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Sample records for neoadjuvant chemoradiation therapy

  1. Neoadjuvant Chemoradiation Therapy Is Beneficial for Clinical Stage T2 N0 Esophageal Cancer Patients Due to Inaccurate Preoperative Staging

    PubMed Central

    Zhang, Jennifer Q.; Hooker, Craig M.; Brock, Malcolm V.; Shin, James; Lee, Sue; How, Remealle; Franco, Noreli; Prevas, Helen; Hulbert, Alicia; Yang, Stephen C.

    2014-01-01

    Background It remains unclear if patients with clinical stage T2 N0 (cT2 N0) esophageal cancer should be offered induction therapy vs surgical intervention alone. Methods This was a retrospective cohort study of cT2 N0 patients undergoing induction therapy, followed by surgical resection, or resection alone, at the Johns Hopkins Hospital from 1989 to 2009. Kaplan-Meier analysis was used to compare all-cause mortality in cT2 N0 patients who had resection alone vs those who had induction chemoradiation therapy, followed by resection. Results A study cohort of 69 patients was identified and divided into two groups: 55 patients (79.7%) received induction therapy and 14 (20.3%) did not. No statistically significant difference in 5-year survival rate was observed for the two groups: 49.5% for the resection-only group and 53.8% for the induction group. More than 50% of cT2 N0 patients were understaged. Conclusions For cT2 N0 esophageal cancer patients, the benefit of neoadjuvant therapy is still unclear. Induction therapy for cT2 N0 did not translate into a statistically significant improvement in survival. However, due to the significant understaging of T2 N0 patients, we recommend neoadjuvant therapy to all cT2N0 patients before operation. PMID:22269708

  2. Interval Between Surgery and Neoadjuvant Chemoradiation Therapy for Distal Rectal Cancer: Does Delayed Surgery Have an Impact on Outcome?

    SciTech Connect

    Habr-Gama, Angelita Perez, Rodrigo Oliva; Proscurshim, Igor; Nunes dos Santos, Rafael Miyashiro; Kiss, Desiderio; Gama-Rodrigues, Joaquim; Cecconello, Ivan

    2008-07-15

    Background: The optimal interval between neoadjuvant chemoradiation therapy (CRT) and surgery in the treatment of patients with distal rectal cancer is controversial. The purpose of this study is to evaluate whether this interval has an impact on survival. Methods and Materials: Patients who underwent surgery after CRT were retrospectively reviewed. Patients with a sustained complete clinical response (cCR) 1 year after CRT were excluded from this study. Clinical and pathologic characteristics and overall and disease-free survival were compared between patients undergoing surgery 12 weeks or less from CRT and patients undergoing surgery longer than 12 weeks from CRT completion and between patients with a surgery delay caused by a suspected cCR and those with a delay for other reasons. Results: Two hundred fifty patients underwent surgery, and 48.4% had CRT-to-surgery intervals of 12 weeks or less. There were no statistical differences in overall survival (86% vs. 81.6%) or disease-free survival rates (56.5% and 58.9%) between patients according to interval ({<=}12 vs. >12 weeks). Patients with intervals of 12 weeks or less had significantly higher rates of Stage III disease (34% vs. 20%; p = 0.009). The delay in surgery was caused by a suspected cCR in 23 patients (interval, 48 {+-} 10.3 weeks). Five-year overall and disease-free survival rates for this subset were 84.9% and 51.6%, not significantly different compared with the remaining group (84%; p = 0.96 and 57.8%; p = 0.76, respectively). Conclusions: Delay in surgery for the evaluation of tumor response after neoadjuvant CRT is safe and does not negatively affect survival. These results support the hypothesis that shorter intervals may interrupt ongoing tumor necrosis.

  3. Residual Tumor After Neoadjuvant Chemoradiation Outside the Radiation Therapy Target Volume: A New Prognostic Factor for Survival in Esophageal Cancer

    SciTech Connect

    Muijs, Christina; Smit, Justin; Karrenbeld, Arend; Beukema, Jannet; Mul, Veronique; Dam, Go van; Hospers, Geke; Kluin, Phillip; Langendijk, Johannes; Plukker, John

    2014-03-15

    Purpose/Objective(s): The aim of this study was to analyze the accuracy of gross tumor volume (GTV) delineation and clinical target volume (CTV) margins for neoadjuvant chemoradiation therapy (neo-CRT) in esophageal carcinoma at pathologic examination and to determine the impact on survival. Methods and Materials: The study population consisted of 63 esophageal cancer patients treated with neo-CRT. GTV and CTV borders were demarcated in situ during surgery on the esophagus, using anatomical reference points to provide accurate information regarding tumor location at pathologic evaluation. To identify prognostic factors for disease-free survival (DFS) and overall survival (OS), a Cox regression analysis was performed. Results: After resection, macroscopic residual tumor was found outside the GTV in 7 patients (11%). Microscopic residual tumor was located outside the CTV in 9 patients (14%). The median follow-up was 15.6 months. With multivariate analysis, only microscopic tumor outside the CTV (hazard ratio [HR], 4.96; 95% confidence interval [CI], 1.03-15.36), and perineural growth (HR, 5.77; 95% CI, 1.27-26.13) were identified as independent prognostic factors for OS. The 1-year OS was 20% for patients with tumor outside the CTV and 86% for those without (P<.01). For DFS, microscopic tumor outside the CTV (HR, 5.92; 95% CI, 1.89-18.54) and ypN+ (HR, 3.36; 95% CI, 1.33-8.48) were identified as independent adverse prognostic factors. The 1-year DFS was 23% versus 77% for patients with or without tumor outside the CTV (P<.01). Conclusions: Microscopic tumor outside the CTV is associated with markedly worse OS after neo-CRT. This may either stress the importance of accurate tumor delineation or reflect aggressive tumor behavior requiring new adjuvant treatment modalities.

  4. MRI Predictive Factors for Tumor Response in Rectal Cancer Following Neoadjuvant Chemoradiation Therapy - Implications for Induction Chemotherapy?

    SciTech Connect

    Yu, Stanley K.T.; Tait, Diana

    2013-11-01

    Purpose: Clinical and magnetic resonance imaging (MRI) characteristics at baseline and following chemoradiation therapy (CRT) most strongly associated with histopathologic response were investigated and survival outcomes evaluated in accordance with imaging and pathological response. Methods and Materials: Responders were defined as mrT3c/d-4 downstaged to ypT0-2 on pathology or low at risk mrT2 downstaged to ypT1 or T0. Multivariate logistic regression of baseline and posttreatment MRI: T, N, extramural venous invasion (EMVI), circumferential resection margin, craniocaudal length <5 cm, and MRI tumor height ≤5 cm were used to identify independent predictor(s) for response. An association between induction chemotherapy and EMVI status was analyzed. Survival outcomes for pathologic and MRI responders and nonresponders were analyzed. Results: Two hundred eighty-one patients were eligible; 114 (41%) patients were pathology responders. Baseline MRI negative EMVI (odds ratio 2.94, P=.007), tumor height ≤5 cm (OR 1.96, P=.02), and mrEMVI status change (positive to negative) following CRT (OR 3.09, P<.001) were the only predictors for response. There was a strong association detected between induction chemotherapy and ymrEMVI status change after CRT (OR 9.0, P<.003). ymrT0-2 gave a positive predictive value of 80% and OR of 9.1 for ypT0-2. ymrN stage accuracy of ypN stage was 75%. Three-year disease-free survival for pathology and MRI responders were similar at 80% and 79% and significantly better than poor responders. Conclusions: Tumor height and mrEMVI status are more important than baseline size and stage of the tumor as predictors of response to CRT. Both MRI- and pathologic-defined responders have significantly improved survival. “Good response” to CRT in locally advanced rectal cancer with ypT0-2 carries significantly better 3-year overall survival and disease-free survival. Use of induction chemotherapy for improving mrEMVI status and knowledge of MRI

  5. Predictors of Survival in Esophageal Squamous Cell Carcinoma with Pathologic Major Response after Neoadjuvant Chemoradiation Therapy and Surgery: The Impact of Chemotherapy Protocols

    PubMed Central

    Li, Chia-Ying; Huang, Pei-Ming; Chu, Pei-Yi; Chen, Po-Ming; Lin, Mong-Wei; Kuo, Shuenn-Wen

    2016-01-01

    Tumor recurrence is an important problem threatening esophageal cancer patients after surgery, even when they achieve a pathologic major response (pMR) after neoadjuvant concurrent chemoradiation therapy (CCRT). The predictors related to overall survival and disease progression for these patients remain elusive. We aimed to identify factors that predict disease progression and overall survival in esophageal squamous cell carcinoma (SCC) patients who achieve a pMR after neoadjuvant CCRT followed by surgery. We conducted a retrospective study to analyze the factors influencing survival and disease progression after esophagectomy for esophageal cancer patients who had a major response to CCRT, which is defined by complete pathological response or microscopic residual disease without lymph node metastasis. From our study cohort, 285 patients underwent CCRT and subsequent esophagectomy; 171 (60%) of these patients achieved pMR. After excluding patients with lymph node metastases, incomplete clinical data, and adenocarcinomas, we enrolled 117 patients in this study. We found that the CCRT regimen was the only factor that influenced overall survival. The overall survival of the patients receiving taxane-incorporated CCRT was superior to that of patients receiving traditional cisplatin and 5-fluorouracil (PF) (P = 0.011). The CCRT regimen can significantly influence the clinical outcome of esophageal SCC patients who achieve pMR after neoadjuvant CCRT and esophagectomy. Incorporation of taxanes into cisplatin-based CCRT may be associated with prolonged survival. PMID:27777949

  6. Self-expanding plastic esophageal stents versus jejunostomy tubes for the maintenance of nutrition during neoadjuvant chemoradiation therapy in patients with esophageal cancer: a retrospective study.

    PubMed

    Siddiqui, A A; Glynn, C; Loren, D; Kowalski, T

    2009-01-01

    In patients undergoing chemoradiotherapy for esophageal cancer, the inability to eat may severely impair nutritional status. We conducted a retrospective study to compare the efficacy of the Polyflex self-expanding silicone stent (PS) versus a jejunostomy tube (JT) for maintaining nutrition during neoadjuvant chemoradiation therapy in patients with esophageal cancer who were scheduled for resectional surgery. Thirty-six patients were treated either with PS placement (12 patients) or JT placement (24 patients) prior to receiving an 8-week course of chemoradiation therapy. Patients were interviewed weekly until cessation of therapy. Patient data were collected on procedural success and complication rates, nutritional status, and dysphagia scores. PS placement was successful in 11 of 12 patients (92%), and those 11 patients were able to resume oral nutrition. Dysphagia scores improved from a mean of 3 to 1 in the PS group (P < 0.005) but did not change significantly in the JT group. PS were removed endoscopically without complications prior to the esophagectomies. Albumin levels and weight increased significantly in both the PS and JT groups. There were no significant differences between groups in the procedural success rates (PS 92% vs. JT 100%, P = 0.33), complication rates (PS 22% vs. JT 4%, P = 0.11), mean increase in weight (PS 4.4 kg vs. JT 4.2 kg, P = 0.59), and mean increase in serum albumin (PS 0.62 g/dL vs. JT 0.44 g/dL, P = 0.05). PS is a safe and effective alternative to a surgical JT for maintaining nutrition in this subset of patients.

  7. Spatial-Temporal [{sup 18}F]FDG-PET Features for Predicting Pathologic Response of Esophageal Cancer to Neoadjuvant Chemoradiation Therapy

    SciTech Connect

    Tan, Shan; Kligerman, Seth; Chen, Wengen; Lu, Minh; Kim, Grace; Feigenberg, Steven; D'Souza, Warren D.; Suntharalingam, Mohan; Lu, Wei

    2013-04-01

    Purpose: To extract and study comprehensive spatial-temporal {sup 18}F-labeled fluorodeoxyglucose ([{sup 18}F]FDG) positron emission tomography (PET) features for the prediction of pathologic tumor response to neoadjuvant chemoradiation therapy (CRT) in esophageal cancer. Methods and Materials: Twenty patients with esophageal cancer were treated with trimodal therapy (CRT plus surgery) and underwent [{sup 18}F]FDG-PET/CT scans both before (pre-CRT) and after (post-CRT) CRT. The 2 scans were rigidly registered. A tumor volume was semiautomatically delineated using a threshold standardized uptake value (SUV) of ≥2.5, followed by manual editing. Comprehensive features were extracted to characterize SUV intensity distribution, spatial patterns (texture), tumor geometry, and associated changes resulting from CRT. The usefulness of each feature in predicting pathologic tumor response to CRT was evaluated using the area under the receiver operating characteristic curve (AUC) value. Results: The best traditional response measure was decline in maximum SUV (SUV{sub max}; AUC, 0.76). Two new intensity features, decline in mean SUV (SUV{sub mean}) and skewness, and 3 texture features (inertia, correlation, and cluster prominence) were found to be significant predictors with AUC values ≥0.76. According to these features, a tumor was more likely to be a responder when the SUV{sub mean} decline was larger, when there were relatively fewer voxels with higher SUV values pre-CRT, or when [{sup 18}F]FDG uptake post-CRT was relatively homogeneous. All of the most accurate predictive features were extracted from the entire tumor rather than from the most active part of the tumor. For SUV intensity features and tumor size features, changes were more predictive than pre- or post-CRT assessment alone. Conclusion: Spatial-temporal [{sup 18}F]FDG-PET features were found to be useful predictors of pathologic tumor response to neoadjuvant CRT in esophageal cancer.

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

    SciTech Connect

    Nakamura, Takatoshi; Yamashita, Keishi; Sato, Takeo; Ema, Akira; Naito, Masanori; Watanabe, Masahiko

    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, 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.

  9. 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

    SciTech Connect

    Sher, David J.; Fidler, Mary Jo; Seder, Christopher W.; Liptay, Michael J.; Koshy, Matthew

    2015-06-01

    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 Gy (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

  10. Association Between Clinically Staged Node-Negative Esophageal Adenocarcinoma and Overall Survival Benefit From Neoadjuvant Chemoradiation

    PubMed Central

    Gabriel, Emmanuel; Attwood, Kristopher; Du, William; Tuttle, Rebecca; Alnaji, Raed M.; Nurkin, Steven; Malhotra, Usha; Hochwald, Steven N.; Kukar, Moshim

    2017-01-01

    Importance While neoadjuvant chemoradiation for esophageal cancer improves oncologic outcomes for a broad group of patients with locally advanced and/or node-positive tumors, it is less clear which specific subset of patients derives most benefit in terms of overall survival (OS). Objective To determine whether neoadjuvant chemoradiation based on esophageal adenocarcinoma histology has similar oncologic outcomes for patients treated with surgery alone when stratified by clinical nodal status. Design, Setting, and Participants A retrospective analysis using the American College of Surgeons National Cancer Database from 1998 to 2006. Patients with esophageal adenocarcinoma histology and clinical stage T1bN1-N3 or T2-T4aN−/+M0 were divided into 2 treatment groups: (1) neoadjuvant chemoradiation followed by surgery and (2) surgery alone. Subset analysis within each treatment group was performed for clinically node-negative patients (cN−) vs node-positive patients (cN+) in conjunction with pathological nodal status. A propensity score–adjusted analysis, which included patient demographics, comorbidity status, and clinical T stage, was also performed. Main Outcome and measures The primary outcome was 3-year OS. Secondary outcomes included margin status, postoperative length of stay, unplanned readmission rate, and 30-day mortality. Results A total of 1309 patients were identified, of whom 539 received neoadjuvant chemoradiation followed by surgery and 770 received surgery alone. Of the 1309 patients, 41.2% (n = 539) received neoadjuvant chemoradiation and 47.2% (n = 618) were cN+. Median follow-up for the entire cohort was 73.3 months (interquartile range, 64.1-93.5 months). The 3-year OS was better for neoadjuvant chemoradiation followed by surgery compared with surgery alone (49% vs 38%, respectively; P < .001). Stratifying based on clinical nodal status, the propensity score–adjusted OS was significantly better for cN+ patients who received neoadjuvant

  11. Local Recurrence After Complete Clinical Response and Watch and Wait in Rectal Cancer After Neoadjuvant Chemoradiation: Impact of Salvage Therapy on Local Disease Control

    SciTech Connect

    Habr-Gama, Angelita; Gama-Rodrigues, Joaquim; São Julião, Guilherme P.; Proscurshim, Igor; Sabbagh, Charles; Lynn, Patricio B.; Perez, Rodrigo O.

    2014-03-15

    Purpose: To review the risk of local recurrence and impact of salvage therapy after Watch and Wait for rectal cancer with complete clinical response (cCR) after chemoradiation therapy (CRT). Methods and Materials: Patients with cT2-4N0-2M0 distal rectal cancer treated with CRT (50.4-54 Gy + 5-fluorouracil-based chemotherapy) and cCR at 8 weeks were included. Patients with cCR were enrolled in a strict follow-up program with no immediate surgery (Watch and Wait). Local recurrence-free survival was compared while taking into account Watch and Wait strategy alone and Watch and Wait plus salvage. Results: 90 of 183 patients experienced cCR at initial assessment after CRT (49%). When early tumor regrowths (up to and including the initial 12 months of follow-up) and late recurrences were considered together, 28 patients (31%) experienced local recurrence (median follow-up time, 60 months). Of those, 26 patients underwent salvage therapy, and 2 patients were not amenable to salvage. In 4 patients, local re-recurrence developed after Watch and Wait plus salvage. The overall salvage rate for local recurrence was 93%. Local recurrence-free survival at 5 years was 69% (all local recurrences) and 94% (after salvage procedures). Thirteen patients (14%) experienced systemic recurrence. The 5-year cancer-specific overall survival and disease-free survival for all patients (including all recurrences) were 91% and 68%, respectively. Conclusions: Local recurrence may develop in 31% of patients with initial cCR when early regrowths (≤12 months) and late recurrences are grouped together. More than half of these recurrences develop within 12 months of follow-up. Salvage therapy is possible in ≥90% of recurrences, leading to 94% local disease control, with 78% organ preservation.

  12. Rectal Cancer: Mucinous Carcinoma on Magnetic Resonance Imaging Indicates Poor Response to Neoadjuvant Chemoradiation

    SciTech Connect

    Oberholzer, Katja; Menig, Matthias; Kreft, Andreas; Schneider, Astrid; Junginger, Theodor; Heintz, Achim; Kreitner, Karl-Friedrich; Hoetker, Andreas M.; Hansen, Torsten; Dueber, Christoph; Schmidberger, Heinz

    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 surgical 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.

  13. The Quality-of-Life Effects of Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer

    SciTech Connect

    Herman, Joseph M.; Narang, Amol K.; Griffith, Kent A.; Zalupski, Mark M.; Reese, Jennifer B.; Gearhart, Susan L.; Azad, Nolifer S.; Chan, June; Olsen, Leah; Efron, Jonathan E.; Lawrence, Theodore S.; Ben-Josef, Edgar

    2013-01-01

    Purpose: Existing studies that examine the effect of neoadjuvant chemoradiation (CRT) for locally advanced rectal cancer on patient quality of life (QOL) are limited. Our goals were to prospectively explore acute changes in patient-reported QOL endpoints during and after treatment and to establish a distribution of scores that could be used for comparison as new treatment modalities emerge. Methods and Materials: Fifty patients with locally advanced rectal cancer were prospectively enrolled at 2 institutions. Validated cancer-specific European Organization for Research and Treatment of Cancer (EORTC QLQ-CR30) and colorectal cancer-specific (EORTC QLQ-CR38 and EORTC QLQ-CR 29) QOL questionnaires were administered to patients 1 month before they began CRT, at week 4 of CRT, and 1 month after they had finished CRT. The questionnaires included multiple symptom scales, functional domains, and a composite global QOL score. Additionally, a toxicity scale was completed by providers 1 month before the beginning of CRT, weekly during treatment, and 1 month after the end of CRT. Results: Global QOL showed a statistically significant and borderline clinically significant decrease during CRT (-9.50, P=.0024) but returned to baseline 1 month after the end of treatment (-0.33, P=.9205). Symptoms during treatment were mostly gastrointestinal (nausea/vomiting +9.94, P<.0001; and diarrhea +16.67, P=.0022), urinary (dysuria +13.33, P<.0001; and frequency +11.82, P=.0006) or fatigue (+16.22, P<.0001). These symptoms returned to baseline after therapy. However, sexual enjoyment (P=.0236) and sexual function (P=.0047) remained persistently diminished after therapy. Conclusions: Rectal cancer patients undergoing neoadjuvant CRT may experience a reduction in global QOL along with significant gastrointestinal and genitourinary symptoms during treatment. Moreover, provider-rated toxicity scales may not fully capture this decrease in patient-reported QOL. Although most symptoms are transient

  14. Expandable polyester silicon-covered stent for malignant esophageal strictures before neoadjuvant chemoradiation: a pilot study.

    PubMed

    Siddiqui, Ali A; Loren, David; Dudnick, Robert; Kowalski, Thomas

    2007-03-01

    Patients with resectable esophageal cancer often require placement of a surgical jejunostomy tube prior to receiving chemoradiation so as to maintain adequate nutrition due to their inability to swallow and eat. This study reports a single institutional experience with the Polyflex self-expanding silicone stent (Riisch; Kernen. Germany) in patients with malignant stenosis receiving chemoradiation prior to esophagectomy. This was a retrospective, nonrandomized study of 6 patients who underwent Polyflex esophageal stent placement across a malignant stricture prior to receiving neoadjuvant chemoradiation. The study assessed procedural success, restoration of oral nutrition, migration, and removal of the Polyflex stent. The outcomes measured were the efficacy of treatment, stent-related complications, and changes in the nutritional status of the patient after stent placement. Stent placement was successful in 5 of 6 patients (83%). Restoration of oral nutrition after stent placement occurred in 5 of 5 patients (100%). Migration of the stent into the stomach occurred in 3 patients (60%) without occurrence of gastric outlet obstruction; there was no proximal migration. Stents were successfully removed endoscopically or at the time of esophagectomy. This early experience suggests that the removable silicone Polyflex stent is an effective alternative to a surgical jejunostomy tube for the management of malignant esophageal stenosis in patients for whom neoadjuvant chemoradiation is planned prior to esophagectomy.

  15. Does Extending the Waiting Time of Low-Rectal Cancer Surgery after Neoadjuvant Chemoradiation Increase the Perioperative Complications?

    PubMed Central

    Timudom, Kittinut; Phothong, Natthawut; Akaraviputh, Thawatchai; Chinswangwatanakul, Vitoon; Pongpaibul, Ananya; Petsuksiri, Janjira; Ithimakin, Suthinee

    2016-01-01

    Background. Traditionally, rectal cancer surgery is recommended 6 to 8 weeks after completing neoadjuvant chemoradiation. Extending the waiting time may increase the tumor response rate. However, the perioperative complication rate may increase. The purpose of this study was to determine the association between extending the waiting time of surgery after neoadjuvant chemoradiation and perioperative outcomes. Methods. Sixty patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiation followed by radical resection at Siriraj hospital between June 2012 and January 2015 were retrospectively analyzed. Demographic data and perioperative outcomes were compared between the two groups. Results. The two groups were comparable in term of demographic parameters. The mean time interval from neoadjuvant chemoradiation to surgery was 6.4 weeks in Group A and 11.7 weeks in Group B. The perioperative outcomes were not significantly different between Groups A and B. Pathologic examination showed a significantly higher rate of circumferential margin positivity in Group A than in Group B (30% versus 9.3%, resp.; P = 0.04). Conclusions. Extending the waiting to >8 weeks from neoadjuvant chemoradiation to surgery did not increase perioperative complications, whereas the rate of circumferential margin positivity decreased. PMID:27738430

  16. Neoadjuvant chemotherapy prior to preoperative chemoradiation or radiation in rectal cancer: should we be more cautious?

    PubMed Central

    Glynne-Jones, R; Grainger, J; Harrison, M; Ostler, P; Makris, A

    2006-01-01

    before surgical resection. In contrast, the data in favour of NACT before radiation or chemoradiation (CRT) is inconclusive, despite the suggestion that response to induction chemotherapy can predict response to subsequent radiotherapy. The observation that spectacular responses to chemotherapy before radical radiotherapy did not result in improved survival, was noted 25 years ago. However, multiple trials in head and neck cancer, nasopharyngeal cancer, non-small-cell lung cancer, small-cell lung cancer and cervical cancer do not support the routine use of NACT either as an alternative, or as additional benefit to CRT. The addition of NACT does not appear to enhance local control over concurrent CRT or radiotherapy alone. Neoadjuvant chemotherapy before CRT or radiation should be used with caution, and only in the context of clinical trials. The evidence base suggests that concurrent CRT with early positioning of radiotherapy appears the best option for patients with locally advanced rectal cancer and in all disease sites where radiation is the primary local therapy. PMID:16465172

  17. Neoadjuvant Chemoradiation for Distal Rectal Cancer: 5-Year Updated Results of a Randomized Phase 2 Study of Neoadjuvant Combined Modality Chemoradiation for Distal Rectal Cancer

    SciTech Connect

    Mohiuddin, Mohammed; Paulus, Rebecca; Mitchell, Edith; Hanna, Nader; Yuen, Albert; Nichols, Romaine; Yalavarthi, Salochna; Hayostek, Cherie; Willett, Christopher

    2013-07-01

    Purpose: To assess the efficacy of 2 different approaches to neoadjuvant chemoradiation for distal rectal cancers. Methods and Materials: One hundred six patients with T3/T4 distal rectal cancers were randomized in a phase 2 study. Patients received either continuous venous infusion (CVI) of 5-Fluorouracil (5-FU), 225 mg/m{sup 2} per day, 7 days per week plus pelvic hyperfractionated radiation (HRT), 45.6 Gy at 1.2 Gy twice daily plus a boost of 9.6 to 14.4 Gy for T3 or T4 cancers (Arm 1), or CVI of 5-FU, 225 mg/m{sup 2} per day, Monday to Friday, plus irinotecan, 50 mg/m{sup 2} once weekly × 4, plus pelvic radiation therapy (RT), 45 Gy at 1.8 Gy per day and a boost of 5.4 Gy for T3 and 9 Gy for T4 cancers (Arm 2). Surgery was performed 4 to 10 weeks later. Results: All eligible patients (n=103) are included in this analysis; 2 ineligible patients were excluded, and 1 patient withdrew consent. Ninety-eight of 103 patients (95%) underwent resection. Four patients did not undergo surgery for either disease progression or patient refusal, and 1 patient died during induction chemotherapy. The median time of follow-up was 6.4 years in Arm 1 and 7.0 years in Arm 2. The pathological complete response (pCR) rates were 30% in Arm 1 and 26% in Arm 2. Locoregional recurrence rates were 16% in Arm 1 and 17% in Arm 2. Five-year survival rates were 61% and 75% and Disease-specific survival rates were 78% and 85% for Arm1 and Arm 2, respectively. Five second primaries occurred in patients on Arm 1, and 1 second primary occurred in Arm 2. Conclusions: High rates of disease-specific survival were seen in each arm. Overall survival appears affected by the development of unrelated second cancers. The high pCR rates with 5-FU and higher dose radiation in T4 cancers provide opportunity for increased R0 resections and improved survival.

  18. Neoadjuvant treatment for advanced esophageal cancer: response assessment before surgery and how to predict response to chemoradiation before starting treatment

    PubMed Central

    Hölscher, Arnulf H.; Schmidt, Matthias; Warnecke-Eberz, Ute

    2015-01-01

    Patients with advanced esophageal cancer (T3-4, N) have a poor prognosis. Chemoradiation or chemotherapy before esophagectomy with adequate lymphadenectomy is the standard treatment for patients with resectable advanced esophageal carcinoma. However, only patients with major histopathologic response (regression to less than 10% of the primary tumor) after preoperative treatment will have a prognostic benefit of preoperative chemoradiation. Using current therapy regimens about 40% to 50% of the patients show major histopathological response. The remaining cohort does not benefit from this neoadjuvant approach but might benefit from earlier surgical resection. Therefore, it is an aim to develop tools for response prediction before starting the treatment and for early response assessment identifying responders. The current review discusses the different imaging techniques and the most recent studies about molecular markers for early response prediction. The results show that [18F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) has a good sensitivity but the specificity is not robust enough for routine clinical use. Newer positron emission tomography detector technology, the combination of FDG-PET with computed tomography, additional evaluation criteria and standardization of evaluation may improve the predictive value. There exist a great number of retrospective studies using molecular markers for prediction of response. Until now the clinical use is missing. But the results of first prospective studies are promising. A future perspective may be the combination of imaging technics and special molecular markers for individualized therapy. Another aspect is the response assessment after finishing neoadjuvant treatment protocol. The different clinical methods are discussed. The results show that until now no non-invasive method is valid enough to assess complete histopathological response. PMID:26157318

  19. 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.

  20. Complete Response after Treatment with Neoadjuvant Chemoradiation with Prolonged Chemotherapy for Locally Advanced, Unresectable Adenocarcinoma of the Pancreas

    PubMed Central

    Pompa, Tiffany A.; Jeurkar, Chetan; Li, Hui; Soundararajan, Suganthi; Poli, Jaganmohan; Styler, Michael

    2017-01-01

    Surgery is the only chance for cure in pancreatic ductal adenocarcinoma. In unresectable, locally advanced pancreatic cancer (LAPC), the National Comprehensive Cancer Network (NCCN) suggests chemotherapy and consideration for radiation in cases of unresectable LAPC. Here we present a rare case of unresectable LAPC with a complete histopathological response after chemoradiation followed by surgical resection. A 54-year-old female presented to our clinic in December 2013 with complaints of abdominal pain and 30-pound weight loss. An MRI demonstrated a mass in the pancreatic body measuring 6.2 × 3.2 cm; biopsy revealed proven ductal adenocarcinoma. Due to splenic vein/artery and contiguous celiac artery encasement, she was deemed surgically unresectable. She was started on FOLFIRINOX therapy (three cycles), intensity modulated radiation to a dose of 54 Gy in 30 fractions concurrent with capecitabine, followed by FOLFIRI, and finally XELIRI. After 8 cycles of ongoing XELIRI completed in March 2015, restaging showed a remarkable decrease in tumor size, along with PET-CT revealing no FDG-avid uptake. She was reevaluated by surgery and taken for definitive resection. Histopathological evaluation demonstrated a complete R0 resection and no residual tumor. Based on this patient and literature review, this strategy demonstrates potential efficacy of neoadjuvant chemoradiation with prolonged chemotherapy, followed by surgery, which may improve outcomes in patients deemed previously unresectable. PMID:28373919

  1. Neoadjuvant Therapy in Differentiated Thyroid Cancer

    PubMed Central

    Le, Valerie H.; Camille, Nadia; Miles, Brett A.; Teng, Marita S.; Genden, Eric M.; Misiukiewicz, Krzysztof J.

    2016-01-01

    Objectives. Invasion of differentiated thyroid cancer (DTC) into surrounding structures can lead to morbid procedures such as laryngectomy and tracheal resection. In these patients, there is a potential role for neoadjuvant therapy. Methods. We identified three studies involving the treatment of DTC with neoadjuvant chemotherapy: two from Slovenia and one from Japan. Results. These studies demonstrate that in selected situations, neoadjuvant chemotherapy can have a good response and allow for a more complete surgical resection, the treatment of DTC. Additionally, the SELECT trial shows that the targeted therapy lenvatinib is effective in the treatment of DTC and could be useful as neoadjuvant therapy for this disease due to its short time to response. Pazopanib has also demonstrated promise in phase II data. Conclusions. Thus, chemotherapy in the neoadjuvant setting could possibly be useful for managing advanced DTC. Additionally, some of the new tyrosine kinase inhibitors (TKIs) hold promise for use in the neoadjuvant setting in DTC. PMID:27747102

  2. Predictive Factors of Tumor Response After Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer

    SciTech Connect

    Moureau-Zabotto, Laurence; Farnault, Bertrand; de Chaisemartin, Cecile; Esterni, Benjamin; Lelong, Bernard; Viret, Frederic; Giovannini, Marc; Monges, Genevieve; Delpero, Jean-Robert; Bories, Erwan; Turrini, Olivier; Viens, Patrice; Salem, Naji

    2011-06-01

    Purpose: Neoadjuvant chemoradiation followed by surgery is the standard of care for locally advanced rectal cancer. The aim of this study was to correlate tumor response to survival and to identify predictive factors for tumor response after chemoradiation. Methods and Materials: From 1998 to 2008, 168 patients with histologically proven locally advanced adenocarcinoma treated by preoperative chemoradiation before total mesorectal excision were retrospectively studied. They received a radiation dose of 45 Gy with a concomitant 5-fluorouracil (5-FU)-based chemotherapy. Analysis of tumor response was based on lowering of the T stage between pretreatment endorectal ultrasound and pathologic specimens. Overall and progression-free survival rates were correlated with tumor response. Tumor response was analyzed with predictive factors. Results: The median follow-up was 34 months. Five-year disease-free survival and overall survival rates were, of 44.4% and 74.5% in the whole population, 83.4% and 83.4%, respectively, in patients with pathological complete response, 38.6% and 71.9%, respectively, in patients with tumor downstaging, and 29.1and 58.9% respectively, in patients with absence of response. A pretreatment carcinoembryonic antigen (CEA) level of <5 ng/ml was significantly independently associated with pathologic complete tumor response (p = 0.019). Pretreatment small tumor size (p = 0.04), pretreatment CEA level of <5 ng/ml (p = 0.008), and chemotherapy with capecitabine (vs. 5-FU) (p = 0.04) were significantly associated with tumor downstaging. Conclusions: Downstaging and complete response after CRT improved progression-free survival and overall survival of locally advanced rectal adenocarcinoma. In multivariate analysis, a pretreatment CEA level of <5 ng/ml was associated with complete tumor response. Thus, small tumor size, a pretreatment CEA level of < 5ng/ml, and use of capecitabine were associated with tumor downstaging.

  3. How reliable is immunohistochemical staining for DNA mismatch repair proteins performed after neoadjuvant chemoradiation?

    PubMed

    Vilkin, Alex; Halpern, Marisa; Morgenstern, Sara; Brazovski, Eli; Gingold-Belfer, Rachel; Boltin, Doron; Purim, Ofer; Kundel, Yulia; Welinsky, Sara; Brenner, Baruch; Niv, Yaron; Levi, Zohar

    2014-10-01

    Immunohistochemistry (IHC) testing for mismatch repair proteins (MMRP) is currently being used primarily in colorectal cancer resection specimens. We aimed to compare the results of IHC staining performed on biopsy specimens obtained at endoscopy with that performed on surgical specimens after neoadjuvant therapy. Thirty-two rectal cancer subjects had paired preneoadjuvant and postneoadjuvant tissue available for IHC staining (MLH1, MSH2, MSH6, and PMS2), whereas 39 rectosigmoid cancer patients who did not receive neoadjuvant treatment served as controls. Each slide received a qualitative (absent, focal, and strong) and quantitative score (immunoreactivity [0-3] × percent positivity [0-4]). The quantitative scores of MMRP from the operative material were significantly lower in the neoadjuvant group than in the control (P < .05 for all).The scores of all MMRP from endoscopic biopsies were not significantly different between the neoadjuvant and the control groups. Disagreement between the endoscopic biopsy and the operative material was evident in 23 of 128 stains (18.5%) in the neoadjuvant group and in 12 of 156 stains (7.7%) in the control group (P = .009). In the neoadjuvant group, a disagreement pattern of "endoscopic strong operative focal" was observed in 28.1% for PMS2, 12.5% for MSH6, 12.5% for MLH1, and 6.3% for MSH2, and in the control group, this same disagreement pattern was found in 12.8% for PMS2, 7.7% for MSH6, 7.7% for MLH1, and 0% for MSH2. Based on our findings, we suggest that for rectal cancer, the endoscopic material rather than the operative material should serve as the primary material for IHC staining.

  4. Neoadjuvant chemoradiation followed by orthotopic liver transplantation in cholangiocarcinomas: the emory experience

    PubMed Central

    Landry, Jerome C.

    2016-01-01

    Background Cholangiocarcinoma (CCA) is a bile duct tumor with a grim prognosis. The median survival after radiotherapy of unresectable disease is 9-12 months. The following is a review of our experience with neoadjuvant (NEO) chemoradiation followed by orthotopic liver transplantation (OLT) for CCA. Methods Ten patients with CCAs were selected as candidates for NEO-OLT between 2008-2011. Patients with unresectable CCA above the cystic duct without intra or extrahepatic metastases were eligible. Primary sclerosing cholangitis (PSC) patients were included due to their poor resection response. Patients initially received external-beam radiation [via conventional fields or volumetric-modulated arc therapy (VMAT)] plus capecitabine (XEL) or 5-fluorouracil (5-FU), followed by either Iridium192 (Ir192) brachytherapy high dose rate (HDR) or external boost. 5-FU or XEL was administered until OLT. Patients underwent periodic surveillance computed tomography (CT)/MRIs after OLT. Primary endpoints included actuarial rates (AR)/crude rates (CR) of overall survival (OS), and local control (LC) at 6, 12, and 24 months. Results Five males and five females were identified. Mean age was 58.3 years (range, 38-71 years). Mean composite radiation dose delivered was 59.0 Gy (range, 54-71.4 Gy). Forty percent of patients had an HDR boost. Fifty percent of patients received XEL during NEO. Two patients were excluded from the analysis as they did not go on to OLT due to metastases (n=1) and death due to GI bleed (n=1). Thirty-eight percent of the OLT patients had a pathological complete response (pCR) after NEO, while 25% required a Whipple due to positive margins. Median follow-up for the OLT group was 23 months (range, 6.5-37 months). Six, twelve, and twenty-four months LC AR was 100%. LC CR was 100% at longest interval (30 months). Six, twelve, and twenty-four months OS AR was 100%, 87.5%, and 87.5%, respectively. Mean OS AR was 30.2 months (95% CI: 22.8-37.7). OS CR was 75% at longest

  5. Pre-treatment high-resolution rectal MRI and treatment response to neoadjuvant chemoradiation

    PubMed Central

    Chang, George J.; You, Y. Nancy; Park, In Ja; Kaur, Harmeet; Hu, Chung-Yuan; Rodriguez-Bigas, Miguel A.; Skibber, John M.; Ernst, Randy D.

    2012-01-01

    Background Use of rectal MRI evaluation of patients with rectal cancer for primary tumor staging and for identification for poor prognostic features is increasing. MR imaging permits precise delineation of tumor anatomy and assessment of mesorectal tumor penetration and radial margin risk. Objective To evaluate the ability of pre-treatment rectal MRI to classify tumor response to neoadjuvant chemoradiation. Design Retrospective, consecutive cohort study, central review. Setting Tertiary academic hospital. Patients 62 consecutive patients with locally advanced (stage cII-cIII)rectal cancer who underwent rectal cancer protocol high resolution MRI prior to surgery(12/09-3/11). Main Outcome Measures Probability of good (ypT0-2N0) vs. poor (≥ypT3N0) response as a function of mesorectal tumor depth, lymph node status, extramural vascular invasion, and grade assessed by uni- and multi-variate logistic regression. Results Tumor response was good in 25, 40.3% and poor in 37, 59.7%.Median interval from MRI to OP was 7.9weeks (IQR: 7.0–9.0). MRI tumor depth was <1 mm in 10 (16.9%), 1–5 mm in 30 (50.8%), and >5 mm in 21(33.9%). LN status was positive in 40 (61.5%) and vascular invasion was present in 16 (25.8%). Tumor response was associated with MRI tumor depth (P=0.001), MRI lymph nodes status (P=<0.001)and vascular invasion (P=0.009). Multivariate regression indicated >5mm MRI tumor depth (OR=0.08, 95% CI=0.01–0.93, p=0.04) and MRI LN positivity (OR=0.12, 95% CI=0.03–0.53, p=0.005) were less likely to achieve a good response to neoadjuvant chemoradiotherapy. Limitations Uncertain generalizability in centers with limited experience with MRI staging for rectal cancer. Conclusion MRI assessment of tumor depth and lymph node status in rectal cancer is associated to tumor response to neoadjuvant chemoradiotherapy. These factors should therefore be considered for stratification of patients for novel treatment strategies reliant on pathologic response to treatment or for

  6. Predictive and Prognostic Molecular Biomarkers for Response to Neoadjuvant Chemoradiation in Rectal Cancer

    PubMed Central

    Dayde, Delphine; Tanaka, Ichidai; Jain, Rekha; Tai, Mei Chee; Taguchi, Ayumu

    2017-01-01

    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. PMID:28272347

  7. Mucinous adenocarcinoma of perianal region: an uncommon disease treated with neo-adjuvant chemo-radiation.

    PubMed

    Purkayastha, Abhishek; Sharma, Neelam; Dutta, Vibha; Bisht, Niharika; Pandya, Tejas

    2016-01-01

    Mucinous adenocarcinoma of the perianal region is an oncologic rarity posing a diagnostic and therapeutic dilemma for treating oncologists due to very few reported cases without definite therapeutic guidelines. It accounts for 2% to 3% of all gastrointestinal malignancies and are historically known to arise from chronic anal fistulas and ischiorectal or perianal abscesses. We hereby report a sporadic and interesting case of perianal mucinous adenocarcinoma in a 56-year-old male initially treated with alternative medicines and local surgery for recurrent fistula in ano of 2 years duration. He presented with complaints of discharging growth in perianal region, painful defecation associated with occasional blood mixed stools of 6 months duration. Incisional biopsy from the ulcer revealed mucinous adenocarcinoma. Contrast enhanced computed tomography (CT) scan and whole body positron emission tomography (PET) scan showed a localized perianal growth which was further confirmed with colonoscopy. With no pre-set treatment protocol for this rare entity, he was managed with neo-adjuvant concurrent chemo-radiation (CCRT) followed by abdominoperineal resection (APR) and adjuvant chemotherapy. Presently he is on 3 monthly follow-up since last 1 year post APR and adjuvant chemotherapy without any evidence of recurrence or distant metastasis. To the best of knowledge, our report may be one of the rarest cases of this disease entity where the duration of anal fistula was merely 2 years in contrast to the established criteria that the fistula precedes carcinoma by at least 10 years.

  8. Mucinous adenocarcinoma of perianal region: an uncommon disease treated with neo-adjuvant chemo-radiation

    PubMed Central

    Sharma, Neelam; Dutta, Vibha; Bisht, Niharika; Pandya, Tejas

    2016-01-01

    Mucinous adenocarcinoma of the perianal region is an oncologic rarity posing a diagnostic and therapeutic dilemma for treating oncologists due to very few reported cases without definite therapeutic guidelines. It accounts for 2% to 3% of all gastrointestinal malignancies and are historically known to arise from chronic anal fistulas and ischiorectal or perianal abscesses. We hereby report a sporadic and interesting case of perianal mucinous adenocarcinoma in a 56-year-old male initially treated with alternative medicines and local surgery for recurrent fistula in ano of 2 years duration. He presented with complaints of discharging growth in perianal region, painful defecation associated with occasional blood mixed stools of 6 months duration. Incisional biopsy from the ulcer revealed mucinous adenocarcinoma. Contrast enhanced computed tomography (CT) scan and whole body positron emission tomography (PET) scan showed a localized perianal growth which was further confirmed with colonoscopy. With no pre-set treatment protocol for this rare entity, he was managed with neo-adjuvant concurrent chemo-radiation (CCRT) followed by abdominoperineal resection (APR) and adjuvant chemotherapy. Presently he is on 3 monthly follow-up since last 1 year post APR and adjuvant chemotherapy without any evidence of recurrence or distant metastasis. To the best of knowledge, our report may be one of the rarest cases of this disease entity where the duration of anal fistula was merely 2 years in contrast to the established criteria that the fistula precedes carcinoma by at least 10 years. PMID:28138619

  9. 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.

  10. Adjuvant chemotherapy in rectal cancer: defining subgroups who may benefit after neoadjuvant chemoradiation and resection

    PubMed Central

    Maas, Monique; Nelemans, Patty J; Valentini, Vincenzo; Crane, Christopher H; Capirci, Carlo; Rödel, Claus; Nash, Garrett M; Kuo, Li-Jen; Glynne-Jones, Rob; García-Aguilar, Julio; Suárez, Javier; Calvo, Felipe A; Pucciarelli, Salvatore; Biondo, Sebastiano; Theodoropoulos, George; Lambregts, Doenja MJ; Beets-Tan, Regina GH; Beets, Geerard L

    2016-01-01

    Recent literature suggests that the benefit of adjuvant chemotherapy (aCT) for rectal cancer patients might depend on the response to neoadjuvant chemoradiation (CRT). Aim was to evaluate whether the effect of aCT in rectal cancer is modified by response to CRT and to identify which patients benefit from aCT after CRT, by means of a pooled analysis of individual patient data from 13 datasets. Patients were categorised into 3 groups: pCR (ypT0N0), ypT1-2 tumour and ypT3-4 tumour. Hazard ratios for the effect of aCT were derived from multivariable Cox regression analyses. Primary outcome measure was recurrence-free survival (RFS). 1723(52%) of 3313 included patients received aCT. 898 patients had a pCR, 966 had a ypT1-2 tumour and 1302 had a ypT3-4 tumour. For 122 patients response category was missing and 25 patients had ypT0N+. Median follow-up for all patients was 51 (0-219) months. Hazard ratios for RFS with 95%CI for patients treated with aCT were 1.25(0.68-2.29), 0.58(0.37-0.89) and 0.83(0.66-1.10) for patients with pCR, ypT1-2 and ypT3-4 tumours, respectively. The effect of aCT in rectal cancer patients treated with CRT differs between subgroups. Patients with a pCR after CRT may not benefit from aCT, whereas patients with residual tumour had superior outcomes when aCT was administered. The test for interaction did not reach statistical significance, but the results support further investigation of a more individualized approach to administer aCT after CRT and surgery based on pathologic staging. PMID:25418551

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

    SciTech Connect

    Koh, Dow-Mu Chau, Ian; Tait, Diana; Wotherspoon, Andrew; Cunningham, David; Brown, Gina

    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. 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.

  12. Identification of Predictive Markers for Response to Neoadjuvant Chemoradiation in Rectal Carcinomas by Proteomic Isotope Coded Protein Label (ICPL) Analysis

    PubMed Central

    Croner, Roland S.; Sevim, Müzeyyen; Metodiev, Metodi V.; Jo, Peter; Ghadimi, Michael; Schellerer, Vera; Brunner, Maximillian; Geppert, Carol; Rau, Tilman; Stürzl, Michael; Naschberger, Elisabeth; Matzel, Klaus E.; Hohenberger, Werner; Lottspeich, Friedrich; Kellermann, Josef

    2016-01-01

    Neoadjuvant chemoradiation (nCRT) is an established procedure in stage union internationale contre le cancer (UICC) II/III rectal carcinomas. Around 53% of the tumours present with good tumor regression after nCRT, and 8%–15% are complete responders. Reliable selection markers would allow the identification of poor or non-responders prior to therapy. Tumor biopsies were harvested from 20 patients with rectal carcinomas, and stored in liquid nitrogen prior to therapy after obtaining patients’ informed consent (Erlangen-No.3784). Patients received standardized nCRT with 5-Fluoruracil (nCRT I) or 5-Fluoruracil ± Oxaliplatin (nCRT II) according to the CAO/ARO/AIO-04 protocol. After surgery, regression grading (Dworak) of the tumors was performed during histopathological examination of the specimens. Tumors were classified as poor (Dworak 1 + 2) or good (Dworak 3 + 4) responders. Laser capture microdissection (LCM) for tumor enrichment was performed on preoperative biopsies. Differences in expressed proteins between poor and good responders to nCRT I and II were identified by proteomic analysis (Isotope Coded Protein Label, ICPL™) and selected markers were validated by immunohistochemistry. Tumors of 10 patients were classified as histopathologically poor (Dworak 1 or 2) and the other 10 tumor samples as histopathologically good (Dworak 3 or 4) responders to nCRT after surgery. Sufficient material in good quality was harvested for ICPL analysis by LCM from all biopsies. We identified 140 differentially regulated proteins regarding the selection criteria and the response to nCRT. Fourteen of these proteins were synchronously up-regulated at least 1.5-fold after nCRT I or nCRT II (e.g., FLNB, TKT, PKM2, SERINB1, IGHG2). Thirty-five proteins showed a complete reciprocal regulation (up or down) after nCRT I or nCRT II and the rest was regulated either according to nCRT I or II. The protein expression of regulated proteins such as PLEC1, TKT, HADHA and TAGLN was

  13. Anastomotic leak rate after low anterior resection for rectal cancer after chemoradiation therapy.

    PubMed

    Phillips, Benjamin R; Harris, Lisa J; Maxwell, Pinckney J; Isenberg, Gerald A; Goldstein, Scott D

    2010-08-01

    Anastomotic leak may be the most concerning complication after colorectal anastomosis. To compare open with laparoscopic rectal resection, we must have accurate leak rates in patients who have received neoadjuvant chemoradiation therapy to serve as a benchmark for comparison. All patients who had preoperative chemoradiation therapy with rectal resection and low pelvic anastomosis for cancer in a single colorectal practice over a 7-year period were retrospectively reviewed. All patients had proximal diversion and a contrast enema study before stoma reversal. Eighty-seven consecutive patients were included in the study. Average age was 58 years. Fifty-nine per cent of patients were male. Sixty-six per cent were smokers. Pathologic T stage was 5 per cent T0, 16 per cent T1, 28 per cent T2, 47 per cent T3, and 5 per cent T4. Seventy-five per cent of patients were pathologically lymph node-negative. Average time to stoma reversal was 122 days. Total anastomotic leak rate was 10.3 per cent (8% clinical leaks). Five (56%) patients with leak successfully underwent reversal of their diverting stoma (average time to reversal, 290 days). Patients who had the complication of anastomotic leakage had less likelihood of stoma reversal and a significantly prolonged time to stoma reversal.

  14. Neoadjuvant chemotherapy first, followed by chemoradiation and then surgery, in the management of locally advanced rectal cancer.

    PubMed

    Cercek, Andrea; Goodman, Karyn A; Hajj, Carla; Weisberger, Emily; Segal, Neil H; Reidy-Lagunes, Diane L; Stadler, Zsofia K; Wu, Abraham J; Weiser, Martin R; Paty, Philip B; Guillem, Jose G; Nash, Garrett M; Temple, Larissa K; Garcia-Aguilar, Julio; Saltz, Leonard B

    2014-04-01

    Standard therapy for locally advanced rectal cancer (LARC) is preoperative chemoradiotherapy and postoperative chemotherapy. At Memorial Sloan-Kettering Cancer Center (MSKCC) the authors began offering FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) as initial treatment for patients with high-risk LARC to target micrometastases while treating the primary tumor. The purpose of this study is to report the safety and efficacy of initial FOLFOX given before chemoradiotherapy on tumor downsizing and pathologic complete response (pathCR) in LARC. The records of patients with stage II/III rectal cancer treated at MSKCC between 2007 and 2012 were reviewed. Of approximately 300 patients with LARC treated at MSKCC, 61 received FOLFOX as initial therapy. Of these 61 patients, 57 received induction FOLFOX (median 7 cycles) followed by chemoradiation, and 4 experienced an excellent response, declined chemoradiation, and underwent total mesorectal excision (TME). Twelve of the 61 patients did not undergo TME: 9 had a complete clinical response (CCR), 1 declined despite persistent tumor, 1 declined because of comorbidities, and 1 developed metastatic disease. Among the 61 patients receiving initial FOLFOX, 22 (36%) had either a pathCR (n=13) or a CCR (n=9). Of the 49 patients who underwent TME, all had R0 resections and 23 (47%) had tumor response greater than 90%, including 13 (27%) who experienced a pathCR. Of the 28 patients who received all 8 cycles of FOLFOX, 8 experienced a pathCR (29%) and 3 a CCR (11%). No serious adverse events occurred that required a delay in treatment during FOLFOX or chemoradiation. FOLFOX and chemoradiation before planned TME results in tumor regression, a high rate of delivery of planned therapy, and a substantial rate of pathCRs, and offers a good platform for nonoperative management in select patients.

  15. (Neo)adjuvant systemic therapy for melanoma.

    PubMed

    van Zeijl, M C T; van den Eertwegh, A J; Haanen, J B; Wouters, M W J M

    2017-03-01

    Surgery still is the cornerstone of treatment for patients with stage II and III melanoma, but despite great efforts to gain or preserve locoregional control with excision of the primary tumour, satellites, intransits, sentinel node biopsy and lymphadenectomy, surgery alone does not seem to improve survival any further. Prognosis for patients with high risk melanoma remains poor with 5-year survival rates of 40 to 80%. Only interferon-2b has been approved as adjuvant therapy since 1995, but clinical integration is low considering the high risk-benefit ratio. In recent years systemic targeted- and immunotherapy have proven to be beneficial in advanced melanoma and could be a promising strategy for (neo)adjuvant treatment of patients with resectable high risk melanomas as well. Randomised, placebo- controlled phase III trials on adjuvant systemic targeted- and immunotherapy are currently being performed using new agents like ipilimumab, pembrolizumab, nivolumab, vemurafenib and dabrafenib plus trametinib. In this article we review the literature on currently known adjuvant therapies and currently ongoing trials of (neo)adjuvant therapies in high risk melanomas.

  16. Aspirin as a neoadjuvant agent during preoperative chemoradiation for rectal cancer

    PubMed Central

    Restivo, Angelo; Cocco, Ivana Maria Francesca; Casula, Giuseppe; Scintu, Francesco; Cabras, Francesco; Scartozzi, Mario; Zorcolo, Luigi

    2015-01-01

    Background: Recently, many studies have suggested a possible adjuvant role of aspirin in colorectal cancer, reporting a positive prognostic effect with its use in patients with established disease. The aim of this study was to investigate the anticancer effect of aspirin use during preoperative chemoradiation for rectal cancer. Methods: Two hundred and forty-one patients with stage II–III rectal cancer and candidates for chemoradiation (CRT) were selected and assigned to two groups: group 1, patients taking aspirin at the time of diagnosis, and group 2, all others. Treatment and oncological outcomes were explored. Results: Aspirin use was associated with a higher rate of tumour downstaging (67.6% vs 43.6%, P=0.01), good pathological response (46% vs 19% P<0.001), and a slightly, although not significant, higher rate of complete pathological response (22% vs 13% P=0.196). Aspirin use was also associated with a better 5-year progression-free survival (86.6% vs 67.1% hazard rate (HR)=0.20; 95% CI=0.07–0.60) and overall survival (90.6% vs 73.2% HR=0.21; 95% CI=0.05–0.89). Although chance of local relapse was similar (HR=0.6; 95% CI=0.06–4.5), aspirin use was associated with a lower risk of developing metastasis (HR=0.30; 95% CI=0.10–0.86). Conclusions: Aspirin might have anticancer activity against rectal cancer during preoperative CRT. This finding could be clinically relevant and should be further investigated with randomised trials. PMID:26372700

  17. Neoadjuvant Chemoradiation With Paclitaxel/Carboplatin for Selected Stage III Non-Small-Cell Lung Cancer: Long-Term Results of a Trimodality Phase II Protocol

    SciTech Connect

    Hehr, Thomas; Friedel, Godehard; Steger, Volker; Spengler, Werner; Eschmann, Susanne M.; Bamberg, Michael; Budach, Wilfried

    2010-04-15

    Purpose: To evaluate, in a Phase II trial conducted August 1998 through January 2001, the efficacy of neoadjuvant chemotherapy followed by chemoradiotherapy and definitive surgery in patients with locally advanced non-small-cell lung cancer (LA-NSCLC), Stages IIIA bulky and selected Stage IIIB. Patients and Methods: Staging of LA-NSCLC included computed tomography of cranium, thorax, and abdomen, whole-body positron emission tomography, and video mediastinoscopy. Induction chemotherapy with weekly paclitaxel and carboplatin was followed by hyperfractionated accelerated thoracic radiotherapy (45 Gy) with simultaneous weekly paclitaxel and carboplatin. Four to six weeks after completion of induction therapy, restaging and resection of primary tumor and lymph nodes was intended. Results: A total of 59 consecutive patients were enrolled, 25% with Stage IIIA bulky disease, 65% with Stage IIIB, and 10% with Stage IV (excluded from further analysis). Forty-one patients completed induction therapy; in 52.4% a functional (positron emission tomography) downstaging was proven. Thirty-two patients (59.3%) underwent complete tumor resection, and 5 patients had an exploratory thoracotomy only. Histopathologic downstaging was proven in 59.4% and complete response in 21.9%. Hospital mortality was 5.4%. Median duration of follow-up for living patients was 62.1 months. Overall median survival was 22.6 months, 58.2 months for completely resected patients. During induction chemotherapy, Grade 3/4 granulocytopenia occurred in 8% of patients; the most common Grade 3/4 toxicity of chemoradiation was esophagitis, in 26.4% of patients. Conclusions: Induction paclitaxel/carboplatin with hyperfractionated accelerated chemoradiotherapy followed by complete tumor resection demonstrates high efficacy in LA-NSCLC and offers a promising chance of long-term survival.

  18. TU-G-BRA-06: PET-Based Treatment Response Assessement for Neoadjuvent Chemoradiation for Pancreatic Adenocarcinoma

    SciTech Connect

    Dalah, E; Tai, A; Oshima, K; Hall, W; Erickson, B; Li, X

    2015-06-15

    Purpose: To address the limitations of the conventional response evaluation criteria in solid tumors (RECIST), and validate PET response criteria in solid tumors (PERCIST1.0). We analyze the relationship between the pathological treatment response (PTR) and PERCIST1.0 for patients treated with neoadjuvent chemoradiation (nCR) for pancreatic adenocarcinoma. Methods: The pre- and post-nCR CT and PET data for a total of 8 patients with resectable, or borderline resectable pancreatic head adenocarcinoma treated with nCR were retrospectively analyzed. These data were compared with the PTR which were graded according to tumor cell destruction (cellularity), with Grade1, 2 or 3 (G1, G2 or G3) for good, moderate, and poor responses, respectively. RECIST-based PET (RECISTPET), and PERCIST1.0 were defined using lean body mass normalized SUV (nSUVlb). RECIST-based CT (RECISTCT) was defined by contouring the whole pancreas head (CTPH). Pre- and post-nSUVlb and SUVbw, PERCIST 1.0, were correlated with PTR using Pearson’s correlation coefficient test. Results: The average mean and SD in nSUVlb for all 8 patients analyzed were lower in post-nCR (1.35±0.34) compared to those at pre-nCR (1.38±0.20). Using PERCIST1.0, 5/8 patients showed stable metabolic disease (SMD), 2/8 partial metabolic response (PMR), and 1/8 progressive metabolic disease (PMD). Using RECISTPET 4/8 showed stable disease (STD), 4/8 partial response (PR), whereas 8/8 showed stable disease (STD) using RECISTCT. PTR were correlated with PERCIST1.0 (R=0.3780/P=0.6071). Pathological tumor size was correlated with RECISTCT (R=0.0727/P=0.8679), and RECISTPET, R=−0.3333/P=0.3798. Conclusion: Chemoradiation treatment response assessment based on metabolic tumor activities using PRECIST1.0 and RECISTPET appears to provide better agreement with pathological assessment as compared to the conventional CT-based assessment using RECISTCT. The integration of these additional radiographic metrics in assessing treatment

  19. Optimal Timing for Assessment of Tumor Response to Neoadjuvant Chemoradiation in Patients With Rectal Cancer: Do All Patients Benefit From Waiting Longer Than 6 Weeks?

    SciTech Connect

    Perez, Rodrigo O.; Habr-Gama, Angelita; Sao Juliao, Guilherme P.; Gama-Rodrigues, Joaquim; Sousa, Afonso H.S.; Campos, Fabio Guilherme; Imperiale, Antonio R.; Lynn, Patricio B.; Proscurshim, Igor; Nahas, Sergio Carlos; Ono, Carla Rachel; Buchpiguel, Carlos Alberto

    2012-12-01

    Purpose: To estimate the metabolic activity of rectal cancers at 6 and 12 weeks after completion of chemoradiation therapy (CRT) by 2-[fluorine-18] fluoro-2-deoxy-D-glucose-labeled positron emission tomography/computed tomography ([{sup 18}FDG]PET/CT) imaging and correlate with response to CRT. Methods and Materials: Patients with cT2-4N0-2M0 distal rectal adenocarcinoma treated with long-course neoadjuvant CRT (54 Gy, 5-fluouracil-based) were prospectively studied ( (ClinicalTrials.org) identifier (NCT00254683)). All patients underwent 3 PET/CT studies (at baseline and 6 and 12 weeks from CRT completion). Clinical assessment was at 12 weeks. Maximal standard uptake value (SUVmax) of the primary tumor was measured and recorded at each PET/CT study after 1 h (early) and 3 h (late) from {sup 18}FDG injection. Patients with an increase in early SUVmax between 6 and 12 weeks were considered 'bad' responders and the others as 'good' responders. Results: Ninety-one patients were included; 46 patients (51%) were 'bad' responders, whereas 45 (49%) patients were 'good' responders. 'Bad' responders were less likely to develop complete clinical response (6.5% vs. 37.8%, respectively; P=.001), less likely to develop significant histological tumor regression (complete or near-complete pathological response; 16% vs. 45%, respectively; P=.008) and exhibited greater final tumor dimension (4.3 cm vs. 3.3 cm; P=.03). Decrease between early (1 h) and late (3 h) SUVmax at 6-week PET/CT was a significant predictor of 'good' response (accuracy of 67%). Conclusions: Patients who developed an increase in SUVmax after 6 weeks were less likely to develop significant tumor downstaging. Early-late SUVmax variation at 6-week PET/CT may help identify these patients and allow tailored selection of CRT-surgery intervals for individual patients.

  20. Novel Neoadjuvant Therapy Paradigms for Bladder Cancer: Results from the National Cancer Center Institute Forum

    PubMed Central

    Dinney, Colin P.N.; Hansel, Donna; McConkey, David; Shipley, William; Hagan, Michael; Dreicer, Robert; Lerner, Seth; Czerniak, Bogdan; Waldman, Fred; Groshen, Susan; True, Lawrence D.; Petricoin, Emanuel; Theodorescu, Dan; Hruszkewycz, Andrew; Bajorin, Dean

    2014-01-01

    Although bladder cancer (BC) is a significant health threat to the US population, integrated clinical and laboratory investigations of this disease lag behind those of other types of cancer. Advances in BC are especially challenged due in part to a general decreased level of funding over the past 5 years. It is ironic that despite the awareness that BC is the 5th most commonly diagnosed solid malignancy in the United States, and one of the most costly to treat, funding for this organ site lags far behind that of other less common malignancies. Moreover, BC offers several unique opportunities for translational research that make it an ideal candidate for investigation. One distinct advantage over other solid tumor sites is that urine and tissue are readily available for translational studies that can direct the development of novel therapy for this disease. The NCI sponsored “Novel Neoadjuvant Therapy for Bladder Cancer” forum held in brought leading clinical and laboratory-based scientists together with the advocacy community to lay the groundwork for collaborative discovery and translation. The goal of the meeting was to bridge the gaps in translational science and develop the concepts for two novel biomarker-driven clinical trials, one in the neoadjuvant presurgical setting and the other in the setting of bladder preservation with chemoradiation. The meeting provided a unique opportunity to launch a collective effort to establish molecular-based therapy for UC. Herein, we summarize the proceedings of this meeting, and the future plans resulting from this forum. PMID:25443274

  1. Current and future role of neoadjuvant therapy for breast cancer.

    PubMed

    Untch, Michael; Konecny, Gottfried E; Paepke, Stefan; von Minckwitz, Gunter

    2014-10-01

    Neoadjuvant systemic chemotherapy is a possible therapeutic approach for the treatment of locally advanced operable, primarily non-operable or inflammatory breast cancer. Neoadjuvant systemic chemotherapy is an option for breast cancer patients who would require adjuvant chemotherapy otherwise based on clinical and histological examination and imaging. The use of neoadjuvant systemic therapy in operable breast cancer is currently increasing because of its advantages that include higher rates of breast conserving surgery and the possibility of measuring early in-vivo response to systemic treatment. The timing of axillary sentinel lymph node diagnosis (i.e. before or after neoadjuvant chemotherapy) is critical in that it may influence the likelihood of axillary preservation. It is not yet clear if neoadjuvant therapy might improve outcomes in certain subgroups of breast cancer patients. Neoadjuvant treatment modalities require a close collaboration between oncology professionals, including surgeons, gynecologists, medical oncologists, radiation oncologists, radiologists and pathologists. The most important parameter for treatment success and improved overall survival is the achievement of a pathologic complete response (pCR), although the role of pCR in patients with luminal A like tumours might be less informative. Identification of patient subgroups with high pCR rates may allow less invasive surgical or radiological interventions. Patients not achieving a pCR may be candidates for postoperative clinical trials exploring novel systemic treatments.

  2. Selective Changes in the Immune Profile of Tumor-Draining Lymph Nodes After Different Neoadjuvant Chemoradiation Regimens for Locally Advanced Cervical Cancer

    SciTech Connect

    Battaglia, Alessandra; Buzzonetti, Alexia; Martinelli, Enrica; Fanelli, Mara; Petrillo, Marco; Ferrandina, Gabriella; Scambia, Giovanni; Fattorossi, Andrea

    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 by 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.

  3. Counterpoint: long-course chemoradiation is preferable in the neoadjuvant treatment of rectal cancer.

    PubMed

    Minsky, Bruce D

    2011-07-01

    There are 2 approaches to preoperative therapy. Short-course (25 Gy in 5 fractions) radiation and long-course (50.4 Gy in 28 fractions) radiation combined with chemotherapy (CMT). Although short-course radiation therapy is used in some European countries, it is not favored in all European countries or North America. Unlike long-course CMT, it cannot be safely combined with adequate doses of systemic concurrent chemotherapy, and, as currently designed, it does not increase sphincter preservation. Long-course CMT remains the preferred regimen for cT3 and/or node-positive disease. With parallel advances in staging, surgery, systemic therapy, and molecular markers, more selective approaches are being investigated.

  4. Symptomatic Pericardial Effusion After Chemoradiation Therapy in Esophageal Cancer Patients

    SciTech Connect

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

    2013-11-01

    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 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. 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

  5. Outcomes and Tolerability of Chemoradiation Therapy for Pancreatic Cancer Patients Aged 75 Years or Older

    SciTech Connect

    Miyamoto, David T.; Mamon, Harvey J.

    2010-07-15

    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 18 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

  6. Prognostic influence of histopathological regression patterns in rectal adenocarcinoma receiving neoadjuvant therapy

    PubMed Central

    Estrada Muñoz, Lourdes; Sastre Varela, Javier; Corona Sánchez, Juan Antonio; Díaz del Arco, Cristina; García Paredes, Beatriz; Córdoba Largo, Sofía; del Puerto Nevado, Laura

    2017-01-01

    Background Neoadjuvant chemoradiation therapy (CRT) is an important management strategy in rectal carcinoma. Different systems grading response have shown varying prognostic influence. Methods To analyze the prognostic influence of pathological response in a series of 183 patients with rectal carcinoma receiving neoadjuvant therapy. To determine the prognostic significance of the histopathological patterns of response. Results A total of 183 patients from two hospitals. The concordance rate between pathologists was good. In total, 18% of the patients showed grade 0 (complete response), 31.7% grade 1, 19.2% grade 2 and 31.1% grade 3 regression. T down-staging was found in 51.9% of the cases. 46 patients recurred and 18 died of disease (median follow-up time: 39 months). We found a statistically significant association between pathological response and pT stage and down-staging. Inflammatory reaction in the tumor bed was significantly associated to regression and prognosis. Cox’s multivariate analysis of survival revealed that down-staging and presence of mucin pools in the tumor bed behaved as significant predictors of recurrence and regression grade and mucin pools as significant predictors of survival. Conclusions Pathological response is an important surrogate marker of prognosis in some large series, but results are varying. There are many systems to grade regression and this makes it difficult to compare the results by different groups. It is important to report the specific pattern of response, for some of them may have prognostic relevance. We feel there is an urgent need to develop standarized protocols and employ a universal regression scheme if we intend to use this factor to guide therapy. PMID:28280608

  7. Anastomotic Complications After Ivor Lewis Esophagectomy in Patients Treated With Neoadjuvant Chemoradiation Are Related to Radiation Dose to the Gastric Fundus

    SciTech Connect

    Vande Walle, Caroline; Ceelen, Wim P.; Boterberg, Tom; Vande Putte, Dirk; Van Nieuwenhove, Yves; Varin, Oswald; Pattyn, Piet

    2012-03-01

    Purpose: Neoadjuvant chemoradiation (CRT) is increasingly used in locally advanced esophageal cancer. Some studies have suggested that CRT results in increased surgical morbidity. We assessed the influence of CRT on anastomotic complications in a cohort of patients who underwent CRT followed by Ivor Lewis esophagectomy. Patients and Methods: Clinical and pathologic data were collected from all patients treated with neoadjuvant CRT (36 Gy combined with 5-fluorouracil and cisplatin) followed by Ivor Lewis esophagectomy. On the radiotherapy (RT) planning computed tomography scans, normal tissue volumes were drawn encompassing the proximal esophageal region and the gastric fundus. Within these volumes, dose-volume histograms were analyzed to generate the total dose to 50% of the volume (D{sub 50}). We studied the ability of the D{sub 50} to predict anastomotic complications (leakage, ischemia, or stenosis). Dose limits were derived using receiver operating characteristics analysis. Results: Fifty-four patients were available for analysis. RT resulted in either T or N downstaging in 51% of patients; complete pathologic response was achieved in 11%. In-hospital mortality was 5.4%, and major morbidity occurred in 36% of patients. Anastomotic complications (AC) developed in 7 patients (13%). No significant influence of the D{sub 50} on the proximal esophagus was noted on the anastomotic complication rate. The median D{sub 50} on the gastric fundus, however, was 33 Gy in patients with AC and 18 Gy in patients without AC (p = 0.024). Using receiver operating characteristics analysis, the D{sub 50} limit on the gastric fundus was defined as 29 Gy. Conclusions: In patients undergoing neoadjuvant CRT followed by Ivor Lewis esophagectomy, the incidence of AC is related to the RT dose on the gastric fundus but not to the dose received by the proximal esophagus. When planning preoperative RT, efforts should be made to limit the median dose on the gastric fundus to 29 Gy with a V

  8. Neoadjuvant therapy for potentially resectable pancreatic cancer: an emerging paradigm?

    PubMed

    Brunner, Thomas B

    2013-04-01

    Although neoadjuvant chemoradiotherapy has been tested for more than two decades and can be safely delivered to patients with non-metastatic pancreatic cancer, no randomised trials have been reported until now. Here we provide an overview of the first randomised trial in patients with potentially resectable cancer and of the latest developments in neoadjuvant therapy for this group of patients. It is necessary to continue to perform clinical trials in this field to accurately identify the effect on survival and quality of life in patients with potentially resectable, borderline resectable and unresectable pancreatic cancer. Aspects of imaging for restaging and clinical prognostic factors are also discussed given they will be useful instruments for future trials.

  9. Clinical and Molecular Methods in Drug Development: Neoadjuvant Systemic Therapy in Breast Cancer as a Model.

    PubMed

    Braga, Sofia

    2016-01-01

    Neoadjuvant chemotherapy (NACT), neoadjuvant endocrine therapy (NAET), and neoadjuvant targeted therapy (NATT), more recently, have been adopted worldwide as standard of care in locally advanced and inoperable BC. These modalities, collectively called neoadjuvant systemic therapy (NAST), are also used for organ preservation and for mechanistic biological studies on drug response and resistance, drug development, and clinical trials. Furthermore, the response to NACT is a valuable indicator of long-term survival. In this work, the advantages and pitfalls of using NAST in BC for studying drug response and resistance for drug development and clinical trials are discussed as well as practical points on how to set up a NAST clinical trial in BC.

  10. HIFU as a Neoadjuvant Therapy in Cancer Treatment

    NASA Astrophysics Data System (ADS)

    Zhong, P.; Xing, F.; Huang, X.; Zhu, H.; Lo, H. W.; Zhong, X.; Pruitt, S.; Robertson, C.

    2011-09-01

    To broaden the application spectrum of HIFU in cancer therapy, we performed a pilot experiment to evaluate the potential of using HIFU as a neoadjuvant therapy prior to surgery. Mice bearing wild-type B16F10 melanoma inoculated subcutaneously were either untreated (control) or treated by HIFU, CPA-7 or HIFU+CPA-7 before surgical resection of the primary tumor two days after HIFU treatment. The animals were then followed for four weeks or up to the humane endpoint to determine local recurrence, distant metastasis, and survival rate. The results demonstrate that animals treated by HIFU+CPA-7 (which is a small molecule that suppresses STAT3 activity) had a significantly lower recurrence rate, and slower growth of the recurrent tumor, with concomitantly higher survival rate, followed by those treated with CPA-7 and HIFU, respectively. Immunological assays revealed that CPA-7 treatment could significantly lower STAT3, and subsequently, Treg activities. In particular, the combination of HIFU and CPA-7 can induce a much stronger anti-tumor immune response than HIFU or surgery alone, as assessed by CTL and IFN-γ secretion. Overall, our results suggest that HIFU in combination with immunotherapy strategies has the potential to be used as a neoadjuvant therapy to prime the host with a strong anti-tumor immune response before surgical resection of the primary tumor. This multimodality, combinational therapy has the potential to greatly broaden the range of HIFU applications in cancer therapy with lower tumor recurrence and improved survival rate.

  11. 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

    SciTech Connect

    Hong, Theodore S.; Moughan, Jennifer; Garofalo, Michael C.; Bendell, Johanna; Berger, Adam C.; Oldenburg, Nicklas B.E.; Anne, Pramila Rani; Perera, Francisco; Jabbour, Salma K.; Nowlan, Adam; DeNittis, Albert; Crane, Christopher

    2015-09-01

    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 of 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.

  12. Resection of borderline resectable pancreatic cancer after neoadjuvant chemoradiation does not depend on improved radiographic appearance of tumor–vessel relationships

    PubMed Central

    Wild, Aaron T.; Raman, Siva P.; Wood, Laura D.; Huang, Peng; Laheru, Daniel A.; Zheng, Lei; De Jesus-Acosta, Ana; Le, Dung T.; Schulick, Richard; Edil, Barish; Ellsworth, Susannah; Pawlik, Timothy M.; Iacobuzio-Donahue, Christine A.; Hruban, Ralph H.; Cameron, John L.; Fishman, Elliot K.; Wolfgang, Christopher L.; Herman, Joseph M.

    2015-01-01

    Objective Neoadjuvant therapy increases rates of margin-negative resection of borderline resectable pancreatic ductal adenocarcinoma (BL-PDAC). Criteria for BL-PDAC resection following neoadjuvant chemotherapy and radiation therapy (NCRT) have not been clearly defined. Methods Fifty consecutive patients with BL-PDAC who received NCRT from 2007 to 2012 were identified. Computed tomography (CT) scans pre- and post-treatment were centrally reviewed. Results Twenty-nine patients (58 %) underwent resection following NCRT, while 21 (42 %) remained unresected. Patients selected for and successfully undergoing resection were more likely to have better performance status and absence of the following features on pre- and post-treatment CT: superior mesenteric vein/portal vein encasement, superior mesenteric artery involvement, tumor involvement of two or more vessels, and questionable/overt metastases (all p <0.05). Tumor volume and degree of tumor–vessel involvement did not significantly change in both groups after NCRT (all p > 0.05). The median overall survival was 22.9 months in resected versus 13.0 months in unresected patients (p < 0.001). Of patients undergoing resection, 93 % were margin-negative, 72 % were node-negative, and 54 % demonstrated moderate pathologic response to NCRT. Conclusion Apparent radiographic extent of vascular involvement does not change significantly after NCRT. Patients without metastatic disease should be chosen for surgical exploration based on adequate performance status and lack of disease progression. PMID:25755849

  13. The influence of neoadjuvant therapy for the prognosis in patients with rectal carcinoma: a retrospective study.

    PubMed

    Li, Qing; Peng, Yu; Wang, Lin-Ang; Wei, Xi; Li, Meng-Xia; Qing, Yi; Xia, Wei; Cheng, Ming; Zi, Dan; Li, Chun-Xue; Wang, Dong

    2016-03-01

    Rectal cancer, defined as a cancerous lesion of the colon distal to the rectosigmoid junction, is the fourth most common cancer cause of death globally. There were 474 patients with rectal cancer who underwent surgery between October 2007 and May 2013 enrolled in our center. Patients were respectively categorized by neoadjuvant therapy. This study aimed to explore the predictive factors that affected the Progression-free survival and overall survival of the patients with rectal cancer. Clinical characteristics of patients were compared with the groups and potential prognostic factors were analyzed by SPSS 19.0. In our study, neoadjuvant therapy increased the anus-retained rate (64.4 vs 53.4 % P = 0.016) and remission rate in the treatment group, compared to the non-treatment group (62.6 vs 34.8 %; P = 0.000). The neoadjuvant concurrent chemoradiotherapy, more operative duration, anus retained and micturition damaged are positive prognostic factors of PFS to patients. Poor differentiation, the tumor of ulcer, invasive, and pT4 stage, contributed the poor factors for PFS of patients (P < 0.05). Additionally, the patients with neoadjuvant concurrent chemoradiotherapy and adjuvant chemotherapy underwent the better prognosis of OS. Adjuvant chemotherapy cannot increase PFS of the patients who accepted neoadjuvant therapy after surgery get pCR, but can improve OS. The anus-retained and neoadjuvant radiotherapy, duration of surgery in rectal cancer have the positive correlation. Micturition damaged and neoadjuvant radiotherapy were positively correlated as well. In conclusion, adjuvant chemotherapy does not improve the PFS of patients with pCR to neoadjuvant therapy, but is good for OS. Further prospective and large population-based clinical studies are needed to establish clinical guidelines for the use of neoadjuvant therapy and adjuvant chemotherapy in patients with rectal cancer.

  14. Adjuvant Chemoradiation Therapy in Gastric Cancer: Critically Reviewing the Past and Visualizing the Next Step Forward

    PubMed Central

    Papadimitriou, Konstantinos; Antoniou, Georgios; Bronte, Giuseppe; Vassiliou, Vassilios; Papamichael, Demetris; Peeters, Marc; Kountourakis, Panteleimon

    2015-01-01

    Gastric cancer remains one of the most common malignancies worldwide. Despite the significant advances in surgical treatment and multimodality strategies, prognosis has modestly improved over the last two decades. Locoregional relapse remains one of the main issues and the combined chemoradiation treatment seems to be one of the preferred approaches. However, more than ten years after the hallmark INT-0116 trial, minimal progress has been made both in terms of effectiveness and toxicity. Moreover, new regimens added to combined therapy failed to prove favourable results. Herein, we attempt a thorough literature review comparing pros and cons of all relative studies and potential bias, targeting well-designed future approaches. PMID:26101524

  15. Adjuvant chemotherapy in rectal cancer: defining subgroups who may benefit after neoadjuvant chemoradiation and resection: a pooled analysis of 3,313 patients.

    PubMed

    Maas, Monique; Nelemans, Patty J; Valentini, Vincenzo; Crane, Christopher H; Capirci, Carlo; Rödel, Claus; Nash, Garrett M; Kuo, Li-Jen; Glynne-Jones, Rob; García-Aguilar, Julio; Suárez, Javier; Calvo, Felipe A; Pucciarelli, Salvatore; Biondo, Sebastiano; Theodoropoulos, George; Lambregts, Doenja M J; Beets-Tan, Regina G H; Beets, Geerard L

    2015-07-01

    Recent literature suggests that the benefit of adjuvant chemotherapy (aCT) for rectal cancer patients might depend on the response to neoadjuvant chemoradiation (CRT). Aim was to evaluate whether the effect of aCT in rectal cancer is modified by response to CRT and to identify which patients benefit from aCT after CRT, by means of a pooled analysis of individual patient data from 13 datasets. Patients were categorized into three groups: pCR (ypT0N0), ypT1-2 tumour and ypT3-4 tumour. Hazard ratios (HR) for the effect of aCT were derived from multivariable Cox regression analyses. Primary outcome measure was recurrence-free survival (RFS). One thousand seven hundred and twenty three (1723) (52%) of 3,313 included patients received aCT. Eight hundred and ninety eight (898) patients had a pCR, 966 had a ypT1-2 tumour and 1,302 had a ypT3-4 tumour. For 122 patients response, category was missing and 25 patients had ypT0N+. Median follow-up for all patients was 51 (0-219) months. HR for RFS with 95% CI for patients treated with aCT were 1.25(0.68-2.29), 0.58(0.37-0.89) and 0.83(0.66-1.10) for patients with pCR, ypT1-2 and ypT3-4 tumours, respectively. The effect of aCT in rectal cancer patients treated with CRT differs between subgroups. Patients with a pCR after CRT may not benefit from aCT, whereas patients with residual tumour had superior outcomes when aCT was administered. The test for interaction did not reach statistical significance, but the results support further investigation of a more individualized approach to administer aCT after CRT and surgery based on pathologic staging.

  16. 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

    SciTech Connect

    Gao, Yuan-Hong; Lin, Jun-Zhong; An, Xin; Luo, Jie-Lin; Cai, Mu-Yan; Cai, Pei-Qiang; Kong, Ling-Heng; Liu, Guo-Chen; Tang, Jing-Hua; Chen, Gong; Pan, Zhi-Zhong; Ding, Pei-Rong

    2014-12-01

    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 consisting 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

  17. Neoadjuvant therapy in muscle-invasive bladder cancer: a model for rational accelerated drug development.

    PubMed

    Balar, Arjun V; Milowsky, Matthew I

    2015-05-01

    Since the advent of cisplatin-based combination therapy in the management of muscle-invasive and advanced bladder cancer, there has been little progress in improving outcomes for patients. Novel therapies beyond cytotoxic chemotherapy are needed. The neoadjuvant paradigm lends to acquiring ample pretreatment and posttreatment tumor tissue as a standard of care, which enables comprehensive biomarker analyses to better understand mechanisms of both response and resistance, which will aid drug development. This article discusses the evolution of neoadjuvant therapy as standard treatment and the role it may serve toward the development of novel therapies.

  18. Improved survival with neoadjuvant therapy and resection for adenocarcinoma of the esophagus.

    PubMed Central

    Stewart, J R; Hoff, S J; Johnson, D H; Murray, M J; Butler, D R; Elkins, C C; Sharp, K W; Merrill, W H; Sawyers, J L

    1993-01-01

    OBJECTIVE: This study sought to determine the impact of preoperative chemotherapy and radiation therapy (neoadjuvant therapy) followed by resection in patients with adenocarcinoma of the esophagus. SUMMARY BACKGROUND DATA: Long-term survival in patients with carcinoma of the esophagus has been poor. An increase in the incidence of adenocarcinoma of the esophagus has been reported recently. METHODS: Fifty-eight patients with biopsy-proven adenocarcinoma of the esophagus treated at this institution from January 1951 through February 1993 were studied. Since 1989, 24 patients were entered prospectively into a multimodality treatment protocol consisting of preoperative cisplatin, 5-fluorouracil (5-FU), and leucovorin with or without etoposide, and concomitant mediastinal radiation (30 Gy). Patients were re-evaluated and offered resection. RESULTS: There were no deaths related to neoadjuvant therapy and toxicity was minimal. Before multimodality therapy was used, the operative mortality rate was 19% (3 of 16 patients). With multimodality therapy, there have been no operative deaths (0 of 23 patients). The median survival time in patients treated before multimodality therapy was 8 months and has yet to be reached for those treated with the neoadjuvant regimen (> 26 months, p < 0.0001). The actuarial survival rate at 24 months was 15% before multimodality therapy and 76% with multimodality therapy. No difference in survival was noted in neoadjuvant protocols with or without etoposide (p = 0.827). CONCLUSIONS: Multimodality therapy with preoperative chemotherapy and radiation therapy followed by resection appears to offer a survival advantage to patients with adenocarcinoma of the esophagus. PMID:8215648

  19. Do Elderly Patients Experience Increased Perioperative or Postoperative Morbidity or Mortality When Given Neoadjuvant Chemoradiation Before Esophagectomy?

    SciTech Connect

    Fogh, Shannon E.; Yu, Anthony; Kubicek, Gregory J.; Scott, Walter; Mitchell, Edith; Rosato, Ernest L.; Berger, Adam C.

    2011-08-01

    Background: The use of induction chemoradiotherapy followed by surgery has been widely used for the treatment of esophageal cancer. The presumed risk of increased postoperative morbidity and mortality with this regimen has led to reluctance to offer this therapy to elderly patients. We compared the perioperative morbidity and mortality of patients 70 years old and older with those of patients younger than 70 who received CRT followed by esophagectomy and sought to identify preoperative risk factors that may predict higher risk of postoperative death or complications. Methods and Materials: We identified 260 patients who underwent preoperative chemoradiotherapy followed by esophagectomy. The association of age with postoperative death and complications was evaluated. The Charlson index, prior cardiac history, and diabetes were identified as preoperative risk factors and were evaluated as potential confounders or effect modifiers. Results: Cardiac disease and the Charlson index were potential modifiers of the effect of age on length of hospital stay (p = 0.08 and p = 0.07, respectively) and postoperative complications (p = 0.1 and p = 0.2) but were not statistically significant. There was a slight nonsignificant decrease in the risk of death in elderly patients after adjustment for the Charlson index (p = 0.2). Conclusion: No significant differences were detected with respect to morbidity and mortality in elderly patients. The presence of cardiac disease, higher scores on the Charlson index, or diabetes did not significantly influence length of stay, postoperative complications, or postoperative death. Given the potential to improve outcomes, this regimen should not be discounted in elderly patients.

  20. Nanoparticle-Based Brachytherapy Spacers for Delivery of Localized Combined Chemoradiation Therapy

    SciTech Connect

    Kumar, Rajiv; Belz, Jodi; Markovic, Stacey; Jadhav, Tej; Fowle, William; Niedre, Mark; Cormack, Robert; Makrigiorgos, Mike G.; Sridhar, Srinivas

    2015-02-01

    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, 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

  1. Neoadjuvant therapy for localized prostate cancer: Examining mechanism of action and efficacy within the tumor

    PubMed Central

    Lou, David Y.; Fong, Lawrence

    2015-01-01

    Objectives Efforts to improve the clinical outcome for patients with localized high-risk prostate cancer have led to the development of neoadjuvant systemic therapies. We review the different modalities of neoadjuvant therapies for localized prostate cancer and highlight emerging treatment approaches including immunotherapy and targeted therapy. Methods We performed a PubMed search of clinical trials evaluating preoperative systemic therapies for treating high-risk prostate cancer published after 2000, and those studies with the highest clinical relevance to current treatment approaches were selected for review. The database at clinicaltrials.gov was queried for neoadjuvant studies in high-risk prostate cancer, and those evaluating novel targeted therapies and immunotherapies are spotlighted here. Results Neoadjuvant chemotherapy has become standard of care for treating some malignancies, including breast and bladder cancers. In prostate cancer, preoperative hormonal therapy or chemotherapy has failed to demonstrate improvements in overall survival. Nevertheless, the emergence of novel treatment modalities such as targeted small molecules and immunotherapy has spawned neoadjuvant clinical trials that provide a unique vantage from which to study mechanism of action and biological potency. Tissue-based biomarkers are being developed to elucidate the biological efficacy of these treatments. With targeted therapy, these can include phospho-proteomic signatures of target pathway activation and deactivation. With immunotherapies, including sipuleucel-T and ipilimumab, recruitment of immune cells to the tumor microenvironment can also be used as robust markers of a biological effect. Such studies can provide insight not only into mechanism of action for these therapies but can also provide paths forward to improving clinical efficacy like with rationally designed combinations and dose selection. Conclusions The use of neoadjuvant androgen-deprivation therapy and

  2. Germline mutations in DNA repair genes may predict neoadjuvant therapy response in triple negative breast patients.

    PubMed

    Spugnesi, Laura; Gabriele, Michele; Scarpitta, Rosa; Tancredi, Mariella; Maresca, Luisa; Gambino, Gaetana; Collavoli, Anita; Aretini, Paolo; Bertolini, Ilaria; Salvadori, Barbara; Landucci, Elisabetta; Fontana, Andrea; Rossetti, Elena; Roncella, Manuela; Naccarato, Giuseppe Antonio; Caligo, Maria Adelaide

    2016-12-01

    Triple negative breast cancers (TNBCs) represent about 15-20% of all breast cancer cases and are characterized by a complex molecular heterogeneity. Some TNBCs exhibit clinical and pathological properties similar to BRCA-mutated tumors, without actually bearing a mutation in BRCA genes. This "BRCAness" phenotype may be explained by germline mutations in other genes involved in DNA repair. Although respond to chemotherapy with alkylating agents, they have a high risk of recurrence and progression. Some studies have shown the efficacy of neoadjuvant therapy in TNBC patients with DNA repair defects, but proper biomarkers of DNA repair deficiency are still needed. Here, we investigated if mutations in DNA repair genes may be correlated with anthracyclines/taxanes neoadjuvant therapy response. DNA from 19 TNBC patients undergoing neoadjuvant therapy were subjected to next generation sequencing of a panel of 24 genes in DNA repair and breast cancer predisposition. In this study, 5 of 19 patients (26%) carried a pathogenic mutation in BRCA1, PALB2, RAD51C and two patients carried a probable pathogenic missense variant. Moreover, VUS (Variants of Unknown Significance) in other genes, predicted to be deleterious by in silico tools, were detected in five patients. Germline mutations in DNA repair genes were found to be associated with the group of TNBC patients who responded to therapy. We conclude that a subgroup of TNBC patients have defects in DNA repair genes, other than BRCA1, and such patients respond favourably to neoadjuvant anthracyclines/taxanes therapy. © 2016 Wiley Periodicals, Inc.

  3. The use of personalized biomarkers and liquid biopsies to monitor treatment response and disease recurrence in locally advanced rectal cancer after neoadjuvant chemoradiation

    PubMed Central

    Carpinetti, Paola; Donnard, Elisa; Bettoni, Fabiana; Asprino, Paula; Koyama, Fernanda; Rozanski, Andrei; Sabbaga, Jorge; Habr-Gama, Angelita; Parmigiani, Raphael B.; Galante, Pedro A.F.; Perez, Rodrigo O.; Camargo, Anamaria A.

    2015-01-01

    Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is the mainstay treatment for locally advanced rectal cancer. Variable degrees of tumor regression are observed after nCRT and alternative treatment strategies, including close surveillance without immediate surgery, have been investigated to spare patients with complete tumor regression from potentially adverse outcomes of radical surgery. However, clinical and radiological assessment of response does not allow accurate identification of patients with complete response. In addition, surveillance for recurrence is similarly important for these patients, as early detection of recurrence allows salvage resections and adjuvant interventions. We report the use of liquid biopsies and personalized biomarkers for monitoring treatment response to nCRT and detecting residual disease and recurrence in patients with rectal cancer. We sequenced the whole-genome of four rectal tumors to identify patient-specific chromosomal rearrangements that were used to monitor circulating tumor DNA (ctDNA) in liquid biopsies collected at diagnosis and during nCRT and follow-up. We compared ctDNA levels to clinical, radiological and pathological response to nCRT. Our results indicate that personalized biomarkers and liquid biopsies may not be sensitive for the detection of microscopic residual disease. However, it can be efficiently used to monitor treatment response to nCRT and detect disease recurrence, preceding increases in CEA levels and radiological diagnosis. Similar good results were observed when assessing tumor response to systemic therapy and disease progression. Our study supports the use of personalized biomarkers and liquid biopsies to tailor the management of rectal cancer patients, however, replication in a larger cohort is necessary to introduce this strategy into clinical practice. PMID:26451609

  4. The use of personalized biomarkers and liquid biopsies to monitor treatment response and disease recurrence in locally advanced rectal cancer after neoadjuvant chemoradiation.

    PubMed

    Carpinetti, Paola; Donnard, Elisa; Bettoni, Fabiana; Asprino, Paula; Koyama, Fernanda; Rozanski, Andrei; Sabbaga, Jorge; Habr-Gama, Angelita; Parmigiani, Raphael B; Galante, Pedro A F; Perez, Rodrigo O; Camargo, Anamaria A

    2015-11-10

    Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is the mainstay treatment for locally advanced rectal cancer. Variable degrees of tumor regression are observed after nCRT and alternative treatment strategies, including close surveillance without immediate surgery, have been investigated to spare patients with complete tumor regression from potentially adverse outcomes of radical surgery. However, clinical and radiological assessment of response does not allow accurate identification of patients with complete response. In addition, surveillance for recurrence is similarly important for these patients, as early detection of recurrence allows salvage resections and adjuvant interventions. We report the use of liquid biopsies and personalized biomarkers for monitoring treatment response to nCRT and detecting residual disease and recurrence in patients with rectal cancer. We sequenced the whole-genome of four rectal tumors to identify patient-specific chromosomal rearrangements that were used to monitor circulating tumor DNA (ctDNA) in liquid biopsies collected at diagnosis and during nCRT and follow-up. We compared ctDNA levels to clinical, radiological and pathological response to nCRT. Our results indicate that personalized biomarkers and liquid biopsies may not be sensitive for the detection of microscopic residual disease. However, it can be efficiently used to monitor treatment response to nCRT and detect disease recurrence, preceding increases in CEA levels and radiological diagnosis. Similar good results were observed when assessing tumor response to systemic therapy and disease progression. Our study supports the use of personalized biomarkers and liquid biopsies to tailor the management of rectal cancer patients, however, replication in a larger cohort is necessary to introduce this strategy into clinical practice.

  5. Persistence of senescent prostate cancer cells following prolonged neoadjuvant androgen deprivation therapy

    PubMed Central

    Blute, Michael L.; Damaschke, Nathan; Wagner, Jennifer; Yang, Bing; Gleave, Martin; Fazli, Ladan; Shi, Fangfang; Abel, E. Jason; Downs, Tracy M.; Huang, Wei; Jarrard, David F.

    2017-01-01

    Purpose Androgen deprivation therapy (ADT) commonly leads to incomplete cell death and the fate of persistent cells involves, in part, a senescent phenotype. Senescence is terminal growth arrest in response to cell stress that is characterized by increased lysosomal-β-galactosidase (GLB1) the origin of senescence associated-β-gal activity (SA-β-gal). In the current study senescence is examined in vivo after ADT use in a neoadjuvant trial. Methods and materials Tissue microarrays were generated from prostate cancer specimens (n = 126) from a multicenter neoadjuvant ADT trial. Arrays were subjected to multiplexed immunofluorescent staining for GLB1, Ki67, cleaved caspase 3 (CC3) and E-cadherin. Automated quantitative imaging was performed using Vectra™ and expression correlated with clinicopathologic features. Results Tissue was analyzed from 59 patients treated with neoadjuvant ADT and 67 receiving no therapy preoperatively. Median follow-up was 85.3 mo and median ADT treatment was 5 mo. In PC treated with neoadjuvant ADT, GLB1 expression increased in intermediate Gleason score (GS 6–7; p = 0.001), but not high grade (GS 8–10) cancer. Significantly higher levels of GLB1 were seen in tissues undergoing neoadjuvant ADT longer than 5 months compared to untreated tissues (p = 0.002). In contrast, apoptosis significantly increased earlier (1–4 mo) after ADT treatment (p<0.5). Conclusions Increased GLB1 after neoadjuvant ADT occurs primarily among more clinically favorable intermediate grade cancers and enrichment of the phenotype occurs in a temporally prolonged fashion. Senescence may explain the persistence of PCa cells after ADT. Given concerns for the detrimental longer term presence of senescent cells, targeting these cells for removal may improve outcomes. PMID:28234906

  6. Prevalence and Predictors of Neoadjuvant Therapy for Stage IIIA Non-Small Cell Lung Cancer in the National Cancer Database: Importance of Socioeconomic Status and Treating Institution

    SciTech Connect

    Sher, David J.; Liptay, Michael J.; Fidler, Mary Jo

    2014-06-01

    Purpose: The optimal locoregional therapy for stage IIIA non-small cell lung cancer (NSCLC) is controversial, with definitive chemoradiation therapy (CRT) and neoadjuvant therapy followed by surgery (NT-S) serving as competing strategies. In this study, we used the National Cancer Database to determine the prevalence and predictors of NT in a large, modern cohort of patients. Methods and Materials: Patients with stage IIIA NSCLC treated with CRT or NT-S between 2003 and 2010 at programs accredited by the Commission on Cancer were included. Predictors were categorized as clinical, time/geographic, socioeconomic, and institutional. In accord with the National Cancer Database, institutions were classified as academic/research program and as comprehensive and noncomprehensive community cancer centers. Logistic regression and random effects multilevel logistic regression were performed for univariable and multivariable analyses, respectively. Results: The cohort consisted of 18,581 patients, 3,087 (16.6%) of whom underwent NT-S (10.6% induction CRT, 6% induction chemotherapy). The prevalence of NT-S was constant over time, but there were significant relative 31% and 30% decreases in pneumonectomy and right-sided pneumonectomy, respectively, over time (P trend <.02). In addition to younger age, lower T stage, and favorable comorbidity score, indicators of higher socioeconomic status were strong independent predictors of NT-S, including white race, higher income, and private/managed insurance. The type of institution (academic/research program vs comprehensive or noncomprehensive community cancer centers, odds ratio 1.54 and 2.08, respectively) strongly predicted NT-S, but treatment volume did not. Conclusions: Neoadjuvant therapy followed by surgery was an uncommon treatment approach in Commission on Cancer programs, and the prevalence of postinduction pneumonectomy decreased over time. Higher socioeconomic status and treatment at academic institutions were significant

  7. Pneumo-CT assessing response to neoadjuvant therapy in esophageal cancer: Imaging-pathological correlation.

    PubMed

    Ulla, Marina; Gentile, Ernestina; Yeyati, Ezequiel Levy; Diez, Maria L; Cavadas, Demetrio; Garcia-Monaco, Ricardo D; Ros, Pablo R

    2013-12-15

    Pneumo-computed tomography (PnCT) is a technique primarily developed and used to study stenotic lesions of the esophagus, gastroesophageal junction and stomach for pre-surgical planning. It helps to define both upper and lower borders of neoplasms located in the aforementioned areas. It achieves maximum lumen distension with CO2 highlighting thickened areas of the esophageal wall, thus allowing an accurate quantification of their extents. Although there are other alternatives for distension (oral contrast agents, water and effervescent granules), they may be suboptimal. Patients with locally advanced esophageal cancer have a dismal prognosis despite surgical resection. Therefore, neoadjuvant treatment strategies using radiation therapy and chemotherapy were developed to improve survival. Neoadjuvant therapy improves esophageal tumor prognosis in a substantial proportion of patients, and the use of imaging techniques is mandatory to detect their response. PnCT combined with virtual endoscopy and multiplanar reconstruction enhances morphologic details in esophageal cancer, and thus would allow an improved assessment of response to neoadjuvant treatment. Therefore, more information could be provided to assess the efficacy of pre-surgical treatment. We describe the potential use of PnCT to assess the response to neoadjuvant therapy in esophageal cancer with an imaging pathologic correlation.

  8. Pneumo-CT assessing response to neoadjuvant therapy in esophageal cancer: Imaging-pathological correlation

    PubMed Central

    Ulla, Marina; Gentile, Ernestina; Yeyati, Ezequiel Levy; Diez, Maria L; Cavadas, Demetrio; Garcia-Monaco, Ricardo D; Ros, Pablo R

    2013-01-01

    Pneumo-computed tomography (PnCT) is a technique primarily developed and used to study stenotic lesions of the esophagus, gastroesophageal junction and stomach for pre-surgical planning. It helps to define both upper and lower borders of neoplasms located in the aforementioned areas. It achieves maximum lumen distension with CO2 highlighting thickened areas of the esophageal wall, thus allowing an accurate quantification of their extents. Although there are other alternatives for distension (oral contrast agents, water and effervescent granules), they may be suboptimal. Patients with locally advanced esophageal cancer have a dismal prognosis despite surgical resection. Therefore, neoadjuvant treatment strategies using radiation therapy and chemotherapy were developed to improve survival. Neoadjuvant therapy improves esophageal tumor prognosis in a substantial proportion of patients, and the use of imaging techniques is mandatory to detect their response. PnCT combined with virtual endoscopy and multiplanar reconstruction enhances morphologic details in esophageal cancer, and thus would allow an improved assessment of response to neoadjuvant treatment. Therefore, more information could be provided to assess the efficacy of pre-surgical treatment. We describe the potential use of PnCT to assess the response to neoadjuvant therapy in esophageal cancer with an imaging pathologic correlation. PMID:24363830

  9. Predictive Biomarkers to Chemoradiation in Locally Advanced Rectal Cancer

    PubMed Central

    Conde-Muíño, Raquel; Cuadros, Marta; Zambudio, Natalia; Segura-Jiménez, Inmaculada; Cano, Carlos; Palma, Pablo

    2015-01-01

    There has been a high local recurrence rate in rectal cancer. Besides improvements in surgical techniques, both neoadjuvant short-course radiotherapy and long-course chemoradiation improve oncological results. Approximately 40–60% of rectal cancer patients treated with neoadjuvant chemoradiation achieve some degree of pathologic response. However, there is no effective method of predicting which patients will respond to neoadjuvant treatment. Recent studies have evaluated the potential of genetic biomarkers to predict outcome in locally advanced rectal adenocarcinoma treated with neoadjuvant chemoradiation. The articles produced by the PubMed search were reviewed for those specifically addressing a genetic profile's ability to predict response to neoadjuvant treatment in rectal cancer. Although tissue gene microarray profiling has led to promising data in cancer, to date, none of the identified signatures or molecular markers in locally advanced rectal cancer has been successfully validated as a diagnostic or prognostic tool applicable to routine clinical practice. PMID:26504848

  10. Predictive Biomarkers to Chemoradiation in Locally Advanced Rectal Cancer.

    PubMed

    Conde-Muíño, Raquel; Cuadros, Marta; Zambudio, Natalia; Segura-Jiménez, Inmaculada; Cano, Carlos; Palma, Pablo

    2015-01-01

    There has been a high local recurrence rate in rectal cancer. Besides improvements in surgical techniques, both neoadjuvant short-course radiotherapy and long-course chemoradiation improve oncological results. Approximately 40-60% of rectal cancer patients treated with neoadjuvant chemoradiation achieve some degree of pathologic response. However, there is no effective method of predicting which patients will respond to neoadjuvant treatment. Recent studies have evaluated the potential of genetic biomarkers to predict outcome in locally advanced rectal adenocarcinoma treated with neoadjuvant chemoradiation. The articles produced by the PubMed search were reviewed for those specifically addressing a genetic profile's ability to predict response to neoadjuvant treatment in rectal cancer. Although tissue gene microarray profiling has led to promising data in cancer, to date, none of the identified signatures or molecular markers in locally advanced rectal cancer has been successfully validated as a diagnostic or prognostic tool applicable to routine clinical practice.

  11. Diffuse optical measurements of head and neck tumor hemodynamics for early prediction of chemoradiation therapy outcomes

    NASA Astrophysics Data System (ADS)

    Dong, Lixin; Kudrimoti, Mahesh; Irwin, Daniel; Chen, Li; Kumar, Sameera; Shang, Yu; Huang, Chong; Johnson, Ellis L.; Stevens, Scott D.; Shelton, Brent J.; Yu, Guoqiang

    2016-08-01

    This study used a hybrid near-infrared diffuse optical instrument to monitor tumor hemodynamic responses to chemoradiation therapy for early prediction of treatment outcomes in patients with head and neck cancer. Forty-seven patients were measured once per week to evaluate the hemodynamic status of clinically involved cervical lymph nodes as surrogates for the primary tumor response. Patients were classified into two groups: complete response (CR) (n=29) and incomplete response (IR) (n=18). Tumor hemodynamic responses were found to be associated with clinical outcomes (CR/IR), wherein the associations differed depending on human papillomavirus (HPV-16) status. In HPV-16 positive patients, significantly lower levels in tumor oxygenated hemoglobin concentration ([HbO2]) at weeks 1 to 3, total hemoglobin concentration at week 3, and blood oxygen saturation (StO2) at week 3 were found in the IR group. In HPV-16 negative patients, significantly higher levels in tumor blood flow index and reduced scattering coefficient (μs‧) at week 3 were observed in the IR group. These hemodynamic parameters exhibited significantly high accuracy for early prediction of clinical outcomes, within the first three weeks of therapy, with the areas under the receiver operating characteristic curves (AUCs) ranging from 0.83 to 0.96.

  12. 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

    SciTech Connect

    Kim, Tae Hyun; Park, Sook Ryun; Ryu, Keun Won; Kim, Young-Woo; Bae, Jae-Moon; Lee, Jun Ho; Choi, Il Ju; Kim, Yeon-Joo; Kim, Dae Yong

    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 chemoradiation 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.

  13. Neoadjuvant antiangiogenic therapy reveals contrasts in primary and metastatic tumor efficacy.

    PubMed

    Ebos, John M L; Mastri, Michalis; Lee, Christina R; Tracz, Amanda; Hudson, John M; Attwood, Kristopher; Cruz-Munoz, William R; Jedeszko, Christopher; Burns, Peter; Kerbel, Robert S

    2014-10-31

    Thousands of cancer patients are currently in clinical trials evaluating antiangiogenic therapy in the neoadjuvant setting, which is the treatment of localized primary tumors prior to surgical intervention. The rationale is that shrinking a tumor will improve surgical outcomes and minimize growth of occult micrometastatic disease-thus delaying post-surgical recurrence and improving survival. But approved VEGF pathway inhibitors have not been tested in clinically relevant neoadjuvant models that compare pre- and post-surgical treatment effects. Using mouse models of breast, kidney, and melanoma metastasis, we demonstrate that primary tumor responses to neoadjuvant VEGFR TKI treatment do not consistently correlate with improved post-surgical survival, with survival worsened in certain settings. Similar negative effects did not extend to protein-based VEGF pathway inhibitors and could be reversed with altered dose, surgical timing, and treatment duration, or when VEGFR TKIs are combined with metronomic 'anti-metastatic' chemotherapy regimens. These studies represent the first attempt to recapitulate the complex clinical parameters of neoadjuvant therapy in mice and identify a novel tool to compare systemic antiangiogenic treatment effects on localized and disseminated disease.

  14. Adjuvant Chemoradiation Therapy After Pancreaticoduodenectomy in Elderly Patients With Pancreatic Adenocarcinoma

    SciTech Connect

    Horowitz, David P.; Hsu, Charles C.; Wang Jingya; Makary, Martin A.; Winter, Jordan M.; Robinson, Ray; Schulick, Richard D.; Cameron, John L.; Pawlik, Timothy M.; Herman, Joseph M.

    2011-08-01

    Purpose: To evaluate the efficacy of adjuvant chemoradiation therapy (CRT) for pancreatic adenocarcinoma patients {>=}75 years of age. Methods: The study group of 655 patients underwent pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma at the Johns Hopkins Hospital over a 12-year period (8/30/1993 to 2/28/2005). Demographic characteristics, comorbidities, intraoperative data, pathology data, and patient outcomes were collected and analyzed by adjuvant treatment status and age {>=}75 years. Cox proportional hazards analysis determined clinical predictors of mortality and morbidity. Results: We identified 166 of 655 (25.3%) patients were {>=}75 years of age and 489 of 655 patients (74.7%) were <75 years of age. Forty-nine patients in the elderly group (29.5%) received adjuvant CRT. For elderly patients, node-positive metastases (p = 0.008), poor/anaplastic differentiation (p = 0.012), and undergoing a total pancreatectomy (p = 0.010) predicted poor survival. The 2-year survival for elderly patients receiving adjuvant therapy was improved compared with surgery alone (49.0% vs. 31.6%, p = 0.013); however, 5-year survival was similar (11.7% vs. 19.8%, respectively, p = 0.310). After adjusting for major confounders, adjuvant therapy in elderly patients had a protective effect with respect to 2-year survival (relative risk [RR] 0.58, p = 0.044), but not 5-year survival (RR 0.80, p = 0.258). Among the nonelderly, CRT was significantly associated with 2-year survival (RR 0.60, p < 0.001) and 5-year survival (RR 0.69, p < 0.001), after adjusting for confounders. Conclusions: Adjuvant therapy after PD is significantly associated with increased 2-year but not 5-year survival in elderly patients. Additional studies are needed to select which elderly patients are likely to benefit from adjuvant CRT.

  15. DNA-Platinum Thin Films for Use in Chemoradiation Therapy Studies

    PubMed Central

    Rezaee, Mohammad; Alizadeh, Elahe; Hunting, Darel; Sanche, Léon

    2012-01-01

    Dry films of platinum chemotherapeutic drugs covalently bound to plasmid DNA (Pt-DNA) represent a useful experimental model to investigate direct effects of radiation on DNA in close proximity to platinum chemotherapeutic agents, a situation of considerable relevance to understand the mechanisms underlying concomitant chemoradiation therapy. In the present paper we determine the optimum conditions for preparation of Pt-DNA films for use in irradiation experiments. Incubation conditions for DNA platination reactions have a substantial effect on the structure of Pt-DNA in the films. The quantity of Pt bound to DNA as a function of incubation time and temperature is measured by inductively coupled plasma mass spectroscopy. Our experiments indicate that chemical instability and damage to DNA in Pt-DNA samples increase when DNA platination occurs at 37°C for 24 hours, the condition which has been extensively used for in vitro studies. Platination of DNA for the formation of Pt-DNA films is optimal at room temperature for reaction times less than 2 hours. By increasing the concentration of Pt compounds relative to DNA and thus accelerating the rate of their mutual binding, it is possible to prepare Pt-DNA samples containing known concentrations of Pt while reducing DNA degradation caused by more lengthy procedures. PMID:21977010

  16. Effects of Treatment Duration During Concomitant Chemoradiation Therapy for Cervical Cancer

    SciTech Connect

    Shaverdian, Narek; Gondi, Vinai; Sklenar, Kathryn L.; Dunn, Emily F.; Petereit, Daniel G.; Straub, Margaret R.; Bradley, Kristin A.

    2013-07-01

    Purpose: To determine whether extended treatment duration (TD) impacts in-field relapse and survival in the setting of concomitant chemoradiation therapy (CRT) for cervical cancer. Methods and Materials: A total of 480 consecutive cervical cancer patients treated with radiation therapy (RT) alone or concomitant CRT for curative intent were retrospectively analyzed. Relapse was defined as in-field with respect to external beam radiation therapy fields. The effects of TD on in-field relapse, disease-free survival (DFS), and overall survival (OS) rates were assessed continuously and categorically within the separate RT and CRT cohorts. Covariates included age, histology, stage, and cumulative dose to point A. In-field relapse, DFS, and OS rates were estimated with Kaplan-Meier analysis; comparisons used log–rank statistic. Multivariate analysis used the Cox proportional hazards model. Results: A total of 372 patients (RT n=206, CRT n=166) were evaluable, with a median follow-up for relapse-free patients of 4.2 years (RT 4.4 years, CRT 4.2 years; P=.807). Treatment duration was longer in the RT cohort (median 55 days; range 35-99 days) versus the CRT cohort (median 51 days; range 35-92 days) (P=.001). In the RT cohort, TD ≥62 days trended to significance for predicting inferior DFS (hazard ratio 1.42, 95% confidence interval 0.86-1.98, P=.086). However, in the CRT cohort, TD assessed continuously or categorically across multiple cutoff thresholds did not predict for in-field relapse, DFS, or OS. Conclusion: With RT alone, extended TD ≥62 days may adversely impact treatment efficacy. With the addition of concomitant chemotherapy to RT, however, extended TD has no effect on treatment efficacy.

  17. Preoperative Chemoradiation Therapy in Combination With Panitumumab for Patients With Resectable Esophageal Cancer: The PACT Study

    SciTech Connect

    Kordes, Sil; Berge Henegouwen, Mark I. van; Hulshof, Maarten C.; Bergman, Jacques J.G.H.M.; Vliet, Hans J. van der; Kapiteijn, Ellen; Laarhoven, Hanneke W.M. van; Richel, Dick J.; Klinkenbijl, Jean H.G.; Meijer, Sybren L.; Wilmink, Johanna W.

    2014-09-01

    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 23 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%.

  18. [11C]Choline PET/CT in therapy response assessment of a neoadjuvant therapy in locally advanced and high risk prostate cancer before radical prostatectomy

    PubMed Central

    Schwarzenböck, Sarah M.; Knieling, Anna; Souvatzoglou, Michael; Kurth, Jens; Steiger, Katja; Eiber, Matthias; Esposito, Irene; Retz, Margitta; Kübler, Hubert; Gschwend, Jürgen E.; Schwaiger, Markus; Krause, Bernd J.; Thalgott, Mark

    2016-01-01

    Purpose Recent studies have shown promising results of neoadjuvant therapy in prostate cancer (PC). The aim of this study was to evaluate the potential of [11C]Choline PET/CT in therapy response monitoring after combined neoadjuvant docetaxel chemotherapy and complete androgen blockade in locally advanced and high risk PC patients. Results In [11C]Choline PET/CT there was a significant decrease of SUVmax and SUVmean (p = 0.004, each), prostate volume (p = 0.005) and PSA value (p = 0.003) after combined neoadjuvant therapy. MRI showed a significant prostate and tumor volume reduction (p = 0.003 and 0.005, respectively). Number of apoptotic cells was significantly higher in prostatectomy specimens of the therapy group compared to pretherapeutic biopsies and the control group (p = 0.02 and 0.003, respectively). Methods 11 patients received two [11C]Choline PET/CT and MRI scans before and after combined neoadjuvant therapy followed by radical prostatectomy and pelvic lymph node dissection. [11C]Choline uptake, prostate and tumor volume, PSA value (before/after neoadjuvant therapy) and apoptosis (of pretherapeutic biopsy/posttherapeutic prostatectomy specimens of the therapy group and prostatectomy specimens of a matched control group without neoadjuvant therapy) were assessed and tested for differences and correlation using SPSS. Conclusions The results showing a decrease in choline uptake after combined neoadjuvant therapy (paralleled by regressive and apoptotic changes in histopathology) confirm the potential of [11C]Choline PET/CT to monitor effects of neoadjuvant therapy in locally advanced and high risk PC patients. Further studies are recommended to evaluate its use during the course of neoadjuvant therapy for early response assessment. PMID:27572317

  19. Induction chemoradiation therapy prior to esophagectomy is associated with superior long-term survival for esophageal cancer.

    PubMed

    Speicher, P J; Wang, X; Englum, B R; Ganapathi, A M; Yerokun, B; Hartwig, M G; D'Amico, T A; Berry, M F

    2015-01-01

    The purpose of this study was to examine the role of induction chemoradiation in the treatment of potentially resectable locally advanced (T2-3N0 and T1-3N+) esophageal cancer utilizing a large national database. The National Cancer Data Base (NCDB) was queried for all patients undergoing esophagectomy for clinical T2-3N0 and T1-3N+ esophageal cancer of the mid- or lower esophagus. Patients were stratified by the use of induction chemoradiation therapy versus surgery-first. Trends were assessed with the Cochran-Armitage test. Predictors of receiving induction therapy were evaluated with multivariable logistic regression. A propensity-matched analysis was conducted to compare outcomes between groups, and the Kaplan-Meier method was used to estimate long-term survival. Within the NCDB, 7921 patients were identified, of which 6103 (77.0%) were treated with chemoradiation prior to esophagectomy, while the remaining 1818 (23.0%) were managed with surgery-first. Use of induction therapy increased over time, with an absolute increase of 11.8% from 2003-2011 (P < 0.001). As revealed by the propensity model, induction therapy was associated with higher rates of negative margins and shorter hospital length of stay, but no differences in unplanned readmission and 30-day mortality rates. In unadjusted survival analysis, induction therapy was associated with better long-term survival compared to a strategy of surgery-first, with 5-year survival rates of 37.2% versus 28.6%, P < 0.001. Following propensity score matching analysis, the use of induction therapy maintained a significant survival advantage over surgery-first (5-year survival: 37.9% vs. 28.7%, P < 0.001). Treatment with induction chemoradiation therapy prior to surgical resection is associated with significant improvement in long-term survival, even after adjusting for confounders with a propensity model. Induction therapy should be considered in all medically appropriate patients with resectable cT2-3N0 and cT1-3N

  20. Prognostic value of pre-therapy platelet elevation in oropharyngeal cancer patients treated with chemoradiation

    PubMed Central

    Shoultz-Henley, Sara; Garden, Adam S.; Mohamed, Abdallah S. R.; Sheu, Tommy; Kroll, Michael H.; Rosenthal, David I.; Gunn, G. Brandon; Hayes, Amos J.; French, Chloe; Eichelberger, Hillary; Kalpathy-Cramer, Jayashree; Smith, Blaine D.; Phan, Jack; Ayoub, Zeina; Lai, Stephen Y.; Pham, Brian; Kies, Merrill; Gold, Kathryn A.; Sturgis, Erich; Fuller, Clifton D.

    2016-01-01

    The purpose of this study is to evaluate potential associations between increased platelets and oncologic outcomes in oropharyngeal cancer patients receiving concurrent chemoradiation. 433 oropharyngeal cancer patients (OPC) treated with intensity modulated radiation therapy (IMRT) with concurrent chemotherapy between 2002 and 2012 were included under an approved IRB protocol. Complete blood count (CBC) data was extracted. Platelet and hemoglobin from the last phlebotomy (PLTpre-chemoRT, Hgbpre-chemoRT) before start of treatment were identified. Patients were risk-stratified using Dahlstrom-Sturgis criteria and were tested for association with survival and disease-control outcomes. Locoregional control (LRC), freedom from distant metastasis (FDM) and overall survival (OS) were decreased (p<0.03, p<0.04, and p<0.0001, respectively) for patients with PLT pre-chemoRT value of ≥350 × 109/L. Actuarial 5-year locoregional control (LRC) and FDM were 83% and 85% for non-thrombcythemic patients while patient with high platelets had 5-year LRC and FDM of 73% and 74%, respectively. Likewise, 5- year OS were better for patients with normal platelet counts by comparison (76% vs. 57%; p<0.0001). Comparison of univariate parametric models demonstrated PLTpre-chemoRT was better among tested models. Multivariate assessment demonstrated improved performance of models which included pre-therapy platelet indices. On Bayesian information criteria analysis, the optimal prognostic model was then used to develop nomograms predicting 3-, 5-, and 10-year OS. In conclusion, pre-treatment platelet elevation is a promising predictor of prognosis, and further work should be done to elucidate the utility of anti-platelets in modifying risk in OPC patients. PMID:26414107

  1. Gastroduodenal Complications After Concurrent Chemoradiation Therapy in Patients With Hepatocellular Carcinoma: Endoscopic Findings and Risk Factors

    SciTech Connect

    Chon, Young Eun; Seong, Jinsil; Kim, Beom Kyung; Cha, Jihye; Kim, Seung Up; Park, Jun Yong; Ahn, Sang Hoon; Han, Kwang-Hyub; Chon, Chae Yoon; Shin, Sung Kwan; Kim, Do Young

    2011-12-01

    Purpose: Concurrent chemoradiation therapy (CCRT) is useful in advanced hepatocellular carcinoma (HCC), but little is known about radiation-induced gastroduodenal complications following therapy. To determine risk factors, we investigated the prevalence and patterns of gastroduodenal complications following CCRT using endoscopy. Methods and Materials: Enrolled in the study were 123 patients treated with CCRT for unresectable HCC between January 1998 and December 2005. Radiation-induced gastroduodenal complications were defined as radiation gastritis/duodenitis, radiation gastric/duodenal ulcer, or other gastroduodenal toxicity associated with radiation, based on Common Terminology Criteria for Adverse Events (CTCAE 3.0). Serious gastroduodenal complications were defined as events occurring within 12 months from completion of CCRT, those requiring prompt therapeutic intervention, or symptoms equivalent to Grade 3 or 4 radiation-related gastroduodenal toxicity, including nausea or vomiting, based on CTCAE 3.0. Results: A month after completion of CCRT, 65 (52.8%) patients displayed endoscopic evidence of radiation-induced gastroduodenal complications. Radiation gastric and duodenal ulcers were found in 32 (26.0%) and 20 (16.3%) patients, respectively; radiation gastritis and duodenitis were found in 50 (40.7%) and 42 (34.1%) patients, respectively. Radiation-related bleeding was observed in 13 patients (10.6%). Serious gastroduodenal complications occurred in 18 patients (14.6%) and were significantly more frequent in patients with liver cirrhosis than in those without cirrhosis (p = 0.043). There were no radiation-related deaths. Conclusions: Endoscopically detectable radiation-induced gastroduodenal complications were common in HCC following CCRT. Although serious complications were uncommon, the frequency was higher in patients with liver cirrhosis; thus, these patients should be closely monitored when receiving CCRT.

  2. Lymph node extramedullary hematopoiesis in breast cancer patients receiving neoadjuvant therapy: a potential diagnostic pitfall.

    PubMed

    Prieto-Granada, Carlos; Setia, Namrata; Otis, Christopher N

    2013-06-01

    Extramedullary hematopoiesis (EMH) develops as a compensatory mechanism associated with hematologic processes but it may occur in association with chemotherapy. Three cases of EMH arising in axillary lymph nodes following neoadjuvant therapy for breast carcinoma are reported herein. Three women ranging in age from 41 to 47 years presented with unilateral breast masses measuring 0.6 to 4.0 cm in greatest dimension and were diagnosed with infiltrating ductal carcinoma, grade III by core needle biopsies. Two of the tumors were triple negative and one was estrogen receptor positive. All patients subsequently received neoadjuvant therapy followed by lumpectomies. No residual carcinoma was identified in postchemotherapy breast resection specimens. One patient underwent a sentinel lymph node procedure, the second patient an axillary lymph node dissection, and the third patient had a core biopsy of an enlarged axillary lymph node. The patient that underwent axillary lymph node dissection had metastatic carcinoma in one of her lymph nodes. Foci of EMH consisting of myeloid, erythroid, and megakaryocytic precursors were present within the nodal parenchyma and/or subcapsular sinuses of axillary lymph nodes of all three cases. Megakaryocytes were immunoreactive with factor VIII, erythroid elements with Glycophorin and myeloid precursors with myeloperoxidase. With increasing use of neoadjuvant therapy for breast carcinoma, EMH within lymph nodes is more likely to be encountered. Hematopoietic precursors present in lymph nodes may potentially be misdiagnosed as metastatic tumor cells, particularly as lobular carcinoma or metaplastic carcinoma. Therefore, caution should be exercised when evaluating axillary lymph nodes in the clinical setting of neoadjuvant therapy for breast carcinoma.

  3. Low-Dose Neoadjuvant External Beam Radiation Therapy for Soft Tissue Sarcoma

    SciTech Connect

    Devisetty, Kiran; Kobayashi, Wendy; Suit, Herman D.; Goldberg, Saveli I.; Niemierko, Andrzej; Chen, Yen-Lin E.; Raskin, Kevin A.; Schwab, Joseph H.; Springfield, Dempsey S.; Yoon, Sam S.; Hornicek, Francis J.; DeLaney, Thomas F.

    2011-07-01

    Purpose: For soft tissue sarcoma, neoadjuvant external beam radiation therapy (EBRT) to 50 Gy has the same local control (LC) and overall survival as postoperative radiation therapy (PORT) to 60 Gy, but with increased wound complications. We examined whether low-dose neoadjuvant EBRT would decrease acute toxicity while maintaining LC. Methods and Materials: From 1971 to 2008, 1,765 patients with nonmetastatic soft tissue sarcoma were treated with radiation therapy at Massachusetts General Hospital. We identified 42 patients treated with low-dose neoadjuvant EBRT (median, 20 Gy; range, 16-26) followed by surgical resection and PORT. PORT included EBRT (25 patients; median, 40 Gy; range, 20-56.2), brachytherapy (13 patients; median, 42 Gy; range, 26-50), and intraoperative radiation therapy (IORT) (4 patients; median, 12.5 Gy; range, 8-20). The median total dose was 63.3 Gy (range, 28-78.4). Results: Median follow-up was 36 months (range, 4-318). Severe acute wound complications were reported in 15 patients (36%) and correlated to PORT technique (16% EBRT, 69% brachytherapy, 50% IORT, p = 0.004). The 5-year LC was 73% and correlated to PORT technique (68% EBRT, 100% brachytherapy, 50% IORT, p = 0.03) and histology (p = 0.05), with a trend to improvement if >60 Gy (p = 0.10). The 5-year overall survival was 65% and correlated to extent of resection (p < 0.001) and margin status (p < 0.001). Conclusions: Despite using low-dose neoadjuvant EBRT, we report a high rate of severe acute wound complications that was strongly associated with brachytherapy. Modification of the brachytherapy technique may decrease acute toxicity while maintaining excellent local control. Further study must be conducted before recommending broader application.

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

    SciTech Connect

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

    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 62.5 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.

  5. Neoadjuvant hormonal therapy for endocrine sensitive breast cancer: a systematic review.

    PubMed

    Charehbili, A; Fontein, D B Y; Kroep, J R; Liefers, G J; Mieog, J S D; Nortier, J W R; van de Velde, C J H

    2014-02-01

    In recent years, studies investigating neoadjuvant therapies have been emerging, because of the additional benefits it provides in terms of facilitating less extensive surgery and the possibility of investigating tumor biological features and response. Neoadjuvant hormonal therapy (NHT) is, in general, considered to be a suitable option for hormone receptor (HR)-positive patients who are unfit for chemotherapy or surgery, and is increasingly being utilized to achieve tumor downsizing before surgery in postmenopausal women. Studies investigating NHT were reviewed for tumor response data. NHT demonstrated similar efficacy to neoadjuvant chemotherapy (NCT) in HR-positive breast cancer patients. Clinical responses ranged from 13.5% to 100%, with treatment periods between 3 and 24 months. In studies comparing tamoxifen with aromatase inhibitors, the latter were superior in terms of tumor response and rates of breast-conserving surgery (BCS). In most studies with treatment durations longer than 3 months, tumor response rates increased. Therefore, longer durations of NHT are feasible and should be considered as an alternative to NCT in selected patients.

  6. Neo-adjuvant chemo(radio)therapy in gastric cancer: Current status and future perspectives

    PubMed Central

    Biondi, Alberto; Lirosi, Maria C; D’Ugo, Domenico; Fico, Valeria; Ricci, Riccardo; Santullo, Francesco; Rizzuto, Antonia; Cananzi, Ferdinando CM; Persiani, Roberto

    2015-01-01

    In the last 20 years, several clinical trials on neoadjuvant chemotherapy and chemo-radiotherapy as a therapeutic approach for locally advanced gastric cancer have been performed. Even if more data are necessary to define the roles of these approaches, the results of preoperative treatments in the combined treatment of gastric adenocarcinoma are encouraging because this approach has led to a higher rate of curative surgical resection. Owing to the results of most recent randomized phase III studies, neoadjuvant chemotherapy for locally advanced resectable gastric cancer has satisfied the determination of level I evidence. Remaining concerns pertain to the choice of the optimal therapy regimen, strict patient selection by accurate pre-operative staging, standardization of surgical procedures, and valid criteria for response evaluation. New well-designed trials will be necessary to find the best therapeutic approach in pre-operative settings and the best way to combine old-generation chemotherapeutic drugs with new-generation molecules. PMID:26690252

  7. Rationale for and review of neoadjuvant therapy prior to radical prostatectomy for patients with high-risk prostate cancer.

    PubMed

    McKay, Rana R; Choueiri, Toni K; Taplin, Mary-Ellen

    2013-09-01

    Despite state of the art local therapy, a significant portion of men with high-risk prostate cancer develop progressive disease. Neoadjuvant systemic therapy prior to radical prostatectomy (RP) is an approach that can potentially maximize survival outcomes in patients with localized disease. This approach is under investigation with a wide array of agents and provides an opportunity to assess pathologic and biologic activity of novel treatments. The aim of this review is to explore the past and present role of neoadjuvant therapy prior to definitive therapy with RP in patients with high-risk localized or locally advanced disease. The results of neoadjuvant androgen-deprivation therapy (ADT), including use of newer agents such as abiraterone, are promising. Neoadjuvant chemotherapy, primarily with docetaxel, with or without ADT has also demonstrated efficacy in men with high-risk disease. Other novel agents targeting the vascular endothelial growth factor receptor (VEGFR), epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), clusterin, and the immune system are currently under investigation and have led to variable results in early clinical trials. Despite optimistic data, approval of neoadjuvant therapy prior to RP in patients with high-risk prostate cancer will depend on positive results from well designed phase III trials.

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

    PubMed Central

    Krishnan, Sunil; Chadha, Awalpreet S.; Suh, Yelin; Chen, Hsiang-Chun; Rao, Arvind; Das, Prajnan; Minsky, Bruce D.; Mahmood, Usama; Delclos, Marc E.; Sawakuchi, Gabriel O.; Beddar, Sam; Katz, Matthew H.; Fleming, Jason B.; Javle, Milind M.; Varadhachary, Gauri R.; Wolff, Robert A.; Crane, Christopher H.

    2016-01-01

    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 was 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. PMID:26972648

  9. Genetic changes of non-small cell lung cancer under neoadjuvant therapy

    PubMed Central

    Warth, Arne; Endris, Volker; Stenzinger, Albrecht; Penzel, Roland; Harms, Alexander; Duell, Thomas; Abdollahi, Amir; Lindner, Michael; Schirmacher, Peter; Muley, Thomas; Dienemann, Hendrik; Fink, Ludger; Morresi-Hauf, Alicia; Pfarr, Nicole; Weichert, Wilko

    2016-01-01

    Background Large scale sequencing efforts defined common molecular alterations in non-small cell lung cancer (NSCLC) and revealed potentially druggable mutations. Yet, systematic data on the changes of the respective molecular profiles under standard therapy in NSCLC are limited. Results 14 out of 68 observed coding mutations (21%) and 6 out of 33 (18%) copy number variations (CNV) were lost or gained during therapy. Mutational and CNV changes clustered in 6/37 (16%) and 3/37 (8%) patients. Changes in clinically relevant mutations were rare but present in single cases for genes such as BRAF and PIK3CA. The type of radiochemotherapy but not the duration of therapy impacted on the frequency of mutational changes. Methods We established a lung cancer specific next-generation sequencing panel covering ~7500 hotspots of 41 genes frequently mutated in NSCLC and performed ultradeep multigene sequencing of 37 corresponding pre- and post-therapeutic formalin fixed paraffin-embedded specimens to discover mutational changes and copy number variations under neo-adjuvant radio- (RTX) and/or chemotherapy (CTX). Conclusion We unraveled changes in common driver gene candidates in NSCLC under neo-adjuvant therapy. Our data shed first light on the genetic changes of NSCLC under conventional therapy and might be taken into account when the relevance of sequential biopsy approaches is discussed. PMID:27105513

  10. Pathologic Stage of Nonsmall Cell Lung Cancer Patients Presenting as Resectable Cases After Neoadjuvant Therapy Did Not Predict the Prognosis.

    PubMed

    Wu, Ching-Yang; Fu, Jui-Ying; Wu, Ching-Feng; Liu, Yun-Hen; Hsieh, Ming-Ju; Wu, Yi-Cheng; Yang, Cheng-Ta; Tsai, Ying-Huang

    2015-10-01

    According to the National Comprehensive Cancer Network (NCCN) guidelines, treatment plans for nonsmall cell lung cancer are to be based on cancer stage. Cancer staging for patients with resectable disease has been based on pathologic stage instead of preoperative clinical stage. However, the possibility of occult mediastinal lymph node metastases could lead to discrepancy between clinical and pathologic stage. While multi-modality treatments may be beneficial for patients with locally advanced disease, most studies have been based on clinical stage. The aim of this study was to identify the beneficial impact of neoadjuvant therapy and the prognostic value of final pathologic stage in these patients. This study enrolled 530 lung cancer patients who received anatomic resection and mediastinal lymph node dissection at Chang Gung Memorial Hospital from January 2005 through June 2011. All resected specimens were examined by pathologists. Postoperative adjuvant therapies were given according to NCCN guideline recommendations. The clinico-pathologic factors of these patients were collected and analyzed. Patients not receiving neoadjuvant therapy had a better probability of disease-free survival (P < 0.001) and overall survival (P = 0.0005), as well as a lower incidence of early relapse. Patients not receiving neoadjuvant therapy had a better disease-free survival rate in stages IA (P < 0.001), IB (P = 0.002), and IIB (P = 0.0117) from the point of view of final pathologic stage. Patients receiving neoadjuvant therapy may experience a higher incidence of early relapse. Neoadjuvant therapy did not show definite benefits in the disease-free and overall survival rates from the point of view of final pathologic stage. Pathologic stage of nonsmall cell lung cancer patients who presented with resectable disease after neoadjuvant therapy did not predict the prognosis.

  11. Neoadjuvant Therapy for Early-Stage Breast Cancer: Current Practice, Controversies, and Future Directions.

    PubMed

    Santa-Maria, Cesar Augusto; Camp, Melissa; Cimino-Mathews, Ashley; Harvey, Susan; Wright, Jean; Stearns, Vered

    2015-11-01

    Research in the fields of surgical, medical, and radiation oncology has changed the landscape of neoadjuvant therapy in breast cancer, yet many areas of controversy still exist. When considering whether a patient is a candidate for neoadjuvant therapy, ideally the initial assessment should be multidisciplinary in nature and should include clinical, radiographic, and pathologic evaluation. Optimization of systemic therapy is dependent upon identifying the patient's breast cancer subtype; the best approach may include targeted agents, as well as the determination of eligibility for enrollment into clinical trials that incorporate novel therapeutics or predictive biomarkers. This article will review a variety of surgical and radiation-based strategies for management of early-stage breast cancer, including surgical options involving the breast and axilla, and the role of radiation based on response to systemic therapy. Key areas of controversy include the ideal systemic treatment for different breast cancer subtypes, the surgical and radiotherapeutic approaches for management of the axilla, and the role of pathologic response rates as a surrogate for survival in drug development.

  12. Modeling Pathologic Response of Esophageal Cancer to Chemoradiation Therapy Using Spatial-Temporal {sup 18}F-FDG PET Features, Clinical Parameters, and Demographics

    SciTech Connect

    Zhang, Hao; Tan, Shan; Chen, Wengen; Kligerman, Seth; Kim, Grace; D'Souza, Warren D.; Suntharalingam, Mohan; Lu, Wei

    2014-01-01

    Purpose: To construct predictive models using comprehensive tumor features for the evaluation of tumor response to neoadjuvant chemoradiation therapy (CRT) in patients with esophageal cancer. Methods and Materials: This study included 20 patients who underwent trimodality therapy (CRT + surgery) and underwent {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) both before and after CRT. Four groups of tumor features were examined: (1) conventional PET/CT response measures (eg, standardized uptake value [SUV]{sub max}, tumor diameter); (2) clinical parameters (eg, TNM stage, histology) and demographics; (3) spatial-temporal PET features, which characterize tumor SUV intensity distribution, spatial patterns, geometry, and associated changes resulting from CRT; and (4) all features combined. An optimal feature set was identified with recursive feature selection and cross-validations. Support vector machine (SVM) and logistic regression (LR) models were constructed for prediction of pathologic tumor response to CRT, cross-validations being used to avoid model overfitting. Prediction accuracy was assessed by area under the receiver operating characteristic curve (AUC), and precision was evaluated by confidence intervals (CIs) of AUC. Results: When applied to the 4 groups of tumor features, the LR model achieved AUCs (95% CI) of 0.57 (0.10), 0.73 (0.07), 0.90 (0.06), and 0.90 (0.06). The SVM model achieved AUCs (95% CI) of 0.56 (0.07), 0.60 (0.06), 0.94 (0.02), and 1.00 (no misclassifications). With the use of spatial-temporal PET features combined with conventional PET/CT measures and clinical parameters, the SVM model achieved very high accuracy (AUC 1.00) and precision (no misclassifications)—results that were significantly better than when conventional PET/CT measures or clinical parameters and demographics alone were used. For groups with many tumor features (groups 3 and 4), the SVM model achieved significantly higher

  13. Dynamics of circulating tumor cells in early breast cancer under neoadjuvant therapy

    PubMed Central

    SERRANO, MARÍA JOSÉ; ROVIRA, PEDRO SÁNCHEZ; MARTÍNEZ-ZUBIAURRE, I.; RODRIGUEZ, MIGUEL DELGADO; FERNÁNDEZ, MÓNICA; LORENTE, JOSE A.

    2012-01-01

    At present, the majority of patients with breast cancer are diagnosed at early stages of disease development. However, a considerable number of such cases develop secondary malignancies after a relatively short period of time. The presence of circulating tumor cells (CTCs) has been proposed as a strong biomarker to predict disease recurrence in metastatic breast cancer. However, the prognostic significance is not clear in early breast cancer. We present results on CTC determination in peripheral blood in non-metastatic breast cancer patients in the context of neoadjuvant treatment. Twenty-six breast cancer patients, scheduled for neoadjuvant therapy, were enrolled in a prospective study, of which 24 were able to complete therapy. CTC assessment was performed by sorting out cytokeratin-positive cells from 10 ml of peripheral blood using immunomagnetic separation, followed by immunocytochemical characterization of cells. Seventeen blood samples out of 24 patients were CTC-positive when collected prior to neoadjuvant chemotherapy. No significant correlations were found between the presence of CTCs and lymph node status (p=0.1), histological type (p=0.802), stage (p=0.43) or overall survival (OS) (p=0.599). Thirteen CTC-positive samples were observed in blood samples collected after treatment. Univariate analyses revealed that the presence of CTCs was related to OS when the detection was positive both before and after treatment (p=0.023). CTCs can be a strong prognostic marker in early breast cancer. The persistence of CTCs before and after treatment can identify a subpopulation of patients with an increased risk of recurrence. PMID:23060920

  14. Quality of Life in a Prospective, Multicenter Phase 2 Trial of Neoadjuvant Full-Dose Gemcitabine, Oxaliplatin, and Radiation in Patients With Resectable or Borderline Resectable Pancreatic Adenocarcinoma

    SciTech Connect

    Serrano, Pablo E.; Herman, Joseph M.; Griffith, Kent A.; Zalupski, Mark M.; Kim, Edward J.; Bekaii-Saab, Tanios S.; Ben-Josef, Edgar; Dawson, Laura A.; Ringash, Jolie; Wei, Alice C.

    2014-10-01

    Purpose: To determine the health-related quality of life (QOL) during and after neoadjuvant chemoradiation therapy and surgery for patients with pancreatic adenocarcinoma. Methods and Materials: Participants of a prospective, phase 2 multi-institutional trial treated with neoadjuvant chemoradiation followed by surgery completed QOL questionnaires (European Organization for Research and Treatment in Cancer Quality of Life Questionnaire version 3.0 [EORTC-QLQ C30], EORTC-Pancreatic Cancer module [EORTC-PAN 26], and Functional Assessment of Cancer Therapy Hepatobiliary and Pancreatic subscale [FACT-Hep]) at baseline, after 2 cycles of neoadjuvant therapy, after surgery, at 6 months from initiation of therapy, and at 6-month intervals for 2 years. Mean scores were compared with baseline. A change >10% was considered a minimal clinically important difference. Results: Of 71 participants in the trial, 55 were eligible for QOL analysis. Compliance ranged from 32% to 74%. The EORTC-QLQ C30 global QOL did not significantly decline after neoadjuvant therapy, whereas the Functional Assessment of Cancer Therapy global health measure showed a statistically, but not clinically significant decline (−8, P=.02). This was in parallel with deterioration in physical functioning (−14.1, P=.001), increase in diarrhea (+16.7, P=.044), and an improvement in pancreatic pain (−13, P=.01) as per EORTC-PAN 26. Because of poor patient compliance in the nonsurgical group, long-term analysis was performed only from surgically resected participants (n=36). Among those, global QOL returned to baseline levels after 6 months, remaining near baseline through the 24-month visit. Conclusions: The study regimen consisting of 2 cycles of neoadjuvant therapy was completed without a clinically significant QOL deterioration. A transient increase in gastrointestinal symptoms and a decrease in physical functioning were seen after neoadjuvant chemoradiation. In those patients who underwent surgical

  15. SU-E-J-268: Change of CT Number During the Course of Chemoradiation Therapy for Pancreatic Cancer

    SciTech Connect

    Chen, X; Dalah, E; Liu, F; Li, X; Zhang, J

    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 Gy 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.

  16. 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.

  17. Results of neoadjuvant therapy followed by esophagectomy for patients with locally advanced thoracic esophageal squamous cell carcinoma

    PubMed Central

    Lin, Dong; Ma, Longfei; Ye, Ting; Pan, Yunjian; Shao, Longlong; Song, Zuodong; Jiang, Shujun

    2017-01-01

    Background For patients diagnosed with locally advanced esophageal cancer, neoadjuvant therapy followed by surgery is the most common approach. However, randomized trials resulted in inconsistent conclusions. We conducted this retrospective study to evaluate the influence of neoadjuvant therapy on postoperative events and the influence on disease-free survival (DFS) and overall survival (OS). Methods We retrospectively reviewed all of the patients underwent surgery following neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma (ESCC) during January 1st, 2013 and December 31st, 2015 in Fudan University Shanghai Cancer Center (FUSCC). Prognostic factors for DFS and OS were identified by univariate and multivariate analyses. Results A total of fifty patients were included. Regarding postoperative morbidities, pneumonia and leakage occurred in 9 (18.0%) and 6 (12.0%) patients, respectively. For the whole patients, the 1-, 2-, 3-year DFS and OS rates were 57.0%, 48.0%, 42.0% and 86.0%, 73.0%, 62.0%, respectively. Lung metastasis and mediastinal node involvement were the most common relapse patterns. Univariate and multivariate analyses confirmed ypTNM stage as an independent prognostic factor for both DFS and OS; while leakage was an independent prognostic factor for DFS. Conclusions Neoadjuvant therapy did not increase postoperative morbidities but did achieve favorable survival. The ypTNM stage was an independent prognostic factor for both DFS and OS. Long-term survival needs further investigation. PMID:28275480

  18. Radiation Therapy Oncology Group Protocol 02-29: A Phase II Trial of Neoadjuvant Therapy With Concurrent Chemotherapy and Full-Dose Radiation Therapy Followed by Surgical Resection and Consolidative Therapy for Locally Advanced Non-small Cell Carcinoma of the Lung

    SciTech Connect

    Suntharalingam, Mohan; Paulus, Rebecca; Edelman, Martin J.; Krasna, Mark; Burrows, Whitney; Gore, Elizabeth; Wilson, Lynn D.; Choy, Hak

    2012-10-01

    Purpose: To evaluate mediastinal nodal clearance (MNC) rates after induction chemotherapy and concurrent, full-dose radiation therapy (RT) in a phase II trimodality trial (Radiation Therapy Oncology Group protocol 0229). Patients and Methods: Patients (n=57) with stage III non-small cell lung cancer (pathologically proven N2 or N3) were eligible. Induction chemotherapy consisted of weekly carboplatin (AUC = 2.0) and paclitaxel 50 mg/m{sup 2}. Concurrent RT was prescribed, with 50.4 Gy to the mediastinum and primary tumor and a boost of 10.8 Gy to all gross disease. The mediastinum was pathologically reassessed after completion of chemoradiation. The primary endpoint of the study was MNC, with secondary endpoints of 2-year overall survival and postoperative morbidity/mortality. Results: The grade 3/4 toxicities included hematologic 35%, gastrointestinal 14%, and pulmonary 23%. Forty-three patients (75%) were evaluable for the primary endpoint. Twenty-seven patients achieved the primary endpoint of MNC (63%). Thirty-seven patients underwent resection. There was a 14% incidence of grade 3 postoperative pulmonary complications and 1 30-day, postoperative grade 5 toxicity (3%). With a median follow-up of 24 months for all patients, the 2-year overall survival rate was 54%, and the 2-year progression-free survival rate was 33%. The 2-year overall survival rate was 75% for those who achieved nodal clearance, 52% for those with residual nodal disease, and 23% for those who were not evaluable for the primary endpoint (P=.0002). Conclusions: This multi-institutional trial confirms the ability of neoadjuvant concurrent chemoradiation with full-dose RT to sterilize known mediastinal nodal disease.

  19. Chemoradiation of rectal cancer.

    PubMed

    Arrazubi, V; Suárez, J; Novas, P; Pérez-Hoyos, M T; Vera, R; Martínez Del Prado, P

    2013-02-01

    The treatment of locally advanced rectal cancer is a challenge. Surgery, chemotherapy and radiotherapy comprise the multimodal therapy that is administered in most cases. Therefore, a multidisciplinary approach is required. Because this cancer has a high rate of local recurrence, efforts have been made to improve clinical outcomes while minimizing toxicity and maintaining quality of life. Thus, total mesorectal excision technique was developed as the standard surgery, and chemotherapy and radiotherapy have been established as neoadjuvant treatment. Both approaches reduce locoregional relapse. Two neoadjuvant treatments have emerged as standards of care: short-course radiotherapy and long-course chemoradiotherapy with fluoropyrimidines; however, long-course chemoradiotherapy might be more appropriate for low-lying neoplasias, bulky tumours or tumours with near-circumferential margins. If neoadjuvant treatment is not administered and locally advanced stage is demonstrated in surgical specimens, adjuvant chemoradiotherapy is recommended. The addition of chemotherapy to the treatment regimen confers a significant benefit. Adjuvant chemotherapy is widely accepted despite scarce evidence of its benefit. The optimal time for surgery after neoadjuvant therapy, the treatment of low-risk T3N0 neoplasms, the convenience of avoiding radiotherapy in some cases and tailoring treatment to pathological response have been recurrent subjects of debate that warrant more extensive research. Adding new drugs, changing the treatment sequence and selecting the treatment based on prognostic or predictive factors other than stage remain experimental.

  20. Neoadjuvant Therapy of DOF Regimen Plus Bevacizumab Can Increase Surgical Resection Ratein Locally Advanced Gastric Cancer: A Randomized, Controlled Study.

    PubMed

    Ma, Junxun; Yao, Sheng; Li, Xiao-Song; Kang, Huan-Rong; Yao, Fang-Fang; Du, Nan

    2015-10-01

    Locally advanced gastric cancer (LAGC) is best treated with surgical resection. Bevacizumab in combination with chemotherapy has shown promising results in treating advanced gastric cancer. This study aimed to investigate the efficacy of neoadjuvant chemotherapy using the docetaxel/oxaliplatin/5-FU (DOF) regimen and bevacizumab in LAGC patients.Eighty LAGC patients were randomized to receive DOF alone (n = 40) or DOF plus bevacizumab (n = 40) as neoadjuvant therapy before surgery. The lesions were evaluated at baseline and during treatment. Circulating tumor cells (CTCs) were counted using the FISH test. Patients were followed up for 3 years to analyze the disease-free survival (DFS) and overall survival (OS).The total response rate was significantly higher in the DOF plus bevacizumab group than the DOF group (65% vs 42.5%, P = 0.0436). The addition of bevacizumab significantly increased the surgical resection rate and the R0 resection rate (P < 0.05). The DOF plus bevacizumab group showed significantly greater reduction in CTC counts after neoadjuvant therapy in comparison with the DOF group (P = 0.0335). Although the DOF plus bevacizumab group had significantly improved DFS than the DOF group (15.2 months vs 12.3 months, P = 0.013), the 2 groups did not differ significantly in OS (17.6 ± 1.8 months vs 16.4 ± 1.9 months, P = 0.776. Cox proportional model analysis showed that number of metastatic lymph nodes, CTC reduction, R0 resection, and neoadjuvant therapy are independent prognostic factors for patients with LAGC.Neoadjuvant of DOF regimen plus bevacizumab can improve the R0 resection rate and DFS in LAGC. These beneficial effects might be associated with the reduction in CTC counts.

  1. Increased expression of long non-coding RNA XIST predicts favorable prognosis of cervical squamous cell carcinoma subsequent to definitive chemoradiation therapy

    PubMed Central

    Kobayashi, Reiko; Miyagawa, Ryu; Yamashita, Hideomi; Morikawa, Teppei; Okuma, Kae; Fukayama, Masashi; Ohtomo, Kuni; Nakagawa, Keiichi

    2016-01-01

    The present retrospective study aimed to examine the association between the expression of long non-protein-coding RNAs (lncRNAs) and clinical prognosis in the pretreatment formalin-fixed, paraffin-embedded (FFPE) tissue samples of cervical squamous cell carcinoma patients that underwent platinum-based chemoradiation therapy. Between 2001 and 2013, 49 consecutive patients with squamous cell cervical carcinoma were selected for the present study (median follow-up period, 44.1 months). The patients possessed an International Federation of Gynecology and Obstetrics stage of IB1/IIA1 (with pelvic lymph node metastasis), IB2 or IIA2-IVA, and had been treated with definitive chemoradiation therapy. The pretreatment FFPE tumor biopsies of the patients obtained diagnosis were used for analysis. Total RNAs were extracted from the FFPE tumor tissues and reverse transcription-quantitative polymerase chain reaction was performed to examine the expression level of lncRNAs. The expression level of X inactive-specific transcript (XIST) demonstrated a significant association with the overall survival rate (P=0.014). The 4-year overall survival rates were 87.1 and 54.4% in the high and low XIST expression groups, respectively. Since the expression of XIST is associated with the overall survival rate, this lncRNA has the potential to become a predictor for the prognosis of cervical squamous cell carcinoma patients that are treated with chemoradiation therapy. Additional studies are required to investigate the underlying mechanisms of XIST that are associated with prognosis. PMID:27899965

  2. Neoadjuvant or adjuvant therapy for resectable gastric cancer? A practice guideline

    PubMed Central

    Earle, Craig C.; Maroun, Jean; Zuraw, Lisa

    2002-01-01

    Objective To make recommendations on the use of neoadjuvant or adjuvant therapy in addition to surgery in patients with resectable gastric cancer (T1–4, N1–2, M0). Options Neoadjuvant or adjuvant treatments compared with “curative” surgery alone. Outcomes Overall survival, disease-free survival, and adverse effects. Evidence The MEDLINE, CANCERLIT and Cochrane Library databases and relevant conference proceedings were searched to identify randomized trials. Values Evidence was selected and reviewed by one member of the Cancer Care Ontario Practice Guidelines Initiative (CCOPGI) Gastrointestinal Cancer Disease Site Group and methodologists. A systematic review of the published literature was combined with a consensus process around the interpretation of the evidence in the context of conventional practice, to develop an evidence-based practice guideline. This report has been reviewed and approved by the Gastrointestinal Cancer Disease Site Group, comprising medical oncologists, radiation oncologists, surgeons, a pathologist and 2 community representatives. Benefits, harms and costs When compared with surgery alone, at 3 years adjuvant chemoradiotherapy has been shown to increase overall survival by 9% (50% v. 41%, p = 0.005) and to improve relapse-free survival from 31% to 48% (p = 0.001). At 5 years, it has been shown to increase overall survival by 11.6% (40% v. 28.4%) and to improve relapse-free survival from 25% to 38% (p < 0.001). Treatment has been associated with toxic deaths in 1% of patients. The most frequent adverse effects (> grade 3 [Southwest Oncology Group toxicity scale] are hematologic (54%), gastrointestinal (33%), influenza-like (9%), infectious (6%) and neurologic (4%). The radiation fields used can possibly damage the left kidney, resulting in hypertension and other renal problems. Furthermore, this therapy could increase the demand on radiation resources. Physicians and patients should understand the tradeoffs between survival benefit

  3. Clinical potential for vitamin D as a neoadjuvant for photodynamic therapy of nonmelanoma skin cancer

    NASA Astrophysics Data System (ADS)

    Maytin, Edward V.; Anand, Sanjay; Rollakanti, Kishore

    2015-03-01

    Nonmelanoma skin cancer (NMSC), comprising basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), is the most common form of human cancer worldwide. Effective therapies include surgical excision, cryotherapy, and ionizing radiation, but all of these cause scarring. ALA-based PDT is a non-scarring modality used routinely for NMSC in Europe but not in the USA, primarily due to lingering uncertainties about efficacy. We have identified three agents (methotrexate, 5-fluorouracil, and vitamin D) that can be used as neoadjuvants, i.e., can be given as a pretreatment prior to ALA-PDT, to improve the efficacy of tumor killing in mouse models of NMSC. Vitamin D (VD3) is the most recent neoadjuvant on this list. In this presentation we make the case that VD3 may be superior to the other agents to improve results of ALA-PDT skin cancer treatment. The active form of VD3 (calcitriol) is available topically as a pharmaceutical grade cream or ointment (FDA-approved for psoriasis), and works well for boosting ALA-PDT tumor treatment in mouse models. For deep tumors not reachable by a topical route, calcitriol can be given systemically and is very effective, but carries a risk of causing hypercalcemia as a side effect. To circumvent this risk, we have conducted experiments with the natural dietary form of VD3 (cholecalciferol), and showed that this improves ALA-PDT efficacy almost to the same extent as calcitriol. Because cholecalciferol does not increase serum calcium levels, this represents a potentially extremely safe approach. Data in mouse models of BCC and SCC will be presented.

  4. Chemoradiation for gastric cancer: controversies, updates and novel techniques

    PubMed Central

    Fan, M; Hu, W

    2015-01-01

    The INT0116 trial established the role of adjuvant chemoradiation (CRT) in the multidisciplinary approach to the management of locally advanced gastric cancer. However, whether adjuvant CRT is indispensable for patients undergoing D2 dissection remains undefined. The adjuvant chemoradiation therapy in stomach cancer (ARTIST) trial, which was designed to compare adjuvant chemotherapy to CRT, failed to demonstrate differences in disease-free and overall survival in the whole study group; however, subgroup analysis indicated that patients with lymph node metastasis may benefit from additional radiation. A follow-up ARTIST II trial is currently under way. The efficacy of adjuvant CRT remains controversial because of variation among studies in the inclusion criteria and treatment delivery methods; however, the identification of patients who would benefit from CRT is critical. Advanced radiotherapy techniques such as intensity-modulated radiotherapy protect normal tissues via motion management and decreased radiation-induced toxicity and contribute to plan optimization. Further studies integrating clinical and molecular factors as well as neoadjuvant CRT are warranted. PMID:25827208

  5. Comparison of neoadjuvant versus a surgery first approach for gastric and esophagogastric cancer.

    PubMed

    Russell, Maria C

    2016-09-01

    Gastric cancer remains a significant worldwide health concern. While surgery is required for cure, all but the earliest of cancers will require multimodality therapy. Chemotherapy and chemoradiation in the neoadjuvant and adjuvant settings have shown to improve overall survival, but the sequencing of treatment is controversial. As healthcare expenses surge, it is increasingly important to impart value to these treatments. This review will look at the intersection of effective treatment and costs for gastric cancer. J. Surg. Oncol. 2016;114:296-303. © 2016 Wiley Periodicals, Inc.

  6. Role of Genetic Polymorphisms in NFKB-Mediated Inflammatory Pathways in Response to Primary Chemoradiation Therapy for Rectal Cancer

    SciTech Connect

    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

    Purpose: 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). Methods and Materials: 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. Results: 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). Conclusions: 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.

  7. Enteral Feeding Tubes in Patients Undergoing Definitive Chemoradiation Therapy for Head-and-Neck Cancer: A Critical Review

    SciTech Connect

    Koyfman, Shlomo A.; Adelstein, David J.

    2012-11-01

    Definitive chemoradiation therapy has evolved as the preferred organ preservation strategy in the treatment of locally advanced head-and-neck cancer (LA-HNC). Dry mouth and dysphagia are among the most common and most debilitating treatment-related toxicities that frequently necessitate the placement of enteral feeding tubes (FT) in these patients to help them meet their nutritional requirements. The use of either a percutaneous endoscopic gastrostomy tube or a nasogastric tube, the choice of using a prophylactic vs a reactive approach, and the effects of FTs on weight loss, hospitalization, quality of life, and long-term functional outcomes are areas of continued controversy. Considerable variations in practice patterns exist in the United States and abroad. This critical review synthesizes the current data for the use of enteral FTs in this patient population and clarifies the relative advantages of different types of FTs and the timing of their use. Recent developments in the biologic understanding and treatment approaches for LA-HNC appear to be favorably impacting the frequency and severity of treatment-related dysphagia and may reduce the need for enteral tube feeding in the future.

  8. Temporal Patterns of Fatigue Predict Pathologic Response in Patients Treated With Preoperative Chemoradiation Therapy for Rectal Cancer

    SciTech Connect

    Park, Hee Chul; Janjan, Nora A.; Mendoza, Tito R.; Lin, Edward H.; Vadhan-Raj, Saroj; Hundal, Mandeep; Zhang Yiqun; Delclos, Marc E.; Crane, Christopher H.; Das, Prajnan; Wang, Xin Shelley; Cleeland, Charles S.; Krishnan, Sunil

    2009-11-01

    Purpose: To investigate whether symptom burden before and during preoperative chemoradiation therapy (CRT) for rectal cancer predicts for pathologic tumor response. Methods and Materials: Fifty-four patients with T3/T4/N+ rectal cancers were treated on a Phase II trial using preoperative capecitabine and concomitant boost radiotherapy. Symptom burden was prospectively assessed before (baseline) and weekly during CRT by patient self-reported questionnaires, the MD Anderson Symptom Inventory (MDASI), and Brief Fatigue Inventory (BFI). Survival probabilities were estimated using the Kaplan-Meier method. Symptom scores according to tumor downstaging (TDS) were compared using Student's t tests. Logistic regression was used to determine whether symptom burden levels predicted for TDS. Lowess curves were plotted for symptom burden across time. Results: Among 51 patients evaluated for pathologic response, 26 patients (51%) had TDS. Fatigue, pain, and drowsiness were the most common symptoms. All symptoms increased progressively during treatment. Patients with TDS had lower MDASI fatigue scores at baseline and at completion (Week 5) of CRT (p = 0.03 for both) and lower levels of BFI 'usual fatigue' at baseline. Conclusion: Lower levels of fatigue at baseline and completion of CRT were significant predictors of pathologic tumor response gauged by TDS, suggesting that symptom burden may be a surrogate for tumor burden. The relationship between symptom burden and circulating cytokines merits evaluation to characterize the molecular basis of this phenomenon.

  9. Prognostic significance of survivin in rectal cancer patients treated with surgery and postoperative concurrent chemo-radiation therapy

    PubMed Central

    Il Yu, Jeong; Lee, Hyebin; Park, Hee Chul; Choi, Doo Ho; Choi, Yoon-La; Do, In-Gu; Kim, Hee Cheol; Lee, Woo Yong; Yun, Seong Hyeon; Cho, Yong Beom; Huh, Jung Wook; Park, Yoon Ah; Park, Young Suk; Park, Joon Oh; Kim, Seung Tae; Park, Won

    2016-01-01

    Background & Aims This study is designed to investigate the expression of survivin and p53 in human rectal cancer tissues and analyze associations between expression and clinical outcomes in terms of disease recurrence and survival duration. Results During follow-up (median 119.0, range 6.6 to 161.3 months), tumor recurrence was detected in 50 patients (43.1%), and local recurrence developed as a first failure site in 13 patients (11.2%). Positive immunostaining of nuclear and cytoplasmic survivin was observed in about one quarter of patients, and about half of all patients had positive staining for p53. Both survivin and p53 were significant prognostic factors of disease-free survival in the univariate analyses, but only survivin remained a significant prognostic factor in the multivariate analysis. Methods We performed a retrospective study with 116 locally advanced rectal cancer patients who underwent total mesorectal excision (TME) followed by postoperative concurrent chemo-radiation therapy (CCRT). Immunohistochemical staining was conducted using antibodies for survivin or p53, and their expression was analyzed using an individual score that combined the percentage of positive cells and staining intensity. Conclusions Overexpression of nuclear and cytoplasmic survivin in locally advanced rectal cancer patients was associated with a higher recurrence rate in rectal cancer patients treated with TME followed by postoperative CCRT. PMID:27391438

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

    SciTech Connect

    Fraunholz, Ingeborg; Falk, Stefan

    2013-08-01

    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 intense 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.

  11. 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

    SciTech Connect

    Nyflot, Matthew J.; Kruser, Tim J.; Traynor, Anne M.; Khuntia, Deepak; Yang, David T.; Hartig, Gregory K.; McCulloch, Timothy M.; Wiederholt, Peggy A.; Gentry, Lindell R.; Hoang, Tien; Jeraj, Robert; and others

    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 curative 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

  12. 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

    PubMed Central

    Nyflot, Matthew J.; Kruser, Tim J.; Traynor, Anne M.; Khuntia, Deepak; Yang, David T.; Hartig, Gregory K.; McCulloch, Timothy M.; Wiederholt, Peggy A.; Gentry, Lindell R.; Hoang, Tien; Jeraj, Robert; Harari, Paul M.

    2015-01-01

    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 curative intent to 70 Gy in 33 fractions with concurrent weekly cisplatin at 30 mg/m2 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 [18F]fluorothymidine positron emission tomography (FLT-PET) (proliferation), [61Cu]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

  13. Inflammatory cytokines are associated with the development of symptom burden in patients with NSCLC undergoing concurrent chemoradiation therapy.

    PubMed

    Wang, Xin Shelley; Shi, Qiuling; Williams, Loretta A; Mao, Li; Cleeland, Charles S; Komaki, Ritsuko R; Mobley, Gary M; Liao, Zhongxing

    2010-08-01

    Elevations in cancer treatment-induced circulating inflammatory cytokines may be partially responsible for the development of significant symptom burden (e.g., pain, fatigue, distress, disturbed sleep) during concurrent chemoradiation therapy (CXRT). Sixty-two patients undergoing CXRT for locally advanced non-small cell lung cancer (NSCLC) reported symptoms weekly for 15 weeks via the M. D. Anderson Symptom Inventory (MDASI). Serum inflammatory cytokines were assessed weekly during therapy via enzyme-linked immunosorbent assay. Dynamic changes in cytokines and associated symptom profiles were estimated using mixed-effect models. MDASI symptom severity increased gradually as CXRT dose accumulated and peaked at week 8. Serum concentrations of interleukin (IL)-6, IL-10, and serum soluble receptor 1 for tumor necrosis factor (sTNF-R1) increased significantly by week 8 (all p<.05). During CXRT, controlled for age, sex, race, body mass index, cancer recurrence, previous treatment status, total radiotherapy dose, and CXRT delivery technique, an increase in sTNF-R1 was significantly related to an increase in the mean score for all 15 MDASI symptoms (estimate, 1.74; SE, 0.69; p<.05) and to a larger radiation dose to normal lung volume (estimate, 1.77; SE, 0.71; p<.01); an increase in serum IL-6 was significantly related to increased mean severity for the five most severe symptoms (pain, fatigue, disturbed sleep, lack of appetite, sore throat) (estimate, 0.32; SE, 0.16; p<.05). These results suggest a role for over-expressed pro-inflammatory cytokines in significant worsening of symptoms in NSCLC patients undergoing CXRT, and warrant further study to identify biological targets for ameliorating treatment-related symptom burden.

  14. Predicting Radiation Pneumonitis After Chemoradiation Therapy for Lung Cancer: An International Individual Patient Data Meta-analysis

    SciTech Connect

    Palma, David A.; Senan, Suresh; Tsujino, Kayoko; Barriger, Robert B.; Rengan, Ramesh; Moreno, Marta; Bradley, Jeffrey D.; Kim, Tae Hyun; Ramella, Sara; Marks, Lawrence B.; De Petris, Luigi; Stitt, Larry; Rodrigues, George

    2013-02-01

    Background: Radiation pneumonitis is a dose-limiting toxicity for patients undergoing concurrent chemoradiation therapy (CCRT) for non-small cell lung cancer (NSCLC). We performed an individual patient data meta-analysis to determine factors predictive of clinically significant pneumonitis. Methods and Materials: After a systematic review of the literature, data were obtained on 836 patients who underwent CCRT in Europe, North America, and Asia. Patients were randomly divided into training and validation sets (two-thirds vs one-third of patients). Factors predictive of symptomatic pneumonitis (grade {>=}2 by 1 of several scoring systems) or fatal pneumonitis were evaluated using logistic regression. Recursive partitioning analysis (RPA) was used to define risk groups. Results: The median radiation therapy dose was 60 Gy, and the median follow-up time was 2.3 years. Most patients received concurrent cisplatin/etoposide (38%) or carboplatin/paclitaxel (26%). The overall rate of symptomatic pneumonitis was 29.8% (n=249), with fatal pneumonitis in 1.9% (n=16). In the training set, factors predictive of symptomatic pneumonitis were lung volume receiving {>=}20 Gy (V{sub 20}) (odds ratio [OR] 1.03 per 1% increase, P=.008), and carboplatin/paclitaxel chemotherapy (OR 3.33, P<.001), with a trend for age (OR 1.24 per decade, P=.09); the model remained predictive in the validation set with good discrimination in both datasets (c-statistic >0.65). On RPA, the highest risk of pneumonitis (>50%) was in patients >65 years of age receiving carboplatin/paclitaxel. Predictors of fatal pneumonitis were daily dose >2 Gy, V{sub 20}, and lower-lobe tumor location. Conclusions: Several treatment-related risk factors predict the development of symptomatic pneumonitis, and elderly patients who undergo CCRT with carboplatin-paclitaxel chemotherapy are at highest risk. Fatal pneumonitis, although uncommon, is related to dosimetric factors and tumor location.

  15. Histopathological regression of gastric adenocarcinoma after neoadjuvant therapy: a critical review.

    PubMed

    Neves Filho, Eduardo Henrique Cunha; de Sant'Ana, Rosane Oliveira; Nunes, Luiz Vianney Saldanha Cidrão; Pires, Adriana Pinheiro Bezerra; da Cunha, Maria do Perpétuo Socorro Saldanha

    2017-02-01

    As the perioperative chemotherapy has been widely implemented on the management of gastric cancer patients, heterogeneity of clinical outcomes has been evidenced in parallel to different histopathological regression pattern of gastric cancer cells. Tumor histological response to preoperative therapy has been graded by various systems in order to categorize the amount of regressive changes induced by chemotherapy in relation to residual tumor. In this context, tumor regression grading (TRG) systems might provide important prognostic information as the variety of tumor response may imply on different clinical outcomes with impact in survival rates. Moreover, gastric cancer behavior varies enormously upon individual factors such as histological classification and tumor anatomic site of involvement that have been shown to affect the TRG interpretation. On the other hand, some studies have assessed the role of molecular markers as a predictor of tumor response to neoadjuvant chemotherapy in terms of TRG. Thus, the aim of this review is to evaluate how TRG has been interpreted in gastric cancer, discuss their clinical and prognostic relevance and also address the molecular markers involved in this process.

  16. Variations in positron emission tomography-computed tomography findings for patients receiving neoadjuvant and non-neoadjuvant therapy for non-small cell lung cancer

    PubMed Central

    Park, Jae Kil; Moon, Seok Whan

    2017-01-01

    Background The aims of this study were to predict locoregional lymph node (LN) metastases using positron emission tomography-computed tomography (PET-CT) and investigate variations in PET-CT findings for patients receiving neoadjuvant (NT) and non-neoadjuvant (non-NT) for non-small cell lung cancer (NSCLC). Methods Data from 578 consecutive patients from January 2010 to December 2015 who met this study inclusion criteria were retrospectively reviewed. All patients underwent curative and complete resections for NSCLC in a Korean hospital. We analyzed the associations between maximum standard uptake value (SUVmax) and pathological stage, compared disease-free survival (DFS) and overall survival (OS), investigated relationships among SUVmax values, evaluated LN status and compared pathologically negative and positive LNs by SUVmax, and assessed the influence of neoadjuvant therapy on SUVmax. All LNs were analyzed separately for N1 and N2. Results (I) For non-NT, we found significantly positive associations between pathological stage and SUVmax (tumor, N1 LN, and N2 LN, all P<0.001). For NT, we found positive correlations between pathological stage and tumor and N2 LN SUVmax, except for N1 LN (tumor P=0.005, N1 LN P=0.981, N2 LN P=0.045); (II) for non-NT, the low SUVmax group had higher DFS and OS than the high SUVmax group (DFS: tumor SUVmax P<0.001, N1 LN SUVmax P=0.002, N2 LN SUVmax P=0.027; OS: tumor SUVmax P<0.001, N1 LN SUVmax P=0.006, N2 LN SUVmax P=0.006). For NT, the low SUVmax group had nonsignificantly higher DFS and OS than the high SUVmax group. When age, sex, and SUVmax were equal, pathological stages were significantly higher for NT than non-NT (P<0.001). Non-NT had significantly higher DFS (P=0.001) and OS (P=0.024) than NT; (III) for non-NT, tumor, N1 LN, and N2 SUVmax were positively associated (all P<0.001). For NT, tumor and N2 SUVmax (P<0.001), and N1 and N2 SUVmax (P=0.025) correlated positively; tumor and N1 LN SUVmax did not (P=0.911); (IV) for

  17. Performance of a Nomogram Predicting Disease-Specific Survival After an R0 Resection for Gastric Cancer in Patients Receiving Postoperative Chemoradiation Therapy

    SciTech Connect

    Dikken, Johan L.; Coit, Daniel G.; Baser, Raymond E.; Gönen, Mithat; Goodman, Karyn A.; Brennan, Murray F.; Jansen, Edwin P.M.; Boot, Henk; Velde, Cornelis J.H. van de; Cats, Annemieke; Verheij, Marcel

    2014-03-01

    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: 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.

  18. Treatment Outcomes, Growth Height, and Neuroendocrine Functions in Patients With Intracranial Germ Cell Tumors Treated With Chemoradiation Therapy

    SciTech Connect

    Odagiri, Kazumasa; Omura, Motoko; Hata, Masaharu; Aida, Noriko; Niwa, Tetsu; Ogino, Ichiro; Kigasawa, Hisato; Adachi, Masataka; Inoue, Tomio

    2012-11-01

    Purpose: We carried out a retrospective review of patients receiving chemoradiation therapy (CRT) for intracranial germ cell tumor (GCT) using a lower dose than those previously reported. To identify an optimal GCT treatment strategy, we evaluated treatment outcomes, growth height, and neuroendocrine functions. Methods and Materials: Twenty-two patients with GCT, including 4 patients with nongerminomatous GCT (NGGCT) were treated with CRT. The median age at initial diagnosis was 11.5 years (range, 6-19 years). Seventeen patients initially received whole brain irradiation (median dose, 19.8 Gy), and 5 patients, including 4 with NGGCT, received craniospinal irradiation (median dose, 30.6 Gy). The median radiation doses delivered to the primary site were 36 Gy for pure germinoma and 45 Gy for NGGCT. Seventeen patients had tumors adjacent to the hypothalamic-pituitary axis (HPA), and 5 had tumors away from the HPA. Results: The median follow-up time was 72 months (range, 18-203 months). The rates of both disease-free survival and overall survival were 100%. The standard deviation scores (SDSs) of final heights recorded at the last assessment tended to be lower than those at initial diagnosis. Even in all 5 patients with tumors located away from the HPA, final height SDSs decreased (p = 0.018). In 16 patients with tumors adjacent to the HPA, 8 showed metabolic changes suggestive of hypothalamic obesity and/or growth hormone deficiency, and 13 had other pituitary hormone deficiencies. In contrast, 4 of 5 patients with tumors away from the HPA did not show any neuroendocrine dysfunctions except for a tendency to short stature. Conclusions: CRT for GCT using limited radiation doses resulted in excellent treatment outcomes. Even after limited radiation doses, insufficient growth height was often observed that was independent of tumor location. Our study suggests that close follow-up of neuroendocrine functions, including growth hormone, is essential for all patients with

  19. Novel Single-Nucleotide Polymorphism Markers Predictive of Pathologic Response to Preoperative Chemoradiation Therapy in Rectal Cancer Patients

    SciTech Connect

    Kim, Jin C.; Ha, Ye J.; Roh, Seon A.; Cho, Dong H.; Choi, Eun Y.; Kim, Tae W.; Kim, Jong H.; Kang, Tae W.; Kim, Seon Y.; Kim, Yong S.

    2013-06-01

    Purpose: Studies aimed at predicting individual responsiveness to preoperative chemoradiation therapy (CRT) are urgently needed, especially considering the risks associated with poorly responsive patients. Methods and Materials: A 3-step strategy for the determination of CRT sensitivity is proposed based on (1) the screening of a human genome-wide single-nucleotide polymorphism (SNP) array in correlation with histopathologic tumor regression grade (TRG); (2) clinical association analysis of 113 patients treated with preoperative CRT; and (3) a cell-based functional assay for biological validation. Results: Genome-wide screening identified 9 SNPs associated with preoperative CRT responses. Positive responses (TRG 1-3) were obtained more frequently in patients carrying the reference allele (C) of the SNP CORO2A rs1985859 than in those with the substitution allele (T) (P=.01). Downregulation of CORO2A was significantly associated with reduced early apoptosis by 27% (P=.048) and 39% (P=.023) in RKO and COLO320DM colorectal cancer cells, respectively, as determined by flow cytometry. Reduced radiosensitivity was confirmed by colony-forming assays in the 2 colorectal cancer cells (P=.034 and .015, respectively). The SNP FAM101A rs7955740 was not associated with radiosensitivity in the clinical association analysis. However, downregulation of FAM101A significantly reduced early apoptosis by 29% in RKO cells (P=.047), and it enhanced colony formation in RKO cells (P=.001) and COLO320DM cells (P=.002). Conclusion: CRT-sensitive SNP markers were identified using a novel 3-step process. The candidate marker CORO2A rs1985859 and the putative marker FAM101A rs7955740 may be of value for the prediction of radiosensitivity to preoperative CRT, although further validation is needed in large cohorts.

  20. Chemoradiation Therapy for Potentially Resectable Gastric Cancer: Clinical Outcomes Among Patients Who Do Not Undergo Planned Surgery

    SciTech Connect

    Kim, Michelle M.; Mansfield, Paul F.; Das, Prajnan; Janjan, Nora A.; Badgwell, Brian D.; Phan, Alexandria T.; Delclos, Marc E.; Maru, Dipen; Ajani, Jaffer A.; Crane, Christopher H.; Krishnan, Sunil

    2008-05-01

    Purpose: We retrospectively analyzed treatment outcomes among resectable gastric cancer patients treated preoperatively with chemoradiation therapy (CRT) but rendered ineligible for planned surgery because of clinical deterioration or development of overt metastatic disease. Methods and Materials: Between 1996 and 2004, 39 patients with potentially resectable gastric cancer received preoperative CRT but failed to undergo surgery. At baseline clinical staging, 33 (85%) patients had T3-T4 disease, and 27 (69%) patients had nodal involvement. Most patients received 45 Gy of radiotherapy with concurrent 5-fluorouracil-based chemotherapy. Twenty-one patients underwent induction chemotherapy before CRT. Actuarial times to local control (LC), distant control (DC), and overall survival (OS) were calculated by the Kaplan-Meier method. Results: The cause for surgical ineligibility was development of metastatic disease (28 patients, 72%; predominantly peritoneal, 18 patients), poor performance status (5 patients, 13%), patient/physician preference (4 patients, 10%), and treatment-related death (2 patients, 5%). With a median follow-up of 8 months (range, 1-95 months), actuarial 1-year LC, DC, and OS were 46%, 12%, and 36%, respectively. Median LC and OS were 11.0 and 10.1 months, respectively. Conclusions: Patients with potentially resectable gastric cancer treated with preoperative CRT are found to be ineligible for surgery principally because of peritoneal progression. Patients who are unable to undergo planned surgery have outcomes comparable to that of patients with advanced gastric cancer treated with chemotherapy alone. CRT provides durable LC for the majority of the remaining life of these patients.

  1. Phase II Study of Preoperative Concurrent Chemoradiation Therapy With S-1 in Patients With T4 Oral Squamous Cell Carcinoma

    SciTech Connect

    Nomura, Tomoko; Murakami, Ryuji; Toya, Ryo; Teshima, Keiko; Nakahara, Aya; Hirai, Toshinori; Hiraki, Akimitsu; Nakayama, Hideki; Yoshitake, Yoshihiro; Ota, Kazutoshi; Obayashi, Takehisa; Yamashita, Yasuyuki; Oya, Natsuo; Shinohara, Masanori

    2010-04-15

    Purpose: To determine the feasibility and efficacy of preoperative concurrent chemoradiation therapy (CCRT) with S-1, an oral fluoropyrimidine derivative, in patients with T4 oral squamous cell carcinoma (SCC). Methods and Materials: Only patients with histologically proven T4 oral SCC were included. Radiotherapy (total dose, 30 Gy) was delivered in 2-Gy daily fractions over a period of 3 weeks. Concurrently, S-1 (80 mg/m{sup 2}/day) was administered orally twice daily for 14 consecutive days. Results: We enrolled 46 patients. All underwent radiotherapy as planned; however, oral S-1 was discontinued in 3 patients who manifested acute toxicity. Grade 3 toxicities were mucositis (20%), anorexia (9%), and neutropenia (4%). We encountered no Grade 4 adverse events or serious postoperative morbidity requiring surgical intervention. After CCRT, 32 of the 46 patients underwent radical resection; in 17 (53%) of the operated patients, the pathologic response was complete. During follow-up ranging from 7 to 58 months (median, 22 months), tumor control failed in 5 (16%) of the 32 operated patients; there were 3 local and 2 regional failures. Of the 14 non-operated patients, 8 (57%) manifested local (n = 7) or regional failure (n = 1). The 3-year overall survival rate for all 46 patients was 69%; it was significantly higher for operated than for non-operated patients (82% vs. 48%; p = 0.0288). Conclusion: Preoperative CCRT with S-1 is feasible and effective in patients with T4 oral SCC. Even in inoperable cases, CCRT with S-1 provides adequate tumor control.

  2. Epigenetic Regulation of KLHL34 Predictive of Pathologic Response to Preoperative Chemoradiation Therapy in Rectal Cancer Patients

    SciTech Connect

    Ha, Ye J.; Kim, Chan W.; Roh, Seon A.; Cho, Dong H.; Park, Jong L.; Kim, Seon Y.; Kim, Jong H.; Choi, Eun K.; Kim, Yong S.; Kim, Jin C.

    2015-03-01

    Purpose: Prediction of individual responsiveness to preoperative chemoradiation therapy (CRT) is urgently needed in patients with poorly responsive locally advanced rectal cancer (LARC). Methods and Materials: Candidate methylation genes associated with radiosensitivity were identified using a 3-step process. In the first step, genome-wide screening of methylation genes was performed in correlation with histopathologic tumor regression grade in 45 patients with LARC. In the second step, the methylation status of selected sites was analyzed by pyrosequencing in 67 LARC patients, including 24 patients analyzed in the first step. Finally, colorectal cancer cell clones with stable KLHL34 knockdown were generated and tested for cellular sensitivity to radiation. Results: Genome-wide screening identified 7 hypermethylated CpG sites (DZIP1 cg24107021, DZIP1 cg26886381, ZEB1 cg04430381, DKK3 cg041006961, STL cg00991794, KLHL34 cg01828474, and ARHGAP6 cg07828380) associated with preoperative CRT responses. Radiosensitivity in patients with hypermethylated KLHL34 cg14232291 was confirmed by pyrosequencing in additional cohorts. Knockdown of KLHL34 significantly reduced colony formation (KLHL34 sh#1: 20.1%, P=.0001 and KLHL34 sh#2: 15.8%, P=.0002), increased the cytotoxicity (KLHL34 sh#1: 14.8%, P=.019 and KLHL34 sh#2: 17.9%, P=.007) in LoVo cells, and increased radiation-induced caspase-3 activity and the sub-G1 population of cells. Conclusions: The methylation status of KLHL34 cg14232291 may be a predictive candidate of sensitivity to preoperative CRT, although further validation is needed in large cohorts using various cell types.

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

    SciTech Connect

    Isohashi, Fumiaki; Yoshioka, Yasuo; Mabuchi, Seiji; Konishi, Koji; Koizumi, Masahiko; Takahashi, Yutaka; Ogata, Toshiyuki; Maruoka, Shintaroh; Kimura, Tadashi; Ogawa, Kazuhiko

    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 and 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

  4. Nomogram Prediction of Survival and Recurrence in Patients With Extrahepatic Bile Duct Cancer Undergoing Curative Resection Followed by Adjuvant Chemoradiation Therapy

    SciTech Connect

    Song, Changhoon; Kim, Kyubo; Chie, Eui Kyu; Kim, Jin Ho; Jang, Jin-Young; Kim, Sun Whe; Han, Sae-Won; Oh, Do-Youn; Im, Seock-Ah; Kim, Tae-You; Bang, Yung-Jue; Ha, Sung W.

    2013-11-01

    Purpose: To develop nomograms for predicting the overall survival (OS) and relapse-free survival (RFS) in patients with extrahepatic bile duct cancer undergoing adjuvant chemoradiation therapy after curative resection. Methods and Materials: From January 1995 through August 2006, a total of 166 consecutive patients underwent curative resection followed by adjuvant chemoradiation therapy. Multivariate analysis using Cox proportional hazards regression was performed, and this Cox model was used as the basis for the nomograms of OS and RFS. We calculated concordance indices of the constructed nomograms and American Joint Committee on Cancer (AJCC) staging system. Results: The OS rate at 2 years and 5 years was 60.8% and 42.5%, respectively, and the RFS rate at 2 years and 5 years was 52.5% and 38.2%, respectively. The model containing age, sex, tumor location, histologic differentiation, perineural invasion, and lymph node involvement was selected for nomograms. The bootstrap-corrected concordance index of the nomogram for OS and RFS was 0.63 and 0.62, respectively, and that of AJCC staging for OS and RFS was 0.50 and 0.52, respectively. Conclusions: We developed nomograms that predicted survival and recurrence better than AJCC staging. With caution, clinicians may use these nomograms as an adjunct to or substitute for AJCC staging for predicting an individual's prognosis and offering tailored adjuvant therapy.

  5. High response rates to neoadjuvant platinum-based therapy in ovarian cancer patients carrying germ-line BRCA mutation.

    PubMed

    Gorodnova, Tatiana V; Sokolenko, Anna P; Ivantsov, Alexandr O; Iyevleva, Aglaya G; Suspitsin, Evgeny N; Aleksakhina, Svetlana N; Yanus, Grigory A; Togo, Alexandr V; Maximov, Sergey Ya; Imyanitov, Evgeny N

    2015-12-28

    Preoperative therapy provides an advantage for clinical drug assessment, as it involves yet untreated patients and facilitates access to the post-treatment biological material. Testing for Slavic founder BRCA mutations was performed for 225 ovarian cancer (OC) patients, who were treated by platinum-based neoadjuvant therapy. 34 BRCA1 and 1 BRCA2 mutation carriers were identified. Complete clinical response was documented in 12/35 (34%) mutation carriers and 8/190 (4%) non-carriers (P = 0.000002). Histopathologic response was observed in 16/35 (46%) women with the germ-line mutation versus 42/169 (25%) patients with the wild-type genotype (P = 0.02). Somatic loss of heterozygosity (LOH) for the remaining wild-type BRCA1 allele was detected only in 7/24 (29%) post-neoadjuvant therapy residual tumor tissues as compared to 9/11 (82%) BRCA1-associated OC, which were not exposed to systemic treatment before the surgery (P = 0.009). Furthermore, comparison of pre- and post-treatment tumor material obtained from the same patients revealed restoration of BRCA1 heterozygosity in 2 out of 3 sample pairs presenting with LOH at diagnosis. The obtained data confirm high sensitivity of BRCA-driven OC to platinating agents and provide evidence for a rapid selection of tumor cell clones without LOH during the course of therapy.

  6. Phase 1 Clinical Trial of Stereotactic Body Radiation Therapy Concomitant With Neoadjuvant Chemotherapy for Breast Cancer

    SciTech Connect

    Bondiau, Pierre-Yves; Courdi, Adel; Bahadoran, Phillipe; Chamorey, Emmanuel; Queille-Roussel, Catherine; Lallement, Michel; Birtwisle-Peyrottes, Isabelle; Chapellier, Claire; Pacquelet-Cheli, Sandrine; Ferrero, Jean-Marc

    2013-04-01

    Purpose: Stereotactic body radiation therapy (SBRT) allows stereotactic irradiation of thoracic tumors. It may have a real impact on patients who may not otherwise qualify for breast-conserving surgery. We conducted a phase 1 trial that tested 5 dose levels of SBRT concomitant with neoadjuvant chemotherapy (NACT) before to surgery. The purpose of the current dose escalation study was to determine the maximum tolerable dose of SBRT in the treatment of breast cancer. Methods and Materials: To define toxicity, we performed dermatologic examinations that included clinical examinations by 2 separate physicians and technical evaluations using colorimetry, dermoscopy, and skin ultrasonography. Dermatologic examinations were performed before NACT, 36 and 56 days after the beginning of NACT, and before surgery. Surgery was performed 4 to 8 weeks after the last chemotherapy session. Efficacy, the primary endpoint, was determined by the pathologic complete response (pCR) rate. Results: Maximum tolerable dose was not reached. Only 1 case of dose-limiting toxicity was reported (grade 3 dermatologic toxicity), and SBRT was overall well tolerated. The pCR rate was 36%, with none being observed at the first 2 dose levels, and the highest rate being obtained at dose level 3 (25.5 Gy delivered in 3 fractions). Furthermore, the breast-conserving surgery rate was up to 92% compared with an 8% total mastectomy rate. No surgical complications were reported. Conclusions: This study demonstrates that SBRT can be safely combined with NACT. Regarding the efficacy endpoints, this trial showed promising results in terms of pCR rate (36%) and breast-conserving rate (92%). The findings provide a strong rationale for extending the study into a phase 2 trial. In view of the absence of correlation between dose and pCR, and given that the data from dose level 3 met the statistical requirements, a dose of 25.5 Gy in 3 fractions should be used for the phase 2 trial.

  7. Factors Predicting Effectiveness of Neoadjuvant Therapy for Esophageal Squamous Cell Carcinoma

    PubMed Central

    Ohkura, Yu; Ueno, Masaki; Iizuka, Toshiro; Haruta, Shusuke; Tanaka, Tsuyoshi; Udagawa, Harushi

    2016-01-01

    Abstract The aim of the study was to elucidate pretreatment factors that can predict the outcome of neoadjuvant chemoradiotherapy or chemotherapy (NAC(R)T) and help us choose treatment strategies appropriate for individual patients. Few studies have investigated whether clinical data obtainable before the treatment can predict the efficacy of NAC(R)T. Of 1540 patients treated for esophageal squamous cell carcinoma (ESCC) at our department between January 2000 and June 2014, those who underwent surgical resection of cStage II or more advanced ESCC after NAC(R)T (113 NACRT and 146 NACT patients) were enrolled in this study. Information all available before the treatment was analyzed to extract factors that can predict the effectiveness of NAC(R)T. NAC(R)T was considered effective when Grade 2 or greater treatment efficacy was achieved based on the histological grading system. NACRT was effective in 51 (45%) of 113 patients. The analysis of 35 pretreatment factors showed that female sex (hazard ratio [HR] = 3.650; 1.181–11.236), absence of dyslipidemia (HR = 3.284; 1.341–8.041), and histologically poorly differentiated tumor (HR = 2.431; 1.052–5.619) were factors predicting NACRT effectiveness. On the other hand, NACT was effective in 21 (14%) of 146 patients. The analysis of pretreatment factors showed that absence of dyslipidemia (HR = 10.204; 1.302–83.33) and therapy with docetaxel, cisplatin, and 5-fluorouracil (HR = 2.097; 1.027–4.280) were factors predicting NACT effectiveness. The findings of this study investigating factors that could predict the outcome of NAC(R)T suggest that the prevalence of dyslipidemia influences the outcome of NAC(R)T for ESCC. PMID:27082598

  8. Metastasized pancreatic carcinoma with neoadjuvant FOLFIRINOX therapy and R0 resection

    PubMed Central

    Schneitler, Sophie; Kröpil, Patric; Riemer, Jasmin; Antoch, Gerald; Knoefel, Wolfram Trudo; Häussinger, Dieter; Graf, Dirk

    2015-01-01

    Patients with metastasized carcinoma of the pancreas have a very poor prognosis, and long-term survival cannot be expected. This case report describes two patients with an initial diagnosis of metastatic pancreatic cancer, both with hepatic metastases and one with an additional peritoneal carcinomatosis. Initially, both patients were treated intravenously with the FOLFIRINOX chemotherapy regimen, consisting of 5-FU, folinic acid, irinotecan and oxaliplatin. Surprisingly, the FOLFIRINOX treatment resulted in complete resolution of the hepatic metastases in both patients, with no lesions detectable by computed tomography scan. Furthermore, treatment response included decreased diameter of the primary tumor in the tail of the pancreas and disappearance of the additional peritoneal carcinomatosis. Both patients were discussed by our multidisciplinary tumor board, which recommended surgical resections of the carcinoma. The R0 resection of the primary tumor was successful in both cases and, interestingly, the resected tissues showed no evidence of the hepatic metastases intraoperatively. In the first case, the patient received a postoperative 6-mo course of adjuvant chemotherapy with gemcitabine. In the second case, the patient continued to receive the FOLFIRINOX regimen for an additional 6 mo postoperatively. At 12 mo after the operation, a nonresectable retroperitoneal lymph node metastasis was detected in the first patient, whereas the second patient remained in complete remission at the time of this report (5 mo after the adjuvant therapy was discontinued). This case report is the first of its kind to describe two cases of hepatic metastatic pancreatic carcinoma that were resectable following treatment with FOLFIRINOX. Further studies are required to examine the role of FOLFIRINOX as a neoadjuvant treatment option in subgroups of patients with initially metastasized pancreatic carcinoma. PMID:26034375

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

    SciTech Connect

    Palma, David A.; Senan, Suresh; Oberije, Cary; Belderbos, Jose; Dios, Núria Rodríguez de; Bradley, Jeffrey D.; Barriger, R. Bryan; Moreno-Jiménez, Marta; Kim, Tae Hyun; Ramella, Sara; Everitt, Sarah; Rengan, Ramesh; Marks, Lawrence B.; De Ruyck, Kim; and others

    2013-11-15

    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) were 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

  10. Thymidylate Synthase Gene Polymorphism Affects the Response to Preoperative 5-Fluorouracil Chemoradiation Therapy in Patients With Rectal Cancer

    SciTech Connect

    Hur, Hyuk; Kang, Jeonghyun; Kim, Nam Kyu; Min, Byung Soh; Lee, Kang Young; Shin, Sang Joon; Keum, Ki Chang; Choi, Junjeong; Kim, Hoguen; Choi, Sung Ho; Lee, Mi-Young

    2011-11-01

    Purpose: This study aims to correlate thymidylate synthase (TS) gene polymorphisms with the tumor response to preoperative 5-fluorouracil (5-FU)-based chemoradiation therapy (CRT) in patients with rectal cancer. Methods and Materials: Forty-four patients with rectal cancer treated with 5-FU-based preoperative CRT were prospectively enrolled in this study. Thymidylate synthase expression and TS gene polymorphisms were evaluated in tumor obtained before preoperative CRT and were correlated with the pathologic response, as assessed by histopathologic staging (pTNM) and tumor regression grade. Results: Patients exhibited 2R/3R and 3R/3R tandem repeat polymorphisms in the TS gene. With regard to TS expression in these genotypes, 2R/3RC and 3RC/3RC were defined as the low-expression group and 2R/3RG, 3RC/3RG, and 3RG/3RG as the high-expression group. There was no significant correlation between TS expression and tumor response. There was no significant difference in the tumor response between patients homozygous for 3R/3R and patients heterozygous for 2R/3R. However, 13 of 14 patients in the low-expression group with a G>C single-nucleotide polymorphism (SNP) (2R/3RC [n = 5] or 3RC/3RC [n = 9]) exhibited a significantly greater tumor downstaging rate, as compared with only 12 of 30 patients in the high-expression group without the SNP (2R/3RG [n = 10], 3RC/3RG [n = 9], or 3RG/3RG [n = 11]) (p = 0.001). The nodal downstaging rate was also significantly greater in this low-expression group, as compared with the high-expression group (12 of 14 vs. 14 of 30, p = 0.014). However, there was no significant difference in the tumor regression grade between these groups. Conclusions: This study suggests that SNPs within the TS enhancer region affect the tumor response to preoperative 5-FU-based CRT in rectal cancer.

  11. Esophageal Cancer: Role of Imaging in Primary Staging and Response Assessment Post Neoadjuvant Therapy.

    PubMed

    Griffin, Yvette

    2016-08-01

    Advances in the early detection and treatment of esophageal cancer have meant improved survival rates for patients with esophageal cancer. Accurate pretreatment and post-neoadjuvant treatment staging of esophageal cancer is essential for assessing operability and determining the optimum treatment plan. This article reviews the multimodality imaging approach in the diagnosis, staging, and assessment of treatment response in esophageal cancer.

  12. A Phase 1/2 and Biomarker Study of Preoperative Short Course Chemoradiation With Proton Beam Therapy and Capecitabine Followed By Early Surgery for Resectable Pancreatic Ductal Adenocarcinoma

    SciTech Connect

    Hong, Theodore S.; Ryan, David P.; Borger, Darrell R.; Blaszkowsky, Lawrence S.; Yeap, Beow Y.; Ancukiewicz, Marek; Deshpande, Vikram; Shinagare, Shweta; Wo, Jennifer Y.; Boucher, Yves; Wadlow, Raymond C.; Kwak, Eunice L.; Allen, Jill N.; Clark, Jeffrey W.; Zhu, Andrew X.; Ferrone, Cristina R.; Mamon, Harvey J.; and others

    2014-07-15

    Purpose: To evaluate the safety, efficacy and biomarkers of short-course proton beam radiation and capecitabine, followed by pancreaticoduodenectomy in a phase 1/2 study in pancreatic ductal adenocarcinoma (PDAC) patients. Methods and Materials: Patients with radiographically resectable, biopsy-proven PDAC were treated with neoadjuvant short-course (2-week) proton-based radiation with capecitabine, followed by surgery and adjuvant gemcitabine. The primary objective was to demonstrate a rate of toxicity grade ≥3 of <20%. Exploratory biomarker studies were performed using surgical specimen tissues and peripheral blood. Results: The phase 2 dose was established at 5 daily doses of 5 GyE. Fifty patients were enrolled, of whom 35 patients were treated in the phase 2 portion. There were no grade 4 or 5 toxicities, and only 2 of 35 patients (4.1%) experienced a grade 3 toxicity event (chest wall pain grade 1, colitis grade 1). Of 48 patients eligible for analysis, 37 underwent pancreaticoduodenectomy. Thirty of 37 (81%) had positive nodes. Locoregional failure occurred in 6 of 37 resected patients (16.2%), and distant recurrence occurred in 35 of 48 patients (72.9%). With median follow-up of 38 months, the median progression-free survival for the entire group was 10 months, and overall survival was 17 months. Biomarker studies showed significant associations between worse survival outcomes and the KRAS point mutation change from glycine to aspartic acid at position 12, stromal CXCR7 expression, and circulating biomarkers CEA, CA19-9, and HGF (all, P<.05). Conclusions: This study met the primary endpoint by showing a rate of 4.1% grade 3 toxicity for neoadjuvant short-course proton-based chemoradiation. Treatment was associated with favorable local control. In exploratory analyses, KRAS{sup G12D} status and high CXCR7 expression and circulating CEA, CA19-9, and HGF levels were associated with poor survival.

  13. Neoadjuvant Radiation Is Associated With Improved Survival in Patients With Resectable Pancreatic Cancer: An Analysis of Data From the Surveillance, Epidemiology, and End Results (SEER) Registry

    SciTech Connect

    Stessin, Alexander M.; Meyer, Joshua E.; Sherr, David L.

    2008-11-15

    Purpose: Cancer of the exocrine pancreas is the fifth leading cause of cancer death in the United States. Neoadjuvant chemoradiation has been investigated in several trials as a strategy for downstaging locally advanced disease to resectability. The aim of the present study is to examine the effect of neoadjuvant radiation therapy (RT) vs. other treatments on long-term survival for patients with resectable pancreatic cancer in a large population-based sample group. Methods and Materials: The Surveillance, Epidemiology, and End Results (SEER) registry database (1994-2003) was queried for cases of surgically resected pancreatic cancer. Retrospective analysis was performed. The endpoint of the study was overall survival. Results: Using Kaplan-Meier analysis we found that the median overall survival of patients receiving neoadjuvant RT was 23 months vs. 12 months with no RT and 17 months with adjuvant RT. Using Cox regression and controlling for independent covariates (age, sex, stage, grade, and year of diagnosis), we found that neoadjuvant RT results in significantly higher rates of survival than other treatments (hazard ratio [HR], 0.55; 95% confidence interval, 0.38-0.79; p = 0.001). Specifically comparing adjuvant with neoadjuvant RT, we found a significantly lower HR for death in patients receiving neoadjuvant RT rather than adjuvant RT (HR, 0.63; 95% confidence interval, 0.45-0.90; p = 0.03). Conclusions: This analysis of SEER data showed a survival benefit for the use of neoadjuvant RT over surgery alone or surgery with adjuvant RT in treating pancreatic cancer. Therapeutic strategies that use neoadjuvant RT should be further explored for patients with resectable pancreatic cancer.

  14. Preoperative Chemoradiation Therapy With Capecitabine/Oxaliplatin and Cetuximab in Rectal Cancer: Long-Term Results of a Prospective Phase 1/2 Study

    SciTech Connect

    Fokas, Emmanouil; Conradi, Lena; Weiss, Christian; Sprenger, Thilo; Middel, Peter; Rau, Tillman; Dellas, Kathrin; Kitz, Julia; Rödel, Franz; Sauer, Rolf; Rüschoff, Josef; Beissbarth, Tim; Arnold, Dirk; Ghadimi, B. Michael; Rödel, Claus; Liersch, Torsten

    2013-12-01

    Purpose: We have previously shown that the addition of cetuximab to chemoradiation therapy failed to improve complete response rates (pCR) in rectal cancer. Here we report the long-term results of the cetuximab added to preoperative radiation therapy with capecitabine and oxaliplatin (CET-CAPOX-RT) phase 1/2 study that evaluated preoperative chemoradiation with cetuximab, capecitabine, and oxaliplatin in patients with rectal cancer. Methods and Materials: The median follow-up was 63 months (range, 5-73 months). Sixty patients were enrolled; 3 patients were excluded due to protocol violation, and 4 died before surgery. Total mesorectal excision was performed in 53 patients, in 85% (n=45) with curative intention (M0-status). Secondary end points including overall survival (OS) disease-free survival (DFS) and cancer-specific survival (CSS) were calculated. The prognostic value of KRAS mutation status was also assessed. Results: Histopathological examination confirmed ypUICC stages 0 (n=4; pCR), I (n=17), II (n=10), III (n=14), and IV (n=8). For patients who underwent surgery (n=53), OS at 1, 3, and 5 years was 88.7%, 83%, and 75.5%, respectively, whereas CSS rates were 94.1%, 88.1%, and 78.1%, respectively. In the 45 patients who were treated with curative intent (M0), the OS rates at 1, 3, and 5 years were 91.1%, 88.9%, and 86.7%, respectively; whereas CSS rates were 97.6%, 95.2%, and 90.3%, respectively; and DFS rates were 90.7%, 88.3%, and 88.3%, respectively. We did not find any locoregional failure in patients with M0-status (n=45). Chronic toxicity was rare. KRAS mutations, as detected in 33.3%, showed no correlation with the clinicopathological parameters nor significance for either OS (P=.112), CSS (P=.264), or DFS (P=.565). Conclusions: Taken together, chemoradiation therapy combined with cetuximab is safe, feasible, and offers excellent survival rates. KRAS mutation status was not a predictive factor. Importantly, lack of improvement in pCR rate did not

  15. Noninvasive Subharmonic Pressure Estimation for Monitoring Breast Cancer Response to Neoadjuvant Therapy

    DTIC Science & Technology

    2013-01-01

    K. Dave, J. Eisenbrey, P. Machado, J. B. Liu, D. A. Merton , B. C. Cavanaugh, F. Forsberg. Subharmonic aided pressure estimation for monitoring...Raichlen, J. B. Liu, C. Miller, J. M. Gonzalez, M. E. McDonald, D. A. Merton , D. Brown, V. Navarro. On the utility of subharmonic contrast...Cavanaugh, P. Machado, J. B. Liu, J. Eisenbrey, J. K. Dave, D. A. Merton . Subharmonic aided pressure estimation for monitoring neoadjuvant

  16. Noninvasive Subharmonic Pressure Estimation for Monitoring Breast Cancer Response to Neoadjuvant Therapy

    DTIC Science & Technology

    2011-09-01

    J. Eisenbrey, P. Machado, J. B. Liu, D. A. Merton , B. C. Cavanaugh, F. Forsberg. Subharmonic aided pressure estimation for monitoring interstitial...Raichlen, J. B. Liu, C. Miller, J. M. Gonzalez, M. E. McDonald, D. A. Merton , D. Brown, V. Navarro. On the utility of subharmonic contrast microbubble...Cavanaugh, P. Machado, J. B. Liu, J. Eisenbrey, J. K. Dave, D. A. Merton . Subharmonic aided pressure estimation for monitoring neoadjuvant chemotherapy

  17. [Downstaging after neoadjuvant therapy for rectal cancer modifies the planned original surgery].

    PubMed

    Scutari, F; Tramutola, G; Morlino, A; Rossi, M T; Manzione, L; Rosati, G; Sopranzi, A

    2008-01-01

    Cancer of the rectum has been for more years burdened with a heavy rate of local relapse about 30%. The introduction of total meso-rectum excision has reduced the rate of up to 5-8%. Later more studies proved how the preoperative radiotherapy was able to reduce the rate of local relapse. The Authors introduce studies about downstaging after neoadjuvant chemoradiotherapy for rectal cancer and discuss about their own series from 2005 to 2007.

  18. PSA Response to Neoadjuvant Androgen Deprivation Therapy Is a Strong Independent Predictor of Survival in High-Risk Prostate Cancer in the Dose-Escalated Radiation Therapy Era

    SciTech Connect

    McGuire, Sean E.; Lee, Andrew K.; Cerne, Jasmina Z.; Munsell, Mark F.; Levy, Lawrence B.; Kudchadker, Rajat J.; Choi, Seungtaek L.; Nguyen, Quynh N.; Hoffman, Karen E.; Pugh, Thomas J.; Frank, Steven J.; Corn, Paul G.; Logothetis, Christopher J.; Kuban, Deborah A.

    2013-01-01

    Purpose: The aim of the study was to evaluate the prognostic value of prostate-specific antigen (PSA) response to neoadjuvant androgen deprivation therapy (ADT) prior to dose-escalated radiation therapy (RT) and long-term ADT in high-risk prostate cancer. Methods and Materials: We reviewed the charts of all patients diagnosed with high-risk prostate cancer and treated with a combination of long-term ADT (median, 24 months) and dose-escalated (median, 75.6 Gy) RT between 1990 and 2007. The associations among patient, tumor, and treatment characteristics with biochemical response to neoadjuvant ADT and their effects on failure-free survival (FFS), time to distant metastasis (TDM), prostate cancer-specific mortality (PCSM) and overall survival (OS) were examined. Results: A total of 196 patients met criteria for inclusion. Median follow-up time for patients alive at last contact was 7.0 years (range, 0.5-18.1 years). Multivariate analysis identified the pre-RT PSA concentration (<0.5 vs {>=}0.5 ng/mL) as a significant independent predictor of FFS (P=.021), TDM (P=.009), PCSM (P=.039), and OS (P=.037). On multivariate analysis, pretreatment PSA (iPSA) and African-American race were significantly associated with failure to achieve a pre-RT PSA of <0.5 ng/mL. Conclusions: For high-risk prostate cancer patients treated with long-term ADT and dose-escalated RT, a pre-RT PSA level {>=}0.5 ng/mL after neoadjuvant ADT predicts for worse survival measures. Both elevated iPSA and African-American race are associated with increased risk of having a pre-RT PSA level {>=}0.5 ng/mL. These patients should be considered for clinical trials that test newer, more potent androgen-depleting therapies such as abiraterone and MDV3100 in combination with radiation.

  19. Phase I Study of Preoperative Short-Course Chemoradiation With Proton Beam Therapy and Capecitabine for Resectable Pancreatic Ductal Adenocarcinoma of the Head

    SciTech Connect

    Hong, Theodore S.; Ryan, David P.; Blaszkowsky, Lawrence S.; Mamon, Harvey J.; Mino-Kenudson, Mari; Adams, Judith; Yeap, Beow; Winrich, Barbara; DeLaney, Thomas F.; Fernandez-Del Castillo, Carlos

    2011-01-01

    Purpose: To evaluate the safety of 1 week of chemoradiation with proton beam therapy and capecitabine followed by early surgery. Methods and Materials: Fifteen patients with localized resectable, pancreatic adenocarcinoma of the head were enrolled from May 2006 to September 2008. Patients received radiation with proton beam. In dose level 1, patients received 3 GyE x 10 (Week 1, Monday-Friday; Week 2, Monday-Friday). Patients in Dose Levels 2 to 4 received 5 GyE x 5 in progressively shortened schedules: level 2 (Week 1, Monday, Wednesday, and Friday; Week 2, Tuesday and Thursday), Level 3 (Week 1, Monday, Tuesday, Thursday, and Friday; Week 2, Monday), Level 4 (Week 1, Monday through Friday). Capecitabine was given as 825 mg/m{sup 2} b.i.d. Weeks 1 and 2 Monday through Friday for a total of 10 days in all dose levels. Surgery was performed 4 to 6 weeks after completion of chemotherapy for Dose Levels 1 to 3 and then after 1 to 3 weeks for Dose Level 4. Results: Three patients were treated at Dose Levels 1 to 3 and 6 patients at Dose Level 4, which was selected as the MTD. No dose limiting toxicities were observed. Grade 3 toxicity was noted in 4 patients (pain in 1; stent obstruction or infection in 3). Eleven patients underwent resection. Reasons for no resection were metastatic disease (3 patients) and unresectable tumor (1 patient). Mean postsurgical length of stay was 6 days (range, 5-10 days). No unexpected 30-day postoperative complications, including leak or obstruction, were found. Conclusions: Preoperative chemoradiation with 1 week of proton beam therapy and capecitabine followed by early surgery is feasible. A Phase II study is underway.

  20. Duodenal Toxicity After Fractionated Chemoradiation for Unresectable Pancreatic Cancer

    SciTech Connect

    Kelly, Patrick; Das, Prajnan; Pinnix, Chelsea C.; Beddar, Sam; Briere, Tina; Pham, Mary; Krishnan, Sunil; Delclos, Marc E.; Crane, Christopher H.

    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 with 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

  1. Neoadjuvant therapy for early-stage breast cancer: the clinical utility of pertuzumab.

    PubMed

    Gollamudi, Jahnavi; Parvani, Jenny G; Schiemann, William P; Vinayak, Shaveta

    2016-01-01

    Approximately 20% of breast cancer patients harbor tumors that overexpress human epidermal growth factor receptor 2 (HER2; also known as ErbB2), a receptor tyrosine kinase that belongs to the epidermal growth factor receptor family of receptor tyrosine kinases. HER2 amplification and hyperactivation drive the growth and survival of breast cancers through the aberrant activation of proto-oncogenic signaling systems, particularly the Ras/MAP kinase and PI3K/AKT pathways. Although HER2-positive (HER2(+)) breast cancer was originally considered to be a highly aggressive form of the disease, the clinical landscape of HER2(+) breast cancers has literally been transformed by the approval of anti-HER2 agents for adjuvant and neoadjuvant settings. Indeed, pertuzumab is a novel monoclonal antibody that functions as an anti-HER2 agent by targeting the extracellular dimerization domain of the HER2 receptor; it is also the first drug to receive an accelerated approval by the US Food and Drug Administration for use in neoadjuvant settings in early-stage HER2(+) breast cancer. Here, we review the molecular and cellular factors that contribute to the pathophysiology of HER2 in breast cancer, as well as summarize the landmark preclinical and clinical findings underlying the approval and use of pertuzumab in the neoadjuvant setting. Finally, the molecular mechanisms operant in mediating resistance to anti-HER2 agents, and perhaps to pertuzumab as well, will be discussed, as will the anticipated clinical impact and future directions of pertuzumab in breast cancer patients.

  2. Neoadjuvant therapy for early-stage breast cancer: the clinical utility of pertuzumab

    PubMed Central

    Gollamudi, Jahnavi; Parvani, Jenny G; Schiemann, William P; Vinayak, Shaveta

    2016-01-01

    Approximately 20% of breast cancer patients harbor tumors that overexpress human epidermal growth factor receptor 2 (HER2; also known as ErbB2), a receptor tyrosine kinase that belongs to the epidermal growth factor receptor family of receptor tyrosine kinases. HER2 amplification and hyperactivation drive the growth and survival of breast cancers through the aberrant activation of proto-oncogenic signaling systems, particularly the Ras/MAP kinase and PI3K/AKT pathways. Although HER2-positive (HER2+) breast cancer was originally considered to be a highly aggressive form of the disease, the clinical landscape of HER2+ breast cancers has literally been transformed by the approval of anti-HER2 agents for adjuvant and neoadjuvant settings. Indeed, pertuzumab is a novel monoclonal antibody that functions as an anti-HER2 agent by targeting the extracellular dimerization domain of the HER2 receptor; it is also the first drug to receive an accelerated approval by the US Food and Drug Administration for use in neoadjuvant settings in early-stage HER2+ breast cancer. Here, we review the molecular and cellular factors that contribute to the pathophysiology of HER2 in breast cancer, as well as summarize the landmark preclinical and clinical findings underlying the approval and use of pertuzumab in the neoadjuvant setting. Finally, the molecular mechanisms operant in mediating resistance to anti-HER2 agents, and perhaps to pertuzumab as well, will be discussed, as will the anticipated clinical impact and future directions of pertuzumab in breast cancer patients. PMID:26937204

  3. DNA Repair Biomarkers Predict Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer

    SciTech Connect

    Alexander, Brian M.; Niemierko, Andrzej; Weaver, David T.; Mak, Raymond H.; Fidias, Panagiotis; Wain, John; Choi, Noah C.

    2012-05-01

    Purpose: The addition of neoadjuvant chemoradiotherapy prior to surgical resection for esophageal cancer has improved clinical outcomes in some trials. Pathologic complete response (pCR) following neoadjuvant therapy is associated with better clinical outcome in these patients, but only 22% to 40% of patients achieve pCR. Because both chemotherapy and radiotherapy act by inducing DNA damage, we analyzed proteins selected from multiple DNA repair pathways, using quantitative immunohistochemistry coupled with a digital pathology platform, as possible biomarkers of treatment response and clinical outcome. Methods and Materials: We identified 79 patients diagnosed with esophageal cancer between October 1994 and September 2002, with biopsy tissue available, who underwent neoadjuvant chemoradiotherapy prior to surgery at the Massachusetts General Hospital and used their archived, formalin-fixed, paraffin-embedded biopsy samples to create tissue microarrays (TMA). TMA sections were stained using antibodies against proteins in various DNA repair pathways including XPF, FANCD2, PAR, MLH1, PARP1, and phosphorylated MAPKAP kinase 2 (pMK2). Stained TMA slides were evaluated using machine-based image analysis, and scoring incorporated both the intensity and the quantity of positive tumor nuclei. Biomarker scores and clinical data were assessed for correlations with clinical outcome. Results: Higher scores for MLH1 (p = 0.018) and lower scores for FANCD2 (p = 0.037) were associated with pathologic response to neoadjuvant chemoradiation on multivariable analysis. Staining of MLH1, PARP1, XPF, and PAR was associated with recurrence-free survival, and staining of PARP1 and FANCD2 was associated with overall survival on multivariable analysis. Conclusions: DNA repair proteins analyzed by immunohistochemistry may be useful as predictive markers for response to neoadjuvant chemoradiotherapy in patients with esophageal cancer. These results are hypothesis generating and need

  4. Phase II Trial of Neoadjuvant Bevacizumab, Capecitabine, and Radiotherapy for Locally Advanced Rectal Cancer

    SciTech Connect

    Crane, Christopher H.; Eng, Cathy; Feig, Barry W.; Das, Prajnan; Skibber, John M.; Chang, George J.; Wolff, Robert A.; Krishnan, Sunil; Hamilton, Stanley; Janjan, Nora A.; Maru, Dipen M.; Ellis, Lee M.; Rodriguez-Bigas, Miguel A.

    2010-03-01

    Purpose: We designed this Phase II trial to assess the efficacy and safety of the addition of bevacizumab to concurrent neoadjuvant capecitabine-based chemoradiation in locally advanced rectal cancer. Methods: Between April 2004 and December 2007, 25 patients with clinically staged T3N1 (n = 20) or T3N0 (n = 5) rectal cancer received neoadjuvant therapy with radiotherapy (50.4 Gy in 28 fractions over 5.5 weeks), bevacizumab every 2 weeks (3 doses of 5 mg/kg), and capecitabine (900 mg/m{sup 2} orally twice daily only on days of radiation), followed by surgical resection a median of 7.3 weeks later. Results: Procedures included abdominoperineal resection (APR; 6 patients), proctectomy with coloanal anastamosis (8 patients), low anterior resection (10 patients), and local excision (1 patient). Eight (32%) of 25 patients had a pathologic complete response, and 6 (24%) of 25 had <10% viable tumor cells in the specimen. No patient had Grade 3 hand-foot syndrome, gastrointestinal toxicity, or significant hematologic toxicity. Three wound complications required surgical intervention (one coloanal anastamostic dehiscence requiring completion APR and two perineal wound dehiscences after initial APR). Five minor complications occurred that resolved without operative intervention. With a median follow-up of 22.7 months (range, 4.5-32.4 months), all patients were alive; one patient has had a recurrence in the pelvis (2-year actuarial rate, 6.2%) and 3 had distant recurrences. Conclusions: The addition of bevacizumab to neoadjuvant chemoradiation resulted in encouraging pathologic complete response without an increase in acute toxicity. The impact of bevacizumab on perineal wound and anastamotic healing due to concurrent bevacizumab requires further study.

  5. 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

  6. Dose-Volume Effects on Patient-Reported Acute Gastrointestinal Symptoms During Chemoradiation Therapy for Rectal Cancer

    SciTech Connect

    Chen, Ronald C.; Mamon, Harvey J.; Ancukiewicz, Marek; Killoran, Joseph H.; Crowley, Elizabeth M.; Blaszkowsky, Lawrence S.; Wo, Jennifer Y.; Ryan, David P.; Hong, Theodore S.

    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 associations 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.

  7. Helical Tomotherapy Versus Conventional Intensity-Modulated Radiation Therapy for Primary Chemoradiation in Cervical Cancer Patients: An Intraindividual Comparison

    SciTech Connect

    Marnitz, Simone; Lukarski, Dusko; Koehler, Christhardt; Wlodarczyk, Waldemar; Ebert, Andreas; Budach, Volker; Schneider, Achim; Stromberger, Carmen

    2011-10-01

    Purpose: To compare intensity-modulated radiotherapy (IMRT) delivered by helical tomotherapy (HT) with conventional IMRT for primary chemoradiation in cervical cancer patients. Methods and Materials: Twenty cervical cancer patients undergoing primary chemoradiation received radiation with HT; 10 patients underwent pelvic irradiation (PEL) and 10 extended-field irradiation (EXT). For treatment planning, the simultaneously integrated boost (SIB) concept was applied. Tumor, pelvic, with or without para-aortic lymph nodes were defined as planning target volume A (PTV-A) with a prescribed dose of 1.8/50.4 Gy (28 fractions). The SIB dose for the parametrium (PTV-B), was 2.12/59.36 Gy. The lower target constraints were 95% of the prescribed dose in 95% of the target volume, and the upper dose constraint was 107%. The irradiated small-bowel volumes were kept as low as possible. For every HT plan, a conventional IMRT plan was calculated and compared with regard to dose-volume histogram, conformity index and conformity number, and homogeneity index. Results: Both techniques allowed excellent target volume coverage and sufficient SB sparing. Conformity index and conformity number results for both PTV-A and PTV-B, homogeneity index for PTV-B, and SB sparing for V45, V50, Dmax, and D1% were significantly better with HT. SB sparing was significantly better for conventional IMRT at low doses (V10). Conclusions: Both HT and conventional IMRT provide optimal treatment of cervical cancer patients. The HT technique was significantly favored with regard to target conformity, homogeneity, and SB sparing. Randomized trials are needed to assess the oncological outcome, toxicity, and clinical relevance of these differences.

  8. Predicting the Response of Breast Cancer to Neoadjuvant Therapy Using a Mechanically Coupled Reaction-Diffusion Model

    PubMed Central

    Weis, Jared A.; Miga, Michael I.; Arlinghaus, Lori R.; Li, Xia; Abramson, Vandana; Chakravarthy, A. Bapsi; Pendyala, Praveen; Yankeelov, Thomas E.

    2015-01-01

    While there is considerable data on the use of mathematical modeling to describe tumor growth and response to therapy, previous approaches are often not of the form that can be easily applied to clinical data to generate testable predictions in individual patients. Thus, there is a clear need to develop and apply clinically-relevant oncological models that are amenable to available patient data and yet retain the most salient features of response prediction. In this study we show how a biomechanical model of tumor growth can be initialized and constrained by serial patient-specific magnetic resonance imaging data, obtained at two time points early in the course of therapy (before initiation and following one cycle of therapy), to predict the response for individual patients with breast cancer undergoing neoadjuvant therapy. Using our mechanics coupled modeling approach, we are able to predict, after the first cycle of therapy, breast cancer patients that would eventually achieve a complete pathological response and those who would not, with receiver operating characteristic area under the curve (AUC) of 0.87, sensitivity of 92%, and specificity of 84%. Our approach significantly outperformed the AUCs achieved by standard (i.e., not mechanically coupled)reaction-diffusion predictive modeling (0.75), simple analysis of the tumor cellularity estimated from imaging data (0.73), and the Response Evaluation Criteria in Solid Tumors (RECIST; 0.71). Thus, we show the potential for mathematical model prediction for use as a prognostic indicator of response to therapy. The work indicates the considerable promise of image-driven biophysical modeling for predictive frameworks within therapeutic applications. PMID:26333809

  9. Neoadjuvant treatment for rectal cancer-A value-based proposition.

    PubMed

    Massarweh, Nader N; Artinyan, Avo; Chang, George J

    2016-09-01

    Over the last decade, the use of neoadjuvant chemo-radiation has been an integral part of the care of patients with locally advanced rectal cancer. However, emerging data are beginning to challenge the current treatment paradigm of neoadjuvant chemo-radiation followed by radical resection and subsequent adjuvant chemotherapy. Going forward, the challenge will be to identify patients for whom radiation can be safely omitted and those for whom it can potentially provide added oncologic value. J. Surg. Oncol. 2016;114:304-310. © 2016 Wiley Periodicals, Inc.

  10. Meta-Analysis for the Therapeutic Effect of Neoadjuvant Therapy in Resectable Esophageal Cancer.

    PubMed

    Zhu, Yusen; Liu, Min; Yun, Xiaojing; Wang, Dongmei; Bai, Yuhuan; Zhang, Guizhi; Ji, Bei; Jing, Changchun

    2016-12-24

    We aimed to review the therapeutic effects of neoadjuvant chemoradiotherapy (NCRT), chemotherapy (NCT), and radiotherapy (NRT) on patients with resectable Esophageal cancer (EsC) by comparison with surgery alone (SA). PubMed, EMBASE and Cochrane were searched for eligible studies published up to March 2015. Cochrane reviews were used for quality assessment. Eight primary outcomes were analyzed. Risk ratios (RRs)/ hazard ratios (HRs) and corresponding 95% confidence intervals (95% CIs) were calculated using the random- or fixed- effects model. Heterogeneity was assessed using the Chi-square-based Q statistic and the I (2) test. Publication bias was examined by the Begg's funnel plot. Totally 24 articles including 4718 EsC cases were eligible for this meta-analysis. The quality of the literatures was relatively high. Significant difference was found in five-year survival rate (RR = 1.45, 95% CI: 1.17-1.79, P < 0.01) between patients treated with NCT and SA, while the eight enrolled primary outcomes were all statistically different between NCRT and SA, and significant difference was identified in three-year survival between NCRT and NCT (RR = 1.35, 95% CI: 1.14-1.60, P < 0.01). No obvious publication bias was observed. NCRT and NCT provide an obvious benefit for EsC treatment over SA, and NCRT possesses a clear advantage compared with NCT.

  11. Health-related quality of life and psychological distress during neoadjuvant endocrine therapy with letrozole to determine endocrine responsiveness in postmenopausal breast cancer.

    PubMed

    Taira, Naruto; Iwata, Hiroji; Hasegawa, Yoshie; Sakai, Takehiko; Higaki, Kenji; Kihara, Kiyohiro; Yamaguchi, Takuhiro; Ohsumi, Shozo; Shimozuma, Kojiro; Ohashi, Yasuo

    2014-05-01

    Trials of adjuvant endocrine therapy for breast cancer have shown that aromatase inhibitors have little impact on global health-related quality of life (HRQoL), but have significant effects on patient-reported endocrine symptoms (ESs). There are few studies of HRQoL and psychological distress during preoperative endocrine therapy performed to determine endocrine responsiveness. The NEOS trial is a multicenter, phase 3 randomized controlled trial in postmenopausal women with hormone receptor-positive breast cancer. The primary aim of the trial was to evaluate the need for adjuvant chemotherapy in patients with clinical T1c-T2N0M0, hormone receptor-positive tumors who responded to neoadjuvant letrozole (LET) administered for 24-28 weeks before surgery. The primary endpoint was disease-free survival and the secondary endpoints included adverse events, HRQoL, and cost-effectiveness. In a HRQoL sub-study, subjects were assessed at baseline and 4 and 16 weeks after starting neoadjuvant LET, using the functional assessment of cancer therapy-breast and its ES subscale, and the hospital anxiety and depression scale. HRQoL and psychosocial distress were analyzed in the uncontrolled phase during 24-28 weeks of neoadjuvant LET therapy in the NEOS trial. From May 16, 2008, to December 14, 2011, 503 patients were recruited into the HRQoL sub-study. The full analysis set included 497 patients with a mean age of 63-years old. The questionnaire response rates at enrollment and 4 and 16 weeks were 94.4, 90.7, and 89.1 %, respectively. There were no significant changes in the FACT-G or B-trial outcome index over time, but the social and family well-being score and the ES subscale deteriorated significantly, and the number of patients with clinically significant hot flush increased significantly. Anxiety, depression, and emotional well-being improved significantly after neoadjuvant LET. Neoadjuvant endocrine therapy with LET had no impact on global HRQoL, but did influence endocrine

  12. Monitoring the response to neoadjuvant hormone therapy for locally advanced breast cancer using three-dimensional time-resolved optical mammography

    NASA Astrophysics Data System (ADS)

    Enfield, Louise; Cantanhede, Gabriel; Douek, Michael; Ramalingam, Vernie; Purushotham, Arnie; Hebden, Jem; Gibson, Adam

    2013-05-01

    Optical mammography is a functional imaging technique that uses near-infrared light to produce three-dimensional breast images of tissue oxygen saturation and hemoglobin concentration. It has been used to monitor the response to neoadjuvant chemotherapy in breast cancer patients. We present the first results on monitoring tumor response to hormone therapy using optical mammography. We present three case studies from postmenopausal women treated with neoadjuvant hormone therapy for locally advanced breast cancer. The women were scanned before starting treatment, once during treatment, and then before surgery. Changes in physiological and optical properties within the tumor and in the rest of the breast were evaluated. At the time of surgery, two patients partially responded to treatment and one did not respond. The patients that partially responded on ultrasound revealed a corresponding recovery to normal in the hemoglobin concentration images, whereas the nonresponder indicated an increase in hemoglobin concentration in the tumor compared to her pretreatment images. These case studies suggest that optical imaging of the breast during neoadjuvant hormone treatment can provide potentially valuable information, and that physiological changes within the tumor can be seen in response to treatment.

  13. PIK3CA Mutations Are Associated With Decreased Benefit to Neoadjuvant Human Epidermal Growth Factor Receptor 2–Targeted Therapies in Breast Cancer

    PubMed Central

    Majewski, Ian J.; Nuciforo, Paolo; Mittempergher, Lorenza; Bosma, Astrid J.; Eidtmann, Holger; Holmes, Eileen; Sotiriou, Christos; Fumagalli, Debora; Jimenez, Jose; Aura, Claudia; Prudkin, Ludmila; Díaz-Delgado, Maria Carmen; de la Peña, Lorena; Loi, Sherene; Ellis, Catherine; Schultz, Nikolaus; de Azambuja, Evandro; Harbeck, Nadia; Piccart-Gebhart, Martine; Bernards, René; Baselga, José

    2015-01-01

    Purpose We investigated whether mutations in the gene encoding the phosphatidylinositol 3-kinase (PI3K) catalytic subunit (PIK3CA) correlates with response to neoadjuvant human epidermal growth factor receptor 2 (HER2) –targeted therapies in patients with breast cancer. Patients and Methods Baseline tissue biopsies were available from patients with HER2-positive early breast cancer who were enrolled onto the Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial (NeoALTTO). Activating mutations in PIK3CA were identified using mass spectrometry–based genotyping. Results PIK3CA mutations were identified in 23% of HER2-positive breast tumors, and these mutations were associated with poorer outcome in all of the treatment arms. Patients treated with a combination of trastuzumab and lapatinib who had wild-type PIK3CA obtained a total pathologic complete response (pCR) rate of 53.1%, which decreased to 28.6% in patients with tumors that carried PIK3CA activating mutations (P = .012). Conclusion Activating mutations in PIK3CA predicted poor pCR in patients with HER2-positive breast cancer treated with neoadjuvant therapies that target HER2. Consequently, the combination of anti-HER2 agents and PI3K inhibitors is being investigated. PMID:25559818

  14. Feasibility of Neoadjuvant Ad-REIC Gene Therapy in Patients with High-Risk Localized Prostate Cancer Undergoing Radical Prostatectomy.

    PubMed

    Kumon, Hiromi; Sasaki, Katsumi; Ariyoshi, Yuichi; Sadahira, Takuya; Araki, Motoo; Ebara, Shin; Yanai, Hiroyuki; Watanabe, Masami; Nasu, Yasutomo

    2015-12-01

    In a phase I/IIa study of in situ gene therapy using an adenovirus vector carrying the human REIC/Dkk-3 gene (Ad-REIC), we assessed the inhibitory effects of cancer recurrence after radical prostatectomy (RP), in patients with high risk localized prostate cancer (PCa). After completing the therapeutic interventions with initially planned three escalating doses of 1.0 × 10(10) , 1.0 × 10(11) , and 1.0 × 10(12) viral particles (VP) in 1.0-1.2 mL (n = 3, 3, and 6), an additional higher dose of 3.0 × 10(12) VP in 3.6 mL (n = 6) was further studied. Patients with recurrence probability of 35% or more within 5 years after RP as calculated by Kattan's nomogram, were enrolled. They received two ultrasound-guided intratumoral injections at 2-week intervals, followed by RP 6 weeks after the second injection. Based on the findings of MRI and biopsy mapping, as a rule, one track injection to the most prominent cancer area was given to initial 12 patients and 3 track injections to multiple cancer areas in additional 6 patients. As compared to the former group, biochemical recurrence-free survival of the latter showed a significantly favorable outcome. Neoadjuvant Ad-REIC, mediating simultaneous induction of cancer selective apoptosis and augmentation of antitumor immunity, is a feasible approach in preventing cancer recurrence after RP. (199).

  15. Neoadjuvant chemotherapy in women with large and locally advanced breast cancer: chemoresistance and prediction of response to drug therapy.

    PubMed

    Chuthapisith, S; Eremin, J M; El-Sheemy, M; Eremin, O

    2006-08-01

    Patients with large and locally advanced breast cancer (LLABC) present with a therapeutic challenge and undergo multimodality treatment. Many such patients receive neoadjuvant chemotherapy (NAC) prior to surgery. However, a number of these patients do not respond well to NAC and only a percentage (usually less than 30%) obtains a complete or optimal response. A range of mechanisms are believed to be involved in this chemoresistance, including ATP binding cassette (ABC) transporter overexpression, dysregulation of apoptosis and possibly increased numbers of cancer stem cells. The chemoresistant processes may be due to more than one mechanism. The ability to predict a response to NAC would be beneficial, targeting expensive and toxic drug treatment to those likely to respond and providing a therapeutic strategy for further post-operative chemotherapy. Currently, many biomarkers have been studied with a view to establishing a predictor of response. However, no single biomarker appears to be effective. Genomics is a novel biotechnological process which is being used to predict response to drug therapy; this work is currently at an early stage of development

  16. Dose-dependent change in biomarkers during neoadjuvant endocrine therapy with fulvestrant: results from NEWEST, a randomized Phase II study.

    PubMed

    Kuter, Irene; Gee, Julia M W; Hegg, Roberto; Singer, Christian F; Badwe, Rajendra A; Lowe, Elizabeth S; Emeribe, Ugochi A; Anderson, Elizabeth; Sapunar, Francisco; Finlay, Pauline; Nicholson, Robert I; Bines, José; Harbeck, Nadia

    2012-05-01

    NEWEST (Neoadjuvant Endocrine Therapy for Women with Estrogen-Sensitive Tumors) is the first study to compare biological and clinical activity of fulvestrant 500 versus 250 mg in the neoadjuvant breast cancer setting. We hypothesized that fulvestrant 500 mg may be superior to 250 mg in blocking estrogen receptor (ER) signaling and growth. A multicenter, randomized, open-label, Phase II study was performed to compare fulvestrant 500 mg (500 mg/month plus 500 mg on day 14 of month 1) versus fulvestrant 250 mg/month for 16 weeks prior to surgery in postmenopausal women with ER+ locally advanced breast cancer. Core biopsies at baseline, week 4, and surgery were assessed for biomarker changes. Primary endpoint: change in Ki67 labeling index (LI) from baseline to week 4 determined by automated computer imaging system (ACIS). Secondary endpoints: ER protein expression and function; progesterone receptor (PgR) expression; tumor response; tolerability. ER and PgR were examined retrospectively using the H score method. A total of 211 patients were randomized (fulvestrant 500 mg: n = 109; 250 mg: n = 102). At week 4, fulvestrant 500 mg resulted in greater reduction of Ki67 LI and ER expression versus 250 mg (-78.8 vs. -47.4% [p < 0.0001] and -25.0 vs. -13.5% [p = 0.0002], respectively [ACIS]); PgR suppression was not significantly different (-22.7 vs. -17.6; p = 0.5677). However, H score detected even greater suppression of ER (-50.3 vs. -13.7%; p < 0.0001) and greater PgR suppression (-80.5 vs. -46.3%; p = 0.0018) for fulvestrant 500 versus 250 mg. At week 16, tumor response rates were 22.9 and 20.6% for fulvestrant 500 and 250 mg, respectively, with considerable decline in all markers by both ACIS and H score. No detrimental effects on endometrial thickness or bone markers and no new safety concerns were identified. This provides the first evidence of greater biological activity for fulvestrant 500 versus 250 mg in depleting ER expression, function, and growth.

  17. 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

    SciTech Connect

    Parlak, Cem; Mertsoylu, Hüseyin; Güler, Ozan Cem; Onal, Cem; Topkan, Erkan

    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 of 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.

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

    SciTech Connect

    Yeo, Seung-Gu; Oh, Jae Hwan; Kim, Dae Yong; Baek, Ji Yeon; Kim, Sun Young; Park, Ji Won; Kim, Min Ju; Chang, Hee Jin; Kim, Tae Hyun; Lee, Jong Hoon; Jang, Hong Seok; Kim, Jun-Gi; Lee, Myung Ah; Nam, Taek-Keun

    2013-05-01

    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 pathologic 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.

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

    SciTech Connect

    Chang, Jee Suk; Choi, Seo Hee; Lee, Youngin; Kim, Kyung Hwan; Park, Jeong Youp; Song, Si Young; Cho, Arthur; Yun, Mijin; Lee, Jong Doo; Seong, Jinsil

    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 detected 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.

  20. Neoadjuvant chemotherapy for invasive bladder cancer.

    PubMed

    Sonpavde, Guru; Sternberg, Cora N

    2012-04-01

    Neoadjuvant cisplatin-based combination chemotherapy is an established standard for resectable muscle-invasive bladder cancer, a disease with a pattern of predominantly distant and early recurrences. Pathologic complete remission appears to be an intermediate surrogate for survival when employing combination chemotherapy. Moreover, baseline host and tumor tissue studies may enable the discovery of biomarkers predictive of activity. The neoadjuvant setting also provides a window of opportunity to evaluate novel biologic agents or rational combinations of biologic agents to obtain a signal of biologic activity. The residual tumor after neoadjuvant therapy may be exploited to study the mechanism of action and resistance. Cisplatin-ineligible patients warrant the evaluation of tolerable neoadjuvant regimens. Given that bladder cancer is characterized by initial localized presentation in the vast majority of cases, the paradigm of neoadjuvant therapy may expedite the development of novel systemic agents.

  1. Combining antiangiogenic therapy with neoadjuvant chemotherapy increases treatment efficacy in stage IIIA (N2) non-small cell lung cancer without increasing adverse effects

    PubMed Central

    Zhao, Xiaoliang; Su, Yanjun; You, Jian; Gong, Liqun; Zhang, Zhenfa; Wang, Meng; Zhao, Zhenqing; Zhang, Zhen; Li, Xiaolin; Wang, Changli

    2016-01-01

    To evaluate the safety and efficacy of combining Endostar antiangiogenic therapy with neoadjuvant chemotherapy for the treatment of stage IIIA (N2) NSCLC, we conducted a randomized, controlled, open-label clinical study of 30 NSCLC patients. Patients were randomly assigned to the test or control groups, which received either two cycles of an NP neoadjuvant chemotherapy regimen combined with Endostar or the NP regimen alone, respectively, at a 2:1 ratio. Efficacy was assessed after 3 weeks, and surgical resection occurred within 4 weeks, in the 26 patients who successfully completed treatment. While total response rates (RR) and clinical benefit rates (CBR) did not differ between the experimental groups, total tumor regression rates (TRR) were higher in the test group than in the control group. Median DFS and OS also did not differ between the test and control groups. Clinical perioperative indicators, including intraoperative blood loss, number of dissected lymph node groups, duration of postoperative indwelling catheter use, and time to postoperative discharge, were comparable in the test and control groups. Finally, hematological and non-hematological toxicities and postoperative pathological indicators, including down-staging ratio, complete resection ratio, and metastatic lymph node ratio, also did not differ between the groups. Overall, combining Endostar with NP neoadjuvant chemotherapy increased therapeutic efficacy without increasing adverse effects in stage IIIA-N2 NSCLC patients. This study is registered with ClinicalTrials.gov (number NCT02497118). PMID:27566586

  2. A Patient with a Large Gastric Tumor and Protein-Losing Gastroenteropathy Successfully Treated with Neoadjuvant TS-1 Combined with CDDP Therapy

    PubMed Central

    Hashimoto, Tatsuya; Yamashita, Yuichi; Shibata, Ryosuke; Satou, Keisuke; Yamana, Ippei; Maki, Kenji; Takeno, Shinsuke; Nimura, Satoshi

    2014-01-01

    Gastric cancer with protein-losing gastroenteropathy is relatively rare worldwide. The most important problem for the treatment of these patients is their low nutritional status and protein level, which can cause severe postoperative complications. We report a 49-year-old Japanese female with a large gastric tumor and protein-losing gastroenteropathy successfully treated with neoadjuvant TS-1 combined with CDDP therapy. She had a type 5 tumor with partially cauliflower-like appearance. Her blood chemistry revealed low serum total protein (3.3 g/dl) and low albumin (1.7 g/dl). She was additionally diagnosed with protein-losing gastroenteropathy based on 99mTc-human serum albumin scintigraphy. Initial neoadjuvant chemotherapy decreased the size of the tumor and led to a marked improvement in her serum protein levels. She then underwent a total gastrectomy and lymph node dissection (D2) with a combined resection of the spleen and gallbladder. Therefore, neoadjuvant chemotherapy may provide a safe treatment before definitive surgery for gastric cancer with protein-losing gastroenteropathy. PMID:25722665

  3. Nuclear NF-κB Expression Correlates With Outcome Among Patients With Head and Neck Squamous Cell Carcinoma Treated With Primary Chemoradiation Therapy

    SciTech Connect

    Balermpas, Panagiotis; Michel, Yvonne; Wagenblast, Jens; Seitz, Oliver; Sipek, Florian; Rödel, Franz; Rödel, Claus; Fokas, Emmanouil

    2013-07-15

    Background: To examine whether nuclear NF-κB expression correlates with outcome in patients with head and neck squamous cell carcinoma (HNSCC) treated with primary chemoradiation therapy (CRT). Methods and Materials: Between 2007 and 2010, 101 patients with locally advanced primary HNSCC were treated with definitive simultaneous CRT. Pretreatment biopsy specimens were analyzed for NF-κB p65 (RelA) nuclear immunoreactivity. A sample was assigned to be positive with more than 5% positive nuclear expression. The predictive relevance of NF-κB and clinicopathologic factors for overall survival (OS), progression-free survival (PFS), local progression-free survival (LPFS), and metastasis-free survival (DMFS) was examined by univariate and multivariate analysis. Results: No significant differences between the groups were observed with regard to age, sex, total radiation dose, fractionation mode, total chemotherapy applied, T stage or grading. Patients with p65 nuclear positive biopsy specimens showed significantly a higher rate of lymph node metastasis (cN2c or cN3 status, P=.034). Within a mean follow-up time of 25 months (range, 2.33-62.96 months) OS, PFS, and DMFS were significantly poorer in the p65 nuclear positive group (P=.008, P=.027, and P=.008, respectively). These correlations remained significant in multivariate analysis. Conclusion: NF-κB/p65 nuclear expression is associated with increased lymphatic and hematogenous tumor dissemination and decreased survival in HNSCC patients treated with primary CRT. Our results may foster further investigation of a predictive relevance of NF-κB/p65 and its role as a suitable target for a molecular-based targeted therapy in HNSCC cancer.

  4. A Phase 1/2 Study of Definitive Chemoradiation Therapy Using Docetaxel, Nedaplatin, and 5-Fluorouracil (DNF-R) for Esophageal Cancer

    SciTech Connect

    Ohnuma, Hiroyuki; Sato, Yasushi; Hirakawa, Masahiro; Okagawa, Yutaka; Osuga, Takahiro; Hayashi, Tsuyoshi; Sato, Tsutomu; Miyanishi, Koji; Kobune, Masayoshi; Takimoto, Rishu; Sagawa, Tamotsu; Hori, Masakazu; Someya, Masanori; Nakata, Kensei; Sakata, Koh-ichi; Takayama, Tetsuji; Kato, Junji

    2015-10-01

    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, 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.

  5. Impact of Weight Change During the Course of Concurrent Chemoradiation Therapy on Outcomes in Stage IIIB Non-Small Cell Lung Cancer Patients: Retrospective Analysis of 425 Patients

    SciTech Connect

    Topkan, Erkan; Parlak, Cem; Selek, Ugur

    2013-11-15

    Purpose: We retrospectively investigated the impact of weight change (WC) during concurrent chemoradiation therapy (C-CRT) on clinical outcomes of stage 3B non-small cell lung cancer (NSCLC) patients. Methods and Materials: A total of 425 patients treated with C-CRT were included. All patients received 60 to 66 Gy of thoracic radiation therapy concurrently with 1 to 3 cycles of platinum-based chemotherapy. Pre- and posttreatment weight measurements on first and last days of C-CRT were used for WC. Patients were divided into 2 groups: group 1 = weight loss (WL); group 2 = weight preservation/gain (WP) for comparative analyses. Results: Following C-CRT, 252 patients (59.3%) experienced WL, while 89 patients (20.9%) and 84 patients (19.8%) showed WP or WG. At median 24.2 months of follow-up, 142 patients (33.4%) were alive (84 WP [48.6%] and 58 WL [23.0%]), and 58 (13.6%) of them were free of disease progression (41 [23.7%] for WP and 17 [6.7%] for WL). Median overall survival (OS), locoregional progression-free survival (LRPFS), progression-free survival (PFS), and distant metastases-free survival (DMFS) for the entire population were 22.8, 14.4, 10.6, and 11.7 months, respectively. Intergroup comparisons between WP and WL cohorts revealed significantly superior OS, LRPFS, PFS, and DMFS in WP patients (P<.05 for each). On multivariate analyses, only WL and advanced T stage were associated with poor prognosis (P<.05). Conclusions: Present results in 425 stage 3B NSCLC patients demonstrated that WL during C-CRT is strongly associated with inferior survival outcomes compared to WP. This emerging finding might be useful by forming an encouraging basis for future investigations in facilitating a way to improve the outcomes of these patients experiencing WL during C-CRT.

  6. MRI for Assessing Response to Neoadjuvant Therapy in Locally Advanced Rectal Cancer Using DCE-MR and DW-MR Data Sets: A Preliminary Report

    PubMed Central

    Petrillo, Mario; Fusco, Roberta; Catalano, Orlando; Sansone, Mario; Avallone, Antonio; Delrio, Paolo; Pecori, Biagio; Tatangelo, Fabiana; Petrillo, Antonella

    2015-01-01

    To evaluate MRI for neoadjuvant therapy response assessment in locally advanced rectal cancer (LARC) using dynamic contrast enhanced-MRI (DCE-MRI) and diffusion weighted imaging (DWI), we have compared magnetic resonance volumetry based on DCE-MRI (V(DCE)) and on DWI (V(DWI)) scans with conventional T2-weighted volumetry (V(C)) in LARC patients after neoadjuvant therapy. Twenty-nine patients with LARC underwent MR examination before and after neoadjuvant therapy. A manual segmentation was performed on DCE-MR postcontrast images, on DWI (b-value 800 s/mm2), and on conventional T2-weighted images by two radiologists. DCE-MRI, DWI, and T2-weigthed volumetric changes before and after treatment were evaluated. Nonparametric sample tests, interobserver agreement, and receiver operating characteristic curve (ROC) were performed. Diagnostic performance linked to DCE-MRI volumetric change was superior to T2-w and DW-MRI volumetric changes performance (specificity 86%, sensitivity 93%, and accuracy 93%). Area Under ROC (AUC) of V(DCE) was greater than AUCs of V(C) and V(DWI) resulting in an increase of 15.6% and 11.1%, respectively. Interobserver agreement between two radiologists was 0.977, 0.864, and 0.756 for V(C), V(DCE), and V(DWI), respectively. V(DCE) seems to be a promising tool for therapy response assessment in LARC. Further studies on large series of patients are needed to refine technique and evaluate its potential value. PMID:26413528

  7. Noninvasive Subharmonic Pressure Estimation for Monitoring Breast Cancer Response to Neoadjuvant Therapy

    DTIC Science & Technology

    2010-09-01

    3, pp. S13, 2010. 11 F. Forsberg. The holy grail : ultrasound microbubbles for therapy. J Ultrasound Med, vol 29, no 3, pp. S17, 2010. F...San Diego, CA, USA.  Noninvasive cardiac subharmonic pressure estimation in vivo.  The holy grail : ultrasound microbubbles for therapy May...DFD.LR.1, 2010. A. Katiyar, K. Sarkar, F.Forsberg. Subharmonic response from ultrasound contrast microbubbles for noninvasive blood pressure

  8. Oncologic safety of breast conserving surgery after tumour downsizing by neoadjuvant therapy: a retrospective single centre cohort study.

    PubMed

    Fitzal, F; Riedl, O; Mittlböck, M; Dubsky, P; Bartsch, R; Steger, G; Jakesz, R; Gnant, M

    2011-05-01

    The objective of this study is to analyse local recurrence rates in patients receiving neoadjuvant chemotherapy (nCT) comparing mastecomized (MX) patients with those undergoing breast conserving therapy (BCT). Patients undergoing breast cancer surgery after nCT (3xCMF or 3-6xED) between 1995 and 2007 at our department were retrospectively analysed. The median follow up was 60 months for 308 patients. Patients who were downsized from MX to BCT with partial or complete response (n = 104) had a similar local recurrence free survival (LRFS) compared to patients who did not experience successful downsizing (n = 67) and finally undergoing MX (LRFS MX-BCT 81% vs. MX-MX 91%; P = 0.79). Uni- and multivariate analyses demonstrated that BCT itself was not an independent prognostic factor for a worse LRFS (P = 0.07 and 0.14). After no pathologic change or progressive disease the risk of local recurrence was increased in patients undergoing BCT (MX-BCT; n = 6 LRFS 66%) compared with MX (n = 44; LRFS 90%; P = 0.04). Overall survival in general was better for the BCT group (n = 197) compared with MX group (n = 111) regardless of clinical response (92% vs. 72%; P < 0.0001). Breast conservation, nodal negativity and low or medium grade histology were prognostic factors for an improved OS (P = 0.02, 0.01, 0.004). In conclusion, our study suggests that BCT is oncologically safe after tumour downsizing by nCT in patients primarily scheduled for mastectomy. These patients, however, should not be treated with breast conservation in the absence of any proven response after nCT.

  9. Role of Adjuvant Chemotherapy in ypT0-2N0 Patients Treated with Preoperative Chemoradiation Therapy and Radical Resection for Rectal Cancer

    SciTech Connect

    Park, In Ja; Kim, Dae Yong; Kim, Hee Cheol; Kim, Nam Kyu; Kim, Hyeong-Rok; Kang, Sung-Bum; Choi, Gyu-Seog; Lee, Kang Young; Kim, Seon-Hahn; Oh, Seung Taek; Lim, Seok-Byung; Kim, Jin Cheon; Oh, Jae Hwan; Kim, Sun Young; Lee, Woo Yong; Lee, Jung Bok; Yu, Chang Sik

    2015-07-01

    Objective: To explore the role of adjuvant chemotherapy for patients with ypT0-2N0 rectal cancer treated by preoperative chemoradiation therapy (PCRT) and radical resection. Patients and Methods: A national consortium of 10 institutions was formed, and patients with ypT0-2N0 mid- and low-rectal cancer after PCRT and radical resection from 2004 to 2009 were included. Patients were categorized into 2 groups according to receipt of additional adjuvant chemotherapy: Adj CTx (+) versus Adj CTx (−). Propensity scores were calculated and used to perform matched and adjusted analyses comparing relapse-free survival (RFS) between treatment groups while controlling for potential confounding. Results: A total of 1016 patients, who met the selection criteria, were evaluated. Of these, 106 (10.4%) did not receive adjuvant chemotherapy. There was no overall improvement in 5-year RFS as a result of adjuvant chemotherapy [91.6% for Adj CTx (+) vs 87.5% for Adj CTx (−), P=.18]. There were no differences in 5-year local recurrence and distant metastasis rate between the 2 groups. In patients who show moderate, minimal, or no regression in tumor regression grade, however, possible association of adjuvant chemotherapy with RFS would be considered (hazard ratio 0.35; 95% confidence interval 0.14-0.88; P=.03). Cox regression analysis after propensity score matching failed to show that addition of adjuvant chemotherapy was associated with improved RFS (hazard ratio 0.81; 95% confidence interval 0.39-1.70; P=.58). Conclusions: Adjuvant chemotherapy seemed to not influence the RFS of patients with ypT0-2N0 rectal cancer after PCRT followed by radical resection. Thus, the addition of adjuvant chemotherapy needs to be weighed against its oncologic benefits.

  10. A Decision Aid for Women Considering Neoadjuvant Systemic Therapy for Operable Invasive Breast Cancer: Development and Protocol of a Phase II Evaluation Study (ANZ1301 DOMINO)

    PubMed Central

    Butow, Phyllis; Hutchings, Elizabeth; Douglas, Charles; Coll, Joseph R; Boyle, Frances M

    2016-01-01

    Background Neoadjuvant systemic therapy is offered to selected women with large and/or highly proliferative operable breast cancers. This option adds further complexity to an already complex breast cancer treatment decision tree. Patient decision aids are an established method of increasing patient involvement and knowledge while decreasing decisional conflict. There is currently no decision aid available for women considering neoadjuvant systemic therapy. Objective We aimed to develop a decision aid for women diagnosed with operable breast cancer and considered suitable for neoadjuvant systemic therapy, and the protocol for a multicenter pre-post study evaluating the acceptability and feasibility of the decision aid. Methods The decision aid was developed through literature review, expert advisory panel, adherence to the International Patient Decision Aid Standards, and iterative review. The protocol for evaluation of the decision aid consists of the following: eligible women will undertake a series of questionnaires prior to and after using the decision aid. The primary endpoint is decision aid acceptability to patients and investigators and the feasibility of use. Secondary endpoints include change in decisional conflict, participant knowledge, and information involvement preference. Feasibility is defined as the proportion of eligible participants who use the decision aid to help inform their treatment decision. Results This study has recruited 29 out of a planned 50 participants at four Australian sites. A 12-month recruitment period is expected with a further 12-months follow-up. Conclusions The decision aid has the potential to allow patients with operable breast cancer, who have been offered neoadjuvant systemic therapy, decreased decisional conflict, and greater involvement in the decision. If this study finds that an online decision aid is feasible and acceptable, it will be made widely available for routine clinical practice. Trial Registration

  11. A Proof-Of-Principle Study of Epigenetic Therapy Added to Neoadjuvant Doxorubicin Cyclophosphamide for Locally Advanced Breast Cancer

    PubMed Central

    González-Fierro, Aurora; de la Cruz-Hernández, Erick; Revilla-Vázquez, Alma; Chávez-Blanco, Alma; Trejo-Becerril, Catalina; Pérez-Cárdenas, Enrique; Taja-Chayeb, Lucia; Bargallo, Enrique; Villarreal, Patricia; Ramírez, Teresa; Vela, Teresa; Candelaria, Myrna; Camargo, Maria F.; Robles, Elizabeth; Dueñas-González, Alfonso

    2006-01-01

    Background Aberrant DNA methylation and histone deacetylation participate in cancer development and progression; hence, their reversal by inhibitors of DNA methylation and histone deacetylases (HDACs) is at present undergoing clinical testing in cancer therapy. As epigenetic alterations are common to breast cancer, in this proof-of-concept study demethylating hydralazine, plus the HDAC inhibitor magnesium valproate, were added to neoadjuvant doxorubicin and cyclophosphamide in locally advanced breast cancer to assess their safety and biological efficacy. Methodology This was a single-arm interventional trial on breast cancer patients (ClinicalTrials.gov Identifier: NCT00395655). After signing informed consent, patients were typed for acetylator phenotype and then treated with hydralazine at 182 mg for rapid-, or 83 mg for slow-acetylators, and magnesium valproate at 30 mg/kg, starting from day –7 until chemotherapy ended, the latter consisting of four cycles of doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 every 21 days. Core-needle biopsies were taken from primary breast tumors at diagnosis and at day 8 of treatment with hydralazine and valproate. Main Findings 16 patients were included and received treatment as planned. All were evaluated for clinical response and toxicity and 15 for pathological response. Treatment was well-tolerated. The most common toxicity was drowsiness grades 1–2. Five (31%) patients had clinical CR and eight (50%) PR for an ORR of 81%. No patient progressed. One of 15 operated patients (6.6%) had pathological CR and 70% had residual disease <3 cm. There was a statistically significant decrease in global 5mC content and HDAC activity. Hydralazine and magnesium valproate up- and down-regulated at least 3-fold, 1,091 and 89 genes, respectively. Conclusions Hydralazine and magnesium valproate produce DNA demethylation, HDAC inhibition, and gene reactivation in primary tumors. Doxorubicin and cyclophosphamide treatment is safe, well

  12. Definitive Chemoradiation Therapy With Docetaxel, Cisplatin, and 5-Fluorouracil (DCF-R) in Advanced Esophageal Cancer: A Phase 2 Trial (KDOG 0501-P2)

    SciTech Connect

    Higuchi, Katsuhiko; Komori, Shouko; Tanabe, Satoshi; Katada, Chikatoshi; Azuma, Mizutomo; Ishiyama, Hiromichi; Sasaki, Tohru; Ishido, Kenji; Katada, Natsuya; Hayakawa, Kazushige; Koizumi, Wasaburo

    2014-07-15

    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, 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.

  13. Reduction in Tumor Volume by Cone Beam Computed Tomography Predicts Overall Survival in Non-Small Cell Lung Cancer Treated With Chemoradiation Therapy

    SciTech Connect

    Jabbour, Salma K.; Kim, Sinae; Haider, Syed A.; Xu, Xiaoting; Wu, Alson; Surakanti, Sujani; Aisner, Joseph; Langenfeld, John; Yue, Ning J.; Haffty, Bruce G.; Zou, Wei

    2015-07-01

    Purpose: We sought to evaluate whether tumor response using cone beam computed tomography (CBCT) performed as part of the routine care during chemoradiation therapy (CRT) could forecast the outcome of unresectable, locally advanced, non-small cell lung cancer (NSCLC). Methods and Materials: We manually delineated primary tumor volumes (TV) of patients with NSCLC who were treated with radical CRT on days 1, 8, 15, 22, 29, 36, and 43 on CBCTs obtained as part of the standard radiation treatment course. Percentage reductions in TV were calculated and then correlated to survival and pattern of recurrence using Cox proportional hazard models. Clinical information including histologic subtype was also considered in the study of such associations. Results: We evaluated 38 patients with a median follow-up time of 23.4 months. The median TV reduction was 39.3% (range, 7.3%-69.3%) from day 1 (D1) to day 43 (D43) CBCTs. Overall survival was associated with TV reduction from D1 to D43 (hazard ratio [HR] 0.557, 95% CI 0.39-0.79, P=.0009). For every 10% decrease in TV from D1 to D43, the risk of death decreased by 44.3%. For patients whose TV decreased ≥39.3 or <39.3%, log-rank test demonstrated a separation in survival (P=.02), with median survivals of 31 months versus 10 months, respectively. Neither local recurrence (HR 0.791, 95% CI 0.51-1.23, P=.29), nor distant recurrence (HR 0.78, 95% CI 0.57-1.08, P=.137) correlated with TV decrease from D1 to D43. Histologic subtype showed no impact on our findings. Conclusions: TV reduction as determined by CBCT during CRT as part of routine care predicts post-CRT survival. Such knowledge may justify intensification of RT or application of additional therapies. Assessment of genomic characteristics of these tumors may permit a better understanding of behavior or prediction of therapeutic outcomes.

  14. Predictive value of initial FDG-PET features for treatment response and survival in esophageal cancer patients treated with chemo-radiation therapy using a random forest classifier

    PubMed Central

    Ruan, Su; Modzelewski, Romain; Pineau, Pascal; Vauclin, Sébastien; Gouel, Pierrick; Michel, Pierre; Di Fiore, Frédéric; Vera, Pierre; Gardin, Isabelle

    2017-01-01

    Purpose In oncology, texture features extracted from positron emission tomography with 18-fluorodeoxyglucose images (FDG-PET) are of increasing interest for predictive and prognostic studies, leading to several tens of features per tumor. To select the best features, the use of a random forest (RF) classifier was investigated. Methods Sixty-five patients with an esophageal cancer treated with a combined chemo-radiation therapy were retrospectively included. All patients underwent a pretreatment whole-body FDG-PET. The patients were followed for 3 years after the end of the treatment. The response assessment was performed 1 month after the end of the therapy. Patients were classified as complete responders and non-complete responders. Sixty-one features were extracted from medical records and PET images. First, Spearman’s analysis was performed to eliminate correlated features. Then, the best predictive and prognostic subsets of features were selected using a RF algorithm. These results were compared to those obtained by a Mann-Whitney U test (predictive study) and a univariate Kaplan-Meier analysis (prognostic study). Results Among the 61 initial features, 28 were not correlated. From these 28 features, the best subset of complementary features found using the RF classifier to predict response was composed of 2 features: metabolic tumor volume (MTV) and homogeneity from the co-occurrence matrix. The corresponding predictive value (AUC = 0.836 ± 0.105, Se = 82 ± 9%, Sp = 91 ± 12%) was higher than the best predictive results found using the Mann-Whitney test: busyness from the gray level difference matrix (P < 0.0001, AUC = 0.810, Se = 66%, Sp = 88%). The best prognostic subset found using RF was composed of 3 features: MTV and 2 clinical features (WHO status and nutritional risk index) (AUC = 0.822 ± 0.059, Se = 79 ± 9%, Sp = 95 ± 6%), while no feature was significantly prognostic according to the Kaplan-Meier analysis. Conclusions The RF classifier can

  15. A Randomized Trial (Irish Clinical Oncology Research Group 97-01) Comparing Short Versus Protracted Neoadjuvant Hormonal Therapy Before Radiotherapy for Localized Prostate Cancer

    SciTech Connect

    Armstrong, John G.; Gillham, Charles M.; Dunne, Mary T.; Fitzpatrick, David A.; Finn, Marie A.; Cannon, Mairin E.; Taylor, Judy C.; O'Shea, Carmel M.; Buckney, Steven J.; Thirion, Pierre G.

    2011-09-01

    Purpose: To examine the long-term outcomes of a randomized trial comparing short (4 months; Arm 1) and long (8 months; Arm 2) neoadjuvant hormonal therapy before radiotherapy for localized prostate cancer. Methods and Materials: Between 1997 and 2001, 276 patients were enrolled and the data from 261 were analyzed. The stratification risk factors were prostate-specific antigen level >20 ng/mL, Gleason score {>=}7, and Stage T3 or more. The intermediate-risk stratum had one factor and the high-risk stratum had two or more. Staging was done from the bone scan and computed tomography findings. The primary endpoint was biochemical failure-free survival. Results: The median follow-up was 102 months. The overall survival, biochemical failure-free survival. and prostate cancer-specific survival did not differ significantly between the two treatment arms, overall or at 5 years. The cumulative probability of overall survival at 5 years was 90% (range, 87-92%) in Arm 1 and 83% (range, 80-86%) in Arm 2. The biochemical failure-free survival rate at 5 years was 66% (range, 62-71%) in Arm 1 and 63% (range, 58-67%) in Arm 2. Conclusion: No statistically significant difference was found in biochemical failure-free survival between 4 months and 8 months of neoadjuvant hormonal therapy before radiotherapy for localized prostate cancer.

  16. Complete Remission of Metastatic Neuroendocrine Paragastric Carcinoma After "Neoadjuvant" Peptide Receptor Radionuclide Therapy and Surgery.

    PubMed

    Schmidt, Matthias C; Uhrhan, Klara; Fischer, Thomas; Schmitz, Stephan; Markiefka, Birgid; Drzezga, Alexander; Stippel, Dirk

    2015-08-01

    A 48-year-old man presenting with upper abdominal pain was diagnosed with neuroendocrine tumor after biopsy of a paragastric mass with multiple liver metastases. (68)Ga-DOTATATE PET/CT showed intense uptake in the paragastric tumor and in multiple liver metastases not allowing primary surgery. Two cycles with cumulative 14.6 GBq (177)Lu-DOTATATE were given resulting in a considerable improvement. Subsequent surgery resulted in a complete remission as demonstrated by (68)Ga-DOTATATE PET/CT. Usually, peptide receptor radionuclide (PRRT) therapy is considered a palliative treatment. Few patients demonstrate a very favorable response allowing resection of the primary tumor after downstaging metastatic disease burden.

  17. Chemoradiation therapy using cyclopamine-loaded liquid-lipid nanoparticles and lutetium-177-labeled core-crosslinked polymeric micelles.

    PubMed

    You, Jian; Zhao, Jun; Wen, Xiaoxia; Wu, Chunhui; Huang, Qian; Guan, Fada; Wu, Richard; Liang, Dong; Li, Chun

    2015-03-28

    Cyclopamine (CPA), a potent inhibitor of the Hedgehog pathway, has produced promising anticancer results in a number of preclinical studies. CPA has also been found to enhance tumor response to radiation therapy. However, CPA is water insoluble. A drug delivery system suitable for systemic administration of CPA is needed before CPA can be considered for clinical translation. We hypothesized that CPA solubilized in a liquid-lipid nanoparticle system (CPA-LLP) for intravenous injection would have desirable pharmacokinetic properties and increased anticancer efficacy. We further hypothesized that CPA-LLP would enhance the response of tumor cells to targeted radiotherapy delivered selectively through intratumoral injection of lutetium-177 bound to core-crosslinked polymeric micelles (CCPM-(177)Lu). We tested the combination therapy in 4T1 murine breast cancer and Miapaca-2 human pancreatic adenocarcinoma models. The results showed that CPA-LLP had higher antitumor cytotoxicity than free CPA (IC50 values [mean±SEM]: 2.7±0.2μM vs. 11.3±1.2μM against 4T1 cells; 1.8±0.2 vs. 17.1±1.26μM against Miapaca-2 cells; p<0.0001). In both cell lines, CPA-LLP resulted in significantly lower clonogenicity than free CPA (p<0.05). Moreover, in both cell lines, CPA-LLP significantly enhanced the cell response to CCPM-(177)Lu radiotherapy as measured by clonogenic assay (p<0.05). In 4T1 and Miapaca-2 mouse xenograft models, the combination of CPA-LLP and CCPM-(177)Lu delayed tumor growth more than either monotherapy did alone. In the 4T1 tumor model, tumor size at 16days after treatment was significantly smaller with the combination therapy than with all the other treatments. In the Miapaca-2 model, the combination therapy resulted in the highest rate of mouse survival and prevented tumor relapse. In conclusion, the combination of CPA-LLP and CCPM-(177)Lu was an effective strategy for treating breast and pancreatic cancer and deserves further investigation.

  18. Factors Predictive of Protracted Course of Radiation Therapy in Patients Treated with Definitive Chemoradiation for Cervical Cancer

    PubMed Central

    Dominello, Michael; Morris, Robert; Miller, Steven

    2016-01-01

    Background There is a benefit to completing definitive chemoradiotherapy (CRT) for cervical cancer within 56 days. However, many patients experience delays due to missed radiation treatments that prolong the overall course of therapy. In order to improve patient care, we performed a quality improvement project to determine factors predictive of protracted treatment and develop strategies to enable timely treatment completion. Methods  Seventy-one patients treated for cervical cancer with CRT were identified. Medical records were reviewed to gather demographic, clinical, and treatment data. Prolonged treatment was defined as >56 days per the American Brachytherapy Society guidelines. The following variables were evaluated using paired t-tests and univariate logistic regression: demographics, Intensity Modulated Radiotherapy (IMRT) versus conventional radiation technique, use of a boost, time to stent placement, time to first brachytherapy (BT), and genitourinary (GU) or gastrointestinal (GI) toxicity. Results The median treatment length for all patients was 59 days. Factors associated with prolonged treatment were time to cervical stent placement (p=0.001), delay ≥2 days between final external beam radiation therapy (EBRT) and initial BT (p=0.0195), any grade GU toxicity (p=0.0007), or GI toxicity (p=0.0002), and the presence of a boost (p=0.0006). Age, stage, and IMRT versus conventional technique were not associated with protracted treatment. Conclusion  In this series of patients, acute toxicity, increased time to cervical stent placement, and time to first BT treatment were associated with prolonged treatment time. The patients who completed treatment in ≤56 days had a lower average time to cervical stent placement, 27 versus 31 days. Our results suggest that cervical stent placement during week four of treatment can enhance patient care and improve outcomes.  PMID:27182472

  19. The Significance of Tumoral ERCC1 Status in Patients With Locally Advanced Cervical Cancer Treated With Chemoradiation Therapy: A Multicenter Clinicopathologic Analysis

    SciTech Connect

    Doll, Corinne M.; Aquino-Parsons, Christina; Pintilie, Melania; Petrillo, Stephanie K.; Milosevic, Michael; Craighead, Peter S.; Clarke, Blaise; Lees-Miller, Susan P.; Fyles, Anthony W.; Magliocco, Anthony M.

    2013-03-01

    Purpose: ERCC1 (excision repair cross-complementation group 1) expression has been shown to be a molecular marker of cisplatin resistance in many tumor sites, but has not been well studied in cervical cancer patients. The purpose of this study was to measure tumoral ERCC1 in patients with locally advanced cervical cancer treated with chemoradiation therapy (CRT) in a large multicenter cohort, and to correlate expression with clinical outcome parameters. Methods and Materials: A total of 264 patients with locally advanced cervical cancer, treated with curative-intent radical CRT from 3 major Canadian cancer centers were evaluated. Pretreatment formalin-fixed, paraffin-embedded tumor specimens were retrieved, and tissue microarrays were constructed. Tumoral ERCC1 (FL297 antibody) was measured using AQUA (R) technology. Statistical analysis was performed to determine the significance of clinical factors and ERCC1 status with progression-free survival (PFS) and overall survival (OS) at 5 years. Results: The majority of patients had International Federation of Gynecology and Obstetrics (FIGO) stage II disease (n=119, 45%); median tumor size was 5 cm. OS was associated with tumor size (HR 1.16, P=.018), pretreatment hemoglobin status (HR 2.33, P=.00027), and FIGO stage. In addition, tumoral ERCC1 status (nuclear to cytoplasmic ratio) was associated with PFS (HR 2.33 [1.05-5.18], P=.038) and OS (HR 3.13 [1.27-7.71], P=.013). ERCC1 status was not significant on multivariate analysis when the model was adjusted for the clinical factors: for PFS (HR 1.49 [0.61-3.6], P=.38); for OS (HR 2.42 [0.94-6.24] P=.067). Conclusions: In this large multicenter cohort of locally advanced cervical cancer patients treated with radical CRT, stage, tumor size, and pretreatment hemoglobin status were significantly associated with PFS and OS. ERCC1 status appears to have prognostic impact on univariate analysis in these patients, but was not independently associated with outcome on

  20. Prognostic Significance of Tumor Response as Assessed by Sequential {sup 18}F-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography During Concurrent Chemoradiation Therapy for Cervical Cancer

    SciTech Connect

    Oh, Dongryul; Lee, Jeong Eun; Huh, Seung Jae; Park, Won; Nam, Heerim; Choi, Joon Young; Kim, Byung-Tae

    2013-11-01

    Purpose: To investigate the prognostic role of metabolic response by the use of serial sets of positron emission tomography/computed tomography (PET/CT) in patients with cervical cancer who were treated with concurrent chemoradiation therapy (CCRT). Methods and Materials: A total of 60 patients who were treated with CCRT between February 2009 and December 2010 were analyzed. Three sequential PET/CT images were acquired for each patient: pre-CCRT, during-CCRT at 4 weeks of CCRT, and 1 month post-CCRT PET/CT. Metabolic responses were assessed qualitatively. The percentage changes in the maximum values of standardized uptake value (ΔSUV{sub max}%) from the PET/CT images acquired pre-CCRT and during-CCRT were calculated. Receiver operating characteristic (ROC) curve analysis was performed to evaluate whether ΔSUV{sub max}% could predict complete response (CR) on the post-CCRT PET/CT and to identify the best cutoff value. Prognostic factors of progression-free survival (PFS) were analyzed. Results: During-CCRT PET/CT showed that 8 patients (13%) had CR, and the other 52 patients (87%) had partial response (PR). On the post-CCRT PET/CT, 43 patients (73%) had CR, 12 patients (20%) had PR, and 4 patients (7%) had progressive disease. The average SUV{sub max} in primary tumors was 16.3 (range, 6.4-53.0) on the pre-CCRT PET/CT images and 5.3 (range, 0-19.4) on the during-CCRT PET/CT images. According to ROC curve analysis, ΔSUV{sub max}% could predict CR response on post-CCRT PET/CT (P<.001, cutoff value of 59.7%). In all patients, the PFS rate was 71.9% at 2 years. Multivariate analysis showed that ΔSUV{sub max}% ≥60% (P=.045) and CR response on the post-CCRT PET/CT (P=.012) were statistically significant predictors of PFS. Conclusion: Metabolic responses on the during-CCRT images at 4 weeks of treatment and 1-month post-CCRT PET/CT images may predict treatment outcomes in patients with cervical cancer. ΔSUV{sub max}% ≥60% at 4 weeks of CCRT may predict CR response

  1. SU-C-BRA-04: Use of Esophageal Wall Thickness in Evaluation of the Response to Chemoradiation Therapy for Esophageal Cancer

    SciTech Connect

    Wang, J; Kligerman, S; Lu, W; Kang, M

    2015-06-15

    Purpose: To quantitatively evaluate the esophageal cancer response to chemoradiation therapy (CRT) by measuring the esophageal wall thickness in CT. Method: Two datasets were used in this study. The first dataset is composed of CT scans of 15 esophageal cancer patients and 15 normal controls. The second dataset is composed of 20 esophageal cancer patients who underwent PET/CT scans before (Pre-CRT) and after CRT (Post-CRT). We first segmented the esophagus using a multi-atlas-based algorithm. The esophageal wall thickness was then computed, on each slice, as the equivalent circle radius of the segmented esophagus excluding the lumen. To evaluate the changes of wall thickness, we computed the standard deviation (SD), coefficient of variation (COV, SD/Mean), and flatness [(Max–Min)/Mean] of wall thickness along the entire esophagus. Results: For the first dataset, the mean wall thickness of cancer patients and normal controls were 6.35 mm and 6.03 mm, respectively. The mean SD, COV, and flatness of the wall thickness were 2.59, 0.21, and 1.27 for the cancer patients and 1.99, 0.16, and 1.13 for normal controls. Statistically significant differences (p < 0.05) were identified in SD and flatness. For the second dataset, the mean wall thickness of pre-CRT and post-CRT patients was 7.13 mm and 6.84 mm, respectively. The mean SD, COV, and flatness were 1.81, 0.26, and 1.06 for pre-CRT and 1.69, 0.26, and 1.06 for post-CRT. Statistically significant difference was not identified for these measurements. Current results are based on the entire esophagus. We believe significant differences between pre- and post-CRT scans could be obtained, if we conduct the measurements at tumor sites. Conclusion: Results show thicker wall thickness in pre-CRT scans and differences in wall thickness changes between normal and abnormal esophagus. This demonstrated the potential of esophageal wall thickness as a marker in the tumor CRT response evaluation. This work was supported in part by

  2. Sequential and Concurrent Chemoradiation: State of the Art.

    PubMed

    Chau, Nicole G; Haddad, Robert I

    2015-12-01

    Most patients diagnosed with head and neck cancer have locally advanced disease. Sequential and concurrent chemoradiation are standard, nonsurgical, curative-intent treatment options. Controversy remains regarding the superiority of one approach to another. Definitive management strategies are evolving with increasing efforts to pursue deintensification of therapy for low-risk patients, and to pursue therapeutic intensification for high-risk patients. Both sequential therapy and concurrent chemoradiation play important roles in shaping treatment paradigms because both approaches may be used to investigate deintensification or intensification strategies. This article examines the latest evidence and state-of-the-art approaches, highlighting ongoing controversies and future directions.

  3. Failure to Achieve a PSA Level {<=}1 ng/mL After Neoadjuvant LHRHA Therapy Predicts for Lower Biochemical Control Rate and Overall Survival in Localized Prostate Cancer Treated With Radiotherapy

    SciTech Connect

    Mitchell, Darren M. McAleese, Jonathan; Park, Richard M.; Stewart, David P.; Stranex, Stephen; Eakin, Ruth L.; Houston, Russell F.; O'Sullivan, Joe M.

    2007-12-01

    Purpose: To investigate whether failure to suppress the prostate-specific antigen (PSA) level to {<=}1 ng/mL after {>=}2 months of neoadjuvant luteinizing hormone-releasing hormone agonist therapy in patients scheduled to undergo external beam radiotherapy for localized prostate carcinoma is associated with reduced biochemical failure-free survival. Methods and Materials: A retrospective case note review of consecutive patients with intermediate- or high-risk localized prostate cancer treated between January 2001 and December 2002 with neoadjuvant hormonal deprivation therapy, followed by concurrent hormonal therapy and radiotherapy was performed. Patient data were divided for analysis according to whether the PSA level in Week 1 of radiotherapy was {<=}1.0 ng/mL. Biochemical failure was determined using the American Society for Therapeutic Radiology and Oncology (Phoenix) definition. Results: A total of 119 patients were identified. The PSA level after neoadjuvant hormonal deprivation therapy was {<=}1 ng/mL in 67 patients and >1 ng/mL in 52. At a median follow-up of 49 months, the 4-year actuarial biochemical failure-free survival rate was 84% vs. 60% (p = 0.0016) in favor of the patients with a PSA level after neoadjuvant hormonal deprivation therapy of {<=}1 ng/mL. The overall survival rate was 94% vs. 77.5% (p = 0.0045), and the disease-specific survival rate at 4 years was 98.5% vs. 82.5%. Conclusions: The results of our study have shown that patients with a PSA level >1 ng/mL at the beginning of external beam radiotherapy after {>=}2 months of neoadjuvant luteinizing hormone-releasing hormone agonist therapy have a significantly greater rate of biochemical failure and lower survival rate compared with those with a PSA level of {<=}1 ng/mL. Patients without adequate PSA suppression should be considered a higher risk group and considered for dose escalation or the use of novel treatments.

  4. FDG-PET/CT Imaging Predicts Histopathologic Treatment Responses after Neoadjuvant Therapy in Adult Primary Bone Sarcomas

    DOE PAGES

    Benz, Matthias R.; Czernin, Johannes; Tap, William D.; ...

    2010-01-01

    Purpose . Tmore » he aim of this study was to prospectively evaluate whether FDG-PET allows an accurate assessment of histopathologic response to neoadjuvant treatment in adult patients with primary bone sarcomas. Methods . Twelve consecutive patients with resectable, primary high grade bone sarcomas were enrolled prospectively. FDG-PET/CT imaging was performed prior to the initiation and after completion of neoadjuvant treatment. Imaging findings were correlated with histopathologic response. Results . Histopathologic responders showed significantly more pronounced decreases in tumor FDG-SUVmax from baseline to late follow up than non-responders ( 64 ± 19 % versus 29 ± 30 %, resp.; P = .03 ). Using a 60% decrease in tumor FDG-uptake as a threshold for metabolic response correctly classified 3 of 4 histopathologic responders and 7 of 8 histopathologic non-responders as metabolic responders and non-responders, respectively (sensitivity, 75%; specificity, 88%). Conclusion . These results suggest that changes in FDG-SUVmax at the end of neoadjuvant treatment can identify histopathologic responders and non-responders in adult primary bone sarcoma patients.« less

  5. First FDA approval of neoadjuvant therapy for breast cancer: pertuzumab for the treatment of patients with HER2-positive breast cancer.

    PubMed

    Amiri-Kordestani, Laleh; Wedam, Suparna; Zhang, Lijun; Tang, Shenghui; Tilley, Amy; Ibrahim, Amna; Justice, Robert; Pazdur, Richard; Cortazar, Patricia

    2014-11-01

    On September 30, 2013, the FDA granted accelerated approval to pertuzumab (Perjecta; Genentech, Inc.) for use in combination with trastuzumab and docetaxel as neoadjuvant treatment of patients with HER2-positive, locally advanced, inflammatory, or early-stage breast cancer (either greater than 2 cm in diameter or node positive) as part of a complete treatment regimen for early breast cancer. The approval was based in part on a randomized multicenter trial in the indicated population that allocated 417 patients to neoadjuvant treatment with trastuzumab-docetaxel (TD), pertuzumab-trastuzumab-docetaxel (PTD), pertuzumab-trastuzumab, or pertuzumab-docetaxel. PTD was administered preoperatively every 3 weeks for four cycles. Following surgery patients received three cycles of 5-fluorouracil, epirubicin, and cyclophosphamide every 3 weeks and trastuzumab every 3 weeks to complete 1 year of therapy. The pathologic complete response rates by the FDA-preferred definition [absence of invasive cancer in the breast and lymph nodes (ypT0/is ypN0)] were 39.3% and 21.5% in the PTD and the TD arms, respectively (P = 0.0063). The most common adverse reactions with PTD were alopecia, diarrhea, nausea, and neutropenia. This approval was based on the totality of evidence, particularly improved survival in the metastatic breast cancer trial, and a fully accrued confirmatory trial.

  6. Microarray profiling of mononuclear peripheral blood cells identifies novel candidate genes related to chemoradiation response in rectal cancer.

    PubMed

    Palma, Pablo; Cuadros, Marta; Conde-Muíño, Raquel; Olmedo, Carmen; Cano, Carlos; Segura-Jiménez, Inmaculada; Blanco, Armando; Bueno, Pablo; Ferrón, J Antonio; Medina, Pedro

    2013-01-01

    Preoperative chemoradiation significantly improves oncological outcome in locally advanced rectal cancer. However there is no effective method of predicting tumor response to chemoradiation in these patients. Peripheral blood mononuclear cells have emerged recently as pathology markers of cancer and other diseases, making possible their use as therapy predictors. Furthermore, the importance of the immune response in radiosensivity of solid organs led us to hypothesized that microarray gene expression profiling of peripheral blood mononuclear cells could identify patients with response to chemoradiation in rectal cancer. Thirty five 35 patients with locally advanced rectal cancer were recruited initially to perform the study. Peripheral blood samples were obtained before neaodjuvant treatment. RNA was extracted and purified to obtain cDNA and cRNA for hybridization of microarrays included in Human WG CodeLink bioarrays. Quantitative real time PCR was used to validate microarray experiment data. Results were correlated with pathological response, according to Mandard´s criteria and final UICC Stage (patients with tumor regression grade 1-2 and downstaging being defined as responders and patients with grade 3-5 and no downstaging as non-responders). Twenty seven out of 35 patients were finally included in the study. We performed a multiple t-test using Significance Analysis of Microarrays, to find those genes differing significantly in expression, between responders (n = 11) and non-responders (n = 16) to CRT. The differently expressed genes were: BC 035656.1, CIR, PRDM2, CAPG, FALZ, HLA-DPB2, NUPL2, and ZFP36. The measurement of FALZ (p = 0.029) gene expression level determined by qRT-PCR, showed statistically significant differences between the two groups. Gene expression profiling reveals novel genes in peripheral blood samples of mononuclear cells that could predict responders and non-responders to chemoradiation in patients with locally advanced

  7. Intense Androgen-Deprivation Therapy With Abiraterone Acetate Plus Leuprolide Acetate in Patients With Localized High-Risk Prostate Cancer: Results of a Randomized Phase II Neoadjuvant Study

    PubMed Central

    Taplin, Mary-Ellen; Montgomery, Bruce; Logothetis, Christopher J.; Bubley, Glenn J.; Richie, Jerome P.; Dalkin, Bruce L.; Sanda, Martin G.; Davis, John W.; Loda, Massimo; True, Lawrence D.; Troncoso, Patricia; Ye, Huihui; Lis, Rosina T.; Marck, Brett T.; Matsumoto, Alvin M.; Balk, Steven P.; Mostaghel, Elahe A.; Penning, Trevor M.; Nelson, Peter S.; Xie, Wanling; Jiang, Zhenyang; Haqq, Christopher M.; Tamae, Daniel; Tran, NamPhuong; Peng, Weimin; Kheoh, Thian; Molina, Arturo; Kantoff, Philip W.

    2014-01-01

    Purpose Cure rates for localized high-risk prostate cancers (PCa) and some intermediate-risk PCa are frequently suboptimal with local therapy. Outcomes are improved by concomitant androgen-deprivation therapy (ADT) with radiation therapy, but not by concomitant ADT with surgery. Luteinizing hormone–releasing hormone agonist (LHRHa; leuprolide acetate) does not reduce serum androgens as effectively as abiraterone acetate (AA), a prodrug of abiraterone, a CYP17 inhibitor that lowers serum testosterone (< 1 ng/dL) and improves survival in metastatic PCa. The possibility that greater androgen suppression in patients with localized high-risk PCa will result in improved clinical outcomes makes paramount the reassessment of neoadjuvant ADT with more robust androgen suppression. Patients and Methods A neoadjuvant randomized phase II trial of LHRHa with AA was conducted in patients with localized high-risk PCa (N = 58). For the first 12 weeks, patients were randomly assigned to LHRHa versus LHRHa plus AA. After a research prostate biopsy, all patients received 12 additional weeks of LHRHa plus AA followed by prostatectomy. Results The levels of intraprostatic androgens from 12-week prostate biopsies, including the primary end point (dihydrotestosterone/testosterone), were significantly lower (dehydroepiandrosterone, Δ4-androstene-3,17-dione, dihydrotestosterone, all P < .001; testosterone, P < .05) with LHRHa plus AA compared with LHRHa alone. Prostatectomy pathologic staging demonstrated a low incidence of complete responses and minimal residual disease, with residual T3- or lymph node–positive disease in the majority. Conclusion LHRHa plus AA treatment suppresses tissue androgens more effectively than LHRHa alone. Intensive intratumoral androgen suppression with LHRHa plus AA before prostatectomy for localized high-risk PCa may reduce tumor burden. PMID:25311217

  8. Is Biochemical Response More Important Than Duration of Neoadjuvant Hormone Therapy Before Radiotherapy for Clinically Localized Prostate Cancer? An Analysis of the 3- Versus 8-Month Randomized Trial

    SciTech Connect

    Alexander, Abraham; Crook, Juanita; Jones, Stuart; Malone, Shawn; Bowen, Julie; Truong, Pauline; Pai, Howard; Ludgate, Charles

    2010-01-15

    Purpose: To ascertain whether biochemical response to neoadjuvant androgen-deprivation therapy (ADT) before radiotherapy (RT), rather than duration, is the critical determinant of benefit in the multimodal treatment of localized prostate cancer, by comparing outcomes of subjects from the Canadian multicenter 3- vs 8-month trial with a pre-RT, post-hormone PSA (PRPH-PSA) <=0.1 ng/ml vs those >0.1 ng/ml. Methods and Materials: From 1995 to 2001, 378 men with localized prostate cancer were randomized to 3 or 8 months of neoadjuvant ADT before RT. On univariate analysis, survival indices were compared between those with a PRPH-PSA <=0.1 ng/ml vs >0.1 ng/ml, for all patients and subgroups, including treatment arm, risk group, and gleason Score. Multivariate analysis identified independent predictors of outcome. Results: Biochemical disease-free survival (bDFS) was significantly higher for those with a PRPH-PSA <=0.1 ng/ml compared with PRPH-PSA >0.1 ng/ml (55.3% vs 49.4%, p = 0.014). No difference in survival indices was observed between treatment arms. There was no difference in bDFS between patients in the 3- and 8-month arms with a PRPH-PSA <=0.1 ng/ml nor those with PRPH-PSA >0.1 ng/ml. bDFS was significantly higher for high-risk patients with PRPH-PSA <=0.1 ng/ml compared with PRPH-PSA >0.1 ng/ml (57.0% vs 29.4%, p = 0.017). Multivariate analysis identified PRPH-PSA (p = 0.041), Gleason score (p = 0.001), initial PSA (p = 0.025), and T-stage (p = 0.003), not ADT duration, as independent predictors of outcome. Conclusion: Biochemical response to neoadjuvant ADT before RT, not duration, appears to be the critical determinant of benefit in the setting of combined therapy. Individually tailored ADT duration based on PRPH-PSA would maximize therapeutic gain, while minimizing the duration of ADT and its related toxicities.

  9. Short- and Long-Term Quality of Life and Bowel Function in Patients With MRI-Defined, High-Risk, Locally Advanced Rectal Cancer Treated With an Intensified Neoadjuvant Strategy in the Randomized Phase 2 EXPERT-C Trial

    SciTech Connect

    Sclafani, Francesco; Peckitt, Clare; Cunningham, David; Tait, Diana; Giralt, Jordi; Glimelius, Bengt; Keränen, Susana Roselló; Bateman, Andrew; Hickish, Tamas; Tabernero, Josep; Thomas, Janet; Brown, Gina; Oates, Jacqueline; Chau, Ian

    2015-10-01

    Objective: Intensified preoperative treatments have been increasingly investigated in locally advanced rectal cancer (LARC), but limited data are available for the impact of these regimens on quality of life (QoL) and bowel function (BF). We assessed these outcome measures in EXPERT-C, a randomized phase 2 trial of neoadjuvant capecitabine combined with oxaliplatin (CAPOX), followed by chemoradiation therapy (CRT), total mesorectal excision, and adjuvant CAPOX with or without cetuximab in magnetic resonance imaging-defined, high-risk LARC. Methods and Materials: QoL was assessed using the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-CR29 questionnaires. Bowel incontinence was assessed using the modified Fecal Incontinence Severity Index questionnaire. Results: Compared to baseline, QoL scores during preoperative treatment were better for symptoms associated with the primary tumor in the rectum (blood and mucus in stool, constipation, diarrhea, stool frequency, buttock pain) but worse for global health status, role functioning, and symptoms related to the specific safety profile of each treatment modality. During follow-up, improved emotional functioning and lessened anxiety and insomnia were observed, but deterioration of body image, increased urinary incontinence, less sexual interest (men), and increased impotence and dyspareunia were observed. Cetuximab was associated with a deterioration of global health status during neoadjuvant chemotherapy but did not have any long-term detrimental effect. An improvement in bowel continence was observed after preoperative treatment and 3 years after sphincter-sparing surgery. Conclusions: Intensifying neoadjuvant treatment by administering induction systemic chemotherapy before chemoradiation therapy improves tumor-related symptoms and does not appear to have a significantly detrimental effect on QoL and BF, in both the short and the long term.

  10. Subharmonic Imaging and Pressure Estimation for Monitoring Neoadjuvant Chemotherapy

    DTIC Science & Technology

    2014-09-01

    12b. DISTRIBUTION CODE 13. ABSTRACT (Maximum 200 Words) Neoadjuvant chemotherapy is currently the standard of care for locally advanced breast cancer ...improve the monitoring of breast cancer treatment response to neoadjuvant therapies in women diagnosed with LABC by imaging tumor angiogenesis with...changed their mind prior to starting the study). 15. SUBJECT TERMS Breast Cancer , Ultrasound Imaging, Ultrasound Contrast Agent, Pressure Estimation

  11. Predictors of Postoperative Complications After Trimodality Therapy for Esophageal Cancer

    SciTech Connect

    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.

    2013-08-01

    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 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.

  12. NEOCENT: a randomised feasibility and translational study comparing neoadjuvant endocrine therapy with chemotherapy in ER-rich postmenopausal primary breast cancer.

    PubMed

    Palmieri, C; Cleator, S; Kilburn, L S; Kim, S B; Ahn, S-H; Beresford, M; Gong, G; Mansi, J; Mallon, E; Reed, S; Mousa, K; Fallowfield, L; Cheang, M; Morden, J; Page, K; Guttery, D S; Rghebi, B; Primrose, L; Shaw, J A; Thompson, A M; Bliss, J M; Coombes, R C

    2014-12-01

    Neoadjuvant endocrine therapy is an alternative to chemotherapy for women with oestrogen receptor (ER)-positive early breast cancer (BC). We aimed to assess feasibility of recruiting patients to a study comparing chemotherapy versus endocrine therapy in postmenopausal women with ER-rich primary BC, and response as well as translational endpoints were assessed. Patients requiring neoadjuvant therapy were randomised to chemotherapy: 6 × 3-weekly cycles FE₁₀₀C or endocrine therapy: letrozole 2.5 mg, daily for 18-23 weeks. Primary endpoints were recruitment feasibility and tissue collection. Secondary endpoints included clinical, radiological and pathological response rates, quality of life and translational endpoints. 63/80 patients approached were eligible, of those 44 (70, 95% CI 57-81) were randomised. 12 (54.5, 95% CI 32.2-75.6) chemotherapy patients showed radiological objective response compared with 13 (59.1, 95% CI 36.4-79.3) letrozole patients. Compared with baseline, mean Ki-67 levels fell in both groups at days 2-4 and at surgery [fold change: 0.24 (95% CI 0.12-0.51) and 0.24; (95% CI 0.15-0.37), respectively]. Plasma total cfDNA levels rose from baseline to week 8 [fold change: chemotherapy 2.10 (95% CI 1.47-3.00), letrozole 1.47(95% CI 0.98-2.20)], and were maintained at surgery in the chemotherapy group [chemotherapy 2.63; 95% CI 1.56-4.41), letrozole 0.95 (95% CI 0.71-1.26)]. An increase in plasma let-7a miRNA was seen at surgery for patients with objective radiological response to chemotherapy. Recruitment and tissue collection endpoints were met; however, a larger trial was deemed unfeasible due to slow accrual. Both regimens were equally efficacious. Dynamic changes were seen in Ki-67 and circulating biomarkers in both groups with increases in cfDNA and let-7a miRNA persisting until surgery for chemotherapy patients.

  13. [A case of small cell carcinoma in the urinary bladder responding to gemcitabine/cisplatin combination therapy as neoadjuvant chemotherapy].

    PubMed

    Shirato, Akitomi; Shimamoto, Kenji; Ozawa, Akira; Tanji, Nozomu; Yokoyama, Masayoshi

    2006-12-01

    We report a case of primary small cell carcinoma of the urinary bladder. A 79-year-old man with the chief complaints of macrohematuria and pollakisuria was admitted to our hospital. Cystoscopy and computed tomography (CT) revealed a non-papillary broad-based bladder tumor. Histological diagnosis was small cell carcinoma of the urinary bladder, and he underwent 3 courses of neoadjuvant chemotherapy including gemcitabine and cisplatin with a preoperative diagnosis of cT3bN0M0. After the chemotherapy, cystoscopy and CT showed complete remission. Total cystectomy with ileal conduit was performed following 3 courses of chemotherapy. Microscopic examination revealed that the small cell carcinoma had disappeared and the converted squamous cell carcinoma remained only in a small part of the specimens. The patient was carefully followed for 10 months after operation, with no tumor recurrence.

  14. Long-term Follow-up Results of a Multi-institutional Phase 2 Study of Concurrent Chemoradiation Therapy for Locally Advanced Cervical Cancer in East and Southeast Asia

    SciTech Connect

    Kato, Shingo; Ohno, Tatsuya; Thephamongkhol, Kullathorn; Chansilpa, Yaowalak; Cao, Jianping; Xu, Xiaoting; Devi, C. R. Beena; Swee, Tang Tieng; Calaguas, Miriam J.C.; Reyes, Rey H. de los; Cho, Chul-Koo; Dung, To Anh; Supriana, Nana; Erawati, Dyah; Mizuno, Hideyuki; Nakano, Takashi; Tsujii, Hirohiko

    2013-09-01

    Purpose: To report the long-term survival and toxicity of a multi-institutional phase 2 study of concurrent chemoradiation therapy (CCRT) for locally advanced cervical cancer in east and southeast Asia. Methods and Materials: Ten institutions from 8 Asian countries participated in the study. Between April 2003 and March 2006, 120 patients (60 with bulky stage IIB and 60 with stage IIIB) were treated with CCRT. Radiation therapy consisted of pelvic external beam radiation therapy and either high-dose-rate or low-dose-rate intracavitary brachytherapy. Five cycles of weekly cisplatin (40 mg/m{sup 2}) were administered during the course of radiation therapy. Treatment results were evaluated by the rates of local control, overall survival, and late toxicities. Results: Median follow-up was 63.7 months, and the follow-up rate at 5 years was 98%. The 5-year local control and overall survival rates for all patients were 76.8% and 55.1%, respectively. The 5-year rates of major late toxicities of the rectum and bladder were 7.9% and 0%, respectively. Conclusions: The long-term results have suggested that CCRT is safe and effective for patients with locally advanced cervical cancer in east and southeast Asia. However, further efforts are needed to improve overall survival.

  15. Short-course radiation versus long-course chemoradiation for rectal cancer.

    PubMed

    Minsky, Bruce D; Rödel, Claus; Valentini, Vincenzo

    2012-10-01

    The 2 broad approaches to preoperative therapy for rectal cancer are chemoradiation and short-course radiation. The outcomes of these 2 approaches reported in nonrandomized trials are not comparable because patients selected for treatment with short-course radiotherapy included those with cT1-3 disease, whereas patients selected for chemoradiation included those with T3 and/or N+ disease. However, more recent trials of short-course radiation have included patients with cT3 and/or N+ disease who also underwent sequential or postoperative chemotherapy, allowing a more relevant comparison with chemoradiation. This article compares the 2 preoperative approaches and addresses their emerging roles.

  16. Comparison of risk of local-regional recurrence after mastectomy or breast conservation therapy for patients treated with neoadjuvant chemotherapy and radiation stratified according to a prognostic index score

    SciTech Connect

    Huang, Eugene H.; Strom, Eric A.; Perkins, George H.; Oh, Julia L.; Chen, Allen M.; Meric-Bernstam, Funda; Hunt, Kelly K.; Sahin, Aysegul A.; Hortobagyi, Gabriel N.; Buchholz, Thomas A. . E-mail: tbuchhol@mdanderson.org

    2006-10-01

    Purpose: We previously developed a prognostic index that stratified patients treated with breast conservation therapy (BCT) after neoadjuvant chemotherapy into groups with different risks for local-regional recurrence (LRR). The purpose of this study was to compare the rates of LRR as a function of prognostic index score for patients treated with BCT or mastectomy plus radiation after neoadjuvant chemotherapy. Methods and Materials: We retrospectively analyzed 815 patients treated with neoadjuvant chemotherapy, surgery, and radiation. Patients were assigned an index score from 0 to 4 and given 1 point for the presence of each factor: clinical N2 to N3 disease, lymphovascular invasion, pathologic size >2 cm, and multifocal residual disease. Results: The 10-year LRR rates were very low and similar between the mastectomy and BCT groups for patients with an index score of 0 or 1. For patients with a score of 2, LRR trended lower for those treated with mastectomy vs. BCT (12% vs. 28%, p = 0.28). For patients with a score of 3 to 4, LRR was significantly lower for those treated with mastectomy vs. BCT (19% vs. 61%, p = 0.009). Conclusions: This analysis suggests that BCT can provide excellent local-regional treatment for the vast majority of patients after neoadjuvant chemotherapy. For the few patients with a score of 3 to 4, LRR was >60% after BCT and was <20% with mastectomy. If these findings are confirmed in larger randomized studies, the prognostic index may be useful in helping to select the type of surgical treatment for patients treated with neoadjuvant chemotherapy, surgery, and radiation.

  17. [Radiation therapy of pancreatic cancer].

    PubMed

    Huguet, F; Mornex, F; Orthuon, A

    2016-09-01

    Currently, the use of radiation therapy for patients with pancreatic cancer is subject to discussion. In adjuvant setting, the standard treatment is 6 months of chemotherapy with gemcitabine and capecitabine. Chemoradiation (CRT) may improve the survival of patients with incompletely resected tumors (R1). This should be confirmed by a prospective trial. Neoadjuvant CRT is a promising treatment especially for patients with borderline resectable tumors. For patients with locally advanced tumors, there is no a standard. An induction chemotherapy followed by CRT for non-progressive patients reduces the rate of local relapse. Whereas in the first trials of CRT large fields were used, the treated volumes have been reduced to improve tolerance. Tumor movements induced by breathing should be taken in account. Intensity modulated radiation therapy allows a reduction of doses to the organs at risk. Whereas widely used, this technique is not recommended.

  18. Four-Week Neoadjuvant Intensity-Modulated Radiation Therapy With Concurrent Capecitabine and Oxaliplatin in Locally Advanced Rectal Cancer Patients: A Validation Phase II Trial

    SciTech Connect

    Arbea, Leire; Martinez-Monge, Rafael; Diaz-Gonzalez, Juan A.; Moreno, Marta; Rodriguez, Javier; Hernandez, Jose Luis; Sola, Jesus Javier; Ramos, Luis Isaac; Subtil, Jose Carlos; Nunez, Jorge; Chopitea, Ana; Cambeiro, Mauricio; Gaztanaga, Miren; Garcia-Foncillas, Jesus; Aristu, Javier

    2012-06-01

    Purpose: To validate tolerance and pathological complete response rate (pCR) of a 4-week preoperative course of intensity-modulated radiation therapy (IMRT) with concurrent capecitabine and oxaliplatin (CAPOX) in patients with locally advanced rectal cancer. Methods and Materials: Patients with T3 to T4 and/or N+ rectal cancer received preoperative IMRT (47.5 Gy in 19 fractions) with concurrent capecitabine (825 mg/m{sup 2} b.i.d., Monday to Friday) and oxaliplatin (60 mg/m{sup 2} on Days 1, 8, and 15). Surgery was scheduled 4 to 6 weeks after the completion of chemoradiation. Primary end points were toxicity and pathological response rate. Local control (LC), disease-free survival (DFS), and overall survival (OS) were also analyzed. Results: A total of 100 patients were evaluated. Grade 1 to 2 proctitis was observed in 73 patients (73%). Grade 3 diarrhea occurred in 9% of the patients. Grade 3 proctitis in 18% of the first 50 patients led to reduction of the dose per fraction to 47.5 Gy in 20 treatments. The rate of Grade 3 proctitis decreased to 4% thereafter (odds ratio, 0.27). A total of 99 patients underwent surgery. A pCR was observed in 13% of the patients, major response (96-100% of histological response) in 48%, and pN downstaging in 78%. An R0 resection was performed in 97% of the patients. After a median follow-up of 55 months, the LC, DFS, and OS rates were 100%, 84%, and 87%, respectively. Conclusions: Preoperative CAPOX-IMRT therapy (47.5 Gy in 20 fractions) is feasible and safe, and produces major pathological responses in approximately 50% of patients.

  19. Neoadjuvant chemotherapy for bladder cancer.

    PubMed

    Black, Peter C; Brown, Gordon A; Grossman, H Barton; Dinney, Colin P

    2006-11-01

    The 30-45% failure rate after radical cystoprostatectomy mandates that we explore and optimize multimodal therapy to achieve better disease control in these patients. Cisplatin-based multi-agent combination chemotherapy has been used with success in metastatic disease and has therefore also been introduced in patients with high-risk but non-metastatic bladder cancer. There is now convincing evidence that chemotherapy given pre-operatively can improve survival in these patients. In this review we establish the need for peri-operative chemotherapy in bladder cancer patients and summarize the evidence for the efficacy of neoadjuvant chemotherapy. The advantages and disadvantages of neoadjuvant versus adjuvant chemotherapy are discussed, and the main shortcomings of both--treatment-related toxicity and the inability to prospectively identify likely responders--are presented. Finally, a risk-adapted approach to neoadjuvant chemotherapy is presented, whereby the highest risk patients are offered treatment while those unlikely to benefit are spared the treatment-related toxicity.

  20. Phase 2 Study of Temozolomide-Based Chemoradiation Therapy for High-Risk Low-Grade Gliomas: Preliminary Results of Radiation Therapy Oncology Group 0424

    SciTech Connect

    Fisher, Barbara J.; Hu, Chen; Macdonald, David R.; Lesser, Glenn J.; Coons, Stephen W.; Brachman, David G.; Ryu, Samuel; Werner-Wasik, Maria; Bahary, Jean-Paul; Liu, Junfeng; Chakravarti, Arnab; Mehta, Minesh

    2015-03-01

    Purpose: Radiation Therapy Oncology Group (RTOG) 0424 was a phase 2 study of a high-risk low-grade glioma (LGG) population who were treated with temozolomide (TMZ) and radiation therapy (RT), and outcomes were compared to those of historical controls. This study was designed to detect a 43% increase in median survival time (MST) from 40.5 to 57.9 months and a 20% improvement in 3-year overall survival (OS) rate from 54% to 65% at a 10% significance level (1-sided) and 96% power. Methods and Materials: Patients with LGGs with 3 or more risk factors for recurrence (age ≥40 years, astrocytoma histology, bihemispherical tumor, preoperative tumor diameter of ≥6 cm, or a preoperative neurological function status of >1) were treated with RT (54 Gy in 30 fractions) and concurrent and adjuvant TMZ. Results: From 2005 to 2009, 129 evaluable patients (75 males and 54 females) were accrued. Median age was 49 years; 91% had a Zubrod score of 0 or 1; and 69%, 25%, and 6% of patients had 3, 4, and 5 risk factors, respectively. Patients had median and minimum follow-up examinations of 4.1 years and 3 years, respectively. The 3-year OS rate was 73.1% (95% confidence interval: 65.3%-80.8%), which was significantly improved compared to that of prespecified historical control values (P<.001). Median survival time has not yet been reached. Three-year progression-free survival was 59.2%. Grades 3 and 4 adverse events occurred in 43% and 10% of patients, respectively. One patient died of herpes encephalitis. Conclusions: The 3-year OS rate of 73.1% for RTOG 0424 high-risk LGG patients is higher than that reported for historical controls (P<.001) and the study-hypothesized rate of 65%.

  1. The status of targeted agents in the setting of neoadjuvant radiation therapy in locally advanced rectal cancers

    PubMed Central

    Hadaki, Maher; Harrison, Mark

    2013-01-01

    or even molecular imaging. These shortcomings probably explain our current relative lack of success in the arena of combining these agents with chemoradiation. PMID:23997939

  2. The status of targeted agents in the setting of neoadjuvant radiation therapy in locally advanced rectal cancers.

    PubMed

    Glynne-Jones, Rob; Hadaki, Maher; Harrison, Mark

    2013-09-01

    even molecular imaging. These shortcomings probably explain our current relative lack of success in the arena of combining these agents with chemoradiation.

  3. 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.

  4. Early Salvage Hormonal Therapy for Biochemical Failure Improved Survival in Prostate Cancer Patients After Neoadjuvant Hormonal Therapy Plus Radiation Therapy-A Secondary Analysis of Irish Clinical Oncology Research Group 97-01

    SciTech Connect

    Mydin, Aminudin R.; Dunne, Mary T.; Finn, Marie A.; Armstrong, John G.

    2013-01-01

    Purpose: To assess the survival benefit of early vs late salvage hormonal therapy (HT), we performed a secondary analysis on patients who developed recurrence from Irish Clinical Oncology Research Group 97-01, a randomized trial comparing 4 vs 8 months neoadjuvant HT plus radiation therapy (RT) in intermediate- and high-risk prostate adenocarcinoma. Methods and Materials: A total of 102 patients from the trial who recurred were analyzed at a median follow-up of 8.5 years. The patients were divided into 3 groups based on the timing of salvage HT: 57 patients had prostate-specific antigen (PSA) {<=}10 ng/mL and absent distant metastases (group 1, early), 21 patients had PSA >10 ng/mL and absent distant metastases (group 2, late), and 24 patients had distant metastases (group 3, late). The endpoint analyzed was overall survival (OS) calculated from 2 different time points: date of enrolment in the trial (OS1) and date of initiation of salvage HT (OS2). Survival was estimated using Kaplan-Meier curves and a Cox regression model. Results: The OS1 differed significantly between groups (P<.0005): OS1 at 10 years was 78% in group 1, 42% in group 2, and 29% in group 3. The OS2 also differed significantly between groups (P<.0005): OS2 at 6 years was 70% in group 1, 47% in group 2, and 22% in group 3. Group 1 had the longest median time from end of RT to biochemical failure compared with groups 2 and 3 (3.3, 0.9, and 1.7 years, respectively; P<.0005). Group 1 also had the longest median PSA doubling time compared with groups 2 and 3 (9.9, 3.6, and 2.4 months, respectively; P<.0005). On multivariate analysis, timing of salvage HT, time from end of RT to biochemical failure, and PSA nadir on salvage HT were significant predictors of survival. Conclusion: Early salvage HT based on PSA {<=}10 ng/mL and absent distant metastases improved survival in patients with prostate cancer after failure of initial treatment with neoadjuvant HT plus RT.

  5. Imaging in evaluation of response to neoadjuvant breast cancer treatment

    PubMed Central

    Ollivier, L; Balu-Maestro, C; Leclère, J

    2005-01-01

    The role of imaging for patients treated with neoadjuvant therapy for breast cancer is not only to evaluate the therapeutic response in terms of tumour shrinkage, but also to predict the histological response to chemotherapy, which is correlated to survival. Surgery and histopathological analysis after neoadjuvant therapy allow for an objective assessment of the accuracy of imaging techniques in evaluating response. The aim of this study is to compare the value of the different conventional and functional imaging techniques for determining response to neoadjuvant chemotherapy in breast cancer treatment. PMID:16154816

  6. Hemoglobin levels do not predict biochemical outcome for localized prostate cancer treated with neoadjuvant androgen-suppression therapy and external-beam radiotherapy

    SciTech Connect

    Pai, Howard Huaihan . E-mail: hpai@bccancer.bc.ca; Ludgate, Charles; Pickles, Tom; Paltiel, Chuck M.Sc.; Agranovich, Alex; Berthelet, Eric; Duncan, Graeme; Kim-Sing, Charmaine; Kwan, Winkle; Lim, Jan; Liu, Mitchell; Tyldesley, Scott

    2006-07-15

    Purpose: To investigate whether hemoglobin (Hb) levels affect outcome in men with localized prostate adenocarcinoma (LPA) treated with neoadjuvant androgen-suppression therapy (NAST) and external-beam radiotherapy (EBRT). Methods and Materials: A total of 563 men with LPA treated with NAST (median: 5.3 months) and EBRT who had Hb levels during treatment were retrospectively reviewed. Patient, tumor, and treatment variables, including the following Hb variables, were subjected to univariate and multivariable analyses to identify factors that predict biochemical control (bNED) and overall survival (OS): pre-EBRT Hb, Hb nadir during EBRT, and change in Hb from pre-EBRT to nadir during EBRT. Results: Median PSA follow-up was 4.25 years. Forty-nine percent of men were anemic during EBRT, with a median Hb of 13.4 g/dL, and 68% experienced a decline in Hb from pre-EBRT to during EBRT of median 0.6 g/dL. Five-year Nadir + 2 bNED and OS rates were similar for anemic and nonanemic patients during EBRT. High percent-positive biopsies, PSA and Gleason score, and use of AA monotherapy predicted worse bNED. High stage and age predicted worse OS. Hb variables were not predictive of bNED or OS. Conclusions: Anemia is a common side effect of NAST and is usually mild. Hb levels, however, do not predict biochemical control or survival.

  7. Pharmacometabolomics study identifies circulating spermidine and tryptophan as potential biomarkers associated with the complete pathological response to trastuzumab-paclitaxel neoadjuvant therapy in HER-2 positive breast cancer

    PubMed Central

    Miolo, Gianmaria; Muraro, Elena; Caruso, Donatella; Crivellari, Diana; Ash, Anthony; Scalone, Simona; Lombardi, Davide; Rizzolio, Flavio; Giordano, Antonio; Corona, Giuseppe

    2016-01-01

    Defining biomarkers that predict therapeutic effects and adverse events is a crucial mandate to guide patient selection for personalized cancer treatments. In the present study, we applied a pharmacometabolomics approach to identify biomarkers potentially associated with pathological complete response to trastuzumab-paclitaxel neoadjuvant therapy in HER-2 positive breast cancer patients. Based on histological response the 34 patients enrolled in the study were subdivided into two groups: good responders (n = 15) and poor responders (n = 19). The pre-treatment serum targeted metabolomics profile of all patients were analyzed by liquid chromatography tandem mass spectrometry and the differences in the metabolomics profile between the two groups was investigated by multivariate partial least squares discrimination analysis. The most relevant metabolites that differentiate the two groups of patients were spermidine and tryptophan. The Good responders showed higher levels of spermidine and lower amounts of tryptophan compared with the poor responders (p < 0.001, q < 0.05). The serum level of these two metabolites identified patients who achieved a pathological complete response with a sensitivity of 90% [0.79–1.00] and a specificity of 0.87% [0.67–1.00]. These preliminary results support the role played by the individual patients' metabolism in determining the response to cancer treatments and may be a useful tool to select patients that are more likely to benefit from the trastuzumab-paclitaxel treatment. PMID:27223427

  8. Response to Neoadjuvant Systemic Therapy for Breast Cancer in BRCA Mutation Carriers and Noncarriers: A Single-Institution Experience

    PubMed Central

    Arun, Banu; Bayraktar, Soley; Liu, Diane D.; Gutierrez Barrera, Angelica M.; Atchley, Deann; Pusztai, Lajos; Litton, Jennifer Keating; Valero, Vicente; Meric-Bernstam, Funda; Hortobagyi, Gabriel N.; Albarracin, Constance

    2011-01-01

    Purpose To compare the pathologic complete response (pCR) rate and relapse-free survival (RFS) and overall survival (OS) after neoadjuvant systemic chemotherapy (NST) in patients with breast cancer with and without deleterious BRCA1 and BRCA2 mutations. Patients and Methods A total of 317 women who underwent BRCA genetic testing and were treated with NST for breast cancer between 1997 and 2009 were included in the study. The Kaplan-Meier product-limit method was used to estimate RFS and OS rates. Logistic regression models were fit to determine the associations between BRCA status, pCR, and survival. Results Fifty-seven (18%) and 23 (7%) patients had BRCA1 and BRCA2 mutations, respectively. Twenty-six (46%) of 57 BRCA1 carriers achieved a pCR, compared with three (13%) of 23 BRCA2 carriers and 53 (22%) of 237 BRCA noncarriers (P < .001). In the multivariate logistic model, BRCA1 status (odds ratio [OR] = 3.16; 95% CI, 1.55 to 6.42; P = .002), estrogen receptor (ER) negativity (OR = 1.96; 95% CI:1.05 to 3.65; P = .03) and concurrent trastuzumab use (OR = 4.18; 95% CI, 2.04 to 8.57; P < .001) remained as independent significant predictors for a pCR. At a median follow-up of 3.2 years, 69 patients (22%) experienced a disease recurrence or death. No significant differences were noted in survival outcomes with respect to BRCA status and type of NST received. However, among BRCA1 carriers, patients who achieved a pCR had better 5-year RFS (P = .001) and OS (P = .01) rates than patients who did not. Conclusion BRCA1 status and ER negativity are independently associated with higher pCR rates in patients with breast cancer. Overall prognosis of breast cancer in BRCA carriers is similar to sporadic breast cancers. PMID:21900106

  9. 17-Week Delay Surgery after Chemoradiation in Rectal Cancer with Complete Pathological Response

    PubMed Central

    Santos, Marisa D.; Gomes, Manuel T.; Moreno, Filipa; Rocha, Anabela; Lopes, Carlos

    2015-01-01

    Neoadjuvant chemoradiation (CRT) followed by curative surgery still remains the standard of care for locally advanced rectal cancer (LARC). The main purpose of this multimodal treatment is to achieve a complete pathological tumor response (ypCR), with better survival. The surgery delay after CRT completion seems to increase tumor response and ypCR rate. Usually, time intervals range from 8 to 12 weeks, but the maximum tumor regression may not be seen in rectal adenocarcinomas until several months after CRT. About this issue, we report a case of a 52-year-old man with LARC treated with neoadjuvant CRT who developed, one month after RT completion, an acute myocardial infarction. The need to increase the interval between CRT and surgery for 17 weeks allowed a curative surgery without morbidity and an unexpected complete tumor response in the resected specimen (given the parameters presented in pelvic magnetic resonance imaging (MRI) performed 11 weeks after radiotherapy completion). PMID:26579325

  10. Combined Chemoradiation Therapy With Twice-Weekly Gemcitabine and Cisplatin for Organ Preservation in Muscle-Invasive Bladder Cancer: Long-Term Results of a Phase 1 Trial

    SciTech Connect

    Azria, David; Riou, Olivier; Rebillard, Xavier; Thezenas, Simon; Thuret, Rodolphe; Fenoglietto, Pascal; Pouessel, Damien; Culine, Stephane

    2014-03-15

    Purpose: Concomitant treatment with radiation therapy and cisplatin (CDDP) remains the gold standard for bladder preservation in the treatment of muscle-invasive bladder cancer (MIBC). We present the long-term results of a phase 1 clinical trial to assess the association of twice-weekly gemcitabine with CDDP and radiation therapy in this setting. Methods and Materials: Patients with pT2-pT4N0M0 MIBC without hydronephrosis or diffuse carcinoma in situ were enrolled in this study. After maximal transurethral resection of the bladder tumor, patients received concomitant radiation therapy (63 Gy in 1.8 fractions) and chemotherapy (CDDP 20 mg/m²/day over 4 days every 21 days and gemcitabine twice a week). The starting dose of gemcitabine was 15 mg/m² with dose escalation to 20, 25, and 30 mg/m². The primary endpoint was the maximum tolerated dose (MTD). Secondary endpoints included toxicity and tumor control. Results: Fourteen patients were enrolled. Dose-limiting toxicity occurred in 2 patients treated with 30 mg/m² gemcitabine (grade 4 thrombocytopenia and severe impairment of World Health Organization performance status, respectively). Nine patients received the complete chemoradiation therapy protocol. The recommended dose of gemcitabine was 25 mg/m². The median follow-up time was 53 months, and the overall and disease-specific 5-year survival rates were 62% and 77%, respectively. Among the patients who received the complete treatment, bladder-intact survival was 76% at 5 years, and the median overall survival was 69.6 months. Conclusions: This regimen was well tolerated. The gemcitabine MTD was 25 mg/m². Bladder preservation and disease control were promising. A multicenter phase 2 randomized trial is ongoing.

  11. Functional genetic polymorphisms in the aromatase gene CYP19 vary the response of breast cancer patients to neoadjuvant therapy with aromatase inhibitors.

    PubMed

    Wang, Liewei; Ellsworth, Katarzyna A; Moon, Irene; Pelleymounter, Linda L; Eckloff, Bruce W; Martin, Yvette N; Fridley, Brooke L; Jenkins, Gregory D; Batzler, Anthony; Suman, Vera J; Ravi, Saranya; Dixon, J Michael; Miller, William R; Wieben, Eric D; Buzdar, Aman; Weinshilboum, Richard M; Ingle, James N

    2010-01-01

    Aromatase (CYP19) is a critical enzyme in estrogen biosynthesis and aromatase inhibitors (AI) are employed widely for endocrine therapy in postmenopausal women with breast cancer. We hypothesized that single nucleotide polymorphisms (SNPs) in the CYP19 gene may alter the effectiveness of AI therapy in the neoadjuvant setting. Genomic DNA was obtained for sequencing from 52 women pre-AI and post-AI treatment in this setting. Additionally, genomic DNA obtained from 82 samples of breast cancer and 19 samples of normal breast tissue was subjected to resequencing. No differences in CYP19 sequence were observed between tumor and germ-line DNA in the same patient. A total of 48 SNPs were identified including 4 novel SNPs when compared with previous resequencing data. For genotype-phenotype association studies, we determined the levels of aromatase activity, estrone, estradiol, and tumor size in patients pre-AI and post-AI treatment. We defined two tightly linked SNPs (rs6493497 and rs7176005 in the 5'-flanking region of CYP19 exon 1.1) that were significantly associated with a greater change in aromatase activity after AI treatment. In a follow-up study of 200 women with early-stage breast cancer who were treated with adjuvant anastrozole, these same two SNPs were also associated with higher plasma estradiol levels in patients pre-AI and post-AI treatment. Electrophoretic mobility shift and reporter gene assays confirmed likely functional effects of these two SNPs on transcription of CYP19. Our findings indicate that two common genetic polymorphisms in the aromatase gene CYP19 vary the response of breast cancer patients to aromatase inhibitors.

  12. Effect of Neoadjuvant Chemoradiotherapy on Locally Advanced Rectal Mucinous Adenocarcinoma: A Propensity Score-Matched Study

    PubMed Central

    Sun, Yan-wu; Lin, Hui-ming; Lu, Xing-rong; Huang, Ying; Xu, Zong-bin; Huang, Sheng-hui; Wang, Xiao-jie

    2017-01-01

    Aims. To compare the surgical and oncological outcomes of rectal mucinous adenocarcinomas treated with neoadjuvant chemoradiotherapy versus surgery alone. Methods. A total of 167 locally advanced rectal mucinous adenocarcinoma patients treated with neoadjuvant chemoradiotherapy and surgery alone between 2008 and 2014 were matched using propensity score; the surgical and oncological outcomes were compared. Results. Ninety-six patients were matched. Postoperative morbidity was similar between groups. Sphincter preservation rate was higher in patients receiving neoadjuvant chemoradiotherapy (79.2% versus 60.4%, P = 0.045), especially for tumors ≥ 3 cm but ≤5 cm from the anal verge (75.0% versus 44.0%, P = 0.036). With a median follow-up of 54.8 months, the 5-year overall survival rate (neoadjuvant chemoradiotherapy versus surgery alone: 79.6% versus 67.1%; P = 0.599) and disease-free survival rate (75.6% versus 64.2%; P = 0.888) were similar. The 5-year local recurrence rate was lower in patients receiving neoadjuvant chemoradiotherapy (7.7% versus 26.0%, P = 0.036), while no difference was observed in distant metastasis. A poor response to chemoradiation was associated with higher local recurrence (P = 0.037). Conclusions. Compared with surgery alone, neoadjuvant chemoradiotherapy was found to increase the sphincter preservation rate and reduce local recurrence, thus being beneficial for locally advanced rectal mucinous adenocarcinoma patients.

  13. Stereotactic Body Radiation Therapy for Pancreatic Cancer.

    PubMed

    Goodman, Karyn A

    2016-01-01

    The role of radiation therapy in the management of pancreatic cancer represents an area of some controversy. However, local disease progression remains a significant cause of morbidity and even mortality for patients with this disease. Stereotactic body radiotherapy (SBRT) is an emerging treatment option for pancreatic cancer, primarily for locally advanced (unresectable) disease as it can provide a therapeutic benefit with significant advantages for patients' quality of life over standard conventional chemoradiation. There may also be a role for SBRT as neoadjuvant therapy for patients with borderline resectable disease to allow conversion to resectability. The objective of this review is to present the data supporting SBRT in pancreatic cancer as well as the potential limitations and caveats of current studies.

  14. Local-Regional Recurrence With and Without Radiation Therapy After Neoadjuvant Chemotherapy and Mastectomy for Clinically Staged T3N0 Breast Cancer

    SciTech Connect

    Nagar, Himanshu; Mittendorf, Elizabeth A.; Strom, Eric A.; Perkins, George H.; Oh, Julia L.; Tereffe, Welela; Woodward, Wendy A.; Gonzalez-Angulo, Ana M.; Hunt, Kelly K.; Buchholz, Thomas A.; Yu, Tse-Kuan

    2011-11-01

    Purpose: The purpose of this study was to determine local-regional recurrence (LRR) risk according to whether postmastectomy radiation therapy (PMRT) was used to treat breast cancer patients with clinical T3N0 disease who received neoadjuvant chemotherapy (NAC) and mastectomy. Methodsand Materials: Clinicopathology data from 162 patients with clinical T3N0 breast cancer who received NAC and underwent mastectomy were retrospectively reviewed. A total of 119 patients received PMRT, and 43 patients did not. The median number of axillary lymph nodes (LNs) dissected was 15. Actuarial rates were calculated using the Kaplan-Meier method and compared using the log-rank test. Results: At a median follow-up of 75 months, 15 of 162 patients developed LRR. For all patients, the 5-year LRR rate was 9% (95% confidence interval [CI], 4%-14%). The 5-year LRR rate for those who received PMRT was 4% (95% CI, 1%-9%) vs. 24% (95% CI, 10%-39%) for those who did not receive PMRT (p <0.001). A significantly higher proportion of irradiated patients had pathology involved LNs and were {<=}40 years old. Among patients who had pathology involved LNs, the LRR rate was lower in those who received PMRT (p <0.001). A similar trend was observed for those who did not have pathology involved LN disease. Among nonirradiated patients, the appearance of pathologic LN disease after NAC was the only clinicopathologic factor examined that significantly correlated with the risk of LRR. Conclusions: Breast cancer patients with clinical T3N0 disease treated with NAC and mastectomy but without PMRT had a significant risk of LRR, even when there was no pathologic evidence of LN involvement present after NAC. PMRT was effective in reducing the LRR rate. We suggest PMRT should be considered for patients with clinical T3N0 disease.

  15. A Phase I study of weekly intravenous oxaliplatin in combination with oral daily capecitabine and radiation therapy in the neoadjuvant treatment of rectal adenocarcinoma

    SciTech Connect

    Fakih, Marwan G. . E-mail: marwan.fakih@roswellpark.org; Rajput, Ashwani; Yang, Gary Y.; Pendyala, Lakshmi; Toth, Karoly; Smith, Judy L.; Lawrence, David D.; Rustum, Youcef M.

    2006-08-01

    Purpose: We conducted a Phase I study to determine the maximum tolerated dose (MTD) of neoadjuvant capecitabine, oxaliplatin, and radiation therapy (RT) in Stage II to III rectal adenocarcinoma. Methods and Materials: Capecitabine was given orally twice daily Monday through Friday concurrently with RT. Oxaliplatin was given i.v. once weekly x 5 (for 5 weeks) starting the first day of RT. RT was given daily except on weekends and holidays at 1.8 Gy per fraction x 28. Escalation for capecitabine or oxaliplatin was to occur in cohorts of three patients until the maximum tolerated dose (MTD) was defined. Endorectal tumor biopsy samples were obtained before and on Day 3 of treatment to explore the effects of treatment on thymidine phosphorylase, thymidylate synthase, dihydropyrimidine dehydrogenase, DNA repair, and apoptosis. Results: Twelve patients were enrolled on this study. Two of 6 patients at dose level (DL) 1 (capecitabine 825 mg/m{sup 2} orally (p.o.) given twice daily (b.i.d.); oxaliplatin 50 mg/m{sup 2}/week) had a dose-limiting diarrhea. One of 6 patients at DL (-)1 (capecitabine 725 mg/m{sup 2} p.o., b.i.d.; oxaliplatin 50 mg/m{sup 2}/week) experienced-dose-limiting diarrhea. Three of 11 patients who underwent resection had a complete pathologic response. No remarkable variations in rectal tumor biologic endpoints were noted on Day 3 of treatment in comparison to baseline. However, a higher apotosis index was observed at baseline and on Day 3 in complete pathologic responders (no statistical analysis performed). Conclusions: Capecitabine 725 mg/m{sup 2} p.o., twice daily in combination with oxaliplatin 50 mg/m{sup 2}/week and RT 50.4 Gy in 28 fractions is the recommended dose for future studies.

  16. Apolipoprotein C-II Is a Potential Serum Biomarker as a Prognostic Factor of Locally Advanced Cervical Cancer After Chemoradiation Therapy

    SciTech Connect

    Harima, Yoko; Ikeda, Koshi; Utsunomiya, Keita; Komemushi, Atsushi; Kanno, Shohei; Shiga, Toshiko; Tanigawa, Noboru

    2013-12-01

    Purpose: To determine pretreatment serum protein levels for generally applicable measurement to predict chemoradiation treatment outcomes in patients with locally advanced squamous cell cervical carcinoma (CC). Methods and Materials: In a screening study, measurements were conducted twice. At first, 6 serum samples from CC patients (3 with no evidence of disease [NED] and 3 with cancer-caused death [CD]) and 2 from healthy controls were tested. Next, 12 serum samples from different CC patients (8 NED, 4 CD) and 4 from healthy controls were examined. Subsequently, 28 different CC patients (18 NED, 10 CD) and 9 controls were analyzed in the validation study. Protein chips were treated with the sample sera, and the serum protein pattern was detected by surface-enhanced laser desorption and ionization–time-of-flight mass spectrometry (SELDI-TOF MS). Then, single MS-based peptide mass fingerprinting (PMF) and tandem MS (MS/MS)-based peptide/protein identification methods, were used to identify protein corresponding to the detected peak. And then, turbidimetric assay was used to measure the levels of a protein that indicated the best match with this peptide peak. Results: The same peak 8918 m/z was identified in both screening studies. Neither the screening study nor the validation study had significant differences in the appearance of this peak in the controls and NED. However, the intensity of the peak in CD was significantly lower than that of controls and NED in both pilot studies (P=.02, P=.04) and validation study (P=.01, P=.001). The protein indicated the best match with this peptide peak at 8918 m/z was identified as apolipoprotein C-II (ApoC-II) using PMF and MS/MS methods. Turbidimetric assay showed that the mean serum levels of ApoC-II tended to decrease in CD group when compared with NED group (P=.078). Conclusion: ApoC-II could be used as a biomarker for detection in predicting and estimating the radiation treatment outcome of patients with CC.

  17. [{sup 18}F]FDG-PET Standard Uptake Value as a Metabolic Predictor of Bone Marrow Response to Radiation: Impact on Acute and Late Hematological Toxicity in Cervical Cancer Patients Treated With Chemoradiation Therapy

    SciTech Connect

    Elicin, Olgun; Callaway, Sharon; Prior, John O.; Bourhis, Jean; Ozsahin, Mahmut; Herrera, Fernanda G.

    2014-12-01

    Purpose: To quantify the relationship between bone marrow (BM) response to radiation and radiation dose by using {sup 18}F-labeled fluorodeoxyglucose positron emission tomography [{sup 18}F]FDG-PET standard uptake values (SUV) and to correlate these findings with hematological toxicity (HT) in cervical cancer (CC) patients treated with chemoradiation therapy (CRT). Methods and Materials: Seventeen women with a diagnosis of CC were treated with standard doses of CRT. All patients underwent pre- and post-therapy [{sup 18}F]FDG-PET/computed tomography (CT). Hemograms were obtained before and during treatment and 3 months after treatment and at last follow-up. Pelvic bone was autosegmented as total bone marrow (BM{sub TOT}). Active bone marrow (BM{sub ACT}) was contoured based on SUV greater than the mean SUV of BM{sub TOT}. The volumes (V) of each region receiving 10, 20, 30, and 40 Gy (V{sub 10}, V{sub 20}, V{sub 30}, and V{sub 40}, respectively) were calculated. Metabolic volume histograms and voxel SUV map response graphs were created. Relative changes in SUV before and after therapy were calculated by separating SUV voxels into radiation therapy dose ranges of 5 Gy. The relationships among SUV decrease, radiation dose, and HT were investigated using multiple regression models. Results: Mean relative pre-post-therapy SUV reductions in BM{sub TOT} and BM{sub ACT} were 27% and 38%, respectively. BM{sub ACT} volume was significantly reduced after treatment (from 651.5 to 231.6 cm{sup 3}, respectively; P<.0001). BM{sub ACT} V{sub 30} was significantly correlated with a reduction in BM{sub ACT} SUV (R{sup 2}, 0.14; P<.001). The reduction in BM{sub ACT} SUV significantly correlated with reduction in white blood cells (WBCs) at 3 months post-treatment (R{sup 2}, 0.27; P=.04) and at last follow-up (R{sup 2}, 0.25; P=.04). Different dosimetric parameters of BM{sub TOT} and BM{sub ACT} correlated with long-term hematological outcome. Conclusions: The volumes of BM

  18. Chemoradiation for rectal cancer: rationale, approaches, and controversies.

    PubMed

    Minsky, Bruce D

    2010-10-01

    The standard adjuvant treatment of cT3 and/or N+ rectal cancer is preoperative chemoradiation. However, there are many controversies regarding this approach. These controversies include the role of short course radiation, whether postoperative adjuvant chemotherapy is necessary for all patients, and if the type of surgery following chemoradiation should be based on the response rate. More accurate imaging techniques and/or molecular markers may help identify patients with positive pelvic nodes to reduce the chance of overtreatment with preoperative therapy. Will more effective systemic agents both improve the results of radiation, as well as modify the need for pelvic radiation? These questions and others remain active areas of clinical investigation.

  19. Short-term clinicopathological outcome of neoadjuvant chemohormonal therapy comprising complete androgen blockade, followed by treatment with docetaxel and estramustine phosphate before radical prostatectomy in Japanese patients with high-risk localized prostate cancer

    PubMed Central

    2012-01-01

    Background To assess the outcome of neoadjuvant chemohormonal therapy comprising complete androgen blockade followed by treatment with docetaxel and estramustine phosphate before radical prostatectomy in Japanese patients with a high risk of localized prostate cancer (PCa). Methods Complete androgen blockade followed by 6 cycles of docetaxel (30 mg/m2) with estramustine phosphate (560 mg) were given to 18 PCa patients before radical prostatectomy. Subsequently, the clinical and pathological outcomes were analyzed. Results No patients had severe adverse events during chemohormonal therapy, and hence they were treated with radical prostatectomy. Two patients (11.1%) achieved pathological complete response. Surgical margins were negative in all patients. At a median follow-up of 18 months, 14 patients (77.8%) were disease-free without PSA recurrence. All 4 patients with PSA recurrence had pathologic T3b or T4 disease and 3 of these 4 patients had pathologic N1 disease. Conclusion We found that neoadjuvant chemohormonal therapy with complete androgen blockade followed by treatment with docetaxel and estramustine phosphate before radical prostatectomy was safe, feasible, and associated with favorable pathological outcomes in patients with a high risk of localized PCa. PMID:22214417

  20. Neoadjuvant therapy for treatment of breast cancer: the way forward, or simply a convenient option for patients?

    PubMed

    Chatterjee, Abhishek; Erban, John K

    2017-02-01

    The complexity of managing early stage breast cancer is well known. Optimal treatment is increasingly multidisciplinary and in the modern era informed by sophisticated molecular tools to help select and guide therapy. Major phase III trials have determined that the order of systemic therapy relative to surgery does not influence important endpoints such as event free survival and overall survival (OS), but questions remain as to how best to utilize these most essential services. For example, there is still uncertainty regarding the ideal timing, intensity, and duration of proposed therapy. For treating physicians, evidence based standardization of these practices is both possible and critically important. Optimization of care will increasingly rely on well-designed studies that have addressed the choice as well as the timing of the steps involved in multidisciplinary breast cancer treatment. Understanding when factors under the oncologist's control will influence outcome, cost and convenience is essential in the era of quality and value-based medical decision making. The timing of surgery before or after chemotherapy for breast cancer is one such factor. Investigators are to be commended for addressing these questions, which may generate additional hypotheses concerning the biology of metastasis and the nature of recurrence.

  1. Neoadjuvant therapy for treatment of breast cancer: the way forward, or simply a convenient option for patients?

    PubMed Central

    Chatterjee, Abhishek

    2017-01-01

    The complexity of managing early stage breast cancer is well known. Optimal treatment is increasingly multidisciplinary and in the modern era informed by sophisticated molecular tools to help select and guide therapy. Major phase III trials have determined that the order of systemic therapy relative to surgery does not influence important endpoints such as event free survival and overall survival (OS), but questions remain as to how best to utilize these most essential services. For example, there is still uncertainty regarding the ideal timing, intensity, and duration of proposed therapy. For treating physicians, evidence based standardization of these practices is both possible and critically important. Optimization of care will increasingly rely on well-designed studies that have addressed the choice as well as the timing of the steps involved in multidisciplinary breast cancer treatment. Understanding when factors under the oncologist’s control will influence outcome, cost and convenience is essential in the era of quality and value-based medical decision making. The timing of surgery before or after chemotherapy for breast cancer is one such factor. Investigators are to be commended for addressing these questions, which may generate additional hypotheses concerning the biology of metastasis and the nature of recurrence. PMID:28210563

  2. Weekly paclitaxel and concurrent pazopanib following doxorubicin and cyclophosphamide as neoadjuvant therapy for HER-negative locally advanced breast cancer: NSABP Foundation FB-6, a phase II study.

    PubMed

    Tan, A R; Johannes, H; Rastogi, P; Jacobs, S A; Robidoux, A; Flynn, P J; Thirlwell, M P; Fehrenbacher, L; Stella, P J; Goel, R; Julian, T B; Provencher, L; Bury, M J; Bhatt, K; Geyer, C E; Swain, S M; Mamounas, E P; Wolmark, N

    2015-01-01

    This multicenter single-arm phase II study evaluated the addition of pazopanib to concurrent weekly paclitaxel following doxorubicin and cyclophosphamide as neoadjuvant therapy in human epidermal growth factor receptor (HER2)-negative locally advanced breast cancer (LABC). Patients with HER2-negative stage III breast cancer were treated with doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) for four cycles every 3 weeks followed by weekly paclitaxel 80 mg/m(2) on days 1, 8, and 15 every 28 days for four cycles concurrently with pazopanib 800 mg orally daily prior to surgery. Post-operatively, pazopanib was given daily for 6 months. The primary endpoint was pathologic complete response (pCR) in the breast and lymph nodes. Between July 2009 and March 2011, 101 patients with stage IIIA-C HER2-negative breast cancer were enrolled. The pCR rate in evaluable patients who initiated paclitaxel and pazopanib was 17 % (16/93). The pCR rate was 9 % (6/67) in hormone receptor-positive tumors and 38 % (10/26) in triple-negative tumors. Pre-operative pazopanib was completed in only 39 % of patients. The most frequent grade 3 and 4 adverse events during paclitaxel and pazopanib were neutropenia (27 %), diarrhea (5 %), ALT and AST elevations (each 5 %), and hypertension (5 %). Although the pCR rate of paclitaxel and pazopanib following AC chemotherapy given as neoadjuvant therapy in women with LABC met the pre-specified criteria for activity, there was substantial toxicity, which led to a high discontinuation rate of pazopanib. The combination does not appear to warrant further evaluation in the neoadjuvant setting for breast cancer.

  3. 18F-fluorodeoxyglucose (FDG) PET/CT after two cycles of neoadjuvant therapy may predict response in HER2-negative, but not in HER2-positive breast cancer.

    PubMed

    Cheng, Jingyi; Wang, Yujie; Mo, Miao; Bao, Xiao; Zhang, Yingjian; Liu, Guangyu; Zhang, Jun; Geng, Daoying

    2015-10-06

    The aim of this prospective study was to assess the ability of 18F-fluorodeoxyglucose ((18)FDG) positron emission tomography/computed tomography (PET/CT) scanning to predict pathological complete response (pCR) in breast cancer, and to investigate whether timing of the scan and trastuzumab treatment influence the accuracy of pCR prediction in human epidermal growth factor receptor 2 (HER2) positive breast cancer patients. We treated 81 locally advanced breast cancer patients with four cycles of neoadjuvant chemotherapy (NAC). HER2-negative breast cancer patients received NAC alone, while HER2-positive breast cancer patients received NAC plus trastuzumab. (18)FDG PET/CT scans were scheduled at baseline and after the second cycle of NAC. Axillary lymph node (ALN) dissection was performed after the last cycle of neoadjuvant therapy. Relative changes in standardized uptake values (SUV) between the two PET/CT scans (ΔSUV) in primary tumors and ALN metastases were calculated. There were 75 patients with 150 PET/CT scans in the final analysis, including 41 HER2-negative and 34 HER2-positive cases. In the HER2-negative group, the ΔSUV predicted overall and ALN pCR; the receiver operating characteristics-areas under curve (ROC-AUC) were 0.87 and 0.80 (P = 0.0014 and 0.031, respectively) and the negative predictive values were 94% and 89% respectively. However, in the HER2-positive group, ΔSUV could predict neither overall nor ALN pCR; the ROC-AUCs were only 0.56 and 0.53, with P = 0.53 and 0.84, respectively. Hence, the ΔSUV after two cycles of neoadjuvant therapy could predict pCR in HER2-negative patients treated with NAC alone, but not in HER2-positive patients treated with NAC plus trastuzumab.

  4. Predictors of Surgery Types after Neoadjuvant Therapy for Advanced Stage Breast Cancer: Analysis from Florida Population-Based Cancer Registry (1996–2009)

    PubMed Central

    Al-Azhri, Jamila; Koru-Sengul, Tulay; Miao, Feng; Saclarides, Constantine; Byrne, Margaret M.; Avisar, Eli

    2015-01-01

    PURPOSE Despite the established guidelines for breast cancer treatment, there is still variability in surgical treatment after neoadjuvant therapy (NT) for women with large breast tumors. Our objective was to identify predictors of the type of surgical treatment: mastectomy versus breast-conserving surgery (BCS) in women with T3/T4 breast cancer who received NT. METHODS Population-based Florida Cancer Data System Registry, Florida’s Agency for Health Care Administration, and US census from 1996 to 2009 were linked for women diagnosed with T3/T4 breast cancer and received NT followed by either BCS or mastectomy. Analysis of multiple variables, such as sociodemographic characteristics (race, ethnicity, socioeconomic status, age, marital status, and urban/rural residency), tumor’s characteristics (estrogen/progesterone receptor status, histology, grade, SEER stage, and regional nodes positivity), treatment facilities (hospital volume and teaching status), patients’ comorbidities, and type of NT, was performed. RESULTS Of 1,056 patients treated with NT for T3/T4 breast cancer, 107 (10%) had BCS and 949 (90%) had mastectomy. After adjusting with extensive covariables, Hispanic patients (adjusted odds ratio (aOR) = [3.50], 95% confidence interval (CI): 1.38–8.84, P = 0.008) were more likely to have mastectomy than BCS. Compared to localized SEER stage, regional stage with direct extension (aOR = [3.24], 95% CI: 1.60–6.54, P = 0.001), regional stage with direct extension and nodes (aOR = [4.35], 95% CI: 1.72–11.03, P = 0.002), and distant stage (aOR = [4.44], 95% CI: 1.81–10.88, P = 0.001) were significantly more likely to have mastectomy than BCS. Compared to patients who received both chemotherapy and hormonal therapy, patients who received hormonal NT only (aOR = [0.29], 95% CI: 0.12–0.68, P = 0.004) were less likely to receive mastectomy. CONCLUSION Our study suggests that Hispanic ethnicity, advanced SEER stage, and type of NT are significant

  5. Regional Lymph Node Uptake of [18F]Fluorodeoxyglucose After Definitive Chemoradiation Therapy Predicts Local-Regional Failure of Locally Advanced Non-Small Cell Lung Cancer: Results of ACRIN 6668/RTOG 0235

    PubMed Central

    Markovina, Stephanie; Duan, Fenghai; Snyder, Bradley S.; Siegel, Barry A.; Machtay, Mitchell; Bradley, Jeffrey

    2015-01-01

    Purpose/Objective(s) ACRIN 6668/RTOG 0235 demonstrated that standardized uptake value (SUV) on post-treatment [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) correlates with survival in locally advanced non-small cell lung cancer (NSCLC). This secondary analysis determines if SUV of regional lymph nodes (RLNs) on post-treatment FDG-PET correlates 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 pre-treatment FDG-PET, and post-treatment FDG-PET data. ACRIN Core Laboratory SUV measurements were used. Event time was calculated 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 pre-treatment FDG-PET, and had SUV data from post-treatment FDG-PET. Maximum SUV was greater for primary tumor than for RLNs before treatment (p<0.001), but not different post-treatment (p=0.320). Post-treatment SUV of RLNs was not associated with overall survival. However, elevated post-treatment SUV of RLNs, both the absolute value and the percent residual activity compared to the pre-treatment SUV, were associated with inferior local-regional control (p<0.001). 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 radiotherapy boost should consider inclusion of both primary tumor and FDG-avid RLNs in the boost volume to maximize local-regional control. PMID:26461002

  6. Safety and Palliative Efficacy of Single-Dose 8-Gy Reirradiation for Painful Local Failure in Patients With Stage IV Non-Small Cell Lung Cancer Previously Treated With Radical Chemoradiation Therapy

    SciTech Connect

    Topkan, Erkan; Yildirim, Berna Akkus; Guler, Ozan Cem; Parlak, Cem; Pehlivan, Berrin; Selek, Ugur

    2015-03-15

    Purpose: To investigate the safety and efficacy of single-dose 8-Gy palliative chest reirradiation (CRI) in metastatic non-small cell lung cancer (M-NSCLC) patients with painful thoracic failures (TF) within the previous radiation portal. Patients and Methods: We retrospectively analyzed the clinical data of 78 M-NSCLC patients who received single-dose 8-Gy CRI for painful TF after concurrent chemoradiation therapy to a total radiation dose of 52 to 66 Gy between 2007 and 2012. Primary endpoints included significant pain relief (SPR) defined as a ≥2 point decrement in the Visual Analogue Scale for Pain inventory (VAS-P), time to pain relief, and duration of pain control. Secondary objectives were survival and prognostic factors. Results: Treatment was well tolerated, with only 5.1% grade 3 pneumonitis and 1.3% grade 2 esophagitis. Pre-CRI median and post-CRI minimum VAS-P were 7 and 3 (P<.001), respectively. SPR was noted in 67 (85.9%) patients, and only 3 (3.9%) scored progressive pain. Median time to lowest VAS-P and duration of pain control were 27 days and 6.1 months, respectively. Median overall survival (OS) was 7.7 months, and the 1-year OS rate was 26.5%. On multivariate analyses, lower Eastern Cooperative Oncology group score (1-2; P<.001), absence of anemia (P=.001), and fewer metastatic sites (1-2; P<.001) were found to be associated with longer OS. Conclusions: Single-dose 8-Gy CRI provides safe, effective, and durable pain palliation for TF in radically irradiated M-NSCLC patients. Because of its convenience, lower cost, and higher comfort, the present protocol can be considered an appropriate option for patients with limited life spans.

  7. Correlation Among Six Biologic Factors (p53, p21{sup WAF1}, MIB-1, EGFR, HER2, and Bcl-2) and Clinical Outcomes After Curative Chemoradiation Therapy in Squamous Cell Cervical Cancer

    SciTech Connect

    Yamashita, Hideomi; Murakami, Naoya; Asari, Takao; Okuma, Kae; Ohtomo, Kuni; Nakagawa, Keiichi

    2009-07-15

    Purpose: The expressions of six cell-cycle-associated proteins were analyzed in cervical squamous cell carcinomas in correlation in a search for prognostic correlations in tumors treated with concurrent chemoradiation therapy (cCRT). Methods and Materials: The expressions of p53, p21/waf1/cip1, molecular immunology borstel-1 (MIB-1), epidermal growth factor receptor (EGFR), human epidermal growth factor receptor type 2 (HER2), and Bcl-2 were studied using an immunohistochemical method in 57 cases of cervical squamous cell carcinoma treated with cCRT. Patients received cCRT between 1998 and 2005. The mean patient age was 61 years (range, 27-82 years). The number of patients with Stage II, III, and IVA disease was 18, 29, and 10, respectively. Results: The number of patients with tumors positive for p53, p21/waf1/cip1, MIB-1, EGFR, HER2, and Bcl-2 was 26, 24, 49, 26, 13, and 11, respectively; no significant correlation was noted. The 5-year overall survival rates of HER2-positive and -negative patients was 76% vs. 44%, which was of borderline significance (p = 0.0675). No significant correlation was noted between overall survival and expressions of p53, p21/waf1/cip1, MIB-1, EGFR, and Bcl-2. No correlation was observed between local control and expression of any of the proteins. Conclusion: Expression of HER2 protein had a weak impact of borderline significance on overall survival in squamous cell carcinoma of the uterine cervix treated with cCRT. However, no clinical associations could be established for p53, p21/waf1/cip1, MIB-1, EGFR, and Bcl-2 protein expressions.

  8. Neoadjuvant Systemic Therapy in Breast Cancer: Association of Contrast-enhanced MR Imaging Findings, Diffusion-weighted Imaging Findings, and Tumor Subtype with Tumor Response.

    PubMed

    Santamaría, Gorane; Bargalló, Xavier; Fernández, Pedro Luis; Farrús, Blanca; Caparrós, Xavier; Velasco, Martin

    2016-11-22

    Purpose To investigate the performance of tumor subtype and various magnetic resonance (MR) imaging parameters in the assessment of tumor response to neoadjuvant systemic therapy (NST) in patients with breast cancer and to outline a model of pathologic response, considering pathologic complete response (pCR) as the complete absence of any residual invasive cancer or ductal carcinoma in situ (DCIS). Materials and Methods This was an institutional review board-approved retrospective study, with waiver of the need to obtain informed consent. From November 2009 to December 2014, 111 patients with histopathologically confirmed invasive breast cancer who were undergoing NST were included (mean age, 54 years; range, 27-84 years). Breast MR imaging was performed before and after treatment. Presence of late enhancement was assessed. Apparent diffusion coefficients (ADCs) were obtained by using two different methods. ADC ratio (mean posttreatment ADC/mean pretreatment ADC) was calculated. pCR was defined as absence of any residual invasive cancer or DCIS. Multivariate regression analysis and receiver operating characteristic analysis were performed. Results According to their immunohistochemical (IHC) profile, tumors were classified as human epidermal growth factor receptor 2 (HER2) positive (n = 51), estrogen receptor (ER) positive/HER2 negative (n = 40), and triple negative (n = 20). pCR was achieved in 19% (21 of 111) of cases; 86% of them were triple-negative or HER2-positive subtypes. Absence of late enhancement at posttreatment MR imaging was significantly associated with pCR (area under the curve [AUC], 0.85). Mean ADC ratio significantly increased when pCR was achieved (P < .001). A κ value of 0.479 was found for late enhancement (P < .001), and the intraclass correlation coefficient for ADCs was 0.788 (P < .001). Good correlation of ADCs obtained with the single-value method and those obtained with the mean-value methods was observed. The model combining the IHC

  9. Neoadjuvant chemotherapy for locally advanced gastric cancer: With or without radiation

    PubMed Central

    Wu, Ai-Wen; Ji, Jia-Fu

    2012-01-01

    The role of perioperative chemotherapy for gastric cancer has been established for gastric cancers in their advanced stage. In most parts of the world, even in Japan and Korea, local recurrence of gastric cancer following curative resection remains a problem. Should radiation be added to chemotherapy to achieve better local and regional control? What is the current evidence? What are the concerns regarding neoadjuvant chemoradiation in terms of safety, efficacy and survival benefit? After a serious review of the literature, the authors conclude that it is still too early to get a definitive answer but radiation seems promising. It may bring a higher pathological response rate. Rationally, more high level clinical trials are needed to confirm the role of radiotherapy in the neoadjuvant setting or to ascertain subsets of patients who may benefit from it. It is of note that surgeons should pay attention to possible complicated circumstances following radiotherapy, maintain proper nutrition status and minimize the occurrence of postoperative complications. As few data are available in Japan and Korea, interpretation and implementation of neoadjuvant radiation or chemoradiation should be done with caution. PMID:22408715

  10. 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

  11. Neoadjuvant treatment for resectable pancreatic adenocarcinoma

    PubMed Central

    Wong, John; Solomon, Naveenraj L; Hsueh, Chung-Tsen

    2016-01-01

    Pancreatic adenocarcinoma is the fourth leading cause of cancer mortality in the United States in both men and women, with a 5-year survival rate of less than 5%. Surgical resection remains the only curative treatment, but most patients develop systemic recurrence within 2 years of surgery. Adjuvant treatment with chemotherapy or chemoradiotherapy has been shown to improve overall survival, but the delivery of treatment remains problematic with up to 50% of patients not receiving postoperative treatment. Neoadjuvant therapy can provide benefits of eradication of micrometastasis and improved delivery of intended treatment. We have reviewed the findings from completed neoadjuvant clinical trials, and discussed the ongoing studies. Combinational cytotoxic chemotherapy such as fluorouracil, leucovorin, irinotecan, and oxaliplatin and gemcitabine plus nanoparticle albumin-bound (nab)-paclitaxel, active in the metastatic setting, are being studied in the neoadjuvant setting. In addition, novel targeted agents such as inhibitor of immune checkpoint are incorporated with cytotoxic chemotherapy in early-phase clinical trial. Furthermore we have explored the utility of biomarkers which can personalize treatment and select patients for target-driven therapy to improve treatment outcome. The treatment of resectable pancreatic adenocarcinoma requires multidisciplinary approach and novel strategies including innovative trials to make progress. PMID:26862486

  12. [Efficacy of neoadjuvant chemotherapy for resectable pancreatic carcinoma].

    PubMed

    Motoi, Fuyuhiko; Kawaguchi, Kei; Aoki, Takeshi; Kudo, Katsumasa; Yabuuchi, Shinichi; Fukase, Koji; Mizuma, Masamichi; Sakata, Naoaki; Otsutomo, Shigeru; Morikawa, Takanori; Hayashi, Hiroki; Nakagawa, Kei; Okada, Takaho; Yoshida, Hiroshi; Naitoh, Takeshi; Katayose, Yu; Egawa, Shinichi; Unno, Michiaki

    2013-11-01

    Surgery followed by adjuvant chemotherapy is standard care for resectable pancreatic carcinoma. The maximum estimated 2-year survival rate associated with this strategy is nearly 50%. The use of neoadjuvant therapy for pancreatic cancer remains controversial, and its efficacy has not been elucidated. To evaluate the efficacy of neoadjuvant chemotherapy for planned pancreatic cancer resection, the oncological outcomes of neoadjuvant gemcitabine plus S-1 combination therapy( GS therapy) and a surgery-first approach were retrospectively compared. Patients with planned pancreatic cancer resection and without major artery abutments were enrolled in this study. There were 39 cases of neoadjuvant GS therapy (N group) and 93 cases of the surgery-first approach( S group). Survival and surrogate markers, including the R0 rate, the "true R0 rate"( R0 with tumor marker normalization after resection), and N0 rate, were compared. The groups did not differ significantly in terms of age, gender, or tumor location. The resection rates of the N and S groups were similar (92% and 86%, respectively). The median survival of the N group (39.4 months) was significantly longer than that of the S group (20.8 months) in intention-to-treat analysis (p=0.0009). The R0, true R0, and N0 rates of the N group (85%, 69%, and 44%, respectively) were higher than those of the S group( 72%, 48%, and 24%, respectively). In conclusion, this retrospective analysis showed that neoadjuvant GS therapy might be more effective than the standard surgery-first strategy in terms of oncological outcomes for resectable pancreatic cancer. A prospective randomized study, Prep-02/JSAP-05, which compares neoadjuvant therapy to the surgery-first approach, is ongoing (UMIN-No. 000009634).

  13. Tumor Volume Changes on 1.5 Tesla Endorectal MRI During Neoadjuvant Androgen Suppression Therapy for Higher-Risk Prostate Cancer and Recurrence in Men Treated Using Radiation Therapy Results of the Phase II CALGB 9682 Study

    SciTech Connect

    D'Amico, Anthony V. Halabi, Susan; Tempany, Clare; Titelbaum, David; Philips, George K.; Loffredo, Marian; McMahon, Elizabeth; Sanford, Ben; Vogelzang, Nicholas J.; Small, Eric J.

    2008-05-01

    Purpose: We prospectively determined whether the change in tumor volume (TV) during 2 months of neoadjuvant androgen suppression therapy (nAST) measured using conventional 1.5 Tesla endorectal magnetic resonance imaging (eMRI) was associated with the risk of recurrence after radiation (RT) and 6 months of AST. Patients and Methods: Between 1997 and 2001, 180 men with clinical stage T1c-T3cN0M0 adenocarcinoma of the prostate were registered. Fifteen were found to be ineligible and the institutional MR radiologist could not assess the TV in 32, leaving 133 for analysis. Multivariable Cox regression analysis was used to assess whether a significant association existed between eMRI-defined TV progression during nAST and time to recurrence adjusting for prostate-specific antigen (PSA) level, Gleason score (8 to 10 or 7 vs. 6 or less) and stage (T3 vs. T1-2). Results: After a median follow up of 6.7 years and adjusting for known prognostic factors, there was a significant increase in the risk of PSA failure (HR, 2.3 [95% CI, 1.1-4.5; p = 0.025) in men with eMRI-defined TV progression during nAST. Specifically, adjusted estimates of PSA failure were significantly higher (p = 0.032) in men with, compared with men without, eMRI-defined TV progression reaching 38% vs. 19%, respectively, by 5 years. Conclusion: Eradicating intraprostatic hormone refractory prostate cancer (HRPC) by maximizing local control and randomized trials assessing whether survival is improved when agents active against HRPC are combined with maximal local therapy are needed in men who progress based on eMRI during nAST.

  14. Efficacy Endpoints of Radiation Therapy Group Protocol 0247: A Randomized, Phase 2 Study of Neoadjuvant Radiation Therapy Plus Concurrent Capecitabine and Irinotecan or Capecitabine and Oxaliplatin for Patients With Locally Advanced Rectal Cancer

    SciTech Connect

    Wong, Stuart J.; Moughan, Jennifer; Meropol, Neal J.; Anne, Pramila Rani; Kachnic, Lisa A.; Rashid, Asif; Watson, James C.; Mitchell, Edith P.; Pollock, Jondavid; Lee, R. Jeffrey; Haddock, Michael; Erickson, Beth A.; Willett, Christopher G.

    2015-01-01

    Purpose: To report secondary efficacy endpoints of Radiation Therapy Oncology Group protocol 0247, primary endpoint analysis of which demonstrated that preoperative radiation therapy (RT) with capecitabine plus oxaliplatin achieved a pathologic complete remission prespecified threshold (21%) to merit further study, whereas RT with capecitabine plus irinotecan did not (10%). Methods and Materials: A randomized, phase 2 trial evaluated preoperative RT (50.4 Gy in 1.8-Gy fractions) with 2 concurrent chemotherapy regimens: (1) capecitabine (1200 mg/m{sup 2}/d Monday-Friday) plus irinotecan (50 mg/m{sup 2}/wk × 4); and (2) capecitabine (1650 mg/m{sup 2}/d Monday-Friday) plus oxaliplatin (50 mg/m{sup 2}/wk × 5) for clinical T3 or T4 rectal cancer. Surgery was performed 4 to 8 weeks after chemoradiation, then 4 to 6 weeks later, adjuvant chemotherapy (oxaliplatin 85 mg/m{sup 2}; leucovorin 400 mg/m{sup 2}; 5-fluorouracil 400 mg/m{sup 2}; 5-fluorouracil 2400 mg/m{sup 2}) every 2 weeks × 9. Disease-free survival (DFS) and overall survival (OS) were estimated univariately by the Kaplan-Meier method. Local–regional failure (LRF), distant failure (DF), and second primary failure (SP) were estimated by the cumulative incidence method. No statistical comparisons were made between arms because each was evaluated individually. Results: A total of 104 patients (median age, 57 years) were treated; characteristics were similar for both arms. Median follow-up for RT with capecitabine/irinotecan arm was 3.77 years and for RT with capecitabine/oxaliplatin arm was 3.97 years. Four-year DFS, OS, LRF, DF, and SP estimates for capecitabine/irinotecan arm were 68%, 85%, 16%, 24%, and 2%, respectively. The 4-year DFS, OS, LRF, DF, and SP failure estimates for capecitabine/oxaliplatin arm were 62%, 75%, 18%, 30%, and 6%, respectively. Conclusions: Efficacy results for both arms are similar to other reported studies but suggest that pathologic complete remission is an

  15. Neuropilin-1 expression identifies a subset of regulatory T cells in human lymph nodes that is modulated by preoperative chemoradiation therapy in cervical cancer.

    PubMed

    Battaglia, Alessandra; Buzzonetti, Alexia; Monego, Giovanni; Peri, Laura; Ferrandina, Gabriella; Fanfani, Francesco; Scambia, Giovanni; Fattorossi, Andrea

    2008-01-01

    We examined the phenotype and function of CD4+ T cells expressing the semaphorin III receptor neuropilin-1 (Nrp1) in human lymph nodes and peripheral blood. In lymph nodes, Nrp1 identified a small regulatory CD4+ CD25(high) T-cell subpopulation (Nrp1+ Treg) that expressed higher levels of Forkhead box P3 (Foxp3) message and protein than Nrp1- Treg, and various molecular markers of activated Treg, i.e. CD45RO, human leucocyte antigen (HLA)-DR and glucocorticoid-induced tumour necrosis factor receptor (GITR). Similarly to conventional Treg, Nrp1+ Treg proliferated poorly in vitro, and exerted contact-dependent in vitro suppression of T-cell proliferation and cytokine secretion. However, Nrp1+ Treg were more efficient than Nrp1- Treg at inducing suppression. Nrp1 was also expressed on a small subpopulation of CD25(int) and CD25- CD4+ T cells that expressed more Foxp3, CD45RO, HLA-DR and GITR than their Nrp1- counterparts. In contrast, in peripheral blood Nrp1 identified a minor CD4+ T-cell subset that did not display the phenotypic features of Treg lacking Foxp3 expression and marginally expressing CD25. Hence, the function of Nrp1+ CD4+ T cells seemingly depends on their anatomical location. In a previous report, we proposed that Treg may curb the anti-tumour T-cell response in cervical cancer. We show here that Treg and Nrp1+ Treg levels dropped in the tumour-draining lymph nodes of patients with cervical cancer following preoperative chemoradiotherapy in a direct relationship with the reduction of tumour mass, suggesting that suppressor cell elimination facilitated the generation of T cells mediating the destruction of the neoplastic cells left behind after cytotoxic therapy.

  16. Chemoradiation With Concomitant Boosts Followed by Radical Surgery in Locally Advanced Cervical Cancer: Long-term Results of the ROMA-2 Prospective Phase 2 Study

    SciTech Connect

    Ferrandina, Gabriella; Gambacorta, Antonietta; Gallotta, Valerio; Smaniotto, Daniela; Fagotti, Anna; Tagliaferri, Luca; Foti, Elvira; Fanfani, Francesco; Autorino, Rosa; Scambia, Giovanni; Valentini, Vincenzo

    2014-11-15

    Purpose: This prospective, phase 2 study aimed at assessing the efficacy of accelerated fractionation radiation therapy by concomitant boosts (CBs) associated with chemoradiation therapy (CRT) of the whole pelvis, in improving the rate of pathological complete response (pCR) to treatment in patients with International Federation of Gynaecology and Obstetrics (FIGO) stage IB2-IVA locally advanced cervical cancer. Methods and Materials: Neoadjuvant CRT included conformal irradiation of the whole pelvis with a total dose of 39.6 Gy (1.8 cGy/fraction, 22 fractions), plus additional irradiation of primary tumor and parametria with 10.8 Gy administered with CBs (0.9 cGy/fraction, 12 fractions, every other day). Concomitant chemotherapy included cisplatin (20 mg/m{sup 2}, days 1-4 and 26-30 of treatment), and capecitabine (1300 mg/m{sup 2}/daily, orally) during the first 2 and the last 2 weeks of treatment. Radical hysterectomy plus pelvic with or without aortic lymphadenectomy was performed within 6 to 8 weeks from CRT. Toxicity was recorded according to Radiation Therapy Oncology Group toxicity criteria and Chassagne grading system. Based on the Simon design, 103 cases were required, and the regimen would be considered active if >45 pCR were registered (α error = 0.05; β error = 0.1). Results: pCR was documented in 51 cases (50.5%), and the regimen was considered active, according to the planned statistical assumptions. At median follow-up of 36 months (range: 7-85 months), the 3-year local failure rate was 7%, whereas the 3-year disease-free and overall survival rates were 73.0% and 86.1%, respectively. Grade 3 leukopenia and neutropenia were reported in only 1 and 2 cases, respectively. Gastrointestinal toxicity was always grade 1 or 2. Conclusions: Addition of CBs in the accelerated fractionation modality to the whole pelvis chemoradiation followed by radical surgery results in a high rate of pathologically assessed complete response to CRT and a very

  17. Intravoxel incoherent motion diffusion‐weighted MRI during chemoradiation therapy to characterize and monitor treatment response in human papillomavirus head and neck squamous cell carcinoma

    PubMed Central

    Paudyal, Ramesh; Oh, Jung Hun; Riaz, Nadeem; Venigalla, Praveen; Li, Jingao; Hatzoglou, Vaios; Leeman, Jonathan; Nunez, David Aramburu; Lu, Yonggang; Deasy, Joseph O.; Lee, Nancy

    2016-01-01

    Purpose Characterize and monitor treatment response in human papillomavirus (HPV) head and neck squamous cell carcinoma (HNSCC) using intra‐treatment (intra‐TX) imaging metrics derived from intravoxel incoherent motion (IVIM) diffusion‐weighted magnetic resonance imaging (DW‐MRI). Materials and Methods Thirty‐four (30 HPV positive [+] and 4 HPV negative [‐]) HNSCC patients underwent a total of 136 MRI including multi‐b value DW‐MRI (pretreatment [pre‐TX] and intra‐TX weeks 1, 2, and 3) at 3.0 Tesla. All patients were treated with chemo‐radiation therapy. Monoexponential (yielding apparent diffusion coefficient [ADC]) and bi‐exponential (yielding perfusion fraction [f], diffusion [D], and pseudo‐diffusion [D*] coefficients) fits were performed on a region of interest and voxel‐by‐voxel basis, on metastatic neck nodes. Response was assessed using RECISTv1.1. The relative percentage change in D, f, and D* between the pre‐ and intra‐TX weeks were used for hierarchical clustering. A Wilcoxon rank‐sum test was performed to assess the difference in metrics within and between the complete response (CR) and non‐CR groups. Results The delta (Δ) change in volume (V)1wk‐0wk for the CR group differed significantly (P = 0.016) from the non‐CR group, while not for V2wk‐0wk and V3wk‐0wk (P > 0.05). The mean increase in ΔD3wk‐0wk for the CR group was significantly higher (P = 0.017) than the non‐CR group. ADC and D showed an increasing trend at each intra‐TX week when compared with pre‐TX in CR group (P < 0.003). Hierarchical clustering demonstrated the existence of clusters in HPV + patients. Conclusion After appropriate validation in a larger population, these IVIM imaging metrics may be useful for individualized treatment in HNSCC patients. Level of Evidence: 2 J. Magn. Reson. Imaging 2017;45:1013–1023 PMID:27862553

  18. The Association Between Chemoradiation-related Lymphopenia and Clinical Outcomes in Patients With Locally Advanced Pancreatic Adenocarcinoma

    PubMed Central

    Wild, Aaron T.; Ye, Xiaobu; Ellsworth, Susannah G.; Smith, Jessica A.; Narang, Amol K.; Garg, Tanu; Campian, Jian; Laheru, Daniel A.; Zheng, Lei; Wolfgang, Christopher L.; Tran, Phuoc T.; Grossman, Stuart A.; Herman, Joseph M.

    2014-01-01

    Objectives Lymphopenia is a common consequence of chemoradiation therapy yet is seldom addressed clinically. This study was conducted to determine if patients with locally advanced pancreatic cancer (LAPC) treated with definitive chemoradiation develop significant lymphopenia and if this affects clinical outcomes. Methods A retrospective analysis of patients with LAPC treated with chemoradiation at a single institution from 1997 to 2011 was performed. Total lymphocyte counts (TLCs) were recorded at baseline and then monthly during and after chemoradiation. The correlation between treatment-induced lymphopenia, established prognostic factors, and overall survival was analyzed using univariate Cox regression analysis. Important factors identified by univariate analysis were selected as covariates to construct a multivariate proportional hazards model for survival. Results A total of 101 patients met eligibility criteria. TLCs were normal in 86% before chemoradiation. The mean reduction in TLC per patient was 50.6% (SD, 40.6%) 2 months after starting chemoradiation (P< 0.00001), and 46% had TLC< 500 cells/mm3. Patients with TLC < 500 cells/mm3 2 months after starting chemoradiation had inferior median survival (8.7 vs. 13.3mo, P= 0.03) and PFS (4.9 vs. 9.0mo, P = 0.15). Multivariate analysis revealed TLC< 500 cells/mm3 to be an independent predictor of inferior survival (HR= 2.879, P= 0.001) along with baseline serum albumin (HR= 3.584, P = 0.0002), BUN (HR = 1.060, P= 0.02), platelet count (HR= 1.004, P = 0.005), and radiation planning target volume (HR= 1.003, P= 0.0006). Conclusions Severe treatment-related lymphopenia occurs frequently after chemoradiation for LAPC and is an independent predictor of inferior survival. PMID:23648440

  19. Phase II study of bevacizumab and preoperative chemoradiation for esophageal adenocarcinoma

    PubMed Central

    Bains, Manjit S.; Park, Do Joong; Janjigian, Yelena Y.; Rusch, Valerie W.; Rizk, Nabil P.; Yoon, Sam S.; Millang, Brittanie; Capanu, Marinela; Goodman, Karyn A.; Ilson, David H.

    2016-01-01

    Background A standard-of-care for locally advanced esophageal and gastroesophageal junction (GEJ) adenocarcinoma is pre-operative chemoradiation. Elevated levels of vascular endothelial growth factor (VEGF) have been associated with worse outcomes following chemoradiation and anti-VEGF therapies can potentiate radiation efficacy. Methods In this single-arm phase II study, we added bevacizumab to induction chemotherapy and concurrent chemoradiation with cisplatin/irinotecan for locally advanced esophageal and GEJ adenocarcinomas. Results Thirty-three patients were enrolled, with all evaluable. All tumors involved the GEJ and 67% were node-positive by endoscopic ultrasound (EUS) and imaging. Twenty-eight patients completed chemoradiation and 26 patients underwent surgery (25 R0 resections). Toxicities were not clearly increased. The pathologic complete response (pCR) rate was 15%. Median progression-free survival (PFS) and overall survival (OS) were 15.1 and 30.5 months respectively. Higher baseline VEGF-A levels were associated with a trend toward improved OS (not reached vs. 21.0 months, P=0.11). Response on positron emission tomography (PET) scan after induction chemotherapy was predictive of PFS and showed trends toward improved OS and pCR rate. Conclusions The addition of bevacizumab to chemoradiation was not associated with clear worsening of toxicities but also led to no improvement in outcomes, when compared to a prior phase II study of 55 patients. Higher baseline VEGF-A levels correlated with a trend toward improved survival and might be used to stratify or select patients for future studies incorporating this or similar agents. PET scan to assess response following induction chemotherapy and change chemotherapy in non-responders during chemoradiation is the subject of a fully-accrued national trial (NCT01333033). PMID:28078107

  20. Changes in serum levels of miR-21, miR-210, and miR-373 in HER2-positive breast cancer patients undergoing neoadjuvant therapy: a translational research project within the Geparquinto trial.

    PubMed

    Müller, Volkmar; Gade, Stephan; Steinbach, Bettina; Loibl, Sibylle; von Minckwitz, Gunter; Untch, Michael; Schwedler, Kathrin; Lübbe, Kristina; Schem, Christian; Fasching, Peter A; Mau, Christine; Pantel, Klaus; Schwarzenbach, Heidi

    2014-08-01

    Trastuzumab and lapatinib are established treatments for patients with HER2 (human epidermal growth factor receptor 2)-positive breast cancer with different mechanisms of action. The focus of this study is to investigate, whether altered expression levels of potentially relevant microRNAs (miRs) in serum are associated with response to trastuzumab or lapatinib. Circulating miR-21, miR-210, and miR-373 were quantified with TaqMan MicroRNA assays in serum of 127 HER2-postive breast cancer patients before and after neoadjuvant therapy and in 19 healthy controls. Patients received chemotherapy combined with either trastuzumab or lapatinib within the prospectively randomized Geparquinto trial. The association between miR levels and pathological response (pCR) to therapy and type of therapy was examined. Serum levels of miR-21 (p = 5.04e-08, p = 1.43e-10), miR-210 (p = 0.00151, p = 1.6e-05), and miR-373 (p = 7.87e-06, p = 1.75e-07) were significantly higher in patients before and after chemotherapy than in healthy women. Concentrations of miR-21 (p = 5.73e-08), miR-210 (p = 0.000724), and miR-373 (p = 0.00209) increased further after chemotherapy. A significant association of higher serum levels of miR-373 with advanced clinical tumor stage could be detected (p < 0.002). An association of miR-21 levels before (p = 0.0091) and after (p = 0.037) chemotherapy with overall survival of the patients could be detected, independent of type of anti-HER2 therapy. No association of circulating miRs with pCR was found. Our findings demonstrate a specific influence of neoadjuvant therapy on the serum levels of miR-21, miR-210, and miR-373 in breast cancer patients together with a prognostic value of miR-21.

  1. Safety and efficacy of quadrapeutics versus chemoradiation in head and neck carcinoma xenograft model

    PubMed Central

    Lukianova-Hleb, Ekaterina Y; Kim, Yoo-Shin; Aryasomayajula, Bhawani; Boulikas, Teni; Phan, Jack; Hung, Mien-Chie; Torchilin, Vladimir P; O’Neill, Brian E; Lapotko, Dmitri O

    2015-01-01

    Chemoradiation is the strongest anti-tumor therapy but in resistant unresectable cancers it often lacks safety and efficacy. We compared our recently developed cell-level combination approach, quadrapeutics, to chemoradiation therapy to establish pre-clinical data for its biodistribution, safety and efficacy in head and neck squamous cell carcinoma (HNSCC), as a clinically challenging aggressive and resistant cancer. In vitro and in vivo models of four carcinomas were treated with standard chemoradiation and quadrapeutics using identical drug and radiation doses. We applied liposomal cisplatin or doxorubicin, colloidal gold, near-infrared laser pulses and radiation, all at low safe doses. The final evaluation used a xenograft model of HNSCC. Quadrapeutics enhanced standard chemoradiation in vitro by reducing head and neck cancer cell proliferation by 1000-fold, inhibiting tumor growth in vivo by 34-fold and improving animal survival by 5-fold, and reducing the side effects to a negligible level. In quadrapeutics, we observed an “inversion” of the drug efficacy of two standard drugs: doxorubicin, a low efficacy drug for the cancers studied, was two times more efficient than cisplatin, the first choice drug in clinic for HNSCC. The radical therapeutic gain of quadrapeutics resulted from the intracellular synergy of the four components employed which we administered in a specific sequence, while the reduction in the toxicity was due to the low doses of all four components. The biodistribution, safety and efficacy data for quadrapeutics in HNSCC ensure its high translational potential and justify the possibility of clinical trials. PMID:26885444

  2. Adjuvant and neoadjuvant treatment in pancreatic cancer.

    PubMed

    Herreros-Villanueva, Marta; Hijona, Elizabeth; Cosme, Angel; Bujanda, Luis

    2012-04-14

    Pancreatic adenocarcinoma is one of the most aggressive human malignancies, ranking 4th among causes for cancer-related death in the Western world including the United States. Surgical resection offers the only chance of cure, but only 15 to 20 percent of cases are potentially resectable at presentation. Different studies demonstrate and confirm that advanced pancreatic cancer is among the most complex cancers to treat and that these tumors are relatively resistant to chemotherapy and radiotherapy. Currently there is no consensus around the world on what constitutes "standard" adjuvant therapy for pancreatic cancer. This controversy derives from several studies, each fraught with its own limitations. Standards of care also vary somewhat with regard to geography and economy, for instance chemo-radiotherapy followed by chemotherapy or vice versa is considered the optimal therapy in North America while chemotherapy alone is the current standard in Europe. Regardless of the efforts in adjuvant and neoadjuvant improved therapy, the major goal to combat pancreatic cancer is to find diagnostic markers, identifying the disease in a pre-metastatic stage and making a curative treatment accessible to more patients. In this review, authors examined the different therapy options for advanced pancreatic patients in recent years and the future directions in adjuvant and neoadjuvant treatments for these patients.

  3. In vivo Quantification of the Effects of Radiation and Presence of Hair Follicle Pores on the Proliferation of Fibroblasts in an Acellular Human Dermis in a Dorsal Skinfold Chamber: Relevance for Tissue Reconstruction following Neoadjuvant Therapy

    PubMed Central

    Maier, Patrick; Hohenberger, Peter; Roessner, Eric Dominic

    2015-01-01

    Introduction In neoadjuvant therapy, irradiation has a deleterious effect on neoangiogenesis. The aim of this study was to examine the post-implantation effects of neoadjuvant irradiation on the survival and proliferation of autologous cells seeded onto an acellular human dermis (hAD; Epiflex). Additionally, we examined the influence of dermal hair follicle pores on viability and proliferation. We used dorsal skinfold chambers implanted in rats and in-situ microscopy to quantify cell numbers over 9 days. Methods 24 rats received a skinfold chamber and were divided into 2 main groups; irradiated and unirradiated. In the irradiated groups 20Gy were applied epicutaneously at the dorsum. Epiflex pieces were cut to size 5x5mm such that each piece had either one or more visible hair follicle pores, or no such visible pores. Fibroblasts were transduced lentiviral with a fluorescent protein for cell tracking. Matrices were seeded statically with 2.5x104 fluorescent fibroblasts and implanted into the chambers. In each of the two main groups, half of the rats received Epiflex with hair follicle pores and half received Epiflex without pores. Scaffolds were examined in-situ at 0, 3, 6 and 9 days after transplantation. Visible cells on the surface were quantified using ImageJ. Results In all groups cell numbers were decreased on day 3. A treatment-dependent increase in cell numbers was observed at subsequent time points. Irradiation had an adverse effect on cell survival and proliferation. The number of cells detected in both irradiated and non-irradiated subjects was increased in those subjects that received transplants with hair follicle pores. Discussion This in-vivo study confirms that radiation negatively affects the survival and proliferation of fibroblasts seeded onto a human dermis transplant. The presence of hair follicle pores in the dermis transplants is shown to have a positive effect on cell survival and proliferation even in irradiated subjects. PMID:25955842

  4. Can pathologic complete response (pCR) be used as a surrogate marker of survival after neoadjuvant therapy for breast cancer?

    PubMed

    Wang-Lopez, Qian; Chalabi, Nassera; Abrial, Catherine; Radosevic-Robin, Nina; Durando, Xavier; Mouret-Reynier, Marie-Ange; Benmammar, Kheir-Eddine; Kullab, Sharif; Bahadoor, Mohun; Chollet, Philippe; Penault-Llorca, Frédérique; Nabholtz, Jean-Marc

    2015-07-01

    Breast cancer is heterogeneous in clinical, morphological, immunohistochemical and biological features, as reflected by several different prognostic subgroups. Neoadjuvant approaches are currently used for the "in vivo" efficacy assessment of treatments. Pathological complete response (pCR) has been reported as a reliable predictive factor of survival in that setting. However, pCR remains a subject of controversy in terms of definition and its evaluation methods. In addition, its predictive value for patient outcome in various breast cancer biological subtypes has been under debate. In this review, we will present the existing definitions of pCR, the impact of its evaluation methods on its rate and the assessment of its predictive value for patient outcome in the molecular subtypes of breast cancer (luminal A and B, Triple Negative and HER2-positive).

  5. Pretreatment performance status and nutrition are associated with early mortality of locally advanced head and neck cancer patients undergoing concurrent chemoradiation.

    PubMed

    Chang, Pei-Hung; Yeh, Kun-Yun; Huang, Jen-Seng; Lai, Chien-Hong; Wu, Tsung-Han; Lan, Yii-Jenq; Tsai, Jason Chien-Sheng; Chen, Eric Yen-Chao; Yang, Shih-Wei; Wang, Cheng-Hsu

    2013-05-01

    Unexpected fatal events in patients with head and neck cancers undergoing concurrent chemoradiation therapy are a clinical concern. Malnutrition, which is reported frequently in head and neck cancer patients, are associated with immunity derangement. The purpose of this study was to identify risk factors for early death of patients undergoing chemoradiation. We retrospectively analyzed the records of 194 stage III, IVA, and IVB head and neck cancer patients who were treated with chemoradiation between 2007 and 2009. We defined early death as death while receiving chemoradiation or within 60 days of treatment completion. Risk factors for early death were tested using univariate and multivariate analyses. Fourteen patients (7.2 %) experienced early death, 78.6 % of whom died of infection. Univariate analysis revealed significant correlations between early death and several pretreatment variables, including Eastern Cooperative Oncology Group performance status (PS) >1, hemoglobin <10 g/dL, albumin <3 g/dL, body mass index (BMI) <19 kg/m(2), and peripheral blood total lymphocyte count <700/μL. Multivariate analysis showed that PS >1, BMI <19 kg/m(2), and peripheral blood total lymphocyte count <700/μL were independent variables associated with early death. Poor performance status and malnutrition before chemoradiation independently predict early death in locally advanced head and neck cancer patients undergoing chemoradiation. Cautious management of head and neck cancer patients with these risk factors is required throughout chemoradiation period.

  6. Are we HER-ting for innovation in neoadjuvant breast cancer trial design?

    PubMed Central

    Snoj, Natasa; Bedard, Philippe L; de Azambuja, Evandro; Cardoso, Fatima; Piccart, Martine

    2009-01-01

    Through the use of surrogate markers of efficacy, neoadjuvant studies may facilitate the implementation of new treatments into clinical practice. However, disease-free survival is the current standard outcome endpoint for registration of a novel treatment. The coupling of smaller neoadjuvant 'proof of principle' studies with larger adjuvant registration trials offers the promise of speeding up the time to market of new therapies. Clever new designs, such as the 'biological window' and 'learn on the way', can provide valuable insight regarding mechanisms of action and resistance of these novel drugs by identifying patients who are most likely to respond to a novel therapy early in the drug development process. Using the ongoing neoadjuvant trials with HER2 (human epidermal growth factor receptor 2)-directed therapy as a paradigm, this article discusses recent innovations in study design and the challenges of conducting translational research in the neoadjuvant setting. PMID:19216727

  7. Iyengar-Yoga Compared to Exercise as a Therapeutic Intervention during (Neo)adjuvant Therapy in Women with Stage I–III Breast Cancer: Health-Related Quality of Life, Mindfulness, Spirituality, Life Satisfaction, and Cancer-Related Fatigue

    PubMed Central

    Lötzke, Désirée; Wiedemann, Florian; Rodrigues Recchia, Daniela; Ostermann, Thomas; Sattler, Daniel; Ettl, Johannes; Kiechle, Marion; Büssing, Arndt

    2016-01-01

    This study aims to test the effects of yoga on health-related quality of life, life satisfaction, cancer-related fatigue, mindfulness, and spirituality compared to conventional therapeutic exercises during (neo)adjuvant cytotoxic and endocrine therapy in women with breast cancer. In a randomized controlled trial 92 women with breast cancer undergoing oncological treatment were randomly enrolled for a yoga intervention (YI) (n = 45) or for a physical exercise intervention (PEI) (n = 47). Measurements were obtained before (t0) and after the intervention (t1) as well as 3 months after finishing intervention (t2) using standardized questionnaires. Life satisfaction and fatigue improved under PEI (p < 0.05) but not under YI (t0 to t2). Regarding quality of life (EORTC QLQ-C30) a direct effect (t0 to t1; p < 0.001) of YI was found on role and emotional functioning, while under PEI only emotional functioning improved. Significant improvements (p < 0.001) were observed at both t1 and t2 also for symptom scales in both groups: dyspnea, appetite loss, constipation, and diarrhea. There was no significant difference between therapies for none of the analyzed variables neither for t1 nor for t2. During chemotherapy, yoga was not seen as more helpful than conventional therapeutic exercises. This does not argue against its use in the recovery phase. PMID:27019663

  8. Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survival. A prospective, single-institution experience.

    PubMed Central

    Yeo, C J; Abrams, R A; Grochow, L B; Sohn, T A; Ord, S E; Hruban, R H; Zahurak, M L; Dooley, W C; Coleman, J; Sauter, P K; Pitt, H A; Lillemoe, K D; Cameron, J L

    1997-01-01

    OBJECTIVE: This study was designed to evaluate prospectively survival after pancreaticoduodenectomy for pancreatic adenocarcinoma, comparing two different postoperative adjuvant chemoradiation protocol to those of no adjuvant therapy. SUMMARY BACKGROUND DATA: Based on limited data from the Gastrointestinal Tumor Study Group, adjuvant chemoradiation therapy has been recommended after pancreaticoduodenectomy for adenocarcinoma of the head, neck, or uncinate process of the pancrease. However, many patients continue to receive no such therapy. METHODS: From October 1991 through September 1995, all patients with resected, pathologically confirmed adenocarcinoma of the head, neck, or uncinate process of the pancreas were reviewed by a multidisciplinary group (surgery, radiation oncology, medical oncology, and pathology) and were offered three options for postoperative treatment after pancreaticoduodenectomy: 1) standard therapy: external beam radiation therapy to the pancreatic bed (4000-4500 cGy) given with two 3-day fluorouracil (5-FU) courses and followed by weekly bolus 5-FU (500 mg/m2 per day) for 4 months; 2) intensive therapy: external beam radiation therapy to the pancreatic bed (5040-5760 cGy) with prophylactic hepatic irradiation (2340-2700 cGy) given with and followed by infusional 5-FU (200 mg/m2 per day) plus leucovorin (5 mg/m2 per day) for 5 of 7 days for 4 months; or 3) no therapy: no postoperative radiation therapy or chemotherapy. RESULTS: Pancreaticoduodenectomy was performed in 174 patients, with 1 in-hospital death (0.6%). Ninety-nine patients elected standard therapy, 21 elected intensive therapy, and 53 patients declined therapy. The three groups were comparable with respect to race, gender, intraoperative blood loss, tumor differentiation, lymph node status, tumor diameter, and resection margin status. Univariate analyses indicated that tumor diameter < 3 cm, intraoperative blood loss < 700 mL, absence of intraoperative blood transfusions, and use

  9. Neoadjuvant endocrine treatment in early breast cancer: An overlooked alternative?

    PubMed

    van Dam, P A; van Dam, V C N; Altintas, S; Papadimitriou, K; Rolfo, C; Trinh, X B

    2016-03-01

    During the last decade neoadjuvant endocrine therapy (NET) has moved from being reserved for elderly and frail non-chemotherapy candidates to a primary systemic modality in selected patients with hormone sensitive breast cancer. Neoadjuvant hormonal treatment in patients with hormone receptor positive, HER-2 negative early breast cancer is proven to be an effective and safe option; it is associated with a higher rate of breast conserving surgery (BCS), may reduce the need for adjuvant chemotherapy and enables a delay of surgery for medical or practical reasons. Clinical responses range from 13% to 100% with at least 3 months of NET. Methods of assessing response should include MRI of the breast, particularly in lobular tumours. In studies comparing tamoxifen with aromatase inhibitors (AI), AI proved to be superior in terms of tumour response and rates of BCS. Change in Ki67 is accepted as a validated endpoint for comparing endocrine neoadjuvant agents. Levels of Ki67 during treatment are more closely related to long-term prognosis than pretreatment Ki67. Neoadjuvant endocrine therapy provides a unique opportunity for studies of endocrine responsiveness and the development of new experimental drugs combined with systemic hormonal treatment.

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

    SciTech Connect

    Noordhuis, Maartje G.; Eijsink, Jasper J.H.; Roossink, Frank; Graeff, Pauline de; Pras, Elisabeth; Schuuring, Ed; Wisman, G. Bea A.; Bock, Geertruida H. de; Zee, Ate G.J. van der

    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 biological 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.

  11. Neoadjuvant chemoradiotherapy for esophageal/gastroesophageal carcinoma

    PubMed Central

    Nurkin, Steven J.; Fong, Mei Ka; Groman, Adrienne; Flaherty, Leayn; Malhotra, Usha; LeVea, Charles M.; Yendamuri, Sai; Warren, Graham W.; Nava, Hector R.; May, Kilian S.

    2013-01-01

    Background Esophageal/gastroesophageal junction (GEJ) adenocarcinoma is increasingly treated with trimodality therapy. We present our experience using carboplatin/paclitaxel and radiotherapy followed by surgery. Methods Consecutive patients with distal esophageal/GEJ adenocarcinoma (≥T2 or N+) treated from July 2010 to October 2011 were identified. Treatment included neoadjuvant carboplatin/paclitaxel with concurrent radiotherapy (CRT) to 50.4 Gy using an IMRT technique and then Ivor Lewis esophagogastrectomy (ILE). PET/CT was performed prior to and after CRT. Patient/treatment characteristics and tumor response were analyzed. Results Over this timeframe, 16 patients completed trimodality therapy. All were male, median age of 60 years (45-72 years). All tumors were grade 2-3 with mean tumor length of 4.4 cm (1-9 cm). A median of 6 cycles (5-9 cycles) neoadjuvant carboplatin/paclitaxel were administered. Average time from diagnosis to CRT completion was 76 days (44-141 days) and 60 days (35-92 days) from CRT end to surgery. Neoadjuvant CRT was well tolerated with mean weight loss of 3.9 kg. All pts had R0 resections. No anastomotic leaks or perioperative mortality occurred. Mean hospital stay was 13 days (8-28 days). Pathologic complete response (pCR) was seen in 38% of patients, microscopic residual disease (isolated tumor cells or <2 mm) in 31%, and macroscopic residual disease remained in 31%. Mean SUV reduction was 41% (0-100%). Of 11 patients with ≥35% SUV decrease, 45% had pCR and 27% had microscopic residual disease. Three patients had signet ring features. Of these, 2 had no SUV reduction and all had gross residual disease, including the only patient with positive nodal disease. Conclusions Trimodality therapy utilizing concurrent carboplatin/paclitaxel and radiotherapy to 50.4 Gy followed by surgery was well tolerated and resulted in significant pathologic complete response or minimal residual disease. Further investigation of predictive factors for

  12. Neoadjuvant treatments for triple-negative breast cancer (TNBC).

    PubMed

    von Minckwitz, G; Martin, M

    2012-08-01

    Neoadjuvant chemotherapy provides a means both of improving subsequent surgical intervention and of testing novel therapies or combinations. Historically, triple-negative breast cancer (TNBC) has responded well in the neoadjuvant setting, with rates of pathological complete response (pCR) commonly higher than for other breast tumour types. However, more than half of TNBC patients do not achieve a pCR and have a very poor prognosis. The lack of drug-targetable receptors on TNBC tumours has made improving the available interventions in TNBC an area of important medical need. The routine use of neoadjuvant anthracycline/taxane combinations in TNBC is currently being supplemented by ongoing investigations of their use with other types of agent. In particular, the substantial proportion of TNBC tumours associated with BRCA1 mutations is driving clinical research into the use of DNA-damaging agents such as platinums, as well as of potentiators of DNA damage such as the investigational agent iniparib and inhibitors of poly-ADP ribose polymerase such as olaparib. Tyrosine kinase receptor inhibitors and microtubule-targeting inhibitors of cell cycling are also under active investigation. The use of neoadjuvant treatment with pCR as a surrogate of overall survival will allow the rapid evaluation and comparison of these and other much-needed new treatments for TNBC.

  13. 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,

  14. Outcome analysis of 300 prostate cancer patients treated with neoadjuvant androgen deprivation and hypofractionated radiotherapy

    SciTech Connect

    Higgins, Geoffrey S. . E-mail: geoffrey.higgins@luht.scot.nhs.uk; McLaren, Duncan B.; Kerr, Gillian R.; Elliott, Tony; Howard, Grahame

    2006-07-15

    Purpose: Neoadjuvant androgen deprivation and radical radiotherapy is an established treatment for localized prostate carcinoma. This study sought to analyze the outcomes of patients treated with relatively low-dose hypofractionated radiotherapy. Methods and Materials: Three hundred patients with T1-T3 prostate cancer were treated between 1996 and 2001. Patients were prescribed 3 months of neoadjuvant androgen deprivation before receiving 5250 cGy in 20 fractions. Patients' case notes and the oncology database were used to retrospectively assess outcomes. Median follow-up was 58 months. Results: Patients presented with prostate cancer with poorer prognostic indicators than that reported in other series. At 5 years, the actuarial cause-specific survival rate was 83.2% and the prostate-specific antigen (PSA) relapse rate was 57.3%. Metastatic disease had developed in 23.4% of patients. PSA relapse continued to occur 5 years from treatment in all prognostic groups. Independent prognostic factors for relapse included treatment near the start of the study period, neoadjuvant oral anti-androgen monotherapy rather than neoadjuvant luteinizing hormone releasing hormone therapy, and diagnosis through transurethral resection of the prostate rather than transrectal ultrasound. Conclusion: This is the largest reported series of patients treated with neoadjuvant androgen deprivation and hypofractionated radiotherapy in the United Kingdom. Neoadjuvant hormonal therapy did not appear to adequately compensate for the relatively low effective radiation dose used.

  15. Changes in neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios during chemoradiation predict for survival and pathologic complete response in trimodality esophageal cancer patients

    PubMed Central

    Hyder, Jalal; Boggs, Drexell Hunter; Hanna, Andrew; Suntharalingam, Mohan

    2016-01-01

    Background Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) predict for survival in cancer patients. In patients receiving multimodality therapy, the effect of therapy on the NLR and PLR is not well understood. We evaluated changes in NLR and PLR among locally advanced esophageal cancer patients who received trimodality therapy. Methods We performed a retrospective analysis of nonmetastatic patients with esophageal cancer who received neoadjuvant chemoradiation therapy (CRT) followed by esophagectomy at our institution between March 2000 and April 2012. NLR and PLR values were obtained for the following time points (TPs): (I) at diagnosis before CRT; (II) after CRT but prior to surgery; and (III) after surgery. We evaluated changes in NLR and PLR using the difference and ratio between TPs. Overall survival (OS) was evaluated by Kaplan-Meier analysis. Univariate and multivariate Cox regression models were applied to evaluate the independent prognostic significance of NLR and PLR. Results This IRB-approved study included the records of 83 consecutive patients with stage II-IV esophageal cancer. The median age was 60 years, and median follow-up was 29.3 months. Patients were treated to a median prescription dose of 50.4 Gy (range, 50.4-56.4 Gy) in 28-33 fractions. Median NLR and PLR were 3.3 and 157.2, 12 and 645, and 11.5 and 391.7 at TPs 1, 2, and 3, respectively. On multivariate analysis, superior OS was associated with PLR ≥250 at TP3 (P=0.03), PLR decrease ≥609.2 between TP2 and TP3 (P=0.02), and PLR ratio (TP3/TP1) ≥1.08 (P=0.03). Inferior progression-free survival (PFS) was associated with NLR ≥36 at TP2 (P=0.0008), NLR increase ≥28.3 between TP1 and TP2 (P=0.0005), and PLR ratio (TP2/TP3) ≥0.38 (P=0.1). Pathologic complete response (PCR) was less likely for adenocarcinoma (AC) histology (P=0.03), NLR ≥10.6 at TP2 (P=0.04), and NLR increase ≥4.6 from TP1 to TP2 (P=0.03). Conclusions To our knowledge, this is the first

  16. Overview of chemoradiation clinical trials for locally advanced non-small cell lung cancer in Japan.

    PubMed

    Okamoto, Isamu

    2008-04-01

    The standard of care for unresectable stage III non-small cell lung cancer (NSCLC) is combined-modality therapy with both chemotherapy and thoracic radiation therapy (TRT). A phase III trial by the West Japan Lung Cancer Group revealed that the combination of mitomycin, vindesine, and cisplatin (MVP) with concurrent TRT yielded a median survival time of 16.6 months and a 5-year survival rate of 16% in patients with unresectable stage III NSCLC. Although evidence indicates that concurrent chemotherapy and TRT (chemoradiation) increases survival to a moderately greater extent than sequential therapeutic approaches, the optimal strategies for such concurrent treatment remain to be defined, and differ between full-dose systemic and low-dose radio-enhancing protocols. Two phase III trials have been initiated in Japan to address these issues and they have recently reported preliminary data. Early results of the Okayama Lung Cancer Study Group (OLCSG) trial, comparing chemoradiation based on divided docetaxel and cisplatin chemotherapy with MVP-based chemoradiation, have been reported. The West Japan Oncology Group (WJOG) is comparing the efficacy and toxicity of TRT and concurrent chemotherapy with either carboplatin-paclitaxel or carboplatin-irinotecan, followed by full-dose consolidation chemotherapy, with the efficacy and toxicity of MVP-based chemoradiation. Several phase I/II studies to test the optimal use of new agents such as S-1 (an oral anticancer drug combining tegafur, 5-chloro-2, 4-dihydroxypyridine, and potassium oxonate) and gefitinib (an inhibitor of the tyrosine kinase activity of the epidermal growth factor receptor) are also ongoing. In addition, radiation dose intensification with three-dimensional planning approaches is currently under evaluation. A phase I clinical trial by WJOG to establish, prospectively, the maximum tolerated dose of three-dimensional hyperfractionated radiotherapy with concurrent weekly chemotherapy (carboplatin-paclitaxel) is

  17. Adjuvant Concurrent Chemoradiation for Adenocarcinoma of the Distal Common Bile Duct

    SciTech Connect

    Hughes, Michael A. . E-mail: michaelaaronhughes@gmail.com; Frassica, Deborah A.; Yeo, Charles J.; Riall, Taylor S.; Lillemoe, Keith D.; Cameron, John L.; Donehower, Ross C.; Laheru, Daniel A.; Hruban, Ralph H.; Abrams, Ross A.

    2007-05-01

    Purpose: To examine the effect of adjuvant chemoradiation for adenocarcinoma of the distal common bile duct (DCBD) after pancreaticoduodenectomy (PD) on local control and survival. Methods and Materials: A total of 34 cases of adenocarcinoma of the DCBD were treated with PD and adjuvant chemoradiation at Johns Hopkins Hospital between 1994 and 2003. Median radiation dose was 5,040 cGy (range, 4,000-5,400 cGy). Concurrent 5-fluorouracil-based chemotherapy was given with radiation therapy, followed by maintenance chemotherapy. Results: The median follow-up of patients alive at the time of analysis was 41 months. Death occurred in 21 of 34 patients (62%) during the follow-up period, all from progressive, distant metastatic disease. Median overall survival was 36.9 months, with a 5-year survival of 35%. On multivariate analysis, only nodal status significantly predicted survival (p < 0.02). For patients with negative and positive lymph nodes, 5-year survival was 100% and 24%, respectively. Actuarial 5-year local control was 70%. Compared with historical controls who underwent PD alone, patients who underwent surgery and adjuvant chemoradiation had significantly longer survival (36.9 months vs. 22 months; p < 0.05). Overall survival was significantly longer for both lymph node negative and lymph node positive patients (p < 0.05). Conclusions: Adjuvant chemoradiation after PD for adenocarcinoma of the DCBD may improve local control and overall survival. The predominant mode of failure is distant metastatic disease, highlighting the need for improved systemic therapy.

  18. Combined preoperative neoadjuvant radiotherapy and chemotherapy for anal and rectal cancer

    SciTech Connect

    Smith, D.E.; Muff, N.S.; Shetabi, H.

    1986-05-01

    Neoadjuvant therapy combining 5-fluorouracil, mitomycin C, and moderate-dose radiotherapy was given preoperatively to 29 patients with adenocarcinoma of the rectum, 3 patients with squamous cell cancer, and 1 patient with basaloid carcinoma of the anus. Significant downstaging, and even eradication, of these lesions was realized in a high percentage of cases. Population-based data for the period of 1979 to 1984 which encompasses the time of our study indicate the survival of those treated by the neoadjuvant therapy was superior to that of patients treated by surgery alone or by surgery followed by radiotherapy. In general, patients with the poorest clinical presentation had been referred for this therapy.

  19. [Neoadjuvant or Adjuvant Chemotherapy for Bladder Cancer?].

    PubMed

    Hupe, M C; Kramer, M W; Kuczyk, M A; Merseburger, A S

    2015-05-01

    Advanced urothelial carcinoma of the bladder is associated with a high metastatic potential. Life expectancy for metastatic patients is poor and rarely exceeds more than one year without further therapy. Neoadjuvant chemotherapy can decrease the tumour burden while reducing the risk of death. Adjuvant chemotherapy has been discussed controversially. Patients with lymph node-positive metastases seem to benefit the most from adjuvant chemotherapy. In selected patients, metastasectomy can prolong survival. In metastastic patients, the combination of gemcitabine and cisplatin has become the new standard regimen due to a lower toxicity in comparison to the combination of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC). For second-line treatment, vinflunine is the only approved therapeutic agent.

  20. Prospective phase II trial of pre-resection thoracoscopic mediastinal restaging following neoadjuvant therapy for IIIA (N2) non-small cell lung cancer: Results of CALGB Protocol # 39803

    PubMed Central

    Jaklitsch, Michael T; Gu, Lin; Demmy, Todd; Harpole, David H; D’Amico, Thomas A; McKenna, Robert J; Krasna, Mark J; Kohman, Leslie J; Swanson, Scott J; DeCamp, Malcolm M; Wang, Xiaofei; Sutherland, Susan; Sugarbaker, David J

    2013-01-01

    Background Accurate pathologic re-staging of N2 stations following neoadjuvant therapy in IIIA(N2) NSCLC is needed. Methods A prospective multi-institutional trial was designed to judge feasibility of VATS restaging ipsilateral nodes in mediastinoscopy proven IIIA(N2) NSCLC following 2 cycles platinum-based chemotherapy and/or > 40 Gy radiotherapy. Goals included biopsy 3 negative N2 node stations, or identify 1 positive N2 node or pleural carcinomatosis. Results Ten institutions accrued 68 subjects. Forty-six (68%) underwent radiation and 66 (97%) had chemotherapy. VATS successfully met pre-study feasibility in 27 pts (40%): three negative stations and confirmed at thoracotomy (7); persistent N2 disease (16) and pleural carcinomatosis (4). Twenty (29 %) found no N2 disease, but did not biopsy 3 stations due to unanticipated nodal obliteration. Thus, 47 VATS (69%, 95% CI: 57 - 80) restaged the mediastinum. VATS was unsuccessful in 21 (31 %) patients: abort procedure (11), or false negative stations (10). Of 21 failures, 15 were right-sided, and 10 had a positive 4R node. Sensitivity of VATS was 67% (95% CI: 47 – 83), and negative predictive value (NPV) was 73% (95% CI: 56 – 86) if including patients with obliterated nodal tissue. Sensitivity was 83% (95% CI: 63 – 95), NPV was 64% (95% CI: 31 – 89) if excluding those patients. Specificity was 100%. There was 1death after thoracotomy Conclusions VATS restaging was within 90% CI of “feasible” and provided pathology of ipsilateral nodes. VATS restaging is limited by radiation and the 4R nodal station. PMID:23768804

  1. Final Report of Multicenter Canadian Phase III Randomized Trial of 3 Versus 8 Months of Neoadjuvant Androgen Deprivation Therapy Before Conventional-Dose Radiotherapy for Clinically Localized Prostate Cancer

    SciTech Connect

    Crook, Juanita Ludgate, Charles; Malone, Shawn; Perry, Gad; Eapen, Libni; Bowen, Julie; Robertson, Susan; Lockwood, Gina M.Math.

    2009-02-01

    Purpose: To evaluate the effect of 3 vs. 8 months of neoadjuvant hormonal therapy before conventional-dose radiotherapy (RT) on disease-free survival for localized prostate cancer. Methods and Materials: Between February 1995 and June 2001, 378 men were randomized to either 3 or 8 months of flutamide and goserelin before 66 Gy RT at four participating centers. The median baseline prostate-specific antigen level was 9.7 ng/mL (range, 1.3-189). Of the 378 men, 26% had low-, 43% intermediate-, and 31% high-risk disease. The two arms were balanced in terms of age, Gleason score, clinical T category, risk group, and presenting prostate-specific antigen level. The median follow-up for living patients was 6.6 years (range, 1.6-10.1). Of the 378 patients, 361 were evaluable, and 290 were still living. Results: The 5-year actuarial freedom from failure rate for the 3- vs. 8-month arms was 72% vs. 75%, respectively (p = 0.18). No difference was found in the failure types between the two arms. The median prostate-specific antigen level at the last follow-up visit for patients without treatment failure was 0.6 ng/mL in the 3-month arm vs. 0.50 ng/mL in the 8-month arm. The disease-free survival rate at 5 years was improved for the high-risk patients in the 8-month arm (71% vs. 42%, p = 0.01). Conclusion: A longer period of NHT before standard-dose RT did not alter the patterns of failure when combined with 66-Gy RT. High-risk patients in the 8-month arm had significant improvement in the 5-year disease-free survival rate.

  2. Tumor control and QoL outcomes of very young children with atypical teratoid/rhabdoid tumor treated with focal only chemo-radiation therapy using pencil beam scanning proton therapy.

    PubMed

    Weber, Damien C; Ares, Carmen; Malyapa, Robert; Albertini, Francesca; Calaminus, Gabriele; Kliebsch, Ulrike; Mikroutsikos, Lorentzos; Morach, Petra; Bolsi, Alessandra; Lomax, Tony; Schneider, Ralf

    2015-01-01

    The aim of this analysis was to assess the early clinical results of pencil beam scanning proton therapy (PT) in the treatment of young children with non-metastatic atypical teratoid/rhabdoid tumor (ATRT) of the CNS. Fifteen children (male, n = 8, 53 %) were treated with PT between May 2008 and January 2013. Mean age at diagnosis was 17.4 ± 7.0 months. The localization was infratentorial in 9 (60 %) patients. Gross total resection of the primary tumors was achieved in 7 (47 %) patients. The dose administered focally under sedation was 54 Gy (RBE). After a median follow-up of 33.4 months (range 9.7-69.2), 3 (20 %), 4 (27 %) and 2 (13 %) patients presented with local failure (LF), distant brain failure (DBF) and spinal failure (SF), respectively. Six patients died, all of tumor progression. The 2-year overall- and progression-free survival was 64.6 and 66.0 %. Tumor location (supratentorial) and the extent of surgical resection (non-gross total resection) were negative prognostic factors for both OS and PFS. PT was well tolerated. No grade >2 acute toxicity was observed. The estimated 2-year toxicity-free survival was 90 %. As assessed by the PedsQoL proxy, no decrease in QoL was observed after PT. We conclude that PBS PT is an effective treatment for young children with ATRT. After PT, with or without concomitant chemotherapy, two third of the patients survived >2 years. Acute toxicity was manageable. Longer follow-up and larger numbers of patients are needed to assess long-term outcomes and treatment-induced toxicity.

  3. 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

  4. Molecular Markers Predict Distant Metastases After Adjuvant Chemoradiation for Rectal Cancer

    SciTech Connect

    Kim, Jun Won; Kim, Yong Bae; Choi, Jun Jeong; Koom, Woong Sub; Kim, Hoguen; Kim, Nam-Kyu; Ahn, Joong Bae; Lee, Ikjae; Cho, Jae Ho; Keum, Ki Chang

    2012-12-01

    Purpose: The outcomes of adjuvant chemoradiation for locally advanced rectal cancer are nonuniform among patients with matching prognostic factors. We explored the role of molecular markers for predicting the outcome of adjuvant chemoradiation for rectal cancer patients. Methods and Materials: The study included 68 patients with stages II to III rectal adenocarcinoma who were treated with total mesorectal excision and adjuvant chemoradiation. Chemotherapy based on 5-fluorouracil and leucovorin was intravenously administered each month for 6-12 cycles. Radiation therapy consisted of 54 Gy delivered in 30 fractions. Immunostaining of surgical specimens for COX-2, EGFR, VEGF, thymidine synthase (TS), and Raf kinase inhibitor protein (RKIP) was performed. Results: The median follow-up was 65 months. Eight locoregional (11.8%) and 13 distant (19.1%) recurrences occurred. Five-year locoregional failure-free survival (LRFFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) rates for all patients were 83.9%, 78.7%, 66.7%, and 73.8%, respectively. LRFFS was not correlated with TNM stage, surgical margin, or any of the molecular markers. VEGF overexpression was significantly correlated with decreased DMFS (P=.045), while RKIP-positive results were correlated with increased DMFS (P=.025). In multivariate analyses, positive findings for COX-2 (COX-2+) and VEGF (VEGF+) and negative findings for RKIP (RKIP-) were independent prognostic factors for DMFS, DFS, and OS (P=.035, .014, and .007 for DMFS; .021, .010, and <.0001 for DFS; and .004, .012, and .001 for OS). The combination of both COX-2+ and VEGF+ (COX-2+/VEGF+) showed a strong correlation with decreased DFS (P=.007), and the combinations of RKIP+/COX-2- and RKIP+/VEGF- showed strong correlations with improved DFS compared with the rest of the patients (P=.001 and <.0001, respectively). Conclusions: Molecular markers can be valuable in predicting treatment outcome of adjuvant

  5. Neoadjuvant Treatment Does Not Influence Perioperative Outcome in Rectal Cancer Surgery

    SciTech Connect

    Ulrich, Alexis; Weitz, Juergen Slodczyk, Matthias; Koch, Moritz; Jaeger, Dirk; Muenter, Marc; Buechler, Markus W.

    2009-09-01

    Purpose: To identify the risk factors for perioperative morbidity in patients undergoing resection of primary rectal cancer, with a specific focus on the effect of neoadjuvant therapy. Methods and Materials: This exploratory analysis of prospectively collected data included all patients who underwent anterior resection/low anterior resection or abdominoperineal resection for primary rectal cancer between October 2001 and October 2006. The study endpoints were perioperative surgical and medical morbidity. Univariate and multivariate analyses of potential risk factors were performed. Results: A total of 485 patients were included in this study; 425 patients (88%) underwent a sphincter-saving anterior resection/low anterior resection, 47 (10%) abdominoperineal resection, and 13 (2%) multivisceral resection. Neoadjuvant chemoradiotherapy was performed in 100 patients (21%), and 168 (35%) underwent neoadjuvant short-term radiotherapy (5 x 5 Gy). Patient age and operative time were independently associated with perioperative morbidity, and operative time, body mass index >27 kg/m{sup 2} (overweight), and resection type were associated with surgical morbidity. Age and a history of smoking were confirmed as independent prognostic risk factors for medical complications. Neoadjuvant therapy was not associated with a worse outcome. Conclusion: The results of this prospective study have identified several risk factors associated with an adverse perioperative outcome after rectal cancer surgery. In addition, neoadjuvant therapy was not associated with increased perioperative complications.

  6. Concomitant boost IMRT-based neoadjuvant chemoradiotherapy for clinical stage II/III rectal adenocarcinoma: results of a phase II study

    PubMed Central

    2014-01-01

    Aim This study was designed to evaluate the efficacy and toxicities of concomitant boost intensity-modulated radiation therapy (IMRT) along with capecitabine and oxaliplatin, followed by a cycle of Xelox, in neoadjuvant course for locally advanced rectal cancer. Materials and methods Patients with histologically confirmed, newly diagnosed, locally advanced rectal adenocarcinoma (cT3-T4 and/or cN+) located within 12 cm of the anal verge were included in this study. Patients received IMRT to the pelvis of 50 Gy and a concomitant boost of 5 Gy to the primary tumor in 25 fractions, and concurrent with oxaliplatin (50 mg/m2 d1 weekly) and capecitabine (625 mg/m2 bid d1–5 weekly). One cycle of Xelox (oxaliplatin 130 mg/m2 on d1 and capecitabine 1000 mg/m2 twice daily d1–14) was given two weeks after the completion of chemoradiation, and radical surgery was scheduled eight weeks after chemoradiation. Tumor response was evaluated by tumor regression grade (TRG) system and acute toxicities were evaluated by NCI-CTC 3.0 criteria. Survival curves were estimated using the Kaplan-Meier method and compared with Log-rank test. Results A total of 78 patients were included between March 2009 and May 2011 (median age 54 years; 62 male). Seventy-six patients underwent surgical resection. Twenty-eight patients underwent sphincter-sparing lower anterior resection and 18 patients (23.7%) were evaluated as pathological complete response (pCR). The incidences of grade 3 hematologic toxicity, diarrhea, and radiation dermatitis were 3.8%, 10.3%, and 17.9%, respectively. The three-year LR (local recurrence), DFS (disease-free survival) and OS (overall survival) rates were 14.6%, 63.8% and 77.4%, respectively. Initial clinical T stage and tumor regression were independent prognostic factors to DFS. Conclusion An intensified regimen of concomitant boost radiotherapy plus concurrent capecitabine and oxaliplatin, followed by one cycle of Xelox, can be safely administered in patients

  7. Concurrent chemoradiation for high-risk prostate cancer.

    PubMed

    Cooper, Benjamin T; Sanfilippo, Nicholas J

    2015-08-10

    There are estimated to be 220800 cases of prostate cancer diagnosed in 2015, making up 26% of all cancer diagnoses. Fortunately, adenocarcinoma of the prostate is often a highly treatable malignancy. Even though the majority of prostate cancer patients present with localized disease, prostate cancer still accounts for over 27000 deaths a year. There is a subset of patients that are likely to recur after locoregional treatment that is thought of as a "high-risk" population. This more aggressive subset includes patients with clinical stage greater than T2b, Gleason score greater than 7, and prostate specific antigen greater than 20 ng/dL. The rate of biochemical relapse in this high risk group is 32%-70% within five years of definitive focal therapy. Given these discouraging outcomes, attempts have been made to improve cure rates by radiation dose escalation, addition of androgen depravation therapy, and addition of chemotherapy either sequentially or concurrently with radiation. One method that has been shown to improve clinical outcomes is the addition of chemotherapy to radiotherapy for definitive treatment. Concurrent chemoradiation with 5-fluorouracil, estramustine phosphate, vincristine, docetaxel, and paclitaxel has been studied in the phase I and/or II setting. These trials have identified the maximum tolerated dose of chemotherapy and radiation that can be safely delivered concurrently and established the safety and feasibility of this technique. This review will focus on the addition of concurrent chemotherapy to radiotherapy in the definitive management of high-risk prostate cancer.

  8. Neoadjuvant treatment sequencing adds value to the care of patients with operable pancreatic cancer.

    PubMed

    Asare, Elliot A; Evans, Douglas B; Erickson, Beth A; Aburajab, Murad; Tolat, Parag; Tsai, Susan

    2016-09-01

    Treatment sequencing for resectable pancreatic cancer remains controversial and there is lack of level one evidence comparing neoadjuvant versus adjuvant strategies. However, a comparison of the cost-effectiveness analysis of the treatment strategies may help to better define the healthcare value of each approach. This review will highlight the rationale for multimodality therapy in the treatment of pancreatic cancer, discuss the advantages and disadvantages of adjuvant therapy, and conceptualize the cost-effectiveness of a neoadjuvant approach with regard to healthcare value. J. Surg. Oncol. 2016;114:291-295. © 2016 Wiley Periodicals, Inc.

  9. Chemoradiation with gemcitabine for cervical cancer in patients with renal failure.

    PubMed

    Cetina, Lucely; Rivera, Lesbia; Candelaria, Myrna; de la Garza, Jaime; Dueñas-González, Alfonso

    2004-09-01

    The prognosis of cervical cancer patients with renal failure secondary to obstructive uropathy is poor. Our objective was to analyze our experience in the management with chemoradiation of untreated cervical cancer patients complicated by obstructive nephropathy and kidney dysfunction. Untreated patients with cervical cancer and renal failure as manifested by raised serum creatinine were treated with pelvic radiotherapy concurrently with weekly gemcitabine at 300 mg/m2. Response, toxicity and renal function pre- and post-therapy were evaluated. Eight FIGO stage IIIB and one IVB patients were treated. Pre-treatment serum creatinine ranged from 1.6 to 18.5 mg/100 ml (median 3.3, mean 6.8) and creatinine clearance varied from 4 to 57 mg/ml/min (median 17, mean 22.1). Four patients had a percutaneous nephrostomy placed and four patients had symptoms from kidney failure. All patient completed chemoradiation. Most patients had grade 3 leukopenia and neutropenia. Dermatitis, colitis and proctitis were common. All patients had improvement in creatinine clearance (pre-therapy 22.78, post-therapy 54.3 mg/ml/min) (p=0.0058) and all but one normalized serum creatinine. Eight (89%) of nine patients achieved complete response and one patient had persistence. At a median follow-up of 11 months (range 6-14), all patients are alive, one with pelvic and another with systemic disease. Ureteral obstruction causing any degree of renal insufficiency should not be a contraindication to receive chemoradiation to attempt cure. In this setting where cisplatin-based therapy is contraindicated, the use of gemcitabine may be considered.

  10. Adjuvant, neoadjuvant, and experimental regimens in overcoming pancreatic ductal adenocarcinoma

    PubMed Central

    Wysocka, Olga; Kulbacka, Julita; Saczko, Jolanta

    2016-01-01

    Pancreatic cancer is one of the most aggressive and deadly malignancies. Despite better understanding of its biology and pathogenesis, contemporary treatment regimens are still insufficient. Along with the introduction of new treatment agents and combination therapy, the response rates are increasing, but these scores do not go with overall survival, and results are frequently conflicting. Therefore, contemporary medicine faces the challenge of expanding the knowledge base and practice on all grounds – pathology, factor risk, diagnosis, and finally surgical and palliative treatment of this disease. This paper provides a review of current adjuvant and neoadjuvant regimens and the role of experimental therapies in pancreatic ductal adenocarcinoma. PMID:27713776

  11. Radiotherapy and chemoradiation after surgery for early cervical cancer

    PubMed Central

    Rogers, Linda; Siu, Shing Shun N; Luesley, David; Bryant, Andrew; Dickinson, Heather O

    2014-01-01

    Background This is an updated version of the original Cochrane review first published in Issue 4, 2009. There is an ongoing debate about the indications for, and value of, adjuvant pelvic radiotherapy after radical surgery in women with early cervical cancer. Certain combinations of pathological risk factors are thought to represent sufficient risk for recurrence, that they justify the use of postoperative pelvic radiotherapy, though this has never been shown to improve overall survival, and use of more than one type of treatment (surgery and radiotherapy) increases the risks of side effects and complications. Objectives To evaluate the effectiveness and safety of adjuvant therapies (radiotherapy, chemotherapy followed by radiotherapy, chemoradiation) after radical hysterectomy for early-stage cervical cancer (FIGO stages IB1, IB2 or IIA). Search methods For the original review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), Issue 4, 2008. The Cochrane Gynaecological Cancer Group Trials Register, MEDLINE (January 1950 to November 2008), EMBASE (1950 to November 2008). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. For this update, we extended the database searches to September 2011 and searched the MetaRegister for ongoing trials. Selection criteria Randomised controlled trials (RCTs) that compared adjuvant therapies (radiotherapy, chemotherapy followed by radiotherapy, or chemoradiation) with no radiotherapy or chemoradiation, in women with a confirmed histological diagnosis of early cervical cancer who had undergone radical hysterectomy and dissection of the pelvic lymph nodes. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Information on grade 3 and 4 adverse events was collected from the trials. Results were pooled using random-effects meta-analyses. Main results Two RCTs

  12. Who Benefits From Adjuvant Radiation Therapy for Gastric Cancer? A Meta-Analysis

    SciTech Connect

    Ohri, Nitin; Garg, Madhur K.; Aparo, Santiago; Kaubisch, Andreas; Tome, Wolfgang; Kennedy, Timothy J.; Kalnicki, Shalom; Guha, Chandan

    2013-06-01

    Purpose: Large randomized trials have demonstrated significant survival benefits with the use of adjuvant chemotherapy or chemoradiation therapy for gastric cancer. The importance of adjuvant radiation therapy (RT) remains unclear. We performed an up-to-date meta-analysis of randomized trials testing the use of RT for resectable gastric cancer. Methods and Materials: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized trials testing adjuvant (including neoadjuvant) RT for resectable gastric cancer. Hazard ratios describing the impact of adjuvant RT on overall survival (OS) and disease-free survival (DFS) were extracted directly from the original studies or calculated from survival curves. Pooled estimates were obtained using the inverse variance method. Subgroup analyses were performed to determine whether the efficacy of RT varies with chemotherapy use, RT timing, geographic region, type of nodal dissection performed, or lymph node status. Results: Thirteen studies met all inclusion criteria and were used for this analysis. Adjuvant RT was associated with a significant improvement in both OS (HR = 0.78, 95% CI: 0.70-0.86, P<.001) and DFS (HR = 0.71, 95% CI: 0.63-0.80, P<.001). In the 5 studies that tested adjuvant chemoradiation therapy against adjuvant chemotherapy, similar effects were seen for OS (HR = 0.83, 95% CI: 0.67-1.03, P=.087) and DFS (HR = 0.77, 95% CI: 0.91-0.65, P=.002). Available data did not reveal any subgroup of patients that does not benefit from adjuvant RT. Conclusion: In randomized trials for resectable gastric cancer, adjuvant RT provides an approximately 20% improvement in both DFS and OS. Available data do not reveal a subgroup of patients that does not benefit from adjuvant RT. Further study is required to optimize the implementation of adjuvant RT for gastric cancer with regard to patient selection and integration with systemic therapy.

  13. The Role of Postmastectomy Radiation Therapy After Neoadjuvant Chemotherapy in Clinical Stage II-III Breast Cancer Patients With pN0: A Multicenter, Retrospective Study (KROG 12-05)

    SciTech Connect

    Shim, Su Jung; Park, Won; Huh, Seung Jae; Choi, Doo Ho; Shin, Kyung Hwan; Lee, Nam Kwon; Suh, Chang-Ok; Keum, Ki Chang; Kim, Yong Bae; Ahn, Seung Do; Kim, Su Ssan; Ha, Sung W.; Chie, Eui Kyu; Kim, Kyubo; Shin, Hyun Soo; Kim, Jin Hee; Lee, Hyung-Sik

    2014-01-01

    Purpose: The purpose of this study was to investigate the role of postmastectomy radiation therapy (PMRT) after neoadjuvant chemotherapy (NAC) in clinical stage II-III breast cancer patients with pN0. Methods and Materials: We retrospectively identified 417 clinical stage II-III breast cancer patients who achieved an ypN0 at surgery after receiving NAC between 1998 and 2009. Of these, 151 patients underwent mastectomy after NAC. The effect of PMRT on disease-free survival (DFS), locoregional recurrence-free survival (LRRFS), and overall survival (OS) was evaluated by multivariate analysis including known prognostic factors using the Kaplan-Meier method and compared using the log–rank test and Cox proportional regression analysis. Results: Of the 151 patients who underwent mastectomy, 105 (69.5%) received PMRT and 46 patients (30.5%) did not. At a median follow-up of 59 months, 5 patients (3.3%) developed LRR (8 sites of recurrence) and 14 patients (9.3%) developed distant metastasis. The 5-year DFS, LRRFS, and OS rates were 91.2, 98.1, and 93.3% with PMRT and 83.0%, 92.3%, and 89.9% without PMRT, respectively (all P values not significant). By univariate analysis, only age (≤40 vs >40 years) was significantly associated with decreased DFS (P=.027). By multivariate analysis, age (≤40 vs >40 years) and pathologic T stage (0-is vs 1 vs 2-4) were significant prognostic factors affecting DFS (hazard ratio [HR] 0.353, 95% confidence interval [CI] 0.135-0.928, P=.035; HR 2.223, 95% CI 1.074-4.604, P=.031, respectively). PMRT showed no correlation with a difference in DFS, LRRFS, or OS by multivariate analysis. Conclusions: PMRT might not be necessary for pN0 patients after NAC, regardless of clinical stage. Prospective randomized clinical trial data are needed to assess whether PMRT can be safely omitted in pN0 patients after NAC and mastectomy for clinical stage II-III breast cancer.

  14. Protection of organs at risk during neoadjuvant chemoradiotherapy for gastric cancer based on a comparison between conformal and intensity-modulated radiation therapy

    PubMed Central

    HAWRYLEWICZ, LESZEK; LESZCZYŃSKI, WOJCIECH; NAMYSŁ-KALETKA, AGNIESZKA; BRONCLIK, IWONA; WYDMAŃSKI, JERZY

    2016-01-01

    The aim of the present study was to compare the techniques of dynamic intensity-modulated radiation therapy (IMRT) and three-dimensional conformal radiotherapy (3DCRT) in patients with gastric cancer. Implementation of the IMRT technique does not significantly affect the minimum and maximum dose levels in the planning target volume (PTV), but more effectively protects the critical organs. The study group consisted of 25 patients. The results of the analysis of the conformity index (CI) and the homogeneity index (HI) showed that the doses in the PTV regions were at a comparable level. The CI for the PTV was 0.95 for the 2-field technique, 0.95 for the 3-field technique, 0.96 for the 4-field technique and 0.94 for the IMRT technique. The CIs for these techniques for the clinical target volume (CTV) were 0.96, 0.96, 0.97 and 0.96, respectively, and the CIs for the gross tumor volume (GTV) were 0.99, 0.99, 0.99 and 0.98, respectively. The HI values for the PTV were 1.12 for the 2-field technique, 1.12 for the 3-field technique, 1.09 for the 4-field technique and 1.09 for the IMRT technique, and the HI values for the CTV were 1.12, 1.12, 1.09 and 1.08 for the same techniques, respectively. The HI values for the GTV were 1.09, 1.09, 1.07 and 1.06, respectively, which indicated significantly superior performance in the regions of healthy tissue. Statistical study was based on Friedman's rank analysis of variance to determine the level of reliability of the tested groups of variables (P<0.001). The present study demonstrated that the IMRT technique in the pre-operative radiotherapy of gastric cancer patients results in superior treatment tolerance and reduces the risk of damage to healthy tissue that is in close proximity to the irradiated area. PMID:27347202

  15. Feasibility of preoperative combined radiation therapy and chemotherapy with 5-fluorouracil and cisplatin in potentially resectable pancreatic adenocarcinoma: The French SFRO-FFCD 97-04 Phase II trial

    SciTech Connect

    Mornex, Francoise . E-mail: francoise.mornex@chu-lyon.fr; Girard, Nicolas; Scoazec, Jean-Yves; Bossard, Nadine; Ychou, Marc; Smith, Denis; Seitz, Jean-Francois; Valette, Pierre-Jean; Roy, Pascal; Rouanet, Philippe; Ducreux, Michel; Partensky, Christian

    2006-08-01

    Purpose More than 80% of patients who undergo a potentially curative resection for pancreatic cancer develop local or distant recurrence. Neoadjuvant chemoradiotherapy might offer potential benefits regarding local and systemic control and survival. This multi-institutional Phase II trial explored the feasibility of preoperative chemoradiation in this situation. Methods and Materials Treatment consisted of concurrent radiotherapy (50 Gy within 5 weeks), and chemotherapy with 5-fluorouracil (300 mg/m{sup 2}/day, 5 days/week, 5 consecutive weeks) and cisplatin (20 mg/m{sup 2}/day, Days 1-5 and 29-33), followed by surgical resection of the pancreatic tumor in patients without progression. Results A total of 41 patients were enrolled. Of these, 38 (93%) received {>=}47 Gy; 30 patients (73%) received {>=}75% of the prescribed doses of chemotherapy. Surgical resection was performed in 26 patients (63%). Because of local or metastatic progression, 5 patients (12%) did not undergo surgery and 10 underwent surgery without resection of the pancreatic tumor. Operative mortality was 2.8%. Among 40 evaluable patients, 27 were successfully treated (67.5%; 95% CI, 50.9-81.4%). Conclusions Pancreatic cancer is chemo-radiosensitive. The proposed pre-operative scheme is feasible, does not prevent successful surgery, and must be tested on a Phase III setting. Yet, the large proportion of tumor progression during and after chemoradiation justifies the use of more efficient drugs such as Gemcitabine, and optimized radiotherapy including new techniques such as intensity-modulated radiation therapy.

  16. Neoadjuvant chemotherapy in muscle-invasive bladder cancer: ready for prime time?

    PubMed

    Pouessel, Damien; Mongiat-Artus, Pierre; Culine, Stéphane

    2013-03-01

    Through a Medline search from January 1, 1998 to February 29, 2012, the literature data supporting the standard use of neoadjuvant or adjuvant chemotherapy in the perioperative setting for muscle-invasive transitional cell carcinoma of the bladder were reviewed. Randomized phase III trials and meta-analyses have shown a significant benefit (level I evidence) in overall survival for neoadjuvant chemotherapy, with a 5% absolute benefit at 5 years, provided cisplatin-based combination regimens are used. Major methodological biases preclude any firm conclusion regarding the routine use of adjuvant therapy. The optimal chemotherapy regimen remains to be determined. Predictive biomarkers are urgently needed in order to determine which patients are more likely to benefit from neoadjuvant chemotherapy.

  17. Neoadjuvant Treatment Approach: The Rosetta Stone for Breast Cancer?

    PubMed

    Generali, Daniele; Ardine, Mara; Strina, Carla; Milani, Manuela; Cappelletti, Maria Rosa; Zanotti, Laura; Forti, Michela; Bedussi, Francesca; Martinotti, Mario; Amoroso, Vito; Sigala, Sandra; Simoncini, Edda; Berruti, Alfredo; Bottini, Alberto

    2015-05-01

    Breast cancer represents a heterogeneous group of diseases with varied biological features, behavior, and response to therapy; thus, management of breast cancer relies on the availability of robust predictive and prognostic factors to support therapy decision-making. Traditionally, neoadjuvant treatment for breast cancer was preserved for locally advanced, converting an inoperable to a surgical resectable cancer. Neoadjuvant trials, additionally, offer: 1) the opportunity to evaluate new treatment options in a faster way and with fewer patients than large adjuvant trials; 2) to identify and validate the prognostic and predictive value of a marker with its association with clinical outcome in relation to the administered treatment. In this setting, thanks to new, affordable technologies which help to detail the molecular profiles of tumors, new trial designs based on new target therapies, like window-of-opportunity, are also suggested, as they represent the chance to identify tumor sensitivity or to overcome tumor resistance to the treatment used, based on its interaction with tumor biology in early tumor stages. However, clinicians and researchers should pay particular attention: In this setting, the safety of patients is paramount, given the exposure of potentially curable patients to investigational agents with limited safety experience, the definition of the study population and the study design, such as adaptive strategies, should limit patient exposure to ineffective agents, and intensify safety monitoring in the course of the treatment. Here, issues related to outcome determination in breast cancer, including some critical points of view, are presented.

  18. 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

    SciTech Connect

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

    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 5 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%).

  19. Sacral Insufficiency Fractures After Preoperative Chemoradiation for Rectal Cancer: Incidence, Risk Factors, and Clinical Course

    SciTech Connect

    Herman, Michael P.; Kopetz, Scott; Bhosale, Priya R.; Eng, Cathy; Skibber, John M.; Rodriguez-Bigas, Miguel A.; Feig, Barry W.; Chang, George J.; Delclos, Marc E.; Krishnan, Sunil; Crane, Christopher H.; Das, Prajnan

    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 with 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.

  20. Postoperative chemoradiation for resected gastric cancer - is the Macdonald Regimen Tolerable? a retrospective multi-institutional study

    PubMed Central

    2011-01-01

    Background Postoperative chemoradiation as per Intergroup-0116 trial ("Macdonald regimen") is considered standard for completely resected high risk gastric cancer. However, many concerns remain with regards to the toxicity of this regimen. To evaluate the safety and tolerability of this regimen in a routine clinical practice setting, we analyzed our experience with its use. As we did not expect a different toxic profile in patients (pts) with positive margins (R1 resection), these were studied together with pts after complete resection (R0). Patients and Methods Postoperative chemoradiation therapy was given according to the original Intergroup-0116 regimen. Overall survival (OS) and disease free survival (DFS) rates were calculated using the Kaplan-Meier method. Comparison of OS and DFS between R0 and R1 pts was done using the log-rank test. Results Between 6/2000 and 12/2007, 166 pts after R0 (129 pts) or R1 (37 pts) resection of locally advanced gastric adenocarcinoma received postoperative chemoradiation; 61% were male and the median age was 63 years (range, 23-86); 78% had T ≥ 3 tumors and 81% had N+ disease; 87% of the pts completed radiotherapy and 54% completed the entire chemoradiation plan; 46.4% had grade ≥ 3 toxicity and 32% were hospitalized at least once for toxicity. Three pts (1.8%) died of toxicity: diarrhea (1), neutropenic sepsis (1) and neutropenic sepsis complicated by small bowel gangrene (1). The most common hematological toxicity was neutropenia, grade ≥ 3 in 30% of pts and complicated by fever in 15%. The most common non-hematological toxicities were nausea, vomiting and diarrhea. With a median follow-up of 51 months (range, 2-100), 62% of the R0 patients remain alive and 61% are free of disease. Median DFS and OS for R0 were not reached. R0 pts had a significantly higher 3-year DFS (60% vs. 29%, p = 0.001) and OS (61% vs. 33%, p = 0.01) compared with R1 pts. Conclusions In our experience, postoperative chemoradiation as per

  1. A pilot phase II study of neoadjuvant triplet chemotherapy regimen in patients with locally advanced resectable colon cancer

    PubMed Central

    Zhou, Haitao; Song, Yan; Jiang, Jun; Niu, Haitao; Zhao, Hong; Liang, Jianwei; Su, Hao; Wang, Zheng; Zhou, Zhixiang; Huang, Jing

    2016-01-01

    Objective This study aims to investigate the feasibility, safety and efficacy of triplet regimen of neoadjuvant chemotherapy in patients with locally advanced resectable colon cancer. Methods Patients with clinical stage IIIb colon cancer received a perioperative triple chemotherapy regimen (oxaliplatin 85 mg/m2 and irinotecan 150 mg/m2, combined with folinic acid 200 mg, 5-fluorouracil 500 mg bolus and then 2,400 mg/m2 by 44 h infusion or capecitabine 1 g/m2 or S-1 40–60 mg b.i.d orally d 1–10, repeated at 2-week intervals) for 4 cycles. Complete mesocolic excision was scheduled 2–6 weeks after completion of neoadjuvant treatment and followed by a further 6 cycles of FOLFOXIRI or XELOX. Primary outcome measures of this stage II trial were feasibility, safety, tolerance and efficacy of neoadjuvant treatment. Results All 23 patients received neoadjuvant chemotherapy and underwent surgery. Twenty-one patients (91.3%) had reductions in tumor volume after neoadjuvant treatment, and 13 patients (56.5%) had grade 3–4 toxicity. No patients had severe complications from surgery. Preoperative therapy resulted in significant down-staging of T-stage and N-stage compared with the baseline clinical stage including one pathological complete response. Conclusions Neoadjuvant triple chemotherapy has high activity and acceptable toxicity and perioperative morbidity, and is feasible, tolerable and effective for locally advanced resectable colon cancer. PMID:28174488

  2. Survival After Chemoradiation in Resected Pancreatic Cancer: The Impact of Adjuvant Gemcitabine

    SciTech Connect

    Baschnagel, Andrew; Shah, Chirag; Margolis, Jeffrey; Nadeau, Laura; Stein, Julie; Jury, Robert; Robertson, John M.

    2012-07-01

    Purpose: To evaluate survival in patients with resected pancreatic cancer treated with concurrent chemoradiation with or without adjuvant gemcitabine (Gem). Methods and Materials: From 1998 to 2010, 86 patients with pancreatic adenocarcinoma who underwent resection were treated with adjuvant concurrent chemoradiation. Thirty-four patients received concurrent 5-fluorouracil-based chemoradiation (5-FU/RT) with traditional field radiation (range, 45-61.2 Gy; median, 50.4 Gy) without further adjuvant therapy. Thirty patients received traditional field 5-FU/RT (range, 45-60.4 Gy; median, 50.4 Gy) with Gem (1,000 mg/m{sup 2} weekly) either before and after radiotherapy or only after radiotherapy. Twenty-two patients received concurrent full-dose Gem (1,000 mg/m{sup 2} weekly)-based chemoradiation (Gem/RT), consisting of involved-field radiation (range, 27-38 Gy; median, 36 Gy) followed by further adjuvant Gem. Results: The median age of the cohort was 65 years (range, 40-80 years). Of the patients, 58 had T3 tumors (67%), 22 had T2 tumors (26%), and 6 had T1 tumors (7%). N1 disease was present in 61 patients (71%), whereas 18 patients (21%) had R1 resections. Performance status, lymph node status, and margin status were all similar among the treatment groups. Median follow-up was 19.0 months. Median overall survival (OS) (19.2 months, 19.0 months, and 21.0 months) and 3-year OS rates (26.5%, 27.2%, and 32.1%) were similar among patients with 5-FU/RT with no adjuvant Gem, those with 5-FU/RT with adjuvant Gem, and those with Gem/RT with adjuvant Gem, respectively (p = 0.88). Patients who received adjuvant Gem had a similar median OS (22.1 months) and 3-year OS rate (29%) compared to patients who did not (19.2 months and 26.5%, respectively) (p = 0.62). There was a trend for improved 3-year OS rates in patients with R0 vs. R1 resections (28.1% vs. 14.2%, p = 0.06) and in patients with T1 and T2 vs. T3 tumors (38% vs. 20%, p = 0.09). Node-negative patients had an improved 3

  3. Standardizing of Pathology in Patients Receiving Neoadjuvant Chemotherapy.

    PubMed

    Bossuyt, Veerle; Symmans, W Fraser

    2016-10-01

    The use of neoadjuvant systemic therapy for the treatment of breast cancer patients is increasing. Pathologic response in the form of pathologic complete response (pCR) and grading systems of partial response, such as the residual cancer burden (RCB) system, gives valuable prognostic information for patients and is used as a primary endpoint in clinical trials. The breast cancer and pathology communities are responding with efforts to standardize pathology in patients receiving neoadjuvant chemotherapy. In this review, we summarize the challenges that postneoadjuvant systemic therapy surgical specimens pose and how pathologists and the multidisciplinary team can work together to optimize handling of these specimens. Multidisciplinary communication is essential. A single, standardized approach to macroscopic and microscopic pathologic examination makes it possible to provide reliable response information. This approach employs a map of tissue sections to correlate clinical, gross, microscopic, and imaging findings in order to report the presence of pCR (ypT0 ypN0 and ypT0/is ypN0) versus residual disease, the ypT and ypN stage using the current AJCC/UICC staging system, and the RCB.

  4. Current neoadjuvant treatment options for HER2-positive breast cancer

    PubMed Central

    Abdel-Razeq, Hikmat; Marei, Lina

    2011-01-01

    Approximately one quarter of patients with breast cancer demonstrate amplification of the human epidermal receptor type 2 (HER2) gene, the expression of which is associated with a relatively poor prognosis independent of other clinical and pathologic variables. Trastuzumab, a humanized recombinant monoclonal antibody specifically directed against the HER2 receptor, has been shown to be biologically active and of considerable clinical utility in HER2-positive breast cancer patients. Neoadjuvant chemotherapy has been used in breast cancer to downstage the tumor and increase the opportunity for breast-conserving surgery. Preoperative chemotherapy can also serve as an in vivo testing of chemotherapy sensitivity. Additionally, a pathologic complete response is usually a surrogate marker of disease-free survival. Following the successful use of trastuzumab in the metastatic and adjuvant settings, many clinical trials have recently reported the successful use of anti-HER2 therapy in combination with different chemotherapy regimens in the neoadjuvant setting with a significantly higher pathologic complete response. With the recent introduction of new anti-HER2 drugs, interest has shifted toward dual HER2 blockade. Two such studies were recently reported, both showing a significant advantage of dual anti-HER2 therapy using lapatinib or pertuzumab in addition to trastuzumab and chemotherapy. However, several key questions need to be investigated further, such as the preferred combination chemotherapy and the optimal duration of trastuzumab in patients who achieve a pathologic complete response following preoperative chemotherapy with trastuzumab. These issues and others are discussed in this review. PMID:21847344

  5. Neoadjuvant strategies for triple negative breast cancer: 'state-of-the-art' and future perspectives.

    PubMed

    Carbognin, Luisa; Furlanetto, Jenny; Vicentini, Cecilia; Nortilli, Rolando; Pilotto, Sara; Brunelli, Matteo; Pellini, Francesca; Pollini, Giovanni Paolo; Bria, Emilio; Tortora, Giampaolo

    2015-01-01

    Neoadjuvant therapy for triple negative breast cancer (TNBC) has recently generated growing interest given the more aggressive biologic characteristics of such subtype and the lack of approved targeted therapies. Systemic chemotherapy represents the mainstay of treatment for TNBC. Although neoadjuvant chemotherapy has consistently demonstrated higher response rates for TNBC compared to non-TNBC, and the pathological complete response predicts long-term outcome, most patient display residual disease with a higher risk of relapse. In order to improve the outcome of TNBC new chemotherapic combinations, including platinum agents, and different targeted agents such as antiangiogenetics, poly-ADP ribose polymerase (PARP) inhibitors and other small molecule inhibitors are being evaluated in neoadjuvant setting. Currently, the research is ongoing to further characterize TNBC from a phenotypical and molecular perspective, in order to identify potential new target agents and to individualize the treatment. In this regard, the neoadjuvant setting may represent the best potential scenario to assess the activity and the sensitivity of novel agents.

  6. Neoadjuvant and adjuvant chemotherapy approaches for invasive bladder cancer.

    PubMed

    Raghavan, Derek; Burgess, Earle; Gaston, Kris E; Haake, Michael R; Riggs, Steven B

    2012-10-01

    Deeply invasive bladder cancer, representing approximately 20% of incident cases, is cured by radical cystectomy or radiotherapy in less than 50% of cases. In an effort to improve cure rates, based on objective response rates in metastatic disease of 40%-70% from combination chemotherapy regimens, systemic chemotherapy has been incorporated into programs of definitive treatment for this disease. Several randomized trials and a meta-analysis have confirmed a survival benefit from neoadjuvant chemotherapy followed by definitive local treatment, reflecting both median survival figures and cure rates. Despite several promising phase II trials, no randomized trial of classical adjuvant chemotherapy for bladder cancer has demonstrated an overall survival benefit, despite increments in disease-free survival. Molecular prognostication has been studied in an effort to improve the utility of systemic therapy for invasive non-metastatic bladder cancer, but randomized trials have not shown associated survival benefit. Despite level 1 evidence of a survival benefit from neoadjuvant MVAC (methotrexate, vinblastine, doxorubicin [Adriamycin], cisplatin) or cisplatin, methotrexate, and vinblastine (CMV) chemotherapy, more than 50% of incident cases do not receive such treatment.

  7. SOLTI NeoPARP: a phase II randomized study of two schedules of iniparib plus paclitaxel versus paclitaxel alone as neoadjuvant therapy in patients with triple-negative breast cancer

    PubMed Central

    Llombart-Cussac, Antonio; Bermejo, Begoña; Villanueva, Cristian; Delaloge, Suzette; Morales, Serafín; Balmaña, Judith; Amillano, Kepa; Bonnefoi, Hervé; Casas, Ana; Manso, Luis; Roché, Henri; Gonzalez-Santiago, Santiago; Gavilá, Joaquín; Sánchez-Rovira, Pedro; Di Cosimo, Serena; Harbeck, Nadia; Charpentier, Eric; Garcia-Ribas, Ignacio; Radosevic-Robin, Nina; Aura, Claudia; Baselga, Jose

    2016-01-01

    Iniparib is an investigational agent with antitumor activity of controversial mechanism of action. Two previous trials in advanced triple-negative breast cancer (TNBC) in combination with gemcitabine and carboplatin showed some evidence of efficacy that was not confirmed. This phase II randomized neoadjuvant study was designed to explore its activity and tolerability with weekly paclitaxel (PTX) as neoadjuvant treatment in TNBC patients. 141 patients with Stage II–IIIA TNBC were randomly assigned to receive PTX (80 mg/m2, d1; n = 47) alone or in combination with iniparib, either once-weekly (PWI) (11.2 mg/kg, d1; n = 46) or twice-weekly (PTI) (5.6 mg/kg, d1, 4; n = 48) for 12 weeks. Primary endpoint was pathologic complete response (pCR) in the breast. pCR rate was similar among the three arms (21, 22, and 19 % for PTX, PWI, and PTI, respectively). Secondary efficacy endpoints were comparable: pCR in breast and axilla (21, 17, and 19 %); best overall response in the breast (60, 61, and 63 %); and breast conservation rate (53, 54, and 50 %). Slightly more patients in the PTI arm presented grade 3/4 neutropenia (4, 0, and 10 %). Grade 1/2 (28, 22, and 29 %), but no grade 3/4 neuropathy, was observed. There were no differences in serious adverse events and treatment-emergent adverse events leading to treatment discontinuation among the three arms. Addition of iniparib to weekly PTX did not add relevant antitumor activity or toxicity. These results do not support further evaluation of the combination of iniparib at these doses plus paclitaxel in early TNBC. PMID:26536871

  8. SOLTI NeoPARP: a phase II randomized study of two schedules of iniparib plus paclitaxel versus paclitaxel alone as neoadjuvant therapy in patients with triple-negative breast cancer.

    PubMed

    Llombart-Cussac, Antonio; Bermejo, Begoña; Villanueva, Cristian; Delaloge, Suzette; Morales, Serafín; Balmaña, Judith; Amillano, Kepa; Bonnefoi, Hervé; Casas, Ana; Manso, Luis; Roché, Henri; Gonzalez-Santiago, Santiago; Gavilá, Joaquín; Sánchez-Rovira, Pedro; Di Cosimo, Serena; Harbeck, Nadia; Charpentier, Eric; Garcia-Ribas, Ignacio; Radosevic-Robin, Nina; Aura, Claudia; Baselga, Jose

    2015-11-01

    Iniparib is an investigational agent with antitumor activity of controversial mechanism of action. Two previous trials in advanced triple-negative breast cancer (TNBC) in combination with gemcitabine and carboplatin showed some evidence of efficacy that was not confirmed. This phase II randomized neoadjuvant study was designed to explore its activity and tolerability with weekly paclitaxel (PTX) as neoadjuvant treatment in TNBC patients. 141 patients with Stage II-IIIA TNBC were randomly assigned to receive PTX (80 mg/m(2), d1; n = 47) alone or in combination with iniparib, either once-weekly (PWI) (11.2 mg/kg, d1; n = 46) or twice-weekly (PTI) (5.6 mg/kg, d1, 4; n = 48) for 12 weeks. Primary endpoint was pathologic complete response (pCR) in the breast. pCR rate was similar among the three arms (21, 22, and 19 % for PTX, PWI, and PTI, respectively). Secondary efficacy endpoints were comparable: pCR in breast and axilla (21, 17, and 19 %); best overall response in the breast (60, 61, and 63 %); and breast conservation rate (53, 54, and 50 %). Slightly more patients in the PTI arm presented grade 3/4 neutropenia (4, 0, and 10 %). Grade 1/2 (28, 22, and 29 %), but no grade 3/4 neuropathy, was observed. There were no differences in serious adverse events and treatment-emergent adverse events leading to treatment discontinuation among the three arms. Addition of iniparib to weekly PTX did not add relevant antitumor activity or toxicity. These results do not support further evaluation of the combination of iniparib at these doses plus paclitaxel in early TNBC.

  9. Adjuvant Therapy: Treatment to Keep Cancer from Returning

    MedlinePlus

    ... or neoadjuvant therapy doesn't come without a price — the side effects can be more than minor ... chemotherapy. Radiation therapy. Radiation therapy uses high-powered energy beams, such as X-rays, to kill cancer ...

  10. Neoadjuvant imatinib in locally advanced gastrointestinal stromal tumors of the stomach: report of three cases.

    PubMed

    Oh, Ji Seon; Lee, Jae-Lyun; Kim, Mi-Jung; Ryu, Min-Hee; Chang, Heung Moon; Kim, Tae Won; Jang, Se Jin; Yook, Jeong Hwan; Oh, Sung Tae; Kim, Byung Sik; Kang, Yoon-Koo

    2006-01-01

    Neoadjuvant imatinib therapy used to treat locally advanced or metastatic gastrointestinal stromal tumors (GI ST) remains under active investigation. We studied three cases of locally advanced gastric GISTs treated with imatinib on a neoadjuvant basis, followed by a complete surgical resection. Three patients were diagnosed with locally advanced unresectable GIST of the stomach and were started on imatinib 400 mg/day. After the imatinib treatment, partial responses were achieved in all patients and the tumors were considered resectable. Surgical resection was done after 7, 11, and 8 months of imatinib therapy, respectively. In one case, a metastatic liver lesion was detected during the imatinib treatment using computed tomography scans, so the imatinib therapy was maintained for 11 months postoperatively. In the other two patients without distant metastasis, imatinib treatment was not restarted after surgery. Mutational analysis revealed a mutation in exon 11 of the c-kit gene in two patients, and wild-type c-kit and PDGFRA in one patient. During pathology review of all three cases, we noted several features common to imatinib treatment. There was no evidence of tumor recurrence in all three patients at respective follow-up visits of 22, 15, and 7 months. These results suggest that the neoadjuvant imatinib therapy is a potentially curative approach for selected patients with locally advanced GIST.

  11. Neoadjuvant paradigm for accelerated drug development: an ideal model in bladder cancer.

    PubMed

    Chism, David D; Woods, Michael E; Milowsky, Matthew I

    2013-01-01

    Neoadjuvant cisplatin-based combination chemotherapy for muscle-invasive bladder cancer (MIBC) has been shown to confer a survival advantage in two randomized clinical trials and a meta-analysis. Despite level 1 evidence supporting its benefit, utilization remains dismal with nearly one-half of patients ineligible for cisplatin-based therapy because of renal dysfunction, impaired performance status, and/or coexisting medical problems. This situation highlights the need for the development of novel therapies for the management of MIBC, a disease with a lethal phenotype. The neoadjuvant paradigm in bladder cancer offers many advantages for accelerated drug development. First, there is a greater likelihood of successful therapy at an earlier disease state that may be characterized by less genomic instability compared with the metastatic setting, with an early readout of activity with results determined in months rather than years. Second, pre- and post-treatment tumor tissue collection in patients with MIBC is performed as the standard of care without the need for research-directed biopsies, allowing for the ability to perform important correlative studies and to monitor tumor response to therapy in "real time." Third, pathological complete response (pT0) predicts for improved outcome in patients with MIBC. Fourth, there is a strong biological rationale with rapidly accumulating evidence for actionable targets in bladder cancer. This review focuses on the neoadjuvant paradigm for accelerated drug development using bladder cancer as the ideal model.

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

    SciTech Connect

    Kim, Sun Young; Shim, Eun Kyung; Yeo, Hyun Yang; Baek, Ji Yeon; Hong, Yong Sang; Kim, Dae Yong; Kim, Tae Won; Kim, Jee Hyun; Im, Seock-Ah; Jung, Kyung Hae; Chang, Hee Jin

    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 (preoperative 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

  13. Chemoradiation and brachytherapy in biliary tract carcinoma: Long-term results

    SciTech Connect

    Deodato, Francesco . E-mail: fdeodato@rm.unicatt.it; Clemente, Gennaro; Mattiucci, Gian Carlo; Macchia, Gabriella; Costamagna, Guido; Giuliante, Felice; Smaniotto, Daniela; Luzi, Stefano; Valentini, Vincenzo; Mutignani, Massimiliano; Nuzzo, Gennaro; Cellini, Numa; Morganti, Alessio G.

    2006-02-01

    Purpose: To evaluate long-term effects of chemoradiation and intraluminal brachytherapy in terms of local control, disease-free survival, overall survival, and symptom relief in patients with unresectable or residual extrahepatic biliary carcinoma. Methods and Materials: Twenty-two patients with unresectable (17 patients) or residual (5 patients) nonmetastatic extrahepatic bile tumors received external beam radiation therapy (39.6-50.4 Gy) between 1991 and 1997. In 21 patients, 5-fluorouracil (96-h continuous infusion, Days 1-4, 1,000 mg/m{sup 2}/day) was administered. Twelve patients received a boost of intraluminal brachytherapy with {sup 192}Ir wires (30-50 Gy) 1 cm from the source axis. Results: During external beam radiotherapy, 10 patients (45.4%) developed Grade 1 to 2 gastrointestinal toxicity. In patients with unresectable tumor who could be evaluated, the clinical response was 28.6% (4 of 14). Two patients showed complete response. In all 22 patients, median durations of local control, disease-free survival, and overall survival were 44.5 months, 16.3 months, and 23.0 months, respectively. Two patients who received external beam radiation therapy and intraluminal brachytherapy developed late duodenal ulceration. In patients with unresectable tumors, median survival was 13.0 months and 22.0 months in those treated with and without brachytherapy, with 16.7% and no 5-year survival, respectively (p = 0.607). Overall 5-year survival was 18.0%: 40% and 11.7% in patients treated with partial resection and in those with unresectable tumor, respectively (p = 0.135). Conclusion: This study confirmed the role of concurrent chemoradiation in advanced biliary carcinoma; the role of intraluminal brachytherapy boost remains to be further analyzed in larger clinical trials.

  14. Evaluating the Role of Interdigitated Neoadjuvant Chemotherapy and Radiation in the Management of High-Grade Soft-Tissue Sarcoma

    PubMed Central

    Raval, Raju R.; Frassica, Deborah; Thornton, Katherine; Meyer, Christian; Ettinger, David S.; Frassica, Frank; Weber, Kristin; Terezakis, Stephanie A.

    2016-01-01

    Objectives High-grade soft-tissue sarcoma (STS) has a poor prognosis. The goal of this study was to review treatment outcomes of patients with high-grade STS treated with interdigitated neoadjuvant chemotherapy (CT) and radiation at our institution. Materials and Methods Patients with high-grade STS (1997 to 2010) were planned for treatment with 3 cycles of neoadjuvant CT, interdigitated preoperative radiation therapy (44 Gy administered in split courses with a potential 16 Gy postoperative boost), and 3 cycles of postoperative CT. Cancer control outcomes at 3 years were analyzed. Results Sixteen patients with high-grade STS were evaluated. Median age was 53 years, the median longest tumor diameter was 14.6 cm, and median follow-up was 33 months. All 16 patients received 2 or 3 cycles of neoadjuvant CT and all patients completed neoadjuvant RT. The estimated 3-year rate for local control was 100%, disease-free survival 62.5%, and overall survival 73.4%. Conclusions Patients with high-grade STS treated with interdigitated neoadjuvant CT and radiation before surgical resection had excellent rates of local control, along with disease-free survival and overall survival similar to previously published reports. This combined-modality approach continues to have a role in the treatment of patients with high-grade STS. PMID:25268069

  15. Risk based neoadjuvant chemotherapy in muscle invasive bladder cancer

    PubMed Central

    Jayaratna, Isuru S.; Navai, Neema

    2015-01-01

    Muscle invasive bladder cancer (MIBC) is an aggressive disease that frequently requires radical cystectomy (RC) to achieve durable cure rates. Surgery is most effective when performed in organ-confined disease, with the best outcomes for those patients with a pT0 result. The goals of neoadjuvant chemotherapy (NC) are to optimize surgical outcomes for a malignancy with limited adjuvant therapies and a lack of effective salvage treatments. Despite level 1 evidence demonstrating a survival benefit, the utilization of NC has been hampered by several issues, including, the inability to predict responders and the perception that NC may delay curative surgery. In this article, we review the current efforts to identify patients that are most likely to derive a benefit from NC, in order to create a risk-adapted paradigm that reserves NC for those who need it. PMID:26816830

  16. A Review of Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer

    PubMed Central

    Li, Yi; Wang, Ji; Ma, Xiaowei; Tan, Li; Yan, Yanli; Xue, Chaofan; Hui, Beina; Liu, Rui; Ma, Hailin; Ren, Juan

    2016-01-01

    Neoadjuvant chemoradiotherapy has become the standard treatment for locally advanced rectal cancer. Neoadjuvant chemoradiotherapy not only can reduce tumor size and recurrence, but also increase the tumor resection rate and anus retention rate with very slight side effect. Comparing with preoperative chemotherapy, preoperative chemoradiotherapy can further reduce the local recurrence rate and downstage. Middle and low rectal cancers can benefit more from neoadjuvant chemradiotherapy than high rectal cancer. It needs to refine the selection of appropriate patients and irradiation modes for neoadjuvant chemoradiotherapy. Different therapeutic reactions to neoadjuvant chemoradiotherapy affect the type of surgical techniques, hence calling for the need of much attention. Furthermore, many problems such as accurate staging before surgery, selection of suitable neoadjuvant chemoradiotherapy method, and sensitivity prediction to preoperative radiotherapy need to be well settled. PMID:27489505

  17. Celiac Node Failure Patterns After Definitive Chemoradiation for Esophageal Cancer in the Modern Era

    SciTech Connect

    Amini, Arya; Xiao Lianchun; Allen, Pamela K.; Suzuki, Akihiro; Hayashi, Yuki; Liao, Zhongxing; Hofstetter, Wayne; Crane, Christopher; Komaki, Ritsuko; Bhutani, Manoop S.; Lee, Jeffrey H.; Ajani, Jaffer A.; Welsh, James

    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. 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

  18. Predictors and Patterns of Recurrence After Definitive Chemoradiation for Anal Cancer

    SciTech Connect

    Das, Prajnan . E-mail: PrajDas@mdanderson.org; Bhatia, Sumita; Eng, Cathy; Ajani, Jaffer A.; Skibber, John M.; Rodriguez-Bigas, Miguel A.; Chang, George J.; Bhosale, Priya; Delclos, Marc E.; Krishnan, Sunil; Janjan, Nora A.; Crane, Christopher H.

    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 showed 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.

  19. [Neoadjuvant, inductive or adjuvant chemotherapy of bladder cancer].

    PubMed

    Ohlmann, C-H; De Santis, M

    2013-11-01

    Perioperative chemotherapy is a standard treatment for patients with muscle-invasive bladder carcinoma undergoing radical cystectomy; however, direct comparisons of neoadjuvant and adjuvant chemotherapy are lacking. Evidence-based data and implementation into daily clinical practice favor neoadjuvant chemotherapy; nevertheless, neoadjuvant chemotherapy is still underused in daily practice compared to adjuvant chemotherapy. If neoadjuvant chemotherapy has not been used and patients are fit enough to receive cisplatin, adjuvant chemotherapy should be considered in patients with pT3-pT4 and/or lymph node metastases.

  20. [Role of neoadjuvant radiotherapy for rectal cancer : Is MRI-based selection a future model?].

    PubMed

    Kulu, Y; Hackert, T; Debus, J; Weber, M-A; Büchler, M W; Ulrich, A

    2016-07-01

    Following the introduction of total mesorectal excision (TME) in the curative treatment of rectal cancer, the role of neoadjuvant therapy has evolved. By improving the surgical technique the local recurrence rate could be reduced by TME surgery alone to below 8 %. Even if local control was further improved by additional preoperative irradiation this did not lead to a general survival benefit. Guidelines advocate that all patients in UICC stage II and III should be pretreated; however, the stage-based indications for neoadjuvant therapy have limitations. This is mainly attributable to the facts that patients with T3 tumors comprise a very heterogeneous prognostic group and preoperative lymph node diagnostics lack accuracy. In contrast, in recent years the circumferential resection margin (CRM) has become an important prognostic parameter. Patients with tumors that are very close to or infiltrate the pelvic fascia (positive CRM) have a higher rate of local recurrence and poorer survival. With high-resolution pelvic magnetic resonance imaging (MRI) examination in patients with rectal cancer, the preoperative CRM can be determined with a high sensitivity and specificity. Improved T staging and better prediction of the resection margins by pelvic MRI potentially facilitate the selection of patients for study-based treatment strategies omitting neoadjuvant radiotherapy.

  1. Neoadjuvant radiochemotherapy for locally advanced gastric cancer: Long-term results of a phase I trial

    SciTech Connect

    Allal, Abdelkarim S. . E-mail: abdelkarim.allal@hcuge.ch; Zwahlen, Daniel; Bruendler, Marie-Anne; Peyer, Raymond de; Morel, Philippe; Huber, Olivier; Roth, Arnaud D.

    2005-12-01

    Purpose: To assess the long-term results of radiation therapy (RT) when added preoperatively to systemic chemotherapy in patients with locally advanced gastric cancer. Methods and Materials: Patients presenting with T3-4 or N+ gastric cancer received two cycles of cisplatin 100 mg/m{sup 2} d1, 5FU 800 mg/m{sup 2} d1-4, and Leucovorin 60 mg twice daily d1-4; one cycle before and one concomitantly with hyperfractionated RT (median dose, 38.4; range, 31.2-45.6 Gy). All patients underwent a total or subtotal gastrectomy with D2 lymph node resection. Results: Nineteen patients were accrued and 18 completed the neoadjuvant therapeutic program. All patients were subsequently operated and no fatality occurred. At a mean follow-up of 8 years for the surviving patients, no severe late toxicity was observed. The 5-year locoregional control, disease-free, and overall survival were of 85%, 41%, and 35%, respectively. The peritoneum was the most frequent site of relapse. Among long terms survivors, no severe (Radiation Therapy Oncology Group Grade 3-4) late complication was reported. Conclusions: The present neoadjuvant treatment does not seem to increase the operative risk, nor the late side effects. The encouraging locoregional control rate suggests that the neoadjuvant approach should be considered for future trials in locally advanced gastric cancer. Also, the frequency of peritoneal recurrence stresses the need for a more efficient systemic or intraperitoneal treatment.

  2. Neoadjuvant tamoxifen synchronizes ERα binding and gene expression profiles related to outcome and proliferation

    PubMed Central

    Severson, Tesa M.; Nevedomskaya, Ekaterina; Peeters, Justine; Kuilman, Thomas; Krijgsman, Oscar; van Rossum, Annelot; Droog, Marjolein; Kim, Yongsoo; Koornstra, Rutger; Beumer, Inès; Glas, Annuska M.; Peeper, Daniel; Wesseling, Jelle; Simon, Iris M.; Wessels, Lodewyk; Linn, Sabine C.; Zwart, Wilbert

    2016-01-01

    Estrogen receptor alpha (ERα)-positive breast cancers are frequently treated with tamoxifen, but resistance is common. It remains elusive how tamoxifen resistance occurs and predictive biomarkers for treatment outcome are needed. Because most biomarker discovery studies are performed using pre-treatment surgical resections, the effects of tamoxifen therapy directly on the tumor cell in vivo remain unexamined. In this study, we assessed DNA copy number, gene expression profiles and ERα/chromatin binding landscapes on breast tumor specimens, both before and after neoadjuvant tamoxifen treatment. We observed neoadjuvant tamoxifen treatment synchronized ERα/chromatin interactions and downstream gene expression, indicating that hormonal therapy reduces inter-tumor molecular variability. ERα-synchronized sites are associated with dynamic FOXA1 action at these sites, which is under control of growth factor signaling. Genes associated with tamoxifen-synchronized sites are capable of differentiating patients for tamoxifen benefit. Due to the direct effects of therapeutics on ERα behavior and transcriptional output, our study highlights the added value of biomarker discovery studies after neoadjuvant drug exposure. PMID:27129152

  3. Prediction of response to chemoradiation in rectal cancer by a gene polymorphism in the epidermal growth factor receptor promoter region

    SciTech Connect

    Spindler, Karen-Lise Garm . E-mail: kalgsp@vgs.vejleamt.dk; Nielsen, Jens Nederby; Lindebjerg, Jan; Brandslund, Ivan; Jakobsen, Anders

    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-eight 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.

  4. Neoadjuvant chemoradiotherapy followed by surgery in locally advanced squamous cell carcinoma of the vulva.

    PubMed

    Gaudineau, A; Weitbruch, D; Quetin, P; Heymann, S; Petit, T; Volkmar, P; Bodin, F; Velten, M; Rodier, J F

    2012-10-01

    Alternative therapies have been sought to alleviate mutilation and morbidity associated with surgery for vulvar neoplasms. Our prime objective was to assess tumor absence in pathological vulvar and nodal specimens following neoadjuvant chemoradiotherapy in locally advanced vulvar neoplasms. Data were retrospectively collected from January 2001 to May 2009 from 22 patients treated with neoadjuvant therapy for locally advanced squamous cell carcinoma of the vulva. Neoadjuvant treatment consisted of inguino-pelvic radiotherapy (50 Gy) in association with chemotherapy when possible. Surgery occurred at intervals of between 5 to 8 weeks. The median age of patients at diagnosis was 74.1 years. All patients were primarily treated with radiotherapy and 15 received a concomitant chemotherapy. Additionally, all patients underwent radical vulvectomy and bilateral inguino-femoral lymphadenectomy. Tumor absence in the vulvar and nodal pathological specimens was achieved for 6 (27%) patients, while absence in the vulvar pathological specimens was only achieved for 10 (45.4%) patients. Postoperative follow-up revealed breakdown of groin wounds, vulvar wounds and chronic lymphedema in 3 (14.3%), 7 (31.8%) and 14 cases (63.6%), respectively. Within a median follow-up time of 2.3 years [interquartile range (IQR), 0.6-4.6], 12 (54.6%) patients experienced complete remission and 6 cases succumbed to metastatic evolution within a median of 2.2 years (IQR, 0.6-4.6), with 1 case also experiencing perineal recurrence. Median survival time, estimated using the Kaplan-Meier method, was 5.1 years (IQR, 1.0-6.8). We suggest that neoadjuvant chemoradiotherapy may represent a reliable and promising strategy in locally advanced squamous cell carcinoma of the vulva.

  5. Neoadjuvant chemoradiotherapy followed by surgery in locally advanced squamous cell carcinoma of the vulva

    PubMed Central

    GAUDINEAU, A.; WEITBRUCH, D.; QUETIN, P.; HEYMANN, S.; PETIT, T.; VOLKMAR, P.; BODIN, F.; VELTEN, M.; RODIER, J.F.

    2012-01-01

    Alternative therapies have been sought to alleviate mutilation and morbidity associated with surgery for vulvar neoplasms. Our prime objective was to assess tumor absence in pathological vulvar and nodal specimens following neoadjuvant chemoradiotherapy in locally advanced vulvar neoplasms. Data were retrospectively collected from January 2001 to May 2009 from 22 patients treated with neoadjuvant therapy for locally advanced squamous cell carcinoma of the vulva. Neoadjuvant treatment consisted of inguino-pelvic radiotherapy (50 Gy) in association with chemotherapy when possible. Surgery occurred at intervals of between 5 to 8 weeks. The median age of patients at diagnosis was 74.1 years. All patients were primarily treated with radiotherapy and 15 received a concomitant chemotherapy. Additionally, all patients underwent radical vulvectomy and bilateral inguino-femoral lymphadenectomy. Tumor absence in the vulvar and nodal pathological specimens was achieved for 6 (27%) patients, while absence in the vulvar pathological specimens was only achieved for 10 (45.4%) patients. Postoperative follow-up revealed breakdown of groin wounds, vulvar wounds and chronic lymphedema in 3 (14.3%), 7 (31.8%) and 14 cases (63.6%), respectively. Within a median follow-up time of 2.3 years [interquartile range (IQR), 0.6–4.6], 12 (54.6%) patients experienced complete remission and 6 cases succumbed to metastatic evolution within a median of 2.2 years (IQR, 0.6–4.6), with 1 case also experiencing perineal recurrence. Median survival time, estimated using the Kaplan-Meier method, was 5.1 years (IQR, 1.0–6.8). We suggest that neoadjuvant chemoradiotherapy may represent a reliable and promising strategy in locally advanced squamous cell carcinoma of the vulva. PMID:23205089

  6. Gene Expression Characterization of HPV Positive Head and Neck Cancer to Predict Response to Chemoradiation.

    PubMed

    Thibodeau, Bryan J; Geddes, Timothy J; Fortier, Laura E; Ahmed, Samreen; Pruetz, Barbara L; Wobb, Jessica; Chen, Peter; Wilson, George D; Akervall, Jan A

    2015-09-01

    Human papillomavirus (HPV) has been shown to have a causal role in the development of head and neck squamous cell carcinoma. While HPV-positive head and neck cancer is associated with a better response to treatment in the majority of patients, there is a subset who does not respond favorably to current therapy. Identification of these patients could prevent unnecessary morbidity and indicate the need for alternative therapeutic options. Tissue samples were obtained from 19 patients with HPV-positive head and neck squamous carcinoma treated with chemoradiation therapy. HPV status was confirmed by polymerase chain reaction analysis through detection of HPV16 E7 in both DNA and RNA. RNA was isolated from tissue samples and subjected to microarray gene expression analysis. In addition to identification of potential genetic biomarkers (including LCE3D, KRTDAP, HMOX1, KRT19, MDK, TSPAN1), differentially expressed genes associated with genomic stability, cell cycle, and DNA damage were detected between responders and non-responders. These results were further validated with publicly available gene expression studies. This pilot study suggests prospective biomarkers that predict response to therapy. The importance of genes involved with genomic stability is highlighted in both development and progression of head and neck squamous cell carcinoma but also recurrence. Potential development of an assay may prove beneficial to clinicians, assisting them to provide alternative care sooner thus lowering morbidity.

  7. Radiation Therapy Oncology Group 0247: A Randomized Phase II Study of Neoadjuvant Capecitabine and Irinotecan or Capecitabine and Oxaliplatin With Concurrent Radiotherapy for Patients With Locally Advanced Rectal Cancer

    SciTech Connect

    Wong, Stuart J.; Winter, Kathryn; Meropol, Neal J.; Anne, Pramila Rani; Kachnic, Lisa; Rashid, Asif; Watson, James C.; Mitchell, Edith; Pollock, Jondavid; Lee, Robert Jeffrey; Haddock, Michael; Erickson, Beth A.; Willett, Christopher G.

    2012-03-15

    Purpose: To evaluate the rate of pathologic complete response (pCR) and the toxicity of two neoadjuvant chemoradiotherapy (chemoRT) regimens for Stage T3-T4 rectal cancer in a randomized Phase II study. Methods and Materials: Patients with Stage T3 or T4 rectal cancer of <12 cm from the anal verge were randomized to preoperative RT (50.4 Gy in 1.8-Gy fractions) with concurrent capecitabine (1,200 mg/m{sup 2}/d Mondays through Friday) and irinotecan (50 mg/m{sup 2} weekly in four doses) (Arm 1) or concurrent capecitabine (1,650 mg/m{sup 2}/d Monday through Friday) and oxaliplatin (50 mg/m{sup 2} weekly in five doses) (Arm 2). Surgery was performed 4-8 weeks after chemoRT, and adjuvant chemotherapy 4-6 weeks after surgery. The primary endpoint was the pCR rate, requiring 48 evaluable patients per arm. Results: A total of 146 patients were enrolled. The protocol chemotherapy was modified because of excessive gastrointestinal toxicity after treatment of 35 patients; 96 were assessed for the primary endpoint-the final regimen described above. The patient characteristics were similar for both arms. After chemoRT, the rate of tumor downstaging was 52% and 60% and the rate of nodal downstaging (excluding N0 patients) was 46% and 40%, for Arms 1 and 2, respectively. The pCR rate for Arm 1 was 10% and for Arm 2 was 21%. For Arm 1 and 2, the preoperative chemoRT rate of Grade 3-4 hematologic toxicity was 9% and 4% and the rate of Grade 3-4 nonhematologic toxicity was 26% and 27%, respectively. Conclusions: Preoperative chemoRT with capecitabine plus oxaliplatin for distal rectal cancer has significant clinical activity (10 of 48 pCRs) and acceptable toxicity. This regimen is currently being evaluated in a Phase III randomized trial (National Surgical Adjuvant Breast and Bowel Project R04).

  8. The proportion of signet ring cell component in patients with localized gastric adenocarcinoma correlates with the degree of response to preoperative chemoradiation

    PubMed Central

    Charalampakis, Nikolaos; Nogueras González, Graciela M.; Elimova, Elena; Wadhwa, Roopma; Shiozaki, Hironori; Shimodaira, Yusuke; Blum, Mariela A.; Rogers, Jane E.; Harada, Kazuto; Matamoros, Aurelio; Sagebiel, Tara; Das, Prajnan; Minsky, Bruce D.; Lee, Jeffrey H.; Weston, Brian; Bhutani, Manoop S.; Estrella, Jeannelyn S.; Badgwell, Brian D.; Ajani, Jaffer A.

    2016-01-01

    Background Patients with localized gastric adenocarcinoma (LGAC), who get preoperative therapy, have heterogeneous/unpredictable outcomes. Predictive clinical variables/biomarkers are not established. Methods We analyzed 107 LGAC patients who had chemoradiation and surgery. LGACs were grouped for: (1) presence/absence of signet ring cell histology (SRC) and (2) histologic grade: G2 or G3. %SRC were assessed (0%, 1–10%, 11–49%, and 50–100%) and correlated with pathologic complete response (pathCR) or chemoradiation (93%). Most had G3 tumors (78%) and SRC (58%). Presence of SRC was associated with a lower rate of pathCR (11% vs. 36%, p=0.004) and the association remained significant even with low percentage of SRC (1–10%; p=0.014). Higher the fraction of SRC, the lower was the probability of pathCR (p=0.03). G3 and SRC led to shorter overall survival (OS) (p=0.046 and p=0.038, respectively). Yp stage independently prognosticated OS and recurrence-free survival (p<0.001). Conclusion Our novel findings suggest that LGACs with SRC are relatively chemoradiation resistant compared to LGACs without SRC. A higher fraction of SRC is associated with higher resistance. Upon validation/biomarker(s) evaluation, reporting of the fraction of SRC may be warranted. PMID:27046280

  9. Analysis of Clinical and Dosimetric Factors Associated With Change in Renal Function in Patients With Gastrointestinal Malignancies After Chemoradiation to the Abdomen

    SciTech Connect

    May, Kilian Salerno; Khushalani, Nikhil I.; Chandrasekhar, Rameela; Wilding, Gregory E.; Iyer, Renuka V.; Ma, Wen W.; Flaherty, Leayn; Russo, Richard C. C.; Fakih, Marwan; Kuvshinoff, Boris W.; Gibbs, John F.; Javle, Milind M.; Yang, Gary Y.

    2010-03-15

    Purpose: To analyze clinical and dosimetric factors associated with change in renal function in patients with gastrointestinal malignancies after chemoradiation to the abdomen. Methods and Materials: A retrospective review of 164 patients with gastrointestinal malignancies treated between 2002 and 2007 was conducted to evaluate change in renal function after concurrent chemotherapy and three-dimensional conformal abdominal radiotherapy (RT). Laboratory and biochemical endpoints were determined before RT and after RT at 6-month intervals. Factors assessed included smoking, diabetes, hypertension, blood urea nitrogen, creatinine, creatinine clearance (CrCl), chemotherapy, and dose-volume parameters. Renal toxicity was assessed by decrease in CrCl and scored using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late radiation morbidity scoring schema. Results: Of 164 patients, 63 had clinical and dosimetric data available. Median follow-up was 17.5 months. Creatinine clearance declined from 98.46 mL/min before RT to 74.20 mL/min one year after chemoradiation (p < 0.0001). Mean decrease in CrCl was 21.37%. Pre-RT CrCl, percentage of bilateral renal volume receiving at least 10 Gy (V{sub 10}), and mean kidney dose were significantly associated with development of Grade >=2 renal complications at 1 year after chemoradiation (p = 0.0025, 0.0170, and 0.0095, respectively). Conclusions: We observed correlation between pre-RT CrCl, V{sub 10}, and mean kidney dose and decline in CrCl 1 year after chemoradiation. These observations can assist in treatment planning and renal dose constraints in patients receiving chemotherapy and abdominal RT and may help identify patients at increased risk for renal complications.

  10. Haemoglobin levels may predict toxicities in patients on pelvic chemoradiation for carcinoma of the cervix—experience of a regional cancer centre

    PubMed Central

    Gangopadhyay, Aparna; Das, Joydeep; Nath, Partha; Biswas, Jaydip

    2014-01-01

    Background Haemoglobin levels and tissue oxygenation influence tumour outcome in carcinoma cervix radiotherapy. The clinical impact of haemoglobin levels on acute normal tissue toxicity during radiation and interaction with chemotherapy in carcinoma of the cervix is underexplored. This paper aims to explore this issue. Methods Treatment toxicity among 227 patients with squamous cell carcinoma of the cervix stages II B–IV A, receiving pelvic radiotherapy or chemoradiation at our institute, were studied prospectively. The baseline and weekly haemoglobin levels during treatment were recorded. Acute toxicities were recorded using Radiation Therapy Oncology Group (RTOG) acute toxicity and Common Terminology Criteria for Adverse Events (CTCAE) criteria, version 4. For the analysis, patients were divided into two groups, depending on nadir haemoglobin levels. A cut-off value for anaemia was selected at 12 gm/dL. Toxicity was compared between anaemic and non-anaemic groups. Results Patients on chemoradiation and having haemoglobin levels >12 gm/dL suffered significantly higher dermatitis (two-tailed p value = 0.0288) and vaginal mucositis (two-tailed p value = 0.0187) of at least RTOG acute toxicity grade 2, compared with the anaemic group. In contrast patients receiving radiotherapy alone did not experience any significantly greater mucocutaneous toxicity if haemoglobin was >12 gm/dL. Anaemia had significantly greater impact on malaise and neutropenia (two-tailed p value <0.0001) of CTCAE grade 1 and above among chemoradiation patients, as opposed to those receiving radiotherapy alone (two-tailed p values = 0.0012 for neutropenia and 0.0422 for malaise). Conclusion Haemoglobin values >12 gm/dL significantly worsen acute mucocutaneous toxicity in locally advanced cervical cancer patients receiving chemoradiation. Similar effects are not observed in the absence of chemotherapy. PMID:24963348

  11. PSA bounces after neoadjuvant androgen deprivation and external beam radiation: Impact on definitions of failure

    SciTech Connect

    Zietman, Anthony L. . E-mail: azietman@partners.org; Christodouleas, John P.; Shipley, William U.

    2005-07-01

    Purpose: To determine the characteristics of prostate specific antigen (PSA) bounces after external beam radiation therapy (EBRT) with neoadjuvant androgen deprivation and their impact on definitions of biochemical failure. Methods and Materials: Characteristics of bounce were calculated for all patients treated by EBRT with neoadjuvant androgen deprivation at our institution between 1992 and 1998 (preexclusion analysis). Calculations were repeated for the subgroup that satisfied additional inclusion/exclusion criteria (postexclusion analysis). The percentage of bounces scoring as false positives according to the ASTRO definition of biochemical failure was compared with those for three alternative definitions (Vancouver, Nadir-plus-two, and Nadir-plus-three) using McNemar's tests. Results: Thirty-nine percent (preexclusion cohort) and 56% (postexclusion cohort) of patients demonstrated a PSA bounce. Twenty percent (preexclusion analysis) and 25% (postexclusion analysis) of these bounces scored as biochemical failure according to the ASTRO definition. The Nadir-plus-three definition scored the smallest percentage of bounces as failure, but the difference between this definition and the ASTRO definition reached statistical significance in neither preexclusion nor postexclusion analyses (p {>=} 0.070). Conclusions: A substantial proportion of patients treated by EBRT with neoadjuvant deprivation experienced a PSA bounce. A large percentage of these bounces scored as biochemical failure according to the ASTRO definition. The Nadir-plus-three definition is less vulnerable to this bias.

  12. Neoadjuvant chemotherapy with trastuzumab in HER2-positive breast cancer: pathologic complete response rate, predictive and prognostic factors

    PubMed Central

    Buzatto, I.P.C.; Ribeiro-Silva, A.; Andrade, J.M.; Carrara, H.H.A.; Silveira, W.A.; Tiezzi, D.G.

    2017-01-01

    The purpose of this study was to retrospectively review the pathologic complete response (pCR) rate from patients (n=86) with stage II and III HER2-positive breast cancer treated with neoadjuvant chemotherapy at our institution from 2008 to 2013 and to determine possible predictive and prognostic factors. Immunohistochemistry for hormone receptors and Ki-67 was carried out. Clinical and pathological features were analyzed as predictive factors of response to therapy. For survival analysis, we used Kaplan-Meier curves to estimate 5-year survival rates and the log-rank test to compare the curves. The addition of trastuzumab to neoadjuvant chemotherapy significantly improved pCR rate from 4.8 to 46.8%, regardless of the number of preoperative trastuzumab cycles (P=0.0012). Stage II patients achieved a higher response rate compared to stage III (P=0.03). The disease-free and overall survivals were not significantly different between the group of patients that received trastuzumab in the neoadjuvant setting (56.3 and 70% at 5 years, respectively) and the group that initiated it post-operatively (75.8 and 88.7% at 5 years, respectively). Axillary pCR post neoadjuvant chemotherapy with trastuzumab was associated with reduced risk of recurrence (HR=0.34; P=0.03) and death (HR=0.21; P=0.02). In conclusion, we confirmed that trastuzumab improves pCR rates and verified that this improvement occurs even with less than four cycles of the drug. Hormone receptors and Ki-67 expressions were not predictive of response in this subset of patients. Axillary pCR clearly denotes prognosis after neoadjuvant target therapy and should be considered to be a marker of resistance, providing an opportunity to investigate new strategies for HER2-positive treatment. PMID:28146217

  13. Cetuximab With Concurrent Chemoradiation for Esophagogastric Cancer: Assessment of Toxicity

    SciTech Connect

    Safran, Howard Suntharalingam, Mohan; Dipetrillo, Thomas; Ng, Thomas; Doyle, L. Austin; Krasna, Mark; Plette, Angela; Evans, Devon; Wanebo, Harold; Akerman, Paul; Spector, Jeremy; Kennedy, Nancy; Kennedy, Teresa

    2008-02-01

    Purpose: To determine the feasibility and toxicity of the addition of cetuximab with paclitaxel, carboplatin, and radiation for patients with esophagogastric cancer on a Phase II study. Methods and Materials: Patients with locoregional esophageal and proximal gastric cancer without distant organ metastases were eligible. All patients received cetuximab, paclitaxel, and carboplatin weekly for 6 weeks with 50.4 Gy radiation. Results: Sixty patients were enrolled, 57 with esophageal cancer and 3 with gastric cancer. Forty-eight had adenocarcinoma and 12 had squamous cell cancer. Fourteen of 60 patients (23%) had Grade 3 dermatologic toxicity consisting of a painful, pruritic acneiform rash on the face outside of the radiation field. The rates of Grades 3 and 4 esophagitis were 12% and 3%, respectively. Three patients had Grade 3/4 cetuximab hypersensitivity reactions and were not assessable for response. Forty of 57 patients (70%) had a complete clinical response after chemoradiation. Conclusion: Cetuximab can be safely administered with chemoradiation for esophageal cancer. Dermatologic toxicity and hypersensitivity reactions were associated with the addition of cetuximab. There was no increase in esophagitis or other radiation-enhanced toxicity.

  14. Neoadjuvant Treatment in Rectal Cancer: Actual Status

    PubMed Central

    Garajová, Ingrid; Di Girolamo, Stefania; de Rosa, Francesco; Corbelli, Jody; Agostini, Valentina; Biasco, Guido; Brandi, Giovanni

    2011-01-01

    Neoadjuvant (preoperative) concomitant chemoradiotherapy (CRT) has become a standard treatment of locally advanced rectal adenocarcinomas. The clinical stages II (cT3-4, N0, M0) and III (cT1-4, N+, M0) according to International Union Against Cancer (IUCC) are concerned. It can reduce tumor volume and subsequently lead to an increase in complete resections (R0 resections), shows less toxicity, and improves local control rate. The aim of this review is to summarize actual approaches, main problems, and discrepancies in the treatment of locally advanced rectal adenocarcinomas. PMID:22295206

  15. Evaluation of a Marker Clip System in Sonographically Guided Core Needle Biopsy for Breast Cancer Localization Before and After Neoadjuvant Chemotherapy

    PubMed Central

    Schulz-Wendtland, R.; Dankerl, P.; Bani, M. R.; Fasching, P. A.; Heusinger, K.; Lux, M. P.; Jud, S. M.; Rauh, C.; Bayer, C. M.; Schrauder, M. G.; Beckmann, M. W.; Uder, M.; Brehm, B.; Loehberg, C. R.

    2017-01-01

    Introduction The placement of intramammary marker clips has proven to be helpful for tumor localization in patients undergoing neoadjuvant chemotherapy and breast-conserving surgery. The purpose of our study was to investigate the feasibility of using a clip marker system for breast cancer localization and its influence on the imaging assessment of treatment responses after neoadjuvant chemotherapy. Patients and Methods Between March and June 2015, a total of 25 patients (n = 25), with a suspicion of invasive breast cancer with diameters of at least 2 cm (cT2), underwent preoperative sonographically guided core needle biopsy using a single-use breast biopsy system (HistoCore™) and intramammary clip marking using a directly adapted clip system based on the established O-Twist Marker™, before their scheduled preoperative neoadjuvant chemotherapy. Localization of the intramammary marker clip was controlled by sonography and digital breast tomosynthesis. Results Sonography detected no dislocation of intrammammary marker clips in 20 of 25 patients (80 %), while digital breast tomosynthesis showed accurate placement without dislocation in 24 patients (96 %) (p < 0.05). There was no evidence of significant clip migration during preoperative follow-up imaging after neoadjuvant chemotherapy. No complication related to the clip marking was noted and there was no difficulty in evaluating the treatment response to neoadjuvant chemotherapy. Among the breast-conserving surgeries performed, no cases were identified in which intraoperative loss of the marker clip had occurred. Conclusion Our study underscores the importance of intramammary marking clip systems before neoadjuvant chemotherapy. Placement of marker clips is advised to facilitate accurate tumor bed localization. With regard to digital breast tomosynthesis, its development continues to improve the quality of diagnostics and the therapy of breast cancer particularly for small breast cancer tumors or in

  16. Intensity-modulated radiotherapy for neoadjuvant treatment of gastric cancer

    SciTech Connect

    Knab, Brian; Rash, Carla; Farrey, Karl; Jani, Ashesh B. . E-mail: jani@rover.uchicago.edu

    2006-01-01

    Radiation therapy plays an integral role in the treatment of gastric cancer in the postsurgery setting, the inoperable/palliative setting, and, as in the case of the current report, in the setting of neoadjuvant therapy prior to surgery. Typically, anterior-posterior/posterior-anterior (AP/PA) or 3-field techniques are used. In this report, we explore the use of intensity-modulated radiotherapy (IMRT) treatment in a patient whose care was transferred to our institution after 3-field radiotherapy (RT) was given to a dose of 30 Gy at an outside institution. If the 3-field plan were continued to 50 Gy, the volume of irradiated liver receiving greater than 30 Gy would have been unacceptably high. To deliver the final 20 Gy, an opposed parallel AP/PA plan and an IMRT plan were compared to the initial 3-field technique for coverage of the target volume as well as dose to the kidneys, liver, small bowel, and spinal cord. Comparison of the 3 treatment techniques to deliver the final 20 Gy revealed reduced median and maximum dose to the whole kidney with the IMRT plan. For this 20-Gy boost, the volume of irradiated liver was lower for both the IMRT plan and the AP/PA plan vs. the 3-field plan. Comparing the IMRT boost plan to the AP/PA boost-dose range (<10 Gy) in comparison to the AP/PA plan; however, the IMRT plan irradiated a smaller liver volume within the higher dose region (>10 Gy) in comparison to the AP/PA plan. The IMRT boost plan also irradiated a smaller volume of the small bowel compared to both the 3-field plan and the AP/PA plan, and also delivered lower dose to the spinal cord in comparison to the AP/PA plan. Comparison of the composite plans revealed reduced dose to the whole kidney using IMRT. The V20 for the whole kidney volume for the composite IMRT plan was 30% compared to approximately 60% for the composite AP/PA plan. Overall, the dose to the liver receiving greater than 30 Gy was lower for the composite IMRT plan and was well below acceptable limits

  17. Evaluation of Neoadjuvant Chemotherapy Response in Women with Locally Advanced Breast Cancer Using Ultrasound Elastography1

    PubMed Central

    Falou, Omar; Sadeghi-Naini, Ali; Prematilake, Sameera; Sofroni, Ervis; Papanicolau, Naum; Iradji, Sara; Jahedmotlagh, Zahra; Lemon-Wong, Sharon; Pignol, Jean-Philippe; Rakovitch, Eileen; Zubovits, Judit; Spayne, Jacqueline; Dent, Rebecca; Trudeau, Maureen; Boileau, Jean Francois; Wright, Frances C; Yaffe, Martin J; Czarnota, Gregory J

    2013-01-01

    PURPOSE: Ultrasound elastography is a new imaging technique that can be used to assess tissue stiffness. The aim of this study was to investigate the potential of ultrasound elastography for monitoring treatment response of locally advanced breast cancer patients undergoing neoadjuvant therapy. METHODS: Fifteen women receiving neoadjuvant chemotherapy had the affected breast scanned before, 1, 4, and 8 weeks following therapy initiation, and then before surgery. Changes in elastographic parameters related to tissue biomechanical properties were then determined and compared to clinical and pathologic tumor response after mastectomy. RESULTS: Patients who responded to therapy demonstrated a significant decrease (P < .05) in strain ratios and strain differences 4 weeks after treatment initiation compared to non-responding patients. Mean strain ratio and mean strain difference for responders was 81 ± 3% and 1 ± 17% for static regions of interest (ROIs) and 81 ± 3% and 6 ± 18% for dynamic ROIs, respectively. In contrast, these parameters were 102±2%, 110±17%, 101±4%, and 109±30% for non-responding patients, respectively. Strain ratio using static ROIs was found to be the best predictor of treatment response, with 100% sensitivity and 100% specificity obtained 4 weeks after starting treatment. CONCLUSIONS: These results suggest that ultrasound elastography can be potentially used as an early predictor of tumor therapy response in breast cancer patients. PMID:23418613

  18. The Effect of Biofeedback Therapy on Anorectal Function After the Reversal of Temporary Stoma When Administered During the Temporary Stoma Period in Rectal Cancer Patients With Sphincter-Saving Surgery: The Interim Report of a Prospective Randomized Controlled Trial.

    PubMed

    Kye, Bong-Hyeon; Kim, Hyung-Jin; Kim, Gun; Yoo, Ri Na; Cho, Hyeon-Min

    2016-05-01

    We evaluated the effect of biofeedback therapy (BFT) on anorectal function after stoma closure when administered during the interval of temporary stoma after sphincter-preserving surgery for rectal cancer.Impaired anorectal function is common after lower anterior resections, though no specific treatment options are currently available to prevent this adverse outcome.Fifty-six patients who underwent neoadjuvant chemoradiation therapy after sphincter-preserving surgery with temporary stoma were randomized into 2 groups: group 1 (received BFT during the temporary stoma period) and group 2 (did not receive BFT). To evaluate anorectal function, anorectal manometry was performed in all patients and subjective symptoms were evaluated using the Cleveland Clinic Incontinence Score. The present study is a report at 6 months after rectal resection.Forty-seven patients, including 21 in group 1 and 26 in group 2, were evaluated by anorectal manometry. Twelve patients (57.1%) in group 1 and 13 patients (50%) in group 2 were scored above 9 points of Cleveland Clinic Incontinence Score, which is the reference value for fecal incontinence (P = 0.770). With time, there was a significant difference (P = 0.002) in the change of mean resting pressure according to time sequence between the BFT and control groups.BFT during the temporary stoma interval had no effect on preventing anorectal dysfunction after temporary stoma reversal at 6 months after rectal resection. However, BFT might be helpful for maintaining resting anal sphincter tone (NCT01661829).

  19. The Effect of Biofeedback Therapy on Anorectal Function After the Reversal of Temporary Stoma When Administered During the Temporary Stoma Period in Rectal Cancer Patients With Sphincter-Saving Surgery

    PubMed Central

    Kye, Bong-Hyeon; Kim, Hyung-Jin; Kim, Gun; Yoo, Ri Na; Cho, Hyeon-Min

    2016-01-01

    Abstract We evaluated the effect of biofeedback therapy (BFT) on anorectal function after stoma closure when administered during the interval of temporary stoma after sphincter-preserving surgery for rectal cancer. Impaired anorectal function is common after lower anterior resections, though no specific treatment options are currently available to prevent this adverse outcome. Fifty-six patients who underwent neoadjuvant chemoradiation therapy after sphincter-preserving surgery with temporary stoma were randomized into 2 groups: group 1 (received BFT during the temporary stoma period) and group 2 (did not receive BFT). To evaluate anorectal function, anorectal manometry was performed in all patients and subjective symptoms were evaluated using the Cleveland Clinic Incontinence Score. The present study is a report at 6 months after rectal resection. Forty-seven patients, including 21 in group 1 and 26 in group 2, were evaluated by anorectal manometry. Twelve patients (57.1%) in group 1 and 13 patients (50%) in group 2 were scored above 9 points of Cleveland Clinic Incontinence Score, which is the reference value for fecal incontinence (P = 0.770). With time, there was a significant difference (P = 0.002) in the change of mean resting pressure according to time sequence between the BFT and control groups. BFT during the temporary stoma interval had no effect on preventing anorectal dysfunction after temporary stoma reversal at 6 months after rectal resection. However, BFT might be helpful for maintaining resting anal sphincter tone (NCT01661829). PMID:27149496

  20. Preoperative hyperfractionated chemoradiation for locally recurrent rectal cancer in patients previously irradiated to the pelvis: A multicentric phase II study

    SciTech Connect

    Valentini, Vincenzo . E-mail: vvalentini@rm.unicatt.it; Morganti, Alessio G.; Gambacorta, M. Antonietta; Mohiuddin, Mohammed; Doglietto, G. Battista; Coco, Claudio; De Paoli, Antonino; Rossi, Carlo; Di Russo, Annamaria; Valvo, Francesca; Bolzicco, Giampaolo; Dalla Palma, Maurizio

    2006-03-15

    -classification (F0: no side-wall involvement; F1, F2, F3: 1, 2, and 3-4 side-walls involved, respectively). Toxicity was evaluated on the basis of the Radiation Therapy Oncology Group (RTOG) criteria. Results: Fifty-nine patients (38 male, 21 female; median age, 62 years; range, 43-77 years) were enrolled in the study, by 12 different Italian radiotherapy departments. Previous surgery was anterior resection in 45 patients (76.3%) and abdominal-perineal resection in 14 patients (23.7%); previous radiotherapy dosage ranged between 30 and 55 Gy (median, 50.4 Gy); the median interval between prior radiation therapy to the onset of reirradiation was 27 months (range, 9-106 months); 44 patients (74.6%) had received some form of previous chemotherapy (concurrent and/or adjuvant). Fifty-one of 59 patients (86.4%) completed chemoradiation without treatment interruptions: 6 patients (10.2%) had temporary treatment interruption due to toxicity or patient compliance, and 2 patients (3.4%) had definitive treatment interruption. The incidence of Grade 3 lower gastrointestinal acute toxicity was only 5.1%. No patient developed Grade 4 acute toxicity. After chemoradiation, 5 patients (8.5%) had complete response (CR), 21 patients (35.6%) had partial response (PR), 31 patients (52.6%) had no change (NC) and 2 patients (3.4%) showed progressive disease (PD). Overall, the response rate (PR + CR) was 44.1% (95% confidence interval, 29.0-58.9%). Twenty of 24 patients (83.3%) with pelvic pain before treatment had symptomatic response. Tumor resection was performed in 30 of 59 patients (50.8%) including 2 local excisions, 4 anterior resections, 18 abdominoperineal resections, and 6 other. Surgical resection resulted as R0 and R1 in 21 patients (35.6%) and 3 patients (5.1%), respectively. The possibility of radical resection was influenced by tumor response to chemoradiation (PD/NC: 7/33; PR/CR: 14/26; p = 0.009). Thirty-three patients received adjuvant chemotherapy, which was completed in 30 (50.8%). At

  1. Preoperative Chemoradiation for Rectal Cancer Using Capecitabine and Celecoxib Correlated With Posttreatment Assessment of Thymidylate Synthase and Thymidine Phosphorylase Expression

    SciTech Connect

    Unger, Keith R.; Romney, Davis A.; Koc, Mehmet; Moskaluk, Christopher A.; Friel, Charles M.; Foley, E.F.; Rich, Tyvin A.

    2011-08-01

    Purpose: Thymidylate synthase (TS) and thymidine phosphorylase (TP) expression have been shown to be predictors of response to therapy. The toxicity, efficacy, surgical morbidity, and immunohistochemical TS and TP expression were assessed in surgical resection specimens after preoperative chemoradiation. Methods and Materials: Twenty patients with clinical stage I to III rectal adenocarcinoma received preoperative chemoradiation and underwent surgical resection 6 weeks later. Results: Posttreatment tumor stages were T1 to T2 and N0 in 30% of patients; T3 to T4 and N0 in 30% of patients; and T1 to T3 and N1 to N2 in 15% of patients. Pathologic complete response (pCR) was evident in 25% and tumor regression occurred in a total of 80% of patients. Anal sphincter-sparing surgery was performed in 80% of cases. Acute and perioperative complications were minimal, with no grade 3/4 toxicity or treatment breaks. Pelvic control was obtained in 90% of patients. With a median follow-up of 65.5 months (range, 8-80 months), the 6-year actuarial survival rate was 75%. Local failure was significantly associated with nonresponse to therapy and with high TS and low TP expression (p = 0.008 and p = 0.04, respectively). Conclusions: The combination of capecitabine, celecoxib, and x-radiation therapy yields excellent response: a 25% pathologic pCR, no acute grade 3/4 toxicity, and minimal surgical morbidity. Nonresponders expressed significantly increased TS levels and decreased TP levels in posttreatment resection specimens compared to responders.

  2. Expense and benefit of neoadjuvant treatment in squamous cell carcinoma of the esophagus

    PubMed Central

    Heise, Joachim W; Heep, Hansjörg; Frieling, Thomas; Sarbia, Mario; Hartmann, Karl A; Röher, Hans-Dietrich

    2001-01-01

    Background The effectiveness of neoadjuvant treatment (NT) prior to resection of squamous cell carcinoma of the esophagus (SCCE) in terms of prolonged survival has not been proven by randomized trials. Facing considerable financial expenses and with concerns regarding the consumption of the patient's remaining survival time, this study aims to provide rationales for pretreating resection candidates. Methods From March 1986 to March 1999, patients undergoing resection for SCCE were documented prospectively. Since 1989, NT was offered to patients with mainly upper and middle third T3 or T4 tumors or T2 N1 stage who were fit for esophagectomy. Until 1993, NT consisted of chemotherapy. Since that time chemoradiation has also been applied. The parameters for expense and benefit of NT are costs, pretreatment time required, postoperative morbidity and mortality, clinical and histopathological response, and actuarial survival. Results Two hundred and three patients were treated, 170 by surgery alone and 33 by NT + surgery. Postoperative morbidity and mortality were 52% to 30% and 12% to 6%, respectively (p = n.s.). The response to NT was detected in 23 patients (70%). In 11 instances (33%), the primary tumor lesion was histopathologically eradicated. Survival following NT + surgery was significantly prolonged in node-positive patients with a median survival of 12 months to 19 months (p = 0.0193). The average pretreatment time was 113 ± 43 days, and reimbursement for NT to the hospital amounted to Euro 9.834. Conclusions NT did not increase morbidity and mortality. Expenses for pretreatment, particularly time and costs, are considerable. However, taking into account that the results are derived from a non-randomized study, patients with regionally advanced tumor stages seem to benefit, as seen by their prolonged survival. PMID:11737874

  3. Future of therapy for rectal cancer.

    PubMed

    Minsky, Bruce D

    2013-06-01

    Since 2004, the standard of care for patients with cT3 and/or N+ rectal cancer has been preoperative chemoradiation followed by surgery and postoperative adjuvant chemotherapy. A number of advances have occurred and are defining the future of rectal cancer therapy. Among these are short course radiation, the impact of postoperative adjuvant chemotherapy, selective radiation and selective surgery, and new chemoradiation regimens with novel agents. This review will examine these developments and assess their impact on the future therapy of rectal cancer.

  4. Aflibercept and Ang1 supplementation improve neoadjuvant or adjuvant chemotherapy in a preclinical model of resectable breast cancer

    PubMed Central

    Wu, Florence T. H.; Paez-Ribes, Marta; Xu, Ping; Man, Shan; Bogdanovic, Elena; Thurston, Gavin; Kerbel, Robert S.

    2016-01-01

    Phase III clinical trials evaluating bevacizumab (an antibody to the angiogenic ligand, VEGF-A) in breast cancer have found improved responses in the presurgical neoadjuvant setting but no benefits in the postsurgical adjuvant setting. The objective of this study was to evaluate alternative antiangiogenic therapies, which target multiple VEGF family members or differentially modulate the Angiopoietin/Tie2 pathway, in a mouse model of resectable triple-negative breast cancer (TNBC). Neoadjuvant therapy experiments involved treating established orthotopic xenografts of an aggressive metastatic variant of the MDA-MB-231 human TNBC cell line, LM2-4. Adjuvant therapies were given after primary tumor resections to treat postsurgical regrowths and distant metastases. Aflibercept (‘VEGF Trap’, which neutralizes VEGF-A, VEGF-B and PlGF) showed greater efficacy than nesvacumab (an anti-Ang2 antibody) as an add-on to neoadjuvant/adjuvant chemotherapy. Concurrent inhibition of Ang1 and Ang2 signaling (through an antagonistic anti-Tie2 antibody) was not more efficacious than selective Ang2 inhibition. In contrast, short-term perioperative BowAng1 (a recombinant Ang1 variant) improved the efficacy of adjuvant chemotherapy. In conclusion, concurrent VEGF pathway inhibition is more likely than Ang/Tie2 pathway inhibition (e.g., anti-Ang2, anti-Ang2/Ang1, anti-Tie2) to improve neoadjuvant/adjuvant chemotherapies for TNBC. Short-term perioperative Ang1 supplementation may also have therapeutic potential in conjunction with adjuvant chemotherapy for TNBC. PMID:27841282

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

    SciTech Connect

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

    2009-07-15

    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 dose 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.

  6. Effectiveness of Chemoradiation for Head and Neck Cancer in an Older Patient Population

    SciTech Connect

    VanderWalde, Noam A.; Meyer, Anne Marie; Deal, Allison M.; Layton, J. Bradley; Liu, Huan; Carpenter, William R.; Weissler, Mark C.; Fleming, Mary E.; and others

    2014-05-01

    Purpose: The purpose of this study was to compare chemoradiation therapy (CRT) with radiation therapy (RT) only in an older patient population with head and neck squamous cell carcinoma (HNSCC). Methods and Materials: Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database (1992-2007), we identified a retrospective cohort of nonmetastatic HNSCC patients and divided them into treatment groups. Comparisons were made between CRT and RT cohorts. Propensity scores for CRT were estimated from covariates associated with receipt of treatment using multivariable logistic regression. Standardized mortality ratio weights (SMRW) were created from the propensity scores and used to balance groups on measured confounders. Multivariable and SMR-weighted Cox proportional hazard models were used to estimate the hazard ratio (HR) of death for receipt of CRT versus RT among the whole group and for separate patient and tumor categories. Results: The final cohort of 10,599 patients was 68% male and 89% white. Median age was 74 years. Seventy-four percent were treated with RT, 26% were treated with CRT. Median follow-up points for CRT and RT survivors were 4.6 and 6.3 years, respectively. On multivariable analysis, HR for death with CRT was 1.13 (95% confidence interval [CI]: 1.07-1.20; P<.01). Using the SMRW model, the HR for death with CRT was 1.08 (95% CI: 1.02-1.15; P=.01). Conclusions: Although the addition of chemotherapy to radiation has proven efficacious in many randomized controlled trials, it may be less effective in an older patient population treated outside of a controlled trial setting.

  7. Outcome With Neck Dissection After Chemoradiation for N3 Head-and-Neck Squamous Cell Carcinoma

    SciTech Connect

    Igidbashian, Levon; Fortin, Bernard; Guertin, Louis; Soulieres, Denis; Coulombe, Genevieve; Belair, Manon; Charpentier, Danielle; Tabet, Jean-Claude; Nguyen-Tan, Phuc Felix

    2010-06-01

    Purpose: To evaluate the role of neck dissection (ND) after chemoradiation therapy (CRT) for head and neck squamous cell carcinoma (HNSCC) with N3 disease. Methods and Materials: From March 1998 to September 2006, 70 patients with HNSCC and N3 neck disease were treated with concomitant CRT as primary therapy. Response to treatment was assessed using clinical examination and computed tomography 6 to 8 weeks posttreatment. Neck dissection was not routinely performed and considered for those with less than complete response. Of the patients, 26 (37.1%) achieved clinical complete response (cCR) after CRT. A total of 31 (44.3%) underwent ND after partial response (cPR-ND). Thirteen patients (29.5%) did not achieve cCR and did not undergo ND for the following reasons: incomplete response/progression at primary site, refusal/contraindication to surgery, metastatic progression, or death. These patients were excluded from the analysis. Outcomes were computed using Kaplan-Meier curves and were compared with log rank tests. Results: Comparing the cCR and cPR-ND groups at 2 years, the disease-free survival was respectively 62.7% and 84.9% (p = 0.048); overall survival was 63.0% and 79.4% (p = 0.26), regional relapse-free survival was 87.8% and 96.0% (p = 0.21); and distant disease-free survival was 67.1% and 92.6% (p = 0.059). In the cPR-ND group, 71.0% had no pathologic evidence of disease (PPV of 29.0%). Conclusions: Patients with N3 disease achieving regional cPR and primary cCR who underwent ND seemed to have better outcomes than patients achieving global cCR without ND. Clinical assessment with computed tomography is not adequate for evaluating response to treatment. Because of the inherent limitations of our study, further confirmatory studies are warranted.

  8. Neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer: which patients benefit?

    PubMed

    Niegisch, Günter; Lorch, Anja; Droller, Michael J; Lavery, Hugh J; Stensland, Kristian D; Albers, Peter

    2013-09-01

    Level I evidence supports neoadjuvant chemotherapy in the treatment of advanced bladder cancer. For the most benefit, it is suggested that neoadjuvant chemotherapy be restricted to patients with clinical T3 disease and/or clinical N+ disease.

  9. Expression of Nuclear Transcription Factor Kappa B in Locally Advanced Human Cervical Cancer Treated With Definitive Chemoradiation

    SciTech Connect

    Garg, Amit K.; Jhingran, Anuja; Klopp, Ann H.; Aggarwal, Bharat B.; Kunnumakkara, Ajai B.; Broadus, Russell R.; Eifel, Patricia J.; Buchholz, Thomas A.

    2010-12-01

    Purpose: Nuclear factor kappa B (NF-{kappa}B), a transcriptional factor that has been shown to be constitutively active in cervical cancer, is part of an important pathway leading to treatment resistance in many tumor types. The purpose of our study was to determine whether expression of NF-{kappa}B in pretreatment specimens and specimens taken shortly after treatment initiation correlated with outcome in cervical cancer patients treated with definitive chemoradiation. Methods and Materials: Eighteen patients with locally advanced cervical cancer were enrolled in a study in which cervical biopsy specimens were obtained before radiation therapy and 48 h after treatment initiation. Matched biopsy specimens from 16 of these patients were available and evaluated for the nuclear expression of NF-{kappa}B protein by immunohistochemical staining. Results: After a median follow-up of 43 months, there were 9 total treatment failures. Nuclear staining for NF-{kappa}B was positive in 3 of 16 pretreatment biopsy specimens (19%) and 5 of 16 postradiation biopsy specimens (31%). Pretreatment expression of NF-{kappa}B nuclear staining correlated with increased rates of local-regional failure (100% vs. 23%, p = 0.01), distant failure (100% vs. 38%, p = 0.055), disease-specific mortality (100% vs. 31%, p = 0.03), and overall mortality (100% vs. 38%, p = 0.055). Conclusions: Our data suggest that pretreatment nuclear expression of NF-{kappa}B may be associated with a poor outcome for cervical cancer patients treated with chemoradiation. Although these data require validation in a larger group of patients, the results support the continued study of the relationship between NF-{kappa}B and outcome in patients treated for carcinoma of the cervix.

  10. The Neoadjuvant Model Is Still the Future for Drug Development in Breast Cancer.

    PubMed

    DeMichele, Angela; Yee, Douglas; Berry, Donald A; Albain, Kathy S; Benz, Christopher C; Boughey, Judy; Buxton, Meredith; Chia, Stephen K; Chien, Amy J; Chui, Stephen Y; Clark, Amy; Edmiston, Kirsten; Elias, Anthony D; Forero-Torres, Andres; Haddad, Tufia C; Haley, Barbara; Haluska, Paul; Hylton, Nola M; Isaacs, Claudine; Kaplan, Henry; Korde, Larissa; Leyland-Jones, Brian; Liu, Minetta C; Melisko, Michelle; Minton, Susan E; Moulder, Stacy L; Nanda, Rita; Olopade, Olufunmilayo I; Paoloni, Melissa; Park, John W; Parker, Barbara A; Perlmutter, Jane; Petricoin, Emanuel F; Rugo, Hope; Symmans, Fraser; Tripathy, Debasish; van't Veer, Laura J; Viscusi, Rebecca K; Wallace, Anne; Wolf, Denise; Yau, Christina; Esserman, Laura J

    2015-07-01

    The many improvements in breast cancer therapy in recent years have so lowered rates of recurrence that it is now difficult or impossible to conduct adequately powered adjuvant clinical trials. Given the many new drugs and potential synergistic combinations, the neoadjuvant approach has been used to test benefit of drug combinations in clinical trials of primary breast cancer. A recent FDA-led meta-analysis showed that pathologic complete response (pCR) predicts disease-free survival (DFS) within patients who have specific breast cancer subtypes. This meta-analysis motivated the FDA's draft guidance for using pCR as a surrogate endpoint in accelerated drug approval. Using pCR as a registration endpoint was challenged at ASCO 2014 Annual Meeting with the presentation of ALTTO, an adjuvant trial in HER2-positive breast cancer that showed a nonsignificant reduction in DFS hazard rate for adding lapatinib, a HER-family tyrosine kinase inhibitor, to trastuzumab and chemotherapy. This conclusion seemed to be inconsistent with the results of NeoALTTO, a neoadjuvant trial that found a statistical improvement in pCR rate for the identical lapatinib-containing regimen. We address differences in the two trials that may account for discordant conclusions. However, we use the FDA meta-analysis to show that there is no discordance at all between the observed pCR difference in NeoALTTO and the observed HR in ALTTO. This underscores the importance of appropriately modeling the two endpoints when designing clinical trials. The I-SPY 2/3 neoadjuvant trials exemplify this approach.

  11. Discordant HER2 expression and response to neoadjuvant chemoradiotherapy in esophagogastric adenocarcinoma

    PubMed Central

    Chan, Ellie; Duckworth, Lizette Vila; Alkhasawneh, Ahmad; Toro, Tania Zuluaga; Lu, Xiaomin; Ben-David, Kfir; Hughes, Steven J.; Rossidis, Georgios; Zlotecki, Robert; Lightsey, Judith; Daily, Karen C.; Dang, Long; Allegra, Carmen J.; King, Brent

    2016-01-01

    Background Targeting human epidermal growth factor receptor 2 (HER2) with trastuzumab in metastatic esophagogastric adenocarcinoma (EGA) improves survival. The impact of HER2 inhibition in combination with chemoradiotherapy (CRT) in early stage EGA is under investigation. This study analyzed the pattern of HER2 overexpression in matched-pair tumor samples of patients who underwent neoadjuvant CRT followed by surgery. Methods All patients with EGA who underwent standard neoadjuvant CRT followed by esophagectomy at the University of Florida were included. Demographics, risk factors, tumor features, and outcome data were analyzed. Descriptive statistics, Chi-square exact test, uni- and multivariate analyses, and Kaplan Meier method were used. HER2 expression determined by immunohistochemical (IHC) was scored as negative (0, 1+), indeterminate (2+) or positive (3+). Results Among 49 sequential patients (41 M/8 F) with matched-pair tumor samples, 9/49 patients (18%) had pathologic complete response (pCR), 10/49 had near pCR or not enough tumor (NET) to examine in the post- treatment samples. Patients with initial HER2 negativity demonstrated conversion to HER2 positivity after neoadjuvant CRT (7/30 cases; 23%). Baseline HER2 overexpression was more common in lower stage/node negative patients (67% in stages I, IIA vs. 33% in stages IIB, III) and did not correlate with treatment response or survival. Conclusions Although limited by a relatively small sample size, our study failed to demonstrate that baseline HER2 protein over-expression in EGA predicts response to standard CRT. However, our data suggested that HER2 was up regulated by CRT resulting in unreliable concordance between pre-treatment (pre-tx) and post-treatment (post-tx) samples. Pre-therapy HER2 expression may not reliably reflect the HER2 status of persistent or recurrent disease. PMID:27034783

  12. Dosimetric Feasibility of Hypofractionated Proton Radiotherapy for Neoadjuvant Pancreatic Cancer Treatment

    SciTech Connect

    Kozak, Kevin R.; Kachnic, Lisa A.; Adams, Judith C; Crowley, Elizabeth M.; Alexander, Brian M.; Mamon, Harvey J.; Ryan, David P.; DeLaney, Thomas F.; Hong, Theodore S. . E-mail: tshong1@partners.org

    2007-08-01

    Purpose: To evaluate tumor and normal tissue dosimetry of a 5 cobalt gray equivalent (CGE) x 5 fraction proton radiotherapy schedule, before initiating a clinical trial of neoadjuvant, short-course proton radiotherapy for pancreatic adenocarcinoma. Methods and Materials: The first 9 pancreatic cancer patients treated with neoadjuvant intensity-modulated radiotherapy (1.8 Gy x 28) at the Massachusetts General Hospital had treatment plans generated using a 5 CGE x 5 fraction proton regimen. To facilitate dosimetric comparisons, clinical target volumes and normal tissue volumes were held constant. Plans were optimized for target volume coverage and normal tissue sparing. Results: Hypofractionated proton and conventionally fractionated intensity-modulated radiotherapy plans both provided acceptable target volume coverage and dose homogeneity. Improved dose conformality provided by the hypofractionated proton regimen resulted in significant sparing of kidneys, liver, and small bowel, evidenced by significant reductions in the mean doses, expressed as percentage prescribed dose, to these structures. Kidney and liver sparing was most evident in low-dose regions ({<=}20% prescribed dose for both kidneys and {<=}60% prescribed dose for liver). Improvements in small-bowel dosimetry were observed in high- and low-dose regions. Mean stomach and duodenum doses, expressed as percentage prescribed dose, were similar for the two techniques. Conclusions: A proton radiotherapy schedule consisting of 5 fractions of 5 CGE as part of neoadjuvant therapy for adenocarcinoma of the pancreas seems dosimetrically feasible, providing excellent target volume coverage, dose homogeneity, and normal tissue sparing. Hypofractionated proton radiotherapy in this setting merits Phase I clinical trial investigation.

  13. Quality of Life During Neoadjuvant Treatment and After Surgery for Resectable Esophageal Carcinoma

    SciTech Connect

    Meerten, Esther van Gaast, Ate van der; Looman, Caspar W.N.; Tilanus, Hugo W.G.; Muller, Karin; Essink-Bot, Marie-Louise

    2008-05-01

    Purpose: Because of the trade-off between the potentially negative quality-of-life (QoL) effects and uncertain favorable survival effect of neoadjuvant chemoradiotherapy (CRT) in patients with resectable esophageal cancer, we assessed heath-related QoL (HRQoL) for up to 1 year postoperatively in these patients treated with preoperative CRT with a non-platinum-based outpatient regimen followed by esophagectomy. Methods and Materials: Patients undergoing neoadjuvant paclitaxel and carboplatin therapy concurrent with radiotherapy followed by surgery completed standardized HRQoL questionnaires before and after CRT and at regular times up to 1 year postoperatively. We analyzed differences in generic Qol core questionnaire [QLQ-C30] and condition-specific (esophageal site-specific [OES-18]) HRQoL scores over time by using a linear mixed-effects model. Results: Mean scores of most HRQoL scales deteriorated significantly during neoadjuvant CRT. The largest deterioration was observed for physical and role-functioning scales. All except two symptom scores worsened significantly. Postoperatively, most mean HRQoL scores improved until recovery to baseline level. Speed of improvement varied. Average taste score returned to baseline 3 months postoperatively, whereas it took 1 year for the average role-functioning score to restore. The emotional-functioning score showed a different pattern; it was worst at baseline and increased over time during CRT and postoperatively. Dysphagia and pain scores worsened considerably during CRT, restored to baseline 3 months postoperatively, and were even significantly better 1 year postoperatively. Conclusions: Preoperative CRT with paclitaxel and carboplatin for patients with resectable esophageal cancer had a considerable temporary negative effect on most aspects of HRQoL. Nonetheless, all HRQoL scores were restored or even improved 1 year postoperatively.

  14. Texture analysis for survival prediction of pancreatic ductal adenocarcinoma patients with neoadjuvant chemotherapy

    NASA Astrophysics Data System (ADS)

    Chakraborty, Jayasree; Langdon-Embry, Liana; Escalon, Joanna G.; Allen, Peter J.; Lowery, Maeve A.; O'Reilly, Eileen M.; Do, Richard K. G.; Simpson, Amber L.

    2016-03-01

    Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in the United States. The five-year survival rate for all stages is approximately 6%, and approximately 2% when presenting with distant disease.1 Only 10-20% of all patients present with resectable disease, but recurrence rates are high with only 5 to 15% remaining free of disease at 5 years. At this time, we are unable to distinguish between resectable PDAC patients with occult metastatic disease from those with potentially curable disease. Early classification of these tumor types may eventually lead to changes in initial management including the use of neoadjuvant chemotherapy or radiation, or in the choice of postoperative adjuvant treatments. Texture analysis is an emerging methodology in oncologic imaging for quantitatively assessing tumor heterogeneity that could potentially aid in the stratification of these patients. The present study derives several texture-based features from CT images of PDAC patients, acquired prior to neoadjuvant chemotherapy, and analyzes their performance, individually as well as in combination, as prognostic markers. A fuzzy minimum redundancy maximum relevance method with leave-one-image-out technique is included to select discriminating features from the set of extracted features. With a naive Bayes classifier, the proposed method predicts the 5-year overall survival of PDAC patients prior to neoadjuvant therapy and achieves the best results in terms of the area under the receiver operating characteristic curve of 0:858 and accuracy of 83:0% with four-fold cross-validation techniques.

  15. 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.

  16. Combined modality therapy for rectal cancer.

    PubMed

    Minsky, Bruce D; Röedel, Claus; Valentini, Vincenzo

    2010-01-01

    The standard adjuvant treatment for cT3 and/or N+ rectal cancer is preoperative chemoradiation. However, there are many controversies regarding this approach. These include the role of short course radiation, whether postoperative adjuvant chemotherapy necessary for all patients and whether the type of surgery after chemoradiation should be based on the response rate. More accurate imaging techniques and/or molecular markers may help identify patients with positive pelvic nodes to reduce the chance of overtreatment with preoperative therapy. Will more effective systemic agents both improve the results of radiation as well as modify the need for pelvic radiation? These questions and others remain active areas of clinical investigation.

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

    SciTech Connect

    Ko, Andrew H.; Venook, Alan P.

    2007-07-01

    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 (800 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.

  18. Chemotherapy as a component of multimodal therapy for gastric carcinoma.

    PubMed

    Kodera, Yasuhiro; Fujiwara, Michitaka; Koike, Masahiko; Nakao, Akimasa

    2006-04-07

    Prognosis of locally advanced gastric cancer remains poor, and several multimodality strategies involving surgery, chemotherapy, and radiation have been tested in clinical trials. Phase III trial testing the benefit of postoperative adjuvant chemotherapy over treatment with surgery alone have revealed little impact on survival, with the exception of some small trials in Western nations. A large trial from the United States exploring postoperative chemoradiation was the first major success in this category. Results from Japanese trials suggest that moderate chemotherapy with oral fluoropyrimidines may be effective against less-advanced (T2-stage) cancer, although another confirmative trial is needed to prove this point. Investigators have recently turned to neoadjuvant chemotherapy, and some promising results have been reported from phase II trials using active drug combinations. In 2005, a large phase III trial testing pre- and postoperative chemotherapy has proven its survival benefit for resectable gastric cancer. Since the rate of pathologic complete response is considered to affect treatment results of this strategy, neoadjuvant chemoradiation that further increases the incidence of pathologic complete response could be a breakthrough, and phase III studies testing this strategy may be warranted in the near future.

  19. A mechanically coupled reaction-diffusion model for predicting the response of breast tumors to neoadjuvant chemotherapy

    NASA Astrophysics Data System (ADS)

    Weis, Jared A.; Miga, Michael I.; Arlinghaus, Lori R.; Li, Xia; Bapsi Chakravarthy, A.; Abramson, Vandana; Farley, Jaime; Yankeelov, Thomas E.

    2013-09-01

    There is currently a paucity of reliable techniques for predicting the response of breast tumors to neoadjuvant chemotherapy. The standard approach is to monitor gross changes in tumor size as measured by physical exam and/or conventional imaging, but these methods generally do not show whether a tumor is responding until the patient has received many treatment cycles. One promising approach to address this clinical need is to integrate quantitative in vivo imaging data into biomathematical models of tumor growth in order to predict eventual response based on early measurements during therapy. In this work, we illustrate a novel biomechanical mathematical modeling approach in which contrast enhanced and diffusion weighted magnetic resonance imaging data acquired before and after the first cycle of neoadjuvant therapy are used to calibrate a patient-specific response model which subsequently is used to predict patient outcome at the conclusion of therapy. We present a modification of the reaction-diffusion tumor growth model whereby mechanical coupling to the surrounding tissue stiffness is incorporated via restricted cell diffusion. We use simulations and experimental data to illustrate how incorporating tissue mechanical properties leads to qualitatively and quantitatively different tumor growth patterns than when such properties are ignored. We apply the approach to patient data in a preliminary dataset of eight patients exhibiting a varying degree of responsiveness to neoadjuvant therapy, and we show that the mechanically coupled reaction-diffusion tumor growth model, when projected forward, more accurately predicts residual tumor burden at the conclusion of therapy than the non-mechanically coupled model. The mechanically coupled model predictions exhibit a significant correlation with data observations (PCC = 0.84, p < 0.01), and show a statistically significant >4 fold reduction in model/data error (p = 0.02) as compared to the non-mechanically coupled model.

  20. Predictors of prostate volume reduction following neoadjuvant cytoreductive androgen suppression

    PubMed Central

    Jethwa, Krishan R.; Furutani, Keith M.; Mynderse, Lance A.; Wilson, Torrence M.; Choo, Richard; King, Bernard F.; Bergstralh, Eric

    2016-01-01

    Purpose Limited duration cytoreductive neoadjuvant hormonal therapy (NHT) is used prior to definitive radiotherapeutic management of prostate cancer to decrease prostate volume. The purpose of this study is to examine the effect of NHT on prostate volume before permanent prostate brachytherapy (PPB), and determine associated predictive factors. Material and methods Between June 1998 and April 2012, a total of 1,110 patients underwent PPB and 207 patients underwent NHT. Of these, 189 (91.3%) underwent detailed planimetric transrectal ultrasound before and after NHT prior to PPB. Regression analysis was used to assess predictors of absolute and percentage change in prostate volume after NHT. Results The median duration of NHT was 4.9 months with inter quartile range (IQR), 4.2-6.6 months. Prostate-specific antigen (PSA) reduced by a median of 97% following NHT. The mean prostate volume before NHT was 62.5 ± 22.1 cm3 (IQR: 46-76 cm3), and after NHT, it was 37.0 ± 14.5 cm3 (IQR: 29-47 cm3). The mean prostate volume reduction was 23.4 cm3 (35.9%). Absolute prostate volume reduction was positively correlated with initial volume and inversely correlated with T-stage, Gleason score, and NCCN risk group. In multivariate regression analyses, initial prostate volume (p < 0.001) remained as a significant predictor of absolute and percent prostate volume reduction. Total androgen suppression was associated with greater percent prostate volume reduction than luteinizing hormone releasing hormone agonist (LHRHa) alone (p = 0.001). Conclusions Prostate volume decreased by approximately one third after 4.9 months of NHT, with total androgen suppression found to be more efficacious in maximizing cytoreduction than LHRHa alone. Initial prostate volume is the greatest predictor for prostate volume reduction. PMID:27895677

  1. Association between breast cancer subtypes and response to neoadjuvant anastrozole.

    PubMed

    Dunbier, Anita K; Anderson, Helen; Ghazoui, Zara; Salter, Janine; Parker, Joel S; Perou, Charles M; Smith, Ian E; Dowsett, Mitch

    2011-07-01

    Considerable heterogeneity exists amongst oestrogen receptor positive (ER+ve) breast cancer in both its molecular profile and response to therapy. Attempts to better define variation amongst breast tumours have led to the definition of four main "intrinsic" subtypes of breast cancer with two of these classes, Luminal A and B, composed almost entirely of ER+ve cancers. In this study we set out to investigate the significance of intrinsic subtypes within a group of ER+ve breast cancers treated with neoadjuvant anastrozole. RNA from tumour biopsies taken from 104 postmenopausal women before and after 2 weeks treatment with anastrozole was analyzed on Illumina 48K microarrays. Gene-expression based subtypes and risk of relapse (ROR) scores for tumours pre- and post-treatment were determined using the PAM50 method. Amongst pre-treatment samples, all intrinsic subtypes were found to be present, although luminal groups were represented most highly. Luminal A and B tumours obtained similar benefit from treatment, as measured by the proportional fall in the proliferation marker Ki67 upon treatment (mean suppression=75.5% vs 75.7%). Tumours classified as basal and Her2-like showed poor reductions in Ki67 upon treatment. Residual Ki67 staining after two weeks remained higher in the Luminal B group. ROR score was significantly associated with anti-proliferative response to AI and with clinical response. These results suggest that in the short-term, Luminal A and B tumours may gain similar benefit from an AI but that the higher residual Ki67 level seen in Luminal B is indicative of poorer long term outcome.

  2. [Neoadjuvant chemotherapy of invasive cancer of the urinary bladder].

    PubMed

    Selivanov, S P; Isaeva, S N; Kovalik, T A; Chén', M N; Aleksandrovich, I N; Kaliev, E A

    2007-01-01

    We studied efficacy of a combination of intraosseous and systemic administration of drugs in patients with invasive cancer of the urinary bladder (UB). A total of 20 patients aged 54-79 years with verified had recurrence, 2 had tumors with continuous growth. T2N0M0 UB carcinoma was diagnosed in 7 patients, T3N0M0--in 12, T6N0M0--in 1 patient. All the patients received systemic chemotherapy with gemzar in a single daily dose 800-1000 mg/m2 on day 1, 7 and 14. On day 2 a single intraosseous 100 mg eloxatin was given. A total of three courses of combined chemotherapy with 4-week interval was used. Intravenous gemzar administration was accompanied with mild leukopenia in 4 patients, moderate leukopenia--in 1, allergic reaction--in 2 patients. This required gemzar discontinuation. No side effects were seen in response to intraosseous administration of eloxatin. The combined chemotherapy produced complete regression of UB cancer in 3 of 18 patients, partial regression--in 12, stabilization--in 3 patients. Neither local nor long-term tumor progression was found. Short-term therapeutic efficacy of combined therapy was 70%. Fifteen patients with partial regression or stabilization have undergone transurethral resection. Duration of a recurrence-free period reached 5 to 72 months (mean 17 months). The neoadjuvant chemotherapy proposed by us allows achievement of a high percentage of regression in patients with invasive UB cancer located in UB cervix and provides concervative surgery including patients over 70 years of age.

  3. Multi-institutional Pooled Analysis on Adjuvant Chemoradiation in Pancreatic Cancer

    SciTech Connect

    Morganti, Alessio G.; Falconi, Massimo; Stiphout, Ruud G.P.M. van; Mattiucci, Gian-Carlo; Alfieri, Sergio; Calvo, Felipe A.; Dubois, Jean-Bernard; Fastner, Gerd; Herman, Joseph M.; Maidment, Bert W.; Miller, Robert C.; Regine, William F.; Reni, Michele; Sharma, Navesh K.; Ippolito, Edy; and others

    2014-11-15

    Purpose: To determine the impact of chemoradiation therapy (CRT) on overall survival (OS) after resection of pancreatic adenocarcinoma. Methods and Materials: A multicenter retrospective review of 955 consecutive patients who underwent complete resection with macroscopically negative margins (R0-1) for invasive carcinoma (T1-4; N0-1; M0) of the pancreas was performed. Exclusion criteria included metastatic or unresectable disease at surgery, macroscopic residual disease (R2), treatment with intraoperative radiation therapy (IORT), and a histological diagnosis of no ductal carcinoma, or postoperative death (within 60 days of surgery). In all, 623 patients received postoperative radiation therapy (RT), 575 patients received concurrent chemotherapy (CT), and 462 patients received adjuvant CT. Results: Median follow-up was 21.0 months. Median OS after adjuvant CRT was 39.9 versus 24.8 months after no adjuvant CRT (P<.001) and 27.8 months after CT alone (P<.001). Five-year OS was 41.2% versus 24.8% with and without postoperative CRT, respectively. The positive impact of CRT was confirmed by multivariate analysis (hazard ratio [HR] = 0.72; confidence interval [CI], 0.60-0.87; P=.001). Adverse prognostic factors identified by multivariate analysis included the following: R1 resection (HR = 1.17; CI = 1.07-1.28; P<.001), higher pT stage (HR = 1.23; CI = 1.11-1.37; P<.001), positive lymph nodes (HR = 1.27; CI = 1.15-1.41; P<.001), and tumor diameter >20 mm (HR = 1.14; CI = 1.05-1.23; P=.002). Multivariate analysis also showed a better prognosis in patients treated in centers with >10 pancreatic resections per year (HR = 0.87; CI = 0.78-0.97; P=.014) Conclusion: This study represents the largest comparative study on adjuvant therapy in patients after resection of carcinoma of the pancreas. Overall survival was better in patients who received adjuvant CRT.

  4. Phase II Study of Consolidation Chemotherapy After Concurrent Chemoradiation in Cervical Cancer: Preliminary Results

    SciTech Connect

    Choi, Chel Hun; Lee, Jeong-Won; Kim, Tae-Joong; Kim, Woo Young; Nam, Hee Rim; Kim, Byoung-Gie . E-mail: huna0@naver.com; Huh, Seung Jae; Lee, Je-Ho; Bae, Duk-Soo

    2007-07-01

    Purpose: Our aim was to determine the efficacy of consolidation chemotherapy after concurrent chemoradiation (CCRT) using high-dose-rate brachytherapy in patients with locally advanced cervical carcinoma. Methods and Materials: Patients with cervical carcinoma (FIGO stage IB2-IVA) were treated with external beam radiation therapy to the whole pelvis (50.4 Gy) and high-dose-rate brachytherapy (24 Gy to point A). Cisplatin 60 mg/m{sup 2} (Day 1) and 5-fluorouracil 1000 mg/m{sup 2} (Days 1-5) were given every 3 weeks starting concurrently with the radiation and followed by 3 more cycles of consolidation for a total of 6 cycles. Results: Thirty patients (94%) received 3 more cycles of post-CCRT consolidation chemotherapy and were evaluable for the toxicity and efficacy of consolidation. The most common toxicities of Grade 2 or higher were nausea or vomiting (47%) and anemia (33%). Late complications of the rectum and bladder occurred in 13% and 6% of the patients, respectively. The clinical complete response rate was 87% (95% CI, 75%-99%). During a median follow-up of 27 months (range, 6-58 months), 5 patients (17%) had recurrence; the sites of failure were 3 (10%) inside the radiation field and 2 (7%) outside the radiation field. The estimated 3-year progression-free survival rate was 83% (95% CI, 67%-99%) and overall survival rate was 91% (95% CI, 79%-100%). Conclusions: Consolidation chemotherapy after CCRT is well tolerated and effective in patients with locally advanced cervical carcinoma. A prospective randomized trial to compare this treatment strategy with standard CCRT seems to be worthwhile.

  5. Cervical necrosis after chemoradiation for cervical cancer: case series and literature review

    PubMed Central

    2013-01-01

    Background The aim of this study was to assess the management of cervical necrosis (CN) following radiotherapy (RT) and the impact of smoking status. This rare complication mimics a neoplastic recurrence, and causes concern among attending physicians. Methods Between July 2008 and March 2013, 5 women on 285 with localized cervical cancer had a CN following RT. Patients were treated with concomitant chemoradiation. The medical records were reviewed to abstract demographic and clinical information until March 2013. Results 1.75% (95% confidence interval: 0.23 to 3.28%) developed CN. All patients were smokers with a mean of 19.5 pack-years (range: 7.5-45 pack-years). All patients were treated with weekly Cisplatin chemotherapy and external beam radiation to the pelvis, 45 Gy in 25 fractions. Four patients received an extra boost with a median dose of 7.2 Gy (range: 5.4-10 Gy). All patients had intracavitary brachytherapy (range: 27.9 to 30 Gy). Clinical presentation was similar for all the cases: vaginal discharge associated with pain. Mean time for time post-radiation therapy to necrosis was 9.3 months (range: 2.2-20.5 months). Standard workup was done to exclude cancer recurrence: biopsies and radiologic imaging. Conservative treatment was performed with excellent results. Resolution of the necrosis was complete after a few months (range: 1 to 4 months). Median follow-up until March 2013 was 19 months. All the patients were alive with no clinical evidence of disease. Conclusions This study, the largest to date, shows that conservative management of CN after RT is effective, and should be attempted. This complication is more common in smokers, and counseling intervention should result in fewer complications of CN. PMID:24053332

  6. Preoperative chemoradiation and IOERT for unresectable or borderline resectable pancreas cancer

    PubMed Central

    Moss, Adyr A.; Rule, William G.; Callister, Matthew G.; Reddy, K. Sudhakar; Mulligan, David C.; Collins, Joseph M.; De Petris, Giovanni; Gunderson, Leonard L.; Borad, Mitesh

    2013-01-01

    Background and objectives Pre-operative chemoradiation (preop CRT) plus intraoperative electron irradiation (IOERT) has been used in the multidisciplinary treatment for patients with locally advanced unresectable or borderline resectable pancreas cancer. This review was performed to evaluate survival, relapse patterns and prognostic factors in patients treated with curative intent. Methods Between January 2002 and December 2010, 48 patients with locally advanced pancreatic ductal adenocarcinoma received preop CRT prior to an attempt at resection and IOERT. 31/48 (65%) patients proceeded to curative-intent surgical resection. Resection status prior to preop CRT was locally unresectable (20 patients) and borderline resectable (11 patients). Preop CRT (45-50.4 Gy/25-28 Fx in 27/31) was delivered with concurrent 5FU or gemcitabine-based regimens. Subsequent gross total resection was achieved in 16 patients (R0, 11; R1, 5). IOERT was delivered in 28 patients (dose, 10-20 Gy). 16 patients also received adjuvant post-operative systemic chemotherapy. Outcomes evaluated include survival, local failure in the EBRT field (LF), central failure in the IOERT field (CF), and distant metastases. Results Resection status was predictive for survival and for patterns of relapse. For patients with at least a gross total resection after preop CRT (R0/R1; n=16) vs. no resection (n=15), both median and overall survival were improved (median 23 vs. 10 months; 2-year, 40% vs. 17%; 3-year, 40% vs. 0%; P=0.002). Liver or peritoneal relapse was documented in 22/31 patients (71%); LF/CF in 5/26 (16%). Conclusions Long term survival and disease control are achievable in select patients with borderline resectable or locally unresectable pancreas cancer when gross total surgical resection is achieved after preop CRT. Continued evaluation of curative-intent combined modality therapy is warranted in this high risk population, but additional strategies are needed to improve resectability and disease

  7. Clinical outcomes following neoadjuvant cisplatin-based chemotherapy for bladder cancer in elderly compared with younger patients.

    PubMed

    Chau, C; Wheater, M; Geldart, T; Crabb, S J

    2015-03-01

    Bladder cancer is a disease of the elderly. Older patients might potentially be undertreated due to assumptions about benefit versus risk. Our objective was to determine outcomes in older patients receiving neoadjuvant chemotherapy for muscle-invasive bladder cancer (MIBC). We hypothesised that appropriately selected elderly patients (≥70 years) with MIBC could have similar clinical outcomes, and be safely treated, with standard neoadjuvant chemotherapy prior to definitive cystectomy or radiotherapy. We utilised a single institution case series analysis of patients with T2-4a N0 M0 transitional cell carcinoma of the bladder treated with cisplatin-based neoadjuvant chemotherapy between 2005 and 2011. Eighty-three patients were eligible. Median age was 68 (range 48-80), 33 patients (40%) were ≥70 years. Overall survival at 3 years was 65.8% (≥70) and 63.2% (<70) (P = 0.653), relapse-free survival at 3 years was 61.6% and 54.8% respectively (P = 0.471). The rates going forward to definitive local therapy (87.9% ≥ 70 and 84.0% < 70) and the pathological complete response rate (31.3% ≥ 70 and 40% < 70) were similar. Disease relapse rate was also similar (63.6% ≥ 70 vs. 60% < 70, P = 0.906). Elderly patients with good functional status and limited comorbidities diagnosed with MIBC receiving standard neoadjuvant chemotherapy followed by cystectomy or radiotherapy can have similar clinical outcomes as their younger counterparts. Prospective studies evaluating the optimum curative management in this elderly population are warranted.

  8. Neoadjuvant chemoradiotherapy followed by esophagectomy vs. surgery alone in the treatment of resectable esophageal squamous cell carcinoma

    PubMed Central

    FUJIWARA, YOSHINORI; YOSHIKAWA, REIGETSU; KAMIKONYA, NORIHIKO; NAKAYAMA, TSUYOSHI; KITANI, KOTARO; TSUJIE, MASANORI; YUKAWA, MASAO; HARA, JOHJI; YAMAMURA, TAKEHIRA; INOUE, MASATOSHI

    2013-01-01

    In order to improve the survival of esophageal cancer patients, a trimodality therapy consisting of esophagectomy in combination with neoadjuvant chemoradiotherapy (CRT) has been developed. In this study, we evaluated whether neoadjuvant CRT improved the outcomes of patients with resectable esophageal squamous cell carcinoma (ESCC) compared to surgery alone. Eighty-eight patients with resectable ESCC were treated with either neoadjuvant CRT followed by surgical resection (Group A, n=52), or surgery alone (Group B, n=36). CRT consisted of 5-fluorouracil (5-FU, 500 mg/m2 on days 1–5) and cisplatin (CDDP, 10–20 mg/kg body weight on days 1–5), repeated after 3 weeks. Survival analysis was performed using the log-rank test with the Kaplan-Meier method. The clinical response of the primary tumor and metastatic nodes was 80.8%. The postoperative complications profile was similar between the two groups, except for anastomotic leakage. The median survival time (MST) was not reached in Group A and was 27.4 months in Group B. The estimated 5-year overall survival (OS) rate was 50.3% in Group A and 39.9% in Group B (P=0.134). As regards stage II/III disease, Group A exhibited a better disease-free survival (DFS) compared to Group B (5-year DFS: 57.2% in Group A vs. 31.4% in Group B; P=0.025). Simultaneous locoregional and distant recurrences were more common in the surgery alone group (Group B, P=0.047). Neoadjuvant CRT with 5-FU and CDDP did not contribute to a better prognosis in patients with resectable ESCC. However, it may be beneficial for patients with stage II/III disease. PMID:24649245

  9. Clinical value of routine serum squamous cell carcinoma antigen in follow-up of patients with locally advanced cervical cancer treated with radiation or chemoradiation

    PubMed Central

    Oh, Jinju; Lee, Hyun Joo; Lee, Tae Sung; Kim, Ju Hyun; Koh, Suk Bong

    2016-01-01

    Objective The objective of this study was to evaluate the clinical benefits of routine squamous cell carcinoma antigen (SCC-Ag) monitoring of patients with locally advanced cervical squamous cell carcinoma treated with radiation or chemoradiation. Methods A total of 53 patients with recurrent cervical squamous cell carcinoma treated with radiotherapy or chemoradiation were enrolled in this study. A retrospective review of medical records was conducted. The role of routine monitoring of serum SCC-Ag was evaluated in terms of cost effectiveness and effect on survival after diagnosis of recurrence. Results Serum SCC-Ag abnormality (≥2.5 ng/mL) was observed in 62.3% of patients when recurrent disease was diagnosed. The first indicator of relapse was abnormal serum SCC-Ag level in 21 patients (39.6%), 10 of whom had asymptomatic recurrent disease amenable to salvage therapy. Adding SCC-Ag measurement to the basic follow up protocol improved the sensitivity for detecting recurrence (The sensitivity of the basic protocol vs. addition of SCC-Ag: 49.1% vs. 88.7%, P<0.001). Twenty-three patients who were candidates for salvage therapy with curative intent showed better survival compared with those who were not candidates for therapy (5-year survival: 36.6% vs. 0%, P=0.012). Conclusion Surveillance with routine serum SCC-Ag monitoring can better detect asymptomatic recurrent disease that is potentially amenable to salvage therapy with curative intent. Early diagnosis of recurrent disease that can be treated with salvage therapy may lead to better survival. PMID:27462593

  10. Mandibular melanotic neuroectodermal tumor of infancy: a role for neoadjuvant chemotherapy.

    PubMed

    Maroun, Christopher; Khalifeh, Ibrahim; Alam, Elie; Akl, Pierre Abi; Saab, Raya; Moukarbel, Roger V

    2016-12-01

    Melanotic Neuroectodermal Tumor of Infancy (MNTI) is a rare, locally aggressive neoplasm with a predilection for the head and neck area, most commonly occurring in the maxilla. The vast majority of treatment modalities for all cases of MNTI to date have involved surgical intervention only, with just 9.6 % involving some sort of chemotherapy, radiotherapy, or a combination of the prior mentioned modalities. There is very limited information available regarding the use of neoadjuvant chemotherapy, due to its rare nature. In this report, a 4 month old girl presented to our clinic with a chief complaint of a large oral mass of about 2.5 months in duration. Intraoral examination showed an oral mass arising from the lingual aspect of inferior alveolar ridge with extensive mandibular invasion. The patient received three cycles of vincristine, Adriamycin, and cyclophosphamide as neodajuvant therapy. Upon completion, the tumor had decreased significantly in size. The patient was then scheduled for surgery and underwent surgical resection of the tumor. We were able to obtain adequate shrinkage of the tumor to allow better resectability, easier surgical access and a more minimally invasive approach with no lip split and a smaller neck incision. In conclusion, we have reported an extremely rare case of MNTI of the mandible that was successfully treated with neoadjuvant chemotherapy and surgical resection. This approach was advantageous to minimize the chance of recurrence and improve resectability in particularly large tumors, while maximizing functional outcomes and minimizing deformity.

  11. Differential clonal evolution in oesophageal cancers in response to neo-adjuvant chemotherapy

    PubMed Central

    Findlay, John M.; Castro-Giner, Francesc; Makino, Seiko; Rayner, Emily; Kartsonaki, Christiana; Cross, William; Kovac, Michal; Ulahannan, Danny; Palles, Claire; Gillies, Richard S.; MacGregor, Thomas P.; Church, David; Maynard, Nicholas D.; Buffa, Francesca; Cazier, Jean-Baptiste; Graham, Trevor A.; Wang, Lai-Mun; Sharma, Ricky A.; Middleton, Mark; Tomlinson, Ian

    2016-01-01

    How chemotherapy affects carcinoma genomes is largely unknown. Here we report whole-exome and deep sequencing of 30 paired oesophageal adenocarcinomas sampled before and after neo-adjuvant chemotherapy. Most, but not all, good responders pass through genetic bottlenecks, a feature associated with higher mutation burden pre-treatment. Some poor responders pass through bottlenecks, but re-grow by the time of surgical resection, suggesting a missed therapeutic opportunity. Cancers often show major changes in driver mutation presence or frequency after treatment, owing to outgrowth persistence or loss of sub-clones, copy number changes, polyclonality and/or spatial genetic heterogeneity. Post-therapy mutation spectrum shifts are also common, particularly C>A and TT>CT changes in good responders or bottleneckers. Post-treatment samples may also acquire mutations in known cancer driver genes (for example, SF3B1, TAF1 and CCND2) that are absent from the paired pre-treatment sample. Neo-adjuvant chemotherapy can rapidly and profoundly affect the oesophageal adenocarcinoma genome. Monitoring molecular changes during treatment may be clinically useful. PMID:27045317

  12. Neoadjuvant Chemotherapy Creates Surgery Opportunities For Inoperable Locally Advanced Breast Cancer

    PubMed Central

    Wang, Minghao; Hou, Lingmi; Chen, Maoshan; Zhou, Yan; Liang, Yueyang; Wang, Shushu; Jiang, Jun; Zhang, Yi

    2017-01-01

    Neoadjuvant chemotherapy (NAC), the systematic chemotherapy given to patients with locally advanced and inoperable breast caner, has been proven to be of great clinical values. Many scientific reports confirmed NAC could effectively eliminate sub-clinical disseminated lesions of tumor, and improve long-term and disease-free survival rate of patients with locally advanced breast cancer (LABC); however, up to now, LABC is still a serious clinical issue given improved screening and early diagnosis. This study, with main focus on inoperable LABC, investigated the values of NAC in converting inoperable LABC into operable status and assessed the prognosis. Sixty-one patients with inoperable LABC were initially treated with neoadjuvant chemotherapy; their local conditions were improved to operable status. Radical surgery was exerted on 49 patients. Original chemotherapy was performed after surgery, followed by local radiotherapy. And endocrine therapy was optional according to the hormone receptor status. The quality of life for most patients with skin diabrosis was obviously improved because their local conditions were under control. For all recruited cases, the survival duration and life quality were significantly improved in patients who finished both NAC and surgery compared to those who did not. Further more, this study demonstrates improved prognostic consequences. PMID:28327615

  13. Changes in ER, PR and HER2 receptors status after neoadjuvant chemotherapy in breast cancer.

    PubMed

    Yang, Yu-Feng; Liao, Ying-Yang; Li, Le-Qun; Xie, Shu-Rui; Xie, Yan-Fang; Peng, Ning-Fu

    2013-12-01

    Previous studies have reported conflicting results regarding the impact of neoadjuvant chemotherapy (NAC) on estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status in breast cancer. Our aim was to investigate whether NAC induces some selective change in the breast biomarkers. We retrospectively detected the immunohistochemical results of ER, PR and HER2 between the core biopsy and surgical excision specimens in 113 patients with NAC. As a control group, we analyzed sample pairs from 102 patients without NAC. Fourteen (12.4%) of 113 patients undergoing NAC showed the ER status modulation in the surgically removed specimen as compared with only 4 (3.9%) of 102 women without NAC (p=0.025). Eighteen (15.9%) of 113 patients given NAC appeared in the PR status alteration in the final surgical specimen, whereas only 7 (6.9%) of 102 patients without NAC did (p=0.038). The HER2 status shift was found in 17 (15.0%) of 113 patients with NAC and in 6 (5.9%) of 102 patients without NAC, respectively (p=0.030). Neoadjuvant chemotherapy does change ER, PR and HER2 status in a statistically significant manner. Retesting these biomarkers of the residual tumor should be considered to improve future tailored adjuvant therapies.

  14. Association of PTP1B with Outcomes of Breast Cancer Patients Who Underwent Neoadjuvant Chemotherapy

    PubMed Central

    Rivera Franco, Monica M.; Leon Rodriguez, Eucario; Martinez Benitez, Braulio; Villanueva Rodriguez, Luisa G.; de la Luz Sevilla Gonzalez, Maria; Armengol Alonso, Alejandra

    2016-01-01

    PTP1B is involved in the oncogenesis of breast cancer. In addition, neoadjuvant therapy has been widely used in breast cancer; thus, a measurement to assess survival improvement could be pathological complete response (pCR). Our objective was to associate PTP1B overexpression with outcomes of breast cancer patients who underwent neoadjuvant chemotherapy. Forty-six specimens were included. Diagnostic biopsies were immunostained using anti-PTP1B antibody. Expression was categorized as negative (<5%) and overexpression (≥5%). Patients’ responses were graded according to the Miller–Payne system. Sixty-three percent of patients overexpressed PTP1B. There was no significant association between PTP1B overexpression and pCR (P = 0.2). However, when associated with intrinsic subtypes, overexpression was higher in human epidermal growth factor receptor 2-positive-enriched specimens (P = 0.02). Ten-year progression-free survival showed no differences. Our preliminary results do not show an association between PTP1B over-expression and pCR; however, given the limited sample and heterogeneous treatment in our cohort, this hypothesis cannot be excluded. PMID:27840578

  15. [Occupational cholangiocarcinoma in a printer that responded to neoadjuvant chemoradiotherapy].

    PubMed

    Nakagawa, Kei; Katayose, Yu; Ishida, Kazuyuki; Hayashi, Hiroki; Morikawa, Takanori; Yoshida, Hiroshi; Motoi, Fuyuhiko; Naitoh, Takeshi; Kubo, Shoji; Unno, Michiaki

    2015-07-01

    A 42-year-old man working at a printing company was referred to our hospital for examination and treatment of icterus. We diagnosed resectable hilar cholangiocarcinoma and provided neoadjuvant chemoradiotherapy, extended right hepatectomy, and extrahepatic bile duct resection. A detailed history revealed that he had used 1,2-dichloropropane as part of his work as an offset colour proof-printer, and he has subsequently been recognized as having occupational cholangiocarcinoma. He has survived without recurrence for more than 2 and half years since the liver resection. In the present report, we describe our valuable experience of neoadjuvant chemoradiotherapy for occupational cholangiocarcinoma.

  16. Neoadjuvant capecitabine, radiotherapy, and bevacizumab (CRAB) in locally advanced rectal cancer: results of an open-label phase II study

    PubMed Central

    2011-01-01

    Background Preoperative capecitabine-based chemoradiation is a standard treatment for locally advanced rectal cancer (LARC). Here, we explored the safety and efficacy of the addition of bevacizumab to capecitabine and concurrent radiotherapy for LARC. Methods Patients with MRI-confirmed stage II/III rectal cancer received bevacizumab 5 mg/kg i.v. 2 weeks prior to neoadjuvant chemoradiotherapy followed by bevacizumab 5 mg/kg on Days 1, 15 and 29, capecitabine 825 mg/m2 twice daily on Days 1-38, and concurrent radiotherapy 50.4 Gy (1.8 Gy/day, 5 days/week for 5 weeks + three 1.8 Gy/day), starting on Day 1. Total mesorectal excision was scheduled 6-8 weeks after completion of chemoradiotherapy. Tumour regression grades (TRG) were evaluated on surgical specimens according to Dworak. The primary endpoint was pathological complete response (pCR). Results 61 patients were enrolled (median age 60 years [range 31-80], 64% male). Twelve patients (19.7%) had T3N0 tumours, 1 patient T2N1, 19 patients (31.1%) T3N1, 2 patients (3.3%) T2N2, 22 patients (36.1%) T3N2 and 5 patients (8.2%) T4N2. Median tumour distance from the anal verge was 6 cm (range 0-11). Grade 3 adverse events included dermatitis (n = 6, 9.8%), proteinuria (n = 4, 6.5%) and leucocytopenia (n = 3, 4.9%). Radical resection was achieved in 57 patients (95%), and 42 patients (70%) underwent sphincter-preserving surgery. TRG 4 (pCR) was recorded in 8 patients (13.3%) and TRG 3 in 9 patients (15.0%). T-, N- and overall downstaging rates were 45.2%, 73.8%, and 73.8%, respectively. Conclusions This study demonstrates the feasibility of preoperative chemoradiotherapy with bevacizumab and capecitabine. The observed adverse events of neoadjuvant treatment are comparable with those previously reported, but the pCR rate was lower. PMID:21880132

  17. Radiation-Related Predictors of Hematologic Toxicity After Concurrent Chemoradiation for Cervical Cancer and Implications for Bone Marrow-Sparing Pelvic IMRT

    SciTech Connect

    Albuquerque, Kevin; Giangreco, David; Morrison, Courtney; Siddiqui, Mohammed; Sinacore, Jim; Potkul, Ronald; Roeske, John

    2011-03-15

    Purpose: To determine factors predictive for hematologic toxicity (HT) associated with concurrent chemoradiation for Stage II through IV cervical cancer. Methods and Materials: The medical records of 40 women receiving concurrent chemoradiation for cervical cancer were reviewed. Hematologic toxicity was defined by use of Common Terminology Criteria for Adverse Events (version 3.0). Variables predicting for HT including age, body mass index, transfusions, and bone marrow volumes irradiated were included in the data analysis. Results: Of the patients, 13 (32.5%) had Grade 0 or 1 HT and 27 (67.5%) had Grade 2 through 4 HT (HT2+). Multiple logistic regression analysis of potential predictors showed that only the volume of bone receiving 20 Gy (V20) for whole pelvic bone tended toward significance for predicting HT2+. A strong correlation was noted between HT2+ and V20 (r = 0.8, p < 0.0001). A partitioning analysis to predict HT2+ showed a cutoff value of 79.42% (approximately 80%) for V20 of whole pelvic bone. That is, if the V20 of the whole pelvis exceeds 80%, the risk of HT2+ developing increases by a factor (odds ratio) of 4.5 (95%, confidence interval, 1.08-18.69) (p < 0.05). Conclusions: We have shown a correlation between bone marrow volume radiated and development of HT. This has implications for use of pelvic intensity-modulated radiation therapy, which can potentially decrease the volume of bone marrow radiated.

  18. Vascularized free tissue transfer for reconstruction of ablative defects in oral and oropharyngeal cancer patients undergoing salvage surgery following concomitant chemoradiation.

    PubMed

    Arce, K; Bell, R B; Potter, J K; Buehler, M J; Potter, B E; Dierks, E J

    2012-06-01

    The purpose of this study was to determine whether chemotherapy delivered concurrently with external beam radiation therapy for loco-regionally advanced head and neck cancer affects the rate or severity of postoperative complications in patients who underwent salvage surgery for recurrent or persistent disease with simultaneous microvascular free flap reconstruction. The primary study group consisted of patients with head and neck malignancies that had undergone surgical salvage with microvascular free flap reconstruction for persistent or recurrent disease following definitive radiation or concomitant chemoradiation treatment. A group of demographically matched patients who underwent microvascular free flap reconstruction for non-malignant and malignant conditions who never received radiation were randomly selected to serve as a control group. The study cohort was divided according to radiation treatment. The overall success rate of flap reconstruction was 92%, with an overall complication rate of 23%. Concurrently administered chemotherapy did not appear to affect the type of or the complication rate. The results of this investigation indicate that microvascular free flap reconstruction of head and neck defects is highly predictable, results in relatively few major complications, and suggests that neither radiation alone nor concomitant chemoradiation has a statistically significant effect on overall flap survival or complication rate.

  19. Impact of Neoadjuvant Radiation on Survival in Stage III Non-Small-Cell Lung Cancer

    SciTech Connect

    Koshy, Matthew; Goloubeva, Olga; Suntharalingam, Mohan

    2011-04-01

    Purpose: The role of surgery in Stage III non-small-cell lung cancer (NSCLC) is controversial. This study was undertaken to assess the impact of neoadjuvant radiation therapy for Stage III NSCLC. Methods and Materials: This was a retrospective study from the Surveillance, Epidemiology, and End Results (SEER) database that included patients who were 18 years and older with NSCLC classified as Stage III and who underwent definitive therapy from 1988 to 2004. Patients were characterized by type of treatment received. Survival functions were estimated by the Kaplan-Meier method, and Cox regression model was used to analyze trends in overall (OS) and cause-specific survival (CSS). Results: A total of 48,131 patients were selected, with a median follow-up of 10 months (range, 0-203 months). By type of treatment, the 3-year OS was 10% with radiation therapy (RT), 37% with surgery (S), 34% with surgery and postoperative radiation (S-RT), and 45% with neoadjuvant radiation followed by surgery (Neo-RT) (p = 0.0001). Multivariable Cox model identified sex, race, laterality, T stage, N stage, and type of treatment as factors affecting survival. Estimated hazard ratios (HR) adjusted for other variables in regression model showed the types of treatment: S (HR, 1.3; 95% confidence interval [CI], 1.2-1.4), S-RT (HR, 1.2; 95% CI, 1.1-1.3), and RT (HR, 2.3; 95% CI, 2.15-2.53) were associated with significantly worse overall survival when compared with Neo-RT (p = 0.0001). Conclusion: This population based study demonstrates that patients with Stage III NSCLC receiving Neo-RT had significantly improved overall survival when compared with other treatment groups.

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

    SciTech Connect

    Dipetrillo, Tom; Pricolo, Victor; Lagares-Garcia, Jorge; Vrees, Matt; Klipfel, Adam; Cataldo, Tom; Sikov, William; McNulty, Brendan; Shipley, Joshua; Anderson, Elliot; Khurshid, Humera; Oconnor, Brigid; Oldenburg, Nicklas B.E.; Radie-Keane, Kathy; Husain, Syed; Safran, Howard

    2012-01-01

    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 performed 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.

  1. Docetaxel as neoadjuvant chemotherapy in patients with advanced cervical carcinoma.

    PubMed

    Vallejo, Carlos T; Machiavelli, Mario R; Pérez, Juan E; Romero, Alberto O; Bologna, Fabrina; Vicente, Hernán; Lacava, Juan A; Ortiz, Eduardo H; Cubero, Alberto; Focaccia, Guillermo; Suttora, Guillermo; Scenna, Mirna; Boughen, José M; Leone, Bernardo A

    2003-10-01

    The purpose of this study was to evaluate the efficacy and toxicity of docetaxel as single-agent neoadjuvant chemotherapy in locoregionally advanced cervical carcinoma. Between April 1998 and August 2000, 38 untreated patients with International Federation of Gynecology and Obstetrics stages IIB to IVA were entered onto this study. The median age was 44 years (range: 25-66 years). Stages: IIB 22 patients, IIIB 15 patients, and IVA 1 pt. Treatment consisted of docetaxel 100 mg/m2 IV infusion during 1 hour. Standard premedication with dexamethasone, diphenhydramine, and ranitidine was used. Cycles were repeated every 3 weeks for three courses, followed by radical surgery when it was judged appropriate, or definitive radiotherapy. Both staging and response assessment were performed by a multidisciplinary team. 106 cycles of therapy were administered; all patients were evaluable for TX, whereas 35 were evaluable for response (3 patients refused further treatment after the first cycle of therapy). Complete response (CR): 1 patient (3%); partial response: 11 patients (31%), for an overall objective response rate of 34% (95% CI: 15-53%); no change (NC): 16 patients (46%); and progressive disease: 7 patients (20%). Six patients (17%) underwent surgery and a pathologic CR was confirmed in 1 of them. The median time to treatment failure and the median survival have not been reached yet. The limiting toxicity was leukopenia in 25 patients (69%) (G1-G2: 14 patients, G3: 10 patients, and G4: 1 patient). Neutropenia: 28 patients (78%) (G1-G2: 10 patients, G3: 8 and G4: 10). Myalgias: 17 patients (47%) (G1-G2: 15 patients and G3: 2 patients). Emesis: 21 patients (55%) (G1-G2: 19 patients and G3: 2 patients). Alopecia G3: 13 patients (36%); rash cutaneous 26 patients (68%) (G1-G2: 22 patients and G3: 4 patients). There were no hypersensitivity reactions or fluid-retention syndrome. The received dose intensity was 91% of that projected. Docetaxel is an active drug against advanced

  2. Molecular Genetic Changes Associated With Colorectal Carcinogenesis Are Not Prognostic for Tumor Regression Following Preoperative Chemoradiation of Rectal Carcinoma

    SciTech Connect

    Zauber, N. Peter Marotta, Steven P.; Berman, Errol; Grann, Alison; Rao, Maithili; Komati, Naga; Ribiero, Kezia; Bishop, D. Timothy

    2009-06-01

    Purpose: Preoperative chemotherapy and radiation has become the standard of care for many patients with rectal cancer. The therapy may have toxicity and delays definitive surgery. It would therefore be desirable to identify those cancers that will not regress with preoperative therapy. We assessed a series of rectal cancers for the molecular changes of loss of heterozygosity of the APC and DCC genes, K-ras mutations, and microsatellite instability, changes that have clearly been associated with rectal carcinogenesis. Methods and Materials: Diagnostic colonoscopic biopsies from 53 patients who received preoperative chemotherapy and radiation were assayed using polymerase chain reaction techniques followed by single-stranded conformation polymorphism and DNA sequencing. Regression of the primary tumor was evaluated using the surgically removed specimen. Results: Twenty-three lesions (45%) were found to have a high degree of regression. None of the molecular changes were useful as indicators of regression. Conclusions: Recognized molecular changes critical for rectal carcinogenesis including APC and DCC loss of heterozygosity, K-ras mutations, and microsatellite instability are not useful as indicators of tumor regression following chemoradiation for rectal carcinoma.

  3. HER-2, p53, p21 and hormonal receptors proteins expression as predictive factors of response and prognosis in locally advanced breast cancer treated with neoadjuvant docetaxel plus epirubicin combination

    PubMed Central

    Tiezzi, Daniel G; Andrade, Jurandyr M; Ribeiro-Silva, Alfredo; Zola, Fábio E; Marana, Heitor RC; Tiezzi, Marcelo G

    2007-01-01

    Background Neoadjuvant chemotherapy has been considered the standard care in locally advanced breast cancer. However, about 20% of the patients do not benefit from this clinical treatment and, predictive factors of response were not defined yet. This study was designed to evaluate the importance of biological markers to predict response and prognosis in stage II and III breast cancer patients treated with taxane and anthracycline combination as neoadjuvant setting. Methods Sixty patients received preoperative docetaxel (75 mg/m2) in combination with epirubicin (50 mg/m2) in i.v. infusion in D1 every 3 weeks after incisional biopsy. They received adjuvant chemotherapy with CMF or FEC, attaining axillary status following definitive breast surgery. Clinical and pathologic response rates were measured after preoperative therapy. We evaluated the response rate to neoadjuvant chemotherapy and the prognostic significance of clinicopathological and immunohistochemical parameters (ER, PR, p51, p21 and HER-2 protein expression). The median patient age was 50.5 years with a median follow up time 48 months after the time of diagnosis. Results Preoperative treatment achieved clinical response in 76.6% of patients and complete pathologic response in 5%. The clinical, pathological and immunohistochemical parameters were not able to predict response to therapy and, only HER2 protein overexpression was associated with a decrease in disease free and overall survival (P = 0.0007 and P = 0.003) as shown by multivariate analysis. Conclusion Immunohistochemical phenotypes were not able to predict response to neoadjuvant chemotherapy. Clinical response is inversely correlated with a risk of death in patients submitted to neoadjuvant chemotherapy and HER2 overexpression is the major prognostic factor in stage II and III breast cancer patients treated with a neoadjuvant docetaxel and epirubicin combination. PMID:17324279

  4. Relationship Between Low Hemoglobin Levels and Outcomes After Treatment With Radiation or Chemoradiation in Patients With Cervical Cancer: Has the Impact of Anemia Been Overstated?

    SciTech Connect

    Bishop, Andrew J.; Allen, Pamela K.; Klopp, Ann H.; Meyer, Larissa A.; Eifel, Patricia J.

    2015-01-01

    Purpose: Previous reports have suggested that anemia increases rates of recurrence after radiation therapy for cervical cancer. However, these studies may not have fully corrected for confounding risk factors. Using a well-characterized cohort of cervical cancer patients, we examined the association between anemia and outcomes before and after the introduction of chemoradiation as standard of care. Methods and Materials: We reviewed the records of 2454 patients who underwent definitive radiation therapy from 1980 through 2011. Minimum hemoglobin level (Hgb{sub min}) was recorded for 2359 patients (96%). Endpoints included freedom from central recurrence (FFCR), freedom from distant metastasis (FFDM), and disease-specific survival (DSS). Results: For the entire cohort, hemoglobin concentrations of 9, 10, and 12 g/dL before and during radiation were all significantly associated with FFCR, FFDM, and DSS (all P<.001) on univariate analysis. However, on multivariate analysis, only Hgb{sub min} less than 10 g/dL during RT (RT-Hgb{sub <10}) remained significant, and it was correlated with lower DSS (P=.02, hazard ratio [HR] = 1.28) and FFDM (P=.03, HR = 1.33) but not with FFCR. In a subset analysis of patients receiving chemoradiation (n=678), RT-Hgb{sub <10} was associated only with DSS (P=.008, HR = 1.49), not with FFCR or FFDM. In this subgroup, despite an association between RT-Hgb{sub <10} and DSS, the use of transfusion was not correlated with benefit. Conclusions: No evidence was found supporting anemia as an independent predictor of central recurrence in patients treated with definitive radiation therapy with or without chemotherapy. Less emphasis on correcting anemia in cervical cancer patients may be warranted.

  5. Phase II Study of Neoadjuvant Bevacizumab and Radiotherapy for Resectable Soft Tissue Sarcomas

    SciTech Connect

    Yoon, Sam S.; Duda, Dan G.; Karl, Daniel L.; Kim, Tae-Min; Kambadakone, Avinash R.; Chen, Yen-Lin; Rothrock, Courtney; Rosenberg, Andrew E.; Nielsen, G. Petur; Kirsch, David G.; Choy, Edwin; Harmon, David C.; Hornicek, Francis J.; Dreyfuss, Jonathan; Ancukiewicz, Marek; and others

    2011-11-15

    Purpose: Numerous preclinical studies have demonstrated that angiogenesis inhibitors can increase the efficacy of radiotherapy (RT). We sought to examine the safety and efficacy of bevacizumab (BV) and RT in soft tissue sarcomas and explore biomarkers to help determine the treatment response. Methods and Materials: Patients with {>=}5 cm, intermediate- or high-grade soft tissue sarcomas at significant risk of local recurrence received neoadjuvant BV alone followed by BV plus RT before surgical resection. Correlative science studies included analysis of the serial blood and tumor samples and serial perfusion computed tomography scans. Results: The 20 patients had a median tumor size of 8.25 cm, with 13 extremity, 1 trunk, and 6 retroperitoneal/pelvis tumors. The neoadjuvant treatment was well tolerated, with only 4 patients having Grade 3 toxicities (hypertension, liver function test elevation). BV plus RT resulted in {>=}80% pathologic necrosis in 9 (45%) of 20 tumors, more than double the historical rate seen with RT alone. Three patients had a complete pathologic response. The median microvessel density decreased 53% after BV alone (p <.05). After combination therapy, the median tumor cell proliferation decreased by 73%, apoptosis increased 10.4-fold, and the blood flow, blood volume, and permeability surface area decreased by 62-72% (p <.05). Analysis of gene expression microarrays of untreated tumors identified a 24-gene signature for treatment response. The microvessel density and circulating progenitor cells at baseline and the reduction in microvessel density and plasma soluble c-KIT with BV therapy also correlated with a good pathologic response (p <.05). After a median follow-up of 20 months, only 1 patient had developed local recurrence. Conclusions: The results from the present exploratory study indicated that BV increases the efficacy of RT against soft tissue sarcomas and might reduce the incidence of local recurrence. Thus, this regimen warrants

  6. Phase 2 Study of Erlotinib Combined With Adjuvant Chemoradiation and Chemotherapy in Patients With Resectable Pancreatic Cancer

    SciTech Connect

    Herman, Joseph M.; Fan, Katherine Y.; Wild, Aaron T.; Hacker-Prietz, Amy; Wood, Laura D.; Blackford, Amanda L.; Ellsworth, Susannah; Zheng, Lei; Le, Dung T.; De Jesus-Acosta, Ana; Hidalgo, Manuel; Donehower, Ross C.; Schulick, Richard D.; Edil, Barish H.; Choti, Michael A.; Hruban, Ralph H.; and others

    2013-07-15

    Purpose: Long-term survival rates for patients with resected pancreatic ductal adenocarcinoma (PDAC) have stagnated at 20% for more than a decade, demonstrating the need to develop novel adjuvant therapies. Gemcitabine-erlotinib therapy has demonstrated a survival benefit for patients with metastatic PDAC. Here we report the first phase 2 study of erlotinib in combination with adjuvant chemoradiation and chemotherapy for resected PDAC. Methods and Materials: Forty-eight patients with resected PDAC received adjuvant erlotinib (100 mg daily) and capecitabine (800 mg/m{sup 2} twice daily Monday-Friday) concurrently with intensity modulated radiation therapy (IMRT), 50.4 Gy over 28 fractions followed by 4 cycles of gemcitabine (1000 mg/m{sup 2} on days 1, 8, and 15 every 28 days) and erlotinib (100 mg daily). The primary endpoint was recurrence-free survival (RFS). Results: The median follow-up time was 18.2 months (interquartile range, 13.8-27.1). Lymph nodes were positive in 85% of patients, and margins were positive in 17%. The median RFS was 15.6 months (95% confidence interval [CI], 13.4-17.9), and the median overall survival (OS) was 24.4 months (95% CI, 18.9-29.7). Multivariate analysis with adjustment for known prognostic factors showed that tumor diameter >3 cm was predictive for inferior RFS (hazard ratio, 4.01; P=.001) and OS (HR, 4.98; P=.02), and the development of dermatitis was associated with improved RFS (HR, 0.27; P=.009). During CRT and post-CRT chemotherapy, the rates of grade 3/4 toxicity were 31%/2% and 35%/8%, respectively. Conclusion: Erlotinib can be safely administered with adjuvant IMRT-based CRT and chemotherapy. The efficacy of this regimen appears comparable to that of existing adjuvant regimens. Radiation Therapy Oncology Group 0848 will ultimately determine whether erlotinib produces a survival benefit in patients with resected pancreatic cancer.

  7. Bevacizumab Addition in Neoadjuvant Treatment Increases the Pathological Complete Response Rates in Patients with HER-2 Negative Breast Cancer Especially Triple Negative Breast Cancer: A Meta-Analysis

    PubMed Central

    Zhang, Jing; Zhang, Binglan; Shi, Changle; Liu, Lei

    2016-01-01

    Background Neoadjuvant therapy is administered to breast cancer patients as an induction process before surgery or radiotherapy to reduce tumor size. Human epidermal growth factor receptor-2 (HER-2) negative breast cancer lacks effective standard target therapy. Bevacizumab has a controversial role in the treatment of breast cancer and we conduct a meta-analysis to evaluate the value of adding bevacizumab in neoadjuvant regimen. Methods Potentially eligible studies were retrieved using PubMed, EMBASE and Medline. Clinical characteristics of patients and statistical data with pathological complete response (pCR) data were collected. Then a meta-analysis model was established to investigate the correlation between administration of bevacizumab in neoadjuvant therapy and pCR rates in HER-2 negative breast cancer. Results Seven eligible studies and 5408 patients were yielded. The pCR rates for “breast” or “breast plus lymph node” were similar. In subgroup analysis, we emphasized on patients with triple-negative breast cancer (TNBC). In the criterion of “lesions in breast” the pooled ORs was 1.55 [1.29, 1.86], P<0.00001 and regarding to the evaluation criterion of “lesions in breast and lymph nodes”, the pooled ORs was 1.48 [1.23, 1.78], P<0.0001, in favor of bevacizumab administration. Conclusion According to our pooled results, we finally find that bevacizumab addition as a neoadjuvant chemotherapy component, for induction use with limited cycle to improve the pCR rates and patients may avoid long-term adverse event and long-term invalid survival improvement. Especially in subgroup analysis, pCR rates could be improved significantly and physicians could consider bevacizumab with caution. As patients could avoid the adverse event caused by long-term using of bevacizumab, long-term quality of life improvement may be achieved, especially in TNBC. PMID:27579484

  8. Mismatch Repair Gene Expression as a Predictor of Tumor Responses in Patients With Rectal Cancer Treated With Preoperative Chemoradiation

    PubMed Central

    Huh, Jung Wook; Kim, Hee Cheol; Kim, Seok Hyung; Park, Yoon Ah; Cho, Yong Beom; Yun, Seong Hyeon; Lee, Woo Yong; Park, Hee Chul; Choi, Doo Ho; Park, Joon Oh; Park, Young Suk; Chun, Ho-Kyung

    2016-01-01

    Abstract This study evaluated the predictive and prognostic value of expression of mismatch repair (MMR) protein, including MLH1, MSH2, and MSH6 in rectal cancer patients with preoperative chemoradiotherapy. MMR protein expression was measured by immunohistochemistry in both pretreatment biopsies (pre-) and pathologic specimens (post-) from 209 patients with locally advanced rectal cancer who underwent preoperative chemoradiotherapy and radical surgery. The patients were followed for a median period of 44 months. A pathologic complete response (pCR) was observed in 30 patients (14.4%). The expression levels of MLH1, MSH2, and MSH6 were not significantly different between the pCR and non-pCR groups. A multivariate analysis revealed that tumor differentiation, postoperative chemotherapy, and pre-MSH6 expression were independent predictors of overall survival; ypN category and perineural invasion were independent predictors of disease-free survival. The pre-MSH6 expression was significantly associated with tumor budding and expression of all MMR proteins. On multivariate analysis, ypN category and post-MSH6 expression were independent predictors for local recurrence. In our study, we observed the independent prognostic value of MSH6 expression in pretreatment tissue on overall survival and MSH6 expression after chemoradiation on local recurrence. Constitutive MSH6 expression before and after preoperative therapy may be a useful tool for prediction of oncologic outcome in locally advanced rectal cancer. PMID:26817916

  9. Concurrent Chemoradiation With Carboplatin-5-Fluorouracil Versus Cisplatin in Locally Advanced Oropharyngeal Cancers: Is More Always Better?

    SciTech Connect

    Barkati, Maroie; Fortin, Bernard; Soulieres, Denis; Clavel, Sebastien; Despres, Phillipe; Charpentier, Danielle; Tabet, Jean-Claude; Guertin, Louis; Olivier, Marie-Jo; Coulombe, Genevieve; Donath, David; Nguyen-Tan, Phuc Felix

    2010-02-01

    Purpose: The optimal chemotherapy regimen remains undefined in the treatment of locally advanced oropharyngeal cancer by concomitant chemoradiation. This article compares two platinum-based chemotherapy regimens. Methods and Materials: In this retrospective study, we reviewed all consecutive patients treated for Stage III or IVA-B oropharyngeal cancer using either a combination of carboplatin and 5-fluorouracil (5FU) every 3 weeks or high-dose cisplatin every 3 weeks concomitant with definitive radiation therapy. Results: A total of 200 patients were treated with carboplatin-5FU and 53 patients with cisplatin. Median potential follow-up was 43 months. The 3-year overall survival rates for carboplatin-5FU and cisplatin respectively were 79.1% and 74.9% (p = 0.628), the 3-year disease-free survival rates were 76.0% and 71.3% (p = 0.799), and the 3-year locoregional control rates were 88.4% and 94.2% (p = 0.244). Conclusions: We could not demonstrate differences between these two regimens, which both proved efficacious. Polychemotherapy and monochemotherapy therefore seem comparable in this retrospective analysis.

  10. Pathological controversies in breast cancer: classification of ductal carcinoma in situ, sentinel lymph nodes and low volume metastatic disease and reporting of neoadjuvant chemotherapy specimens.

    PubMed

    Provenzano, E; Brown, J P; Pinder, S E

    2013-02-01

    The pathological classification of breast cancer is constantly being updated to reflect the advances in our clinical and biological understanding of the disease. This overview examines new insights into the classification and molecular biology of ductal carcinoma in situ, the pathological handling of sentinel lymph node biopsies and the identification of low volume disease (micrometastases and isolated tumour cells) and the handling and reporting of specimens after neoadjuvant therapy. The molecular subtypes of invasive breast cancer are also represented in ductal carcinoma in situ. It is hoped that alongside traditional histological features, such as cytological grade and the presence of necrosis, this will lead to better classification systems with improved prediction of clinical behaviour, in particular the risk of progression to invasive cancer, and enable more targeted management. Sentinel lymph node biopsy is now the standard of care for early stage breast cancer in clinically node-negative patients. However, the handling and reporting of these specimens remains controversial, largely related to the uncertainties regarding the clinical significance of micrometastases and isolated tumour cells. The increasing use of neoadjuvant therapies has introduced challenges for the pathologist in the handling and interpretation of these specimens. Grading the tumour response, particularly the identification of a complete pathological response, is prognostically important. However, there is still marked variability in reporting these specimens in routine practice, and consensus guidelines for the histopathology reporting of breast cancers after neoadjuvant chemotherapy based on robust, validated evidence are presently lacking.

  11. In Vitro and In Vivo Enhancement of Chemoradiation Using the Oral PARP Inhibitor ABT-888 in Colorectal Cancer Cells

    SciTech Connect

    Shelton, Joseph W.; Waxweiler, Timothy V.; Landry, Jerome; Gao, Huiying; Xu, Yanbo; Wang, Lanfang; El-Rayes, Bassel; Shu, Hui-Kuo G.

    2013-07-01

    Purpose: Poly(ADP-ribose) polymerase plays a critical role in the recognition and repair of DNA single-strand breaks and double-strand breaks (DSBs). ABT-888 is an orally available inhibitor of this enzyme. This study seeks to evaluate the use of ABT-888 combined with chemotherapy and radiation therapy (RT) in colorectal carcinoma models. Methods and Materials: RT clonogenic assays were performed on HCT116 and HT29 cells treated with 5-fluorouracil, irinotecan, or oxaliplatin with or without ABT. The surviving fraction at 2 Gy and dose-modifying factor at 10% survival were analyzed. Synergism was assessed by isobologram analysis for combination therapies. γH2AX and neutral comet assays were performed to assess the effect of therapy on DSB formation/repair. In vivo assessments were made by use of HCT116 cells in a xenograft mouse model. Tumor growth delay was measured at a volume of 500 mm{sup 3}. Results: Both lines were radiosensitized by ABT alone, and ABT further increased chemotherapy dose-modifying factors to the 1.6 to 1.8 range. All combinations were synergistic (combination indices <0.9). ABT treatment significantly increased DSB after RT (γH2AX, 69% vs 43%; P=.017) and delayed repair. We found tumor growth delays of 7.22 days for RT; 11.90 days for RT and ABT; 13.5 days for oxaliplatin, RT, and ABT; 14.17 days for 5-fluorouracil, RT, and ABT; and 23.81 days for irinotecan, RT, and ABT. Conclusion: ABT-888 radiosensitizes at similar or higher levels compared with classic chemotherapies and acts synergistically with these chemotherapies to enhance RT effects. In vivo confirmation of these results indicates a potential role for combining its use with existing chemoradiation regimens.

  12. 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

    SciTech Connect

    Sarna, Linda Swann, Suzanne; Langer, Corey; Werner-Wasik, Maria; Nicolaou, Nicos; Komaki, Ritsuko; Machtay, Mitchell; Byhardt, Roger; Wasserman, Todd; Movsas, Benjamin

    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 symptoms 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.

  13. Multimodality therapy for head and neck cancer.

    PubMed

    Klein, Mary K

    2003-05-01

    The refinement of radiation therapy techniques should result in a decrease in morbidity in canine and feline nasal carcinoma patients and should further allow for the addition of adjuvant therapies. Patients with large oral tumors that are incompletely excised should have radiation therapy added to their treatment regimen. Tumors with significant metastatic potential, such as melanoma, should be considered for addition of chemotherapy. Carboplatin has activity in melanomas and is being added at several institutions, but trial results are not yet available. Chemoradiation has become the treatment of choice for human head and neck squamous cell carcinomas but remains largely unexplored in veterinary medicine. Hopefully, development of chemoradiation will benefit feline squamous cell carcinoma patients, because current treatment regimens are largely ineffective. Immunotherapy agents and targeted biologic therapeutics seem to hold promise for the future.

  14. Refining Patient Selection for Neoadjuvant Chemotherapy before Radical Cystectomy

    PubMed Central

    Culp, Stephen H.; Dickstein, Rian J.; Grossman, H. Barton; Pretzsch, Shanna M.; Porten, Sima; Daneshmand, Siamak; Cai, Jie; Groshen, Susan; Siefker-Radtke, Arlene; Millikan, Randall E.; Czerniak, Bogdan; Navai, Neema; Wszolek, Matthew F.; Kamat, Ashish M.; Dinney, Colin P. N.

    2014-01-01

    Purpose We evaluated the survival of patients with muscle invasive bladder cancer undergoing radical cystectomy without neoadjuvant chemotherapy to confirm the utility of existing clinical tools to identify low risk patients who could be treated with radical cystectomy alone and a high risk group most likely to benefit from neoadjuvant chemotherapy. Materials and Methods We identified patients with muscle invasive bladder cancer who underwent radical cystectomy without neoadjuvant chemotherapy at our institution between 2000 and 2010. Patients were considered high risk based on the clinical presence of hydroureteronephrosis, cT3b-T4a disease, and/or histological evidence of lymphovascular invasion, micropapillary or neuroendocrine features on transurethral resection. We evaluated survival (disease specific, progression-free and overall) and rate of pathological up staging. An independent cohort of patients from another institution was used to confirm our findings. Results We identified 98 high risk and 199 low risk patients eligible for analysis. High risk patients exhibited decreased 5-year overall survival (47.0% vs 64.8%) and decreased disease specific (64.3% vs 83.5%) and progression-free (62.0% vs 84.1%) survival probabilities compared to low risk patients (p <0.001). Survival outcomes were confirmed in the validation subset. On final pathology 49.2% of low risk patients had disease up staged. Conclusions The 5-year disease specific survival of low risk patients was greater than 80%, supporting the distinction of high risk and low risk muscle invasive bladder cancer. The presence of high risk features identifies patients with a poor prognosis who are most likely to benefit from neoadjuvant chemotherapy, while many of those with low risk disease can undergo surgery up front with good expectations and avoid chemotherapy associated toxicity. PMID:23911605

  15. Subharmonic Imaging and Pressure Estimation for Monitoring Neoadjuvant Chemotherapy

    DTIC Science & Technology

    2013-09-01

    441-. 7. Mauri D ., Pavlidis N, and Ioannidis JPA, Neoadjuvant Versus Adjuvant Systemic Treatment in Breast Cancer: A Meta-Analysis. J. Natl. Cancer...imaging modality and 3D SHAPE in an in vitro flow phantom using the modified US scanner (month 3). d . Prepare regulatory submissions for clinical...neovascularity in women compared to CD31 stained specimens (Months 5 - 23). d . Perform statistical analyses and write final report (months 23 - 24).

  16. Randomized trial of neoadjuvant chemotherapy in oropharyngeal carcinoma

    PubMed Central

    Domenge, C; Hill, C; Lefebvre, J L; De Raucourt, D; Rhein, B; Wibault, P; Marandas, P; Coche-Dequeant, B; Stromboni-Luboinski, M; Sancho-Garnier, H; Luboinski, B

    2000-01-01

    The objective of the study was to evaluate the effect of neoadjuvant chemotherapy on the survival of patients with oropharyngeal cancer. Patients with a squamous cell carcinoma of the oropharynx for whom curative radiotherapy or surgery was considered feasible were entered in a multicentric randomized trial comparing neoadjuvant chemotherapy followed by loco-regional treatment to the same loco-regional treatment without chemotherapy. The loco-regional treatment consisted either of surgery plus radiotherapy or of radiotherapy alone. Three cycles of chemotherapy consisting of Cisplatin (100 mg/m2) on day 1 followed by a 24-hour i.v. infusion of fluorouracil (1000 mg/m2/day) for 5 days were delivered every 21 days. 2–3 weeks after the end of chemotherapy, local treatment was performed. The trial was conducted by the Groupe d'Etude des Tumeurs de la Tête Et du Cou (GETTEC). A total of 318 patients were enrolled in the study between 1986 and 1992. Overall survival was significantly better (P = 0.03) in the neoadjuvant chemotherapy group than in the control group, with a median survival of 5.1 years versus 3.3 years in the no chemotherapy group. The effect of neoadjuvant chemotherapy on event-free survival was smaller and of borderline significance (P = 0.11). Stratification of the results on the type of local treatment, surgery plus radiotherapy or radiotherapy alone, did not reveal any heterogeneity in the effect of chemotherapy. © 2000 Cancer Research Campaign http://www.bjcancer.com PMID:11189100

  17. Decreased identification rate of sentinel lymph node after neoadjuvant chemotherapy.

    PubMed

    Kang, Seok Hyung; Kim, Seok-Ki; Kwon, Youngmee; Kang, Han-Sung; Kang, Jae Hee; Ro, Jungsil; Lee, Eun Sook

    2004-10-01

    We prospectively studied the feasibility of sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy by comparing the identification rate and the false-negative rate (FNR) with the results obtained from the patients without chemotherapy. From October 2001 to March 2003, a total of 284 consecutive patients who underwent SLNB and axillary lymph node dissection (ALND) at the Center for Breast Cancer, National Cancer Center were enrolled. Of the 284 patients, 54 underwent neoadjuvant chemotherapy prior to operation. The sentinel lymph node (SLN) was mapped by radioactive colloid alone or in combination with blue dye. All SLNs were evaluated by 2 mm serial sections after hematoxylin-eosin staining. The overall SLN identification rate was 91.9% (261/284): 72.2% (39/54) of the patients after chemotherapy and 96.5% (222/230) of the patients without chemotherapy. These results suggest that preoperative chemotherapy significantly affects lymphatic mapping ( p< 0.001). Among the patients with chemotherapy, there were 3 false negatives in 39 successfully mapped tumors, yielding an FNR of 11.1% (3/27), a negative prediction value (NPV) of 80.0% (12/15), and an accuracy of 92.3% (36/39). There were 10 false negatives among 222 successfully detected patients without chemotherapy, yielding an FNR of 9.9% (10/101), an NPV of 92.4% (121/131), and an accuracy of 95.5% (212/222). These results were not statistically different when compared ( p > 0.05). Although the SLN identification rate significantly decreased after neoadjuvant chemotherapy, SLNB could accurately predict axillary status. Thus SLNB can be an alternative to ALND even after neoadjuvant chemotherapy in cases of successful identification of the SLN.

  18. Treatment of Locally Advanced Pancreatic Cancer: The Role of Radiation Therapy

    SciTech Connect

    Johung, Kimberly; Saif, Muhammad Wasif; Chang, Bryan W.

    2012-02-01

    Pancreatic cancer remains associated with an extremely poor prognosis. Surgical resection can be curative, but the majority of patients present with locally advanced or metastatic disease. Treatment for patients with locally advanced disease is controversial. Therapeutic options include systemic therapy alone, concurrent chemoradiation, or induction chemotherapy followed by chemoradiation. We review the evidence to date regarding the treatment of locally advanced pancreatic cancer (LAPC), as well as evolving strategies including the emerging role of targeted therapies. We propose that if radiation is used for patients with LAPC, it should be delivered with concurrent chemotherapy and following a period of induction chemotherapy.

  19. Role of Postmastectomy Radiation After Neoadjuvant Chemotherapy in Stage II-III Breast Cancer

    SciTech Connect

    Fowble, Barbara L.; Einck, John P.; Kim, Danny N.; McCloskey, Susan; Mayadev, Jyoti; Yashar, Catheryn; Chen, Steven L.; Hwang, E. Shelley

    2012-06-01

    Purpose: To identify a cohort of women treated with neoadjuvant chemotherapy and mastectomy for whom postmastectomy radiation therapy (PMRT) may be omitted according to the projected risk of local-regional failure (LRF). Methods and Materials: Seven breast cancer physicians from University of California cancer centers created 14 hypothetical clinical case scenarios, identified, reviewed, and abstracted the available literature (MEDLINE and Cochrane databases), and formulated evidence tables with endpoints of LRF, disease-free survival, and overall survival. Using the American College of Radiology appropriateness criteria methodology, appropriateness ratings for postmastectomy radiation were assigned for each scenario. Finally, an overall summary risk assessment table was developed. Results: Of 24 sources identified, 23 were retrospective studies from single institutions. Consensus on the appropriateness rating, defined as 80% agreement in a category, was achieved for 86% of the cases. Distinct LRF risk categories emerged. Clinical stage II (T1-2N0-1) patients, aged >40 years, estrogen receptor-positive subtype, with pathologic complete response or 0-3 positive nodes without lymphovascular invasion or extracapsular extension, were identified as having {<=}10% risk of LRF without radiation. Limited data support stage IIIA patients with pathologic complete response as being low risk. Conclusions: In the absence of randomized trial results, existing data can be used to guide the use of PMRT in the neoadjuvant chemotherapy setting. Using available studies to inform appropriateness ratings for clinical scenarios, we found a high concordance of treatment recommendations for PMRT and were able to identify a cohort of women with a low risk of LRF without radiation. These low-risk patients will form the basis for future planned studies within University of California Athena Breast Health Network.

  20. Utilization of Neoadjuvant Chemotherapy Varies in the Treatment of Women with Invasive Breast Cancer

    PubMed Central

    Onitilo, Adedayo A.; Onesti, Jill K.; Single, Richard M.; Engel, Jessica M.; James, Ted A.; Aiello Bowles, Erin J.; Feigelson, Heather Spencer; Barney, Tom; McCahill, Laurence E.

    2013-01-01

    Background Treatment with neoadjuvant chemotherapy (NAC) has made it possible for some women to be successfully treated with breast conservation therapy (BCT ) who were initially considered ineligible. Factors related to current practice patterns of NAC use are important to understand particularly as the surgical treatment of invasive breast cancer has changed. The goal of this study was to determine variations in neoadjuvant chemotherapy use in a large multi-center national database of patients with breast cancer. Methods We evaluated NAC use in patients with initially operable invasive breast cancer and potential impact on breast conservation rates. Records of 2871 women ages 18-years and older diagnosed with 2907 invasive breast cancers from January 2003 to December 2008 at four institutions across the United States were examined using the Breast Cancer Surgical Outcomes (BRCASO) database. Main outcome measures included NAC use and association with pre-operatively identified clinical factors, surgical approach (partial mastectomy [PM] or total mastectomy [TM]), and BCT failure (initial PM followed by subsequent TM). Results Overall, NAC utilization was 3.8%l. Factors associated with NAC use included younger age, pre-operatively known positive nodal status, and increasing clinical tumor size. NAC use and BCT failure rates increased with clinical tumor size, and there was significant variation in NAC use across institutions. Initial TM frequency approached initial PM frequency for tumors >30-40mm; BCT failure rate was 22.7% for tumors >40mm. Only 2.7% of patients undergoing initial PM and 7.2% undergoing initial TM received NAC. Conclusions NAC use in this study was infrequent and varied among institutions. Infrequent NAC use in patients suggests that NAC may be underutilized in eligible patients desiring breast conservation. PMID:24376822

  1. A marker of homologous recombination predicts pathological complete response to neoadjuvant chemotherapy in primary breast cancer

    PubMed Central

    Graeser, Monika; McCarthy, Afshan; Lord, Christopher J; Savage, Kay; Hills, Margaret; Salter, Janine; Orr, Nicholas; Parton, Marina; Smith, Ian E; Reis-Filho, Jorge S; Dowsett, Mitch; Ashworth, Alan; Turner, Nicholas

    2010-01-01

    Purpose To assess the prevalence of defective homologous recombination (HR) based DNA repair in sporadic primary breast cancers, examine the clincopathological features that correlate of with defective HR and the relationship with neoadjuvant chemotherapy response. Experimental Design We examined a cohort of 68 patients with sporadic primary breast cancer who received neoadjuvant anthracylcine based chemotherapy, with core biopsies taken 24 hours after the first cycle of chemotherapy. We assessed RAD51 focus formation, a marker of HR competence, by immunofluorescence in post chemotherapy biopsies along with geminin as a marker of proliferative cells. We assessed the RAD51 score as the proportion of proliferative cells with RAD51 foci. Results A low RAD51 score was present in 26% of cases (15/57, 95% CI, 15-40%). Low RAD51 score correlated with high histological grade (p=0.031) and high baseline Ki67 (p=0.005). Low RAD51 score was more frequent in triple negative breast cancers compared to ER and/or HER2 positive breast cancer (67% vs 19% respectively, p=0.0036). Low RAD51 score was strongly predictive of pathological complete response to chemotherapy, with 33% low RAD51 score cancers achieving pathological complete response compared to 3% of other cancers (p=0.011). Conclusions Our results suggest that defective HR, as indicated by low RAD51 score, may be one of the factors that underlie sensitivity to anthracycline based chemotherapy. Defective HR is frequent in triple negative breast cancer, but is also present in a subset of other subtypes, identifying breast cancers that may benefit from therapies that target defective HR, such as PARP inhibitors. PMID:20802015

  2. Cardiovascular Morbidity After Radiotherapy or Chemoradiation in Patients With Cervical Cancer

    SciTech Connect

    Maduro, John H.; Dekker, Helena A. den; Pras, Elisabeth; Vries, Elisabeth G. de; Zee, Ate G. van der; Klokman, Willem J.; Reyners, Anna K.; Leeuwen, Flora E. van; Langendijk, Johannes A.; Bock, Geertruida H. de; Gietema, Jourik A.

    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. 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.

  3. Assessment of tumor regression of esophageal adenocarcinomas after neoadjuvant chemotherapy: comparison of 2 commonly used scoring approaches.

    PubMed

    Karamitopoulou, Eva; Thies, Svenja; Zlobec, Inti; Ott, Katja; Feith, Marcus; Slotta-Huspenina, Julia; Lordick, Florian; Becker, Karen; Langer, Rupert

    2014-11-01

    Histopathologic determination of tumor regression provides important prognostic information for locally advanced gastroesophageal carcinomas after neoadjuvant treatment. Regression grading systems mostly refer to the amount of therapy-induced fibrosis in relation to residual tumor or the estimated percentage of residual tumor in relation to the former tumor site. Although these methods are generally accepted, currently there is no common standard for reporting tumor regression in gastroesophageal cancers. We compared the application of these 2 major principles for assessment of tumor regression: hematoxylin and eosin-stained slides from 89 resection specimens of esophageal adenocarcinomas following neoadjuvant chemotherapy were independently reviewed by 3 pathologists from different institutions. Tumor regression was determined by the 5-tiered Mandard system (fibrosis/tumor relation) and the 4-tiered Becker system (residual tumor in %). Interobserver agreement for the Becker system showed better weighted κ values compared with the Mandard system (0.78 vs. 0.62). Evaluation of the whole embedded tumor site showed improved results (Becker: 0.83; Mandard: 0.73) as compared with only 1 representative slide (Becker: 0.68; Mandard: 0.71). Modification into simplified 3-tiered systems showed comparable interobserver agreement but better prognostic stratification for both systems (log rank Becker: P=0.015; Mandard P=0.03), with independent prognostic impact for overall survival (modified Becker: P=0.011, hazard ratio=3.07; modified Mandard: P=0.023, hazard ratio=2.72). In conclusion, both systems provide substantial to excellent interobserver agreement for estimation of tumor regression after neoadjuvant chemotherapy in esophageal adenocarcinomas. A simple 3-tiered system with the estimation of residual tumor in % (complete regression/1% to 50% residual tumor/>50% residual tumor) maintains the highest reproducibility and prognostic value.

  4. Tumor regression grade of urothelial bladder cancer after neoadjuvant chemotherapy: a novel and successful strategy to predict survival.

    PubMed

    Fleischmann, Achim; Thalmann, George N; Perren, Aurel; Seiler, Roland

    2014-03-01

    Histopathologic tumor regression grades (TRGs) after neoadjuvant chemotherapy predict survival in different cancers. In bladder cancer, corresponding studies have not been conducted. Fifty-six patients with advanced invasive urothelial bladder cancer received neoadjuvant chemotherapy before cystectomy and lymphadenectomy. TRGs were defined as follows: TRG1: complete tumor regression; TRG2: >50% tumor regression; TRG3: 50% or less tumor regression. Separate TRGs were assigned for primary tumors and corresponding lymph nodes. The prognostic impact of these 2 TRGs, the highest (dominant) TRG per patient, and competing tumor features reflecting tumor regression (ypT/ypN stage, maximum diameter of the residual tumor) were determined. Tumor characteristics in initial transurethral resection of the bladder specimens were tested for response prediction. The frequency of TRGs 1, 2, and 3 in the primary tumors were n=16, n=19, and n=21; corresponding data from the lymph nodes were n=31, n=9, and n=16. Interobserver agreement in determination of the TRG was strong (κ=0.8). Univariately, all evaluated parameters were significantly (P ≤ 0.001) related to overall survival; however, the segregation of the Kaplan-Meier curves was best for the dominant TRG. In multivariate analysis, only dominant TRG predicted overall survival independently (P=0.035). In transurethral resection specimens of the chemotherapy-naive bladder cancer, the only tumor feature with significant (P<0.03) predictive value for therapy response was a high proliferation rate. In conclusion, among all parameters reflecting tumor regression, the dominant TRG was the only independent risk factor. A favorable chemotherapy response is associated with a high proliferation rate in the initial chemotherapy-naive bladder cancer. This feature might help personalize neoadjuvant chemotherapy.

  5. Radiation plus chemotherapy as adjuvant therapy for rectal cancer.

    PubMed

    Minsky, Bruce D

    2002-04-01

    The most common neo-adjuvant therapy for rectal cancer is chemotherapy and concurrent radiation therapy. In general, it is delivered pre-operatively for patients with clinical evidence of T(3-4) disease or post-operatively in patients who have undergone surgery and have T(3) and/or N(1-2) disease. This chapter reviews the rationale and results for neo-adjuvant therapy, the selection process for pre-operative versus post-operative treatment, and new approaches and controversies.

  6. Acupuncture for Dysphagia after Chemoradiation in Head and Neck Cancer: Rationale and Design of a Randomized, Sham-Controlled Trial

    PubMed Central

    Lu, Weidong; Wayne, Peter M.; Davis, Roger B.; Buring, Julie E.; Li, Hailun; Goguen, Laura A.; Rosenthal, David S.; Tishler, Roy B.; Posner, Marshall R.; Haddad, Robert I.

    2012-01-01

    Introduction Dysphagia is a common side effect following chemoradiation therapy (CRT) in head and neck cancer (HNC) patients. Current dysphagia management includes swallowing therapy and dilation procedures, but these treatments have limitations. While acupuncture has been reported to positively impact swallowing function and quality of life (QOL) in patients with dysphagia, current evidence is inconclusive. Material and Methods In an ongoing trial, 42 squamous cell carcinoma HNC patients, who are receiving platinum-based CRT with curative intent, are being recruited from a comprehensive cancer center. They are randomized to 12 sessions of either active acupuncture or to sham acupuncture during and following CRT over a 24-week period. Blinded research staff assesses outcomes at baseline, 20 weeks post-CRT (end of acupuncture), and 12 months after baseline (6-month follow-up). The primary outcome is change in M.D. Anderson Dysphagia Inventory score from baseline to 12 months. Secondary outcomes include QOL measures pertaining to HNC patients. In addition, a subset of study patients are tested for salivary flow rates and cytokines, including plasma transforming growth factor –β1 and interleukin 6 (n=10 per arm), to preliminarily explore the biological mechanisms of acupuncture for dysphagia. Discussion This paper addresses unique challenges related to study design in nonpharmacological, sham-controlled acupuncture trials including development of evidence-based credible verum and sham treatment protocols, blinding, and assuring fidelity of treatment. Results of this study will inform the feasibility of conducting a large scale trial and will provide preliminary evidence regarding the value of acupuncture for dysphagia in HNC patients. PMID:22406102

  7. Methodologies in the modeling of combined chemo-radiation treatments

    NASA Astrophysics Data System (ADS)

    Grassberger, C.; Paganetti, H.

    2016-11-01

    The variety of treatment options for cancer patients has increased significantly in recent years. Not only do we combine radiation with surgery and chemotherapy, new therapeutic approaches such as immunotherapy and targeted therapies are starting to play a bigger role. Physics has made significant contributions to radiation therapy treatment planning and delivery. In particular, treatment plan optimization using inverse planning techniques has improved dose conformity considerably. Furthermore, medical physics is often the driving force behind tumor control and normal tissue complication modeling. While treatment optimization and outcome modeling does focus mainly on the effects of radiation, treatment modalities such as chemotherapy are treated independently or are even neglected entirely. This review summarizes the published efforts to model combined modality treatments combining radiation and chemotherapy. These models will play an increasing role in optimizing cancer therapy not only from a radiation and drug dosage standpoint, but also in terms of spatial and temporal optimization of treatment schedules.

  8. 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

    SciTech Connect

    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.

    2014-03-15

    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.

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

    SciTech Connect

    Lee, Taek Sang; Kang, Soon Beom; Kim, Young Tak; Park, Byung Joo; Kim, Yong Man; Lee, Jong Min; Kim, Seok Mo; Kim, Young Tae; Kim, Jae Hoon; Kim, Kyung Tai

    2013-06-01

    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 patient 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.

  10. Prognostic relevance of the mitotic count and the amount of viable tumour after neoadjuvant chemotherapy for primary, localised, high-grade soft tissue sarcoma

    PubMed Central

    Andreou, D; Werner, M; Pink, D; Traub, F; Schuler, M; Gosheger, G; Jobke, B; Reichardt, P; Tunn, P U

    2015-01-01

    Background: We sought to examine whether mitotic count (MC) and the amount of viable tumour (VT) following neoadjuvant systemic chemotherapy (SC) for primary, localised, high-grade soft tissue sarcoma (STS) correlate with prognosis. Methods: Retrospective analysis of 57 patients who underwent SC involving a combination of an anthracycline and an alkylating agent, followed by surgical resection between 2001 and 2011. Results: The amount of VT after chemotherapy was significantly associated with disease-specific survival (DSS) and event-free survival (EFS). Patients with <10% VT had a DSS of 94% at 5 years, compared with 61% for patients with ⩾10% VT (P=0.033); EFS was 75%, compared with 48% (P=0.030). Patients with an MC of ⩾20/10 high power fields (HPF) after chemotherapy had a significantly lower DSS (33% vs 84% at 5 years, P<0.001) and EFS (40% vs 63% at 5 years, P=0.019) than patients with an MC of <20/10 HPF. Conclusions: The MC and the amount of VT after neoadjuvant therapy for primary, localised, high-grade STS appear to correlate with prognosis. If these results are validated prospectively, then they could provide a rational for the design of neoadjuvant treatment modification/escalation studies, analogue to the EURAMOS-1 trial for bone sarcomas. PMID:25535732

  11. Association between SPARC mRNA Expression, Prognosis and Response to Neoadjuvant Chemotherapy in Early Breast Cancer: A Pooled in-silico Analysis

    PubMed Central

    Ignatiadis, Michail; Desmedt, Christine; Fumagalli, Debora; Veys, Isabelle; Larsimont, Denis; Piccart, Martine; Michiels, Stefan; Sotiriou, Christos

    2013-01-01

    Introduction SPARC is an important regulator of the extracellular matrix and has been suggested to improve delivery of albumin-bound cytotoxics. However, little is known regarding its role in breast cancer (BC). Methods We conducted a pooled analysis of publically available datasets, in which BC patients who received no systemic therapy or received neoadjuvant chemotherapy were eligible. Patients were assigned to molecular subtypes using PAM-50. We computed a SPARC module (SPARC7), composed of genes with an absolute correlation with SPARC >0.7. In the systemically untreated cohort, we evaluated 1) expression of SPARC/SPARC7 according to breast cancer subtype, 2) association between SPARC/SPARC7 and biological processes related to proliferation, immune and stroma, and 3) association between SPARC/SPARC7 and relapse-free survival in a Cox model in all patients and in the different molecular subtypes adjusted for tumor size, nodal status, histological grade, and age. In the neoadjuvant cohort, we evaluated the association between SPARC and pCR in a logistic regression model, adjusted for the same clinicopathologic factors. Results 948 (10 datasets), and 791 (8 datasets) patients were included in the systemically untreated and neoadjuvant cohorts, respectively. High SPARC expression was associated with small tumor size, low histological grade and luminal-A tumors (all p<0.0001). There was a positive correlation between SPARC and stroma-related modules but negative correlation with proliferation modules. High SPARC expression was associated with poor prognosis in patients with basal and HER2+ breast cancer even after adjusting for clinicopathologic parameters. In the neoadjuvant cohort, a subgroup analysis suggested that high SPARC is associated with low rates of pCR in the HER2 subtype. Same results were observed on replacing SPARC by SPARC7. Conclusion This analysis suggests a potential role of SPARC in determining prognosis and response to primary chemotherapy in

  12. Can we avoid dose escalation for intermediate-risk prostate cancer in the setting of short-course neoadjuvant androgen deprivation?

    PubMed Central

    Shakespeare, Thomas P; Wilcox, Shea W; Aherne, Noel J

    2016-01-01

    Background Both dose-escalated external beam radiotherapy (DE-EBRT) and androgen deprivation therapy (ADT) improve the outcomes in patients with intermediate-risk prostate cancer. Despite this, there are only few reports evaluating DE-EBRT for patients with intermediate-risk prostate cancer receiving neoadjuvant ADT, and virtually no studies investigating dose escalation >74 Gy in this setting. We aimed to determine whether DE-EBRT >74 Gy improved the outcomes for patients with intermediate-risk prostate cancer who received neoadjuvant ADT. Findings In our institution, patients with intermediate-risk prostate cancer were treated with neoadjuvant ADT and DE-EBRT, with doses sequentially increasing from 74 Gy to 76 Gy and then to 78 Gy between 2006 and 2012. We identified 435 patients treated with DE-EBRT and ADT, with a median follow-up of 70 months. For the 74 Gy, 76 Gy, and 78 Gy groups, five-year biochemical disease-free survival rates were 95.0%, 97.8%, and 95.3%, respectively; metastasis-free survival rates were 99.1%, 100.0%, and 98.6%, respectively; and prostate cancer-specific survival rate was 100% for all three dose levels. There was no significant benefit for dose escalation either on univariate or multivariate analysis for any outcome. Conclusion There was no benefit for DE-EBRT >74 Gy in our cohort of intermediate-risk prostate cancer patients treated with neoadjuvant ADT. Given the higher risks of toxicity associated with dose escalation, it may be feasible to omit dose escalation in this group of patients. Randomized studies evaluating dose de-escalation should be considered. PMID:27073327

  13. Neoadjuvant Gemcitabine Chemotherapy followed by Concurrent IMRT Simultaneous Boost Achieves High R0 Resection in Borderline Resectable Pancreatic Cancer Patients

    PubMed Central

    Huang, Xiaolun; Knoble, Jeanna L.; Aguila, Fernando N.; Patel, Tara; Chambers, Lowell W.; Hu, Honglin; Liu, Hao

    2016-01-01

    Background To study the feasibility of down stage the borderline resectable pancreatic cancer (BRPC) to resectable disease, we reported our institutional results using an intensity-modulated radiation therapy (IMRT) simultaneous integrated boost (SIB) dose escalation approach to improve R0 resectability. Methods We reviewed our past 7 years of experience of using neoadjuvant induction chemotherapy with Gemcitabine followed by concurrent chemoradiaiton for BRPC. During the concurrent, chemo was 5-FU and radiation were IMRT with SIB technique to target the key areas with dose escalation to 5600 in 28 fractions. The key areas were defined by PET positive area. This was followed by restaging imaging to rule out distant metastases before resection. Results 25 finished dose escalation protocol. 2 of the 25 cases developed distant metastases, 23 (92%) patients without distant metastases underwent pancreatectomy. Among the those received pancreatectomy, 22 (95%) achieved negative margin (R0). The gastrointestinal toxicity > grade 2 was 8% and there was no grade 4 toxicity. Conclusion Neoadjuvant Gemcitabine-based induction chemotherapy followed by 5-FU-based IMRT-SIB is a feasible option in improving the likelihood of R0 resection rate in BRPC without compromising the organs at risk for toxicity. PMID:27935952

  14. Over expression of hRad9 protein correlates with reduced chemosensitivity in breast cancer with administration of neoadjuvant chemotherapy.

    PubMed

    Yun, Haiqin; Shi, Ranran; Yang, Qingrui; Zhang, Xiaofang; Wang, Yan; Zhou, Xingchen; Mu, Kun

    2014-12-18

    Human Rad 9 (hRad9), part of the Rad9-Hus1-Rad1 complex plays an important role in DNA damage repair as an up-stream regulator of checkpoint signaling, however little is known about its role in response to chemotherapy of breast cancer and whether hRad9 inhibition can potentiate the cytotoxic effects of chemotherapy on breast cancer cells remains to be elucidated. Fifty cases of breast cancer receiving neoadjuvant therapy were collected. All these cases were revised and classified into chemotherapy sensitive (CS) or chemotherapy resistant (CR) group according to the Miller and Payne (MP) grading system. Immunohistochemically, hRad9 positive tumours showed nuclear and/or cytoplasmic staining. hRad9 over-expression was associated with an impaired neoadjuvant chemotherapy response. A significant correlation was found between expression of hRad9 and Cyclin D1. In vitro, hRad9 was knocked down using siRNA in breast cancer cell line MCF-7 and MDA-MB-231. Deregulated expression of Rad9 accompanied by down expression of chk1 enhanced the sensitivity of human breast cancer cells to doxorubicin. Our work suggests that hRad9 might be a potential predictor for the response to chemotherapy in patients with breast cancer and its clinical value as a target for improving chemosensitivity needs further exploration.

  15. A 3q gene signature associated with triple negative breast cancer organ specific metastasis and response to neoadjuvant chemotherapy

    PubMed Central

    Qian, Jun; Chen, Heidi; Ji, Xiangming; Eisenberg, Rosana; Chakravarthy, A. Bapsi; Mayer, Ingrid A.; Massion, Pierre P.

    2017-01-01

    Triple negative breast cancers (TNBC) are aggressive tumors, with high rates of metastatic spread and targeted therapies are critically needed. We aimed to assess the prognostic and predictive value of a 3q 19-gene signature identified previously from lung cancer in a collection of 4,801 breast tumor gene expression data. The 3q gene signature had a strong association with features of aggressiveness such as high grade, hormone receptor negativity, presence of a basal-like or TNBC phenotype and reduced distant metastasis free survival. The 3q gene signature was strongly associated with lung metastasis only in TNBC (P < 0.0001, Hazard ratio (HR) 1.44, 95% confidence interval (CI), 1.31–1.60), significantly associated with brain but not bone metastasis regardless of TNBC status. The association of one 3q driver gene FXR1 with distant metastasis in TNBC (P = 0.01) was further validated by immunohistochemistry. In addition, the 3q gene signature was associated with better response to neoadjuvant chemotherapy in TNBC (P < 0.0001) but not in non-TNBC patients. Our study suggests that the 3q gene signature is a novel prognostic marker for lung and/or brain metastasis and a predictive marker for the response to neoadjuvant chemotherapy in TNBC, implying a potential role for 3q genes in the mechanism of organ-specific metastasis. PMID:28387221

  16. Over expression of hRad9 protein correlates with reduced chemosensitivity in breast cancer with administration of neoadjuvant chemotherapy

    PubMed Central

    Yun, Haiqin; Shi, Ranran; Yang, Qingrui; Zhang, Xiaofang; Wang, Yan; Zhou, Xingchen; Mu, Kun

    2014-01-01

    Human Rad 9 (hRad9), part of the Rad9-Hus1-Rad1 complex plays an important role in DNA damage repair as an up-stream regulator of checkpoint signaling, however little is known about its role in response to chemotherapy of breast cancer and whether hRad9 inhibition can potentiate the cytotoxic effects of chemotherapy on breast cancer cells remains to be elucidated. Fifty cases of breast cancer receiving neoadjuvant therapy were collected. All these cases were revised and classified into chemotherapy sensitive (CS) or chemotherapy resistant (CR) group according to the Miller and Payne (MP) grading system. Immunohistochemically, hRad9 positive tumours showed nuclear and/or cytoplasmic staining. hRad9 over-expression was associated with an impaired neoadjuvant chemotherapy response. A significant correlation was found between expression of hRad9 and Cyclin D1. In vitro, hRad9 was knocked down using siRNA in breast cancer cell line MCF-7 and MDA-MB-231. Deregulated expression of Rad9 accompanied by down expression of chk1 enhanced the sensitivity of human breast cancer cells to doxorubicin. Our work suggests that hRad9 might be a potential predictor for the response to chemotherapy in patients with breast cancer and its clinical value as a target for improving chemosensitivity needs further exploration. PMID:25520248

  17. 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

    SciTech Connect

    Leong, Trevor; Joon, Daryl Lim; Willis, David; Jayamoham, Jayasingham; Spry, Nigel; Harvey, Jennifer; Di Iulio, Juliana; Milner, Alvin; Mann, G. Bruce; Michael, Michael

    2011-03-01

    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, 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.

  18. What is the optimal neo-adjuvant treatment for liver metastasis?

    PubMed Central

    Haraldsdottir, Sigurdis; Wu, Christina; Bloomston, Mark

    2013-01-01

    Colorectal cancer is the third most common cancer in the Western population and has a 5-year overall survival of 5–10% when metastatic. Approximately 30% of the patients with metastatic colorectal cancer have limited disease apparently isolated to the liver and, if this can be resected, the 5-year overall survival is improved to 30–60%. Therefore, it is important to identify patients who have both resectable disease and those with initially unresectable tumors who can potentially be downsized with chemotherapy to allow resection. First-line doublet chemotherapy regimens lead to response rates of 50–60%, triplet chemotherapy regimens may result in a response rate of up to 70%, and biological agents may add to responses or induce morphologic changes that facilitate disease resection. Surgical advances in recent years have also increased resectability rates and have challenged prior rules of resectability. Local therapies including ablation and radiation, often performed in conjunction with resection, may further aid in control of disease. The aim of this article is to focus on the role of neoadjuvant therapy in the treatment of colorectal liver metastases. PMID:23858331

  19. Delaying surgery after neoadjuvant chemoradiotherapy improves prognosis of rectal cancer

    PubMed Central

    Mihmanlı, Mehmet; Kabul Gürbulak, Esin; Akgün, İsmail Ethem; Celayir, Mustafa Fevzi; Yazıcı, Pınar; Tunçel, Deniz; Bek, Tuba Tülin; Öz, Ayhan; Ömeroğlu, Sinan

    2016-01-01

    AIM To investigate the prognostic effect of a delayed interval between neoadjuvant chemoradiotherapy (CRT) and surgery in locally advanced rectal cancer. METHODS We evaluated 87 patients with locally advanced mid- or distal rectal cancer undergoing total mesorectal excision following an interval period after neoadjuvant CRT at Şişli Hamidiye Etfal Training and Research Hospital, Istanbul between January 2009 and January 2014. Patients were divided into two groups according to the interval before surgery: < 8 wk (group I) and ≥ 8 wk (group II). Data related to patients, cancer characteristics and pathological examination were collected and analyzed. RESULTS When the distribution of timing between group I (n = 45) and group II (n = 42) was viewed, comparison of interval periods (median ± SD) of groups showed a significant difference of as 5 ± 1.28 wk in group I and 10.1 ± 2.2 wk in group II (P < 0.001). The median follow-up period for all patients was 34.5 (9.9-81) mo. group II had significantly higher rates of pathological complete response (pCR) than group I had (19% vs 8.9%, P = 0.002). Rate of tumor regression grade (TRG) poor response was 44.4% in group I and 9.5% in group II (P < 0.002). A poor pathological response was associated with worse disease-free survival (P = 0.009). The interval time did not show any association with local recurrence (P = 0.79). CONCLUSION Delaying the neoadjuvant CRT-surgery interval may provide nodal down-staging, improve pCR rate, and decrease the rate of TRG poor response. PMID:27672428

  20. TU-CD-BRB-09: Prediction of Chemo-Radiation Outcome for Rectal Cancer Based On Radiomics of Tumor Clinical Characteristics and Multi-Parametric MRI

    SciTech Connect

    Nie, K; Yue, N; Shi, L; Hu, X; Chen, Q; Sun, X; Niu, T

    2015-06-15

    Purpose: To evaluate the tumor clinical characteristics and quantitative multi-parametric MR imaging features for prediction of response to chemo-radiation treatment (CRT) in locally advanced rectal cancer (LARC). Methods: Forty-three consecutive patients (59.7±6.9 years, from 09/2013 – 06/2014) receiving neoadjuvant CRT followed by surgery were enrolled. All underwent MRI including anatomical T1/T2, Dynamic Contrast Enhanced (DCE)-MRI and Diffusion-Weighted MRI (DWI) prior to the treatment. A total of 151 quantitative features, including morphology/Gray Level Co-occurrence Matrix (GLCM) texture from T1/T2, enhancement kinetics and the voxelized distribution from DCE-MRI, apparent diffusion coefficient (ADC) from DWI, along with clinical information (carcinoembryonic antigen CEA level, TNM staging etc.), were extracted for each patient. Response groups were separated based on down-staging, good response and pathological complete response (pCR) status. Logistic regression analysis (LRA) was used to select the best predictors to classify different groups and the predictive performance were calculated using receiver operating characteristic (ROC) analysis. Results: Individual imaging category or clinical charateristics might yield certain level of power in assessing the response. However, the combined model outperformed than any category alone in prediction. With selected features as Volume, GLCM AutoCorrelation (T2), MaxEnhancementProbability (DCE-MRI), and MeanADC (DWI), the down-staging prediciton accuracy (area under the ROC curve, AUC) could be 0.95, better than individual tumor metrics with AUC from 0.53–0.85. While for the pCR prediction, the best set included CEA (clinical charateristics), Homogeneity (DCE-MRI) and MeanADC (DWI) with an AUC of 0.89, more favorable compared to conventional tumor metrics with an AUC ranging from 0.511–0.79. Conclusion: Through a systematic analysis of multi-parametric MR imaging features, we are able to build models with

  1. Influence of secreted frizzled receptor protein 1 (SFRP1) on neoadjuvant chemotherapy in triple negative breast cancer does not rely on WNT signaling

    PubMed Central

    2014-01-01

    Background Triple negative breast cancer (TNBC) is characterized by lack of expression of both estrogen and progesterone receptor as well as lack of overexpression or amplification of HER2. Despite an increased probability of response to chemotherapy, many patients resistant to current chemotherapy regimens suffer from a worse prognosis compared to other breast cancer subtypes. However, molecular determinants of response to chemotherapy specific to TNBC remain largely unknown. Thus, there is a high demand for biomarkers potentially stratifying triple negative breast cancer patients for neoadjuvant chemotherapies or alternative therapies. Methods In order to identify genes correlating with both the triple negative breast cancer subtype as well as response to neoadjuvant chemotherapy we employed publicly available gene expression profiles of patients, which had received neoadjuvant chemotherapy. Analysis of tissue microarrays as well as breast cancer cell lines revealed correlation to the triple negative breast cancer subtype. Subsequently, effects of siRNA-mediated knockdown on response to standard chemotherapeutic agents as well as radiation therapy were analyzed. Additionally, we evaluated the molecular mechanisms by which SFRP1 alters the carcinogenic properties of breast cancer cells. Results SFRP1 was identified as being significantly overexpressed in TNBC compared to other breast cancer subtypes. Additionally, SFRP1 expression is significantly correlated with an increased probability of positive response to neoadjuvant chemotherapy. Knockdown of SFRP1 in triple negative breast cancer cells renders the cells more resistant to standard chemotherapy. Moreover, tumorigenic properties of the cells are modified by knockdown, as shown by both migration or invasion capacity as well reduced apoptotic events. Surprisingly, we found that these effects do not rely on Wnt signaling. Furthermore, we show that pro-apoptotic as well as migratory pathways are differentially

  2. Neoadjuvant chemotherapy of breast cancer with pirarubicin versus epirubicin in combination with cyclophosphamide and docetaxel.

    PubMed

    Gu, Xi; Jia, Shi; Wei, Wei; Zhang, Wen-Hai

    2015-07-01

    Breast cancers (BC) are treated with surgery, radiotherapy, and chemotherapy. Neoadjuvant chemotherapy (NACT) is an emerging treatment option in many cancers and is given before primary therapy to shrink tumor size. The efficacy of NACT in varied settings of BC, such as inoperable tumors, borderline resectable tumors, and breast-conserving surgery, has been debated extensively in literature, and the results remain unclear and depended on a wide variety of factors such as cancer type, disease extent, and the specific combination of chemotherapy drugs. This study was performed to examine the efficacy, toxicity, and tolerability of pirarubicin (THP) and epirubicin (EPI) in combination with docetaxel and cyclophosphamide in a NACT setting for BC. A total of 48 patients with stage II or III breast cancers were randomly divided into two groups: THP group and EPI group. The patients in THP group received 2-4 cycles of neoadjuvant chemotherapy with DTC regimen (docetaxel, THP, cyclophosphamide), while patients in the EPI group received 2-4 cycles of DEC regimen (docetaxel, EPI, cyclophosphamide) before surgery. The incidence of adverse reactions and the efficacy of the treatment regimen were compared between the two groups. Prognostic evaluation indexes were estimated by Kaplan-Meier survival analysis, including the 5-year disease-free survival (DFS) and overall survival (OS). The overall response rate in THP group was 83.3 %, and the EPI group showed a response rate of 79.2 %, with no statistically significant difference in response rate between the two groups. The incidence of cardiac toxicity, myelosuppression, nausea, and vomiting in the THP group was significantly lower than the EPI group (all P < 0.05). The incidence of hepatic toxicity, alopecia, and diarrhea in the THP group was also lower than the EPI group, but these differences were not statistically significant. The 5-year DFS and OS in THP versus EPI groups were 80 versus 76 % (DFS) and 86 versus 81 % (OS

  3. Modern management of locally advanced cervical carcinoma.

    PubMed

    Dueñas-Gonzalez, Alfonso; Cetina, Lucely; Mariscal, Ignacio; de la Garza, Jaime

    2003-10-01

    Radiation was until recently the key and only modality for the routine treatment of locally advanced cervical carcinoma. However after years of studying multi-modality treatments as an alternative to radiation alone in randomized phase III trials, the standard treatment has changed to chemo-radiation based on cisplatin. Three recent meta-analyses have confirmed that cisplatin-based chemo-radiation adds an absolute 12% benefit in five-year survival over radiation therapy alone. Neoadjuvant chemotherapy followed by radiation has not been of proven benefit, but when neoadjuvant chemotherapy is followed by surgery, an absolute increase of 15% in five-year survival over radiation alone is seen. This benefit in survival is comparable to that obtained with the current chemo-radiation schedules based on cisplatin. Despite these encouraging results there remains room for improvement as the five-year survival of patients treated with chemo-radiation ranges from nearly 80% in bulky IB tumours to only 25% in stage IVA disease. Other therapeutic approaches need to be fully evaluated including the use of chemo-radiation after neoadjuvant chemotherapy; the use of new drug combinations and the multi-modality combination of neoadjuvant chemotherapy followed by radical surgery plus adjuvant chemo-radiation. Likewise, the addition of radiosensitizers to cisplatin, preoperative chemo-radiation and/or adjuvant chemotherapy may eventually improve the currents results of cisplatin-based chemo-radiation. Nevertheless, it is hard to foresee a dramatic increase in cure rate, even with the most optimal combination of cytotoxic drugs, surgery and radiation, and thus the testing of molecular targeted therapies against cervical cancer is a logical step to follow.

  4. Concurrent chemoradiation versus radiotherapy alone for the treatment of locally advanced cervical cancer in a low-resource setting.

    PubMed

    Pereira, Elena; Cooper, Hoover Henriquez; Zelaya, Pedro Guillermo; Creasman, William; Price, Fredric V; Gupta, Vishal; Chuang, Linus

    2017-02-01

    Our goal was to determine the clinical treatment response following radiation administered with or without chemotherapy for locally advanced cervical cancers in Honduras. This is a retrospective study of patients treated with either concurrent chemoradiation (CCRT) or external beam radiation therapy (EBRT) alone at a hospital in Tegucigalpa, Honduras. 70 Gy of EBRT to the pelvis was given in all cases. Brachytherapy was not available. Chemotherapy was given when available. Extrafascial hysterectomy was performed 6 weeks after completion of treatment in patients with a complete clinical response (cCR). Records for 165 women with locally advanced cervical cancer were reviewed; 25 (15.2%) stage IB2, 15 (9.1%) stage IIA, 90 (54.5%) stage IIB, and 35 (21.2%) stage IIIB. Ninety (54.5%) patients received EBRT alone; 75 (45.5%) received CCRT. Twenty-three (33.3%) of CCRT patients received weekly cisplatin, the remainder receiving other agents. Seventy (77.8%) of the 90 patients who received EBRT had a cCR; 25 out of 75 (33.3%) patients in the CCRT group achieved a cCR. The CCRT group treated with weekly cisplatin achieved an 80% cCR; while the CCRT group given alternative agents had only a 31% cCR. Patients unable to receive platinum-based CCRT had the worst outcome, and their responses were inferior to patients who received EBRT. The challenges of treating women with locally advanced cervical cancer in a low-resource setting are multifactorial and include treatment delays, the lack of brachytherapy and the unpredictable availability of chemotherapy.

  5. Long-Term Regional Control in the Observed Neck Following Definitive Chemoradiation for Node-Positive Oropharyngeal Squamous Cell Cancer

    PubMed Central

    Goenka, Anuj; Morris, Luc G.T.; Rao, Shyam S.; Wolden, Suzanne L.; Wong, Richard J.; Kraus, Dennis H.; Ohri, Nisha; Setton, Jeremy; Lok, Benjamin H.; Riaz, Nadeem; Mychalczak, Borys R.; Schoder, Heiko; Ganly, Ian; Shah, Jatin P.; Pfister, David G.; Zelefsky, Michael J.; Lee, Nancy Y.

    2015-01-01

    Traditionally, patients treated with chemoradiotherapy for node-positive oropharyngeal squamous cell carcinoma (N+ OPSCC) have undergone a planned neck dissection (ND) after treatment. Recently, negative post-treatment positron-emission tomography (PET)/computed tomography (CT) imaging has been found to have a high negative predictive value for the presence of residual disease in the neck. Here we present the first comprehensive analysis of a large, uniform cohort of N+ OPSCC patients achieving a PET/CT-based complete response (CR) after chemoradiotherapy, and undergoing observation, rather than ND. From 2002 to 2009, 302 patients with N+ OPSCC treated with 70 Gy intensity-modulated radiation therapy and concurrent chemotherapy underwent post-treatment clinical assessment including PET/CT. CR was defined as no evidence of disease on clinical examination and post-treatment PET/CT. ND was reserved for patients with chemoradiation, based on clinical and PET/CT assessment, have a high probability of regional control, with a 2.3% regional failure rate, and may be safely observed without planned ND. PMID:23436584

  6. Salvage surgery in post-chemoradiation laryngeal and hypopharyngeal carcinoma: outcome and review.

    PubMed

    Putten, L; Bree, R; Doornaert, P A; Buter, J; Eerenstein, S E J; Rietveld, D H F; Kuik, D J; Leemans, C R

    2015-06-01

    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

  7. Cervix Regression and Motion During the Course of External Beam Chemoradiation for Cervical Cancer

    SciTech Connect

    Beadle, Beth M.; Jhingran, Anuja; Salehpour, Mohammad; Sam, Marianne; Iyer, Revathy B.; Eifel, Patricia J.

    2009-01-01

    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 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. 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.

  8. Neo-adjuvant radiotherapy in rectal cancer

    PubMed Central

    Glimelius, Bengt

    2013-01-01

    In rectal cancer treatment, attention has focused on the local primary tumour and the regional tumour cell deposits to diminish the risk of a loco-regional recurrence. Several large randomized trials have also shown that combinations of surgery, radiotherapy and chemotherapy have markedly reduced the risk of a loco-regional recurrence, but this has not yet had any major influence on overall survival. The best results have been achieved when the radiotherapy has been given preoperatively. Preoperative radiotherapy improves loco-regional control even when surgery has been optimized to improve lateral clearance, i.e., when a total mesorectal excision has been performed. The relative reduction is then 50%-70%. The value of radiotherapy has not been tested in combination with more extensive surgery including lateral lymph node clearance, as practised in some Asian countries. Many details about how the radiotherapy is performed are still open for discussion, and practice varies between countries. A highly fractionated radiation schedule (5 Gy × 5), proven efficacious in many trials, has gained much popularity in some countries, whereas a conventionally fractionated regimen (1.8-2.0 Gy × 25-28), often combined with chemotherapy, is used in other countries. The additional therapy adds morbidity to the morbidity that surgery causes, and should therefore be administered only when the risk of loco-regional recurrence is sufficiently high. The best integration of the weakest modality, to date the drugs (conventional cytotoxics and biologicals) is not known. A new generation of trials exploring the best sequence of treatments is required. Furthermore, there is a great need to develop predictors of response, so that treatment can be further individualized and not solely based upon clinical factors and anatomic imaging. PMID:24379566

  9. Resection of colorectal liver metastases following neoadjuvant chemotherapy

    PubMed Central

    Chiappa, A; Bertani, E; Biffi, R; Pace, U; Viale, G; Pruneri, G; Zampino, G; Fazio, N; Orsi, F; Bonomo, G; Monfardini, L; Vigna, P Della; Andreoni, B

    2007-01-01

    Background/aims: Hepatic resection in metastatic disease from colorectal cancer offers the best chance in selected cases for long-term survival. Neoadjuvant chemotherapy (NACT) has been advocated in some cases initially deemed irresectable, with few reports of the efficacy of such a strategy and the influence of the response to chemotherapy on the outcome of radical hepatic resection. Methodology: Between December 1995 and May 2005, 27 patients with colorectal liver metastases (seven males, 20 females, mean age: 58 ± 8 years; range: 40–75) were treated with neoadjuvant chemotherapy. A seven-year survival analysis was performed. Chemotherapy included mainly 5-fluorouracil, leucovorin and either oxaliplatin or irinotecan for a median of eight courses. Results: A total of 16 patients (59%) had synchronous and 11 (41%) metachronous metastases. During pre-operative chemotherapy, tumour regression occurred in ten cases (37%), stable disease in a further ten patients (37%) and progressive disease developed in seven cases (26%). The five-year overall survival for NACT responders was 64% and only 15% for non-responders (p=0.044). Conclusions: The response to chemotherapy is likely to be a significant prognostic factor affecting survival after liver resection for cure. PMID:22275956

  10. Combined chemoradiation for the management of nasal natural killer (NK)/T-cell lymphoma: elucidating the significance of systemic chemotherapy.

    PubMed

    Guo, Ye; Lu, Jiade J; Ma, Xuejun; Wang, Biyun; Hong, Xiaonan; Li, Xiaoqiu; Li, Jin

    2008-01-01

    The objective of this analysis was to evaluate the efficacy and treatment outcome of CHOP and CHOP combined with nitrosourea chemotherapy in natural killer (NK)/T-cell lymphoma of the nasal cavity. Sixty-three patients with NK/T-cell lymphoma of the nasal cavity were treated with CHOP or CHOP combined with oral nitrosourea chemotherapy between January 1997 and June 2005. By the Ann Arbor Lymphoma Staging Classification, 57 patients (90%) had Stage IE or IIE disease and six patients (10%) had Stage III or IV disease. All patients with Stage IE or IIE disease were intended to be treated curatively with combined chemoradiation; and patients who had Stage III or IV disease were treated with chemotherapy alone with curative intention. Chemotherapy consisted of: (1) up to six cycles of the standard CHOP based regimen, or (2) up to six cycles of the standard CHOP based regimen with oral Semustine dosed at 120 mg (or Lomustine dosed at 100mg) on day 1 of each chemotherapy cycle. External beam radiation therapy was delivered by daily conventional fractionation by Co-60 or 6MVx linear accelerator for patients with Stage IE or IIE disease. The radiation dose to the tumor bed was between 36 and 50 Gy with a median dose of 45 Gy. Fifty-three patients received chemotherapy prior to radiation, and four patients were treated with involved field radiation before chemotherapy. The median follow up for all 44 surviving patients was 31 months (range: 6-104 months). The 2-year progression-free survival (PFS) and overall survival (OS) rates were 60% and 70%, respectively. The PFS and OS of patients who were treated with or without oral nitrosourea in addition to CHOP were 73% vs. 44% (P=0.035) and 75% vs. 64% (P=0.276), respectively. Nine patients with Stage IE or IIE diseases developed disease progression during their planned treatment and died within 10 months after the initiation of treatment; Six patients who achieved complete response (CR) after planned chemoradiation developed

  11. Ki67 Proliferation Index as a Tool for Chemotherapy Decisions During and After Neoadjuvant Aromatase Inhibitor Treatment of Breast Cancer: Results From the American College of Surgeons Oncology Group Z1031 Trial (Alliance).

    PubMed

    Ellis, Matthew J; Suman, Vera J; Hoog, Jeremy; Goncalves, Rodrigo; Sanati, Souzan; Creighton, Chad J; DeSchryver, Katherine; Crouch, Erika; Brink, Amy; Watson, Mark; Luo, Jingqin; Tao, Yu; Barnes, Michael; Dowsett, Mitchell; Budd, G Thomas; Winer, Eric; Silverman, Paula; Esserman, Laura; Carey, Lisa; Ma, Cynthia X; Unzeitig, Gary; Pluard, Timothy; Whitworth, Pat; Babiera, Gildy; Guenther, J Michael; Dayao, Zoneddy; Ota, David; Leitch, Marilyn; Olson, John A; Allred, D Craig; Hunt, Kelly

    2017-04-01

    Purpose To determine the pathologic complete response (pCR) rate in estrogen receptor (ER) -positive primary breast cancer triaged to chemotherapy when the protein encoded by the MKI67 gene (Ki67) level was > 10% after 2 to 4 weeks of neoadjuvant aromatase inhibitor (AI) therapy. A second objective was to examine risk of relapse using the Ki67-based Preoperative Endocrine Prognostic Index (PEPI). Methods The American College of Surgeons Oncology Group (ACOSOG) Z1031A trial enrolled postmenopausal women with stage II or III ER-positive (Allred score, 6 to 8) breast cancer whose treatment was randomly assigned to neoadjuvant AI therapy with anastrozole, exemestane, or letrozole. For the trial ACOSOG Z1031B, the protocol was amended to include a tumor Ki67 determination after 2 to 4 weeks of AI. If the Ki67 was > 10%, patients were switched to neoadjuvant chemotherapy. A pCR rate of > 20% was the predefined efficacy threshold. In patients who completed neoadjuvant AI, stratified Cox modeling was used to assess whether time to recurrence differed by PEPI = 0 score (T1 or T2, N0, Ki67 < 2.7%, ER Allred > 2) versus PEPI > 0 disease. Results Only two of the 35 patients in ACOSOG Z1031B who were switched to neoadjuvant chemotherapy experienced a pCR (5.7%; 95% CI, 0.7% to 19.1%). After 5.5 years of median follow-up, four (3.7%) of the 109 patients with a PEPI = 0 score relapsed versus 49 (14.4%) of 341 of patients with PEPI > 0 (recurrence hazard ratio [PEPI = 0 v PEPI > 0], 0.27; P = .014; 95% CI, 0.092 to 0.764). Conclusion Chemotherapy efficacy was lower than expected in ER-positive tumors exhibiting AI-resistant proliferation. The optimal therapy for these patients should be further investigated. For patients with PEPI = 0 disease, the relapse risk over 5 years was only 3.6% without chemotherapy, supporting the study of adjuvant endocrine monotherapy in this group. These Ki67 and PEPI triage approaches are being definitively studied in the ALTERNATE trial (Alternate

  12. Mifepristone improves chemo-radiation response in glioblastoma xenografts

    PubMed Central

    2013-01-01

    Background We have investigated the ability of Mifepristone, an anti-progestin and anti-glucocorticoid drug, to modulate the antitumor effect of current standard clinical treatment in glioblastoma xenografts. Methods The effect of radiation alone or combined with Mifepristone and Temozolamide was evaluated on tumor growth in glioblastoma xenografts, both in terms of preferentially triggering tumor cell death and inhibiting angiogenesis. Tumor size was measured once a week using a caliper and tumor metabolic-activity was carried out by molecular imaging using a microPET/CT scanner. The effect of Mifepristone on the expression of angiogenic factors after concomitant radio-chemotherapy was determined using a quantitative real-time PCR analysis of VEGF gene expression. Results The analysis of the data shows a significant antitumoral effect by the simultaneous administration of radiation-Mifepristone-Temozolamide in comparison with radiation alone or radiation-Temozolamide. Conclusion Our results suggest that Mifepristone could improve the efficacy of chemo-radiotherapy in Glioblastoma. The addition of Mifepristone to standard radiation-Temozolamide therapy represents a potential approach as a chemo-radio-sensitizer in treating GBMs, which have very limited treatment options. PMID:23530939

  13. Gene Expression Profiling to Predict Outcome After Chemoradiation in Head and Neck Cancer

    SciTech Connect

    Pramana, Jimmy; Brekel, Michiel van den; Velthuysen, Marie-Louise F. van; Wessels, Lodewijk F.A.; Nuyten, Dimitry S.; Hofland, Ingrid; Atsma, Douwe; Pimentel, Nuno; Hoebers, Frank J.P.; Rasch, Coen; Begg, Adrian C.

    2007-12-01

    Purpose: The goal of the present study was to improve prediction of outcome after chemoradiation in advanced head and neck cancer using gene expression analysis. Materials and Methods: We collected 92 biopsies from untreated head and neck cancer patients subsequently given cisplatin-based chemoradiation (RADPLAT) for advanced squamous cell carcinomas (HNSCC). After RNA extraction and labeling, we performed dye swap experiments using 35k oligo-microarrays. Supervised analyses were performed to create classifiers to predict locoregional control and disease recurrence. Published gene sets with prognostic value in other studies were also tested. Results: Using supervised classification on the whole series, gene sets separating good and poor outcome could be found for all end points. However, when splitting tumors into training and validation groups, no robust classifiers could be found. Using Gene Set Enrichment analysis, several gene sets were found to be enriched in locoregional recurrences, although with high false-discovery rates. Previously published signatures for radiosensitivity, hypoxia, proliferation, 'wound,' stem cells, and chromosomal instability were not significantly correlated with outcome. However, a recently published signature for HNSCC defining a 'high-risk' group was shown to be predictive for locoregional control in our dataset. Conclusion: Gene sets can be found with predictive potential for locoregional control after combined radiation and chemotherapy in HNSCC. How treatment-specific these gene sets are needs further study.

  14. Restaging locally advanced rectal cancer by different imaging modalities after preoperative chemoradiation: a comparative study

    PubMed Central

    2013-01-01

    Background To compare the accuracy of different imaging modalities, alone and in combination in predicting findings at surgery after preoperative chemoradiation for locally advanced rectal cancer. Methods Following chemoradiation, tumors were reclassified on the basis of findings on pelvic computed tomography (CT) (94 patients), endorectal ultrasonography (EUS) (138 patients) alone or by both CT and EUS (80 patients). The ability of the imaging modalities, to predict the pathologic T status, N status, and TNM stage at surgery was evaluated and compared. Results Mean age of the patients was 64.5 years (range 28–88 years); 55% were male. CT and EUS combined had a positive predictive value of 20% for pathologic pT1 stage, 29% for pT1, 29% for pT2, and 58% for pT3. Predictive values for the operative TNM stage were 50% for stage I, 45% for stage II, and 31% for stage III. These values did not exceed those for each modality alone. Conclusion The performance of preoperative CT and EUS in predicting the T and TNM stage of rectal cancer at surgery is poor. Neither modality alone nor the two combined is sufficiently accurate to serve as the basis for decisions regarding treatment modification. PMID:24286200

  15. Carcinosarcoma of the fallopian tube with disappearance of carcinoma cells by neoadjuvant chemotherapy: case study.

    PubMed

    Takemoto, Y; Ota, T; Aoki, Y; Ogura, K; Ogishima, D; Matsumoto, T

    2015-01-01

    The authors report a case of carcinosarcoma (CS) of the fimbria of the fallopian tube in which carcinoma cells disappeared with neoadjuvant chemotherapy (NAC). A 74-year-old woman visited the present hospital with a large pelvic mass and pleural effusion. A magnetic resonance image of the tumor was highly suggestive of ovarian carcinoma. Due to the presence of both serous.adenocarcinoma cells in pleural effusion and pulmonary thrombosis, the patient was given NAC consisting of carboplatin plus paclitaxel (TC) and anticoagulant therapy with warfarin potassium. With six courses of NAC, the pleural effusion and pulmonary thrombosis disappeared, and the tumor decreased 36.2% in greatest diameter. Maximum debulking surgery was then performed. The tumor was found to be located in the fimbria of the right fallopian tube. Hysterectomy and bilateral salpingo-oophorectomy were performed, and histologic examination revealed chondrosarcoma with the presence of necrotic epithelial cells. The necrotic areas were interspersed with papillary structures, and immunohistochemical study showed positivity for CK7 and negativity for CK20, p53, and estrogen receptor (ER), indicating serous adenocarcinoma. Thus, heterologous CS with disappearance of viable carcinoma cells by NAC was diagnosed. The patient was given adjuvant chemotherapy consisting of three courses of TC, and there has been no evidence of disease for 20 months. The authors' experience in this case of gynecologic CS indicates that a serous adenocarcinomatous component of tubal CS can be well cured by TC-based NAC.

  16. Monitoring breast masses with ultrasound tomography in patients undergoing neoadjuvant chemotherapy

    NASA Astrophysics Data System (ADS)

    Lupinacci, Jessica; Duric, Neb; Littrup, Peter; Wang, Ding; Li, Cuiping; Schmidt, Steven; Rama, Olsi; Bey-Knight, Lisa; Myc, Lukasz

    2009-02-01

    As part of an ongoing assessment of the in-vivo performance of a operator independent breast imaging device, based on acoustic tomography, we report on new results obtained with patients undergoing neoadjuvant chemotherapy. Five patients were examined with the prototype on multiple occasions corresponding in time to their chemotherapy sessions. Images of reflection, sound speed and attenuation, representing the entire volume of the breast, were reconstructed from the exam data and analyzed for time-dependent changes during the treatment period. It was found that changes in acoustic properties of the tumors could be measured directly from the images. The measured properties include reflectivity, sound speed and attenuation, leading to measurable changes in the volume, shape and internal attributes of the tumors. These measurements were used to monitor the response of the tumors to the therapy with the long term goal of correlating results with pathological and clinical outcomes. Comparisons with tumor size changes based on traditional US and MRI indicates potential for accurate, quantifiable tracking of tumor volume. Furthermore, our tentative results also show declines in internal properties of the tumors, possibly relating to a reduction in tissue stiffness and/or density. Future work will include an expansion of the study to a larger cohort of patients for determining the statistical significance of our findings.

  17. Histomorphological Factors Predicting the Response to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer

    PubMed Central

    Jung, Yoon Yang; Hyun, Chang Lim; Jin, Min-Sun; Park, In Ae; Chung, Yul Ri; Shim, Bobae; Lee, Kyu Ho

    2016-01-01

    Purpose There is no standard targeted therapy for the treatment of triple-negative breast cancer (TNBC). Therefore, its management heavily depends on adjuvant chemotherapy. Using core needle biopsy, this study evaluated the histological factors of TNBC predicting the response to chemotherapy. Methods One hundred forty-three TNBC patients who received single-regimen neoadjuvant chemotherapy (NAC) with the combination of doxorubicin, cyclophosphamide, and docetaxel were enrolled. The core needle biopsy specimens acquired before NAC were used to analyze the clinicopathologic variables and overall performance of the predictive model for therapeutic response. Results Independent predictors of pathologic complete response after NAC were found to be higher number of tumor infiltrating lymphocytes (p=0.007), absence of clear cytoplasm (p=0.008), low necrosis (p=0.018), and high histologic grade (p=0.039). In the receiver operating characteristics curve analysis, the area under curve for the combination of these four variables was 0.777. Conclusion The present study demonstrated that a predictive model using the above four variables can predict therapeutic response to single-regimen NAC with the combination of doxorubicin, cyclophosphamide, and docetaxel in TNBC. Therefore, adding these morphologic variables to clinical and genomic signatures might enhance the ability to predict the therapeutic response to NAC in TNBC. PMID:27721875

  18. [A case report of metastatic anal fistula cancer treated with neoadjuvant chemotherapy].

    PubMed

    Murata, Akihiro; Takatsuka, Satoshi; Shinkawa, Hiroji; Kaizaki, Ryoji; Hori, Takaaki; Ikehara, Teruyuki

    2014-11-01

    A 69-year-old man with perianal pain was diagnosed with an anal fistula and a rectal tumor by magnetic resonance imaging and pulmonary tuberculosis by computed tomography. A colonoscopy confirmed the presence of a circular mass in the rectum 6 cm from the anal verge. Histological examination revealed a moderately differentiated adenocarcinoma. Initially, seton drainage was used to improve the perianal pain. After 2 months of anti-tuberculosis therapy, the patient underwent low anterior resection for the rectal cancer. Six months after surgery, a perianal tumor was detected at the postoperative site of the anal fistula. Biopsy of the tumor revealed adenocarcinoma. Because the histological appearance of the second tumor was identical to the rectal cancer, it was diagnosed as a metastatic anal fistula cancer. The tumor shrunk after 3 courses of neoadjuvant chemotherapy with S-1 plus oxaliplatin (SOX) plus bevacizumab and there was no evidence of distant metastasis. Local resection of the anal fistula cancer was performed. Six months postoperatively, the patient is doing well and shows no sign of recurrence.

  19. Study of the prediction system for clinical response to M-VAC neoadjuvant chemotherapy for bladder cancer.

    PubMed

    Takata, R; Obara, W; Fujioka, T

    2010-01-01

    Neoadjuvant chemotherapy for invasive bladder cancer, involving a regimen of M-VAC, can manage micrometastasis and improve the prognosis. However, some patients suffer from severe adverse drug reactions without any effect, and no method yet exists for predicting the response of an individual patient to chemotherapy. Our purpose in this study is to establish a method for predicting the response to the M-VAC therapy. We analyzed gene-expression profiles of biopsy materials from 40 invasive bladder cancers using a cDNA microarray consisting of 27 648 genes, after populations of cancer cells had been purified by laser-microbeam microdissection. We identified 14 predictive genes that were expressed differently between nine responder and nine non-responder tumors and devised a prediction-scoring system that clearly separated the responder group from the non-responder group. This system accurately predicted the clinical response for 19 of the 22 additional test cases. The group of patients with positive predictive scores had significantly longer survival times than that with negative scores. As real-time RT-PCR data were highly concordant with the cDNA microarray data for those 14 genes, we developed a quantitative RT-PCR-based prediction system that could be feasible for routine clinical use. Taken together, our results suggest that the sensitivity of an invasive bladder cancer to the M-VAC neoadjuvant chemotherapy can be predicted by expression patterns in this set of genes, a step toward achievement of "personalized therapy" for treatment of this disease.

  20. EndoPredict predicts for the response to neoadjuvant chemotherapy in ER-positive, HER2-negative breast cancer.

    PubMed

    Bertucci, François; Finetti, Pascal; Viens, Patrice; Birnbaum, Daniel

    2014-12-01

    The EndoPredict (EP) signature is a prognostic 11-gene expression signature specifically developed in ER+/HER2- node-negative/positive breast cancer. It is associated with relapse-free survival in patients treated with adjuvant hormone therapy, suggesting that EP low-risk patients could be treated with adjuvant hormone therapy alone whereas high-risk patients would deserve addition of adjuvant chemotherapy. Thus, it is important to determine whether EP high-risk patients are or are not more sensitive to chemotherapy than low-risk patients. Here, we have assessed the EP predictive value for pathological complete response to neoadjuvant chemotherapy in ER+/HER2- breast cancer. We gathered gene expression and histoclinical data of 553 pre-treatment ER+/HER2- breast carcinomas treated with anthracycline-based neoadjuvant chemotherapy. We searched for correlation between the pathological complete response (pCR) and the EP score-based classification. The overall pCR rate was 12%. Fifty-one percent of samples were classified as low-risk according to the EP score and 49% as high-risk. EP classification was associated with a pCR rate of 7% in the low-risk group and 17% in the high-risk group (p < 0.001). In multivariate analysis, the EP score remained significantly associated with pCR. Many genes upregulated in the high-risk tumours were involved in cell proliferation, whereas many genes upregulated in the low-risk tumours were involved in ER-signalling and stroma. Despite higher chemosensitivity, the high-risk group was associated with worse disease-free survival. In conclusion, EP high-risk ER+/HER2- breast cancers are more likely to respond to anthracycline-based chemotherapy.

  1. Tracking the genomic evolution of esophageal adenocarcinoma through neoadjuvant chemotherapy

    PubMed Central

    Kumar, Sacheen; Abbassi-Ghadi, Nima; Salm, Max; Mitter, Richard; Horswell, Stuart; Rowan, Andrew; Phillimore, Benjamin; Biggs, Jennifer; Begum, Sharmin; Matthews, Nik; Hochhauser, Daniel; Hanna, George B; Swanton, Charles

    2015-01-01

    Esophageal adenocarcinomas (EACs) are associated with dismal prognosis. Deciphering the evolutionary histories of this disease may shed light on therapeutically tractable targets and reveal dynamic mutational processes during the disease course and following neoadjuvant chemotherapy (NAC). We exome sequenced 40 tumor regions from 8 patients with operable EACs, before and after platinum-containing NAC. This revealed the evolutionary genomic landscape of EACs with the presence of heterogeneous driver mutations, parallel evolution, early