Olivier; Saran, Frank; Nishikawa, Ryo; Henriksson, Roger; Mason, Warren P; Wick, Wolfgang; Butowski, Nicholas; Ligon, Keith L; Gerstner, Elizabeth R; Colman, Howard; de Groot, John; Chang, Susan; Mellinghoff, Ingo; Young, Robert J; Alexander, Brian M; Colen, Rivka; Taylor, Jennie W; Arrillaga-Romany, Isabel; Mehta, Arnav; Huang, Raymond Y; Pope, Whitney B; Reardon, David; Batchelor, Tracy; Prados, Michael; Galanis, Evanthia; Wen, Patrick Y; Cloughesy, Timothy F

2018-04-05

In the current study, we pooled imaging data in newly diagnosed GBM patients from international multicenter clinical trials, single institution databases, and multicenter clinical trial consortiums to identify the relationship between post-operative residual enhancing tumor volume and overall survival (OS). Data from 1,511 newly diagnosed GBM patients from 5 data sources were included in the current study: 1) a single institution database from UCLA (N=398; Discovery); 2) patients from the Ben and Cathy Ivy Foundation for Early Phase Clinical Trials Network Radiogenomics Database (N=262 from 8 centers; Confirmation); 3) the chemoradiation placebo arm from an international phase III trial (AVAglio; N=394 from 120 locations in 23 countries; Validation); 4) the experimental arm from AVAglio examining chemoradiation plus bevacizumab (N=404 from 120 locations in 23 countries; Exploratory Set 1); and 5) an Alliance (N0874) Phase I/II trial of vorinostat plus chemoradiation (N=53; Exploratory Set 2). Post-surgical, residual enhancing disease was quantified using T1 subtraction maps. Multivariate Cox regression models were used to determine influence of clinical variables, MGMT status, and residual tumor volume on OS. A log-linear relationship was observed between post-operative, residual enhancing tumor volume and OS in newly diagnosed GBM treated with standard chemoradiation. Post-operative tumor volume is a prognostic factor for OS (P<0.01), regardless of therapy, age, and MGMT promoter methylation status. Post-surgical, residual contrast-enhancing disease significantly negatively influences survival in patients with newly diagnosed glioblastoma treated with chemoradiation with or without concomitant experimental therapy.

Cardiovascular Morbidity After Radiotherapy or Chemoradiation in Patients With Cervical Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maduro, John H.; Department of Medical Oncology, University of Groningen and University Medical Center Groningen, Groningen; Dekker, Helena A. den

2010-12-01

Purpose: To evaluate the risk of cardiovascular events (CVE) in patients with cervical cancer treated with radiotherapy or chemoradiation. Methods and Materials: The incidence of CVE in patients treated between 1989 and 2002 by radiotherapy or chemoradiation was compared with a Dutch reference population. Standardized incidence ratios (SIRs) were calculated for myocardial infarction (MI), angina pectoris (AP), congestive heart failure (CHF), cerebrovascular accident (CVA) separately and for any cardiac event combined (MI, AP, and CHF). Results: In 277 patients with a median follow-up of 4.5 years (range, 0.1-17 years) and a median survival of 9.2 years, 27 cardiac events occurred.more » The 5-, 10-, and 15-year actuarial incidence of any cardiac event were 9, 14, and 16%, respectively. For the whole population, the SIR for MI was elevated (2.05, 95% CI: 1.12-3.43). The radiotherapy group (n = 132) was older and had more cardiovascular risk factors than the chemoradiation group (n = 145). The SIR for MI in the radiotherapy group was 2.88 (95% CI: 1.44-5.15) and in the chemoradiation group 1.00 (95% CI: 0.21-7.47). In multivariate analyses, there was no relation between treatment modality and the risk for MI. Conclusions: In this cohort of cervical cancer patients, an increased risk for developing a MI was observed. This increased risk of MI, in combination with the high prevalence of cardiovascular risk factors in cervical cancer patients, urges the need to explore strategies to reduce their risk for cardiovascular morbidity.« less

Management of normal tissue toxicity associated with chemoradiation (primary skin, esophagus, and lung).

PubMed

Yazbeck, Victor Y; Villaruz, Liza; Haley, Marsha; Socinski, Mark A

2013-01-01

Nearly one quarter of patients with lung cancer present with locally advanced disease where concurrent chemoradiotherapy is the current standard of care for patients with good performance status. Cisplatin-based concurrent chemoradiotherapy consistently showed an improvement in survival compared with sequential chemoradiotherapy, at the expense of an increase in the toxicity profile. Over the past decades, several encouraging biomarkers such as transforming growth factor-beta and radioprotective agents such as amifostine were studied but without reaching approval for patient care. We reviewed the prevalence and risk factors for different adverse effects associated with the combined chemoradiotherapy modality, especially dermatitis, mucositis, esophagitis, and pneumonitis. These adverse effects can further be divided into acute, subacute, and chronic. Dermatitis is usually rare and responds well to topical steroids and usual skin care. Acute esophagitis occurs in 30% of patients and is treated with proton pump inhibitors, promotility agents, local anesthetic, and dietary changes. Radiation pneumonitis is a subacute complication seen in 15% of patients and is usually managed with steroids. Chronic adverse effects such as radiation fibrosis and esophageal stricture occur approximately 6 months after completion of radiation therapy and are usually permanent. In this review, complications of chemoradiotherapy for patients with locally advanced lung cancer are delineated, and approaches to their management are described. Given that treatment interruption is associated with a worse outcome, patients are aggressively treated with a curative intent. Therefore, planning for treatment adverse effects improves patient tolerance, compliance, and outcome.

Etoposide and cisplatin versus paclitaxel and carboplatin with concurrent thoracic radiotherapy in unresectable stage III non-small cell lung cancer: a multicenter randomized phase III trial.

PubMed

Liang, J; Bi, N; Wu, S; Chen, M; Lv, C; Zhao, L; Shi, A; Jiang, W; Xu, Y; Zhou, Z; Wang, W; Chen, D; Hui, Z; Lv, J; Zhang, H; Feng, Q; Xiao, Z; Wang, X; Liu, L; Zhang, T; Du, L; Chen, W; Shyr, Y; Yin, W; Li, J; He, J; Wang, L

2017-04-01

The optimal chemotherapy regimen administered currently with radiation in patients with stage III non-small cell lung cancer (NSCLC) remains unclear. A multicenter phase III trial was conducted to compare the efficacy of concurrent thoracic radiation therapy with either etoposide/cisplatin (EP) or carboplatin/paclitaxel (PC) in patients with stage III NSCLC. Patients were randomly received 60-66 Gy of thoracic radiation therapy concurrent with either etoposide 50 mg/m2 on days 1-5 and cisplatin 50 mg/m2 on days 1 and 8 every 4 weeks for two cycles (EP arm), or paclitaxel 45 mg/m2 and carboplatin (AUC 2) on day 1 weekly (PC arm). The primary end point was overall survival (OS). The study was designed with 80% power to detect a 17% superiority in 3-year OS with a type I error rate of 0.05. A total of 200 patients were randomized and 191 patients were treated (95 in the EP arm and 96 in the PC arm). With a median follow-up time of 73 months, the 3-year OS was significantly higher in the EP arm than that of the PC arm. The estimated difference was 15.0% (95% CI 2.0%-28.0%) and P value of 0.024. Median survival times were 23.3 months in the EP arm and 20.7 months in the PC arm (log-rank test P = 0.095, HR 0.76, 95%CI 0.55-1.05). The incidence of Grade ≥2 radiation pneumonitis was higher in the PC arm (33.3% versus 18.9%, P = 0.036), while the incidence of Grade ≥3 esophagitis was higher in the EP arm (20.0% versus 6.3%, P = 0.009). EP might be superior to weekly PC in terms of OS in the setting of concurrent chemoradiation for unresectable stage III NSCLC. NCT01494558. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Relative Value of Restaging MRI, CT, and FDG-PET Scan After Preoperative Chemoradiation for Rectal Cancer.

PubMed

Schneider, Daniel A; Akhurst, Timothy J; Ngan, Samuel Y; Warrier, Satish K; Michael, Michael; Lynch, Andrew C; Te Marvelde, Luc; Heriot, Alexander G

2016-03-01

Management of rectal cancer has become multidisciplinary and is driven by the stage of the disease, with increased focus on restaging rectal cancer after neoadjuvant therapy. The purpose of this study was to assess the relative impact of restaging after preoperative chemoradiation with FDG-PET scan, CT, and MRI in the management of patients with rectal cancer. This was a retrospective study from a single institution. This study was conducted at a tertiary cancer center. A total of 199 patients met the inclusion criteria: patients with rectal adenocarcinoma; staged with positron emission tomography, CT, and MRI; T2 to T4, N0 to N2, M0 to M1; treated with neoadjuvant chemoradiation 50.4 Gy and infusional 5-fluorouracil; and restaged 4 weeks after chemoradiation before surgery between 2003 and 2013. Comparisons of the tumor stage among different imaging modalities before and after neoadjuvant chemoradiation were performed. The impact of restaging on the management plan was assessed. The stage at presentation was T2, 8.04%; T3, 65.33%; T4, 26.63%; N0, 17.09%; N1, 47.74%; N2, 34.67%; M0, 81.91%; and M1, 18.09%. Changes in disease stage postneoadjuvant chemoradiation were observed in 99 patients (50%). The management plans of 29 patients (15%) were changed. The impact of each restaging modality on management for all of the patients was positron emission tomography, 11%; CT, 4%; and MRI, 4%. In patients with metastatic disease at primary staging, the relative impact of each restaging modality in changing management was positron emission tomography, 32%; CT, 18%; and MRI, 6%. This study was limited by its single-center and retrospective design. Operations were performed 4 weeks after restaging. Changes in the extent of disease after long-course chemoradiotherapy result in changes of management in a significant percentage of patients. Positron emission tomography has the most significant impact in the change of management overall, and its use in restaging advanced rectal cancer should be further explored.

Regional Lymph Node Uptake of [{sup 18}F]Fluorodeoxyglucose After Definitive Chemoradiation Therapy Predicts Local-Regional Failure of Locally Advanced Non-Small Cell Lung Cancer: Results of ACRIN 6668/RTOG 0235

DOE Office of Scientific and Technical Information (OSTI.GOV)

Markovina, Stephanie; Duan, Fenghai; Snyder, Bradley S.

2015-11-01

Purpose: The American College of Radiology Imaging Network (ACRIN) 6668/Radiation Therapy Oncology Group (RTOG) 0235 study demonstrated that standardized uptake values (SUV) on post-treatment [{sup 18}F]fluorodeoxyglucose-positron emission tomography (FDG-PET) correlated with survival in locally advanced non-small cell lung cancer (NSCLC). This secondary analysis determined whether SUV of regional lymph nodes (RLNs) on post-treatment FDG-PET correlated with patient outcomes. Methods and Materials: Included for analysis were patients treated with concurrent chemoradiation therapy, using radiation doses ≥60 Gy, with identifiable FDG-avid RLNs (distinct from primary tumor) on pretreatment FDG-PET, and post-treatment FDG-PET data. ACRIN core laboratory SUV measurements were used. Event time was calculatedmore » from the date of post-treatment FDG-PET. Local-regional failure was defined as failure within the treated RT volume and reported by the treating institution. Statistical analyses included Wilcoxon signed rank test, Kaplan-Meier curves (log rank test), and Cox proportional hazards regression modeling. Results: Of 234 trial-eligible patients, 139 (59%) had uptake in both primary tumor and RLNs on pretreatment FDG-PET and had SUV data from post-treatment FDG-PET. Maximum SUV was greater for primary tumor than for RLNs before treatment (P<.001) but not different post-treatment (P=.320). Post-treatment SUV of RLNs was not associated with overall survival. However, elevated post-treatment SUV of RLNs, both the absolute value and the percentage of residual activity compared to the pretreatment SUV were associated with inferior local-regional control (P<.001). Conclusions: High residual metabolic activity in RLNs on post-treatment FDG-PET is associated with worse local-regional control. Based on these data, future trials evaluating a radiation therapy boost should consider inclusion of both primary tumor and FDG-avid RLNs in the boost volume to maximize local-regional control.« less

Pulmonary Artery Invasion, High-Dose Radiation, and Overall Survival in Patients With Non-Small Cell Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, Cheng-Bo; Department of Oncology, Shengjing Hospital of China Medical University, Shenyang; Wang, Wei-Li

2014-06-01

Purpose: To investigate whether high-dose radiation to the pulmonary artery (PA) affects overall survival (OS) in patients with non-small cell lung cancer (NSCLC). Methods and Materials: Patients with medically inoperable/unresectable NSCLC treated with definitive radiation therapy in prospective studies were eligible for this study. Pulmonary artery involvement was defined on the basis of pretreatment chest CT and positron emission tomography/CT fusion. Pulmonary artery was contoured according to the Radiation Therapy Oncology Group protocol 1106 atlas, and dose-volume histograms were generated. Results: A total of 100 patients with a minimum follow-up of 1 year for surviving patients were enrolled: 82.0% underwent concurrentmore » chemoradiation therapy. Radiation dose ranged from 60 to 85.5 Gy in 30-37 fractions. Patients with PA invasion of grade ≤2, 3, 4, and 5 had 1-year OS and median survival of 67% and 25.4 months (95% confidence interval [CI] 15.7-35.1), 62% and 22.2 months (95% CI 5.8-38.6), 90% and 35.8 months (95% CI 28.4-43.2), and 50% and 7.0 months, respectively (P=.601). Two of the 4 patients with grade 5 PA invasion died suddenly from massive hemorrhage at 3 and 4.5 months after completion of radiation therapy. Maximum and mean doses to PA were not significantly associated with OS. The V45, V50, V55, and V60 of PA were correlated significantly with a worse OS (P<.05). Patients with V45 >70% or V60 >37% had significantly worse OS (13.3 vs 37.9 months, P<.001, and 13.8 vs 37.9 months, P=.04, respectively). Conclusions: Grade 5 PA invasion and PA volume receiving more than 45-60 Gy may be associated with inferior OS in patients with advanced NSCLC treated with concurrent chemoradiation.« less

Clinical outcomes and prognostic factors in cisplatin versus cetuximab chemoradiation for locally advanced p16 positive oropharyngeal carcinoma.

PubMed

Barney, Christian L; Walston, Steve; Zamora, Pedro; Healy, Erin H; Nolan, Nicole; Diavolitsis, Virginia M; Neki, Anterpreet; Rupert, Robert; Savvides, Panos; Agrawal, Amit; Old, Matthew; Ozer, Enver; Carrau, Ricardo; Kang, Stephen; Rocco, James; Teknos, Theodoros; Grecula, John C; Wobb, Jessica; Mitchell, Darrion; Blakaj, Dukagjin; Bhatt, Aashish D

2018-04-01

Randomized trials evaluating cisplatin versus cetuximab chemoradiation (CRT) for p16+ oropharyngeal cancer (OPC) have yet to report preliminary data. Meanwhile, as a preemptive step toward morbidity reduction, the off-trial use of cetuximab in p16+ patients is increasing, even in those who could potentially tolerate cisplatin. The purpose of this study was to compare the efficacy of cisplatin versus cetuximab CRT in the treatment of p16+ OPC and to identify prognostic factors and predictors of tumor response. Cases of p16+ OPC treated with cisplatin or cetuximab CRT at our institution from 2010 to 2014 were identified. Recursive partitioning analysis (RPA) classification was used to determine low-risk (LR-RPA) and intermediate-risk (IR-RPA) groups. Log-rank/Kaplan-Meier and Cox Regression methods were used to compare groups. We identified 205 patients who received cisplatin (n = 137) or cetuximab (n = 68) CRT in the definitive (n = 178) or postoperative (n = 27) setting. Median follow-up was 3 years. Cisplatin improved 3-year locoregional control (LRC) [92.7 vs 65.4%], distant metastasis-free survival (DMFS) [88.3 vs 71.2%], recurrence-free survival (RFS) [86.6 vs 50.6%], and overall survival (OS) [92.6 vs 72.2%] compared to cetuximab [all p < .001]. Concurrent cisplatin improved 3-year OS for LR-RPA (97.1 vs 80.3%, p < .001) and IR-RPA (97.1 vs 80.3%, p < .001) groupings. When treating p16+ OPC with CRT, the threshold for substitution of cisplatin with cetuximab should be maintained appropriately high in order to prolong survival times and optimize locoregional and distant tumor control. When cetuximab is used in cisplatin-ineligible patients, altered fractionation RT should be considered in an effort to improve LRC. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effect of Brain Stem and Dorsal Vagus Complex Dosimetry on Nausea and Vomiting in Head and Neck Intensity-Modulated Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ciura, Katherine; McBurney, Michelle; Nguyen, Baongoc

Intensity-modulated radiation therapy (IMRT) is becoming the treatment of choice for many head and neck cancer patients. IMRT reduces some toxicities by reducing radiation dose to uninvolved normal tissue near tumor targets; however, other tissues not irradiated using previous 3D techniques may receive clinically significant doses, causing undesirable side effects including nausea and vomiting (NV). Irradiation of the brainstem, and more specifically, the area postrema and dorsal vagal complex (DVC), has been linked to NV. We previously reported preliminary hypothesis-generating dose effects associated with NV in IMRT patients. The goal of this study is to relate brainstem dose to NVmore » symptoms. We retrospectively studied 100 consecutive patients that were treated for oropharyngeal cancer with IMRT. We contoured the brainstem, area postrema, and DVC with the assistance of an expert diagnostic neuroradiologist. We correlated dosimetry for the 3 areas contoured with weekly NV rates during IMRT. NV rates were significantly higher for patients who received concurrent chemotherapy. Post hoc analysis demonstrated that chemoradiation cases exhibited a trend towards the same dose-response relationship with both brainstem mean dose (p = 0.0025) and area postrema mean dose (p = 0.004); however, both failed to meet statistical significance at the p {<=} 0.002 level. Duration of toxicity was also greater for chemoradiation patients, who averaged 3.3 weeks with reported Common Terminology Criteria for Adverse Events (CTC-AE), compared with an average of 2 weeks for definitive RT patients (p = 0.002). For definitive RT cases, no dose-response trend could be ascertained. The mean brainstem dose emerged as a key parameter of interest; however, no one dose parameter (mean/median/EUD) best correlated with NV. This study does not address extraneous factors that would affect NV incidence, including the use of antiemetics, nor chemotherapy dose schedule specifics before and during RT. A prospective study will be required to depict exactly how IMRT dose affects NV.« less

Individualized Radical Radiotherapy of Non-Small-Cell Lung Cancer Based on Normal Tissue Dose Constraints: A Feasibility Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baardwijk, Angela van; Bosmans, Geert; Boersma, Liesbeth

2008-08-01

Purpose: Local recurrence is a major problem after (chemo-)radiation for non-small-cell lung cancer. We hypothesized that for each individual patient, the highest therapeutic ratio could be achieved by increasing total tumor dose (TTD) to the limits of normal tissues, delivered within 5 weeks. We report first results of a prospective feasibility trial. Methods and Materials: Twenty-eight patients with medically inoperable or locally advanced non-small-cell lung cancer, World Health Organization performance score of 0-1, and reasonable lung function (forced expiratory volume in 1 second > 50%) were analyzed. All patients underwent irradiation using an individualized prescribed TTD based on normal tissuemore » dose constraints (mean lung dose, 19 Gy; maximal spinal cord dose, 54 Gy) up to a maximal TTD of 79.2 Gy in 1.8-Gy fractions twice daily. No concurrent chemoradiation was administered. Toxicity was scored using the Common Terminology Criteria for Adverse Events criteria. An {sup 18}F-fluoro-2-deoxy-glucose-positron emission tomography-computed tomography scan was performed to evaluate (metabolic) response 3 months after treatment. Results: Mean delivered dose was 63.0 {+-} 9.8 Gy. The TTD was most often limited by the mean lung dose (32.1%) or spinal cord (28.6%). Acute toxicity generally was mild; only 1 patient experienced Grade 3 cough and 1 patient experienced Grade 3 dysphagia. One patient (3.6%) died of pneumonitis. For late toxicity, 2 patients (7.7%) had Grade 3 cough or dyspnea; none had severe dysphagia. Complete metabolic response was obtained in 44% (11 of 26 patients). With a median follow-up of 13 months, median overall survival was 19.6 months, with a 1-year survival rate of 57.1%. Conclusions: Individualized maximal tolerable dose irradiation based on normal tissue dose constraints is feasible, and initial results are promising.« less

Radiobiological Determination of Dose Escalation and Normal Tissue Toxicity in Definitive Chemoradiation Therapy for Esophageal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Warren, Samantha, E-mail: Samantha.warren@oncology.ox.ac.uk; Partridge, Mike; Carrington, Rhys

2014-10-01

Purpose: This study investigated the trade-off in tumor coverage and organ-at-risk sparing when applying dose escalation for concurrent chemoradiation therapy (CRT) of mid-esophageal cancer, using radiobiological modeling to estimate local control and normal tissue toxicity. Methods and Materials: Twenty-one patients with mid-esophageal cancer were selected from the SCOPE1 database (International Standard Randomised Controlled Trials number 47718479), with a mean planning target volume (PTV) of 327 cm{sup 3}. A boost volume, PTV2 (GTV + 0.5 cm margin), was created. Radiobiological modeling of tumor control probability (TCP) estimated the dose required for a clinically significant (+20%) increase in local control as 62.5more » Gy/25 fractions. A RapidArc (RA) plan with a simultaneously integrated boost (SIB) to PTV2 (RA{sub 62.5}) was compared to a standard dose plan of 50 Gy/25 fractions (RA{sub 50}). Dose-volume metrics and estimates of normal tissue complication probability (NTCP) for heart and lungs were compared. Results: Clinically acceptable dose escalation was feasible for 16 of 21 patients, with significant gains (>18%) in tumor control from 38.2% (RA{sub 50}) to 56.3% (RA{sub 62.5}), and only a small increase in predicted toxicity: median heart NTCP 4.4% (RA{sub 50}) versus 5.6% (RA{sub 62.5}) P<.001 and median lung NTCP 6.5% (RA{sub 50}) versus 7.5% (RA{sub 62.5}) P<.001. Conclusions: Dose escalation to the GTV to improve local control is possible when overlap between PTV and organ-at-risk (<8% heart volume and <2.5% lung volume overlap for this study) generates only negligible increase in lung or heart toxicity. These predictions from radiobiological modeling should be tested in future clinical trials.« less

The Role of Dual-Time Combined 18-Fluorideoxyglucose Positron Emission Tomography and Computed Tomography in the Staging and Restaging Workup of Locally Advanced Rectal Cancer, Treated With Preoperative Chemoradiation Therapy and Radical Surgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Capirci, Carlo; Rubello, Domenico; Pasini, Felice

2009-08-01

Purpose: In patients with locally advanced rectal cancer (LARC) staging and, after preoperative chemo-radiation therapy (CRT), restaging workup could be useful to tailor therapeutic approaches. Fluorine-18-fluorodeoxyglucose positron emission tomography ([{sup 18}F]FDG-PET) is a promising tool for monitoring the effect of antitumor therapy. This study was aimed to evaluate the possible role of dual time sequential FDG-PET scans in the staging and restaging workup of LARC. Methods and Materials: Eighty-seven consecutive patients with LARC were enrolled. CRT consisted of external-beam intensified radiotherapy (concurrent boost), with concomitant chemotherapy PVI 5-FU (300mg/m{sup 2}/day) followed 8-10 weeks later by surgery. All patients underwent [{supmore » 18}F]FDG-PET/CT before and 5-6 weeks later after the completion of CRT. Measurements of FDG uptake (SUV{sub max}), and percentage of SUV{sub max} difference (Response Index = RI) between pre- and post-CRT [{sup 18}F]FDG-PET scans were evaluated. Results: Six of 87 patients were excluded due to protocol deviation. Following CRT, 40/81 patients (49%) were classified as responders according to Mandard's criteria (TRG1-2). The mean pre-CRT SUV{sub max} was significantly higher than post-CRT (15.8, vs 5.9; p < 0.001). The mean RI was significantly higher in responders than in nonresponder patients (71.3% vs 38%; p = 0.0038). Using a RI cut-off of 65% for defining response to therapy, the following parameters have been obtained: 84.5% sensitivity, 80% specificity, 81.4% positive predictive value, 84.2% negative predictive value, and 81% overall accuracy. Conclusion: These results suggest the potential role of [{sup 18}F]FDG-PET in the restaging workup after preoperative CRT in LARC. RI seems the best predictor to identify CRT response.« less

Preoperative Chemoradiation Therapy in Combination With Panitumumab for Patients With Resectable Esophageal Cancer: The PACT Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kordes, Sil, E-mail: s.kordes@amc.uva.nl; Berge Henegouwen, Mark I. van; Hulshof, Maarten C.

Purpose: Preoperative chemoradiation therapy (CRT) has become the standard treatment strategy for patients with resectable esophageal cancer. This multicenter phase 2 study investigated the efficacy of the addition of the epidermal growth factor receptor (EGFR) inhibitor panitumumab to a preoperative CRT regimen with carboplatin, paclitaxel, and radiation therapy in patients with resectable esophageal cancer. Methods and Materials: Patients with resectable cT1N1M0 or cT2-3N0 to -2M0 tumors received preoperative CRT consisting of panitumumab (6 mg/kg) on days 1, 15, and 29, weekly administrations of carboplatin (area under the curve [AUC] = 2), and paclitaxel (50 mg/m{sup 2}) for 5 weeks and concurrent radiation therapy (41.4 Gy in 23more » fractions, 5 days per week), followed by surgery. Primary endpoint was pathologic complete response (pCR) rate. We aimed at a pCR rate of more than 40%. Furthermore, we explored the predictive value of biomarkers (EGFR, HER 2, and P53) for pCR. Results: From January 2010 until December 2011, 90 patients were enrolled. Patients were diagnosed predominantly with adenocarcinoma (AC) (80%), T3 disease (89%), and were node positive (81%). Three patients were not resected due to progressive disease. The primary aim was unmet, with a pCR rate of 22%. Patients with AC and squamous cell carcinoma reached a pCR of 14% and 47%, respectively. R0 resection was achieved in 95% of the patients. Main grade 3 toxicities were rash (12%), fatigue (11%), and nonfebrile neutropenia (11%). None of the biomarkers was predictive for response. Conclusions: The addition of panitumumab to CRT with carboplatin and paclitaxel was safe and well tolerated but could not improve pCR rate to the preset criterion of 40%.« less

Predictors of chemoradiation related febrile neutropenia prophylaxis in older adults - Experience from a limited resource setting.

PubMed

Gangopadhyay, Aparna

2018-01-01

To identify risk factors that lower efficacy of antibiotic prophylaxis of febrile neutropenia among older patients on chemoradiation. Audit of institutional data showed that older adults are at higher risk of febrile neutropenia during chemoradiation. In limited resource settings widespread use of Granulocyte-Colony Stimulating Factor (G-CSF) is not economically feasible and antibiotics are used commonly. Despite compliance with antibiotics, prophylaxis is inadequate in many patients owing to patient and tumor related factors. Data from records of 219 older patients receiving antibiotic prophylaxis during chemoradiation were studied. Baseline assessment data and predisposing factors for febrile neutropenia were recorded. All patients received prophylactic fluoroquinolones. Incidence of febrile neutropenia and association with predisposing factors at baseline was analyzed by multiple logistic regression. 38.4% developed febrile neutropenia despite compliance. Multiple logistic regression revealed geriatric assessment (G8) score and tumor stage to be significant predictors of febrile neutropenia while on antibiotics ( p  < 0.0001). Odds ratios for two significant predictors G8 score and tumor stage, respectively, were 2.9 (95% CI 1.8036-4.6815) and 2.7 (95% CI 1.7501-4.1318). Correlation between these two significant predictors was found to be low in our cohort (Spearman's coefficient of rank correlation (rho) - 0.431, p  < 0.0001). G8 score and tumor burden are significant predictors of efficacy of antibiotic prophylaxis among older adults receiving chemoradiation. In older patients having poor G8 scores and advanced tumors, antibiotic prophylaxis is unsuitable. Interestingly, co-morbidities and poor performance status did not impact efficacy of antibiotic prophylaxis among our elderly patients.

Long-term survival benefit of upfront chemotherapy in patients with newly diagnosed borderline resectable pancreatic cancer.

PubMed

Shrestha, Bikram; Sun, Yifei; Faisal, Farzana; Kim, Victoria; Soares, Kevin; Blair, Alex; Herman, Joseph M; Narang, Amol; Dholakia, Avani S; Rosati, Lauren; Hacker-Prietz, Amy; Chen, Linda; Laheru, Daniel A; De Jesus-Acosta, Ana; Le, Dung T; Donehower, Ross; Azad, Nilofar; Diaz, Luis A; Murphy, Adrian; Lee, Valerie; Fishman, Elliot K; Hruban, Ralph H; Liang, Tingbo; Cameron, John L; Makary, Martin; Weiss, Matthew J; Ahuja, Nita; He, Jin; Wolfgang, Christopher L; Huang, Chiung-Yu; Zheng, Lei

2017-07-01

The use of neoadjuvant chemotherapy or radiation for borderline resectable pancreatic adenocarcinoma (BL-PDAC) is increasing. However, the impact of neoadjuvant chemotherapy and radiation therapy on the outcome of BL-PDAC remains to be elucidated. We performed a retrospective analysis of 93 consecutive patients who were diagnosed with BL-PDAC and primarily followed at Johns Hopkins Hospital between February 2007 and December 2012. Among 93 patients, 62% received upfront neoadjuvant chemotherapy followed by chemoradiation, whereas 20% received neoadjuvant chemoradiation alone and 15% neoadjuvant chemotherapy alone. Resectability following all neoadjuvant therapy was 44%. Patients who underwent resection with a curative intent had a median overall survival (mOS) of 25.8 months, whereas those who did not undergo surgery had a mOS of 11.9 months. However, resectability and overall survival were not significantly different between the three types of neoadjuvant therapy. Nevertheless, 22% (95% CI, 0.13-0.36) of the 58 patients who received upfront chemotherapy followed by chemoradiation remained alive for a minimum of 48 months compared to none of the 19 patients who received upfront chemoradiation. Among patients who underwent curative surgical resection, 32% (95% CI, 0.19-0.55) of those who received upfront chemotherapy remained disease free at least 48 months following surgical resection, whereas none of the eight patients who received upfront chemoradiation remained disease free beyond 24 months following surgical resection. Neoadjuvant therapy with upfront chemotherapy may result in long-term survival in a subpopulation of patients with BL-PDAC. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Prevalence of swallowing and speech problems in daily life after chemoradiation for head and neck cancer based on cut-off scores of the patient-reported outcome measures SWAL-QOL and SHI.

PubMed

Rinkel, Rico N; Verdonck-de Leeuw, Irma M; Doornaert, Patricia; Buter, Jan; de Bree, Remco; Langendijk, Johannes A; Aaronson, Neil K; Leemans, C René

2016-07-01

The objective of this study is to assess swallowing and speech outcome after chemoradiation therapy for head and neck cancer, based on the patient-reported outcome measures Swallowing Quality of Life Questionnaire (SWAL-QOL) and Speech Handicap Index (SHI), both provided with cut-off scores. This is a cross-sectional study. Department of Otolaryngology/Head and Neck Surgery of a University Medical Center. Sixty patients, 6 months to 5 years after chemoradiation for head and neck squamous cell carcinoma. Swallowing Quality of Life Questionnaire (SWAL-QOL) and SHI, both validated in Dutch and provided with cut-off scores. Associations were tested between the outcome measures and independent variables (age, gender, tumor stage and site, and radiotherapy technique, time since treatment, comorbidity and food intake). Fifty-two patients returned the SWAL-QOL and 47 the SHI (response rate 87 and 78 %, respectively). Swallowing and speech problems were present in 79 and 55 %, respectively. Normal food intake was noticed in 45, 35 % had a soft diet and 20 % tube feeding. Patients with soft diet and tube feeding reported more swallowing problems compared to patients with normal oral intake. Tumor subsite was significantly associated with swallowing outcome (less problems in larynx/hypopharynx compared to oral/oropharynx). Radiation technique was significantly associated with psychosocial speech problems (less problems in patients treated with IMRT). Swallowing and (to a lesser extent) speech problems in daily life are frequently present after chemoradiation therapy for head and neck cancer. Future prospective studies will give more insight into the course of speech and swallowing problems after chemoradiation and into efficacy of new radiation techniques and swallowing and speech rehabilitation programs.

[Lung Resection after Definitive and Neo-Adjuvant Chemoradiation for Stage IIIA/B Locally Advanced Non-Small Cell Lung Cancer: a Retrospective Analysis].

PubMed

Schreiner, Waldemar; Gavrychenkova, Sofiia; Dudek, Wojciech; Lettmaier, Sebastian; Rieker, Ralf; Fietkau, Rainer; Sirbu, Horia

2018-06-01

The outcomes of so called "salvage" resections after definitive chemoradiation vs. curative resections after neoadjuvant chemoradiation therapy (IT-resection) in patients with stage IIIA/B locally advanced non-small cell lung cancer have rarely been compared. The aim of our study was to compare perioperative results, postoperative and recurrence-free survival and to identify relevant prognostic survival factors for both therapy strategies. Between June 2008 and May 2017, 43 patients underwent pulmonary resection following induction therapy (group 1) and 14 patients underwent salvage resection after definitive chemoradiation (group 2). Retrospective analysis was performed of demographic factors, tumour stage and location, initial therapy, preoperative regression status, perioperative morbidity and mortality, postoperative and recurrence-free survival. In group 2, significantly higher radiation dose was applied (p < 0.001) and the interval between chemoradiation and lung resection was significantly longer (p = 0.02). In addition, significantly higher perioperative blood loss and more frequent blood transfusions were noted (p = 0.003 and 0.005, respectively). Perioperative morbidity and mortality were statistically comparable in the two groups (p = 0.72 and 0.395, respectively). Postoperative 5 year survival in group 1 was 55%, in group 2 48% (log-rank p = 0.353). Five year recurrence-free survival in group 1 was 53%, in group 2 42% (log-rank p = 0.180). Diffuse metastasis occurred mostly in group 2, whereas in group 1 oligometastasis was more frequently noted. Postoperative outcome after salvage resection seems statistically comparable to results following curative resection after induction therapy. Diffuse distant metastasis is frequently noted. Careful patient selection is required. Georg Thieme Verlag KG Stuttgart · New York.

Focused Attention Deficits in Patients with Alzheimer's Disease and Mild Cognitive Impairment

ERIC Educational Resources Information Center

Levinoff, E.J.; Saumier, D.; Chertkow, H.

2005-01-01

Reaction time (RT) tasks take various forms, and can assess psychomotor speed, (i.e., simple reaction time task), and focused attention (i.e., choice reaction time (CRT) task). If cues are provided before stimulus presentation (i.e., cued choice reaction time (CCRT) task), then a cueing effect can also be assessed. A limited number of studies have…

Intelligibility Evaluation of Pathological Speech through Multigranularity Feature Extraction and Optimization.

PubMed

Fang, Chunying; Li, Haifeng; Ma, Lin; Zhang, Mancai

2017-01-01

Pathological speech usually refers to speech distortion resulting from illness or other biological insults. The assessment of pathological speech plays an important role in assisting the experts, while automatic evaluation of speech intelligibility is difficult because it is usually nonstationary and mutational. In this paper, we carry out an independent innovation of feature extraction and reduction, and we describe a multigranularity combined feature scheme which is optimized by the hierarchical visual method. A novel method of generating feature set based on S -transform and chaotic analysis is proposed. There are BAFS (430, basic acoustics feature), local spectral characteristics MSCC (84, Mel S -transform cepstrum coefficients), and chaotic features (12). Finally, radar chart and F -score are proposed to optimize the features by the hierarchical visual fusion. The feature set could be optimized from 526 to 96 dimensions based on NKI-CCRT corpus and 104 dimensions based on SVD corpus. The experimental results denote that new features by support vector machine (SVM) have the best performance, with a recognition rate of 84.4% on NKI-CCRT corpus and 78.7% on SVD corpus. The proposed method is thus approved to be effective and reliable for pathological speech intelligibility evaluation.

Phase 2 Study of Concurrent Cetuximab Plus Definitive Thoracic Radiation Therapy Followed by Consolidation Docetaxel Plus Cetuximab in Poor Prognosis or Elderly Patients With Locally Advanced Non-Small Cell Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dilling, Thomas J.; Extermann, Martine; Kim, Jongphil

Background: Recursive partitioning analysis has shown that Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≥2, male sex, and age ≥70 years are prognostic of poor outcome in locally advanced non-small cell lung cancer (LA-NSCLC) patients. Concurrent chemoradiation therapy (CRT) improves survival, but toxicity is a concern in this frail patient cohort. We therefore opened this trial of concurrent definitive thoracic radiation therapy (XRT) and cetuximab, followed by consolidation docetaxel plus cetuximab. Methods and Materials: Eligible patients had pathologically proven, unresectable LA-NSCLC (stage IIA-“dry” IIIB). They had ECOG PS 2 or weight loss ≥5% in 3 months or were aged ≥70 years. Themore » primary objective was progression-free survival (PFS). Secondary objectives included overall survival (OS) and overall response rate (ORR). Results: From May 2008 to November 2010, a total of 32 patients were evaluated in our single-institution, institutional review board–approved prospective clinical trial. Three patients were screen failures and 2 more withdrew consent before treatment, leaving 27 evaluable patients. One was removed because of poor therapy compliance, and 2 were taken off trial because of grade 3 cetuximab-related toxicities but were followed up under intent-to-treat analysis. The median follow-up and OS were 10.5 months. The median PFS was 7.5 months. The ORR was 59.3%. Eight early/sudden deaths were reported. Upon review, 6 patients developed severe pulmonary complications. Conclusions: Patients enrolled in this trial had improved OS compared with poor-PS historical controls (10.5 vs 6.4 months) and comparable OS to good-PS historical controls (10.5 vs 11.9 months) treated with XRT alone. However, pulmonary toxicity is a concern. Consolidative cetuximab/docetaxel, in conjunction with high-dose radiation therapy, is a putative cause.« less

A Multicenter Phase II Trial of S-1 With Concurrent Radiation Therapy for Locally Advanced Pancreatic Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ikeda, Masafumi, E-mail: masikeda@east.ncc.go.jp; Ioka, Tatsuya; Ito, Yoshinori

2013-01-01

Purpose: The aim of this trial was to evaluate the efficacy and toxicity of S-1 and concurrent radiation therapy for locally advanced pancreatic cancer (PC). Methods and Materials: Locally advanced PC patients with histologically or cytologically confirmed adenocarcinoma or adenosquamous carcinoma, who had no previous therapy were enrolled. Radiation therapy was delivered through 3 or more fields at a total dose of 50.4 Gy in 28 fractions over 5.5 weeks. S-1 was administered orally at a dose of 80 mg/m{sup 2} twice daily on the day of irradiation during radiation therapy. After a 2- to 8-week break, patients received amore » maintenance dose of S-1 (80 mg/m{sup 2}/day for 28 consecutive days, followed by a 14-day rest period) was then administered until the appearance of disease progression or unacceptable toxicity. The primary efficacy endpoint was survival, and the secondary efficacy endpoints were progression-free survival, response rate, and serum carbohydrate antigen 19-9 (CA19-9) response; the safety endpoint was toxicity. Results: Of the 60 evaluable patients, 16 patients achieved a partial response (27%; 95% confidence interval [CI], 16%-40%). The median progression-free survival period, overall survival period, and 1-year survival rate of the evaluable patients were 9.7 months (95% CI, 6.9-11.6 months), 16.2 months (95% CI, 13.5-21.3 months), and 72% (95%CI, 59%-82%), respectively. Of the 42 patients with a pretreatment serum CA19-9 level of {>=}100 U/ml, 34 (81%) patients showed a decrease of greater than 50%. Leukopenia (6 patients, 10%) and anorexia (4 patients, 7%) were the major grade 3-4 toxicities with chemoradiation therapy. Conclusions: The effect of S-1 with concurrent radiation therapy in patients with locally advanced PC was found to be very favorable, with only mild toxicity.« less

Arterio-biliary fistula as rare complication of chemoradiation therapy for intrahepatic cholangiocarcinoma

PubMed Central

Hayano, Koichi; Miura, Fumihiko; Amano, Hodaka; Toyota, Naoyuki; Wada, Keita; Kato, Kenichiro; Takada, Tadahiro; Asano, Takehide

2010-01-01

Significant hemobilia due to arterio-biliary fistula is a very rare complication of chemoradiation therapy (CRT) for unresectable intrahepatic cholangiocarcinoma (ICC). Here we report a case of arterio-biliary fistula after CRT for unresectable ICC demonstrated by angiographic examinations. This fistula was successfully treated by endovascular embolization. Hemobilia is a rare complication, but arterio-biliary fistula should be considered after CRT of ICC. PMID:21160700

EGFR Targeted Therapies and Radiation: Optimizing Efficacy by Appropriate Drug Scheduling and Patient Selection

PubMed Central

Cuneo, Kyle C.; Nyati, Mukesh K.; Ray, Dipankar; Lawrence, Theodore S.

2015-01-01

The epidermal growth factor receptor (EGFR) plays an important role in tumor progression and treatment resistance for many types of malignancies including head and neck, colorectal, and nonsmall cell lung cancer. Several EGFR targeted therapies are efficacious as single agents or in combination with chemotherapy. Given the toxicity associated with chemoradiation and poor outcomes seen in several types of cancers, combinations of EGFR targeted agents with or without chemotherapy have been tested in patients receiving radiation. To date, the only FDA approved use of an anti-EGFR therapy in combination with radiation therapy is for locally advanced head and neck cancer. Given the important role EGFR plays in lung and colorectal cancer and the benefit of EGFR inhibition combined with chemotherapy in these disease sites, it is perplexing why EGFR targeted therapies in combination with radiation or chemoradiation have not been more successful. In this review we summarize the clinical findings of EGFR targeted therapies combined with radiation and chemoradiation regimens. We then discuss the interaction between EGFR and radiation including radiation induced EGFR signaling, the effect of EGFR on DNA damage repair, and potential mechanisms of radiosensitization. Finally, we examine the potential pitfalls with scheduling EGFR targeted therapies with chemoradiation and the use of predictive biomarkers to improve patient selection. PMID:26205191

An unusual case of isolated, serial metastases of gallbladder carcinoma involving the chest wall, axilla, breast and lung parenchyma

PubMed Central

Jeyaraj, Pamela; Sio, Terence T.; Iott, Matthew J.

2013-01-01

In the English literature, only 9 cases of adenocarcinoma of the gallbladder with cutaneous metastasis have been reported so far. One case of multiple cutaneous metastases along with deposits in the breast tissue has been reported. We present a case of incidental metastatic gallbladder carcinoma with no intra-abdominal disease presenting as a series of four isolated cutaneous right chest wall, axillary nodal, breast, and pulmonary metastases following resection and adjuvant chemoradiation for her primary tumor. In spite of the metastatic disease coupled with the aggressive nature of the cancer, this patient reported that her energy level had returned to baseline with a good appetite and a stable weight indicating a good performance status and now is alive at 25 months since diagnosis. Her serially-presented, oligometastatic diseases were well-controlled by concurrent chemoradiotherapy and stereotactic radiation therapy. We report this case study because of its rarity and for the purpose of complementing current literature with an additional example of cutaneous metastasis from adenocarcinoma of the gallbladder. PMID:23772306

Chemoradiotherapy for stage III non-small cell lung cancer: have we reached the limit?

PubMed

Xu, Peng; Le Pechoux, Cecile

2015-12-01

Lung cancer is the leading cause of cancer-related mortality in men and the second leading cause in women. Approximately 85% of lung cancer patients have non-small cell lung cancer (NSCLC), and most present with advanced stage at diagnosis. The current treatment for such patients is chemoradiation (CRT) provided concurrently preferably or sequentially with chemotherapy, using conventionally fractionated radiation doses in the range of 60 to 66 Gy in 30 to 33 fractions. An individual patient data based metaanalysis has shown that in good performance status (PS), concomitant CRT was associated to improved survival by 4.5% compared to sequential combination (5-year survival rate of 15.1% and 10.6% respectively). In the recent years, improvement of modern technique of radiotherapy (RT) and new chemotherapy drugs may be favorable for the patients. Furthermore, the positron emission tomography-computed tomography (PET-CT) contributes to improved delineation of RT especially in terms of nodal involvement. Improving outcomes for patients with stage III disease remains a challenge, this review will address the questions that are considered fundamental to improving outcome in patients with stage III NSCLC.

One patient - three head and neck primaries: nasopharyngeal, tongue and thyroid cancers

PubMed Central

2013-01-01

Background We report a rare case of three head and neck malignancies in one patient. Squamous cell carcinoma of tongue and papillary thyroid carcinoma occurred as metachronous cancers in a patient with primary nasopharyngeal carcinoma. These three pathologically distinct malignancies of head and neck region in one patient is a rare phenomenon and is not reported so far. Case presentation A 60 year old Saudi female patient presented in March 2011 with locally advanced nasopharyngeal carcinoma. After completion of concurrent chemoradiation in June 2011, she developed two new primaries i-e thyroid cancer and tongue cancer in May 2012 along with recurrent nasopharyngeal carcinoma. We discuss histopathologic features, diagnostic tools and treatment modalities for this rarely existing case. Conclusion High index of suspicion and thorough work up is essential in follow up of patients with head and neck primary cancers. The effect of field cancerization and environmental factors need to be explored in greater depths in such selected cases. However, which patients are at increased risk of triplet primaries, is still unknown. PMID:24164964

Chemoselection: A Paradigm for Optimization of Organ Preservation in Locally Advanced Larynx Cancer

PubMed Central

Vainshtein, Jeffrey M.; Wu, Vivian F.; Spector, Matthew E.; Bradford, Carol R.; Wolf, Gregory T.; Worden, Francis P.

2014-01-01

Summary Definitive chemoradiation (CRT) and laryngectomy followed by postoperative radiotherapy (RT) are both considered standard of care options for the management of advanced laryngeal cancer. While organ preservation with chemoradiotherapy is often the preferred up-front approach for appropriately selected candidates, the functional benefits of organ preservation must be carefully balanced against the considerable morbidity of salvage laryngectomy in patients who fail primary chemoradiation. Up-front identification of patients who are likely to require surgical salvage, therefore, is an important aim of any organ preserving approach in order to minimize morbidity while maximizing organ preservation. To this end, a strategy of “chemoselection”, using the primary tumor's response after one cycle of induction chemotherapy as an in vivo method of selecting responders for definitive chemoradiation while reserving primary surgical management for non-responders, has been employed extensively at our institution. The rationale, treatment results, and future directions of this approach are discussed. PMID:24053204

In vivo Raman spectroscopy of cervix cancers

NASA Astrophysics Data System (ADS)

Rubina, S.; Sathe, Priyanka; Dora, Tapas Kumar; Chopra, Supriya; Maheshwari, Amita; Krishna, C. Murali

2014-03-01

Cervix-cancer is the third most common female cancer worldwide. It is the leading cancer among Indian females with more than million new diagnosed cases and 50% mortality, annually. The high mortality rates can be attributed to late diagnosis. Efficacy of Raman spectroscopy in classification of normal and pathological conditions in cervix cancers on diverse populations has already been demonstrated. Our earlier ex vivo studies have shown the feasibility of classifying normal and cancer cervix tissues as well as responders/non-responders to Concurrent chemoradiotherapy (CCRT). The present study was carried out to explore feasibility of in vivo Raman spectroscopic methods in classifying normal and cancerous conditions in Indian population. A total of 182 normal and 132 tumor in vivo Raman spectra, from 63 subjects, were recorded using a fiberoptic probe coupled HE-785 spectrometer, under clinical supervision. Spectra were acquired for 5 s and averaged over 3 times at 80 mW laser power. Spectra of normal conditions suggest strong collagenous features and abundance of non-collagenous proteins and DNA in case of tumors. Preprocessed spectra were subjected to Principal Component-Linear Discrimination Analysis (PCLDA) followed by leave-one-out-cross-validation. Classification efficiency of ~96.7% and 100% for normal and cancerous conditions respectively, were observed. Findings of the study corroborates earlier studies and suggest applicability of Raman spectroscopic methods in combination with appropriate multivariate tool for objective, noninvasive and rapid diagnosis of cervical cancers in Indian population. In view of encouraging results, extensive validation studies will be undertaken to confirm the findings.

Comparison of abdominoperineal resection and low anterior resection in lower and middle rectal cancer.

PubMed

Omidvari, Shapour; Hamedi, Sayed Hasan; Mohammadianpanah, Mohammad; Razzaghi, Samira; Mosalaei, Ahmad; Ahmadloo, Niloofar; Ansari, Mansour; Pourahmad, Saeideh

2013-09-01

This study aimed to investigate local control and survival rates following abdominoperineal resection (APR) compared with low anterior resection (LAR) in lower and middle rectal cancer. In this retrospective study, 153 patients with newly histologically proven rectal adenocarcinoma located at low and middle third that were treated between 2004 and 2010 at a tertiary hospital. The tumors were pathologically staged according to the 7th edition of the American Joint Committee on Cancer (AJCC) staging system. Surgery was applied for 138 (90%) of the patients, of which 96 (70%) underwent LAR and 42 were (30%) treated with APR. Total mesorectal excision was performed for all patients. In addition, 125 patients (82%) received concurrent (neoadjuvant, adjuvant or palliative) pelvic chemoradiation, and 134 patients (88%) received neoadjuvant, adjuvant or concurrent chemotherapy. Patients' follow-up ranged from 4 to 156 (median 37) months. Of 153 patients, 89 were men and 64 were women with a median age of 57 years. One patient (0.7%) was stage 0, 15 (9.8%) stage I, 63 (41.2%) stage II, 51 (33.3%) stage III and 23 (15%) stage IV. There was a significant difference between LAR and APR in terms of tumor distance from anal verge, disease stage and combined modality therapy used. However, there was no significant difference regarding 5-year local control, disease free and overall survival rates between LAR and APR. LAR can provide comparable local control, disease free and overall survival rates compared with APR in eligible patients with lower and middle rectal cancer. Copyright © 2013. Production and hosting by Elsevier B.V.

A retrospective evaluation of furosemide and mannitol for prevention of cisplatin-induced nephrotoxicity.

PubMed

Mach, C M; Kha, C; Nguyen, D; Shumway, J; Meaders, K M; Ludwig, M; Williams-Brown, M Y; Anderson, M L

2017-06-01

Nephrotoxicity is a recognized side effect of cisplatin chemotherapy. However, the optimal strategy for preventing cisplatin-induced nephrotoxicity, if any, remains unclear. The primary objective for this study was to determine whether mannitol or furosemide provides better nephroprotection when administered with hydration prior to weekly, low-dose cisplatin concurrently with whole pelvic radiotherapy. Clinical data were abstracted from all women who underwent chemoradiation for FIGO IB2-IVA cervical cancer at a regional safety net health system between January 2009 and December 2014. Creatinine clearance was estimated using the IDMS-traceable MDRD Study Equation. Descriptive statistics were used to summarize patient demographics. Cox proportional hazard models were used to identify factors associated with hypomagnesemia and survival. A total of 133 women received 656 weekly doses of single-agent cisplatin (40 mg/m 2 ) concomitant with whole pelvic radiation. Furosemide (20 mg) was administered intravenously prior to 341 cisplatin doses, whereas mannitol (24 g) was administered prior to 315 doses. Significant magnesium wasting was observed after the second weekly cisplatin infusion regardless of whether furosemide or mannitol was utilized. Repetitive low-dose cisplatin infusion had no impact on measured levels of serum creatinine or estimated glomerular filtration rate. Prior history of hypertension, diabetes mellitus, hepatitis C infection and acute gastrointestinal toxicity were each associated with early onset of hypomagnesemia. Repetitive administration of low-dose cisplatin concurrent with whole pelvic radiation is associated with magnesium wasting. However, choice of diuretic with pretreatment hydration had no significant impact on the severity of this adverse effect. © 2017 John Wiley & Sons Ltd.

Environmental Technology Verification Test Report of Mobile Source Selective Catalytic Reduction, Johnson Matthey SCCRT, Version 1, Selective Catalytic Reduction Technology with a Catalyzed Continuously Regenerating Trap

EPA Science Inventory

The Johnson Matthey SCCRT, v.1 technology is a urea-based SCR system combined with a CCRT filter designed for on-highway light, medium, and heavy heavy-duty diesel, urban and non-urban, bus exhaust gas recirculation (EGR)-or non-EGR-equipped engines for use with commercial ultra-...

Randomized phase II--study evaluating EGFR targeting therapy with cetuximab in combination with radiotherapy and chemotherapy for patients with locally advanced pancreatic cancer--PARC: study protocol [ISRCTN56652283].

PubMed

Krempien, R; Muenter, M W; Huber, P E; Nill, S; Friess, H; Timke, C; Didinger, B; Buechler, P; Heeger, S; Herfarth, K K; Abdollahi, A; Buchler, M W; Debus, J

2005-10-11

Pancreatic cancer is the fourth commonest cause of death from cancer in men and women. Advantages in surgical techniques, radiation therapy techniques, chemotherapeutic regimes, and different combined-modality approaches have yielded only a modest impact on the prognosis of patients with pancreatic cancer. Thus there is clearly a need for additional strategies. One approach involves using the identification of a number of molecular targets that may be responsible for the resistance of cancer cells to radiation or to other cytotoxic agents. As such, these molecular determinants may serve as targets for augmentation of the radiotherapy or chemotherapy response. Of these, the epidermal growth factor receptor (EGFR) has been a molecular target of considerable interest and investigation, and there has been a tremendous surge of interest in pursuing targeted therapy of cancers via inhibition of the EGFR. The PARC study is designed as an open, controlled, prospective, randomized phase II trial. Patients in study arm A will be treated with chemoradiation using intensity modulated radiation therapy (IMRT) combined with gemcitabine and simultaneous cetuximab infusions. After chemoradiation the patients receive gemcitabine infusions weekly over 4 weeks. Patients in study arm B will be treated with chemoradiation using intensity modulated radiation therapy (IMRT) combined with gemcitabine and simultaneous cetuximab infusions. After chemoradiation the patients receive gemcitabine weekly over 4 weeks and cetuximab infusions over 12 weeks. A total of 66 patients with locally advanced adenocarcinoma of the pancreas will be enrolled. An interim analysis for patient safety reasons will be done one year after start of recruitment. Evaluation of the primary endpoint will be performed two years after the last patient's enrollment. The primary objective of this study is to evaluate the feasibility and the toxicity profile of trimodal therapy in pancreatic adenocarcinoma with chemoradiation therapy with gemcitabine and intensity modulated radiation therapy (IMRT) and EGFR-targeted therapy using cetuximab and to compare between two different methods of cetuximab treatment schedules (concomitant versus concomitant and sequential cetuximab treatment). Secondary objectives are to determine the role and the mechanism of cetuximab in patient's chemoradiation regimen, the response rate, the potential of this combined modality treatment to concert locally advanced lesions to potentially resectable lesions, the time to progression interval and the quality of life.

[Rectal squamous cell carcinoma treatment: Retrospective experience in two French university hospitals, review and proposals].

PubMed

Schernberg, A; Servagi-Vernat, S; Loganadane, G; Touboul, E; Bosset, J-F; Huguet, F

2016-12-01

After publishing a retrospective series of 23 patients treated for a rectal squamous cell carcinoma with exclusive curative and conservative intent chemoradiation, we aim to propose a review of the literature about this rare tumour. We identified 11 retrospective studies, on 106 patients, treated between 2007 and 2016. Treatment of rectal squamous cell carcinoma should be similar to anal carcinoma, based on exclusive chemoradiation, displaying a 5-year overall survival rate over 80%, while it was 32% in surgical series. Baseline explorations should be similar as for anal carcinoma, with an interest in PET-CT at diagnosis and monitoring, after a delay over 6 weeks after chemoradiation. Intensity-modulated radiotherapy is legitimate, to a prophylactic dose between 36 and 45Gy, and over 54Gy to the tumour. Concomitant chemotherapy should combine an antimetabolite (5-fluorouracil or capecitabine) and mitomycin C, or cisplatin. This treatment seems well tolerated, associated with grade 2 or above toxicity below 30%. Follow-up should be established on anal squamous cell carcinoma schedule, with endoscopic ultrasonography and PET-CT. Rectal squamous cell carcinoma is a rare tumour; it management should be based on anal curative and conservative intent chemoradiation. Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

A phase II study of preoperative chemoradiation with tegafur-uracil plus leucovorin for locally advanced rectal cancer with pharmacogenetic analysis.

PubMed

Kim, Sun Young; Baek, Ji Yeon; Oh, Jae Hwan; Park, Sung Chan; Sohn, Dae Kyung; Kim, Min Ju; Chang, Hee Jin; Kong, Sun-Young; Kim, Dae Yong

2017-03-27

This study aimed to evaluate the efficacy of a high dose of oral tegafur-uracil (400 mg/m 2 ) plus leucovorin with preoperative chemoradiation of locally advanced rectal cancer and to explore the impact of polymorphisms of cytochrome P 2A6 (CYP2A6), uridine monophosphate synthetase (UMPS), and ATP-binding cassette B1 (ABCB1) on clinical outcome. Patients with cT3 or cT4 rectal cancer were enrolled and were given tegafur-uracil 400 mg/m 2 /day and leucovorin 90 mg/m 2 /day for 7 days a week during preoperative chemoradiation (50.4 Gy/28 fractions) in this phase II trial. Primary endpoint was pathologic complete response rate, and the secondary endpoint was to explore the association between clinical outcomes and genetic polymorphisms CYP2A6 (*4, *7, *9 and *10), UMPS G638C, and three ABCB1 genotypes (C1236T, C3435T, and G2677T). Ninety-one patients were given study treatment, and 90 underwent surgery. Pathologic complete response was noted in 10 patients (11.1%). There was no grade 4 or 5 toxicity; 20 (22.0%) experienced grade 3 toxicities, including diarrhea (10, 11.0%), abdominal pain (2, 2.2%), and anemia (2, 2.2%). Relapse-free survival and overall survival at 5 years were 88.6% and 94.2%, respectively. Patients with the UMPS 638 CC genotype experienced significantly more frequent grade 2 or 3 diarrhea (p for trend = 0.018). Preoperative chemoradiation with tegafur-uracil 400 mg/m 2 /day with leucovorin was feasible, but did not meet the expected pathologic complete response rate. The UMPS 638 CC genotype might be a candidate biomarker predicting toxicity in patients receiving tegafur-uracil/leucovorin-based preoperative chemoradiation for locally advanced rectal cancer. ISRCTN11812525 , registered on 25 July 2016. Retrospectively registered.

Psychodynamic psychotherapy for social phobia: a treatment manual based on supportive-expressive therapy.

PubMed

Leichsenring, Falk; Beutel, Manfred; Leibing, Eric

2007-01-01

Social phobia is a very frequent mental disorder characterized by an early onset, a chronic unremitting course, severe psychosocial impairments and high socioeconomic costs. To date, no manual for the psychodynamic treatment of social phobia exists. After a brief description of the disorder, a manual for a short-term psychodynamic treatment of social phobia is presented. The treatment is based on Luborsky s supportive-expressive (SE) therapy, which is complemented by treatment elements specific to social phobia. The treatment includes the characteristic elements of SE therapy, that is, setting goals, focus on the Core Conflictual Relationship Theme (CCRT) associated with the patient s symptoms, interpretive interventions to enhance insight into the CCRT, and supportive interventions, in particular fostering a helping alliance. In order to tailor the treatment more specifically to social phobia, treatment elements have been added, for example informing the patient about the disorder and the treatment, a specific focus on shame and on unrealistic demands, and encouraging the patient to confront anxiety-producing situations. More directive interventions are included as well, such as specific prescriptions to stop persisting self-devaluations. The treatment manual is presently being used in a large-scale randomized controlled multicenter study comparing short-term psychodynamic psychotherapy and cognitive-behavioral therapy in the treatment of social phobia.

Cervix regression and motion during the course of external beam chemoradiation for cervical cancer.

PubMed

Beadle, Beth M; Jhingran, Anuja; Salehpour, Mohammad; Sam, Marianne; Iyer, Revathy B; Eifel, Patricia J

2009-01-01

To evaluate the magnitude of cervix regression and motion during external beam chemoradiation for cervical cancer. Sixteen patients with cervical cancer underwent computed tomography scanning before, weekly during, and after conventional chemoradiation. Cervix volumes were calculated to determine the extent of cervix regression. Changes in the center of mass and perimeter of the cervix between scans were used to determine the magnitude of cervix motion. Maximum cervix position changes were calculated for each patient, and mean maximum changes were calculated for the group. Mean cervical volumes before and after 45 Gy of external beam irradiation were 97.0 and 31.9 cc, respectively; mean volume reduction was 62.3%. Mean maximum changes in the center of mass of the cervix were 2.1, 1.6, and 0.82 cm in the superior-inferior, anterior-posterior, and right-left lateral dimensions, respectively. Mean maximum changes in the perimeter of the cervix were 2.3 and 1.3 cm in the superior and inferior, 1.7 and 1.8 cm in the anterior and posterior, and 0.76 and 0.94 cm in the right and left lateral directions, respectively. Cervix regression and internal organ motion contribute to marked interfraction variations in the intrapelvic position of the cervical target in patients receiving chemoradiation for cervical cancer. Failure to take these variations into account during the application of highly conformal external beam radiation techniques poses a theoretical risk of underdosing the target or overdosing adjacent critical structures.

Randomized, Double-Blind, Placebo-Controlled Trial of Shuanghua Baihe Tablets to Prevent Oral Mucositis in Patients With Nasopharyngeal Cancer Undergoing Chemoradiation Therapy.

PubMed

Zheng, Baomin; Zhu, Xiaodong; Liu, Mengzhong; Yang, Zhenzhou; Yang, Ling; Lang, Jinyi; Shi, Mei; Wu, Gang; He, Xia; Chen, Xiaozhong; Xi, Xuping; Zhao, Dan; Zhu, Guangying

2018-02-01

Oral mucositis is a common unpreventable complication associated with chemoradiation therapy. Shuanghua Baihe tablets have been approved by the Chinese Food and Drug Administration for treating recurrent oral mucosa ulceration. This study assessed whether Shuanghua Baihe tablets could prevent oral mucositis during chemoradiation therapy for locally advanced nasopharyngeal carcinoma. This multicenter, randomized, double-blind, placebo-controlled trial was conducted at 11 hospitals in China between January 22, 2014, and September 21, 2015. Eligible patients (N=240, 18-70 years old) with pathologically diagnosed locally advanced nasopharyngeal carcinoma were randomly assigned (computer-block randomization; 1:1) to receive Shuanghua Baihe tablets or a placebo (4 tablets, 3 times a day, for 7 weeks) at the initiation of chemoradiation therapy. Administration of Shuanghua Baihe tablets could be ended if grade 3 or higher oral mucositis developed and patients were unwilling to continue taking the drug. The primary endpoints were oral mucositis incidence and latency. The incidence of oral mucositis during this study was significantly lower in the Shuanghua Baihe group (85.0%; 95% confidence interval [CI], 78.6%-91.4%) than in the placebo group (96.6%; 95% CI, 93.4%-99.9%; P=.0028). The median latency period was 28 days in the Shuanghua Baihe group and 14 days in the placebo group (hazard ratio, 0.17; 95% CI, 0.12-0.23; P<.0001). Compared with placebo, Shuanghua Baihe tablets significantly reduced the oral mucositis severity scores recorded by the investigators (Oral Mucositis Score, 24.0 [range, 0.0-67.8] vs 57.5 [range, 0.0-98.0]; P<.0001), full-time nurses (Oral Assessment Guide score, 462.0 [range, 392.0-664.7] vs 520.4 [range, 392.0-714.0]; P<.0001), and patients (score for soreness of mouth and throat, 4.0 [range, 0-10] vs 6.0 [range, 0-10]; P<.0001). No serious adverse events were observed, and the incidence of mild or moderate gastrointestinal adverse events associated with Shuanghua Baihe tablets was 3.3%. The short-term response rate was similar in patients receiving Shuanghua Baihe tablets and those receiving placebo during chemoradiation therapy during this study. Shuanghua Baihe tablets reduced the occurrence, latency, and severity of oral mucositis in patients with nasopharyngeal cancer during chemoradiation therapy treatment. Copyright © 2017. Published by Elsevier Inc.

Quality of Life in Rectal Cancer Patients After Chemoradiation: Watch-and-Wait Policy Versus Standard Resection - A Matched-Controlled Study.

PubMed

Hupkens, Britt J P; Martens, Milou H; Stoot, Jan H; Berbee, Maaike; Melenhorst, Jarno; Beets-Tan, Regina G; Beets, Geerard L; Breukink, Stéphanie O

2017-10-01

Fifteen to twenty percent of patients with locally advanced rectal cancer have a clinical complete response after chemoradiation therapy. These patients can be offered nonoperative organ-preserving treatment, the so-called watch-and-wait policy. The main goal of this watch-and-wait policy is an anticipated improved quality of life and functional outcome in comparison with a total mesorectal excision, while maintaining a good oncological outcome. The aim of this study was to compare the quality of life of watch-and-wait patients with a matched-controlled group of patients who underwent chemoradiation and surgery (total mesorectal excision group). This was a matched controlled study. This study was conducted at multiple centers. The study population consisted of 2 groups: 41 patients after a watch-and-wait policy and 41 matched patients after chemoradiation and surgery. Patients were matched on sex, age, tumor stage, and tumor height. All patients were disease free at the moment of recruitment after a minimal follow-up of 2 years. Quality of life was measured by validated questionnaires covering general quality of life (Short Form 36, European Organization for Research and Treatment of Cancer QLQ-C30), disease-specific total mesorectal excision (European Organization for Research and Treatment of Cancer QLQ-CR38), defecation problems (Vaizey and low anterior resection syndrome scores), sexual problems (International Index of Erectile Function and Female Sexual Function Index), and urinary dysfunction (International Prostate Symptom Score). The watch-and-wait group showed better physical and cognitive function, better physical and emotional roles, and better global health status compared with the total mesorectal excision group. The watch-and-wait patients showed fewer problems with defecation and sexual and urinary tract function. This study only focused on watch-and-wait patients who achieved a sustained complete response for 2 years. In addition, this is a study with a limited number of patients and with quality-of-life measurements on nonpredefined and variable intervals after surgery. After a successful watch-and-wait approach, the quality of life was better than after chemoradiation and surgery on several domains. However, chemoradiation therapy on its own is not without long-term side effects, because one-third of the watch-and-wait patients experienced major low anterior resection syndrome symptoms, compared with 66.7% of the patients in the total mesorectal excision group. See Video Abstract at http://links.lww.com/DCR/A395.

Gemcitabine-induced rectus abdominus radiation recall.

PubMed

Fakih, Marwan G

2006-05-09

Radiation recall has been described in the context of gemcitabine chemotherapy. However, this phenomenon has been largely limited to skin. We hereby report a case of radiation recall dermatitis and myositis occurring on gemcitabine monotherapy, five months after completing chemoradiation for locally advanced pancreatic cancer. Radiation recall resolved spontaneously with withdrawal of gemcitabine. This is the second case report that describes gemcitabine-induced radiation recall in rectus abdominus muscles after gemcitabine-based radiation therapy. Given the wide use of gemcitabine following chemoradiation for pancreatic cancer, providers should be aware of this potential complication.

A phase I, dose-finding study of sorafenib in combination with gemcitabine and radiation therapy in patients with unresectable pancreatic adenocarcinoma: a Grupo Español Multidisciplinario en Cáncer Digestivo (GEMCAD) study.

PubMed

Aparicio, Jorge; García-Mora, Carmen; Martín, Marta; Petriz, Ma Lourdes; Feliu, Jaime; Sánchez-Santos, Ma Elena; Ayuso, Juan Ramón; Fuster, David; Conill, Carlos; Maurel, Joan

2014-01-01

Sorafenib, an oral inhibitor of B-raf, VEGFR2, and PDGFR2-beta, acts against pancreatic cancer in preclinical models. Due to the radio-sensitization activity of both sorafenib and gemcitabine, we designed a multicenter, phase I trial to evaluate the safety profile and the recommended dose of this combination used with concomitant radiation therapy. Patients with biopsy-proven, unresectable pancreatic adenocarcinoma (based on vascular invasion detected by computed tomography) were treated with gemcitabine (300 mg/m2 i.v. weekly ×5 weeks) concurrently with radiation therapy (45 Gy in 25 fractions) and sorafenib (escalated doses in a 3+3 design, from 200 to 800 mg/day). Radiation portals included the primary tumor but not the regional lymph nodes. Patients with planning target volumes (PTV) over 500 cc were excluded. Cases not progressing during chemoradiation were allowed to continue with sorafenib until disease progression. Twelve patients were included. Three patients received 200 mg/day, 6 received 400 mg/day, and 3 received 800 mg/day; PTVs ranged from 105 to 500 cc. No dose-limiting toxicities occurred. The most common grade 2 toxicities were fatigue, neutropenia, nausea, and raised serum transaminases. Treatment was discontinued in one patient because of a reversible posterior leukoencephalopathy. There were no treatment-related deaths. The addition of sorafenib to concurrent gemcitabine and radiation therapy showed a favorable safety profile in unresectable pancreatic adenocarcinoma. A dose of 800 mg/day is recommended for phase II evaluation. EudraCT 2007-003211-31 ClinicalTrials.gov 00789763.

Phase II Trial of Hyperfractionated Intensity-Modulated Radiation Therapy and Concurrent Weekly Cisplatin for Stage III and IVa Head-and-Neck Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maguire, Patrick D., E-mail: pmaguire@nhroc.co; Papagikos, Michael; Hamann, Sue

2011-03-15

Purpose: To investigate a novel chemoradiation regimen designed to maximize locoregional control (LRC) and minimize toxicity for patients with advanced head-and-neck squamous cell carcinoma (HNSCC). Methods and Materials: Patients received hyperfractionated intensity modulated radiation therapy (HIMRT) in 1.25-Gy fractions b.i.d. to 70 Gy to high-risk planning target volume (PTV). Intermediate and low-risk PTVs received 60 Gy and 50 Gy, at 1.07, and 0.89 Gy per fraction, respectively. Concurrent cisplatin 33 mg/m{sup 2}/week was started Week 1. Patients completed the Quality of Life Radiation Therapy Instrument pretreatment (PRE), at end of treatment (EOT), and at 1, 3, 6, 9, and 12more » months. Overall survival (OS), progression-free (PFS), LRC, and toxicities were assessed. Results: Of 39 patients, 30 (77%) were alive without disease at median follow-up of 37.5 months. Actuarial 3-year OS, PFS, and LRC were 80%, 82%, and 87%, respectively. No failures occurred in the electively irradiated neck and there were no isolated neck failures. Head and neck QOL was significantly worse in 18 of 35 patients (51%): mean 7.8 PRE vs. 3.9 EOT. By month 1, H and N QOL returned near baseline (mean 6.2, SD = 1.7). The most common acute Grade 3+ toxicities were mucositis (38%), fatigue (28%), dysphagia (28%), and leukopenia (26%). Conclusions: Hyperfractionated IMRT with low-dose weekly cisplatin resulted in good LRC with acceptable toxicity and QOL. Lack of elective nodal failures despite very low dose per fraction has led to an attempt to further minimize toxicity by reducing elective nodal doses in our subsequent protocol.« less

Preoperative Capecitabine and Pelvic Radiation in Locally Advanced Rectal Cancer-Is it Equivalent to 5-FU Infusion Plus Leucovorin and Radiotherapy?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chan, Alexander K., E-mail: alexc@cancerboard.ab.c; Wong, Alfred O.; Jenken, Daryl A.

2010-04-15

Purpose: The aim of this retrospective case-matching study was to compare the treatment outcomes and acute toxicity of preoperative radiotherapy (RT) with capecitabine vs. preoperative RT with intermittent 5-fluorouracil (5-FU) infusion, leucovorin, and mitomycin C in rectal cancer. Methods and Materials: We matched 34 patients who were treated with preoperative concurrent capecitabine and 50 Gy of RT by their clinical T stage (T3 or T4) and the tumor location (<=7 cm or >7 cm from the anal verge) with another 68 patients who were treated with preoperative intermittent 5-FU infusion, leucovorin, mitomycin C, and 50 Gy of RT for amore » comparison of the pathologic tumor response, local control, distant failure, and survival rates. Results: The pathologic complete response rate was 21% with capecitabine and 18% with 5-FU and leucovorin (p = 0.72). The rate of T downstaging after chemoradiation was 59% for both groups. The rate of sphincter-sparing resection was 38% after capecitabine plus RT and 43% after 5-FU plus RT (p = 0.67). At 3 years, there was no significant difference in the local control rate (93% for capecitabine and 92% for 5-FU and leucovorin), relapse-free rate (74% for capecitabine and 73% for 5-FU and leucovorin), or disease-specific survival rate (86% for capecitabine and 77% for 5-FU and leucovorin). The acute toxicity profile was comparable, with little Grade 3 and 4 toxicity. Conclusions: When administered with concurrent preoperative RT, both capecitabine and intermittent 5-FU infusion with leucovorin modulation provided comparable pathologic tumor response, local control, relapse-free survival, and disease-specific survival rates in rectal cancer.« less

Preoperative chemoradiation with paclitaxel-carboplatin or with fluorouracil-oxaliplatin-folinic acid (FOLFOX) for resectable esophageal and junctional cancer: the PROTECT-1402, randomized phase 2 trial.

PubMed

Messager, Mathieu; Mirabel, Xavier; Tresch, Emmanuelle; Paumier, Amaury; Vendrely, Véronique; Dahan, Laetitia; Glehen, Olivier; Vasseur, Frederique; Lacornerie, Thomas; Piessen, Guillaume; El Hajbi, Farid; Robb, William B; Clisant, Stéphanie; Kramar, Andrew; Mariette, Christophe; Adenis, Antoine

2016-05-18

Often curative treatment for locally advanced resectable esophageal or gastro-esophageal junctional cancer consists of concurrent neoadjuvant radiotherapy and chemotherapy followed by surgery. Currently, one of the most commonly used chemotherapy regimens in this setting is a combination of a fluoropyrimidin and of a platinum analogue. Due to the promising results of the recent CROSS trial, another regimen combining paclitaxel and carboplatin is also widely used by European and American centers. No clinical study has shown the superiority of one treatment over the other. The objective of this Phase II study is to clarify clinical practice by comparing these two chemotherapy treatments. Our aim is to evaluate, in operable esophageal and gastro-esophageal junctional cancer, the complete resection rate and severe postoperative morbidity rate associated with these two neoadjuvant chemotherapeutic regimens (carboplatin-paclitaxel or fluorouracil-oxaliplatin-folinic acid) when each is combined with the radiation regime utilized in the CROSS trial. PROTECT is a prospective, randomized, multicenter, open arms, phase II trial. Eligible patients will have a histologically confirmed adenocarcinoma or squamous cell carcinoma and be treated with neoadjuvant radiochemotherapy followed by surgery for stage IIB or stage III resectable esophageal cancer. A total of 106 patients will be randomized to receive either 3 cycles of FOLFOX combined to concurrent radiotherapy (41.4 Grays) or carboplatin and paclitaxel with the same radiation regimen, using a 1:1 allocation ratio. This ongoing trial offers the unique opportunity to compare two standards of chemotherapy delivered with a common regimen of preoperative radiation, in the setting of operable locally advanced esophageal or gastro-esophageal junctional tumors. NCT02359968 (ClinicalTrials.gov) (registration date: 9 FEB 2015), EudraCT: 2014-000649-62 (registration date: 10 FEB 2014).

Improving outcomes in veterans with oropharyngeal squamous cell carcinoma through implementation of a multidisciplinary clinic.

PubMed

Light, Tyler; Rassi, Edward El; Maggiore, Ronald J; Holland, John; Reed, Julie; Suriano, Kathleen; Stooksbury, Marcelle; Tobin, Nora; Gross, Neil; Clayburgh, Daniel

2017-06-01

Treatment of head and neck cancer is complex, and a multidisciplinary clinic may improve the coordination of care. The value of a head and neck multidisciplinary clinic has not yet been established in oropharyngeal squamous cell carcinoma (SCC). A retrospective review was conducted of Veterans Affairs patients with oropharyngeal SCC undergoing concurrent chemoradiation before and after implementation of the head and neck multidisciplinary clinic. Fifty-two patients before and 54 patients after multidisciplinary clinic were included in this study. Age, tobacco use, and p16+ status were similar between groups. With multidisciplinary clinic, time to treatment decreased, and utilization of supportive services, including speech pathology, dentistry, and nutrition increased. The 5-year disease-specific survival rate increased from 63% to 81% (p = .043) after implementation of the multidisciplinary clinic. Multivariate analysis showed that disease stage (p = .016), p16 status (p = .006), and multidisciplinary clinic participation (p = .042) were predictors of disease-specific survival. Implementation of a multidisciplinary clinic improved care coordination and disease-specific survival in patients with oropharyngeal SCC. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1106-1112, 2017. © 2017 Wiley Periodicals, Inc.

Xerostomia in patients treated for oropharyngeal carcinoma: comparing linear accelerator-based intensity-modulated radiation therapy with helical tomotherapy.

PubMed

Fortin, Israël; Fortin, Bernard; Lambert, Louise; Clavel, Sébastien; Alizadeh, Moein; Filion, Edith J; Soulières, Denis; Bélair, Manon; Guertin, Louis; Nguyen-Tan, Phuc Felix

2014-09-01

In comparison to sliding-window intensity-modulated radiation therapy (sw-IMRT), we hypothesized that helical tomotherapy (HT) would achieve similar locoregional control and, at the same time, decrease the parotid gland dose, thus leading to a xerostomia reduction. The association between radiation techniques, mean parotid dose, and xerostomia incidence, was reviewed in 119 patients with advanced oropharyngeal carcinoma treated with concurrent chemoradiation using sw-IMRT (n = 59) or HT (n = 60). Ipsilateral and contralateral parotid mean doses were significantly lower for patients treated with HT versus sw-IMRT: 24 Gy versus 32 Gy ipsilaterally and 20 Gy versus 25 Gy contralaterally. The incidence of grade ≥2 xerostomia was significantly lower in the HT group than in the sw-IMRT group: 12% versus 78% at 6 months, 3% versus 51% at 12 months, and 0% versus 25% at 24 months. Total parotid mean dose <25 Gy was strongly associated to a lower incidence of grade ≥2 xerostomia at 6, 12, and 24 months. This retrospective series suggests that using HT can better spare the parotid glands while respecting quantitative analysis of normal tissue effects in the clinic (QUANTEC)'s criteria. Copyright © 2013 Wiley Periodicals, Inc.

Outcome of Radiation Monotherapy for High-risk Patients with Stage I Esophageal Cancer.

PubMed

Shirakawa, Yasuhiro; Noma, Kazuhiro; Maeda, Naoaki; Tanabe, Shunsuke; Kuroda, Shinji; Kagawa, Shunsuke; Katsui, Kuniaki; Katayama, Norihisa; Kanazawa, Susumu; Fujiwara, Toshiyoshi

2017-04-01

Currently, chemoradiation is the most widely used nonsurgical treatment for esophageal cancer. However, some patients, particularly the very elderly or those with severe vital organ dysfunction, face difficulty with the chemotherapy component. We therefore examined the outcome of radiation therapy (RT) alone for patients with esophageal cancer at our facility. Between January 2005 and December 2014, 84 patients underwent RT at our hospital, and 78 of these patients received concomitant chemotherapy. The remaining 6 patients underwent RT alone; these patients were considered to be high-risk and to have no lymph node metastasis (stage I). Five of them received irradiation up to a curative dose: 4 showed a complete response (CR) and 1 showed a partial response (PR). Of the patients exhibiting CR, 3 are currently living recurrence-free, whereas 1 patient underwent endoscopic submucosal dissection (ESD) as salvage therapy for local recurrence, with no subsequent recurrence. High-risk stage I esophageal cancer patients can be treated radically with RT alone under certain conditions. In the future, to broaden the indications for RT monotherapy to include some degree of advanced cancers, a novel concurrent therapy should be identified.

Changes in Cervical Cancer FDG Uptake During Chemoradiation and Association With Response

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kidd, Elizabeth A., E-mail: ekidd@stanford.edu; Thomas, Maria; Siegel, Barry A.

2013-01-01

Purpose: Previous research showed that pretreatment uptake of F-18 fluorodeoxyglucose (FDG), as assessed by the maximal standardized uptake value (SUV{sub max}) and the variability of uptake (FDG{sub hetero}), predicted for posttreatment response in cervical cancer. In this pilot study, we evaluated the changes in SUV{sub max} and FDG{sub hetero} during concurrent chemoradiation for cervical cancer and their association with post-treatment response. Methods and Materials: Twenty-five patients with stage Ib1-IVa cervical cancer were enrolled. SUV{sub max}, FDG{sub hetero}, and metabolic tumor volume (MTV) were recorded from FDG-positron emission tomography (PET)/computed tomography (CT) scans performed pretreatment and during weeks 2 and 4more » of treatment and were evaluated for changes and association with response assessed on 3-month post-treatment FDG-PET/CT. Results: For all patients, the average pretreatment SUV{sub max} was 17.8, MTV was 55.4 cm{sup 3}, and FDG{sub hetero} was -1.33. A similar decline in SUV{sub max} was seen at week 2 compared with baseline and week 4 compared with week 2 (34%). The areas of highest FDG uptake in the tumor remained relatively consistent on serial scans. Mean FDG{sub hetero} decreased during treatment. For all patients, MTV decreased more from week 2 to week 4 than from pretreatment to week 2. By week 4, the average SUV{sub max} had decreased by 57% and the MTV had decreased by 30%. Five patients showed persistent or new disease on 3-month post-treatment PET. These poor responders showed a higher average SUV{sub max}, larger MTV, and greater heterogeneity at all 3 times. Week 4 SUV{sub max} (P=.037), week 4 FDG{sub hetero} (P=.005), pretreatment MTV (P=.008), and pretreatment FDG{sub hetero} (P=.008) were all significantly associated with post-treatment PET response. Conclusions: SUV{sub max} shows a consistent rate of decline during treatment and declines at a faster rate than MTV regresses. Based on this pilot study, pretreatment and week 4 of treatment represent the best time points for prediction of response.« less

Institutional Enrollment and Survival Among NSCLC Patients Receiving Chemoradiation: NRG Oncology Radiation Therapy Oncology Group (RTOG) 0617.

PubMed

Eaton, Bree R; Pugh, Stephanie L; Bradley, Jeffrey D; Masters, Greg; Kavadi, Vivek S; Narayan, Samir; Nedzi, Lucien; Robinson, Cliff; Wynn, Raymond B; Koprowski, Christopher; Johnson, Douglas W; Meng, Joanne; Curran, Walter J

2016-09-01

The purpose of this analysis is to evaluate the effect of institutional accrual volume on clinical outcomes among patients receiving chemoradiation for locally advanced non-small cell lung cancer (LA-NSCLC) on a phase III trial. Patients with LA-NSCLC were randomly assigned to 60 Gy or 74 Gy radiotherapy (RT) with concurrent carboplatin/paclitaxel +/- cetuximab on NRG Oncology RTOG 0617. Participating institutions were categorized as low-volume centers (LVCs) or high-volume centers (HVCs) according to the number of patients accrued (≤3 vs > 3). All statistical tests were two-sided. Range of accrual for LVCs (n = 195) vs HVCs (n = 300) was 1 to 3 vs 4 to 18 patients. Baseline characteristics were similar between the two cohorts. Treatment at a HVC was associated with statistically significantly longer overall survival (OS) and progression-free survival (PFS) compared with treatment at a LVC (median OS = 26.2 vs 19.8 months; HR = 0.70, 95% CI = 0.56 to 0.88, P = .002; median PFS: 11.4 vs 9.7 months, HR = 0.80, 95% CI = 0.65-0.99, P = .04). Patients treated at HVCs were more often treated with intensity-modulated RT (54.0% vs 39.5%, P = .002), had a lower esophageal dose (mean = 26.1 vs 28.0 Gy, P = .03), and had a lower heart dose (median = V5 Gy 38.2% vs 54.1%, P = .006; V50 Gy 3.6% vs 7.3%, P < .001). Grade 5 adverse events (AEs) (5.3% vs 9.2%, P = .09) and RT termination because of AEs (1.3% vs 4.1%, P = .07) were less common among patients treated at HVCs. HVC remained independently associated with longer OS (P = .03) when accounting for other factors. Treatment at institutions with higher clinical trial accrual volume is associated with longer OS among patients with LA-NSCLC participating in a phase III trial. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Significance of ERBB2 Overexpression in Therapeutic Resistance and Cancer-Specific Survival in Muscle-Invasive Bladder Cancer Patients Treated With Chemoradiation-Based Selective Bladder-Sparing Approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Inoue, Masaharu; Koga, Fumitaka, E-mail: f-koga@cick.jp; Yoshida, Soichiro

2014-10-01

Purpose: To investigate the associations of ERBB 2 overexpression with chemoradiation therapy (CRT) resistance and cancer-specific survival (CSS) in muscle-invasive bladder cancer (MIBC) patients treated with the CRT-based bladder-sparing protocol. Methods and Materials: From 1997 to 2012, 201 patients with cT2-4aN0M0 bladder cancer were treated with CRT (40 Gy with concurrent cisplatin) following transurethral resection of bladder tumor (TURBT). Basically, patients with tumors that showed good CRT response and were amenable to segmental resection underwent partial cystectomy (PC) with pelvic lymph node dissection for bladder preservation; otherwise, radical cystectomy (RC) was recommended. Included in this study were 119 patients in whom TURBTmore » specimens were available for immunohistochemical analysis of ERBB 2 expression. Following CRT, 30 and 65 patients underwent PC or RC, respectively; the remaining 24 patients did not undergo cystectomy. Tumors were defined as CRT-resistant when patients did not achieve complete response after CRT. Associations of ERBB 2 overexpression with CRT resistance and CSS were evaluated. Results: CRT resistance was observed clinically in 56% (67 of 119 patients) and pathologically (in cystectomy specimens) in 55% (52 of 95 patients). ERBB 2 overexpression was observed in 45 patients (38%). On multivariate analysis, ERBB 2 overexpression was an independent predictor for CRT resistance clinically (odds ratio, 3.6; P=.002) and pathologically (odds ratio, 2.9; P=.031). ERBB 2 overexpression was associated with shorter CSS (5-year CSS rates, 56% vs 87% for the ERBB 2 overexpression group vs the others; P=.001). ERBB 2 overexpression was also an independent risk factor for bladder cancer death at all time points of our bladder-sparing protocol (pre-CRT, post-CRT, and post-cystectomy). Conclusions: ERBB 2 overexpression appears relevant to CRT resistance and unfavorable CSS in MIBC patients treated with the CRT-based bladder-sparing protocol. ERBB 2-targeting treatment may improve the outcomes of such patients.« less

Hematologic Nadirs During Chemoradiation for Anal Cancer: Temporal Characterization and Dosimetric Predictors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Andrew Y.; Golden, Daniel W.; Bazan, Jose G.

Purpose: Pelvic bone marrow (BM) constraints may offer a means to reduce the toxicity commonly associated with chemoradiation for anal cancer. We conducted a bi-institutional analysis of dose-volume metrics in a time-sensitive fashion to devise practical metrics to minimize hematologic toxicity. Methods and Materials: Fifty-six anal cancer patients from 2 institutions received definitive radiation therapy (median primary dose of 54 Gy) using intensity modulated radiation therapy (IMRT, n=49) or 3-dimensional (3D) conformal therapy (n=7) with concurrent 5-fluorouracil (5-FU) and mitomycin C. Weekly blood counts were retrospectively plotted to characterize the time course of cytopenias. Dose-volume parameters were correlated with blood countsmore » at a standardized time point to identify predictors of initial blood count nadirs. Results: Leukocytes, neutrophils, and platelets reached a nadir at week 3 of treatment. Smaller volumes of the pelvic BM correlated most strongly with lower week 3 blood counts, more so than age, sex, body mass index (BMI), or dose metrics. Patients who had ≥750 cc of pelvic BM spared from doses of ≥30 Gy had 0% grade 3+ leukopenia or neutropenia at week 3. Higher V40 Gy to the lower pelvic BM (LP V40) also correlated with cytopenia. Patients with an LP V40 >23% had higher rates of grade 3+ leukopenia (29% vs 4%, P=.02), grade 3+ neutropenia (33% vs 8%, P=.04), and grade 2+ thrombocytopenia (32% vs 7%, P=.04) at week 3. On multivariate analysis, pelvic BM volume and LP V40 remained associated with leukocyte count, and all marrow subsite volumes remained associated with neutrophil counts at week 3 (P<.1). Conclusions: Larger pelvic BM volumes correlate with less severe leukocyte and neutrophil nadirs, suggesting that larger total “marrow reserve” can mitigate cytopenias. Sparing a critical marrow reserve and limiting the V40 Gy to the lower pelvis may reduce the risk of hematologic toxicity.« less

Precision Hypofractionated Radiation Therapy in Poor Performing Patients With Non-Small Cell Lung Cancer: Phase 1 Dose Escalation Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Westover, Kenneth D.; Loo, Billy W.; Gerber, David E.

2015-09-01

Purpose: Treatment regimens for locally advanced non-small cell lung cancer (NSCLC) give suboptimal clinical outcomes. Technological advancements such as radiation therapy, the backbone of most treatment regimens, may enable more potent and effective therapies. The objective of this study was to escalate radiation therapy to a tumoricidal hypofractionated dose without exceeding the maximally tolerated dose (MTD) in patients with locally advanced NSCLC. Methods and Materials: Patients with stage II to IV or recurrent NSCLC and Eastern Cooperative Oncology Group performance status of 2 or greater and not candidates for surgical resection, stereotactic radiation, or concurrent chemoradiation were eligible. Highly conformal radiationmore » therapy was given to treat intrathoracic disease in 15 fractions to a total of 50, 55, or 60 Gy. Results: Fifty-five patients were enrolled: 15 at the 50-Gy, 21 at the 55-Gy, and 19 at the 60-Gy dose levels. A 90-day follow-up was completed in each group without exceeding the MTD. With a median follow-up of 12.5 months, there were 93 grade ≥3 adverse events (AEs), including 39 deaths, although most AEs were considered related to factors other than radiation therapy. One patient from the 55- and 60-Gy dose groups developed grade ≥3 esophagitis, and 5, 4, and 4 patients in the respective dose groups experienced grade ≥3 dyspnea, but only 2 of these AEs were considered likely related to therapy. There was no association between fraction size and toxicity (P=.24). The median overall survival was 6 months with no significant differences between dose levels (P=.59). Conclusions: Precision hypofractionated radiation therapy consisting of 60 Gy in 15 fractions for locally advanced NSCLC is generally well tolerated. This treatment regimen could provide patients with poor performance status a potent alternative to chemoradiation. This study has implications for the cost effectiveness of lung cancer therapy. Additional studies of long-term safety and efficacy of this therapy are warranted.« less

Significance of ERBB2 overexpression in therapeutic resistance and cancer-specific survival in muscle-invasive bladder cancer patients treated with chemoradiation-based selective bladder-sparing approach.

PubMed

Inoue, Masaharu; Koga, Fumitaka; Yoshida, Soichiro; Tamura, Tomoki; Fujii, Yasuhisa; Ito, Eisaku; Kihara, Kazunori

2014-10-01

To investigate the associations of ERBB 2 overexpression with chemoradiation therapy (CRT) resistance and cancer-specific survival (CSS) in muscle-invasive bladder cancer (MIBC) patients treated with the CRT-based bladder-sparing protocol. From 1997 to 2012, 201 patients with cT2-4aN0M0 bladder cancer were treated with CRT (40 Gy with concurrent cisplatin) following transurethral resection of bladder tumor (TURBT). Basically, patients with tumors that showed good CRT response and were amenable to segmental resection underwent partial cystectomy (PC) with pelvic lymph node dissection for bladder preservation; otherwise, radical cystectomy (RC) was recommended. Included in this study were 119 patients in whom TURBT specimens were available for immunohistochemical analysis of ERBB 2 expression. Following CRT, 30 and 65 patients underwent PC or RC, respectively; the remaining 24 patients did not undergo cystectomy. Tumors were defined as CRT-resistant when patients did not achieve complete response after CRT. Associations of ERBB 2 overexpression with CRT resistance and CSS were evaluated. CRT resistance was observed clinically in 56% (67 of 119 patients) and pathologically (in cystectomy specimens) in 55% (52 of 95 patients). ERBB 2 overexpression was observed in 45 patients (38%). On multivariate analysis, ERBB 2 overexpression was an independent predictor for CRT resistance clinically (odds ratio, 3.6; P=.002) and pathologically (odds ratio, 2.9; P=.031). ERBB 2 overexpression was associated with shorter CSS (5-year CSS rates, 56% vs 87% for the ERBB 2 overexpression group vs the others; P=.001). ERBB 2 overexpression was also an independent risk factor for bladder cancer death at all time points of our bladder-sparing protocol (pre-CRT, post-CRT, and post-cystectomy). ERBB 2 overexpression appears relevant to CRT resistance and unfavorable CSS in MIBC patients treated with the CRT-based bladder-sparing protocol. ERBB 2-targeting treatment may improve the outcomes of such patients. Copyright © 2014 Elsevier Inc. All rights reserved.

Racial Survival Disparity in Head and Neck Cancer Results from Low Prevalence of Human Papillomavirus Infection in Black Oropharyngeal Cancer Patients

PubMed Central

Settle, Kathleen; Posner, Marshall R.; Schumaker, Lisa M.; Tan, Ming; Suntharalingam, Mohan; Goloubeva, Olga; Strome, Scott E.; Haddad, Robert I.; Patel, Shital S.; Cambell, Earl V.; Sarlis, Nicholas; Lorch, Jochen; Cullen, Kevin J.

2015-01-01

The burden of squamous cell carcinoma of the head and neck (SCCHN) is greater for blacks than for whites, especially in oropharyngeal cases. We previously showed retrospectively that disease-free survival was significantly greater in white than in black SCCHN patients treated with chemoradiation, the greatest difference occurring in the oropharyngeal subgroup. Oropharyngeal cancer is increasing in incidence and in its association with human papillomavirus (HPV) infection; HPV-positive oropharyngeal cancer patients have significantly better outcomes (versus HPV-negative). These collective data led to the present analyses of overall survival (OS) in our retrospective cohort and of OS and HPV status (tested prospectively in pretreatment biopsy specimens) in the phase 3, multicenter TAX 324 trial of induction chemotherapy followed by concurrent chemoradiation in SCCHN patients. Median OS in the retrospective cohort of 106 white and 95 black SCCHN patients was 52.1 months (white) versus only 23.7 months (black; P = 0.009), due entirely to OS in the subgroup of patients with oropharyngeal cancer—69.4 months (whites) versus 25.2 months (blacks; P = 0.0006); no significant difference by race occurred in survival of non-oropharyngeal SCCHN (P = 0.58). In TAX 324, 196 white patients and 28 black patients could be assessed for HPV status. Median OS was significantly worse for black patients (20.9 months) than for white patients (70.6 months; P = 0.03) and dramatically improved in HPV-positive (not reached) versus HPV-negative (26.6 months, 5.1 hazard ratio) oropharyngeal patients (P < 0.0001), 49% of whom were HPV-16 positive. Overall, HPV positivity was 34% in white versus 4% in black patients (P = 0.0004). Survival was similar for black and white HPV-negative patients (P = 0.56). This is the first prospective assessment of confirmed HPV status in black versus white SCCHN patients. Worse OS for black SCCHN patients was driven by oropharyngeal cancer outcomes, and that for black oropharyngeal cancer patients by a lower prevalence of HPV infection. These findings have important implications for the etiology, prevention, prognosis, and treatment of SCCHN. PMID:19641042

Racial survival disparity in head and neck cancer results from low prevalence of human papillomavirus infection in black oropharyngeal cancer patients.

PubMed

Settle, Kathleen; Posner, Marshall R; Schumaker, Lisa M; Tan, Ming; Suntharalingam, Mohan; Goloubeva, Olga; Strome, Scott E; Haddad, Robert I; Patel, Shital S; Cambell, Earl V; Sarlis, Nicholas; Lorch, Jochen; Cullen, Kevin J

2009-09-01

The burden of squamous cell carcinoma of the head and neck (SCCHN) is greater for blacks than for whites, especially in oropharyngeal cases. We previously showed retrospectively that disease-free survival was significantly greater in white than in black SCCHN patients treated with chemoradiation, the greatest difference occurring in the oropharyngeal subgroup. Oropharyngeal cancer is increasing in incidence and in its association with human papillomavirus (HPV) infection; HPV-positive oropharyngeal cancer patients have significantly better outcomes (versus HPV-negative). These collective data led to the present analyses of overall survival (OS) in our retrospective cohort and of OS and HPV status (tested prospectively in pretreatment biopsy specimens) in the phase 3, multicenter TAX 324 trial of induction chemotherapy followed by concurrent chemoradiation in SCCHN patients. Median OS in the retrospective cohort of 106 white and 95 black SCCHN patients was 52.1 months (white) versus only 23.7 months (black; P = 0.009), due entirely to OS in the subgroup of patients with oropharyngeal cancer--69.4 months (whites) versus 25.2 months (blacks; P = 0.0006); no significant difference by race occurred in survival of non-oropharyngeal SCCHN (P = 0.58). In TAX 324, 196 white patients and 28 black patients could be assessed for HPV status. Median OS was significantly worse for black patients (20.9 months) than for white patients (70.6 months; P = 0.03) and dramatically improved in HPV-positive (not reached) versus HPV-negative (26.6 months, 5.1 hazard ratio) oropharyngeal patients (P < 0.0001), 49% of whom were HPV-16 positive. Overall, HPV positivity was 34% in white versus 4% in black patients (P = 0.0004). Survival was similar for black and white HPV-negative patients (P = 0.56). This is the first prospective assessment of confirmed HPV status in black versus white SCCHN patients. Worse OS for black SCCHN patients was driven by oropharyngeal cancer outcomes, and that for black oropharyngeal cancer patients by a lower prevalence of HPV infection. These findings have important implications for the etiology, prevention, prognosis, and treatment of SCCHN.

Comparison between the Prebolus T1 Measurement and the Fixed T1 Value in Dynamic Contrast-Enhanced MR Imaging for the Differentiation of True Progression from Pseudoprogression in Glioblastoma Treated with Concurrent Radiation Therapy and Temozolomide Chemotherapy.

PubMed

Nam, J G; Kang, K M; Choi, S H; Lim, W H; Yoo, R-E; Kim, J-H; Yun, T J; Sohn, C-H

2017-12-01

Glioblastoma is the most common primary brain malignancy and differentiation of true progression from pseudoprogression is clinically important. Our purpose was to compare the diagnostic performance of dynamic contrast-enhanced pharmacokinetic parameters using the fixed T1 and measured T1 on differentiating true from pseudoprogression of glioblastoma after chemoradiation with temozolomide. This retrospective study included 37 patients with histopathologically confirmed glioblastoma with new enhancing lesions after temozolomide chemoradiation defined as true progression ( n = 15) or pseudoprogression ( n = 22). Dynamic contrast-enhanced pharmacokinetic parameters, including the volume transfer constant, the rate transfer constant, the blood plasma volume per unit volume, and the extravascular extracellular space per unit volume, were calculated by using both the fixed T1 of 1000 ms and measured T1 by using the multiple flip-angle method. Intra- and interobserver reproducibility was assessed by using the intraclass correlation coefficient. Dynamic contrast-enhanced pharmacokinetic parameters were compared between the 2 groups by using univariate and multivariate analysis. The diagnostic performance was evaluated by receiver operating characteristic analysis and leave-one-out cross validation. The intraclass correlation coefficients of all the parameters from both T1 values were fair to excellent (0.689-0.999). The volume transfer constant and rate transfer constant from the fixed T1 were significantly higher in patients with true progression ( P = .048 and .010, respectively). Multivariate analysis revealed that the rate transfer constant from the fixed T1 was the only independent variable (OR, 1.77 × 10 5 ) and showed substantial diagnostic power on receiver operating characteristic analysis (area under the curve, 0.752; P = .002). The sensitivity and specificity on leave-one-out cross validation were 73.3% (11/15) and 59.1% (13/20), respectively. The dynamic contrast-enhanced parameter of rate transfer constant from the fixed T1 acted as a preferable marker to differentiate true progression from pseudoprogression. © 2017 by American Journal of Neuroradiology.

Neoadjuvant Chemotherapy Followed by Radical Surgery Versus Concomitant Chemotherapy and Radiotherapy in Patients With Stage IB2, IIA, or IIB Squamous Cervical Cancer: A Randomized Controlled Trial.

PubMed

Gupta, Sudeep; Maheshwari, Amita; Parab, Pallavi; Mahantshetty, Umesh; Hawaldar, Rohini; Sastri Chopra, Supriya; Kerkar, Rajendra; Engineer, Reena; Tongaonkar, Hemant; Ghosh, Jaya; Gulia, Seema; Kumar, Neha; Shylasree, T Surappa; Gawade, Renuka; Kembhavi, Yogesh; Gaikar, Madhuri; Menon, Santosh; Thakur, Meenakshi; Shrivastava, Shyam; Badwe, Rajendra

2018-06-01

Purpose We compared the efficacy and toxicity of neoadjuvant chemotherapy followed by radical surgery versus standard cisplatin-based chemoradiation in patients with locally advanced squamous cervical cancer. Patients and Methods This was a single-center, phase III, randomized controlled trial ( ClinicalTrials.gov identifier: NCT00193739). Eligible patients were between 18 and 65 years old and had stage IB2, IIA, or IIB squamous cervical cancer. They were randomly assigned, after stratification by stage, to receive either three cycles of neoadjuvant chemotherapy using paclitaxel and carboplatin once every 3 weeks followed by radical hysterectomy or standard radiotherapy with concomitant cisplatin once every week for 5 weeks. Patients in the neoadjuvant group received postoperative adjuvant radiation or concomitant chemotherapy and radiotherapy, if indicated. The primary end point was disease-free survival (DFS), defined as survival without relapse or death related to cancer, and secondary end points included overall survival and toxicity. Results Between September 2003 and February 2015, 635 patients were randomly assigned, of whom 633 (316 patients in the neoadjuvant chemotherapy plus surgery group and 317 patients in the concomitant chemoradiation group) were included in the final analysis, with a median follow-up time of 58.5 months. The 5-year DFS in the neoadjuvant chemotherapy plus surgery group was 69.3% compared with 76.7% in the concomitant chemoradiation group (hazard ratio, 1.38; 95% CI, 1.02 to 1.87; P = .038), whereas the corresponding 5-year OS rates were 75.4% and 74.7%, respectively (hazard ratio, 1.025; 95% CI, 0.752 to 1.398; P = .87). The delayed toxicities at 24 months or later after treatment completion in the neoadjuvant chemotherapy plus surgery group versus the concomitant chemoradiation group were rectal (2.2% v 3.5%, respectively), bladder (1.6% v 3.5%, respectively), and vaginal (12.0% v 25.6%, respectively). Conclusion Cisplatin-based concomitant chemoradiation resulted in superior DFS compared with neoadjuvant chemotherapy followed by radical surgery in locally advanced cervical cancer.

Preoperative radiotherapy and local excision of rectal cancer: Long-term results of a randomised study.

PubMed

Wawok, Przemysław; Polkowski, Wojciech; Richter, Piotr; Szczepkowski, Marek; Olędzki, Janusz; Wierzbicki, Ryszard; Gach, Tomasz; Rutkowski, Andrzej; Dziki, Adam; Kołodziejski, Leszek; Sopyło, Rafał; Pietrzak, Lucyna; Kryński, Jacek; Wiśniowska, Katarzyna; Spałek, Mateusz; Pawlewicz, Konrad; Polkowski, Marcin; Kowalska, Teresa; Paprota, Krzysztof; Jankiewicz, Małgorzata; Radkowski, Andrzej; Chalubińska-Fendler, Justyna; Michalski, Wojciech; Bujko, Krzysztof

2018-06-01

It is uncertain whether local control is acceptable after preoperative radiotherapy and local excision (LE). An optimal preoperative dose/fractionation schedule has not yet been established. In a phase III study, patients with cT1-2N0M0 or borderline cT2/T3N0M0 < 4 cm rectal adenocarcinomas were randomised to receive either 5 × 5 Gy plus 1 × 4 Gy boost or chemoradiation: 50.4 Gy in 28 fractions plus 3 × 1.8 Gy boost and 5-fluorouracil with leucovorin bolus. LE was performed 6-8 weeks later. Patients with ypT0-1R0 disease were observed. Completion total mesorectal excision (CTME) was recommended for poor responders, i.e. ypT1R1/ypT2-3. Of 61 randomised patients, 10 were excluded leaving 51 for analysis; 29 in the short-course group and 22 in the chemoradiation group. YpT0-1R0 was observed in 66% of patients in the short-course group and in 86% in the chemoradiation group, p = 0.11. CTME was performed only in 46% of patients with ypT1R1/ypT2-3. The median follow-up was 8.7 years. Local recurrence incidences and overall survival at 10 years were respectively for the short-course group vs. the chemoradiation group 35% vs. 5%, p = 0.036 and 47% vs. 86%, p = 0.009. In total, local recurrence at 10 years was 79% for ypT1R1/T2-3 without CTME. This trial suggests that in the LE setting, both local recurrence and survival are worse after short-course radiotherapy than after chemoradiation. Because of the risk of bias, a confirmatory study is desirable. Lack of CTME is associated with an unacceptably high local recurrence rate. Copyright © 2018 Elsevier B.V. All rights reserved.

SU-F-J-222: Using PET Imaging to Evaluate Proliferation and Blood Flow in Irradiated and Non-Irradiated Bone Marrow 1 Year After Chemoradiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

McGuire, S; Ponto, L; Menda, Y

Purpose: To compare proliferation and blood flow in pelvic and thoracic bone marrow 1 year after pelvic chemoradiation. Methods: Sixteen pelvic cancer patients were enrolled in an IRB-approved protocol to acquire FLT PET images during radiation therapy simulation (baseline) and 1 year after chemoradiation therapy. Three subjects also had optional O-15 water PET images acquired 1 year after chemoradiation therapy. Baseline FLT PET images were used to create IMRT plans to spare pelvic bone marrow identified as regions with FLT SUV ≥ 2 without compromising PTV coverage or OAR sparing. Marrow VOIs were defined using a 50% maximum pixel valuemore » threshold on baseline FLT PET images (VIEW, PMOD version 3.5) in the sacrum and thoracic spine representing irradiated and non-irradiated regions, respectively. FLT PET and O-15 water PET images acquired 1 year after therapy were co-registered to baseline images (FUSION PMOD) and the same VOIs were used to measure proliferation (FLT SUV) and blood flow (O-15 water uptake). Separate image-based input functions were used for blood flow quantitation in each VOI. Results: Mean 1 year FLT SUV in sacral and thoracic VOIs for were 1.1 ± 0.4 and 6.5 ± 1.7, respectively for N = 16 subjects and were 1.2 ± 0.2 and 5.6 ± 1.6, respectively for N = 3 subjects who also underwent O-15 water imaging. Blood flow measures in equivalent sacral and thoracic marrow regions (N = 3) were 21.3 ± 8.7 and 18.3 ± 4.9 mL/min/100mL respectively. Conclusion: Decreased bone marrow proliferation measured by FLT SUV does not appear to correspond to decreased blood flow as measured by O-15 water PET imaging. Based on this small sample at a single time point, reduced blood supply does not explain reductions in bone marrow proliferative activity 1 year after chemoradiation therapy.« less

Anorectal Function and Quality of Life in Patients With Early Stage Rectal Cancer Treated With Chemoradiation and Local Excision.

PubMed

Lynn, Patricio B; Renfro, Lindsay A; Carrero, Xiomara W; Shi, Qian; Strombom, Paul L; Chow, Oliver; Garcia-Aguilar, Julio

2017-05-01

Little is known about anorectal function and quality of life after chemoradiation followed by local excision, which is an alternative to total mesorectal excision for selected patients with early rectal cancer. The purpose of this study was to prospectively assess anorectal function and health-related quality of life of patients with T2N0 rectal cancer who were treated with an alternative approach. This was a prospective, phase II trial. The study was multicentric (American College of Surgeons Oncology Group trial Z6041). Patients with stage cT2N0 rectal adenocarcinomas were treated with an oxaliplatin/capecitabine-based chemoradiation regimen followed by local excision. Anorectal function and quality of life were assessed at enrollment and 1 year postoperatively with the Fecal Incontinence Severity Index, Fecal Incontinence Quality of Life scale, and Functional Assessment of Cancer Therapy-Colorectal Questionnaire. Results were compared, and multivariable analysis was performed to identify predictors of outcome. Seventy-one patients (98%) were evaluated at enrollment and 66 (92%) at 1 year. Compared with baseline, no significant differences were found on Fecal Incontinence Severity Index scores at 1 year. Fecal Incontinence Quality of Life results were significantly worse in the lifestyle (p < 0.001), coping/behavior (p < 0.001), and embarrassment (p = 0.002) domains. There were no differences in the Functional Assessment of Cancer Therapy overall score, but the physical well-being subscale was significantly worse and emotional well-being was improved after surgery. Treatment with the original chemoradiation regimen predicted worse depression/self-perception and embarrassment scores in the Fecal Incontinence Quality of Life, and male sex was predictive of worse scores in the Functional Assessment of Cancer Therapy overall score and trial outcome index. Small sample size, relatively short follow-up, and absence of information before cancer diagnosis were study limitations. Chemoradiation followed by local excision had minimal impact on anorectal function 1 year after surgery. Overall quality of life remained stable, with mixed effects on different subscales. This information should be used to counsel patients about expected outcomes.

Clinical Utility of Multimodality Imaging with Dynamic Contrast-Enhanced MRI, Diffusion-Weighted MRI, and 18F-FDG PET/CT for the Prediction of Neck Control in Oropharyngeal or Hypopharyngeal Squamous Cell Carcinoma Treated with Chemoradiation

PubMed Central

Chan, Sheng-Chieh; Lin, Yu-Chun; Yen, Tzu-Chen; Liao, Chun-Ta; Chang, Joseph Tung-Chieh; Ko, Sheung-Fat; Wang, Hung- Ming; Chang, Chee-Jen; Wang, Jiun-Jie

2014-01-01

The clinical usefulness of pretreatment imaging techniques for predicting neck control in patients with oropharyngeal or hypopharyngeal squamous cell carcinoma (OHSCC) treated with chemoradiation remains unclear. In this prospective study, we investigated the role of pretreatment dynamic contrast-enhanced perfusion MR imaging (DCE-PWI), diffusion-weighted MR imaging (DWI), and [18F]fluorodeoxyglucose-positron emission tomography (18F-FDG PET)/CT derived imaging markers for the prediction of neck control in OHSCC patients treated with chemoradiation. Patients with untreated OHSCC scheduled for chemoradiation between August, 2010 and July, 2012 were eligible for the study. Clinical variables and the following imaging parameters of metastatic neck lymph nodes were examined in relation to neck control: transfer constant, volume of blood plasma, and volume of extracellular extravascular space (Ve) on DCE-PWI; apparent diffusion coefficient (ADC) on DWI; maximum standardized uptake value, metabolic tumor volume, and total lesion glycolysis on 18F-FDG PET/CT. There were 69 patients (37 with oropharynx SCC and 32 with hypopharynx SCC) with successful pretreatment DCE-PWI and DWI available for analysis. After a median follow-up of 31 months, 25 (36.2%) participants had neck failure. Multivariate analysis identified hemoglobin level <14.3 g/dL (P = 0.019), Ve <0.23 (P = 0.040), and ADC >1.14×10−3 mm2/s (P = 0.003) as independent prognostic factors for 3-year neck control. A prognostic scoring system was formulated by summing up the three significant predictors of neck control. Patients with scores of 2–3 had significantly poorer neck control and overall survival rates than patients with scores of 0–1. We conclude that hemoglobin levels, Ve, and ADC are independent pretreatment prognostic factors for neck control in OHSCC treated with chemoradiation. Their combination may identify a subgroup of patients at high risk of developing neck failure. PMID:25531391

A phase 1 trial of ABT-510 concurrent with standard chemoradiation for patients with newly diagnosed glioblastoma.

PubMed

Nabors, Louis B; Fiveash, John B; Markert, James M; Kekan, Manasi S; Gillespie, George Y; Huang, Zhi; Johnson, Martin J; Meleth, Sreelatha; Kuo, Huichien; Gladson, Candece L; Fathallah-Shaykh, Hassan M

2010-03-01

To determine the maximum tolerated dose of ABT-510, a thrombospondin-1 mimetic drug with antiangiogenic properties, when used concurrently with temozolomide and radiotherapy in patients with newly diagnosed glioblastoma. Phase 1 dose-escalation clinical trial. Comprehensive Cancer Center, University of Alabama at Birmingham. Patients A total of 23 patients with newly diagnosed, histologically verified glioblastoma enrolled between April 2005 and January 2007. Four cohorts of 3 patients each received subcutaneous ABT-510 injection at doses of 20, 50, 100, or 200 mg/d. The maximum cohort was expanded to 14 patients to obtain additional safety and gene expression data. The treatment plan included 10 weeks of induction phase (temozolomide and radiotherapy with ABT-510 for 6 weeks plus ABT-510 monotherapy for 4 weeks) followed by a maintenance phase of ABT-510 and monthly temozolomide. Patients were monitored with brain magnetic resonance imaging and laboratory testing for dose-limiting toxicities, defined as grades 3 or 4 nonhematological toxicities and grade 4 hematological toxicities. Therapy was discontinued if 14 maintenance cycles were completed, disease progression occurred, or if the patient requested withdrawal. Disease progression, survival statistics, and gene expression arrays were analyzed. There were no grade 3 or 4 dose-limiting toxicity events that appeared related to ABT-510 for the dose range of 20 to 200 mg/d. A maximum tolerated dose was not defined. Most adverse events were mild, and injection-site reactions. The median time to tumor progression was 45.9 weeks, and the median overall survival time was 64.4 weeks. Gene expression analysis using TaqMan low-density arrays identified angiogenic genes that were differentially expressed in the brains of controls compared with patients with newly diagnosed glioblastoma, and identified FGF-1 and TIE-1 as being downregulated in patients who had better clinical outcomes. ABT-510, at subcutaneous doses up to 200 mg/d, is tolerated well with concurrent temozolomide and radiotherapy in patients with newly diagnosed glioblastoma, and low-density arrays provide a useful method of exploring gene expression profiles.

Survival outcomes with concurrent chemoradiation for elderly patients with locally advanced head and neck cancer according to the National Cancer Data Base.

PubMed

Amini, Arya; Jones, Bernard L; McDermott, Jessica D; Serracino, Hilary S; Jimeno, Antonio; Raben, David; Ghosh, Debashis; Bowles, Daniel W; Karam, Sana D

2016-05-15

The overall survival (OS) benefit of concurrent chemoradiotherapy (CRT) for head and neck squamous cell carcinoma patients older than 70 years is debated. This study examines the outcomes of elderly patients receiving CRT versus radiotherapy (RT) alone. The National Cancer Data Base was queried for patients older than 70 years with nonmetastatic oropharyngeal, laryngeal, or hypopharyngeal cancer (T3-4 or N(+)). CRT was defined as chemotherapy started within 14 days of the initiation of RT. Univariate analysis, multivariate analysis (MVA), propensity score matching (PSM), and recursive partitioning analysis (RPA) were performed. The study included 4042 patients: 2538 (63%) received CRT. The median follow-up was 19 months. The unadjusted median OS was longer with the addition of CRT (P < .001). OS was superior with CRT in the MVA (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.58-0.68; P < .001) and PSM analyses (HR, 0.73; 95% CI, 0.66-0.80; P < .001) in comparison with RT alone. According to RPA, CRT was associated with longer OS for patients 81 years or younger with low comorbidity scores and either T1-2/N2-3 disease or T3-4/N0-3 disease. The survival benefit with CRT disappeared for 2 subgroups in the 71- to 81-year age range: those with T1-2, N1, and Charlson-Deyo 0-1 (CD0-1) disease and those with T3-4, N1+, and CD1+ disease. Patients who were older than 81 years did not have increased survival with CRT. The receipt of CRT was associated with a longer duration of RT (odds ratio, 1.74; 95% CI, 1.50-2.01; P < .001). Patients older than 70 years should not be denied concurrent chemotherapy solely on the basis of age; additional factors, including the performance status and the tumor stage, should be taken into account. Cancer 2016;122:1533-43. © 2016 American Cancer Society. © 2016 American Cancer Society.

Phase 2 Study of Docetaxel, Cisplatin, and Concurrent Radiation for Technically Resectable Stage III-IV Squamous Cell Carcinoma of the Head and Neck

DOE Office of Scientific and Technical Information (OSTI.GOV)

Inohara, Hidenori, E-mail: hinohara@ent.med.osaka-u.ac.jp; Takenaka, Yukinori; Yoshii, Tadashi

2015-04-01

Purpose: We investigated the efficacy and safety of weekly low-dose docetaxel and cisplatin therapy concurrent with conventionally fractionated radiation in patients with technically resectable stage III-IV squamous cell carcinoma of the head and neck. Methods and Materials: Between March 2004 and October 2011, we enrolled 117 patients, of whom 116 were analyzable (43 had oropharyngeal cancer, 54 had hypopharyngeal cancer, and 19 had laryngeal cancer), and 85 (73%) had stage IV disease. Radiation consisted of 66 Gy in 33 fractions. Docetaxel, 10 mg/m{sup 2}, followed by cisplatin, 20 mg/m{sup 2}, administered on the same day were given once a week for 6 cycles.more » The primary endpoint was overall complete response (CR) rate after chemoradiation therapy. Human papillomavirus (HPV) DNA in oropharyngeal cancer was examined by PCR. Results: Of 116 patients, 82 (71%) completed treatment per protocol; 102 (88%) received the full radiation therapy dose; and 90 (78%) and 12 (10%) patients received 6 and 5 chemotherapy cycles, respectively. Overall CR rate was 71%. After median follow-up of 50.9 months (range: 15.6-113.9 months for surviving patients), 2-year and 4-year overall survival rates were 82% and 68%, respectively. Cumulative 2-year and 4-year local failure rates were 27% and 28%, respectively, whereas distant metastasis rates were 15% and 22%, respectively. HPV status in oropharyngeal cancer was not associated with treatment efficacy. Acute toxicity included grade 3 and 4 in-field mucositis in 73% and 5% of patients, respectively, whereas myelosuppression and renal injury were minimal. No patients died of toxicity. Feeding tube dependence in 8% and tracheostomy in 1% of patients were evident at 2 years postchemoradiation therapy in patients who survived without local treatment failure. Conclusions: Local control and survival with this regimen were satisfactory. Although acute toxicity, such as mucositis, was common, late toxicity, such as laryngoesophageal dysfunction, was minimal. Therapy using weekly low-dose docetaxel and cisplatin concurrent with radiation warrants further evaluation.« less

Failure Patterns in Patients with Esophageal Cancer Treated with Definitive Chemoradiation

PubMed Central

Welsh, James; Settle, Stephen H.; Amini, Arya; Xiao, Lianchun; Suzuki, Akihiro; Hayashi, Yuki; Hofstetter, Wayne; Komaki, Ritsuko; Liao, Zhongxing; Ajani, Jaffer A.

2012-01-01

Purpose Local failure after definitive chemoradiation therapy for unresectable esophageal cancer remains problematic. Little is known about the failure pattern based on modern day radiation treatment volumes. We hypothesized that most local failures would be within the gross tumor volume (GTV), where the bulk of the tumor burden resides. Methods and Materials We reviewed treatment volumes for 239 patients who underwent definitive chemoradiation therapy and compared this information with failure patterns on follow-up positron emission (PET). Failures were categorized as within the GTV, the larger clinical target volume (CTV, which encompasses microscopic disease), or the still larger planning target volume (PTV, which encompasses setup variability) or outside the radiation field. Results At a median follow-up time of 52.6 months (95% CI: 46.1 – 56.7 months), 119 patients (50%) had experienced local failure, 114 (48%) had distant failure, and 74 (31%) had no evidence of failure. Of all local failures, 107 (90%) were in the GTV, 27 (23%) in the CTV; and 14 (12%) in the PTV. In multivariate analysis, GTV failure was associated with tumor status (T3/T4 vs. T1/T2: OR=6.35, p value =0.002), change in standardized uptake value on PET before and after treatment (decrease >52%: OR=0.368, p value = 0.003) and tumor length (>8 cm: 4.08, p value = 0.009). Conclusions Most local failures after definitive chemoradiation for unresectable esophageal cancer occur in the GTV. Future therapeutic strategies should focus on enhancing local control. PMID:22565611

A Combined Pharmacokinetic and Radiologic Assessment of Dynamic Contrast-Enhanced Magnetic Resonance Imaging Predicts Response to Chemoradiation in Locally Advanced Cervical Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Semple, Scott; Harry, Vanessa N. MRCOG.; Parkin, David E.

2009-10-01

Purpose: To investigate the combination of pharmacokinetic and radiologic assessment of dynamic contrast-enhanced magnetic resonance imaging (MRI) as an early response indicator in women receiving chemoradiation for advanced cervical cancer. Methods and Materials: Twenty women with locally advanced cervical cancer were included in a prospective cohort study. Dynamic contrast-enhanced MRI was carried out before chemoradiation, after 2 weeks of therapy, and at the conclusion of therapy using a 1.5-T MRI scanner. Radiologic assessment of uptake parameters was obtained from resultant intensity curves. Pharmacokinetic analysis using a multicompartment model was also performed. General linear modeling was used to combine radiologic andmore » pharmacokinetic parameters and correlated with eventual response as determined by change in MRI tumor size and conventional clinical response. A subgroup of 11 women underwent repeat pretherapy MRI to test pharmacokinetic reproducibility. Results: Pretherapy radiologic parameters and pharmacokinetic K{sup trans} correlated with response (p < 0.01). General linear modeling demonstrated that a combination of radiologic and pharmacokinetic assessments before therapy was able to predict more than 88% of variance of response. Reproducibility of pharmacokinetic modeling was confirmed. Conclusions: A combination of radiologic assessment with pharmacokinetic modeling applied to dynamic MRI before the start of chemoradiation improves the predictive power of either by more than 20%. The potential improvements in therapy response prediction using this type of combined analysis of dynamic contrast-enhanced MRI may aid in the development of more individualized, effective therapy regimens for this patient group.« less

Radiation-induced liver disease as a mimic of liver metastases at serial PET/CT during neoadjuvant chemoradiation of distal esophageal cancer.

PubMed

Grant, Michael J; Didier, Ryne A; Stevens, Jeffrey S; Beyder, Dmitry D; Hunter, John G; Thomas, Charles R; Coakley, Fergus V

2014-10-01

To determine the frequency and appearance of radiation-induced liver disease on PET/CT in patients undergoing serial imaging during neoadjuvant chemoradiation of distal esophageal cancer. In this IRB-approved, HIPAA-compliant retrospective analysis, we identified 112 patients with distal esophageal cancer treated by neoadjuvant chemoradiation who had serial PET/CT imaging available for review. Two readers reviewed all studies in consensus and recorded those cases where new foci of visually detectable increased FDG avidity appeared in the liver during therapy. The etiology of such foci was determined from corresponding findings at CT or MRI, by hepatic biopsy during surgery, by characteristic evolution on post-operative imaging, or by a combination of these methods. New foci of FDG avidity developed in the liver during neoadjuvant therapy in 10 of 112 (9%) patients, of whom nine (8%) were determined to have radiation-induced liver disease based on further imaging and/or biopsy and one of whom had developed interval metastatic disease based on biopsy. In the cases of radiation-induced liver disease, the abnormal foci were found only in the caudate and left hepatic lobes, near the primary tumor, while the patient who developed interval metastatic disease had involvement of the inferior right hepatic lobe, remote from the radiation therapy field. New foci of increased FDG avidity are commonly seen in the caudate and left hepatic lobes of the liver during neoadjuvant chemoradiation of distal esophageal cancer, and these findings generally reflect radiation-induced liver disease rather than metastatic disease.

Role of Adjuvant Therapy for Node-Negative Lung Cancer Invading the Chest Wall.

PubMed

Gao, Sarah J; Corso, Christopher D; Blasberg, Justin D; Detterbeck, Frank C; Boffa, Daniel J; Decker, Roy H; Kim, Anthony W

2017-03-01

The present study investigated the effect of adjuvant chemotherapy and radiation on survival among patients undergoing chest wall resection for T3N0 non-small cell lung cancer (NSCLC). Patients with T3N0 NSCLC who underwent chest wall resection were identified in the National Cancer Data Base in 2004 to 2012. The cohort was divided into patients who had received adjuvant chemotherapy, radiation therapy, chemoradiation therapy, or no adjuvant treatment. Kaplan-Meier and log-rank tests were used to compare overall survival, and a bootstrapped Cox proportional hazards model was used to determine the significant contributors to survival. A subset analysis was performed with stratification by margin status and tumor size. Of 759 patients identified, 42.0% underwent surgery alone, 23.3% underwent surgery followed by chemotherapy, 22.3% underwent surgery followed by chemoradiation therapy, and 12.3% underwent surgery followed by radiotherapy alone. Tumors > 4 cm benefited from adjuvant chemotherapy and radiation therapy in the multivariable analysis, and those ≤ 4 cm benefited only from adjuvant chemotherapy. The subgroup analysis by margin status identified that margin-positive patients with tumors > 4 cm benefited significantly from either adjuvant chemoradiation therapy or radiation therapy alone. T3N0 NSCLC with chest wall invasion requires unique management compared with other stage IIB tumors. An important determinant of management is tumor size, with tumors ≤ 4 cm benefiting from adjuvant chemotherapy and tumors > 4 cm benefiting from adjuvant chemotherapy if margin negative and adjuvant chemoradiation therapy or radiotherapy if margin positive. Copyright © 2016 Elsevier Inc. All rights reserved.

Rectal Cancer: Mucinous Carcinoma on Magnetic Resonance Imaging Indicates Poor Response to Neoadjuvant Chemoradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oberholzer, Katja, E-mail: oberholz@radiologie.klinik.uni-mainz.de; Menig, Matthias; Kreft, Andreas

2012-02-01

Purpose: To assess response of locally advanced rectal carcinoma to chemoradiation with regard to mucinous status and local tumor invasion found at pretherapeutic magnetic resonance imaging (MRI). Methods and Materials: A total of 88 patients were included in this prospective study of patients with advanced mrT3 and mrT4 carcinomas. Carcinomas were categorized by MRI as mucinous (mucin proportion >50% within the tumor volume), and as nonmucinous. Patients received neoadjuvant chemoradiation consisting of 50.4 Gy (1.8 Gy/fraction) and 5-fluorouracil on Days 1 to 5 and Days 29 to 33. Therapy response was assessed by comparing pretherapeutic MRI with histopathology of surgicalmore » specimens (minimum distance between outer tumor edge and circumferential resection margin = CRM, T, and N category). Results: A mucinous carcinoma was found in 21 of 88 patients. Pretherapeutic mrCRM was 0 mm (median) in the mucinous and nonmucinous group. Of the 88 patients, 83 underwent surgery with tumor resection. The ypCRM (mm) at histopathology was significantly lower in mucinous carcinomas than in nonmucinous carcinomas (p {<=} 0.001). Positive resection margins (ypCRM {<=} 1 mm) were found more frequently in mucinous carcinomas than in nonmucinous ones (p {<=} 0.001). Treatment had less effect on local tumor stage in mucinous carcinomas than in nonmucinous carcinomas (for T downsizing, p = 0.012; for N downstaging, p = 0.007). Disease progression was observed only in patients with mucinous carcinomas (n = 5). Conclusion: Mucinous status at pretherapeutic MRI was associated with a noticeably worse response to chemoradiation and should be assessed by MRI in addition to local tumor staging to estimate response to treatment before it is initiated.« less

Health-Related Quality of Life in SCALOP, a Randomized Phase 2 Trial Comparing Chemoradiation Therapy Regimens in Locally Advanced Pancreatic Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hurt, Christopher N., E-mail: hurtcn@cardiff.ac.uk; Mukherjee, Somnath; Bridgewater, John

Purpose: Chemoradiation therapy (CRT) for patients with locally advanced pancreatic cancer (LAPC) provides survival benefits but may result in considerable toxicity. Health-related quality of life (HRQL) measurements during CRT have not been widely reported. This paper reports HRQL data from the Selective Chemoradiation in Advanced Localised Pancreatic Cancer (SCALOP) trial, including validation of the QLQ-PAN26 tool in CRT. Methods and Materials: Patients with locally advanced, inoperable, nonmetastatic carcinoma of the pancreas were eligible. Following 12 weeks of induction gemcitabine plus capecitabine (GEMCAP) chemotherapy, patients with stable and responding disease were randomized to a further cycle of GEMCAP followed by capecitabine- or gemcitabine-basedmore » CRT. HRQL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the EORTC Pancreatic Cancer module (PAN26). Results: A total of 114 patients from 28 UK centers were registered and 74 patients randomized. There was improvement in the majority of HRQL scales during induction chemotherapy. Patients with significant deterioration in fatigue, appetite loss, and gastrointestinal symptoms during CRT recovered within 3 weeks following CRT. Differences in changes in HRQL scores between trial arms rarely reached statistical significance; however, where they did, they favored capecitabine therapy. PAN26 scales had good internal consistency and were able to distinguish between subgroups of patients experiencing toxicity. Conclusions: Although there is deterioration in HRQL following CRT, this resolves within 3 weeks. HRQL data support the use of capecitabine- over gemcitabine-based chemoradiation. The QLQ-PAN26 is a reliable and valid tool for use in patients receiving CRT.« less

Magnetic Resonance Imaging Assessment of Squamous Cell Carcinoma of the Anal Canal Before and After Chemoradiation: Can MRI Predict for Eventual Clinical Outcome?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goh, Vicky, E-mail: vicky.goh@stricklandscanner.org.u; Gollub, Frank K.; Liaw, Jonathan

2010-11-01

Purpose: To describe the MRI appearances of squamous cell carcinoma of the anal canal before and after chemoradiation and to assess whether MRI features predict for clinical outcome. Methods and Materials: Thirty-five patients (15 male, 20 female; mean age 60.8 years) with histologically proven squamous cell cancer of the anal canal underwent MRI before and 6-8 weeks after definitive chemoradiation. Images were reviewed retrospectively by two radiologists in consensus blinded to clinical outcome: tumor size, signal intensity, extent, and TNM stage were recorded. Following treatment, patients were defined as responders by T and N downstaging and Response Evaluation Criteria inmore » Solid Tumors (RECIST). Final clinical outcome was determined by imaging and case note review: patients were divided into (1) disease-free and (2) with relapse and compared using appropriate univariate methods to identify imaging predictors; statistical significance was at 5%. Results: The majority of tumors were {<=}T2 (23/35; 65.7%) and N0 (21/35; 60%), mean size 3.75cm, and hyperintense (++ to +++, 24/35 patients; 68%). Following chemoradiation, there was a size reduction in all cases (mean 73.3%) and a reduction in signal intensity in 26/35 patients (74.2%). The majority of patients were classified as responders (26/35 (74.2%) patients by T and N downstaging; and 30/35 (85.7%) patients by RECIST). At a median follow-up of 33.5 months, 25 patients (71.4%) remained disease-free; 10 patients (28.6%) had locoregional or metastatic disease. Univariate analysis showed that no individual MRI features were predictive of eventual outcome. Conclusion: Early assessment of response by MRI at 6-8 weeks is unhelpful in predicting future clinical outcome.« less

Neoadjuvant conformal chemoradiation with induction chemotherapy for rectal adenocarcinoma. A prospective observational study.

PubMed

Fekete, Zsolt; Muntean, Alina-Simona; Hica, Ştefan; Rancea, Alin; Resiga, Liliana; Csutak, Csaba; Todor, Nicolae; Nagy, Viorica Magdalena

2014-06-01

The purpose of this prospective observational study was to evaluate the rate and the prognostic factors for down-staging and complete response for rectal adenocarcinoma after induction chemotherapy and neoadjuvant chemoradiation followed by surgery, and to analyze the rate of sphincter-saving surgery. We included from March 2011 to October 2013 a number of 88 patients hospitalized with locally advanced rectal adenocarcinoma in the Prof. Dr. Ion Chiricuta Institute of Oncology, Cluj. The treatment schedule included 2-4 cycles of Oxaliplatin plus a fluoropyrimidine followed by concomitant chemoradiation with a dose of 50 Gy in 25 fractions combined with a fluoropyrimidine monotherapy. The rate of T down-staging was 49.4% (40/81 evaluable patients). Independent prognostic factors for T down-staging were: age >57 years (p<0.01), cN0 (p<0.01), distance from anal verge >5 cm (p<0.01), initial CEA <6.2 ng/ml (p<0.01), higher number of chemotherapy cycles with Oxaliplatin (pROC=0.05) and protraction of radiotherapy of >35 days (p<0.01). Nine patients from 81 (11.1%) presented complete response (7 pathological and 2 clinical); the independent prognostic factors were stage cT2 versus cT3-4 (p<0.01), initial tumor size ≤3.5 cm and distance from anal verge >5 cm (p=0.03). Sixty-eight patients (79.1%) underwent radical surgery and among them 35 patients (51.5 %) had a sphincter saving procedure. Induction chemotherapy with neoadjuvant chemoradiation produced important down-staging in rectal adenocarcinoma. Independent prognostic factors for T down-staging were: age, cN0, distance from anal verge, initial CEA, the number of Oxaliplatin cycles and duration of radiotherapy; for complete response: cT2, initial tumor size and distance from the anal verge.

Preclinical Evaluation of Genexol-PM, a Nanoparticle Formulation of Paclitaxel, as a Novel Radiosensitizer for the Treatment of Non-Small Cell Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Werner, Michael E.; Cummings, Natalie D.; Sethi, Manish

2013-07-01

Purpose: A key research objective in radiation oncology is to identify agents that can improve chemoradiation therapy. Nanoparticle (NP) chemotherapeutics possess several properties, such as preferential accumulation in tumors, that are uniquely suited for chemoradiation therapy. To facilitate the clinical translation of NP chemotherapeutics in chemoradiation therapy, we conducted preclinical evaluation of Genexol-PM, the only clinically approved NP chemotherapeutic with a controlled drug release profile, as a radiosensitizer using non-small cell lung cancer (NSCLC) as a model disease. Methods and Materials: The physical characteristics and drug release profile of Genexol-PM were characterized. Genexol-PM's efficacy as a radiosensitizer was evaluated inmore » vitro using NSCLC cell lines and in vivo using mouse xenograft models of NSCLC. Paclitaxel dose to normal lung and liver after Genexol-PM administration were quantified and compared with that after Taxol administration. Results: Genexol-PM has a size of 23.91 ± 0.41 nm and surface charge of −8.1 ± 3.1 mV. It releases paclitaxel in a controlled release profile. In vitro evaluation of Genexol-PM as a radiosensitizer showed it is an effective radiosensitizer and is more effective than Taxol, its small molecule counterpart, at the half maximal inhibitory concentration. In vivo study of Genexol-PM as a radiosensitizer demonstrated that it is more effective as a radiosensitizer than Taxol. We also found that Genexol-PM leads to lower paclitaxel exposure to normal lung tissue than Taxol at 6 hours postadministration. Conclusions: We have demonstrated that Genexol-PM is more effective than Taxol as a radiosensitizer in the preclinical setting and holds high potential for clinical translation. Our data support the clinical evaluation of Genexol-PM in chemoradiation therapy for NSCLC.« less

Epidermal growth factor receptor gene polymorphisms predict pelvic recurrence in patients with rectal cancer treated with chemoradiation.

PubMed

Zhang, Wu; Park, David J; Lu, Bo; Yang, Dong Yun; Gordon, Michael; Groshen, Susan; Yun, Jim; Press, Oliver A; Vallböhmer, Daniel; Rhodes, Katrin; Lenz, Heinz-Josef

2005-01-15

An association between epidermal growth factor receptor (EGFR) signaling pathway and response of cancer cells to ionizing radiation has been reported. Recently, a polymorphic variant in the EGFR gene that leads to an arginine-to-lysine substitution in the extracellular domain at codon 497 within subdomain IV of EGFR has been identified. The variant EGFR (HER-1 497K) may lead to attenuation in ligand binding, growth stimulation, tyrosine kinase activation, and induction of proto-oncogenes myc, fos, and jun. A (CA)(n) repeat polymorphism in intron 1 of the EGFR gene that alters EGFR expression in vitro and in vivo has also been described. In the current pilot study, we assessed both polymorphisms in 59 patients with locally advanced rectal cancer treated with adjuvant or neoadjuvant chemoradiation therapy using PCR-RFLP and a 5'-end [gamma-(33)P]ATP-labeled PCR protocol. We tested whether either polymorphism alone or in combination can be associated with local recurrence in the setting of chemoradiation treatment. We found that patients with HER-1 497 Arg/Arg genotype or lower number of CA repeats (both alleles <20) tended to have a higher risk of local recurrence (P = 0.24 and 0.31, respectively). Combined analysis showed the highest risk for local recurrence was seen in patients who possessed both a HER-1 497 Arg allele and <20 CA repeats (P = 0.05, log-rank test). Our data suggest that the HER-1 R497K and EGFR intron 1 (CA)(n) repeat polymorphisms may be potential indicators of radiosensitivity in patients with rectal cancer treated with chemoradiation.

Prediction of response to chemoradiation in rectal cancer by a gene polymorphism in the epidermal growth factor receptor promoter region

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spindler, Karen-Lise Garm; Nielsen, Jens Nederby; Lindebjerg, Jan

2006-10-01

Purpose: Epidermal growth factor receptor (EGFR) has been associated with radioresistance in solid tumors. Recently a polymorphism in the Sp1 recognition site of the EGFR promoter region was identified. The present study investigated the predictive value of this polymorphism for the outcome of chemoradiation in locally advanced rectal cancer. Methods and Materials: The study included 77 patients with locally advanced T3 rectal tumors. Treatment consisted of preoperative radiation therapy at a total tumor dose of 65 Gy and concomitant chemotherapy with Uftoral. Blood samples from 63 patients were evaluated for Sp1 -216 G/T polymorphism by polymerase chain reaction analysis. Forty-eightmore » primary tumor biopsies were available for EGFR immunostaining. Patients underwent surgery 8 weeks after treatment. Pathologic response evaluation was performed according to the tumor regression grade (TRG) system. Results: Forty-nine percent had major response (TRG1-2) and 51% moderate response (TRG 3-4) to chemoradiation. The rates of major response were 34% (10/29) in GG homozygote patients compared with 65% (22/34) in patients with T containing variants (p = 0.023). Fifty-eight percent of biopsies were positive for EGFR expression (28/48). The major response rates with regard to EGFR immunostaining were not significantly different. EGFR-positive tumors were found in 83% of the GG homozygote patients compared with 38% of patients with TT or GT variants (p = 0.008). Conclusions: There was a significant correlation between EGFR Sp1 -216 G/T polymorphism and treatment response to chemoradiation in locally advanced rectal cancer. Further investigations of a second set of patient and other treatment schedules are warranted.« less

Impact of fraction size on locally advanced oropharyngeal and nasopharyngeal cancers treated with chemoradiation.

PubMed

Spiotto, Michael T; Koshy, Matthew

2017-05-01

Although chemoradiation regimens have used various fraction sizes, it remains unclear how differences in fraction size impact outcomes. Using the National Cancer Database, we identified patients with nasopharynx or oropharynx cancers treated between 2004 and 2012 with chemoradiation using fraction sizes of 1.8Gy (n=1612), 2Gy (n=8092) or 2.12Gy (n=1660). Comparisons between fraction sizes were made in the entire cohort and in a propensity matched cohort. Median follow-up was 38.1m. Patients receiving 2.12Gy per fraction were more likely to be treated from 2007 to 2012, to be treated at an academic center, to have T3-T4 tumors and to have oropharyngeal primaries. The 3year overall survival for patients treated with 1.8Gy, 2Gy and 2.12Gy fraction sizes was 72.9%, 77.8% and 83.3%, respectively (P<0.0001). 2.12Gy fraction size was associated with improved survival in patients with nasopharynx cancer (P=0.03), base of tongue cancer (P<0.0001) and tonsil cancer (P=0.0002). On multivariate analysis, improved survival was associated with 2.12Gy fraction sizes compared to 2Gy (HR 1.23, 95% CI 1.09-1.40, P=0.001) or 1.8Gy (HR 1.36, 95% CI 1.17-1.58; P<0.0001) fractions sizes. Chemoradiation regimens using 2.12Gy fraction sizes likely have a potential advantage in select nasopharynx and oropharynx cancer patients based on age, treatment facility and radiotherapy technique. However, it remains unclear if this survival advantage reflected improved disease control due to lack of locoregional control data. Copyright © 2017 Elsevier Ltd. All rights reserved.

Selective Changes in the Immune Profile of Tumor-Draining Lymph Nodes After Different Neoadjuvant Chemoradiation Regimens for Locally Advanced Cervical Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Battaglia, Alessandra; Buzzonetti, Alexia; Martinelli, Enrica

2010-04-15

Purpose: To assess how neoadjuvant chemoradiation regimens modulate the immune system state in tumor-draining lymph nodes (TDLN), in the setting of advanced cervical cancer. Methods and Materials: Tumor-draining lymph nodes of patients undergoing chemotherapy only (nonirradiated, NI-TDLN) and chemoradiation with lower-dose (39.6 Gy, LD-TDLN) and higher-dose radiation (50 Gy, HD-TDLN) were analyzed by multicolor flow cytometry. Results: Enlarging our previous data, LD-TDLN showed features overall indicative of an enhanced antitumor response as compared with NI-TDLN, namely a significant Th1 and Tc1 polarization and a lower amount of the potent CD4{sup +}Foxp3{sup +}CD25{sup high} regulatory T cell (Treg) subset identified bymore » neuropilin-1 expression. Conversely, compared with NI-TDLN, HD-TDLN showed features overall indicative of an impaired antitumor response, namely a significantly inverted CD4/CD8 cell ratio, a higher Nrp1{sup +}Treg frequency, and a higher frequency of CCR4{sup +}Treg, a Treg subset facilitated in migrating out from TDLN to suppress the immune response against distant cancer cells. Moreover, the Th1 and Tc1 polarization induced by LD radiation was lost, and there was an unfavorable tolerogenic/immunogenic dendritic cell ratio compared with LD-TDLN. Conclusions: Even minor differences in radiation dose in neoadjuvant regimens for locally advanced cervical cancer are crucial for determining the balance between a tolerogenic and an efficacious antitumor immune response in TDLN. Because most of the anticancer immune response takes place in TDLN, the present findings also emphasize the importance of chemoradiation protocols in the context of immunotherapeutic trials.« less

Sacral Insufficiency Fractures After Preoperative Chemoradiation for Rectal Cancer: Incidence, Risk Factors, and Clinical Course

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herman, Michael P.; Kopetz, Scott; Bhosale, Priya R.

2009-07-01

Purpose: Sacral insufficiency (SI) fractures can occur as a late side effect of pelvic radiation therapy. Our goal was to determine the incidence, risk factors, and clinical course of SI fractures in patients treated with preoperative chemoradiation for rectal cancer. Materials and Methods: Between 1989 and 2004, 562 patients with non-metastatic rectal adenocarcinoma were treated with preoperative chemoradiation followed by mesorectal excision. The median radiotherapy dose was 45 Gy. The hospital records and radiology reports of these patients were reviewed to identify those with pelvic fractures. Radiology images of patients with pelvic fractures were then reviewed to identify those withmore » SI fractures. Results: Among the 562 patients, 15 had SI fractures. The 3-year actuarial rate of SI fractures was 3.1%. The median time to SI fractures was 17 months (range, 2-34 months). The risk of SI fractures was significantly higher in women compared to men (5.8% vs. 1.6%, p = 0.014), and in whites compared with non-whites (4% vs. 0%, p = 0.037). On multivariate analysis, gender independently predicted for the risk of SI fractures (hazard ratio, 3.25; p = 0.031). Documentation about the presence or absence of pain was available for 13 patients; of these 7 (54%) had symptoms requiring pain medications. The median duration of pain was 22 months. No patient required hospitalization or invasive intervention for pain control. Conclusions: SI fractures were uncommon in patients treated with preoperative chemoradiation for rectal cancer. The risk of SI fractures was significantly higher in women. Most cases of SI fractures can be managed conservatively with pain medications.« less

Small Bowel Dose Parameters Predicting Grade ≥3 Acute Toxicity in Rectal Cancer Patients Treated With Neoadjuvant Chemoradiation: An Independent Validation Study Comparing Peritoneal Space Versus Small Bowel Loop Contouring Techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Banerjee, Robyn, E-mail: robynbanerjee@gmail.com; Chakraborty, Santam; Nygren, Ian

Purpose: To determine whether volumes based on contours of the peritoneal space can be used instead of individual small bowel loops to predict for grade ≥3 acute small bowel toxicity in patients with rectal cancer treated with neoadjuvant chemoradiation therapy. Methods and Materials: A standardized contouring method was developed for the peritoneal space and retrospectively applied to the radiation treatment plans of 67 patients treated with neoadjuvant chemoradiation therapy for rectal cancer. Dose-volume histogram (DVH) data were extracted and analyzed against patient toxicity. Receiver operating characteristic analysis and logistic regression were carried out for both contouring methods. Results: Grade ≥3more » small bowel toxicity occurred in 16% (11/67) of patients in the study. A highly significant dose-volume relationship between small bowel irradiation and acute small bowel toxicity was supported by the use of both small bowel loop and peritoneal space contouring techniques. Receiver operating characteristic analysis demonstrated that, for both contouring methods, the greatest sensitivity for predicting toxicity was associated with the volume receiving between 15 and 25 Gy. Conclusion: DVH analysis of peritoneal space volumes accurately predicts grade ≥3 small bowel toxicity in patients with rectal cancer receiving neoadjuvant chemoradiation therapy, suggesting that the contours of the peritoneal space provide a reasonable surrogate for the contours of individual small bowel loops. The study finds that a small bowel V15 less than 275 cc and a peritoneal space V15 less than 830 cc are associated with a less than 10% risk of grade ≥3 acute toxicity.« less

Acute toxicity of definitive chemoradiation in patients with inoperable or irresectable esophageal carcinoma

PubMed Central

2014-01-01

Background Definitive chemoradiation (dCRT) is considered curative intent treatment for patients with inoperable or irresectable esophageal cancer. Acute toxicity data focussing on dCRT are lacking. Methods A retrospective analysis of patients treated with dCRT consisting of 6 cycles of paclitaxel 50 mg/m2 and carboplatin AUC2 concomitant with radiotherapy (50.4 Gy\\1.8Gy) from 2006 through 2011 at a single tertiary center was performed. Toxicity, hospital admissions and survival were analysed. Results 127 patients were treated with definitive chemoradiation. 33 patients were medically inoperable, 94 patients were irresectable, Despite of a significantly smaller tumor length in inoperable patients grade ≥3 toxicity was significantly recorded more often in the inoperable patients (44%) than in irresectable patients (20%) (p < 0.05) Hospital admission occurred more often in the inoperable patients (39%) than in the irresectable patients (22%) (p < 0.05) Median number of cycles of chemotherapy was five for inoperable patients (p = 0.01), while six cycles could be administered to patients with irresectable disease. Recurrence and survival were not significantly different. The odds ratio for developing toxicity ≥ grade 3 was 2.6 (95% CI 1.0-6.4 p < 0.05) for being an inoperable patient and 1.2 (95% CI 1.0-1.4 p = 0.02) per 10 extra micromol/l creatinine. Conclusions Our data show that acute toxicity of definitive chemoradiation is worse in patients with medically inoperable esophageal carcinoma compared to patients with irresectable esophageal cancer and mainly occurs in the 5th cycle of treatment. Improvement of supportive care should be undertaken in this more fragile group. PMID:24485047

Preoperative enteral access is not necessary prior to multimodality treatment of esophageal cancer.

PubMed

Jenkins, Thomas K; Lopez, Alexandra N; Sarosi, George A; Ben-David, Kfir; Thomas, Ryan M

2018-04-01

Surgical enteral access prior to multimodality treatment for esophageal cancer is controversial as dysphagia is often used for feeding tube referral. We hypothesized that enteral access before neoadjuvant chemoradiation for esophageal cancer provides no benefit compared to that placed during definitive esophagectomy. Patients undergoing esophagectomy for esophageal malignancy from 2007 - 2014 were retrospectively identified. Clinicopathologic factors were recorded including preoperative enteral access, weight change, nutritional laboratory works, and perioperative complications. Of 156 identified patients, 99 (63.5%) received neoadjuvant chemoradiation and comprised the study cohort. Fifty (50.5%) underwent enteral access (gastrostomy [14], jejunostomy [32], other [4]; "Access Group") prior to chemoradiation followed by esophagectomy and were compared to 49 "No-Access" patients who underwent enteral access during esophagectomy. Clinicopathologic variables were similar between cohorts. The Access and No-Access cohorts had similar reported dysphagia (86% vs 75.5%, respectively; P = .2) and mean preesophagectomy serum albumin (3.9 vs 4 gm/dL, respectively; P = .2). Weight loss ± 6-month periesophagectomy was similar between access versus No-Access cohorts (-11.2% vs -15.4%, respectively; P = .1). Weight loss during this period was likewise similar for patients with dysphagia in the Access (-11%) versus No-Access group (-15.2%, P = .1). No difference in complication rates was noted between Access (64%) and No-Access groups (51%, P = .2). Despite healthcare provider bias, there seems to be no nutritional or perioperative benefit for enteral access before neoadjuvant chemoradiation for esophageal malignancy. Patients with esophageal malignancy should therefore proceed to appropriate neoadjuvant and surgical therapy with enteral access performed during definitive resection or reserved for those with frank obstruction on endoscopy. Published by Elsevier Inc.

Individualized threshold for tumor segmentation in 18F-FDG PET/CT imaging: The key for response evaluation of neoadjuvant chemoradiation therapy in patients with rectal cancer?

PubMed

Fagundes, Theara C; Mafra, Arnoldo; Silva, Rodrigo G; Castro, Ana C G; Silva, Luciana C; Aguiar, Priscilla T; Silva, Josiane A; P Junior, Eduardo; Machado, Alexei M; Mamede, Marcelo

2018-02-01

The standard treatment for locally advanced rectal cancer (RC) consists of neoadjuvant chemoradiation followed by radical surgery. Regardless the extensive use of SUVmax in 18F-FDG PET tumor uptake as representation of tumor glycolytic consumption, there is a trend to apply metabolic volume instead. Thus, the aim of the present study was to evaluate a noninvasive method for tumor segmentation using the 18F-FDG PET imaging in order to predict response to neoadjuvant chemoradiation therapy in patients with rectal cancer. The sample consisted of stage II and III rectal cancer patients undergoing 18F-FDG PET/CT examination before and eight weeks after neoadjuvant therapy. An individualized tumor segmentation methodology was applied to generate tumor volumes (SUV2SD) and compare with standard SUVmax and fixed threshold (SUV40%, SUV50% and SUV60%) pre- and post-therapy. Therapeutic response was assessed in the resected specimens using Dworak's protocol recommendations. Several variables were generated and compared with the histopathological results. Seventeen (17) patients were included and analyzed. Significant differences were observed between responders (Dworak 3 and 4) and non-responders for SUVmax-2 (p<0.01), SUV2SD-2 (p<0.05), SUV40%-2 (p<0.05), SUV50%-2 (p<0.05) and SUV60%-2 (p<0.05). ROC analyses showed significant areas under the curve (p<0.01) for the proposed methodology with sensitivity and specificity varying from 60% to 83% and 73% to 82%, respectively. The present study confirmed the predictive power of the variables using a noninvasive individualized methodology for tumor segmentation based on 18F-FDG PET/CT imaging for response evaluation in patients with rectal cancer after neoadjuvant chemoradiation therapy.

Distant Metastasis Risk Stratification for Patients Undergoing Curative Resection Followed by Adjuvant Chemoradiation for Extrahepatic Bile Duct Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Kyubo; Chie, Eui Kyu, E-mail: ekchie93@snu.ac.kr; Jang, Jin-Young

2012-09-01

Purpose: To analyze the prognostic factors predicting distant metastasis in patients undergoing adjuvant chemoradiation for extrahepatic bile duct (EHBD) cancer. Methods and Materials: Between January 1995 and August 2006, 166 patients with EHBD cancer underwent resection with curative intent, followed by adjuvant chemoradiation. There were 120 males and 46 females, and median age was 61 years (range, 34-86). Postoperative radiotherapy was delivered to tumor bed and regional lymph nodes (median dose, 40 Gy; range, 34-56 Gy). A total of 157 patients also received fluoropyrimidine chemotherapy as a radiosensitizer, and fluoropyrimidine-based maintenance chemotherapy was administered to 127 patients. Median follow-up durationmore » was 29 months. Results: The treatment failed for 97 patients, and the major pattern of failure was distant metastasis (76 patients, 78.4%). The 5-year distant metastasis-free survival rate was 49.4%. The most common site of distant failure was the liver (n = 36). On multivariate analysis, hilar tumor, tumor size {>=}2 cm, involved lymph node, and poorly differentiated tumor were associated with inferior distant metastasis-free survival (p = 0.0348, 0.0754, 0.0009, and 0.0078, respectively), whereas T stage was not (p = 0.8081). When patients were divided into four groups based on these risk factors, the 5-year distant metastasis-free survival rates for patients with 0, 1, 2, and 3 risk factors were 86.4%, 59.9%, 32.5%, and 0%, respectively (p < 0.0001). Conclusion: Despite maintenance chemotherapy, distant metastasis was the major pattern of failure in patients undergoing adjuvant chemoradiation for EHBD cancer after resection with curative intent. Intensified chemotherapy is warranted to improve the treatment outcome, especially in those with multiple risk factors.« less

Radiation Therapy for Locally Advanced Esophageal Cancer.

PubMed

Chun, Stephen G; Skinner, Heath D; Minsky, Bruce D

2017-04-01

The treatment of locally advanced esophageal cancer is controversial. For patients who are candidates for surgical resection, multiple prospective clinical trials have demonstrated the advantages of neoadjuvant chemoradiation. For patients who are medically inoperable, definitive chemoradiation is an alternative approach with survival rates comparable to trimodality therapy. Although trials of dose escalation are ongoing, the standard radiation dose remains 50.4 Gy. Modern radiotherapy techniques such as image-guided radiation therapy with motion management and intensity-modulated radiation therapy are strongly encouraged with a planning objective to maximize conformity to the intended target volume while reducing dose delivered to uninvolved normal tissues. Copyright © 2016 Elsevier Inc. All rights reserved.

Using [{sup 18}F]Fluorothymidine Imaged With Positron Emission Tomography to Quantify and Reduce Hematologic Toxicity Due to Chemoradiation Therapy for Pelvic Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

McGuire, Sarah M., E-mail: sarah-mcguire@uiowa.edu; Bhatia, Sudershan K.; Sun, Wenqing

Purpose: The purpose of the present prospective clinical trial was to determine the efficacy of [{sup 18}F]fluorothymidine (FLT)-identified active bone marrow sparing for pelvic cancer patients by correlating the FLT uptake change during and after chemoradiation therapy with hematologic toxicity. Methods and Materials: Simulation FLT positron emission tomography (PET) images were used to spare pelvic bone marrow using intensity modulated radiation therapy (IMRT BMS) for 32 patients with pelvic cancer. FLT PET scans taken during chemoradiation therapy after 1 and 2 weeks and 30 days and 1 year after completion of chemoradiation therapy were used to evaluate the acute and chronic dose responsemore » of pelvic bone marrow. Complete blood counts were recorded at each imaging point to correlate the FLT uptake change with systemic hematologic toxicity. Results: IMRT BMS plans significantly reduced the dose to the pelvic regions identified with FLT uptake compared with control IMRT plans (P<.001, paired t test). Radiation doses of 4 Gy caused an ∼50% decrease in FLT uptake in the pelvic bone marrow after either 1 or 2 weeks of chemoradiation therapy. Additionally, subjects with more FLT-identified bone marrow exposed to ≥4 Gy after 1 week developed grade 2 leukopenia sooner than subjects with less marrow exposed to ≥4 Gy (P<.05, Cox regression analysis). Apparent bone marrow recovery at 30 days after therapy was not maintained 1 year after chemotherapy. The FLT uptake in the pelvic bone marrow regions that received >35 Gy was 18.8% ± 1.8% greater at 30 days after therapy than at 1 year after therapy. The white blood cell, platelet, lymphocyte, and neutrophil counts at 1 year after therapy were all lower than the pretherapy levels (P<.05, paired t test). Conclusions: IMRT BMS plans reduced the dose to FLT-identified pelvic bone marrow for pelvic cancer patients. However, reducing hematologic toxicity is challenging owing to the acute radiation sensitivity (∼4 Gy) and chronic suppression of activity in bone marrow receiving radiation doses >35 Gy, as measured by the FLT uptake change correlated with the complete blood cell counts.« less

Zambian pre-service junior high school science teachers' chemical reasoning and ability

NASA Astrophysics Data System (ADS)

Banda, Asiana

The purpose of this study was two-fold: examine junior high school pre-service science teachers' chemical reasoning; and establish the extent to which the pre-service science teachers' chemical abilities explain their chemical reasoning. A sample comprised 165 junior high school pre-service science teachers at Mufulira College of Education in Zambia. There were 82 males and 83 females. Data were collected using a Chemical Concept Reasoning Test (CCRT). Pre-service science teachers' chemical reasoning was established through qualitative analysis of their responses to test items. The Rasch Model was used to determine the pre-service teachers' chemical abilities and item difficulty. Results show that most pre-service science teachers had incorrect chemical reasoning on chemical concepts assessed in this study. There was no significant difference in chemical understanding between the Full-Time and Distance Education pre-service science teachers, and between second and third year pre-service science teachers. However, there was a significant difference in chemical understanding between male and female pre-service science teachers. Male pre-service science teachers showed better chemical understanding than female pre-service science teachers. The Rasch model revealed that the pre-service science teachers had low chemical abilities, and the CCRT was very difficult for this group of pre-service science teachers. As such, their incorrect chemical reasoning was attributed to their low chemical abilities. These results have implications on science teacher education, chemistry teaching and learning, and chemical education research.

Inducing Cold-Sensitivity in the Frigophilic Fly Drosophila montana by RNAi

PubMed Central

Cook, Nicola; Tournière, Océane; Sneddon, Tanya; Ritchie, Michael G.

2016-01-01

Cold acclimation is a critical physiological adaptation for coping with seasonal cold. By increasing their cold tolerance individuals can remain active for longer at the onset of winter and can recover more quickly from a cold shock. In insects, despite many physiological studies, little is known about the genetic basis of cold acclimation. Recently, transcriptomic analyses in Drosophila virilis and D. montana revealed candidate genes for cold acclimation by identifying genes upregulated during exposure to cold. Here, we test the role of myo-inositol-1-phosphate synthase (Inos), in cold tolerance in D. montana using an RNAi approach. D. montana has a circumpolar distribution and overwinters as an adult in northern latitudes with extreme cold. We assessed cold tolerance of dsRNA knock-down flies using two metrics: chill-coma recovery time (CCRT) and mortality rate after cold acclimation. Injection of dsRNAInos did not alter CCRT, either overall or in interaction with the cold treatment, however it did induced cold-specific mortality, with high levels of mortality observed in injected flies acclimated at 5°C but not at 19°C. Overall, injection with dsRNAInos induced a temperature-sensitive mortality rate of over 60% in this normally cold-tolerant species. qPCR analysis confirmed that dsRNA injection successfully reduced gene expression of Inos. Thus, our results demonstrate the involvement of Inos in increasing cold tolerance in D. montana. The potential mechanisms involved by which Inos increases cold tolerance are also discussed. PMID:27832122

The role of systemic therapy in the management of sinonasal cancer: A critical review.

PubMed

Bossi, Paolo; Saba, Nabil F; Vermorken, Jan B; Strojan, Primoz; Pala, Laura; de Bree, Remco; Rodrigo, Juan Pablo; Lopez, Fernando; Hanna, Ehab Y; Haigentz, Missak; Takes, Robert P; Slootweg, Piet J; Silver, Carl E; Rinaldo, Alessandra; Ferlito, Alfio

2015-12-01

Due to the rarity and the variety of histological types of sinonasal cancers, there is a paucity of data regarding strategy for their optimal treatment. Generally, outcomes of advanced and higher grade tumors remain unsatisfactory, despite the employment of sophisticated surgical approaches, technical advances in radiation techniques and the use of heavy ion particles. In this context, we critically evaluated the role of systemic therapy as part of a multidisciplinary approach to locally advanced disease. Induction chemotherapy has shown encouraging activity and could have a role in the multimodal treatment of patients with advanced sinonasal tumors. For epithelial tumors, the most frequently employed chemotherapy is cisplatin, in combination with either 5-fluorouracil, taxane, ifosfamide, or vincristine. Only limited experiences with concurrent chemoradiation exist with sinonasal cancer. The role of systemic treatment for each histological type (intestinal-type adenocarcinoma, sinonasal undifferentiated carcinoma, sinonasal neuroendocrine carcinoma, olfactory neuroblastoma, sinonasal primary mucosal melanoma, sarcoma) is discussed. The treatment of SNC requires a multimodal approach. Employment of systemic therapy for locally advanced disease could result in better outcomes, and optimize the therapeutic armamentarium. Further studies are needed to precisely define the role of systemic therapy and identify the optimal sequencing for its administration in relation to local therapies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Rectal Cancer Diagnosed after Cesarean Section in Which High Microsatellite Instability Indicated the Presence of Lynch Syndrome

PubMed Central

Okuda, Tomohiro; Ishii, Hiroshi; Yamashita, Sadao; Matsuo, Seiki; Okimura, Hiroyuki

2015-01-01

We report a case of rectal cancer with microsatellite instability (MSI) that probably resulted from Lynch syndrome and that was diagnosed after Cesarean section. The patient was a 28-year-old woman (gravid 1, para 1) without a significant medical history. At 35 gestational weeks, vaginal ultrasonography revealed a 5 cm tumor behind the uterine cervix, which was diagnosed as a uterine myoma. The tumor gradually increased in size and blocked the birth canal, resulting in the patient undergoing an emergency Cesarean section. Postoperatively, the tumor was diagnosed as rectal cancer with MSI. After concurrent chemoradiation therapy, a lower anterior resection was performed. The patient's family history revealed she met the criteria of the revised Bethesda guidelines for testing the colorectal tumor for MSI. Testing revealed that the tumor did indeed show high MSI and, combined with the family history, suggested this could be a case of Lynch syndrome. Our findings emphasize the importance of considering the possibility of Lynch syndrome in pregnant women with colorectal cancer, particularly those with a family history of this condition. We suggest that the presence of Lynch syndrome should also be considered for any young woman with endometrial, ovarian, or colorectal cancer. PMID:26064726

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Shinn-Yn; Department of Medical Imaging and Radiological Sciences, College of Medicine, Chang Gung University, Taiwan; Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taiwan

Purpose: This report is the second analysis of a prospective randomized trial to investigate the impact of {sup 18}F-fluorodeoxyglucose positron emission tomography (FDG-PET) on cervical cancer patients with enlarged pelvic lymph nodes identified by magnetic resonance imaging. Methods and Materials: Patients with newly diagnosed cervical cancer with enlarged pelvic lymph nodes but free of enlarged para-aortic lymph nodes (PALN) were eligible. Patients were randomized to receive either pretreatment FDG-PET (PET arm) or not (control arm). The whole pelvis was the standard irradiation field for all patients except those with FDG-avid extrapelvic findings. Results: In all, 129 patients were enrolled. Pretreatmentmore » PET detected extrapelvic metastases in 7 patients. No new patient experienced treatment failure during the additional 4-year follow-up period. There were no significant differences between the PET arm and the control arm regarding overall survival, disease-free survival, and freedom from extrapelvic metastasis. In the control arm, 8 of 10 patients with PALN relapse had limited extrapelvic nodal failures; their 5-year disease-specific survival was 34.3%. By contrast, only 1 of 5 patients with PALN relapse in the PET arm experienced such limited failures; their 5-year survival rate was 0%. Conclusions: Although the pretreatment detection of PALN did not translate into survival benefit, it indeed decreased the need for extended-field concurrent chemoradiation therapy.« less

Radiation recall gastritis secondary to combination of gemcitabine and erlotinib in pancreatic cancer and response to PPI - a case report.

PubMed

Choi, Seong Ji; Kim, Hyo Jung; Kim, Jae Seon; Bak, Young-Tae; Kim, Jun Suk

2016-08-02

Radiation recall gastritis is rare but can be induced after concurrent chemoradiation for pancreatic cancer. We report a patient with pancreatic cancer who developed radiation-recall gastritis related to a combination of gemcitabine and erlotinib. A 54-year-old female with unresectable pancreatic cancer received gemcitabine in combination with radiation therapy followed by chemotherapy with gemcitabine and erlotinib. After completing 2 cycles of chemotherapy, the patient had epigastric pain, nausea, and vomiting. Abdominal computed tomography (CT) scan revealed diffuse wall thickening of the stomach, and esophagogastroduodenoscopy (EGD) showed multiple gastric ulcers. The patient was treated with proton pump inhibitors (PPI) and was continued on maintenance chemotherapy. Two months later, the patient presented with the similar symptoms and persistent gastric ulcers were observed during subsequent EGD. Nevertheless, the patient's symptom had resolved with PPI therapy. Thus, the patient underwent maintenance chemotherapy with gemcitabine and erlotinib for additional 4 cycles. Eventually, follow-up abdominal CT Scan and EGD at 6 months demonstrated resolution of the gastric ulcers. Physicians should be aware of the possibility of radiation recall gastritis associated with a combination of gemcitabine and erlotinib. Administration of PPIs may mitigate the adverse effects of gemcitabine and erlotinib in the presence of radiation recall gastritis; however further studies are warranted.

Rare metastasis of nasopharyngeal carcinoma to the thyroid gland with subsequent metastatic abdominal lymph nodes: A case report and literature review.

PubMed

Cai, Changjing; Shen, Hong; Liu, Wenqiang; Ma, Junli; Zhang, Yan; Yin, Ling; Li, Jindong; Shen, Liangfang; Zeng, Shan

2017-11-01

Thyroid metastasis from nasopharyngeal carcinoma is rare. Metastasis of nasopharyngeal carcinoma to the thyroid gland with subsequent metastatic abdominal lymph nodes hasn't been reported before. We want to share our experience about the treatment choice. A 27-year-old man was diagnosed with nasopharyngeal nonkeratinizing carcinoma in August 2004. In March 2013 he underwent a thyroid carcinoma radical operation, and histological examination revealed metastasis to the thyroid gland from nasopharyngeal carcinoma. An 18F-FDG-PET/CT scan and biopsy showed metastatic abdominal lymph nodes of nasopharyngeal carcinoma in April 2015. A 27-year-old man was diagnosed with metastasis of nasopharyngeal carcinoma to the thyroid gland with subsequent metastatic abdominal lymph nodes. The patient was treated with concurrent chemotherapy and radiotherapy for nasopharyngeal carcinoma and metastasis to the thyroid gland. The metastases to the abdominal lymph nodes received chemotherapy. After 6 cycles of chemotherapy with gemcitabine, cisplatin, and 5-fluorouracil for metastasis to the abdominal lymph nodes, the patient is currently asymptomatic with stable disease and improved quality of life. The treatment choice for metastasis of nasopharyngeal carcinoma depends on the clinical disease extent, and surgery and/or chemo-radiation therapy must be drafted to the individual patient in order to improve the prognosis and quality of life.

Head and Neck Cancer: An Overview

PubMed Central

Stepnick, David; Gilpin, David

2010-01-01

Ablative surgery for malignancies of the upper aerodigestive tract is the most common reason why the reconstructive surgeon is called upon to reconstruct adult head and neck defects. An understanding of the pathophysiology and treatment of head and neck malignancy is vital to the reconstructive surgeon so that restoration of both form and function can be achieved. It is important to understand the behavior of cancers of each head and neck subsite, as staging and ultimately the treatment of tumors from each subsite is different. Historically, the standard treatment of head and neck cancer was surgery and/or primary radiation therapy with surgical salvage for failure. Beginning in the 1980s, advances in chemotherapy and concurrent delivery with radiation offered new options to standard surgical therapy. Over the past two decades, the concept of organ preservation using chemotherapy together with radiation therapy has been definitively established. Yet, even with the strides made over these two decades with chemoradiation, surgical treatment of head and neck cancer and reconstruction thereof will be an important treatment option for the foreseeable future. Therefore, the relationship between the extirpative and reconstructive surgeon is vital, and a clear understanding of the biology and behavior of head and neck malignancy is crucial to successful patient outcomes. PMID:22550431

Optimal Use of Combined Modality Therapy in the Treatment of Esophageal Cancer.

PubMed

Shaikh, Talha; Meyer, Joshua E; Horwitz, Eric M

2017-07-01

Esophageal cancer is associated with a poor prognosis with 5-year survival rates of approximately 15% to 20%. Although patients with early stage disease may adequately be treated with a single modality, combined therapy typically consisting of neoadjuvant chemoradiation followed by esophagectomy is being adopted increasingly in patients with locally advanced disease. In patients who are not surgical candidates, definitive chemoradiation is the preferred treatment approach. All patients with newly diagnosed esophageal cancer should be evaluated in the multidisciplinary setting by a surgeon, radiation oncologist, and medical oncologist owing to the importance of each specialty in the management of these patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Fuel Property, Emission Test, and Operability Results from a Fleet of Class 6 Vehicles Operating on Gas-to-Liquid Fuel and Catalyzed Diesel Particle Filters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alleman, T. L.; Eudy, L.; Miyasato, M.

A fleet of six 2001 International Class 6 trucks operating in southern California was selected for an operability and emissions study using gas-to-liquid (GTL) fuel and catalyzed diesel particle filters (CDPF). Three vehicles were fueled with CARB specification diesel fuel and no emission control devices (current technology), and three vehicles were fueled with GTL fuel and retrofit with Johnson Matthey's CCRT diesel particulate filter. No engine modifications were made.

Chemoradiation related acute morbidity in carcinoma cervix and correlation with hematologic toxicity: a South Indian prospective study.

PubMed

Kumaran, Aswathy; Guruvare, Shyamala; Sharan, Krishna; Rai, Lavanya; Hebbar, Shripad

2014-01-01

To assess chemoradiation related acute morbidity in women with carcinoma cervix and to find and correlation between hematologic toxicity and organ system specific damage. A prospective study was carried out between August 2012 and July 2013 enrolling 79 women with cancer cervix receiving chemo-radiotherapy. Weekly assessment of acute morbidity was done using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4 and the toxicities were graded. Anemia [77 (97.5%)], vomiting [75 (94.8%)] and diarrhea [72 (91.1%)], leukopenia [11 (13.9%)], cystitis [28 (35.4%], dermatitis [19 (24.1%)] and fatigue [29 (36.71%)] were the acute toxicities noted. The toxicities were most severe in 3rd and 5th week. All women could complete radiotherapy except two due to causes unrelated to radiation morbidity; seven (8.86%) had to discontinue chemotherapy due to leukopenia and intractable diarrhea. Though there was no correlation between anemia and other toxicities, it was found that all with leukopenia had diarrhea. Chemoradiation for cancer cervix is on the whole well tolerated. Leukopenia and severe diarrhea were the acute toxicities that compelled discontinuation of chemotherapy in two women. Though anemia had no correlation with gastrointestinal toxicity, all of those with leukopenia had diarrhea.

Improved outcomes with intensity modulated radiation therapy combined with temozolomide for newly diagnosed glioblastoma multiforme.

PubMed

Aherne, Noel J; Benjamin, Linus C; Horsley, Patrick J; Silva, Thomaz; Wilcox, Shea; Amalaseelan, Julan; Dwyer, Patrick; Tahir, Abdul M R; Hill, Jacques; Last, Andrew; Hansen, Carmen; McLachlan, Craig S; Lee, Yvonne L; McKay, Michael J; Shakespeare, Thomas P

2014-01-01

Purpose. Glioblastoma multiforme (GBM) is optimally treated by maximal debulking followed by combined chemoradiation. Intensity modulated radiation therapy (IMRT) is gaining widespread acceptance in other tumour sites, although evidence to support its use over three-dimensional conformal radiation therapy (3DCRT) in the treatment of gliomas is currently lacking. We examined the survival outcomes for patients with GBM treated with IMRT and Temozolomide. Methods and Materials. In all, 31 patients with GBM were treated with IMRT and 23 of these received chemoradiation with Temozolomide. We correlated survival outcomes with patient functional status, extent of surgery, radiation dose, and use of chemotherapy. Results. Median survival for all patients was 11.3 months, with a median survival of 7.2 months for patients receiving 40.05 Gray (Gy) and a median survival of 17.4 months for patients receiving 60 Gy. Conclusions. We report one of the few series of IMRT in patients with GBM. In our group, median survival for those receiving 60 Gy with Temozolomide compared favourably to the combined therapy arm of the largest randomised trial of chemoradiation versus radiation to date (17.4 months versus 14.6 months). We propose that IMRT should be considered as an alternative to 3DCRT for patients with GBM.

Improved Outcomes with Intensity Modulated Radiation Therapy Combined with Temozolomide for Newly Diagnosed Glioblastoma Multiforme

PubMed Central

Aherne, Noel J.; Benjamin, Linus C.; Horsley, Patrick J.; Silva, Thomaz; Wilcox, Shea; Amalaseelan, Julan; Dwyer, Patrick; Tahir, Abdul M. R.; Hill, Jacques; Last, Andrew; Hansen, Carmen; McLachlan, Craig S.; Lee, Yvonne L.; McKay, Michael J.; Shakespeare, Thomas P.

2014-01-01

Purpose. Glioblastoma multiforme (GBM) is optimally treated by maximal debulking followed by combined chemoradiation. Intensity modulated radiation therapy (IMRT) is gaining widespread acceptance in other tumour sites, although evidence to support its use over three-dimensional conformal radiation therapy (3DCRT) in the treatment of gliomas is currently lacking. We examined the survival outcomes for patients with GBM treated with IMRT and Temozolomide. Methods and Materials. In all, 31 patients with GBM were treated with IMRT and 23 of these received chemoradiation with Temozolomide. We correlated survival outcomes with patient functional status, extent of surgery, radiation dose, and use of chemotherapy. Results. Median survival for all patients was 11.3 months, with a median survival of 7.2 months for patients receiving 40.05 Gray (Gy) and a median survival of 17.4 months for patients receiving 60 Gy. Conclusions. We report one of the few series of IMRT in patients with GBM. In our group, median survival for those receiving 60 Gy with Temozolomide compared favourably to the combined therapy arm of the largest randomised trial of chemoradiation versus radiation to date (17.4 months versus 14.6 months). We propose that IMRT should be considered as an alternative to 3DCRT for patients with GBM. PMID:24563782

Patient's Skeletal Muscle Radiation Attenuation and Sarcopenic Obesity are Associated with Postoperative Morbidity after Neoadjuvant Chemoradiation and Resection for Rectal Cancer.

PubMed

Berkel, Annefleur E M; Klaase, Joost M; de Graaff, Feike; Brusse-Keizer, Marjolein G J; Bongers, Bart C; van Meeteren, Nico L U

2018-06-13

To investigate the relation between skeletal muscle measurements (muscle mass, radiation attenuation, and sarcopenic obesity), postoperative morbidity, and survival after treatment of locally advanced rectal cancer. This explorative retrospective study identified 99 consecutive patients who underwent neoadjuvant chemoradiation and surgery between January 2007 and May 2012. Skeletal muscle mass was measured as total psoas area and total abdominal muscle area (TAMA) at 3 anatomical levels using the patient's preoperative computed tomography scan. Radiation attenuation was measured using corresponding mean Hounsfield units for TAMA. Sarcopenic obesity was defined as body mass index above 25 kg·m-2 combined with skeletal muscle mass index below the sex-specific median. Postoperative complications were graded by using the -Clavien-Dindo classification. Twenty-five patients (25.3%) developed a grade 3-5 complication. Lower radiation attenuation was independently associated with overall (p = 0.003) and grade 3-5 complications (p = 0.002). Sarcopenic obesity was associated with overall complications (all p < 0.05). Skeletal muscle measurements and survival were not significantly related. Radiation attenuation was associated with overall and grade 3-5 postoperative morbidity after neoadjuvant chemoradiation and non-laparoscopic resection for rectal cancer. Sarcopenic obesity was associated with overall complications. © 2018 S. Karger AG, Basel.

Utility of the transnasal esophagoscope in the management of chemoradiation-induced esophageal stenosis.

PubMed

Peng, Kevin A; Feinstein, Aaron J; Salinas, Jonathan B; Chhetri, Dinesh K

2015-03-01

This study aimed to describe management of esophageal stenosis after chemoradiation therapy for head and neck squamous cell carcinoma (HNSCC), with particular emphasis on techniques and outcomes with the use of the transnasal esophagoscope (TNE) in the office as well as operating room settings. Retrospective analysis of all patients with esophageal stenosis following head and neck cancer radiation, with or without chemotherapy, and managed with TNE-assisted esophageal dilation over a 5-year period. Preoperative and postoperative swallowing function were assessed objectively with the Functional Outcome Swallowing Scale (FOSS; ranging from score 0, a normal diet, to score 5, complete dependence on nonoral nutrition). Twenty-five patients met inclusion criteria. The mean pretreatment FOSS score was 4.4, whereas the mean posttreatment FOSS score was 2.7 (Wilcoxon signed-rank test, P<.001). Prior to dilation, 16 patients were completely gastrostomy-tube dependent (FOSS 5), of whom 12 (75%) were able to tolerate oral nutrition for a majority of their diet following treatment according to our protocol. No complications were noted. Dysphagia following chemoradiation therapy for HNSCC is often related to esophageal stenosis. With the aid of TNE, we have developed a successful treatment strategy for esophageal stenosis with improved success rates. © The Author(s) 2014.

Once-a-Week Versus Once-Every-3-Weeks Cisplatin Chemoradiation for Locally Advanced Head and Neck Cancer: A Phase III Randomized Noninferiority Trial.

PubMed

Noronha, Vanita; Joshi, Amit; Patil, Vijay Maruti; Agarwal, Jaiprakash; Ghosh-Laskar, Sarbani; Budrukkar, Ashwini; Murthy, Vedang; Gupta, Tejpal; D'Cruz, Anil K; Banavali, Shripad; Pai, Prathamesh S; Chaturvedi, Pankaj; Chaukar, Devendra; Pande, Nikhil; Chandrasekharan, Arun; Talreja, Vikas; Vallathol, Dilip Harindran; Mathrudev, Vijayalakshmi; Manjrekar, Aparna; Maske, Kamesh; Bhelekar, Arati Sanjay; Nawale, Kavita; Kannan, Sadhana; Gota, Vikram; Bhattacharjee, Atanu; Kane, Shubhada; Juvekar, Shashikant L; Prabhash, Kumar

2018-04-10

Purpose Chemoradiation with cisplatin 100 mg/m 2 given once every 3 weeks is the standard of care in locally advanced head and neck squamous cell cancer (LAHNSCC). Increasingly, low-dose once-a-week cisplatin is substituted because of perceived lower toxicity and convenience. However, there is no level 1 evidence of comparable efficacy to cisplatin once every 3 weeks. Patients and Methods In this phase III randomized trial, we assessed the noninferiority of cisplatin 30 mg/m 2 given once a week compared with cisplatin 100 mg/m 2 given once every 3 weeks, both administered concurrently with curative intent radiotherapy in patients with LAHNSCC. The primary end point was locoregional control (LRC); secondary end points included toxicity, compliance, response, progression-free survival, and overall survival. Results Between 2013 and 2017, we randomly assigned 300 patients, 150 to each arm. Two hundred seventy-nine patients (93%) received chemoradiotherapy in the adjuvant setting. At a median follow-up of 22 months, the estimated cumulative 2-year LRC rate was 58.5% in the once-a-week arm and 73.1% in the once-every-3-weeks arm, leading to an absolute difference of 14.6% (95% CI, 5.7% to 23.5%); P = .014; hazard ratio (HR), 1.76 (95% CI, 1.11 to 2.79). Acute toxicities of grade 3 or higher occurred in 71.6% of patients in the once-a-week arm and in 84.6% of patients in the once-every-3-weeks arm ( P = .006). Estimated median progression-free survival in the once-a-week arm was 17.7 months (95% CI, 0.42 to 35.05 months) and in the once-every-3-weeks arm, 28.6 months (95% CI, 15.90 to 41.30 months); HR, 1.24 (95% CI, 0.89 to 1.73); P = .21. Estimated median overall survival in the once-a-week arm was 39.5 months and was not reached in the once-every-3-weeks arm (HR, 1.14 [95% CI, 0.79 to 1.65]; P = .48). Conclusion Once-every-3-weeks cisplatin at 100 mg/m 2 resulted in superior LRC, albeit with more toxicity, than did once-a-week cisplatin at 30 mg/m 2 , and should remain the preferred chemoradiotherapy regimen for LAHNSCC in the adjuvant setting.

SU-F-T-106: A Dosimetric Study of Intensity Modulated Radiation Therapy to Decrease Radiation Dose to the Thoracic Vertebral Bodies in Patients Receiving Concurrent Chemoradiation for Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

DiCostanzo, Dominic; Barney, Christian L.; Bazan, Jose G.

Purpose: Recent clinical studies have shown a correlation between radiation dose to the thoracic vertebral bodies (TVB) and the development of hematologic toxicity (HT) in patients receiving chemoradiation (CRT) for lung cancer (LuCa). The feasibility of a bone-marrow sparing (BMS) approach in this group of patients is unknown. We hypothesized that radiation dose to the TVB can be reduced with an intensity modulated radiation therapy(IMRT)/volumetric modulated arc radiotherapy(VMAT) without affecting plan quality. Methods: We identified LuCa cases treated with curative intent CRT using IMRT/VMAT from 4/2009 to 2/2015. The TVBs from T1–T10 were retrospectively contoured. No constraints were placed onmore » the TVB structure initially. A subset were re-planned with BMS-IMRT/VMAT with an objective or reducing the mean TVB dose to <23 Gy. The following data were collected on the initial and BMS plans: mean dose to planning target volume (PTV), lungs-PTV, esophagus, heart; lung V20; cord max dose. Pairwise comparisons were performed using the signed rank test. Results: 94 cases received CRT with IMRT/VMAT. We selected 11 cases (7 IMRT, 4 VMAT) with a range of initial mean TVB doses (median 35.7 Gy, range 18.9–41.4 Gy). Median prescription dose was 60 Gy. BMS-IMRT/VMAT significantly reduced the mean TVB dose by a median of 10.2 Gy (range, 1.0–16.7 Gy, p=0.001) and reduced the cord max dose by 2.9 Gy (p=0.014). BMS-IMRT/VMAT had no impact on lung mean (median +17 cGy, p=0.700), lung V20 (median +0.5%, p=0.898), esophagus mean (median +13 cGy, p=1.000) or heart mean (median +16 cGy, p=0.365). PTV-mean dose was not affected by BMS-IMRT/VMAT (median +13 cGy, p=0.653). Conclusion: BMS-IMRT/VMAT was able to significantly reduce radiation dose to the TVB without compromising plan quality. Prospective evaluation of BMS-IMRT/VMAT in patients receiving CRT for LuCa is warranted to determine if this approach results in clinically significant reductions in HT.« less

Definitive Chemoradiation Therapy With Docetaxel, Cisplatin, and 5-Fluorouracil (DCF-R) in Advanced Esophageal Cancer: A Phase 2 Trial (KDOG 0501-P2)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Higuchi, Katsuhiko, E-mail: k.higu@kitasato-u.ac.jp; Komori, Shouko; Tanabe, Satoshi

Purpose: A previous phase 1 study suggested that definitive chemoradiation therapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-R) is tolerable and active in patients with advanced esophageal cancer (AEC). This phase 2 study was designed to confirm the efficacy and toxicity of DCF-R in AEC. Methods and Materials: Patients with previously untreated thoracic AEC who had T4 tumors or M1 lymph node metastasis (M1 LYM), or both, received intravenous infusions of docetaxel (35 mg/m{sup 2}) and cisplatin (40 mg/m{sup 2}) on day 1 and a continuous intravenous infusion of 5-fluorouracil (400 mg/m{sup 2}/day) on days 1 to 5, every 2 weeks,more » plus concurrent radiation. The total radiation dose was initially 61.2 Gy but was lowered to multiple-field irradiation with 50.4 Gy to decrease esophagitis and late toxicity. Consequently, the number of cycles of DCF administered during radiation therapy was reduced from 4 to 3. The primary endpoint was the clinical complete response (cCR) rate. Results: Characteristics of the 42 subjects were: median age, 62 years; performance status, 0 in 14, 1 in 25, 2 in 3; TNM classification, T4M0 in 20, non-T4M1LYM in 12, T4M1LYM in 10; total scheduled radiation dose: 61.2 Gy in 12, 50.4 Gy in 30. The cCR rate was 52.4% (95% confidence interval [CI]: 37.3%-67.5%) overall, 33.3% in the 61.2-Gy group, and 60.0% in the 50.4-Gy group. The median progression-free survival was 11.1 months, and the median survival was 29.0 months with a survival rate of 43.9% at 3 years. Grade 3 or higher major toxicity consisted of leukopenia (71.4%), neutropenia (57.2%), anemia (16.7%), febrile neutropenia (38.1%), anorexia (31.0%), and esophagitis (28.6%). Conclusions: DCF-R frequently caused myelosuppression and esophagitis but was highly active and suggested to be a promising regimen in AEC. On the basis of efficacy and safety, a radiation dose of 50.4 Gy is recommended for further studies of DCF-R.« less

Long-Term Follow-Up of a Prospective Trial of Trimodality Therapy of Weekly Paclitaxel, Radiation, and Androgen Deprivation in High-Risk Prostate Cancer With or Without Prior Prostatectomy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hussain, Arif, E-mail: ahussain@som.umaryland.edu; Department of Medicine, University of Maryland School of Medicine, Baltimore, MD; Baltimore VA Medical Center, Baltimore, MD

2012-01-01

Purpose: Weekly paclitaxel, concurrent radiation, and androgen deprivation (ADT) were evaluated in patients with high-risk prostate cancer (PC) with or without prior prostatectomy (RP). Methods and Materials: Eligible post-RP patients included: pathological T3 disease, or rising prostate-specific antigen (PSA) {>=}0.5 ng/mL post-RP. Eligible locally advanced PC (LAPC) patients included: 1) cT2b-4N0N+, M0; 2) Gleason score (GS) 8-10; 3) GS 7 + PSA 10-20 ng/mL; or 4) PSA 20-150 ng/mL. Treatment included ADT (4 or 24 months), weekly paclitaxel (40, 50, or 60 mg/m{sup 2}/wk), and pelvic radiation therapy (total dose: RP = 64.8 Gy; LAPC = 70.2 Gy). Results: Fifty-ninemore » patients were enrolled (LAPC, n = 29; RP, n = 30; ADT 4 months, n = 29; 24 months, n = 30; whites n = 29, African Americans [AA], n = 28). Baseline characteristics (median [range]) were: age 67 (45-86 years), PSA 5.9 (0.1-92.1 ng/mL), GS 8 (6-9). At escalating doses of paclitaxel, 99%, 98%, and 95% of doses were given with radiation and ADT, respectively, with dose modifications required primarily in RP patients. No acute Grade 4 toxicities occurred. Grade 3 toxicities were diarrhea 15%, urinary urgency/incontinence 10%, tenesmus 5%, and leukopenia 3%. Median follow-up was 75.3 months (95% CI: 66.8-82.3). Biochemical progression occurred in 24 (41%) patients and clinical progression in 11 (19%) patients. The 5- and 7-year OS rates were 83% and 67%. There were no differences in OS between RP and LAPC, 4- and 24-month ADT, white and AA patient categories. Conclusions: In addition to LAPC, to our knowledge, this is the first study to evaluate concurrent chemoradiation with ADT in high-risk RP patients. With a median follow-up of 75.3 months, this trial also represents the longest follow-up of patients treated with taxane-based chemotherapy with EBRT in high-risk prostate cancer. Concurrent ADT, radiation, and weekly paclitaxel at 40 mg/m{sup 2}/week in RP patients and 60 mg/m{sup 2}/week in LAPC patients is feasible and well-tolerated.« less

Nanoparticle-based brachytherapy spacers for delivery of localized combined chemoradiation therapy.

PubMed

Kumar, Rajiv; Belz, Jodi; Markovic, Stacey; Jadhav, Tej; Fowle, William; Niedre, Mark; Cormack, Robert; Makrigiorgos, Mike G; Sridhar, Srinivas

2015-02-01

In radiation therapy (RT), brachytherapy-inert source spacers are commonly used in clinical practice to achieve high spatial accuracy. These implanted devices are critical technical components of precise radiation delivery but provide no direct therapeutic benefits. Here we have fabricated implantable nanoplatforms or chemoradiation therapy (INCeRT) spacers loaded with silica nanoparticles (SNPs) conjugated containing a drug, to act as a slow-release drug depot for simultaneous localized chemoradiation therapy. The spacers are made of poly(lactic-co-glycolic) acid (PLGA) as matrix and are physically identical in size to the commercially available brachytherapy spacers (5 mm × 0.8 mm). The silica nanoparticles, 250 nm in diameter, were conjugated with near infrared fluorophore Cy7.5 as a model drug, and the INCeRT spacers were characterized in terms of size, morphology, and composition using different instrumentation techniques. The spacers were further doped with an anticancer drug, docetaxel. We evaluated the in vivo stability, biocompatibility, and biodegradation of these spacers in live mouse tissues. The electron microscopy studies showed that nanoparticles were distributed throughout the spacers. These INCeRT spacers remained stable and can be tracked by the use of optical fluorescence. In vivo optical imaging studies showed a slow diffusion of nanoparticles from the spacer to the adjacent tissue in contrast to the control Cy7.5-PLGA spacer, which showed rapid disintegration in a few days with a burst release of Cy7.5. The docetaxel spacers showed suppression of tumor growth in contrast to control mice over 16 days. The imaging with the Cy7.5 spacer and therapeutic efficacy with docetaxel spacers supports the hypothesis that INCeRT spacers can be used for delivering the drugs in a slow, sustained manner in conjunction with brachytherapy, in contrast to the rapid clearance of the drugs when administered systemically. The results demonstrate that these spacers with tailored release profiles have potential in improving the combined therapeutic efficacy of chemoradiation therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

Influence of the baseline 18F-fluoro-2-deoxy-D-glucose positron emission tomography results on survival and pathologic response in patients with gastroesophageal cancer undergoing chemoradiation.

PubMed

Javeri, Heta; Xiao, Lianchun; Rohren, Eric; Komaki, Ritsuko; Hofstetter, Wayne; Lee, Jeffrey H; Maru, Dipen; Bhutani, Manoop S; Swisher, Stephen G; Wang, Xuemei; Ajani, Jaffer A

2009-02-01

In patients with esophageal cancer who receive chemoradiation, tools to predict/prognosticate outcome before administering therapy are lacking. The authors evaluated initial standardized unit value (iSUV) of 18F-fluoro-2-deoxy-D-glucose positron emission tomography and its association with overall survival and the degree of pathologic response after surgery. The authors analyzed 161 patients with esophageal adenocarcinoma who had chemoradiation followed by surgery. The log-rank test, univariate Cox proportional hazards model, Kaplan-Meier survival plot, and Fisher exact test were used to analyze dichotomized iSUV and its association with overall survival and pathologic response. The median age of 161 patients was 61 years (range, 26-80 years) and the majority of patients had lower esophageal or gastroesophageal junction involvement. All patients received fluoropyrimidine and, most commonly, a taxane or platinum compound with concomitant radiation. The median radiation dose was 45 grays (Gy) (range, 45 Gy-50.4 Gy). The median iSUV for all patients was 10.1 (range, 0-58). Using the Fisher exact test, iSUV was not found to be associated with the location of the primary cancer. iSUV higher than the median (10.1) was associated with a better pathologic response (P = .06). Patients with primary cancer with iSUV >10.1 had a lower risk for death (hazards ratio of 0.56) compared with those with iSUV < or = 10.1. Higher iSUV was nonsignificantly associated with improved survival (P = .07). Data from the current study suggest that lower iSUV is associated with poor survival and lower probability of response to chemoradiation. iSUV needs to be further evaluated because it may be used to complement other imaging or biomarker assessments to individualize therapy. (c) 2008 American Cancer Society.

Changes in multimodality functional imaging parameters early during chemoradiation predict treatment response in patients with locally advanced head and neck cancer.

PubMed

Wong, Kee H; Panek, Rafal; Dunlop, Alex; Mcquaid, Dualta; Riddell, Angela; Welsh, Liam C; Murray, Iain; Koh, Dow-Mu; Leach, Martin O; Bhide, Shreerang A; Nutting, Christopher M; Oyen, Wim J; Harrington, Kevin J; Newbold, Kate L

2018-05-01

To assess the optimal timing and predictive value of early intra-treatment changes in multimodality functional and molecular imaging (FMI) parameters as biomarkers for clinical remission in patients receiving chemoradiation for head and neck squamous cell carcinoma (HNSCC). Thirty-five patients with stage III-IVb (AJCC 7th edition) HNSCC prospectively underwent 18 F-FDG-PET/CT, and diffusion-weighted (DW), dynamic contrast-enhanced (DCE) and susceptibility-weighted MRI at baseline, week 1 and week 2 of chemoradiation. Patients with evidence of persistent or recurrent disease during follow-up were classed as non-responders. Changes in FMI parameters at week 1 and week 2 were compared between responders and non-responders with the Mann-Whitney U test. The significance threshold was set at a p value of <0.05. There were 27 responders and 8 non-responders. Responders showed a greater reduction in PET-derived tumor total lesion glycolysis (TLG 40% ; p = 0.007) and maximum standardized uptake value (SUV max ; p = 0.034) after week 1 than non-responders but these differences were absent by week 2. In contrast, it was not until week 2 that MRI-derived parameters were able to discriminate between the two groups: larger fractional increases in primary tumor apparent diffusion coefficient (ADC; p < 0.001), volume transfer constant (K trans ; p = 0.012) and interstitial space volume fraction (V e ; p = 0.047) were observed in responders versus non-responders. ADC was the most powerful predictor (∆ >17%, AUC 0.937). Early intra-treatment changes in FDG-PET, DW and DCE MRI-derived parameters are predictive of ultimate response to chemoradiation in HNSCC. However, the optimal timing for assessment with FDG-PET parameters (week 1) differed from MRI parameters (week 2). This highlighted the importance of scanning time points for the design of FMI risk-stratified interventional studies.

Prospective single-arm study of intraoperative radiotherapy for locally advanced or recurrent rectal cancer.

PubMed

Tan, Jennifer; Heriot, Alexander G; Mackay, Jack; Van Dyk, Sylvia; Bressel, Mathias Ab; Fox, Chris D; Hui, Andrew C; Lynch, A Craig; Leong, Trevor; Ngan, Samuel Y

2013-10-01

This study aims to evaluate the feasibility and outcomes of intraoperative radiotherapy (IORT) using high-dose-rate (HDR) brachytherapy for locally advanced or recurrent rectal cancers. Despite preoperative chemoradiation, patients with locally advanced or recurrent rectal cancers undergoing surgery remain at high risk of local recurrence. Intensification of radiation with IORT may improve local control. This is a prospective non-randomised study. Eligible patients were those with T4 rectal cancer or pelvic recurrence, deemed suitable for radical surgery but at high risk of positive resection margins, without evidence of metastasis. Chemoradiation was followed by radical surgery. Ten gray (Gy) was delivered to tumour bed via an IORT applicator at time of surgery. There were 15% primary and 85% recurrent cancers. The 71% received preoperative chemoradiation. R0, R1 and R2 resections were 70%, 22% and 7%, respectively. IORT was successfully delivered in 27 of 30 registered patients (90% (95% confidence interval (CI) = 73-98) ) at a median reported time of 12 weeks (interquartile range (IQR) = 10-16) after chemoradiation. Mean IORT procedure and delivery times were 63 minutes (range 22-105 minutes). Ten patients (37% (95% CI = 19-58) ) experienced grade 3 or 4 toxicities (three wound, four abscesses, three soft tissue, three bowel obstructions, three ureteric obstructions and two sensory neuropathies). Local recurrence-free, failure-free and overall survival rates at 2.5 years were 68% (95% CI = 52-89), 37% (95% CI = 23-61) and 82% (95% CI = 68-98), respectively. The addition of IORT to radical surgery for T4 or recurrent rectal cancer is feasible. It can be delivered safely with low morbidity and good tumour outcomes. © 2013 The Authors. Journal of Medical Imaging and Radiation Oncology © 2013 The Royal Australian and New Zealand College of Radiologists.

Chemoradiation for Advanced Head and Neck Cancer: Potential for Improving Results to Match Those of Current Treatment Modalities for Early-Stage Tumors-Long-Term Results of Hyperfractionated Chemoradiation With Carbogen Breathing and Anemia Correction With Erythropoietin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Villar, Alfonso; Martinez, Jose Carlos; Serdio, Jose Luis de

2008-04-01

Purpose: To attempt to improve results of chemoradiation for head and neck cancer. Methods and Materials: From March 1996 to April 2007, 98 patients with head and neck cancer (15 Stage III and 83 Stage IV) were treated with a twice-daily hyperfractionated schedule. Eleven patients presented with N0, 11 with N1, 13 with N2A, 17 with N2B, 24 with N2C, and 22 with N3. Each fraction of treatment consisted of 5 mg/m{sup 2} of carboplatin plus 115 cGy with carbogen breathing. Treatment was given 5 days per week up to total doses of 350 mg/m{sup 2} of carboplatin plus 8050more » cGy in 7 weeks. Anemia was corrected with erythropoietin. Results: Ninety-six patients tolerated the treatment as scheduled. All patients tolerated the planned radiation dose. Local toxicity remained at the level expected with irradiation alone. Chemotherapy toxicity was moderate. Ninety-seven complete responses were achieved. After 11 years of follow-up (median, 81 months), actuarial locoregional control, cause-specific survival, overall survival, and nodal control rates at 5 and 10 years were, respectively, 83% and 83%, 68% and 68%, 57% and 55%, and 100% and 100%. Median follow-up of disease-free survivors was 80 months. No significant differences in survival were observed between the different subsites or between the pretreatment node status groups (N0 vs. N+, N0 vs. N1, N0 vs. N2A, N0 vs. N2B, N0 vs. N2C, and N0 vs. N3). Conclusions: Improving results of chemoradiation for advanced head and neck cancer up to the level obtained with current treatments for early-stage tumors is a potentially reachable goal.« less

SU-F-R-55: Early Detection of Treatment Induced Bone Marrow Injury During Chemoradiation Therapy Using Quantitative CT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, X; Song, Y; Erickson, B

Purpose: Acute hematologic toxicity associated with bone marrow injury is a common complication of chemoradiation therapy (CRT) for pelvic malignancies. In this work, we investigate the feasibility of using quantitative CT to detect bone marrow injury during CRT. Methods: Daily CTs were acquired during routine CT-guided radiation therapy using a CT-on-rails for 15 cervical cancer patients. All patients treated with a radiation dose of 45.0 to 50.4 Gy in 1.8 Gy/fraction along with chemotherapy. For each patient, the contours of bone marrow were generated in L4, L5 and sacrum on the first daily CT and then populated to other dailymore » CTs by rigid registration using MIM (MIM Software Inc., Cleveland, OH) with manual editing if possible. A series of CT texture parameters, including Hunsfield Unit (HU) histogram, mean HU, entropy, energy, in bone marrow contours were calculated using MATLAB on each daily CT and were correlated with the completed blood counts (CBC) collected weekly for each patient. The correlations were analyzed with Pearson correlation tests. Results: For all patient data analyzed, mean HU in bone marrow decreased during CRT delivery. From the first to the last fraction the average mean HU reduction is 58.1 ± 13.6 HU (P<0.01). This decrease can be observed as early as after first 5 fractions and is strongly associated with the changes of most CBC quantities, such as the reductions of white and blood cell counts (r=0.97, P=0.001). The reduction of HU is spatially varied. Conclusion: Chemoradiation induced bone marrow injury can be detected during the delivery of CRT using quantitative CT. Chemoradiation results in reductions in mean HU, which are strongly associated with the change in the pretrial blood cell counts. Early detection of bone marrow injury with commonly available CT opens a door to improve bone marrow sparing, reducing risk of hematologic toxicity.« less

Prognostic Relevance of Lymph Node Regression After Neoadjuvant Chemoradiation for Esophageal Cancer.

PubMed

Philippron, Annouck; Bollschweiler, Elfriede; Kunikata, Ayumi; Plum, Patrick; Schmidt, Claudia; Favi, Francesco; Drebber, Uta; Hölscher, Arnulf H

2016-01-01

Prognostic factors after preoperative chemoradiation for patients with advanced esophageal cancer are under discussion. Treatment response measured in the primary tumor is a well-defined prognostic marker. The prognostic relevance of tumor regression in lymph nodes (LNs), eg, histomorphologic characteristics must be evaluated in a larger series of patients. From 1997-2010, 403 patients with cT3N×M0 esophageal cancer underwent preoperative chemoradiation followed by transthoracic esophagectomy. Histopathologic response of the primary tumor was graded in resected specimens as "minor" (≥10% vital residual tumor cells) or "major." The LNs of all patients without LN metastases (ypN0 n = 222, adenocarcinoma n = 129, squamous cell carcinoma n = 93) were reevaluated for central fibrosis. Univariate and multivariate analyses were performed on histomorphologic criteria of examined LNs and used to correlate these with tumor response and prognosis. The 5-year survival rate (5YSR) for all patients was 30%. Overall, 5480 LNs were reevaluated for the existence of central fibrosis in ypN0 cases. The prognostic relevance of the LN regression (LNR) grading system was confirmed for all patients with univariate (P < 0.001) and multivariate (P = 0.02) analyses. In results, the 5YSR for ypN0 patients overall was 37%, for patients with major response by the primary tumor was 42%, and for minor responders was 19% (P < 0.001). Analyzing LNR in major responders, the group with less than 3 LNs with central fibrosis (n = 52) showed significantly better prognosis (5YSR = 63%) compared to those with more (5YSR = 34%), (P = 0.016). Conclusion includes morphologic signs of metastatic LNR after chemoradiation, such as central fibrosis, are of prognostic relevance for patients with advanced esophageal cancer, especially for those with major response of the primary tumor. Copyright © 2016 Elsevier Inc. All rights reserved.

Changes of saliva microbiota in nasopharyngeal carcinoma patients under chemoradiation therapy.

PubMed

Xu, Yuan; Teng, Fei; Huang, Shi; Lin, Zhengmei; Yuan, Xiao; Zeng, Xiaowei; Yang, Fang

2014-02-01

A growing body of evidence has implicated human oral microbiota in the aetiology of oral and systemic diseases. Nasopharyngeal carcinoma (NPC), an epithelial-originated malignancy, has a complex aetiology not yet fully understood. Chemoradiation therapy of NPC can affect oral microbiota and is usually accompanied by plaque accumulation. Thus, the study aimed to understand the diversity, divergence and development of the oral microbiota in NPC patients and their associated treatment, which might provide useful insights into disease aetiology and treatment side effects. A longitudinal study was designed that included three Chinese adults with NPC. Saliva samples were collected at three time points: prior to the chemoradiation treatment (carcinoma baseline, or CB), 7 months post-treatment (carcinoma-after-therapy phase 1 or CA1) and 12 months post-treatment (carcinoma-after-therapy phase 2 or CA2). Pyrosequencing of the bacterial 16S ribosomal DNA (rDNA) V1-V3 hypervariable region was employed to characterise the microbiota. Saliva samples of three healthy subjects from our former study were employed as healthy controls. Principal coordinates analysis (PCoA), Metastats and random forest prediction models were used to reveal the key microbial members associated with NPC and its treatment programme. (1) In total, 412 bacterial species from at least 107 genera and 13 phyla were found in the saliva samples of the NPC patients. (2) PCoA revealed that not only were the microbiota from NPC patients distinct from those of healthy controls (p<0.001) but also that separation was found on the saliva microbiota between pre- and post-therapy (p<0.001) in the NPC samples. (3) At the genus level and the operational taxonomic unit (OTU) level, Streptococcus was found with lower abundance in NPC samples. (4) Chemoradiation therapy did not incur similar changes in microbiota structure among the three NPC patients; the microbiota in one of them stayed largely steady, while those in the other two showed significant alteration. This is the first study employing culture-independent techniques to interrogate the phylogenetic diversity, divergence and temporal development of oral microbiota in NPC patients. Our results indicated that certain bacterial taxa might be associated with NPC and that oral microbiota of NPC patients might respond to the chemoradiation therapy in a host-specific manner. Further investigation with larger sample size should help to validate the links between oral microbiota and NPC. Copyright © 2013 Elsevier Ltd. All rights reserved.

Immune reactivity does not predict chemotherapy response, organ preservation, or survival in advanced laryngeal cancer.

PubMed

Wolf, Gregory T; Bradford, Carol R; Urba, Susan; Smith, Allison; Eisbruch, Avraham; Chepeha, Douglas B; Teknos, Theodoros N; Worden, Frank; Dawson, Laura; Terrell, Jeffrey E; Hogikyan, Norman D

2002-08-01

To determine whether pretreatment lymphocyte subpopulations correlate with tumor response to induction chemotherapy as part of an organ preservation treatment approach in patients with advanced laryngeal cancer. A prospective clinical trial in patients with advanced laryngeal cancer was undertaken to determine whether the frequency of late salvage laryngectomy and overall survival could be improved using one cycle of neoadjuvant chemotherapy to select patients for organ preservation. Pretreatment peripheral blood lymphocyte subpopulations for CD3, CD4, CD8, NK, and B cells were correlated with tumor response to induction chemotherapy, larynx preservation, and survival, to determine whether immune parameters could be useful in patient selection. The study setting was a tertiary referral academic health center. Studied were 53 patients with stage III (42%) or IV (57%) larynx cancer. Most patients had supraglottic cancers (73%) and positive clinical nodes (51%). Sixty-eight percent had greater than 50% tumor response after one cycle of induction chemotherapy and then received concurrent chemoradiation and two cycles of adjuvant chemotherapy. Lymphocyte subpopulations were measured in 39 patients. Mean follow-up was 23.3 months (range, 5-61 mo). A total of 18 (34%) patients underwent laryngectomy. Only 4 cases were late salvage resections (13-35 mo after treatment). Fourteen cases were planned surgery after initial chemotherapy. Of the lymphocyte subpopulations measured, CD8 levels were significantly lower in stage IV patients and tended to be lower in patients with successful organ preservation. However, no significant differences in lymphocyte subpopulations were found among responders and nonresponders to chemotherapy. Overall survival was 88%. One cycle of neoadjuvant chemotherapy was effective in selecting patients for organ preservation. The regimen of definitive concurrent and adjuvant chemotherapy was associated with an unexpectedly high 2-year survival rate. Lymphocyte subsets were not significant predictors of responding patients or survival. Further study of other biological markers useful in selecting patients for organ preservation are needed.

Phase I dose escalation study of capecitabine and erlotinib concurrent with radiation in locally advanced pancreatic cancer.

PubMed

Jiang, Yixing; Mackley, Heath B; Kimchi, Eric T; Zhu, Junjia; Gusani, Niraj; Kaifi, Jussuf; Staveley-O'Carroll, Kevin F; Belani, Chandra P

2014-07-01

Pancreatic cancer is one of the leading causes of cancer-related deaths worldwide. The median survival of locally advanced nonoperable disease is approximately 9 months. 5-FU-based chemoradiotherapy has been the standard treatment. However, the survival benefit of this approach is modest. To improve the efficacy of 5-FU-based chemoradiation therapy, we evaluated the safety and feasibility of the combination of capecitabine and erlotinib with radiotherapy in this group of patients. A traditional "3 + 3" dose escalation design was adopted in the study. A total of four dose levels were designed. For safety purpose, a minus I dose level (-I) was also planned. The -I level consisted of capecitabine 600 mg/m² and erlotinib 50 mg daily, and the remaining four dose levels were as follows: level I: capecitabine 600 mg/m² bid (twice daily); level II: 700 mg/m² bid; level III: 825 mg/m² bid; and level IV: 925 mg/m² bid. Erlotinib was administered at 100 mg daily at all dose levels. Erlotinib and capceitabine were given continuously Monday through Friday concurrent with radiotherapy (50.4 Gy in 28 fractions). A total of 18 patients were consented. Fifteen patients were enrolled and completed therapy. No dose-limiting toxicity was observed. The most frequent side effects were lymphopenia, nausea, vomiting, diarrhea, electrolyte imbalances, and skin rashes. The majority of the toxicities were grade 1 and 2. No objective response was observed. The median progression-free survival was 0.59 years (95 % CI 0.31-1.1), and the median overall survival was 1.1 years (95 % CI 0.62-1.59). The combination of capecitabine and erlotinib with radiotherapy in locally advanced pancreatic cancer is well tolerated and feasible at the dose level of capecitabine 925 mg/m² bid and erlotinib 100 mg daily.

Potential of Proton Therapy to Reduce Acute Hematologic Toxicity in Concurrent Chemoradiation Therapy for Esophageal Cancer.

PubMed

Warren, Samantha; Hurt, Christopher N; Crosby, Thomas; Partridge, Mike; Hawkins, Maria A

2017-11-01

Radiation therapy dose escalation using a simultaneous integrated boost (SIB) is predicted to improve local tumor control in esophageal cancer; however, any increase in acute hematologic toxicity (HT) could limit the predicted improvement in patient outcomes. Proton therapy has been shown to significantly reduce HT in lung cancer patients receiving concurrent chemotherapy. Therefore, we investigated the potential of bone marrow sparing with protons for esophageal tumors. Twenty-one patients with mid-esophageal cancer who had undergone conformal radiation therapy (3D50) were selected. Two surrogates for bone marrow were created by outlining the thoracic bones (bone) and only the body of the thoracic vertebrae (TV) in Eclipse. The percentage of overlap of the TV with the planning treatment volume was recorded for each patient. Additional plans were created retrospectively, including a volumetric modulated arc therapy (VMAT) plan with the same dose as for 3D50; a VMAT SIB plan with a dose prescription of 62.5 Gy to the high-risk subregion within the planning treatment volume; a reoptimized TV-sparing VMAT plan; and a proton therapy plan with the same SIB dose prescription. The bone and TV dose metrics were recorded and compared across all plans and variations with respect to PTV and percentage of overlap for each patient. The 3D50 plans showed the highest bone mean dose and TV percentage of volume receiving ≥30 Gy (V 30Gy ) for each patient. The VMAT plans irradiated a larger bone V 10Gy than did the 3D50 plans. The reoptimized VMAT62.5 VT plans showed improved sparing of the TV volume, but only the proton plans showed significant sparing for bone V 10Gy and bone mean dose, especially for patients with a larger PTV. The results of the present study have shown that proton therapy can reduced bone marrow toxicity. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Hyperfractionated Accelerated Radiation Therapy (HART) of 70.6 Gy With Concurrent 5-FU/Mitomycin C Is Superior to HART of 77.6 Gy Alone in Locally Advanced Head and Neck Cancer: Long-term Results of the ARO 95-06 Randomized Phase III Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Budach, Volker, E-mail: volker.budach@charite.de; Stromberger, Carmen; Poettgen, Christoph

2015-04-01

Purpose: To report the long-term results of the ARO 95-06 randomized trial comparing hyperfractionated accelerated chemoradiation with mitomycin C/5-fluorouracil (C-HART) with hyperfractionated accelerated radiation therapy (HART) alone in locally advanced head and neck cancer. Patients and Methods: The primary endpoint was locoregional control (LRC). Three hundred eighty-four patients with stage III (6%) and IV (94%) oropharyngeal (59.4%), hypopharyngeal (32.3%), and oral cavity (8.3%) cancer were randomly assigned to 30 Gy/2 Gy daily followed by twice-daily 1.4 Gy to a total of 70.6 Gy concurrently with mitomycin C/5-FU (C-HART) or 16 Gy/2 Gy daily followed by twice-daily 1.4 Gy to a total dose of 77.6 Gy alone (HART). Statisticalmore » analyses were done with the log-rank test and univariate and multivariate Cox regression analyses. Results: The median follow-up time was 8.7 years (95% confidence interval [CI]: 7.8-9.7 years). At 10 years, the LRC rates were 38.0% (C-HART) versus 26.0% (HART, P=.002). The cancer-specific survival and overall survival rates were 39% and 10% (C-HART) versus 30.0% and 9% (HART, P=.042 and P=.049), respectively. According to multivariate Cox regression analysis, the combined treatment was associated with improved LRC (hazard ratio [HR]: 0.6 [95% CI: 0.5-0.8; P=.002]). The association between combined treatment arm and increased LRC appeared to be limited to oropharyngeal cancer (P=.003) as compared with hypopharyngeal or oral cavity cancer (P=.264). Conclusions: C-HART remains superior to HART in terms of LRC. However, this effect may be limited to oropharyngeal cancer patients.« less

Preoperative Chemoradiation With Irinotecan and Capecitabine in Patients With Locally Advanced Resectable Rectal Cancer: Long-Term Results of a Phase II Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hong, Yong Sang; Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul; Kim, Dae Yong

Purpose: Preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer has shown benefit over postoperative CRT; however, a standard CRT regimen has yet to be defined. We performed a prospective concurrent CRT Phase II study with irinotecan and capecitabine in patients with locally advanced rectal cancer to investigate the efficacy and safety of this regimen. Methods and Materials: Patients with locally advanced, nonmetastatic, and mid-to-lower rectal cancer were enrolled. Radiotherapy was delivered in 1.8-Gy daily fractions for a total of 45 Gy in 25 fractions, followed by a coned-down boost of 5.4 Gy in 3 fractions. Concurrent chemotherapy consisted of 40more » mg/m{sup 2} of irinotecan per week for 5 consecutive weeks and 1,650 mg/m{sup 2} of capecitabine per day for 5 days per week (weekdays only) from the first day of radiotherapy. Total mesorectal excision was performed within 6 {+-} 2 weeks. The pathologic responses and survival outcomes were included for the study endpoints. Results: In total, 48 patients were enrolled; 33 (68.7%) were men and 15 (31.3%) were women, and the median age was 59 years (range, 32-72 years). The pathologic complete response rate was 25.0% (11 of 44; 95% confidence interval, 12.2-37.8) and 8 patients (18.2% [8 of 44]) showed near-total tumor regression. The 5-year disease-free and overall survival rates were 75.0% and 93.6%, respectively. Grade 3 toxicities included leukopenia (3 [6.3%]), neutropenia (1 [2.1%]), infection (1 [2.1%]), alanine aminotransferase elevation (1 [2.1%]), and diarrhea (1 [2.1%]). There was no Grade 4 toxicity or treatment-related death. Conclusions: Preoperative CRT with irinotecan and capecitabine with treatment-free weekends showed very mild toxicity profiles and promising results in terms of survival.« less

[Retrospective analysis of 24 recurrent glioblastoma after chemoradiation and treated with nitrosoureas or irinotecan and bevacizumab].

PubMed

Vauleon, Elodie; Mesbah, Habiba; Gedouin, Daniel; Lecouillard, Isabelle; Louvel, Guillaume; Hamlat, Abderrahmane; Riffaud, Laurent; Carsin, Béatrice; Quillien, Véronique; Audrain, Odile; Lesimple, Thierry

2012-02-01

Despite progress in the initial management of glioblastoma (GB), the vast majority of patients will experience recurrence within 2-3 years. The medical treatment of these recurrences is being modified by the use of antiangiogenic therapies. Twenty-four patients, who relapsed from GB after chemoradiation followed by adjuvant temozolomide in Rennes, were treated by conventional chemotherapy (nitrosourea) or by the combination of irinotecan and bevacizumab. In this retrospective analysis, overall survival from diagnosis of recurrence was significantly longer in patients treated with the combination of bevacizumab and irinotecan than with nitrosourea (5 months versus 11.5 months). The combination of irinotecan and bevacizumab appeared to provide clinical benefit to patients with recurrent GB.

An examination of three methods of psychodynamic formulation based on the same videotaped interview.

PubMed

Perry, J C; Luborsky, L; Silberschatz, G; Popp, C

1989-08-01

While psychodynamic theory and therapy are approaching their centennial, the science of psychodynamics is still in an earlier developmental stage. Any scientific field generates the most controversy and excitement when it is still developing. For psychodynamic psychology this means that its basic units of observation as well as its rules for justifying clinical inference in formulating and testing dynamic hypotheses require more development. In short, we are still evaluating different methods for both discovering and validating psychodynamic propositions. This is especially true for central features of dynamic psychology, including intrapsychic conflict, relationships, and transference patterns. This report compares three different methods for making a dynamic case formulation: 1) the Core Conflictual Relationship Theme (CCRT) of Luborsky (Crits-Christoph and Luborsky 1985a,b; Luborsky 1976, 1977, 1984, and companion paper in this issue; Levine and Luborsky 1981), 2) the Plan Diagnosis (PD) method of Silberschatz, Curtis and colleagues of the Mount Zion group (Caston 1986; Curtis and Silberschatz 1986; Rosenberg et al. 1986; Curtis et al. 1988) and, 3) the Idiographic Conflict Formulation (ICF) of Perry and Cooper (1985, 1986, and companion paper in this issue). Each has a slightly different focus. The CCRT focuses on relationship patterns as the central feature of individual dynamics and transference in or out of the treatment situation. The Plan Diagnosis focuses on dynamic features related to transference, resistance and insight in therapy. The Idiographic Conflict Formulation focuses on stress and internal conflict, and the individual's adaptation to them in or out of treatment.

Vitamin D Supplementation is a Promising Therapy for Pancreatic Ductal Adenocarcinoma in Conjunction with Current Chemoradiation Therapy.

PubMed

Mukai, Yosuke; Yamada, Daisaku; Eguchi, Hidetoshi; Iwagami, Yoshifumi; Asaoka, Tadafumi; Noda, Takehiro; Kawamoto, Koichi; Gotoh, Kunihito; Kobayashi, Shogo; Takeda, Yutaka; Tanemura, Masahiro; Mori, Masaki; Doki, Yuichiro

2018-04-19

The cancer-associated fibroblasts (CAFs) in pancreatic ductal adenocarcinoma (PDAC) are well known to play a dominant role in distant metastasis. Nevertheless, the effect on CAFs with current chemoradiation therapies remains uncertain. This study aimed to reveal the role of CAFs under current chemoradiation therapy (CRT) and investigate the factors regulating CAFs. α-SMA-positive cells in 86 resected PDAC specimens with/without preoperative CRT were evaluated by immunohistochemistry. Various factors, including the plasma levels of vitamin D, were investigated for association with the number of CAFs or distant metastasis-free survival (DMFS). Human pancreatic satellite cells (hPSCs) extracted from clinical specimens were used to validate the factors. All PDAC samples contained CAFs but the number varied widely. Multivariate analysis for DMFS indicated a larger number of CAFs was a significant risk factor. Univariate analysis for the number of CAFs identified two clinical factors: preoperative CRT and lower plasma levels of vitamin D. In subgroup analysis, the higher plasma level of vitamin D was a dominant factor for longer DMFS in PDAC patients after preoperative CRT. These results were validated by using extracted hPSCs. Irradiation activated stromal cells into CAFs facilitating malignant characteristics of PDAC and the change was inhibited by vitamin D supplementation in vitro. In conjunction with established current therapies, vitamin D supplementation may be an effective treatment for PDAC patients by inactivating CAFs.

Primary Mucoepidermoid Carcinoma of the Lacrimal Sac -  a Case Report and Literature Review.

PubMed

Janakiram, T N; Sagar, S; Sharma, S B; Subramaniam, V

Lacrimal sac tumors are very rare and are often missed because patients present with features consistent with chronic dacryocystitis. Squamous cell carcinoma is the common-est lacrimal sac malignancy. Although primary mucoepidermoid carcinomas of the lacrimal sac are rare, they are locally aggressive. Furthermore, their proximity to vital structures and the skull base makes them potentially life-threatening. Multidisciplinary management is required, and wide excision followed by chemoradiation is the recommended treatment. Here, we report a 65-year-old male who presented with watering eyes and a mass in the region of the medial canthus. A dia-gnosis of primary mucoepidermoid carcinoma of the lacrimal sac was made, and the case was managed successfully with radical surgery and reconstruction. The tumor was resected using the extended Lynch-Howarth incision and the resulting defect was reconstructed using a forehead flap. Histopathological examination of the excised specimen revealed mucoepidermoid carcinoma. Immunohistochemical analysis revealed that the speci-men was positive for epithelial growth factor receptor and Ki-67 protein. The patient was referred for post-operative chemoradiation. The literature is reviewed and pathological features, including immunohistochemistry are discussed. Primary mucoepidermoid carcinoma of the lacrimal sac is a rare, locally aggressive tumor that is often mistaken for dacryocystitis. The treatment of choice is radical surgery followed by chemoradiation. lacrimal sac -  mucoepidermoid carcinoma -  epithelial growth factor receptor -  Ki-67 protein.

Performance of a Nomogram Predicting Disease-Specific Survival After an R0 Resection for Gastric Cancer in Patients Receiving Postoperative Chemoradiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dikken, Johan L.; Department of Surgery, Leiden University Medical Center, Leiden; Coit, Daniel G.

Purpose: The internationally validated Memorial Sloan-Kettering Cancer Center (MSKCC) gastric carcinoma nomogram was based on patients who underwent curative (R0) gastrectomy, without any other therapy. The purpose of the current study was to assess the performance of this gastric cancer nomogram in patients who received chemoradiation therapy after an R0 resection for gastric cancer. Methods and Materials: In a combined dataset of 76 patients from the Netherlands Cancer Institute (NKI), and 63 patients from MSKCC, who received postoperative chemoradiation therapy (CRT) after an R0 gastrectomy, the nomogram was validated by means of the concordance index (CI) and a calibration plot. Results:more » The concordance index for the nomogram was 0.64, which was lower than the CI of the nomogram for patients who received no adjuvant therapy (0.80). In the calibration plot, observed survival was approximately 20% higher than the nomogram-predicted survival for patients receiving postoperative CRT. Conclusions: The MSKCC gastric carcinoma nomogram significantly underpredicted survival for patients in the current study, suggesting an impact of postoperative CRT on survival in patients who underwent an R0 resection for gastric cancer, which has been demonstrated by randomized controlled trials. This analysis stresses the need for updating nomograms with the incorporation of multimodal strategies.« less

Transition of the Combustion of Condensed Systems into an Explosion

DTIC Science & Technology

1975-02-06

tubes iwholly L 1 ed,’ with exrlnsives. Figure Cb de ,-cts the tube which w-.as used ty Gi’pson ar’J !Ma’L"ek for the study of the transition of ccrtUS...continuous optical recording c_’ the trocess of the tlii-sitiOTI CT’ crmsr.ion into aCetonatio.. it is schematically’ de -cicted on rg c The tube...r thlis zur-ose Zverev designed a special electronic amelifier. hIs amplifIer had a sc.*w resnonse, which made it rossible to use the ciezoelectric

High dose chemoradiation for unresectable hilar cholangiocarcinomas using intensity modulated external beam radiotherapy: a single tertiary care centre experience

PubMed Central

Mehta, Shaesta; Kalyani, Nikhil; Chaudhari, Suresh; Dharia, Tejas; Shetty, Nitin; Chopra, Supriya; Goel, Mahesh; Kulkarni, Suyash; Shrivastava, Shyam Kishore

2017-01-01

Background We present results of patients diagnosed with unresectable hilar cholangiocarcinomas treated with high dose radiotherapy and concurrent chemotherapy. Methods From Aug 2005 to Dec 2012, 68 consecutive patients were treated. Fifty patients (group 1) presenting to us with obstructive jaundice were planned for endobiliary brachytherapy (EBBT 14 Gy) followed external beam radiotherapy (EBRT 45 Gy). Twenty-two patients (group 2) who had previously undergone biliary drainage underwent EBRT (57 Gy). All patients received injection Gemcitabine 300 mg/m2/weekly along with EBRT. Results Twenty-nine patients in group 1 and 22 patients in group 2 completed the treatment. Twenty-six (55%) patients achieved complete radiological response, 16 (64%) belonging to group 1 and 8 (44%) of group 2 (P=0.05). The median overall survival (MOS) was 17.5 and 16 months for group 1 and 2 respectively (P=0.07). The 1- and 2-year survival was 63%, and 18% for group I and 61% and 22% for group II respectively. The MOS was 5 months and 1 year survival was 14% for patients receiving EBBT only. MOS was significantly better after complete response (P=0.001). Conclusions Intensity modulated radiotherapy (IMRT) modulated high dose radiotherapy used either alone or with brachytherapy demonstrates potential to prolonged overall survival in unresectable hilar cholangiocarcinomas. PMID:28280622

Chemoradiation in elderly esophageal cancer patients: rationale and design of a phase I/II multicenter study (OSAGE).

PubMed

Servagi-Vernat, Stéphanie; Créhange, Gilles; Bonnetain, Franck; Mertens, Cécile; Brain, Etienne; Bosset, Jean François

2017-07-13

The management of elderly patients with cancer is a therapeutic challenge and a public health problem. Definitive chemoradiotherapy (CRT) is an accepted standard treatment for patients with locally advanced esophageal cancer who cannot undergo surgery. However, there are few reports regarding tolerance to CRT in elderly patients. We previously reported results for CRT in patients aged ≥75 years. Following this first phase II trial, we propose to conduct a phase I/II study to evaluate the combination of carboplatin and paclitaxel, with concurrent RT in unresectable esophageal cancer patients aged 75 years or older. This prospective multicenter phase I/II study will include esophageal cancer in patients aged 75 years or older. Study procedures will consist to determinate the tolerated dose of chemotherapy (Carboplatin, paclitaxel) and of radiotherapy (41.4-45 and 50.4 Gy) in the phase I. Efficacy will be assessed using a co-primary endpoint encompassing health related quality of life and the progression-free survival in the phase II with the dose recommended of CRT in the phase I. This geriatric evaluation was defined by the French geriatric oncology group (GERICO). This trial has been designed to assess the tolerated dose of CRT in selected patient aged 75 years or older. Clinicaltrials.gov ID: NCT02735057 . Registered on 18 March 2016.

High-grade squamous intraepithelial lesion arising adjacent to vulvar lymphangioma circumscriptum: a tertiary institutional experience

PubMed Central

Bae, Go Eun; Yoon, Gun; Song, Yong Jung; Kim, Hyun-Soo

2016-01-01

Lymphangioma circumscriptum of the vulva occurs in patients who have undergone radical hysterectomy, lymph node dissection, or radiation therapy for management of advanced uterine cancer. Since vulvar lymphangioma circumscriptum typically presents as multiple, grossly verrucous vesicles of various sizes, it may be impossible to clinically distinguish vulvar lymphangioma circumscriptum from other vulvoperineal cutaneous diseases. In the present study, 16 (1.6%) out of the 1,024 vulvar biopsy or excision specimens were diagnosed as lymphangioma circumscriptum. In two (12.5%) out of the 16 cases, unusual histopathological findings were observed. Both patients had previously undergone radical hysterectomy with lymph node dissection and postoperative radiation therapy or concurrent chemoradiation therapy for advanced cervical cancer. Microscopic examination revealed high-grade squamous intraepithelial lesions, which were located immediately adjacent to the normal squamous epithelium covering the dilated subepithelial lymphatic vessels. Further, human papillomavirus genotyping confirmed that both patients were infected with high-risk human papillomavirus. High-grade squamous intraepithelial lesion cannot be grossly distinguished from vulvar lymphangioma circumscriptum because the multiple, verrucous vesicles that constitute the characteristic gross appearance of vulvar lymphangioma circumscriptum hinder its distinction. In this regard, our cases of high-grade squamous intraepithelial lesion, located adjacent to vulvar lymphangioma circumscriptum, support the notion that active surgical excision is necessary for the treatment of vulvar lymphangioma circumscriptum. PMID:27329721

Neoadjuvant chemoradiation and surgery improves survival outcomes compared with definitive chemoradiation in the treatment of stage IIIA N2 non-small-cell lung cancer.

PubMed

Darling, Gail E; Li, Fei; Patsios, Demetris; Massey, Christine; Wallis, Adam G; Coate, Linda; Keshavjee, Shaf; Pierre, Andrew; De Perrot, Marc; Yasufuku, Kazuhiro; Cypel, Marcelo; Waddell, Tom

2015-11-01

The objective of this study was to compare survival in patients with stage IIIA (N2) non-small-cell lung cancer (NSCLC) treated with definitive chemoradiation (CRT) or surgery plus neoadjuvant chemoradiation or chemotherapy (CRTS). A retrospective analysis of 242 patients with stage IIIA (N2) NSCLC treated with curative intent between 1997 and 2007, identified 215 patients with surgically resectable disease. Overall survival outcomes were analysed using the Kaplan-Meier plots, log-rank tests and Cox proportional hazards models adjusting for age, gender, histology, smoking history and performance status. Recurrences were compared using competing risks methods, including the proportional subdistribution hazards regression model. CRTS was used to treat 104 patients and CRT in 111. Comparing CRTS with CRT patients, median age was 60 vs 62, 50 (48%) vs 69 (62%) were male and 65 (62.5%) vs 60 (54%) had adenocarcinoma. Of CRTS patients, 83 (80%) had a lobectomy. CRTS patients compared with CRT patients had decreased risk of recurrence at any site [hazard ratio (HR) = 0. 46, 95% confidence interval (CI): 0.32-0.64 P < 0.0001], local recurrence (HR = 0.50, 95% CI: 0.29-0.87, P = 0.013), loco--regional recurrence (HR = 0.51, 95% CI: 0.33-0.78, P = 0.002) and death (HR: 0.45, 95% CI: 0.33-0.62, P < 0.0001) with a median survival of 4.2 years vs 1.7 years). Risk of distant recurrence was also reduced in the surgical group (HR: 0.57; 95% CI: 0.38-0.87, P = 0.017). Treatment-related mortality was low in both cohorts. For patients with surgically resectable stage IIIA (N2) NSCLC, neoadjuvant therapy plus surgery reduces loco-regional and distant recurrence and improves survival. Treatment-related mortality was not significantly increased compared with the patients treated with CRT alone. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Nanoparticle-Based Brachytherapy Spacers for Delivery of Localized Combined Chemoradiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumar, Rajiv, E-mail: r.kumar@neu.edu; Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts; Belz, Jodi

Purpose: In radiation therapy (RT), brachytherapy-inert source spacers are commonly used in clinical practice to achieve high spatial accuracy. These implanted devices are critical technical components of precise radiation delivery but provide no direct therapeutic benefits. Methods and Materials: Here we have fabricated implantable nanoplatforms or chemoradiation therapy (INCeRT) spacers loaded with silica nanoparticles (SNPs) conjugated containing a drug, to act as a slow-release drug depot for simultaneous localized chemoradiation therapy. The spacers are made of poly(lactic-co-glycolic) acid (PLGA) as matrix and are physically identical in size to the commercially available brachytherapy spacers (5 mm × 0.8 mm). The silica nanoparticles, 250 nm in diameter,more » were conjugated with near infrared fluorophore Cy7.5 as a model drug, and the INCeRT spacers were characterized in terms of size, morphology, and composition using different instrumentation techniques. The spacers were further doped with an anticancer drug, docetaxel. We evaluated the in vivo stability, biocompatibility, and biodegradation of these spacers in live mouse tissues. Results: The electron microscopy studies showed that nanoparticles were distributed throughout the spacers. These INCeRT spacers remained stable and can be tracked by the use of optical fluorescence. In vivo optical imaging studies showed a slow diffusion of nanoparticles from the spacer to the adjacent tissue in contrast to the control Cy7.5-PLGA spacer, which showed rapid disintegration in a few days with a burst release of Cy7.5. The docetaxel spacers showed suppression of tumor growth in contrast to control mice over 16 days. Conclusions: The imaging with the Cy7.5 spacer and therapeutic efficacy with docetaxel spacers supports the hypothesis that INCeRT spacers can be used for delivering the drugs in a slow, sustained manner in conjunction with brachytherapy, in contrast to the rapid clearance of the drugs when administered systemically. The results demonstrate that these spacers with tailored release profiles have potential in improving the combined therapeutic efficacy of chemoradiation therapy.« less

Relationship Between Radiation Therapy Dose and Outcome in Patients Treated With Neoadjuvant Chemoradiation Therapy and Surgery for Stage IIIA Non-Small Cell Lung Cancer: A Population-Based, Comparative Effectiveness Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sher, David J., E-mail: david_sher@rush.edu; Fidler, Mary Jo; Seder, Christopher W.

Purpose: To compare, using the National Cancer Database, survival, pathologic, and surgical outcomes in patients with stage IIIA non-small cell lung cancer treated with differential doses of neoadjuvant chemoradiation therapy, with the aim to discern whether radiation dose escalation was associated with a comparative effectiveness benefit and/or toxicity risk. Methods and Materials: Patients in the National Cancer Database with stage IIIA non-small cell lung cancer treated with neoadjuvant chemoradiation therapy and surgery between 1998 and 2005 were analyzed. Dose strata were divided between 36 to 45 Gy (low-dose radiation therapy, LD-RT), 45 to 54 Gy (inclusive, standard-dose, SD-RT), and 54 to 74 Gymore » (high-dose, HD-RT). Outcomes included overall survival, residual nodal disease, positive surgical margin status, hospital length of stay, and adverse surgical outcomes (30-day mortality or readmission). Results: The cohort consisted of 1041 patients: 233 (22%) LD-RT, 584 (56%) SD-RT, and 230 (22%) HD-RT. The median, 3-year, and 5-year overall survival outcomes were 34.9 months, 48%, and 37%, respectively. On univariable analysis, patients treated with SD-RT experienced prolonged overall survival (median 38.3 vs 31.8 vs 29.0 months for SD-RT, LD-RT, and HD-RT, respectively, P=.0089), which was confirmed on multivariable analysis (hazard ratios 0.77 and 0.81 vs LD and HD, respectively). Residual nodal disease was seen less often after HD-RT (25.5% vs 31.8% and 37.5% for HD-RT, LD-RT, and SD-RT, respectively, P=.0038). Patients treated with SD-RT had fewer prolonged hospital stays. There were no differences in positive surgical margin status or adverse surgical outcomes between the cohorts. Conclusions: Neoadjuvant chemoradiation therapy between 45 and 54 Gy was associated with superior survival in comparison with doses above and below this threshold. Although this conclusion is limited by selection bias, clear candidates for trimodality therapy do not seem to achieve additional benefit with dose escalation.« less

Impact of sarcopenia on outcomes of locally advanced esophageal cancer patients treated with neoadjuvant chemoradiation followed by surgery

PubMed Central

Venkat, Puja S.; Jin, William; Leuthold, Susan; Latifi, Kujtim; Almhanna, Khaldoun; Pimiento, Jose M.; Fontaine, Jacques-Pierre; Hoffe, Sarah E.; Frakes, Jessica M.

2017-01-01

Background Sarcopenia is an independent predictor of clinical outcomes in multiple gastrointestinal cancers. Total psoas area (TPA), as measured on a single cross-sectional CT image at the L4 vertebral body level, has been correlated with sarcopenia. We sought to evaluate whether TPA was predictive of acute grade ≥3 toxicity, pathologic response, and overall survival in patients with locally advanced esophageal cancer receiving tri-modality therapy. Methods An institutional database of esophageal cancer patients treated with neoadjuvant chemoradiation followed by surgery was queried. Of 77 patients treated from 2008 to 2012 with intensity modulated radiation therapy (IMRT) and image guided radiation therapy (IGRT), 56 patients were eligible based on having CT imaging that included the L4 vertebral body. The L4 vertebra was identified on axial CT and the psoas muscle was manually contoured bilaterally to determine the skeletal muscle index. Sarcopenia was defined by the presence of the psoas area less than the median of the cohort. Acute toxicity was defined as within 3 months of radiotherapy based on Common Terminology Criteria for Adverse Events. ROC curve, logistic regression, and Kaplan Meier estimates were used when appropriate. Results Sarcopenia was associated with increased acute grade ≥3 toxicity from chemoradiation by ROC analysis using a cut off of 841.5 mm2/m2 (P=0.003, AUC 0.709, sensitivity 60.9%, specificity 78.8%) and logistic regression (P=0.002). Patients with TPA <841.5 mm2/m2 were 5.78 times more likely to develop grade 3 or higher toxicity (P=0.004). Sarcopenia did not predict a difference in overall survival (P=0.217) and was not significant for pathologic complete response or favorable pathologic response (TRG 0/1). Conclusions In our cohort of patients, sarcopenia was associated with a significant increase in acute grade ≥3 toxicity with chemoradiation, suggesting a potential role for neoadjuvant patient selection strategies. There was no difference in pathologic response or overall survival. PMID:29184684

Childhood Esthesioneuroblastoma Treatment (PDQ®)—Health Professional Version

Cancer.gov

Treatment options for children with esthesioneuroblastoma include surgery, radiation, chemotherapy, and chemoradiation. Treatment is determined by the Kadish staging system. Get detailed treatment information for childhood esthesioneuroblastoma in this summary for clinicians.

Nasopharyngeal Cancer Treatment (PDQ®)—Health Professional Version

Cancer.gov

Nasopharyngeal cancer treatment options include radiation therapy, chemoradiation followed by adjuvant chemotherapy, surgery, and chemotherapy. Get detailed information about the treatment of newly diagnosed and recurrent nasopharyngeal cancer in this summary for clinicians.

Oropharyngeal Cancer Treatment (PDQ®)—Health Professional Version

Cancer.gov

Oropharyngeal cancer treatment options may include radiation therapy, surgery, chemoradiation, chemotherapy alone, and immunotherapy. Get detailed information about the treatment for newly diagnosed and recurrent oropharyngeal cancer in this summary for clinicians.

Rectal Cancer Treatment (PDQ®)—Health Professional Version

Cancer.gov

Rectal cancer treatment options include surgery, radiation therapy, chemoradiation, chemotherapy, targeted therapy, ablation, and surveillance. Get detailed information about the treatment of newly diagnosed and recurrent rectal cancer in this summary for clinicians.

Vulvar Cancer Treatment (PDQ®)—Health Professional Version

Cancer.gov

Vulvar cancer treatment options include a variety of surgical procedures, topical imiquimod, radiation therapy, chemotherapy, and chemoradiation. Get detailed treatment information for newly diagnosed and recurrent vulvar cancer in this summary for clinicians.

Restaging after neoadjuvant chemoradiation in rectal cancers: is histology the key in patient selection?

PubMed Central

Singhal, Nitin; Vallam, Karthik; Engineer, Reena; Ostwal, Vikas; Arya, Supreeta

2016-01-01

Background Neoadjuvant chemoradiation is the standard of care for locally advanced rectal cancer. However, there is no clarity regarding the necessity for restaging scans to rule out systemic progression of disease post chemoradiation with existing literature being divided on the need for the same. Methods Data from a prospectively maintained database was retrospectively analysed. All locally advanced rectal cancers (node positive/T4/T3 with threatened or involved CRM) were included. Biopsy proof of adenocarcinoma and CT scan of abdomen and chest were mandatory. Grade of tumor and response to CTRT on restaging magnetic resonance imaging (MRI) were documented. Results Out of 119 patients subjected to CTRT, 72 underwent definitive total mesorectal excision while 13 patients progressed locoregionally on restaging MR pelvis and 15 other patients progressed systemically while the rest defaulted. Patients with poorly differentiated (PD) cancers were compared to those with well/moderately differentiated (WMD) tumors. PD tumors had a significantly higher rate of local progression (32.1% vs. 5.6% %, P=0.0011) and systemic progression (35.7% vs. 6.9%, P=0.0008) as compared to WMD tumors. Only one-third (9/28) of PD patients underwent TME while the rest progressed. Conclusions Selecting poorly differentiated tumors alone for restaging CECT abdomen and thorax will be a cost effective strategy as the rate of progression is very high. Also patients with PD tumors need to be consulted about the high probability of progression of disease. PMID:27284467

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beadle, Beth M.; Jhingran, Anuja; Salehpour, Mohammad

Purpose: To evaluate the magnitude of cervix regression and motion during external beam chemoradiation for cervical cancer. Methods and Materials: Sixteen patients with cervical cancer underwent computed tomography scanning before, weekly during, and after conventional chemoradiation. Cervix volumes were calculated to determine the extent of cervix regression. Changes in the center of mass and perimeter of the cervix between scans were used to determine the magnitude of cervix motion. Maximum cervix position changes were calculated for each patient, and mean maximum changes were calculated for the group. Results: Mean cervical volumes before and after 45 Gy of external beam irradiationmore » were 97.0 and 31.9 cc, respectively; mean volume reduction was 62.3%. Mean maximum changes in the center of mass of the cervix were 2.1, 1.6, and 0.82 cm in the superior-inferior, anterior-posterior, and right-left lateral dimensions, respectively. Mean maximum changes in the perimeter of the cervix were 2.3 and 1.3 cm in the superior and inferior, 1.7 and 1.8 cm in the anterior and posterior, and 0.76 and 0.94 cm in the right and left lateral directions, respectively. Conclusions: Cervix regression and internal organ motion contribute to marked interfraction variations in the intrapelvic position of the cervical target in patients receiving chemoradiation for cervical cancer. Failure to take these variations into account during the application of highly conformal external beam radiation techniques poses a theoretical risk of underdosing the target or overdosing adjacent critical structures.« less

Prognostic Significance of Carbohydrate Antigen 19-9 in Unresectable Locally Advanced Pancreatic Cancer Treated With Dose-Escalated Intensity Modulated Radiation Therapy and Concurrent Full-Dose Gemcitabine: Analysis of a Prospective Phase 1/2 Dose Escalation Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vainshtein, Jeffrey M., E-mail: jvainsh@med.umich.edu; Schipper, Matthew; Zalupski, Mark M.

2013-05-01

Purpose: Although established in the postresection setting, the prognostic value of carbohydrate antigen 19-9 (CA19-9) in unresectable locally advanced pancreatic cancer (LAPC) is less clear. We examined the prognostic utility of CA19-9 in patients with unresectable LAPC treated on a prospective trial of intensity modulated radiation therapy (IMRT) dose escalation with concurrent gemcitabine. Methods and Materials: Forty-six patients with unresectable LAPC were treated at the University of Michigan on a phase 1/2 trial of IMRT dose escalation with concurrent gemcitabine. CA19-9 was obtained at baseline and during routine follow-up. Cox models were used to assess the effect of baseline factorsmore » on freedom from local progression (FFLP), distant progression (FFDP), progression-free survival (PFS), and overall survival (OS). Stepwise forward regression was used to build multivariate predictive models for each endpoint. Results: Thirty-eight patients were eligible for the present analysis. On univariate analysis, baseline CA19-9 and age predicted OS, CA19-9 at baseline and 3 months predicted PFS, gross tumor volume (GTV) and black race predicted FFLP, and CA19-9 at 3 months predicted FFDP. On stepwise multivariate regression modeling, baseline CA19-9, age, and female sex predicted OS; baseline CA19-9 and female sex predicted both PFS and FFDP; and GTV predicted FFLP. Patients with baseline CA19-9 ≤90 U/mL had improved OS (median 23.0 vs 11.1 months, HR 2.88, P<.01) and PFS (14.4 vs 7.0 months, HR 3.61, P=.001). CA19-9 progression over 90 U/mL was prognostic for both OS (HR 3.65, P=.001) and PFS (HR 3.04, P=.001), and it was a stronger predictor of death than either local progression (HR 1.46, P=.42) or distant progression (HR 3.31, P=.004). Conclusions: In patients with unresectable LAPC undergoing definitive chemoradiation therapy, baseline CA19-9 was independently prognostic even after established prognostic factors were controlled for, whereas CA19-9 progression strongly predicted disease progression and death. Future trials should stratify by baseline CA19-9 and incorporate CA19-9 progression as a criterion for progressive disease.« less

Pancreatic Cancer Treatment (PDQ®)—Health Professional Version

Cancer.gov

Pancreatic cancer treatment options depend on disease stage and include surgery, radiation, chemotherapy, chemoradiation, and palliative therapy. Get detailed information about the treatment of newly diagnosed and recurrent pancreatic cancer in this summary for clinicians.

Thymoma and Thymic Carcinoma Treatment (PDQ®)—Health Professional Version

Cancer.gov

Thymoma and thymic carcinoma treatment options include surgery, radiation therapy, chemotherapy, chemoradiation, and corticosteroids. Get detailed information about treatment of newly diagnosed and recurrent thymoma and thymic cancer in this summary for clinicians.

Clinical outcome of elderly patients (≥ 70 years) with esophageal cancer undergoing definitive or neoadjuvant radio(chemo)therapy: a retrospective single center analysis.

PubMed

Walter, Franziska; Böckle, David; Schmidt-Hegemann, Nina-Sophie; Köpple, Rebecca; Gerum, Sabine; Boeck, Stefan; Angele, Martin; Belka, Claus; Roeder, Falk

2018-05-16

To analyse the outcome of elderly patients (≥70 years) with esophageal cancer treated with curative intent radio(chemo)therapy. Fifty five patients (median 75 years) receiving curative intent radio(chemo)therapy for esophageal cancer from 1999 to 2015 were retrospectively analyzed. Most patients showed locally advanced disease (T3/4:78%, N+:58%) with squamous cell histology (74%). Charlson comorbidity score was > 1 in 27%. 48 patients (87%) received definitive treatment while 7 patients were treated neoadjuvantly. RT was carried out as 3D-conformal treatment or IMRT. Concurrent chemotherapy was applied in 85%, mainly cisplatin/5-FU or mitomycin/5-FU. 18 FDG-PET/CT staging was used in 65%. Median follow-up was 11 months (1-68) and 21 months in survivors. 1- and 2-year rates of LRC, DC, FFTF and OS were 60%/45, 81%/72, 55%/41 and 46%/26% for the entire cohort. In univariate analysis, addition of surgery was associated with improved LRC and FFTF, nodal involvement with improved DC and lower T stage, lower Charlson score and use of PET-CT with improved OS. In multivariate analysis, lower T stage and lower Charlson score remained significant for OS. Patients treated after 2008 showed a significantly improved FFTF (1-year FFTF 64% vs 35%) and OS (1-year OS 66% vs 24%). Maximum (chemo)radiation related grade3+ toxicity was observed in 80% including 7 deaths (13%). Grade5 toxicity was significantly associated with Charlson score (CS > 1:33% vs CS ≤ 1:5%) and treatment period (24% before vs 3% after 2008). The patients treated after 2008 included significantly more SCCs, less T4 stages, had a higher percentage of PET-CT staging and were treated with smaller field lengths. Trends were also observed for lower Charlson scores and increased use of IMRT. Curative intent (chemo)radiation of elderly patients with esophageal cancer may result in considerable toxicity and unfavorable outcome. However, a clear improvement over time was observed in our cohort, probably based on improved patient selection. In patients with less advanced stages and lower comorbidity similar results as in younger cohorts seem achievable with modern staging and treatment approaches. Age per se should not be a decisive factor, but careful attention should be paid regarding patient selection including a structured and tight follow-up strategy.

Dosimetric Predictors of Patient-Reported Xerostomia and Dysphagia With Deintensified Chemoradiation Therapy for HPV-Associated Oropharyngeal Squamous Cell Carcinoma.

PubMed

Chera, Bhishamjit S; Fried, David; Price, Alex; Amdur, Robert J; Mendenhall, William; Lu, Chiray; Das, Shiva; Sheets, Nathan; Marks, Lawrence; Mavroidis, Panayiotis

2017-08-01

To estimate the association between different dose-volume metrics of the salivary glands and pharyngeal constrictors with patient reported severity of xerostomia/dysphagia in the setting of deintensified chemoradiation therapy (CRT). Forty-five patients were treated on a phase 2 study assessing the efficacy of deintensified CRT for favorable-risk, HPV-associated oropharyngeal squamous cell carcinoma. Patients received 60 Gy intensity modulated radiation therapy with concurrent weekly cisplatin (30 mg/m 2 ), and reported the severity of their xerostomia/dysphagia (before and after treatment) using the patient-reported outcome version of the Common Terminology Criteria for Adverse Events (CTCAE) (PRO-CTCAE). Individual patient dosimetric data of the contralateral parotid and submandibular glands and pharyngeal constrictors were correlated with changes in PRO-CTCAE severity. A change in severity (from baseline) of ≥2 was considered clinically meaningful. Associations between dose-volume metrics and patient outcomes were assessed with receiver operating characteristic (ROC) curve and logistic regression model. Six months after CRT, patients reporting <2 change in xerostomia severity (n=14) had an average D mean = 22 ± 9 Gy to the sum of the contralateral glands (parotid + submandibular) compared with the patients reporting ≥2 change (n=21), who had an average D mean = 34 ± 8 Gy. V15 to V55 for the combined contralateral glands showed the strongest association with xerostomia (area under the curve [AUC] = 0.83-0.86). Based on the regression analysis, a 20% risk of toxicity was associated with V15 = 48%, V25 = 30%, and D mean =21 Gy. Six months after CRT, patients reporting <2 change in dysphagia severity (n=26) had an average V55 = 76 ± 13 (%) to the superior pharyngeal constrictor compared with the patients reporting ≥2 change in severity (n=9), who had average V55 = 89 ± 13 (%). V55to V60 had the strongest association with dysphagia (AUC = 0.70-0.75). Based on the regression analysis, a 20% risk of toxicity was associated with V55 = 78%, V60 = 40%. The findings at 12 months were similar. After deintensified CRT, the rate of patient-reported xerostomia/dysphagia appears to be associated with the V15 of the combined contralateral salivary glands and V55 to V60 of the superior pharyngeal constrictors. Copyright © 2017 Elsevier Inc. All rights reserved.

What is the optimal radiation dose for non-operable esophageal cancer? Dissecting the evidence in a meta-analysis.

PubMed

Chen, Yong; Zhu, Hui-Ping; Wang, Tao; Sun, Chang-Jiang; Ge, Xiao-Lin; Min, Ling-Feng; Zhang, Xian-Wen; Jia, Qing-Qing; Yu, Jie; Yang, Jian-Qi; Allgayer, Heike; Abba, Mohammed L; Zhang, Xi-Zhi; Sun, Xin-Chen

2017-10-24

The standard radiation dose 50.4 Gy with concurrent chemotherapy for localized inoperable esophageal cancer as supported by INT-0123 trail is now being challenged since a radiation dose above 50 Gy has been successfully administered with an observable dose-response relationship and insignificant untoward effects. Therefore, to ascertain the treatment benefits of different radiation doses, we performed a meta-analysis with 18 relative publications. According to our findings, a dose between 50 and 70 Gy appears optimal and patients who received ≥ 60 Gy radiation had a significantly better prognosis (pooled HR = 0.78, P = 0.004) as compared with < 60 Gy, especially in Asian countries (pooled HR = 0.75, P = 0.003). However, contradictory results of treatment benefit for ≥ 60 Gy were observed in two studies from Western countries, and the pooled treatment benefit of ≥ 60 Gy radiation was inconclusive (pooled HR = 0.86, P = 0.64). There was a marginal benefit in locoregional control in those treated with high dose (> 50.4/51 Gy) radiation when compared with those treated with low dose (≤ 50.4/51 Gy) radiation (pooled OR = 0.71, P = 0.06). Patients that received ≥ 60 Gy radiation had better locoregional control (OR = 0.29, P = 0.001), and for distant metastasis control, neither the > 50.4 Gy nor the ≥ 60 Gy treated group had any treatment benefit as compared to the groups that received ≤ 50.4 Gy and < 60 Gy group respectively. Taken together, a dose range of 50 to 70 Gy radiation with CCRT is recommended for non-operable EC patients. A dose of ≥ 60 Gy appears to be better in improving overall survival and locoregional control, especially in Asian countries, while the benefit of ≥ 60 Gy radiation in Western countries still remains controversial.

[The possibility of local control of cancer by neoadjuvant chemoradiation therapy with gemcitabine and surgical resection for advanced cholangiocarcinoma].

PubMed

Nakagawa, Kei; Katayose, Yu; Rikiyama, Toshiki; Okaue, Adoru; Unno, Michiaki

2009-11-01

Surgical resection is the gold standard of treatment for cholangiocarcinoma. However, there are also many recurrences after operation, because of the anatomical background and the tendency of invasion. We thought that eliminating the remnant of the cancer could yield a better prognosis. Therefore, an introduction of the neoadjuvant chemoradiation therapy with gemcitabine and surgical resection for advanced cholangiocarcinoma patient (NACRAC) was planned. The safety of NACRAC was confirmed by a pilot study. The recommended dose of gemcitabine (600 mg/m2) was determined by a phase I study. A phase II study is now being performed for evaluating the effectiveness and safety. NACRAC may control the frontal part of the tumor with difficult distinctions made by MDCT, and abolishing the cancer remnant is expected. The possibility of extended prognosis by NACRAC can be considered.

[A case of a geriatric patient with stage IV anal canal cancer showing complete response to chemoradiation therapy].

PubMed

Kuroda, Masatoshi; Hirai, Ryuji; Ikeda, Eiji; Tsuji, Hisashi; Takagi, Shoji; Yamano, Toshihisa; Yoshitomi, Seiji

2012-11-01

We present a case in which chemoradiation therapy was effective in a geriatric patient with Stage IV anal canal cancer. The patient is an 81-year-old woman who complained of proctorrhagia and anal pain. She was referred to us by her family doctor who suspected rectal cancer. Tumors as large as 6.5 cm in diameter mainly on the right side of the rectum as well as 2 palpable enlarged lymph nodes on the right inguinal area, were found during the initial physical examination. Squamous cell carcinoma was elevated to 16 ng/mL. A CT scan revealed that irregularly shaped masses as large as 7 cm in diameter were externally exposed on the right side of the rectum along with enlarged lymph nodes on the right inguinal area and metastasis at S7 lesion in the liver. Squamous cell carcinoma was diagnosed from biopsy results. Due to her age, the chemotherapy regimen was S-1+CDDP with radiation therapy and 4-port irradiation (50.4 Gy) of the primary tumor, interior of the pelvis, and inguinal lymph nodes. Partial response was observed upon completion of treatment, and complete response was obtained after 6 months. She is currently an outpatient taking S-1: 60 mg/day orally. There is no indication of cancer recurrence after 1 year and 3 months, and she continues to visit an outpatient clinic for regular follow-ups. These results demonstrate the effectiveness of chemoradiation therapy for geriatric patients with Stage IV anal canal cancer.

Sequential versus "sandwich" sequencing of adjuvant chemoradiation for the treatment of stage III uterine endometrioid adenocarcinoma.

PubMed

Lu, Sharon M; Chang-Halpenny, Christine; Hwang-Graziano, Julie

2015-04-01

To compare the efficacy and tolerance of adjuvant chemotherapy and radiotherapy delivered in sequential (chemotherapy followed by radiation) versus "sandwich" fashion (chemotherapy, interval radiation, and remaining chemotherapy) after surgery in patients with FIGO stage III uterine endometrioid adenocarcinoma. From 2004 to 2011, we identified 51 patients treated at our institution fitting the above criteria. All patients received surgical staging followed by adjuvant chemoradiation (external-beam radiation therapy (EBRT) with or without high-dose rate (HDR) vaginal brachytherapy (VB)). Of these, 73% and 27% of patients received their adjuvant therapy in sequential and sandwich fashion, respectively. There were no significant differences in clinical or pathologic factors between patients treated with either regimen. Thirty-nine (76%) patients had stage IIIC disease. The majority of patients received 6 cycles of paclitaxel with carboplatin or cisplatin. Median EBRT dose was 45 Gy and 54% of patients received HDR VB boost (median dose 21 Gy). There were no significant differences in the estimated 5-year overall survival, local progression-free survival, and distant metastasis-free survival between the sequential and sandwich groups: 87% vs. 77% (p=0.37), 89% vs. 100% (p=0.21), and 78% vs. 85% (p=0.79), respectively. No grade 3-4 genitourinary or gastrointestinal toxicities were reported in either group. There was a trend towards higher incidence of grade 3-4 hematologic toxicity in the sandwich group. Adjuvant chemoradiation for FIGO stage III endometrioid uterine cancer given in either sequential or sandwich fashion appears to offer equally excellent early clinical outcomes and acceptably low toxicity. Copyright © 2015 Elsevier Inc. All rights reserved.

The effect of honey on mucositis induced by chemoradiation in head and neck cancer.

PubMed

Maiti, Pradip Kumar; Ray, Amitabh; Mitra, Tarak Nath; Jana, Utpal; Bhattacharya, Jibak; Ganguly, Subir

2012-07-01

The aim of this study was to evaluate the effect of pure natural honey on radiation-induced mucositis. Fifty-five patients diagnosed with head and neck cancer requiring radiation to the oropharyngeal mucosal area were divided into two groups (study arm-28 and control arm-27) to receive either chemoradiation or chemoradiation plus topical application of honey. Patients were treated using a telecobalt machine at 2 Gy per day, five times a week up to a total dose of 66 Gy. in the study arm, patients were advised to take 20 ml of honey 15 minutes before, 15 minutes after and similar amount at bed time. Patients were evaluated every week for the development of radiation mucositis using the WHO grading system. There was significant reduction in the symptomatic grades 3 and 4 mucositis in honey-treated patients compared to controls ie, 18% versus 41% for grade 3 and 4% versus 22% for grade 4 mucositis. Seventy-one per cent of patients treated with topical honey showed no change or a positive gain in body weight. In the control group also 22% had no weight loss, though none showed weight gain. Furthermore, it didn't affect blood sugar level when initial fasting blood sugar level was < 150 mg%. Honey is a cheap, simple, easily available and effective agent in reducing radiation-induced mucositis. Within the limits of this study the results showed the application of natural honey is effective in managing radiation induced mucositis, which warrants further multicentric randomised trials to validate the findings.

Analysis of Local Control in Patients Receiving IMRT for Resected Pancreatic Cancers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yovino, Susannah; Maidment, Bert W.; Herman, Joseph M.

2012-07-01

Purpose: Intensity-modulated radiotherapy (IMRT) is increasingly incorporated into therapy for pancreatic cancer. A concern regarding this technique is the potential for geographic miss and decreased local control. We analyzed patterns of first failure among patients treated with IMRT for resected pancreatic cancer. Methods and Materials: Seventy-one patients who underwent resection and adjuvant chemoradiation for pancreas cancer are included in this report. IMRT was used for all to a median dose of 50.4 Gy. Concurrent chemotherapy was 5-FU-based in 72% of patients and gemcitabine-based in 28%. Results: At median follow-up of 24 months, 49/71 patients (69%) had failed. The predominant failuremore » pattern was distant metastases in 35/71 patients (49%). The most common site of metastases was the liver. Fourteen patients (19%) developed locoregional failure in the tumor bed alone in 5 patients, regional nodes in 4 patients, and concurrently with metastases in 5 patients. Median overall survival (OS) was 25 months. On univariate analysis, nodal status, margin status, postoperative CA 19-9 level, and weight loss during treatment were predictive for OS. On multivariate analysis, higher postoperative CA19-9 levels predicted for worse OS on a continuous basis (p < 0.01). A trend to worse OS was seen among patients with more weight loss during therapy (p = 0.06). Patients with positive nodes and positive margins also had significantly worse OS (HR for death 2.8, 95% CI 1.1-7.5; HR for death 2.6, 95% CI 1.1-6.2, respectively). Grade 3-4 nausea and vomiting was seen in 8% of patients. Late complication of small bowel obstruction occurred in 4 (6%) patients. Conclusions: This is the first comprehensive report of patterns of failure among patients treated with adjuvant IMRT for pancreas cancer. IMRT was not associated with an increase in local recurrences in our cohort. These data support the use of IMRT in the recently activated EORTC/US Intergroup/RTOG 0848 adjuvant pancreas trial.« less

RECQ1 A159C Polymorphism Is Associated With Overall Survival of Patients With Resected Pancreatic Cancer: A Replication Study in NRG Oncology Radiation Therapy Oncology Group 9704

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Donghui, E-mail: dli@mdanderson.org; Moughan, Jennifer; Crane, Christopher

Purpose: To confirm whether a previously observed association between RECQ1 A159C variant and clinical outcome of resectable pancreatic cancer patients treated with preoperative chemoradiation is reproducible in another patient population prospectively treated with postoperative chemoradiation. Methods and Materials: Patients were selected, according to tissue availability, from eligible patients with resected pancreatic cancer who were enrolled on the NRG Oncology Radiation Therapy Oncology Group 9704 trial of 5-fluorouacil (5-FU)-based chemoradiation preceded and followed by 5-FU or gemcitabine. Deoxyribonucleic acid was extracted from paraffin-embedded tissue sections, and genotype was determined using the Taqman method. The correlation between genotype and overall survival wasmore » analyzed using a Kaplan-Meier plot, log-rank test, and multivariate Cox proportional hazards models. Results: In the 154 of the study's 451 eligible patients with evaluable tissue, genotype distribution followed Hardy-Weinberg equilibrium (ie, 37% had genotype AA, 43% AC, and 20% CC). The RECQ1 variant AC/CC genotype carriers were associated with being node positive compared with the AA carrier (P=.03). The median survival times (95% confidence interval [CI]) for AA, AC, and CC carriers were 20.6 (16.3-26.1), 18.8 (14.2-21.6), and 14.2 (10.3-21.0) months, respectively. On multivariate analysis, patients with the AC/CC genotypes were associated with worse survival than patients with the AA genotype (hazard ratio [HR] 1.54, 95% CI 1.07-2.23, P=.022). This result seemed slightly stronger for patients on the 5-FU arm (n=82) (HR 1.64, 95% CI 0.99-2.70, P=.055) than for patients on the gemcitabine arm (n=72, HR 1.46, 95% CI 0.81-2.63, P=.21). Conclusions: Results of this study suggest that the RECQ1 A159C genotype may be a prognostic or predictive factor for resectable pancreatic cancer patients who are treated with adjuvant 5-FU before and after 5-FU-based chemoradiation. Further study is needed in patients treated with gemcitabine to determine whether an association exists.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rothschild, Sacha; Bucher, Stephan E.; Bernier, Jacques

Purpose: To establish the feasibility and tolerability of gefitinib (ZD1839, Iressa) with radiation (RT) or concurrent chemoradiation (CRT) with cisplatin (CDDP) in patients with advanced non-small cell lung cancer (NSCLC). Patients and Methods: In this multicenter Phase I study, 5 patients with unresectable NSCLC received 250 mg gefitinib daily starting 1 week before RT at a dose of 63 Gy (Step 1). After a first safety analysis, 9 patients were treated daily with 250 mg gefitinib plus CRT in the form of RT and weekly CDDP 35 mg/m{sup 2} (Step 2). Gefitinib was maintained for up to 2 years untilmore » disease progression or toxicity. Results: Fourteen patients were assessed in the two steps. In Step 1 (five patients were administered only gefitinib and RT), no lung toxicities were seen, and there was no dose-limiting toxicity (DLT). Adverse events were skin and subcutaneous tissue reactions, limited to Grade 1-2. In Step 2, two of nine patients (22.2%) had DLT. One patient suffered from dyspnea and dehydration associated with neutropenic pneumonia, and another showed elevated liver enzymes. In both steps combined, 5 of 14 patients (35.7%) experienced one or more treatment interruptions. Conclusions: Gefitinib (250 mg daily) in combination with RT and CDDP in patients with Stage III NSCLC is feasible, but CDDP likely enhances toxicity. The impact of gefitinib on survival and disease control as a first-line treatment in combination with RT remains to be determined.« less

The effect of dose escalation on gastric toxicity when treating lower oesophageal tumours: a radiobiological investigation.

PubMed

Carrington, Rhys; Staffurth, John; Warren, Samantha; Partridge, Mike; Hurt, Chris; Spezi, Emiliano; Gwynne, Sarah; Hawkins, Maria A; Crosby, Thomas

2015-11-19

Using radiobiological modelling to estimate normal tissue toxicity, this study investigates the effects of dose escalation for concurrent chemoradiation therapy (CRT) in lower third oesophageal tumours on the stomach. 10 patients with lower third oesophageal cancer were selected from the SCOPE 1 database (ISCRT47718479) with a mean planning target volume (PTV) of 348 cm(3). The original 3D conformal plans (50 Gy3D) were compared to newly created RapidArc plans of 50 GyRA and 60 GyRA, the latter using a simultaneous integrated boost (SIB) technique using a boost volume, PTV2. Dose-volume metrics and estimates of normal tissue complication probability (NTCP) were compared. There was a significant increase in NTCP of the stomach wall when moving from the 50 GyRA to the 60 GyRA plans (11-17 %, Wilcoxon signed rank test, p = 0.01). There was a strong correlation between the NTCP values of the stomach wall and the volume of the stomach wall/PTV 1 and stomach wall/PTV2 overlap structures (R = 0.80 and R = 0.82 respectively) for the 60 GyRA plans. Radiobiological modelling suggests that increasing the prescribed dose to 60 Gy may be associated with a significantly increased risk of toxicity to the stomach. It is recommended that stomach toxicity be closely monitored when treating patients with lower third oesophageal tumours with 60 Gy.

High Dose Rate Brachytherapy in Two 9 Gy Fractions in the Treatment of Locally Advanced Cervical Cancer - a South Indian Institutional Experience.

PubMed

Ghosh, Saptarshi; Rao, Pamidimukkala Bramhananda; Kotne, Sivasankar

2015-01-01

Although 3D image based brachytherapy is currently the standard of treatment in cervical cancer, most of the centres in developing countries still practice orthogonal intracavitary brachytherapy due to financial constraints. The quest for optimum dose and fractionation schedule in high dose rate (HDR) intracavitary brachytherapy (ICBT) is still ongoing. While the American Brachytherapy Society recommends four to eight fractions of each less than 7.5 Gy, there are some studies demonstrating similar efficacy and comparable toxicity with higher doses per fraction. To assess the treatment efficacy and late complications of HDR ICBT with 9 Gy per fraction in two fractions. This is a prospective institutional study in Southern India carried on from 1st June 2012 to 31st July 2014. In this period, 76 patients of cervical cancer satisfying our inclusion criteria were treated with concurrent chemo-radiation following ICBT with 9 Gy per fraction in two fractions, five to seven days apart. The median follow-up period in the study was 24 months (range 10.6 - 31.2 months). The 2 year actuarial local control rate, disease-free survival and overall survival were 88.1%, 84.2% and 81.8% respectively. Although 38.2% patients suffered from late toxicity, only 3 patients had grade III late toxicity. In our experience, HDR brachytherapy with 9 Gy per fraction in two fractions is an effective dose fractionation for the treatment of cervical cancer with acceptable toxicity.

Determination of cytokine protein levels in oral secretions in patients undergoing radiotherapy for head and neck malignancies

PubMed Central

2012-01-01

Background Cytokines may be elevated in tumor and normal tissues following irradiation. Cytokine expression in these tissues may predict for toxicity or tumor control. The purpose of this pilot study was to determine the feasibility of measuring local salivary cytokine levels using buccal sponges in patients receiving chemo-radiation for head and neck malignancies. Patients and methods 11 patients with epithelial malignancies of the head and neck were recruiting to this study. All patients received radiotherapy to the head and neck region with doses ranging between 60 – 67.5 Gy. Chemotherapy was delivered concurrently with radiation in all patients. Salivary samples were obtained from high dose and low dose regions prior to treatment and at three intervals during treatment for assessment of cytokine levels (IL-4, IL-6, IL-8, IL-10, EGF, MCP-1, TNF-α, and VEGF). Results Cytokine levels were detectable in the salivary samples. Salivary cytokine levels of IL-4, IL-6, IL-8, EGF, MCP-1, TNF- α , and VEGF were higher in the high dose region compared to the low dose region at all time points (p < 0.05). A trend toward an increase in cytokine levels as radiation dose increased was observed for IL-6, IL-8, MCP-1, and TNF-α. Conclusion Assessment of salivary cytokine levels may provide a novel method to follow local cytokine levels during radiotherapy and may provide a mechanism to study cytokine levels in a regional manner. PMID:22537315

Chemoradiation May Help Some Patients with Bladder Cancer Avoid Radical Surgery

Cancer.gov

Researchers in the United Kingdom have found that adding chemotherapy to radiation therapy as a treatment for bladder cancer may reduce the risk of a recurrence more than radiation alone, without causing a substantial increase in side effects.

Pulmonary Rehabilitation in Improving Lung Function in Patients With Locally Advanced Non-Small Cell Lung Cancer Undergoing Chemoradiation

ClinicalTrials.gov

2017-04-12

Cachexia; Fatigue; Pulmonary Complications; Radiation Toxicity; Recurrent Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

PROSPECT Eligibility and Clinical Outcomes: Results From the Pan-Canadian Rectal Cancer Consortium.

PubMed

Bossé, Dominick; Mercer, Jamison; Raissouni, Soundouss; Dennis, Kristopher; Goodwin, Rachel; Jiang, Di; Powell, Erin; Kumar, Aalok; Lee-Ying, Richard; Price-Hiller, Julie; Heng, Daniel Y C; Tang, Patricia A; MacLean, Anthony; Cheung, Winson Y; Vickers, Michael M

2016-09-01

The PROSPECT trial (N1048) is evaluating the selective use of chemoradiation in patients with cT2N1 and cT3N0-1 rectal cancer undergoing sphincter-sparing low anterior resection. We evaluated outcomes of PROSPECT-eligible and -ineligible patients from a multi-institutional database. Data from patients with locally advanced rectal cancer who received chemoradiation and low anterior resection from 2005 to 2014 were retrospectively collected from 5 Canadian centers. Overall survival, disease-free survival (DFS), recurrence-free survival (RFS), and time to local recurrence (LR) were estimated using the Kaplan-Meier method, and a multivariate analysis was performed adjusting for prognostic factors. A total of 566 (37%) of 1531 patients met the PROSPECT eligibility criteria. Eligible patients were more likely to have better PS (P = .0003) and negative circumferential resection margin (P < .0001). PROSPECT eligibility was associated with improved DFS (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.61-0.91), overall survival (HR, 0.73; 95% CI, 0.57-0.95), and RFS (HR, 0.68; 95% CI, 0.54-0.86) in univariate analyses. In multivariate analysis, only RFS remained significantly improved for PROSPECT-eligible patients (HR, 0.75; 95% CI, 0.57-1.00, P = .0499). The 3-year DFS and freedom from LR for PROSPECT-eligible patients were 79.1% and 97.4%, respectively, compared to 71.1% and 96.8% for PROSPECT-ineligible patients. Real-world data corroborate the eligibility criteria used in the PROSPECT study; the criteria identify a subgroup of patients in whom risk of recurrence is lower and in whom selective use of chemoradiation should be actively examined. Copyright © 2016 Elsevier Inc. All rights reserved.

Dose-Volume Effects on Patient-Reported Acute Gastrointestinal Symptoms During Chemoradiation Therapy for Rectal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Ronald C.; Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts

2012-07-15

Purpose: Research on patient-reported outcomes (PROs) in rectal cancer is limited. We examined whether dose-volume parameters of the small bowel and large bowel were associated with patient-reported gastrointestinal (GI) symptoms during 5-fluorouracil (5-FU)-based chemoradiation treatment for rectal cancer. Methods and Materials: 66 patients treated at the Brigham and Women's Hospital or Massachusetts General Hospital between 2006 and 2008 were included. Weekly during treatment, patients completed a questionnaire assessing severity of diarrhea, urgency, pain, cramping, mucus, and tenesmus. The association between dosimetric parameters and changes in overall GI symptoms from baseline through treatment was examined by using Spearman's correlation. Potential associationsmore » between these parameters and individual GI symptoms were also explored. Results: The amount of small bowel receiving at least 15 Gy (V15) was significantly associated with acute symptoms (p = 0.01), and other dosimetric parameters ranging from V5 to V45 also trended toward association. For the large bowel, correlations between dosimetric parameters and overall GI symptoms at the higher dose levels from V25 to V45 did not reach statistical significance (p = 0.1), and a significant association was seen with rectal pain from V15 to V45 (p < 0.01). Other individual symptoms did not correlate with small bowel or large bowel dosimetric parameters. Conclusions: The results of this study using PROs are consistent with prior studies with physician-assessed acute toxicity, and they identify small bowel V15 as an important predictor of acute GI symptoms during 5-FU-based chemoradiation treatment. A better understanding of the relationship between radiation dosimetric parameters and PROs may allow physicians to improve radiation planning to optimize patient outcomes.« less

Influence of the Extent and Dose of Radiation on Complications After Neoadjuvant Chemoradiation and Subsequent Esophagectomy With Gastric Tube Reconstruction With a Cervical Anastomosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koëter, M.; Kathiravetpillai, N.; Gooszen, J.A.

Purpose: To determine, in a large series, the influence of the extent and dose of radiation to the fundus of the stomach and mediastinum on the development and severity of anastomotic complications in patients with esophageal cancer treated with neoadjuvant chemoradiation followed by esophagectomy with cervical anastomosis. Methods and Materials: Between 2005 and 2012, 364 consecutive patients with esophageal cancer treated with neoadjuvant chemoradiation (41.4 Gy combined with chemotherapy) followed by esophagectomy were included. The future anastomotic region in the fundus was determined, and the mean dose, V20-V40, and upper planning target volume border in relation to mediastinal length, expressed as themore » mediastinal ratio, were calculated. Results: Anastomotic leakage occurred in 22% and anastomotic stenosis in 41%. Logistic regression analysis revealed no influence of age, comorbidity, mean fundus dose, V20-V40, or the mediastinal ratio on the incidence of anastomotic leakage or anastomotic stenosis. In 28% of the patients severe complications (Clavien-Dindo score of ≥IIIB) occurred. The presence of multiple comorbidities (hazard ratio 2.4 [95% confidence interval 1.3-4.5], P=.006) and a mediastinal ratio of 0.5 to 1.0 (hazard ratio 1.9 [95% confidence interval 1.0-3.5], P=.036) were both independent predictors of severe complications. Conclusion: With a mean radiation dose of 24.2 Gy to the future anastomotic region of the gastric fundus, the radiation dose was not associated with the incidence of anastomotic leakage or anastomotic stenosis. The incidence of severe complications was associated with a high superior mediastinal planning target volume border.« less

Management of Chemoradiation-Induced Mucositis in Head and Neck Cancers With Oral Glutamine

PubMed Central

Panda, Niharika; Dash, Manoj Kumar; Mohanty, Sumita; Samantaray, Sagarika

2016-01-01

Purpose Head and neck cancers are the third most common cancers worldwide. Oral mucositis is the most common toxicity seen in patients who receive chemoradiation to treat head and neck cancer. The aim of this study was to evaluate the efficacy and safety of oral glutamine supplementation in these patients. Materials and Methods From December 2013 to December 2014, we randomly assigned to two arms 162 patients who had squamous cell carcinoma of the head and neck. Patients in arm A were given oral glutamine once per day, whereas those in arm B served as negative control subjects. All patients received radiotherapy given as 70 Gy in 35 fractions over 7 weeks with an injection of cisplatin once per week. Patients were assessed once per week to evaluate for the onset and severity of mucositis, pain, use of analgesics, and for Ryle tube feeding. Results We observed that 53.1% of patients developed mucositis toward the fifth week in the glutamine arm compared with 55.5% of patients in the control arm at the third week. None in the glutamine arm compared with 92.35% of patients in the control arm developed G3 mucositis. Rates of adverse events like pain, dysphagia, nausea, edema, and cough, as well as use of analgesics and Ryle tube feeding, were significantly lower in the glutamine arm than in the control arm. Conclusion This study highlights that the onset as well as the severity of mucositis in patients receiving glutamine was significantly delayed. None of the patients receiving glutamine developed G3 mucositis. Hence, the findings emphasize the use of oral glutamine supplementation as a feasible and affordable treatment option for mucositis in patients with head and neck cancers who are receiving chemoradiation. PMID:28717702

The Influence of Total Nodes Examined, Number of Positive Nodes, and Lymph Node Ratio on Survival After Surgical Resection and Adjuvant Chemoradiation for Pancreatic Cancer: A Secondary Analysis of RTOG 9704

DOE Office of Scientific and Technical Information (OSTI.GOV)

Showalter, Timothy N.; Winter, Kathryn A.; Berger, Adam C., E-mail: adam.berger@jefferson.edu

2011-12-01

Purpose: Lymph node status is an important predictor of survival in pancreatic cancer. We performed a secondary analysis of Radiation Therapy Oncology Group (RTOG) 9704, an adjuvant chemotherapy and chemoradiation trial, to determine the influence of lymph node factors-number of positive nodes (NPN), total nodes examined (TNE), and lymph node ratio (LNR ratio of NPN to TNE)-on OS and disease-free survival (DFS). Patient and Methods: Eligible patients from RTOG 9704 form the basis of this secondary analysis of lymph node parameters. Actuarial estimates for OS and DFS were calculated using Kaplan-Meier methods. Cox proportional hazards models were performed to evaluatemore » associations of NPN, TNE, and LNR with OS and DFS. Multivariate Cox proportional hazards models were also performed. Results: There were 538 patients enrolled in the RTOG 9704 trial. Of these, 445 patients were eligible with lymph nodes removed. Overall median NPN was 1 (min-max, 0-18). Increased NPN was associated with worse OS (HR = 1.06, p = 0.001) and DFS (HR = 1.05, p = 0.01). In multivariate analyses, both NPN and TNE were associated with OS and DFS. TNE > 12, and >15 were associated with increased OS for all patients, but not for node-negative patients (n = 142). Increased LNR was associated with worse OS (HR = 1.01, p < 0.0001) and DFS (HR = 1.006, p = 0.002). Conclusion: In patients who undergo surgical resection followed by adjuvant chemoradiation, TNE, NPN, and LNR are associated with OS and DFS. This secondary analysis of a prospective, cooperative group trial supports the influence of these lymph node parameters on outcomes after surgery and adjuvant therapy using contemporary techniques.« less

Treatment Recommendations for Locally Advanced, Non-Small-Cell Lung Cancer: The Influence of Physician and Patient Factors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Irwin H.; Hayman, James A.; Landrum, Mary Beth

2009-08-01

Purpose: To determine the impact of patient age, comorbidity, and physician factors on treatment recommendations for locally advanced, unresectable non-small-cell lung cancer (NSCLC). Methods and Materials: We surveyed radiation oncologists regarding their recommendations for treatment (chemoradiation, radiation alone, chemotherapy alone, or no therapy) for hypothetical patients with Stage IIIB NSCLC who varied by age (55 vs. 80 years) and comorbid illness (none, moderate, or severe chronic obstructive pulmonary disease [COPD]). Multinomial logistic regression was used to assess the impact of physician and practice characteristics on radiation oncologists' treatment recommendations for three scenarios with the least agreement. Results: Of 214 radiationmore » oncologists, nearly all (99%) recommended chemoradiation for a healthy 55 year old. However, there was substantial variability in recommendations for a 55 year old with severe COPD, an 80-year-old with moderate COPD, and an 80-year-old with severe COPD. Physicians seeing a lower volume of lung cancer patients were statistically less likely to recommend radiotherapy for younger or older patients with severe COPD (both p < 0.05), but the impact was modest. Conclusions: Nearly all radiation oncologists report following the evidence-based recommendation of chemoradiation for young, otherwise healthy patients with locally advanced, unresectable NSCLC, but there is substantial variability in treatment recommendations for older or sicker patients, probably related to the lack of clinical trial data for such patients. The physician and practice characteristics we examined only weakly affected treatment recommendations. Additional clinical trial data are necessary to guide recommendations for treatment of elderly patients and patients with poor pulmonary function to optimize their management.« less

Patterns of care, predictors and outcomes of chemotherapy for uterine carcinosarcoma: a National Cancer Database analysis.

PubMed

Rauh-Hain, J Alejandro; Starbuck, Kristen D; Meyer, Larissa A; Clemmer, Joel; Schorge, John O; Lu, Karen H; Del Carmen, Marcela G

2015-10-01

Evaluate rates of chemotherapy and radiotherapy delivery in the treatment of uterine carcinosarcoma, and compare clinical outcomes of treated and untreated patients. The National Cancer Database was queried to identify patients diagnosed with uterine carcinosarcoma between 2003 and 2011. The impact of chemotherapy on survival was analyzed using the Kaplan-Meier method. Factors predictive of outcome were compared using the Cox proportional hazards model. A total of 10,609 patients met study eligibility criteria. Stages I, II, III, and IV disease accounted for 2997 (28.2%), 642 (6.1%), 2037 (19.2%), and 1316 (12.4%) of the study population, respectively. Most patients (91.0%) underwent definitive surgery, and lymphadenectomy was performed in 68.7% of the patients. Chemotherapy was administered in 2378 (22.4%) patients, radiotherapy to 2196 (20.7%), adjuvant chemo-radiation to 1804 (17.0%), and 4231 (39.9%) of women did not received adjuvant therapy. Utilization of chemotherapy became more frequent over time. Over the entire study period, after adjusting for race, period of diagnosis, facility location, facility type, insurance provider, stage, age, treatment modality, lymph node dissection, socioeconomic status, and comorbidity index, there was an association between treatment modality and survival. The lowest hazard ratio observed was in patients that received chemo-radiation. The strongest quantitative predictor of death was stage at the time of diagnosis. In addition, surgical treatment, lymph node dissection, most recent time-periods, lower comorbidity index, and higher socioeconomic status were associated with improved survival. The overall rates of chemotherapy use have increased over time. Adjuvant chemotherapy and chemo-radiation were associated with improved survival. Copyright © 2015 Elsevier Inc. All rights reserved.

Influence of the Extent and Dose of Radiation on Complications After Neoadjuvant Chemoradiation and Subsequent Esophagectomy With Gastric Tube Reconstruction With a Cervical Anastomosis.

PubMed

Koëter, M; Kathiravetpillai, N; Gooszen, J A; van Berge Henegouwen, M I; Gisbertz, S S; van der Sangen, M J C; Luyer, M D P; Nieuwenhuijzen, G A P; Hulshof, M C C M

2017-03-15

To determine, in a large series, the influence of the extent and dose of radiation to the fundus of the stomach and mediastinum on the development and severity of anastomotic complications in patients with esophageal cancer treated with neoadjuvant chemoradiation followed by esophagectomy with cervical anastomosis. Between 2005 and 2012, 364 consecutive patients with esophageal cancer treated with neoadjuvant chemoradiation (41.4 Gy combined with chemotherapy) followed by esophagectomy were included. The future anastomotic region in the fundus was determined, and the mean dose, V20-V40, and upper planning target volume border in relation to mediastinal length, expressed as the mediastinal ratio, were calculated. Anastomotic leakage occurred in 22% and anastomotic stenosis in 41%. Logistic regression analysis revealed no influence of age, comorbidity, mean fundus dose, V20-V40, or the mediastinal ratio on the incidence of anastomotic leakage or anastomotic stenosis. In 28% of the patients severe complications (Clavien-Dindo score of ≥IIIB) occurred. The presence of multiple comorbidities (hazard ratio 2.4 [95% confidence interval 1.3-4.5], P=.006) and a mediastinal ratio of 0.5 to 1.0 (hazard ratio 1.9 [95% confidence interval 1.0-3.5], P=.036) were both independent predictors of severe complications. With a mean radiation dose of 24.2 Gy to the future anastomotic region of the gastric fundus, the radiation dose was not associated with the incidence of anastomotic leakage or anastomotic stenosis. The incidence of severe complications was associated with a high superior mediastinal planning target volume border. Copyright © 2016 Elsevier Inc. All rights reserved.

Treatment, survival, and costs of laryngeal cancer care in the elderly.

PubMed

Gourin, Christine G; Dy, Sydney M; Herbert, Robert J; Blackford, Amanda L; Quon, Harry; Forastiere, Arlene A; Eisele, David W; Frick, Kevin D

2014-08-01

To examine associations between treatment and volume with survival and costs in elderly patients with laryngeal squamous cell cancer (SCCA). Retrospective cross-sectional analysis of Surveillance, Epidemiology, and End Results-Medicare data. We evaluated 2,370 patients diagnosed with laryngeal SCCA from 2004 to 2007 using cross-tabulations, multivariate logistic and generalized linear regression modeling, and survival analysis. Chemoradiation was significantly associated with supraglottic tumors (relative risk ratio: 2.6, 95% confidence interval [CI]: 1.7-4.0), additional cancer-directed treatment (odds ratio [OR]: 1.8, 95% CI: 1.2-2.7), and a reduced likelihood of surgical salvage (OR: 0.3, 95% CI: 0.2-0.6). Surgery with postoperative radiation was associated with significantly improved survival (hazard ratio [HR]: 0.7, 95% CI: 0.6-0.9), after controlling for patient and tumor variables including salvage. High-volume care was not associated with survival for nonoperative treatment but was associated with improved survival (HR: 0.7, 95% CI: 0.5-0.8) among surgical patients. Initial treatment and 5-year overall costs for chemoradiation were higher than for all other treatment categories. High-volume care was associated with significantly lower costs of care for surgical patients but was not associated with differences in costs of care for nonoperative treatment. Chemoradiation in elderly patients with laryngeal cancer was associated with increased costs, additional cancer-directed treatment, and a reduced likelihood of surgical salvage. Surgery with postoperative radiation was associated with improved survival in this cohort, and high-volume hospital surgical care was associated with improved survival and lower costs. These findings have implications for improving the quality of laryngeal cancer treatment at a time of both rapid growth in the elderly population and diminishing healthcare resources. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Predictors of Postoperative Complications After Trimodality Therapy for Esophageal Cancer

PubMed Central

Wang, Jingya; Wei, Caimiao; Tucker, Susan L.; Myles, Bevan; Palmer, Matthew; Hofstetter, Wayne L.; Swisher, Stephen G.; Ajani, Jaffer A.; Cox, James D.; Komaki, Ritsuko; Liao, Zhongxing; Lin, Steven H.

2013-01-01

Purpose While trimodality therapy for esophageal cancer has improved patient outcomes, surgical complication rates remain high. The goal of this study was to identify modifiable factors associated with postoperative complications after neoadjuvant chemoradiation. Methods and Materials From 1998 to 2011, 444 patients were treated at our institution with surgical resection after chemoradiation. Postoperative (pulmonary, gastrointestinal [GI], cardiac, wound healing) complications were recorded up to 30 days postoperatively. Kruskal-Wallis tests and χ2 or Fisher exact tests were used to assess associations between continuous and categorical variables. Multivariate logistic regression tested the association between perioperative complications and patient or treatment factors that were significant on univariate analysis. Results The most frequent postoperative complications after trimodality therapy were pulmonary (25%) and GI (23%). Lung capacity and the type of radiation modality used were independent predictors of pulmonary and GI complications. After adjusting for confounding factors, pulmonary and GI complications were increased in patients treated with 3-dimensional conformal radiation therapy (3D-CRT) versus intensity modulated radiation therapy (IMRT; odds ratio [OR], 2.018; 95% confidence interval [CI], 1.104–3.688; OR, 1.704; 95% CI, 1.03–2.82, respectively) and for patients treated with 3D-CRT versus proton beam therapy (PBT; OR, 3.154; 95% CI, 1.365–7.289; OR, 1.55; 95% CI, 0.78–3.08, respectively). Mean lung radiation dose (MLD) was strongly associated with pulmonary complications, and the differences in toxicities seen for the radiation modalities could be fully accounted for by the MLD delivered by each of the modalities. Conclusions The radiation modality used can be a strong mitigating factor of postoperative complications after neoadjuvant chemoradiation. PMID:23845841

Predictors of Postoperative Complications After Trimodality Therapy for Esophageal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Jingya; Wei, Caimiao; Tucker, Susan L.

2013-08-01

Purpose: While trimodality therapy for esophageal cancer has improved patient outcomes, surgical complication rates remain high. The goal of this study was to identify modifiable factors associated with postoperative complications after neoadjuvant chemoradiation. Methods and Materials: From 1998 to 2011, 444 patients were treated at our institution with surgical resection after chemoradiation. Postoperative (pulmonary, gastrointestinal [GI], cardiac, wound healing) complications were recorded up to 30 days postoperatively. Kruskal-Wallis tests and χ{sup 2} or Fisher exact tests were used to assess associations between continuous and categorical variables. Multivariate logistic regression tested the association between perioperative complications and patient or treatment factorsmore » that were significant on univariate analysis. Results: The most frequent postoperative complications after trimodality therapy were pulmonary (25%) and GI (23%). Lung capacity and the type of radiation modality used were independent predictors of pulmonary and GI complications. After adjusting for confounding factors, pulmonary and GI complications were increased in patients treated with 3-dimensional conformal radiation therapy (3D-CRT) versus intensity modulated radiation therapy (IMRT; odds ratio [OR], 2.018; 95% confidence interval [CI], 1.104-3.688; OR, 1.704; 95% CI, 1.03-2.82, respectively) and for patients treated with 3D-CRT versus proton beam therapy (PBT; OR, 3.154; 95% CI, 1.365-7.289; OR, 1.55; 95% CI, 0.78-3.08, respectively). Mean lung radiation dose (MLD) was strongly associated with pulmonary complications, and the differences in toxicities seen for the radiation modalities could be fully accounted for by the MLD delivered by each of the modalities. Conclusions: The radiation modality used can be a strong mitigating factor of postoperative complications after neoadjuvant chemoradiation.« less

Dysphagia after sequential chemoradiation therapy for advanced head and neck cancer.

PubMed

Goguen, Laura A; Posner, Marshall R; Norris, Charles M; Tishler, Roy B; Wirth, Lori J; Annino, Donald J; Gagne, Adele; Sullivan, Christopher A; Sammartino, Daniel E; Haddad, Robert I

2006-06-01

Assess impact of sequential chemoradiation therapy (SCRT) for advanced head and neck cancer (HNCA) on swallowing, nutrition, and quality of life. Prospective cohort study of 59 patients undergoing SCRT for advanced head and neck cancer. Follow-up median was 47.5 months. Regional Cancer Center. Median time to gastrostomy tube removal was 21 weeks. Eighteen of 23 patients who underwent modified barium swallow demonstrated aspiration; none developed pneumonia. Six of 7 with pharyngoesophageal stricture underwent successful dilatation. Functional Assessment of Cancer Therapy-Head and Neck Scale questionnaires at median 6 months after treatment revealed "somewhat" satisfaction with swallowing. At the time of analysis, 97% have the gastronomy tube removed and take soft/regular diet. Early after treatment dysphagia adversely affected weight, modified barium swallow results, and quality of life. Diligent swallow therapy, and dilation as needed, allowed nearly all patients to have their gastronomy tubes removed and return to a soft/regular diet. Dysphagia is significant after SCRT but generally slowly recovers 6 to 12 months after SCRT. C-4.

Nasopharyngeal carcinoma with central nervous system metastases: Two case reports and a review of the literature.

PubMed

Shen, Chunying; Ying, Hongmei; Lu, Xueguan; Hu, Chaosu

2017-12-01

Central nervous system (CNS) metastases are rarely seen in patients with nasopharyngeal carcinoma (NPC). Two NPC patients developed CNS metastases were collected in Fudan University Shanghai Cancer Center. The medical records were reviewed to document patients' characteristics, treatment, and outcomes. In addition, we also provide an overview of the literature concerning this scenario. Both patients were staged T4N1M0 with pathologically confirmed CNS metastases from nasopharyngeal carcinoma. After the completion of initial chemoradiotherapy, metastases to CNS including brain and/or spine occurred during follow-up. Surgical resection combined with palliative chemoradiation was offered to alleviate the symptoms. Although multiple treatment modalities were given, both patients succumbed to disease progression. The mechanism for CNS metastases is postulated through hematogenous route or cerebral spinal fluid spread. Good symptoms amelioration can be achieved with aggressive treatments such as surgery followed by palliative chemoradiation, but prognoses are ominous due to systematic disease dissemination.

Anal Cancer: An Examination of Radiotherapy Strategies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Glynne-Jones, Rob; Lim, Faye

2011-04-01

The Radiation Therapy Oncology Group 9811, ACCORD-03, and ACT II Phase III trials in anal cancer showed no benefit for cisplatin-based induction and maintenance chemotherapy, or radiation dose-escalation >59 Gy. This review examines the efficacy and toxicity of chemoradiation (CRT) in anal cancer, and discusses potential alternative radiotherapy strategies. The evidence for the review was compiled from randomized and nonrandomized trials of radiation therapy and CRT. A total of 103 retrospective/observational studies, 4 Phase I/II studies, 16 Phase II prospective studies, 2 randomized Phase II studies, and 6 Phase III trials of radiotherapy or chemoradiation were identified. There are nomore » meta-analyses based on individual patient data. A 'one-size-fits-all' approach for all stages of anal cancer is inappropriate. Early T1 tumors are probably currently overtreated, whereas T3/T4 lesions might merit escalation of treatment. Intensity-modulated radiotherapy or the integration of biological therapy may play a role in future.« less

Evidence and evidence gaps of laryngeal cancer surgery

PubMed Central

Wiegand, Susanne

2016-01-01

Surgical treatment of laryngeal cancer has been established for decades. In addition to total laryngectomy, which was first performed in 1873, a large number or organ preservation surgical techniques, like open partial laryngectomy, transoral laser microsurgery, and transoral robotic surgery have been developed. Studies on laryngeal cancer surgery are mainly retrospective case series and cohort studies. The evolution of chemoradiation protocols and their analysis in prospective randomized trials have led to an increasing acceptance of non-surgical treatment procedures. In addition to an improvement of prognosis, in recent years the preservation of function and maintenance of life quality after primary therapy of laryngeal cancer has increasingly become the focus of therapy planning. Significant late toxicity after chemoradiation has been identified as an important issue. This leads to a reassessment of surgical concepts and initiation of studies on laryngeal cancer surgery which was additionally stimulated by the advent of transoral robotic surgery in the US. Improving the evidence base of laryngeal cancer surgery by successful establishment of surgical trials should be the future goal. PMID:28025603

Comprehensive Population-Averaged Arterial Input Function for Dynamic Contrast–Enhanced vMagnetic Resonance Imaging of Head and Neck Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Onxley, Jennifer D.; Yoo, David S.; Muradyan, Naira

2014-07-01

Purpose: To generate a population-averaged arterial input function (PA-AIF) for quantitative analysis of dynamic contrast-enhanced MRI data in head and neck cancer patients. Methods and Materials: Twenty patients underwent dynamic contrast-enhanced MRI during concurrent chemoradiation therapy. Imaging consisted of 2 baseline scans 1 week apart (B1/B2) and 1 scan after 1 week of chemoradiation therapy (Wk1). Regions of interest (ROIs) in the right and left carotid arteries were drawn on coronal images. Plasma concentration curves of all ROIs were averaged and fit to a biexponential decay function to obtain the final PA-AIF (AvgAll). Right-sided and left-sided ROI plasma concentration curves were averagedmore » separately to obtain side-specific AIFs (AvgRight/AvgLeft). Regions of interest were divided by time point to obtain time-point-specific AIFs (AvgB1/AvgB2/AvgWk1). The vascular transfer constant (K{sub trans}) and the fractional extravascular, extracellular space volume (V{sub e}) for primaries and nodes were calculated using the AvgAll AIF, the appropriate side-specific AIF, and the appropriate time-point-specific AIF. Median K{sub trans} and V{sub e} values derived from AvgAll were compared with those obtained from the side-specific and time-point-specific AIFs. The effect of using individual AIFs was also investigated. Results: The plasma parameters for AvgAll were a{sub 1,2} = 27.11/17.65 kg/L, m{sub 1,2} = 11.75/0.21 min{sup −1}. The coefficients of repeatability (CRs) for AvgAll versus AvgLeft were 0.04 min{sup −1} for K{sub trans} and 0.02 for V{sub e}. For AvgAll versus AvgRight, the CRs were 0.08 min{sup −1} for K{sub trans} and 0.02 for V{sub e}. When AvgAll was compared with AvgB1/AvgB2/AvgWk1, the CRs were slightly higher: 0.32/0.19/0.78 min{sup −1}, respectively, for K{sub trans}; and 0.07/0.08/0.09 for V{sub e}. Use of a PA-AIF was not significantly different from use of individual AIFs. Conclusion: A PA-AIF for head and neck cancer was generated that accounts for differences in right carotid artery versus left carotid artery, day-to-day fluctuations, and early treatment-induced changes. The small CRs obtained for K{sub trans} and V{sub e} indicate that side-specific AIFs are not necessary. However, a time-point-specific AIF may improve pharmacokinetic accuracy.« less

Genetic Mutations in Blood and Tissue Samples in Predicting Response to Treatment in Patients With Locally Advanced Rectal Cancer Undergoing Chemoradiation

ClinicalTrials.gov

2017-09-08

Mucinous Adenocarcinoma of the Rectum; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Rectum; Stage IIA Rectal Cancer; Stage IIB Rectal Cancer; Stage IIC Rectal Cancer; Stage IIIA Rectal Cancer; Stage IIIB Rectal Cancer; Stage IIIC Rectal Cancer

Randomized phase II trial evaluating two paclitaxel and cisplatin-containing chemoradiation regimens as adjuvant therapy in resected gastric cancer (RTOG-0114).

PubMed

Schwartz, Gary K; Winter, Kathryn; Minsky, Bruce D; Crane, Christopher; Thomson, P John; Anne, Pramila; Gross, Howard; Willett, Christopher; Kelsen, David

2009-04-20

The investigational arm of INT0116, a fluorouracil (FU) and leucovorin-containing chemoradiotherapy regimen, is a standard treatment for patients with resected gastric cancer with a 2-year disease-free survival rate (DFS) of 52%. Toxicity is also significant. More beneficial and safer regimens are needed. We performed a randomized phase II study among 39 cancer centers to evaluate two paclitaxel and cisplatin-containing regimens, one with FU (PCF) and the other without (PC) in patients with resected gastric cancer. Patients received two cycles of postoperative chemotherapy followed by 45 Gy of radiation with either concurrent FU and paclitaxel or paclitaxel and cisplatin. The primary objective was to show an improvement in 2-year DFS to 67% as compared with INT 0116. From May 2001 to February 2004 (study closure), 78 patients entered this study, and 73 were evaluable. At the planned interim analysis of 22 patients on PCF, grade 3 or higher GI toxicity was 59%. This was significantly worse than INT0116, and this arm was closed. Accrual continued on PC. The median DFS was 14.6 months for PCF and has not been reached for PC. For PC the 2-year DFS is 52% (95% CI, 36% to 68%). Though PC appears to be safe and the median DFS favorable, the DFS failed to exceed the lower bound of 52.9% for the targeted 67% DFS at 2 years and can not be recommended as the adjuvant arm for future randomized trials.

Randomized Phase II Trial Evaluating Two Paclitaxel and Cisplatin–Containing Chemoradiation Regimens As Adjuvant Therapy in Resected Gastric Cancer (RTOG-0114)

PubMed Central

Schwartz, Gary K.; Winter, Kathryn; Minsky, Bruce D.; Crane, Christopher; Thomson, P. John; Anne, Pramila; Gross, Howard; Willett, Christopher; Kelsen, David

2009-01-01

Purpose The investigational arm of INT0116, a fluorouracil (FU) and leucovorin–containing chemoradiotherapy regimen, is a standard treatment for patients with resected gastric cancer with a 2-year disease-free survival rate (DFS) of 52%. Toxicity is also significant. More beneficial and safer regimens are needed. Patients and Methods We performed a randomized phase II study among 39 cancer centers to evaluate two paclitaxel and cisplatin–containing regimens, one with FU (PCF) and the other without (PC) in patients with resected gastric cancer. Patients received two cycles of postoperative chemotherapy followed by 45 Gy of radiation with either concurrent FU and paclitaxel or paclitaxel and cisplatin. The primary objective was to show an improvement in 2-year DFS to 67% as compared with INT 0116. Results From May 2001 to February 2004 (study closure), 78 patients entered this study, and 73 were evaluable. At the planned interim analysis of 22 patients on PCF, grade 3 or higher GI toxicity was 59%. This was significantly worse than INT0116, and this arm was closed. Accrual continued on PC. The median DFS was 14.6 months for PCF and has not been reached for PC. For PC the 2-year DFS is 52% (95% CI, 36% to 68%). Conclusion Though PC appears to be safe and the median DFS favorable, the DFS failed to exceed the lower bound of 52.9% for the targeted 67% DFS at 2 years and can not be recommended as the adjuvant arm for future randomized trials. PMID:19273696

Factors Affecting Myocardial Infarction in Cervical Cancer Patients: A Population-Based Study

PubMed Central

Hsieh, Chen-Hsi; Chiou, Wen-Yen; Lee, Ching-Chih; Lee, Moon-Sing; Lin, Hon-Yi; Su, Yu-Chieh; Hung, Shih-Kai

2013-01-01

Background Radiotherapy (RT) or concurrent chemoradiation therapy has been suggested to increase the risk of coronary heart disease for cervical cancer patients, but the results of studies have been inconsistent. Therefore, we aimed to investigate the factors which influence the risk of developing myocardial infarction (MI) in cervical cancer patients with a large, nationwide cohort. Methods The study analyzed data from the 1996 to 2010 National Health Insurance Research Database provided by the National Health Research Institutes in Taiwan. The assessed number of patients with cervical cancer with radiotherapy only, surgery with bilateral oophorectomy only, and with appendectomy were 308, 323 and 229, respectively. The Kaplan-Meier method and the Cox proportional hazards model were used to assess the risk of myocardial infarction. Results The adjusted hazard ratio for cervical cancer in patients with MI was 1.97 (95% CI, 0.97 - 3.91; P = 0.05) for the group that received RT alone, and 2.13 (95% CI, 1.11 - 3.75; P = 0.01) for the surgery group when compared with controls. The more risk comorbidities they have, the higher the risk of myocardial infarction would be for the patients. Conclusion The incidence of MI was significantly higher among cervical cancer patients with RT alone or surgery with bilateral oophorectomy alone than among general populations. RT might be as a factor to increase risk as bilateral oophorectomy. Whether RT itself triggers menopause or impairs the ovarian hormone production that increases the risk of MI needs to be further investigated. PMID:24171059

Localized delivery of chemotherapy to the cervix for radiosensitization.

PubMed

Hodge, Lucy S; Downs, Levi S; Chura, Justin C; Thomas, Sajeena G; Callery, Patrick S; Soisson, A Patrick; Kramer, Paul; Wolfe, Stephen S; Tracy, Timothy S

2012-10-01

Chemoradiation is the mainstay of therapy for advanced cervical cancer, with the most effective treatment regimens involving combinations of radiosensitizing agents. However, administration of radiosensitizing chemotherapeutics concurrently with pelvic radiation is not without side effects. The aim of this study was to examine the utility of localized drug delivery as a means of improving drug targeting of radiosensitizing chemotherapeutics to the cervix while limiting systemic toxicities. An initial proof-of-concept study was performed in 14 healthy women following local administration of diazepam utilizing a novel cervical delivery device (CerviPrep™). Uterine vein and peripheral blood samples were collected and diazepam was measured using a GC-MS method. In the follow-up study, gemcitabine was applied to the cervix in 17 women undergoing hysterectomy for various gynecological malignancies. Cervical tissue, uterine vein blood samples, and peripheral plasma were collected, and gemcitabine and its deaminated metabolite 2',2'-difluorodeoxyuridine (dFdU) were measured using HPLC-UV and LC/MS methods. Targeted delivery of diazepam to the cervix was consistent with parent drug detectable in the uterine vein of 13 of 14 women. In the second study, pharmacologically relevant concentrations of gemcitabine (0.01-6.6 nmol/g tissue) were detected in the cervical tissue of 11 of 16 available specimens with dFdU measureable in 15 samples (0.04-8.8 nmol/g tissue). Neither gemcitabine nor its metabolites were detected in the peripheral plasma of any subject. Localized drug delivery to the cervix is possible and may be useful in limiting toxicity associated with intravenous administration of chemotherapeutics for radiosensitization. Copyright © 2012 Elsevier Inc. All rights reserved.

Prospective study of neoadjuvant chemoradiotherapy using intensity-modulated radiotherapy and 5 fluorouracil for locally advanced rectal cancer - toxicities and response assessment.

PubMed

Simson, David K; Mitra, Swarupa; Ahlawat, Parveen; Saxena, Upasna; Sharma, Manoj Kumar; Rawat, Sheh; Singh, Harpreet; Bansal, Babita; Sripathi, Lalitha Kameshwari; Tanwar, Aditi

2018-01-01

The past 2 decades witnessed the strengthening of evidence favoring the role of neoadjuvant chemoradiation (CHRT) in the treatment of locally advanced rectal cancer. The study aims to evaluate the response and acute toxicities to neoadjuvant CHRT using intensity-modulated radiotherapy (IMRT) in the treatment of rectal cancer. Predictive factors to achieve pathological complete response (pCR) were analyzed, as a secondary endpoint. All consecutive patients who underwent IMRT as part of neoadjuvant CHRT in the treatment of rectal cancer between August 2014 and December 2016 at a tertiary cancer care center were accrued for the study. The cohort underwent CHRT with IMRT technique at a dose of 50.4 Gy in 28 fractions concurrent with continuous infusion of 5 fluorouracil during the first and the last 4 days of CHRT. Surgery was performed 6 weeks later and the pathological response to CHRT was noted. Forty-three subjects were accrued for the study. Radiation dermatitis and diarrhea were the only observed grade ≥3 acute toxicities. Sphincter preservation rate (SPR) was 43.3%. pCR was observed in 32.6%. Univariate and multivariate logistic regression showed that carcinoembryonic antigen was the only independent predictive factor to achieve pCR. IMRT as part of neoadjuvant CHRT in the treatment of locally advanced rectal cancer is well tolerated and gives comparable results with respect to earlier studies in terms of pathological response and SPR. Further randomized controlled studies are needed to firmly state that IMRT is superior to 3-dimensional conformal radiotherapy.

Arterial chemoradiotherapy for carcinomas of the external auditory canal and middle ear.

PubMed

Fujiwara, Masayuki; Yamamoto, Satoshi; Doi, Hiroshi; Takada, Yasuhiro; Odawara, Soichi; Niwa, Yasue; Ishikura, Reiichi; Kamikonya, Norihiko; Terada, Tomonori; Uwa, Nobuhiro; Sagawa, Kosuke; Hirota, Shozo

2015-03-01

The purpose of this study was to estimate the efficacy of superselective arterial chemoradiotherapy for locally advanced carcinomas of the external auditory canal and middle ear. A retrospective study of clinical data for consecutive patients with locally advanced carcinomas of the external auditory canal and middle ear. Thirteen patients with locally advanced carcinomas of the external auditory canal and middle ear (T3: one patient, T4: 12 patients) were reviewed. The median follow-up duration in the living patients was 33 months. The total dose of radiation therapy was 60 Gy using conventional fractionation. Four, five, or six courses of a superselective arterial infusion (cisplatin 50 mg) were given weekly. The overall survival and progression-free survival rates at 2 years, calculated by the Kaplan-Meier method, were 58.7% and 53.8%, respectively. No late-phase adverse effects due to chemoradiation and no adverse effects due to catheterization were observed. These results suggest that superselective arterial chemoradiation can be a treatment option for locally advanced carcinomas of the external auditory canal and middle ear. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Current and future treatment options for esophageal cancer in the elderly.

PubMed

Bollschweiler, Elfriede; Plum, Patrick; Mönig, Stefan P; Hölscher, Arnulf H

2017-07-01

Esophageal cancer is the eighth most common cancer globally and has the sixth worst prognosis because of its aggressiveness and poor survival. Data regarding cancer treatment in older patients is limited because the elderly have been under-represented in clinical trials. Therefore, we reviewed the existing literature regarding treatment results for elderly patients (70+ years). Areas covered: We used pubmed to analyze the actual literature according to elderly esophageal cancer patients with subheading of incidence, esophagectomy, chemoradiation or chemotherapy. The main points of interest were treatment options for patients with Barrett's esophagus or early carcinoma, advanced tumor stages, and inoperable cancer. Expert opinion: The incidence of esophageal cancer has been increasing over the past thirty years, with a rapid increase of esophageal adenocarcinoma in Western industrialized nations. Patients aged over 60 years have been particularly affected. In this review, we have shown that elderly patients with esophageal cancer have various alternatives for adequate treatment. Clinical evaluation of comorbidity is necessary to make treatment decisions. Therapeutic options for early carcinomas are endoscopic or surgical resection. For elderly patients with advanced carcinomas, preoperative chemoradiation or chemotherapy should be discussed.

Predictive and Prognostic Molecular Biomarkers for Response to Neoadjuvant Chemoradiation in Rectal Cancer.

PubMed

Dayde, Delphine; Tanaka, Ichidai; Jain, Rekha; Tai, Mei Chee; Taguchi, Ayumu

2017-03-07

The standard of care in locally advanced rectal cancer is neoadjuvant chemoradiation (nCRT) followed by radical surgery. Response to nCRT varies among patients and pathological complete response is associated with better outcome. However, there is a lack of effective methods to select rectal cancer patients who would or would not have a benefit from nCRT. The utility of clinicopathological and radiological features are limited due to lack of adequate sensitivity and specificity. Molecular biomarkers have the potential to predict response to nCRT at an early time point, but none have currently reached the clinic. Integration of diverse types of biomarkers including clinicopathological and imaging features, identification of mechanistic link to tumor biology, and rigorous validation using samples which represent disease heterogeneity, will allow to develop a sensitive and cost-effective molecular biomarker panel for precision medicine in rectal cancer. Here, we aim to review the recent advance in tissue- and blood-based molecular biomarker research and illustrate their potential in predicting nCRT response in rectal cancer.

CLOSURE OF LARYNGECTOMY DEFECTS IN THE AGE OF CHEMORADIATION THERAPY

PubMed Central

Hanasono, Matthew M.; Lin, Derrick; Wax, Mark K.

2014-01-01

The use of chemoradiation therapy in laryngeal cancer has resulted in significant reconstructive challenges. Although reconstruction of salvage laryngectomy defects remains controversial, current literature supports aggressive management of these defects with vascularized tissue, even when there is sufficient pharyngeal tissue present for primary closure. Significant advancement in reconstructive techniques has permitted improved outcomes in patients with advanced disease who require total laryngopharyngectomy or total laryngoglossectomy. Use of enteric and fasciocutaneous flaps result in good patient outcomes. Finally, wound complication rates after salvage surgery approach 60% depending on comorbid conditions such as cardiac insufficiency, hypothyroidism, or extent of previous treatment. Neck dehiscence, great vessel exposure, fistula formation, or cervical skin necrosis results in complex wounds that can often be treated initially with negative pressure dressings followed by definitive reconstruction. The timing of repair and approach to the vessel-depleted neck also present challenges in this patient population. Currently, there is significant institutional bias in the management of the patient with postchemoradiation salvage laryngectomy. Future prospective multi-institutional studies are certainly needed to more clearly define optimal treatment of these difficult patients. PMID:21416549

Celiac Node Failure Patterns After Definitive Chemoradiation for Esophageal Cancer in the Modern Era

DOE Office of Scientific and Technical Information (OSTI.GOV)

Amini, Arya; UC Irvine School of Medicine, Irvine, California; Xiao Lianchun

2012-06-01

Purpose: The celiac lymph node axis acts as a gateway for metastatic systemic spread. The need for prophylactic celiac nodal coverage in chemoradiation therapy for esophageal cancer is controversial. Given the improved ability to evaluate lymph node status before treatment via positron emission tomography (PET) and endoscopic ultrasound, we hypothesized that prophylactic celiac node irradiation may not be needed for patients with localized esophageal carcinoma. Methods and Materials: We reviewed the radiation treatment volumes for 131 patients who underwent definitive chemoradiation for esophageal cancer. Patients with celiac lymph node involvement at baseline were excluded. Median radiation dose was 50.4 Gy.more » The location of all celiac node failures was compared with the radiation treatment plan to determine whether the failures occurred within or outside the radiation treatment field. Results: At a median follow-up time of 52.6 months (95% CI 46.1-56.7 months), 6 of 60 patients (10%) without celiac node coverage had celiac nodal failure; in 5 of these patients, the failures represented the first site of recurrence. Of the 71 patients who had celiac coverage, only 5 patients (7%) had celiac region relapse. In multivariate analyses, having a pretreatment-to-post-treatment change in standardized uptake value on PET >52% (odds ratio [OR] 0.198, p = 0.0327) and having failure in the clinical target volume (OR 10.72, p = 0.001) were associated with risk of celiac region relapse. Of those without celiac coverage, the 6 patients that later developed celiac failure had a worse median overall survival time compared with the other 54 patients who did not fail (median overall survival time: 16.5 months vs. 31.5 months, p = 0.041). Acute and late toxicities were similar in both groups. Conclusions: Although celiac lymph node failures occur in approximately 1 of 10 patients, the lack of effective salvage treatments and subsequent low morbidity may justify prophylactic treatment in distal esophageal cancer patients.« less

National evaluation of multidisciplinary quality metrics for head and neck cancer.

PubMed

Cramer, John D; Speedy, Sedona E; Ferris, Robert L; Rademaker, Alfred W; Patel, Urjeet A; Samant, Sandeep

2017-11-15

The National Quality Forum has endorsed quality-improvement measures for multiple cancer types that are being developed into actionable tools to improve cancer care. No nationally endorsed quality metrics currently exist for head and neck cancer. The authors identified patients with surgically treated, invasive, head and neck squamous cell carcinoma in the National Cancer Data Base from 2004 to 2014 and compared the rate of adherence to 5 different quality metrics and whether compliance with these quality metrics impacted overall survival. The metrics examined included negative surgical margins, neck dissection lymph node (LN) yield ≥ 18, appropriate adjuvant radiation, appropriate adjuvant chemoradiation, adjuvant therapy within 6 weeks, as well as overall quality. In total, 76,853 eligible patients were identified. There was substantial variability in patient-level adherence, which was 80% for negative surgical margins, 73.1% for neck dissection LN yield, 69% for adjuvant radiation, 42.6% for adjuvant chemoradiation, and 44.5% for adjuvant therapy within 6 weeks. Risk-adjusted Cox proportional-hazard models indicated that all metrics were associated with a reduced risk of death: negative margins (hazard ratio [HR] 0.73; 95% confidence interval [CI], 0.71-0.76), LN yield ≥ 18 (HR, 0.93; 95% CI, 0.89-0.96), adjuvant radiation (HR, 0.67; 95% CI, 0.64-0.70), adjuvant chemoradiation (HR, 0.84; 95% CI, 0.79-0.88), and adjuvant therapy ≤6 weeks (HR, 0.92; 95% CI, 0.89-0.96). Patients who received high-quality care had a 19% reduced adjusted hazard of mortality (HR, 0.81; 95% CI, 0.79-0.83). Five head and neck cancer quality metrics were identified that have substantial variability in adherence and meaningfully impact overall survival. These metrics are appropriate candidates for national adoption. Cancer 2017;123:4372-81. © 2017 American Cancer Society. © 2017 American Cancer Society.

SU-E-J-268: Change of CT Number During the Course of Chemoradiation Therapy for Pancreatic Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, X; Dalah, E; Liu, F

2015-06-15

Purpose: It has been observed radiation can induce changes in CT number (CTN) inside tumor during the course of radiation therapy (RT) for several tumor sites including lung and head and neck, suggesting that the CTN change may be potentially used to assess RT response. In this study, we investigate the CTN changes inside tumor during the course of chemoradiation therapy (CRT) for pancreatic cancer. Methods: Daily diagnostic-quality CT data acquired during IGRT for 17 pancreatic head cancer patients using an in-room CT (CTVision, Siemens) were analyzed. All patients were treated with a radiation dose of 50.4 in 1.8 Gymore » per fraction. On each daily CT set, The contour of the pancreatic head, included in the treatment target, was generated by populating the pancreatic head contour from the planning CT or MRI using an auto-segmentation tool based on deformable registration (ABAS, Elekta) with manual editing if necessary. The CTN at each voxel in the pancreatic head contour was extracted and the 3D distribution of the CTNs was processed using MATLAB. The mean value of CTN distribution was used to quantify the daily CTN change in the pancreatic head. Results: Reduction of CTN in pancreatic head was observed during the CRT delivery in 14 out the 17 (82%) patients studied. Although the average reduction is only 3.5 Houncefield Unit (HU), this change is significant (p<0.01). Among them, there are 7 patients who had a CTN drop larger than 5 HU, ranging from 6.0 to 11.8 HU. In contrast to this trend, CTN was increased in 3 patients. Conclusion: Measurable changes in the CT number in tumor target were observed during the course of chemoradiation therapy for the pancreas cancer patients, indicating this radiation-induced CTN change may be used to assess treatment response.« less

Definitive Chemoradiation Therapy Following Surgical Resection or Radiosurgery Plus Whole-Brain Radiation Therapy in Non-Small Cell Lung Cancer Patients With Synchronous Solitary Brain Metastasis: A Curative Approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parlak, Cem, E-mail: cemparlak@gmail.com; Mertsoylu, Hüseyin; Güler, Ozan Cem

2014-03-15

Purpose/Objectives: The aim of this study was to evaluate the impact of definitive thoracic chemoradiation therapy following surgery or stereotactic radiosurgery (SRS) and whole-brain radiation therapy (WBRT) on the outcomes of patients with non-small cell lung cancer (NSCLC) with synchronous solitary brain metastasis (SSBM). Methods and Materials: A total of 63 NSCLC patients with SSBM were retrospectively evaluated. Patients were staged using positron emission tomography-computed tomography in addition to conventional staging tools. Thoracic radiation therapy (TRT) with a total dose of 66 Gy in 2 Gy fractions was delivered along with 2 cycles of cisplatin-based chemotherapy following either surgery plus 30 Gy ofmore » WBRT (n=33) or SRS plus 30 Gy of WBRT (n=30) for BM. Results: Overall, the treatment was well tolerated. All patients received planned TRT, and 57 patients (90.5%) were also able to receive 2 cycles of chemotherapy. At a median follow-up of 25.3 months (7.1-52.1 months), the median months of overall, locoregional progression-free, neurological progression-free, and progression-free survival were 28.6, 17.7, 26.4, and 14.6, respectively. Both univariate and multivariate analyses revealed that patients with a T1-T2 thoracic disease burden (P=.001), a nodal stage of N0-N1 (P=.003), and no weight loss (P=.008) exhibited superior survival. Conclusions: In the present series, surgical and radiosurgical treatments directed toward SSBM in NSCLC patients were equally effective. The similarities between the present survival outcomes and those reported in other studies for locally advanced NSCLC patients indicate the potentially curative role of definitive chemoradiation therapy for highly selected patients with SSBM.« less

Role of genetic polymorphisms in NFKB-mediated inflammatory pathways in response to primary chemoradiation therapy for rectal cancer.

PubMed

Dzhugashvili, Maia; Luengo-Gil, Ginés; García, Teresa; González-Conejero, Rocío; Conesa-Zamora, Pablo; Escolar, Pedro Pablo; Calvo, Felipe; Vicente, Vicente; Ayala de la Peña, Francisco

2014-11-01

To investigate whether polymorphisms of genes related to inflammation are associated with pathologic response (primary endpoint) in patients with rectal cancer treated with primary chemoradiation therapy (PCRT). Genomic DNA of 159 patients with locally advanced rectal cancer treated with PCRT was genotyped for polymorphisms rs28362491 (NFKB1), rs1213266/rs5789 (PTGS1), rs5275 (PTGS2), and rs16944/rs1143627 (IL1B) using TaqMan single nucleotide polymorphism genotyping assays. The association between each genotype and pathologic response (poor response vs complete or partial response) was analyzed using logistic regression models. The NFKB1 DEL/DEL genotype was associated with pathologic response (odds ratio [OR], 6.39; 95% confidence interval [CI], 0.78-52.65; P=.03) after PCRT. No statistically significant associations between other polymorphisms and response to PCRT were observed. Patients with the NFKB1 DEL/DEL genotype showed a trend for longer disease-free survival (log-rank test, P=.096) and overall survival (P=.049), which was not significant in a multivariate analysis that included pathologic response. Analysis for 6 polymorphisms showed that patients carrying the haplotype rs28362491-DEL/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G (13.7% of cases) had a higher response rate to PCRT (OR, 8.86; 95% CI, 1.21-64.98; P=.034) than the reference group (rs28362491-INS/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G). Clinically significant (grade ≥2) acute organ toxicity was also more frequent in patients with that same haplotype (OR, 4.12; 95% CI, 1.11-15.36; P=.037). Our results suggest that genetic variation in NFKB-related inflammatory pathways might influence sensitivity to primary chemoradiation for rectal cancer. If confirmed, an inflammation-related radiogenetic profile might be used to select patients with rectal cancer for preoperative combined-modality treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

Association of Aurora-A (STK15) Kinase Polymorphisms With Clinical Outcome of Esophageal Cancer Treated With Preoperative Chemoradiation

PubMed Central

Pan, Jennifer Y.; Ajani, Jaffer A.; Gu, Jian; Gong, Yubo; Quin, Angel; Hung, Maosheng; Wu, Xifeng; Izzo, Julie G.

2013-01-01

BACKGROUND: Aurora-A/STK15 is a serine/threonine kinase critical for regulated chromosome segregation and cytokinesis. We investigated the association between 2 nonsynonymous single nucleotide polymorphisms in the coding region of STK15, T91A (Phe31Ile) and G169A (Val57Ile), and clinical outcome of esophageal cancer treated with preoperative chemoradiation. METHODS: Genotypes at Phe31Ile and Val57Ile were assessed from peripheral blood lymphocytes of 190 esophageal cancer patients and were correlated to response to treatment, recurrence rate, risk of death, disease-free survival (DFS) and median survival time (MTS). RESULTS: All patients had resectable esophageal or gastroesophageal junction cancer and received preoperative chemoradiation followed by esophagectomy. The heterozygous variant Phe31/Ile variant was significantly associated with tumor recurrence (odds ratio [OR] = 4.39; 95% confidence interval [CI], 2.12-8.94; P < .001), shorter DFS (P = .0001), and shorter MTS (P = .012). For patients receiving cisplatin-based therapy, only the variant Phe31/Ile had an adverse effect on response (OR = 2.8; 95% CI, 1.01-5.17; P = .048) and MTS (P = .026). The variant 91A-169G haplotype carried a significant risk for lack of complete response (OR = 2.54; 95% CI, 1.15-5.54) and higher rate of recurrence (OR = 2.73; 95%CI, 1.00-7.29). The presence of at least 1 variant allele at each locus further increased the risk of recurrence (adjusted OR = 6.21; 95% CI, 2.28-17.11; P = <.001), and was associated significantly shorter DFS (P = .003). CONCLUSIONS: Our study shows that functional SNPs in the STK15 gene are associated with higher rate of recurrence, higher likelihood of chemoratiotherapy-resistance, shorter DFS, and shorter MTS. Confirmation of our data and understanding the mechanisms through which STK15 functional SNPs mediate resistance to chemoradiotherapy are warranted. PMID:22213102

Effect of valproic acid on seizure control and on survival in patients with glioblastoma multiforme

PubMed Central

Kerkhof, Melissa; Dielemans, Janneke C. M.; van Breemen, Melanie S.; Zwinkels, Hanneke; Walchenbach, Robert; Taphoorn, Martin J.; Vecht, Charles J.

2013-01-01

Background To examine the efficacy of valproic acid (VPA) given either with or without levetiracetam (LEV) on seizure control and on survival in patients with glioblastoma multiforme (GBM) treated with chemoradiation. Methods A retrospective analysis was performed on 291 patients with GBM. The efficacies of VPA and LEV alone and as polytherapy were analyzed in 181 (62%) patients with seizures with a minimum follow-up of 6 months. Cox-regression survival analysis was performed on 165 patients receiving chemoradiation with temozolomide of whom 108 receiving this in combination with VPA for at least 3 months. Results Monotherapy with either VPA or LEV was instituted in 137/143 (95.8%) and in 59/86 (68.6%) on VPA/LEV polytherapy as the next regimen. Initial freedom from seizure was achieved in 41/100 (41%) on VPA, in 16/37 (43.3%) on LEV, and in 89/116 (76.7%) on subsequent VPA/LEV polytherapy. At the end of follow-up, seizure freedom was achieved in 77.8% (28/36) on VPA alone, in 25/36 (69.5%) on LEV alone, and in 38/63 (60.3%) on VPA/LEV polytherapy with ongoing seizures on monotherapy. Patients using VPA in combination with temozolomide showed a longer median survival of 69 weeks (95% confidence interval [CI]: 61.7–67.3) compared with 61 weeks (95% CI: 52.5–69.5) in the group without VPA (hazard ratio, 0.63; 95% CI: 0.43–0.92; P = .016), adjusting for age, extent of resection, and O6-DNA methylguanine-methyltransferase promoter methylation status. Conclusions Polytherapy with VPA and LEV more strongly contributes to seizure control than does either as monotherapy. Use of VPA together with chemoradiation with temozolomide results in a 2-months’ longer survival of patients with GBM. PMID:23680820

PubMed Central

PUTTEN, L.; DOORNAERT, P.A.; BUTER, J.; EERENSTEIN, S.E.J.; RIETVELD, D.H.F.; KUIK, D.J.; LEEMANS, C.R.

2015-01-01

SUMMARY Our objective was to evaluate recurrence patterns of hypopharyngeal and laryngeal carcinoma after chemoradiation and options for salvage surgery, with special emphasis on elderly patients. In a retrospective study all patients who underwent chemoradiation for hypopharyngeal and laryngeal carcinoma in a tertiary care academic center from 1990 through 2010 were evaluated. Primary outcome measures were the survival and complication rates of patients undergoing salvage surgery, especially in elderly patients. Secondary outcome measures were the predictors for salvage surgery for patients with locoregional recurrence after failed chemoradiotherapy. A review of the literature was performed. Of the 136 included patients, 60 patients had recurrent locoregional disease, of whom 22 underwent salvage surgery. Fifteen patients underwent a total laryngectomy with neck dissection(s) and 7 neck dissection without primary tumour surgery. Independent predictors for salvage surgery within the group of 60 patients with recurrent disease, were age under the median of 59 years (p = 0.036) and larynx vs. hypopharynx (p = 0.002) in multivariate analyses. The complication rate was 68% (14% major and 54% minor), with fistulas in 23% of the patients. Significantly more wound related complications occurred in patients with current excessive alcohol use (p = 0.04). Five-year disease free control rate of 35%, overall survival rate of 27% and disease specific survival rate of 35% were found. For the 38 patients who were not suitable for salvage surgery, median survival was 12 months. Patients in whom the tumour was controlled had a 5-year overall survival of 70%. In patients selected for salvage surgery age was not predictive for complications and survival. In conclusion, at two years follow-up after chemoradiation 40% of the patients were diagnosed with recurrent locoregional disease. One third underwent salvage surgery with 35% 5-year disease specific survival and 14% major complications. Older patients selected for salvage surgery had a similar complication rate and survival as younger patients. PMID:26246660

The effects of exercise on pain, fatigue, insomnia, and health perceptions in patients with operable advanced stage rectal cancer prior to surgery: a pilot trial.

PubMed

Brunet, Jennifer; Burke, Shaunna; Grocott, Michael P W; West, Malcolm A; Jack, Sandy

2017-02-23

Promoting quality of life (QoL) is a key priority in cancer care. We investigated the hypothesis that, in comparison to usual care, exercise post-neoadjuvant chemoradiation therapy/prior to surgical resection will reduce pain, fatigue, and insomnia, and will improve physical and mental health perceptions in patients with locally advanced stage rectal cancer. In this non-randomized controlled pilot trial, patients in the supervised exercise group (EG; M age  = 64 years; 64% male) and in the control group (CG; M age  = 72 years; 69% male) completed the European Organization for Research and Treatment of Cancer core Quality of Life questionnaire and the RAND 36-Item Health Survey three times: pre-neoadjuvant chemoradiation therapy (Time 1; n EC  = 24; n CG  = 11), post-neoadjuvant chemoradiation therapy/pre-exercise intervention (Time 2; n EC  = 23; n CG  = 10), and post-exercise intervention (Time 3; n EC  = 22; n CG  = 10). The 6-week exercise intervention was delivered in hospital and comprised of interval aerobic training. Patients trained in pairs three times per week for 30 to 40 min. Data were analyzed by Mann-Whitney tests and by Wilcoxon matched-pairs signed-rank tests. No significant between-group differences in changes were found for any of the outcomes. In both groups, fatigue levels decreased and physical health perceptions increased from pre- to post-exercise intervention. Pain levels also decreased from pre- to post-exercise intervention, albeit not significantly. The findings from this study can be used to guide a more definitive trial as they provide preliminary evidence regarding the potential effects of pre-operative exercise on self-reported pain, fatigue, insomnia, and health perceptions in patients with locally advanced rectal cancer. This study has been registered with clinicaltrials.gov (NCT01325909; March 29, 2011).

Prognostic factors, patterns of recurrence and toxicity for patients with esophageal cancer undergoing definitive radiotherapy or chemo-radiotherapy.

PubMed

Haefner, Matthias F; Lang, Kristin; Krug, David; Koerber, Stefan A; Uhlmann, Lorenz; Kieser, Meinhard; Debus, Juergen; Sterzing, Florian

2015-07-01

The aim of this study was to evaluate the effectiveness and tolerability of definitive chemo-radiation or radiotherapy alone in patients with esophageal cancer. We retrospectively analyzed the medical records of n = 238 patients with squamous cell carcinoma or adenocarcinoma of the esophagus treated with definitive radiotherapy with or without concomitant chemotherapy at our institution between 2000 and 2012. Patients of all stages were included to represent actual clinical routine. We performed univariate and multivariate analysis to identify prognostic factors for overall survival (OS) and progression-free survival (PFS). Moreover, treatment-related toxicity and patterns of recurrence were assessed. Patients recieved either chemo-radiation (64%), radiotherapy plus cetuximab (10%) or radiotherapy alone (26%). In 69%, a boost was applied, resulting in a median cumulative dose of 55.8 Gy; the remaining 31% received a median total dose of 50 Gy. For the entire cohort, the median OS and PFS were 15.0 and 11.0 months, respectively. In multivariate analysis, important prognostic factors for OS and PFS were T stage (OS: P = 0.005; PFS: P = 0.006), M stage (OS: P = 0.015; PFS: P = 0.003), concomitant chemotherapy (P < 0.001) and radiation doses of >55 Gy (OS: P = 0.019; PFS: P = 0.022). Recurrences occurred predominantly as local in-field relapse or distant metastases. Toxicity was dominated by nutritional impairment (12.6% with G3/4 dysphagia) and chemo-associated side effects. Definitive chemo-radiation in patients with esophageal cancer results in survival rates comparable with surgical treatment approaches. However, local and distant recurrence considerably restrict prognosis. Further advances in radio-oncological treatment strategies are necessary for improving outcome. © The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Toxicity Profile and Pharmacokinetic Study of A Phase I Low-Dose Schedule-Dependent Radiosensitizing Paclitaxel Chemoradiation Regimen for Inoperable Non-Small-Cell Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Yuhchyau; Pandya, Kishan J.; Feins, Richard

Purpose: We report the toxicity profile and pharmacokinetic data of a schedule-dependent chemoradiation regimen using pulsed low-dose paclitaxel for radiosensitization in a Phase I study for inoperable non-small-cell lung cancer. Methods and Materials: Paclitaxel at escalating doses of 15 mg/m{sup 2}, 20 mg/m{sup 2}, and 25 mg/m{sup 2} were infused on Monday, Wednesday, and Friday with daily chest radiation in cohorts of 6 patients. Daily radiation was delayed for maximal G2/M arrest and apoptotic effect, an observation from preclinical investigations. Plasma paclitaxel concentration was determined by high-performance liquid chromatography. Results: Dose-limiting toxicities included 3 of 18 patients with Grade 3more » pneumonitis and 3 of 18 patients with Grade 3 esophagitis. There was no Grade 4 or 5 pneumonitis or esophagitis. There was also no Grade 3 or 4 neutropenia, thrombocytopenia, anemia or neuropathy. For Dose Levels I (15 mg/m{sup 2}), II (20 mg/m{sup 2}), and III (25 mg/m{sup 2}), the mean peak plasma level was 0.23 {+-} 0.06 {mu}mol/l, 0.32 {+-} 0.05 {mu}mol/l, and 0.52 {+-} 0.14 {mu}mol/l, respectively; AUC was 0.44 {+-} 0.09 {mu}mol/l, 0.61 {+-} 0.1 {mu}mol/l, and 0.96 {+-} 0.23 {mu}mol/l, respectively; and duration of drug concentration >0.05 {mu}mol/l (t > 0.05 {mu}mol/l) was 1.6 {+-} 0.3 h, 1.9 {+-} 0.2 h, and 3.0 {+-} 0.9 h, respectively. Conclusion: Pulsed low-dose paclitaxel chemoradiation is associated with low toxicity. Pharmacokinetic data showed that plasma paclitaxel concentration >0.05 {mu}mol/l for a minimum of 1.6 h was sufficient for effective radiosensitization.« less

Anal sphincter dysfunction in patients treated with primary radiotherapy for anal cancer: a study with the functional lumen imaging probe.

PubMed

Haas, Susanne; Faaborg, Pia; Liao, Donghua; Laurberg, Søren; Gregersen, Hans; Lundby, Lilly; Christensen, Peter; Krogh, Klaus

2018-04-01

Sphincter-sparing radiotherapy or chemoradiation are standard treatments for patients with anal cancer. The ultimate treatment goal is full recovery from anal cancer with preserved anorectal function. Unfortunately, long-term survivors often suffer from severe anorectal symptoms. The aim of the present study was to characterize changes in anorectal physiology after radiotherapy for anal cancer. We included 13 patients (10 women, age 63.4 ± 1.9) treated with radiotherapy or chemoradiation for anal cancer and 14 healthy volunteers (9 women, age 61.4 ± 1.5). Symptoms were assessed with scores for fecal incontinence and low anterior resection syndrome. Anorectal physiology was examined with anorectal manometry and the Functional Lumen Imaging Probe. Patients had a median Wexner fecal incontinence score of 5 (0-13) and a median LARS score of 29 (0-39). Compared to healthy volunteers, patients had lower mean (±SE) anal -resting (38 ± 5 vs. 71 ± 6, p < .001) and -squeeze pressures (76 ± 11 vs. 165 ± 15, p < .001). Patients also had lower anal yield pressure (15.5 ± 1.3 mmHg vs. 28.0 ± 2.0 mmHg, p < .001), higher distensibility, and lower resistance to flow (reduced resistance ratio of the anal canal during distension, q = 5.09, p < .001). No differences were found in median (range) rectal volumes at first sensation (70.5 (15-131) vs. 57 (18-132) ml, p > .4), urge (103 (54-176) vs. 90 (32-212), p > .6) or maximum tolerable volume (173 (86-413) vs. 119.5 (54-269) ml, p > .10). Patients treated with radiotherapy or chemoradiation for anal cancer have low anal resting and squeeze pressures as well as reduced resistance to distension and flow.

Nintedanib Compared With Placebo in Treating Against Radiation-Induced Pneumonitis in Patients With Non-small Cell Lung Cancer That Cannot Be Removed by Surgery and Are Undergoing Chemoradiation Therapy

ClinicalTrials.gov

2017-07-08

Radiation-Induced Pneumonitis; Stage IIA Non-Small Cell Lung Carcinoma; Stage IIB Non-Small Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer