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Sample records for neoadjuvant chemotherapy nact

  1. The Role of Carboplatin in the Neoadjuvant Chemotherapy Treatment of Triple Negative Breast Cancer

    PubMed Central

    Castrellon, Aurelio Bartolome; Pidhorecky, Ihor; Valero, Vicente; Raez, Luis Estuardo

    2017-01-01

    Triple negative breast (TNBC) cancer constitutes a heterogeneous group of disease with histologic and molecular differences. Complete pathologic response to neoadjuvant chemotherapy (NACT) in TNBC is associated with improved outcomes. Efforts have been made in identifying drug combinations that will increase the response rate to preoperative chemotherapy. In this review we present recent studies that have incorporated carboplatin (Cb) in the NACT of TNBC. We discuss the homologous recombination deficiency score and the somatic or germline mutation for BRCA as potential biomarkers for future selection of patients that could benefit from the addition of Cb to NACT. PMID:28382189

  2. Complications after radical gastrectomy following FOLFOX7 neoadjuvant chemotherapy for gastric cancer

    PubMed Central

    2011-01-01

    Background This study assessed the postoperative morbidity and mortality occurring in the first 30 days after radical gastrectomy by comparing gastric cancer patients who did or did not receive the FOLFOX7 regimen of neoadjuvant chemotherapy. Methods We completed a retrospective analysis of 377 patients after their radical gastrectomies were performed in our department between 2005 and 2009. Two groups of patients were studied: the SURG group received surgical treatment immediately after diagnosis; the NACT underwent surgery after 2-6 cycles of neoadjuvant chemotherapy. Results There were 267 patients in the SURG group and 110 patients in the NACT group. The NACT group had more proximal tumours (P = 0.000), more total/proximal gastrectomies (P = 0.000) and longer operative time (P = 0.005) than the SURG group. Morbidity was 10.0% in the NACT patients and 17.2% in the SURG patients (P = 0.075). There were two cases of postoperative death, both in the SURG group (P = 1.000). No changes in complications or mortality rate were observed between the SURG and NACT groups. Conclusion The FOLFOX7 neoadjuvant chemotherapy is not associated with increased postoperative morbidity, indicating that the FOLFOX7 neoadjuvant chemotherapy is a safe choice for the treatment of local advanced gastric cancer. PMID:21942969

  3. The role of neoadjuvant chemotherapy in patients with advanced (stage IIIC) epithelial ovarian cancer

    PubMed Central

    Škof, Erik; Merlo, Sebastjan; Pilko, Gasper

    2016-01-01

    Abstract Background Primary treatment of patients with advanced epithelial ovarian cancer consists of chemotherapy either before (neoadjuvant chemotherapy, NACT) or after primary surgery (adjuvant chemotherapy). The goal of primary treatment is no residual disease after surgery (R0 resection) what is associated with an improvement in survival of patients. There is, however, no evidence of survival benefits in patients with R0 resections after prior NACT. Methods We retrospectively reviewed the records of patients who were treated with diagnosis of epithelial ovarian cancer at Institute of Oncology Ljubljana in the years 2005–2007. The differences in the rates of R0 resections, progression free survival (PFS), overall survival (OS) and in five-year and eight-year survival rates between patients treated with NACT and patients who had primary surgery were compared. Results Overall 160 patients had stage IIIC epithelial ovarian cancer. Eighty patients had NACT and eighty patients had primary surgery. Patients in NACT group had higher rates of R0 resection (42% vs. 20%; p = 0.011) than patients after primary surgery. PFS was 14.1 months in NACT group and 17.7 months after primary surgery (p = 0.213). OS was 24.8 months in NACT group and 31.6 months after primary surgery (p = 0.012). In patients with R0 resections five-year and eight-year survival rates were 20.6% and 17.6% in NACT group compared to 62.5% and 62.5% after primary surgery (p < 0.0001), respectively. Conclusions Despite higher rates of R0 resections achieved by NACT, survival of patients treated with NACT was inferior to survival of patients who underwent primary surgery. NACT should only be offered to patients with advanced epithelial cancer who are not candidates for primary surgery. PMID:27679552

  4. 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

  5. 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

    Neoadjuvant chemotherapy (NACT) is a term originally used to describe the administration of chemotherapy preoperatively before surgery. The original rationale for administering NACT or so-called induction chemotherapy to shrink or downstage a locally advanced tumour, and thereby facilitate more effective local treatment with surgery or radiotherapy, has been extended with the introduction of more effective combinations of chemotherapy to include reducing the risks of metastatic disease. It seems logical that survival could be lengthened, or organ preservation rates increased in resectable tumours by NACT. In rectal cancer NACT is being increasingly used in locally advanced and nonmetastatic unresectable tumours. Randomised studies in advanced colorectal cancer show high response rates to combination cytotoxic therapy. This evidence of efficacy coupled with the introduction of novel molecular targeted therapies (such as Bevacizumab and Cetuximab), and long waiting times for radiotherapy have rekindled an interest in delivering NACT in locally advanced rectal cancer. In contrast, this enthusiasm is currently waning in other sites such as head and neck and nasopharynx cancer where traditionally NACT has been used. So, is NACT in rectal cancer a real advance or just history repeating itself? In this review, we aimed to explore the advantages and disadvantages of the separate approaches of neoadjuvant, concurrent and consolidation chemotherapy in locally advanced rectal cancer, drawing on theoretical principles, preclinical studies and clinical experience both in rectal cancer and other disease sites. Neoadjuvant chemotherapy may improve outcome in terms of disease-free or overall survival in selected groups in some disease sites, but this strategy has not been shown to be associated with better outcomes than postoperative adjuvant chemotherapy. In particular, there is insufficient data in rectal cancer. The evidence for benefit is strongest when NACT is administered

  6. 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.

  7. Impact of Hyperglycemia on Outcomes among Patients Receiving Neoadjuvant Chemotherapy for Bulky Early Stage Cervical Cancer

    PubMed Central

    Lu, Huai-wu; Zhang, Bing-zhong; Wang, Li-juan; Lin, Zhong-qiu

    2016-01-01

    Background The impact of hyperglycemia on survival of patients undergoing neoadjuvant chemotherapy (NACT) for bulky early stage cervical cancer (BESCC) has not been explored. Method Records of patients who received NACT and radical hysterectomy in our institution between January 2005 and June 2010 were reviewed. Results In total, 347 patients were included. The median follow-up time was 37 months (range: 4–65). Patients with hyperglycemia (fasting blood glucose ≥ 100 mg/dl) had shorter recurrence-free survival (RFS) (univariate hazard ratio [HR] = 1.95, 95% confidence interval [CI] [1.16, 3.28], P = 0.010) and cancer-specific survival (CSS) (univariate HR = 2.24, 95% CI [1.33, 3.78], P = 0.002) compared with those with euglycemia (fasting blood glucose <100 mg/dl). In multivariate analysis, positive surgical margins, parametrium invasion, node metastasis, hyperglycemia and complete response to NACT independently predicted recurrence and cancer-specific death. To further validate the prognostic value of hyperglycemia, we conducted a subgroup analysis based on patient baseline characteristics and prognostic effect of hyperglycemia remained significant in all subgroups. On multivariable logistic regression analysis, euglycemia before NACT, squamous cell tumor and pre-treatment squamous cell carcinoma antigen levels < 3.5 ng/ml were identified as independent predictors of complete response after NACT. Conclusions FBG ≥100 mg/dl is a negative prognostic predictor for cervical cancer patients receiving NACT for BESCC. Patients with hyperglycemia are less likely to achieve complete response after NACT. Our findings underscore the clinical utility of hyperglycemia screening of for cervical cancer patients. PMID:27851819

  8. 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.

  9. [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.

  10. 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.

  11. 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

  12. Association between dynamic features of breast DCE-MR imaging and clinical response of neoadjuvant chemotherapy: a preliminary analysis

    NASA Astrophysics Data System (ADS)

    Huang, Lijuan; Fan, Ming; Li, Lihua; Zhang, Juan; Shao, Guoliang; Zheng, Bin

    2016-03-01

    Neoadjuvant chemotherapy (NACT) is being used increasingly in the management of patients with breast cancer for systemically reducing the size of primary tumor before surgery in order to improve survival. The clinical response of patients to NACT is correlated with reduced or abolished of their primary tumor, which is important for treatment in the next stage. Recently, the dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is used for evaluation of the response of patients to NACT. To measure this correlation, we extracted the dynamic features from the DCE- MRI and performed association analysis between these features and the clinical response to NACT. In this study, 59 patients are screened before NATC, of which 47 are complete or partial response, and 12 are no response. We segmented the breast areas depicted on each MR image by a computer-aided diagnosis (CAD) scheme, registered images acquired from the sequential MR image scan series, and calculated eighteen features extracted from DCE-MRI. We performed SVM with the 18 features for classification between patients of response and no response. Furthermore, 6 of the 18 features are selected to refine the classification by using Genetic Algorithm. The accuracy, sensitivity and specificity are 87%, 95.74% and 50%, respectively. The calculated area under a receiver operating characteristic (ROC) curve is 0.79+/-0.04. This study indicates that the features of DCE-MRI of breast cancer are associated with the response of NACT. Therefore, our method could be helpful for evaluation of NACT in treatment of breast cancer.

  13. Robotic Stereotactic Radioablation Concomitant With Neo-Adjuvant Chemotherapy for Breast Tumors

    SciTech Connect

    Bondiau, Pierre-Yves; Bahadoran, Phillipe; Lallement, Michel; Birtwisle-Peyrottes, Isabelle; Chapellier, Claire; Chamorey, Emmanuel; Courdi, Adel; Quielle-Roussel, Catherine; Thariat, Juliette; Ferrero, Jean-Marc

    2009-11-15

    Purpose: Robotic stereotactic radioablation (RSR) allows stereotactic irradiation of thoracic tumors; however, it has never been used for breast tumors and may have a real potential. We conducted a Phase I study, including neoadjuvant chemotherapy (NACT), a two-level dose-escalation study (6.5 Gy x 3 fractions and 7.5 Gy x 3 fractions) using RSR and breast-conserving surgery followed by conventional radiotherapy. Materials and Methods: To define toxicity, we performed a dermatologic exam (DE) including clinical examination by two independent observers and technical examination by colorimetry, dermoscopy, and skin ultrasound. DE was performed before NACT (DE0), at 36 days (DE1), at 56 days (DE2), after the NACT treatment onset, and before surgery (DE3). Surgery was performed 4-8 weeks after the last chemotherapy session. A pathologic examination was also performed. Results: There were two clinical complete responses and four clinical partial responses at D56 and D85. Maximum tolerable dose was not reached. All patients tolerated RSR with no fatigue; 2 patients presented with mild pain after the third fraction of the treatment. There was no significant toxicity measured with ultrasound and dermoscopy tests. Postoperative irradiation (50 Gy) has been delivered without toxicity. Conclusion: The study showed the feasibility of irradiation with RSR combined with chemotherapy and surgery for breast tumors. There was no skin toxicity at a dose of 19.5 Gy or 22.5 Gy delivered in three fractions combined with chemotherapy. Lack of toxicity suggested that the dose could be increased further. Pathologic response was acceptable.

  14. Pathological response after neoadjuvant bevacizumab- or cetuximab-based chemotherapy in resected colorectal cancer liver metastases.

    PubMed

    Pietrantonio, Filippo; Mazzaferro, Vincenzo; Miceli, Rosalba; Cotsoglou, Christian; Melotti, Flavia; Fanetti, Giuseppe; Perrone, Federica; Biondani, Pamela; Muscarà, Cecilia; Di Bartolomeo, Maria; Coppa, Jorgelina; Maggi, Claudia; Milione, Massimo; Tamborini, Elena; de Braud, Filippo

    2015-07-01

    Neoadjuvant chemotherapy (NACT) prior to liver resection is advantageous for patients with colorectal cancer liver metastases (CLM). Bevacizumab- or cetuximab-based NACT may affect patient outcome and curative resection rate, but comparative studies on differential tumour regression grade (TRG) associated with distinct antibodies-associated regimens are lacking. Ninety-three consecutive patients received NACT plus bevacizumab (n = 46) or cetuximab (n = 47) followed by CLM resection. Pathological response was determined in each resected metastasis as TRG rated from 1 (complete) to 5 (no response). Except for KRAS mutations prevailing in bevacizumab versus cetuximab (57 vs. 21 %, p = 0.001), patients characteristics were well balanced. Median follow-up was 31 months (IQR 17-48). Bevacizumab induced significantly better pathological response rates (TRG1-3: 78 vs. 34 %, p < 0.001) as well as complete responses (TRG1: 13 vs. 0 %, p = 0.012) with respect to cetuximab. Three-year progression-free survival (PFS) and overall survival (OS) were not significantly different in the two cohorts. At multivariable analysis, significant association with pathological response was found for number of resected metastases (p = 0.015) and bevacizumab allocation (p < 0.001), while KRAS mutation showed only a trend. Significant association with poorer PFS and OS was found for low grades of pathological response (p = 0.009 and p < 0.001, respectively), R2 resection or presence of extrahepatic disease (both p < 0.001) and presence of KRAS mutation (p = 0.007 and p < 0.001, respectively). Bevacizumab-based regimens, although influenced by the number of metastases and KRAS status, improve significantly pathological response if compared to cetuximab-based NACT. Possible differential impact among regimens on patient outcome has still to be elucidated.

  15. [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.

  16. Normalization of compression-induced hemodynamics in patients responding to neoadjuvant chemotherapy monitored by dynamic tomographic optical breast imaging (DTOBI)

    PubMed Central

    Sajjadi, Amir Y.; Isakoff, Steven J.; Deng, Bin; Singh, Bhawana; Wanyo, Christy M.; Fang, Qianqian; Specht, Michelle C.; Schapira, Lidia; Moy, Beverly; Bardia, Aditya; Boas, David A.; Carp, Stefan A.

    2017-01-01

    We characterize novel breast cancer imaging biomarkers for monitoring neoadjuvant chemotherapy (NACT) and predicting outcome. Specifically, we recruited 30 patients for a pilot study in which NACT patients were imaged using dynamic tomographic optical breast imaging (DTOBI) to quantify the hemodynamic changes due to partial mammographic compression. DTOBI scans were obtained pre-treatment (referred to as day 0), as well as 7 and 30 days into therapy on female patients undergoing NACT. We present data for the 13 patients who participated in both day 0 and 7 measurements and had evaluable data, of which 7 also returned for day 30 measurements. We acquired optical images over 2 minutes following 4-8 lbs (18-36 N) of compression. The timecourses of tissue-volume averaged total hemoglobin (HbT), as well as hemoglobin oxygen saturation (SO2) in the tumor vs. surrounding tissues were compared. Outcome prediction metrics based on the differential behavior in tumor vs. normal areas for responders (>50% reduction in maximum diameter) vs. non-responders were analyzed for statistical significance. At baseline, all patients exhibit an initial decrease followed by delayed recovery in HbT, and SO2 in the tumor area, in contrast to almost immediate recovery in surrounding tissue. At day 7 and 30, this contrast is maintained in non-responders; however, in responders, the contrast in hemodynamic time-courses between tumor and normal tissue starts decreasing at day 7 and substantially disappears at day 30. At day 30 into NACT, responding tumors demonstrate “normalization” of compression induced hemodynamics vs. surrounding normal tissue whereas non-responding tumors did not. This data suggests that DTOBI imaging biomarkers, which are governed by the interplay between tissue biomechanics and oxygen metabolism, may be suitable for guiding NACT by offering early predictions of treatment outcome. PMID:28270967

  17. Neoadjuvant chemotherapy in locally advanced nasopharyngeal carcinoma: Defining high-risk patients who may benefit before concurrent chemotherapy combined with intensity-modulated radiotherapy

    PubMed Central

    Du, Xiao-Jing; Tang, Ling-Long; Chen, Lei; Mao, Yan-Ping; Guo, Rui; Liu, Xu; Sun, Ying; Zeng, Mu-Sheng; Kang, Tie-Bang; Shao, Jian-Yong; Lin, Ai-Hua; Ma, Jun

    2015-01-01

    The purpose of this study was to create a prognostic model for distant metastasis in patients with locally advanced NPC who accept concurrent chemotherapy combined with intensity-modulated radiotherapy (CCRT) to identify high-risk patients who may benefit from neoadjuvant chemotherapy (NACT). A total of 881 patients with newly-diagnosed, non-disseminated, biopsy-proven locoregionally advanced NPC were retrospectively reviewed; 411 (46.7%) accepted CCRT and 470 (53.3%) accepted NACT followed by CCRT. Multivariate analysis demonstrated N2–3 disease, plasma Epstein–Barr virus (EBV) DNA > 4000 copies/mL, serum albumin ≤46 g/L and platelet count >300 k/cc were independent prognostic factors for distant metastasis in the CCRT group. Using these four factors, a prognostic model was developed, as follows: 1) low-risk group: 0–1 risk factors; and 2) high-risk group: 2–4 risk factors. In the high-risk group, patients who accepted NACT + CCRT had significantly higher distant metastasis-free survival and progression-free survival rates than the CCRT group (P = 0.001; P = 0.011). This simple prognostic model for distant metastasis in locoregionally advanced NPC may facilitate with the selection of high-risk patients who may benefit from NACT prior to CCRT. PMID:26564805

  18. 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.

  19. 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

  20. 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.

  1. Chemotherapy for bladder cancer: treatment guidelines for neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and metastatic cancer.

    PubMed

    Sternberg, Cora N; Donat, S Machele; Bellmunt, Joaquim; Millikan, Randall E; Stadler, Walter; De Mulder, Pieter; Sherif, Amir; von der Maase, Hans; Tsukamoto, Taiji; Soloway, Mark S

    2007-01-01

    To determine the optimal use of chemotherapy in the neoadjuvant, adjuvant, and metastatic setting in patients with advanced urothelial cell carcinoma, a consensus conference was convened by the World Health Organization (WHO) and the Société Internationale d'Urologie (SIU) to critically review the published literature on chemotherapy for patients with locally advanced bladder cancer. This article reports the development of international guidelines for the treatment of patients with locally advanced bladder cancer with neoadjuvant and adjuvant chemotherapy. Bladder preservation is also discussed, as is chemotherapy for patients with metastatic urothelial cancer. The conference panel consisted of 10 medical oncologists and urologists from 3 continents who are experts in this field and who reviewed the English-language literature through October 2004. Relevant English-language literature was identified with the use of Medline; additional cited works not detected on the initial search regarding neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and chemotherapy for patients with metastatic urothelial cancer were reviewed. Evidence-based recommendations for diagnosis and management of the disease were made with reference to a 4-point scale. Results of the authors' deliberations are presented as a consensus document. Meta-analysis of randomized trials on cisplatin-containing combination neoadjuvant chemotherapy revealed a 5% difference in favor of neoadjuvant chemotherapy. No randomized trials have yet compared survival with transurethral resection of bladder tumor alone versus cystectomy for the management of patients with muscle-invasive disease. Collaborative international adjuvant chemotherapy trials are needed to assist researchers in assessing the true value of adjuvant chemotherapy. Systemic cisplatin-based combination chemotherapy is the only current modality that has been shown in phase 3 trials to improve survival in responsive patients

  2. Neoadjuvant Chemotherapy in Locally Advanced and Borderline Resectable Nonsquamous Sinonasal Tumors (Esthesioneuroblastoma and Sinonasal Tumor with Neuroendocrine Differentiation)

    PubMed Central

    Patil, Vijay M.; Joshi, Amit; Noronha, Vanita; Sharma, Vibhor; Zanwar, Saurabh; Dhumal, Sachin; Kane, Shubhada; Pai, Prathamesh; D'Cruz, Anil; Chaturvedi, Pankaj; Bhattacharjee, Atanu; Prabhash, Kumar

    2016-01-01

    Introduction. Sinonasal tumors are chemotherapy responsive which frequently present in advanced stages making NACT a promising option for improving resection and local control in borderline resectable and locally advanced tumours. Here we reviewed the results of 25 such cases treated with NACT. Materials and Methods. Sinonasal tumor patients treated with NACT were selected for this analysis. These patients received NACT with platinum and etoposide for 2 cycles. Patients who responded and were amenable for gross total resection underwent surgical resection and adjuvant CTRT. Those who responded but were not amenable for resection received radical CTRT. Patients who progressed on NACT received either radical CTRT or palliative radiotherapy. Results. The median age of the cohort was 42 years (IQR 37–47 years). Grades 3-4 toxicity with NACT were seen in 19 patients (76%). The response rate to NACT was 80%. Post-NACT surgery was done in 12 (48%) patients and radical chemoradiation in 9 (36%) patients. The 2-year progression free survival and overall survival were 75% and 78.5%, respectively. Conclusion. NACT in sinonasal tumours has a response rate of 80%. The protocol of NACT followed by local treatment is associated with improvement in outcomes as compared to our historical cohort. PMID:26955484

  3. 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.

  4. Early response to neoadjuvant chemotherapy can help predict long-term survival in patients with cervical cancer

    PubMed Central

    Shen, Jian; Zhou, Hang; Yang, Runfeng; Wang, Lin; Liu, Jiong; Zhang, Jincheng; Sun, Haiying; Jia, Yao; Du, Xiaofang; Wang, Haoran; Deng, Song; Ding, Ting; Jiang, Jingjing; Lu, Yunping; Li, Shuang; Wang, Shixuan; Ma, Ding

    2016-01-01

    It is still controversial whether cervical cancer patients with clinical responses after neoadjuvant chemotherapy (NACT) have a better long-term survival or not. This study was designed to investigate the effect of the clinical response on the disease-free survival (DFS) of cervical cancer patients undergoing NACT. A total of 853 patients from a retrospective study were used to evaluate whether the clinical response was an indicator for the long-term response, and 493 patients from a prospective cohort study were used for further evaluation. The survival difference was detected by log-rank test, univariate and multivariate Cox regression and a pooled analysis. The log-rank test revealed that compared with non-responders, the DFS of responders was significantly higher in the retrospective data (P = 0.007). Univariate Cox regression showed that the clinical response was an indicator of long-term survival in the retrospective study (HR 1.83, 95% CI 1.18-2.85, P = 0.007). In a multivariate Cox model, the clinical response was still retained as an independent significant prognostic factor in the retrospective study (HR 1.59, 95% CI 1.01-2.50, P = 0.046). The result was also validated in the prospective data with similar results. These findings implied that the clinical response can be regarded as an independent predictor of DFS. PMID:27557523

  5. 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

  6. Correlation of clinicopathological outcomes with changes in IHC4 status after NACT in locally advanced breast cancers: do pre-NACT ER/PR status act as better prognosticators?

    PubMed Central

    Chatterjee, Sanjoy; Saha, Animesh; Arun, Indu; Nayak, Sonali Susmita; Sinha, Subir; Agrawal, Sanjit; Parihar, Mayur; Ahmed, Rosina

    2015-01-01

    Background Following neoadjuvant chemotherapy (NACT) for breast cancer, changes in estrogen receptor (ER), progesterone receptor (PR), HER2 status, and Ki-67 index (IHC4 status) and its correlation with pathological complete response (pCR) or relapse-free survival (RFS) rates could lead to better understanding of tumor management. Patients and methods Pre- and post-NACT IHC4 status and its changes were analyzed in 156 patients with breast cancer. Associations between pCR, RFS rates to IHC4 status pre- and post-NACT were investigated. Results pCR was found in 25.3% patients. Both ER and PR positive tumors had the lowest (14.3%) pCR compared to ER and PR negative (29%) or either ER-/PR-positive (38.6%) tumors. PR positivity was significantly associated with less likelihood of pCR (15% versus 34%). The pCR rate was low for luminal A subtype (13.68%) compared to 24.36%, 26.31%, and 33.33% for luminal B, HER2-enriched, and triple-negative subtypes, respectively. There was significant reduction in ER expression and Ki-67 index post-NACT. RFS of patients in whom the hormonal status changed from positive to negative was better compared to those of patients in whom the hormonal status changed from negative to positive. Conclusion Although changes in IHC4 occurred post-NACT, pre-NACT hazard ratio status prognosticated RFS better. pCR and RFS rates were lower in PR-positive tumors. PMID:26677343

  7. Genome-wide association study identifies four SNPs associated with response to platinum-based neoadjuvant chemotherapy for cervical cancer

    PubMed Central

    Li, Xiong; Huang, Kecheng; Zhang, Qinghua; Zhou, Jin; Sun, Haiying; Tang, Fangxu; Zhou, Hang; Hu, Ting; Wang, Shaoshuai; Jia, Yao; Yang, Ru; Chen, Yile; Cheng, Xiaodong; Lv, Weiguo; Wu, Li; Xing, Hui; Wang, Lin; Zhou, Shasha; Yao, Yuan; Wang, Xiaoli; Suolang, Quzhen; Shen, Jian; Xi, Ling; Hu, Junbo; Wang, Hui; Chen, Gang; Gao, Qinglei; Xie, Xing; Wang, Shixuan; Li, Shuang; Ma, Ding

    2017-01-01

    To identify genomic markers associated with the response to neoadjuvant chemotherapy (NACT) in patients with cervical cancer, we performed a three-stage genome-wide association study (GWAS) in the Han Chinese population. A total of 596 patients with stage IA2-IIIB cervical cancer were enrolled in this study. One single nucleotide polymorphism (SNP) (rs6812281, per allele OR = 2.37, P = 9.0 × 10−9) located at 4q34.3 reached GWAS significance (P < 5.0 × 10−8). Another three SNPs, rs4590782 (10q26.2, P = 1.59 × 10−5, per allele OR = 0.48), rs1742101 (14q32.11, P = 7.11 × 10−6, per allele OR = 0.52), and rs1364121 (16q23.3, P = 3.15 × 10−6, per allele OR = 1.98), exhibited strong evidence of associations with response to neoadjuvant chemotherapy. Patients with a C allele (CT + CC) of rs4590782 had better 5-year overall survival rates (82.9% vs. 75.8%, P = 0.083) and 5-year disease-free survival rate (80.8% vs. 72.7%, P = 0.021) than those without a C allele. Our findings help to characterize the genetic etiology of the response to neoadjuvant chemotherapy in patients with cervical cancer. PMID:28120872

  8. [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).

  9. 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

  10. 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.

  11. Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in nasopharyngeal carcinoma patients with cervical nodal necrosis

    PubMed Central

    Lan, Mei; Chen, Chunyan; Huang, Ying; Tian, Li; Duan, Zhijun; Han, Fei; Liao, Junfang; Deng, Meiling; Sio, Terence T.; Prayongrat, Anussara; Zheng, Lie; Wu, Shaoxiong; Lu, Taixiang

    2017-01-01

    The effectiveness of neoadjuvant chemotherapy (NACT) followed by concurrent chemoradiotherapy (CCRT) compared with CCRT alone in nasopharyngeal carcinoma (NPC) patients who presented with cervical nodal necrosis (CNN) is unknown. A total of 792 patients with stage T1-4N1-3M0 NPC and presented with CNN based on magnetic resonance imaging were retrospectively reviewed. Propensity score matching method was used to balance treatment arms for baseline characteristics. Eventually, 508 patients were propensity-matched on a 1:1 basis to create two groups (NACT + CCRT and CCRT groups). Survival rates were calculated by Kaplan–Meier method and differences were compared by using the log-rank test. The 5-year disease specific survival, disease-free survival and distant metastasis-free survival were significantly higher in NACT + CCRT group relative to the matched CCRT group (82.1% vs. 72.5%, P = 0.021; 70.3% vs. 54.1%, P < 0.001; 81.9% vs. 67.3%, P < 0.001, respectively). Although the rates of grade 3–4 leucopenia and mucositis were higher in NACT + CCRT group than CCRT group, compliance with the combined treatment was good and no significant difference was observed between two groups. NACT followed by CCRT was relatively safe and could achieve better survival than CCRT alone in NPC patients with CNN by reducing the risk of death, tumor progression and distant metastasis. PMID:28211482

  12. 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 genome doubling events and an association between high intratumor heterogeneity and poor response to NAC. Multi-region sequencing demonstrated a significant reduction in T>G mutations within a CTT context when comparing early and late mutational processes and the presence of a platinum signature with enrichment of C>A mutations within a CpC context following NAC. EACs are characterized by early chromosomal instability leading to amplifications containing targetable oncogenes persisting through chemotherapy, providing a rationale for future therapeutic approaches. PMID:26003801

  13. Neoadjuvant chemotherapy followed by conization to spare fertility in cases of locally advanced cervical cancer: A case report and review of the literature

    PubMed Central

    Feng, Yanling; Cao, Tiefeng; Wang, Yin; Huang, He; Xie, Yujie; Liu, Jihong

    2016-01-01

    The average age when cervical cancer is diagnosed is decreasing, resulting in a larger proportion of patients seeking fertility preservation. Therefore, a less radical approach that aims to preserve the potential for fertility during the treatment of cervical carcinoma is crucial. The present study reported a case of a patient with stage IB2 cervical cancer who exhibited pathological complete regression to neoadjuvant chemotherapy (NACT). This patient underwent deep cervical conization and laparoscopic lymphadenectomy to preserve her fertility. The patient gave birth at 29 weeks of gestation and exhibited no recurrent disease until May 2016 (72 months after surgery). This is the first, to the best of our knowledge, IB2 case treatment by NACT, followed by conization plus lymphadenectomy, producing favorable oncological and obstetrical outcome. The present study, together with data from a limited number of published articles, offers a new perspective in the preservation of fertility in young women with cervical cancer. Additional studies are required in a selected population. PMID:27699036

  14. Optimal pathological response indicated better long-term outcome among patients with stage IB2 to IIB cervical cancer submitted to neoadjuvant chemotherapy

    PubMed Central

    Huang, Kecheng; Sun, Haiying; Chen, Zhilan; Li, Xiong; Wang, ShaoShuai; Zhao, Xiaolin; Tang, Fangxu; Jia, Yao; Hu, Ting; Du, Xiaofang; Wang, Haoran; Lu, Zhiyong; Huang, Jia; Gui, Juan; Wang, Xiaoli; Zhou, Shasha; Wang, Lin; Zhang, Jincheng; Guo, Lili; Yang, Ru; Shen, Jian; Zhang, Qinghua; Li, Shuang; Wang, Shixuan

    2016-01-01

    The role of pathological response in long-term outcome is still unclear in cervical cancer patients treated with neoadjuvant chemotherapy (NACT) in China. This study aimed to investigate the effect of optimal pathologic response (OPR) on survival in the patients treated with NACT and radical hysterectomy. First, 853 patients with stage IB2-IIB cervical cancer were included in a retrospective analysis; a Cox proportional hazards model was used to investigate the relationship between pathological response and disease-free survival (DFS). In the retrospective database, 64 (7.5%) patients were found to have achieved an OPR (residual disease <3 mm stromal invasion); in the multivariate Cox model, the risk of death was much greater in the non-OPR group than in the OPR group (HR, 2.61; 95%CI, 1.06 to 6.45; P = 0.037). Next, the role of OPR was also evaluated in a prospective cohort of 603 patients with cervical cancer. In the prospective cohort, 56 (9.3%) patients were found to have achieved an OPR; the log-rank tests showed that the risk of recurrence was higher in the non-OPR patients than in the OPR group (P = 0.05). After combined analysis, OPR in cervical cancer was found to be an independent prognostic factor for DFS. PMID:27325186

  15. Neoadjuvant chemotherapy and pathologic response: a retrospective cohort

    PubMed Central

    de Andrade, Diocésio Alves Pinto; Zucca-Matthes, Gustavo; Vieira, René Aloísio da Costa; de Andrade, Cristiane Thomaz de Aquino Exel; da Costa, Allini Mafra; Monteiro, Aurélio Julião de Castro; Lago, Lissandra Dal; Nunes, João Soares

    2013-01-01

    ABSTRACT Objective: To evaluate the complete pathologic response attained by patients diagnosed with locally advanced breast cancer submitted to neoadjuvant chemotherapy based on the doxorubicin/ cyclophosphamide regimen followed by paclitaxel. Methods: A retrospective cohort of patients with locally advanced breast cancer, admitted to the Hospital de Câncer de Barretos between 2006 and 2008 submitted to the doxorubicin/cyclophosphamide protocol followed by paclitaxel (4 cycles of doxorubicin 60mg/m2 and cyclophosphamide 600mg/m2 every 21 days; 4 cycles of paclitaxel 175mg/m2 every 21 days). The following variables were assessed: age, menopause, performance status, initial clinical staging, anthropometric data, chemotherapy (dose – duration), toxicity profile, post-treatment staging, surgery, pathologic complete response rate, disease-free survival, and pathological characteristics (type and histological degree, hormonal profile and lymph node involvement). Statistical analysis was performed using a 5% level of significance. Results: Of the 434 patients evaluated, 136 were excluded due to error in staging or because they had received another type of chemotherapy. Median age was 50 years, all with performance status 0-1. Median initial clinical size of tumor was 65mm and the median final clinical size of the tumor was 22mm. Fifty-one (17.1%) patients experienced a pathologic complete response. Those with a negative hormonal profile or who were triple-negative (negative Her-2 and hormonal profile) experienced a favorable impact on the pathologic complete response. Conclusion: Neoadjuvant chemotherapy with doxorubicin/ cyclophosphamide followed by paclitaxel provided a pathologic complete response in the population studied in accordance with that observed in the literature. Triple-negative patients had a greater chance of attaining this response. PMID:24488382

  16. Immediate radical trachelectomy versus neoadjuvant chemotherapy followed by conservative surgery for patients with stage IB1 cervical cancer with tumors 2cm or larger: A literature review and analysis of oncological and obstetrical outcomes.

    PubMed

    Pareja, Rene; Rendón, Gabriel J; Vasquez, Monica; Echeverri, Lina; Sanz-Lomana, Carlos Millán; Ramirez, Pedro T

    2015-06-01

    Radical trachelectomy is the treatment of choice in women with early-stage cervical cancer wishing to preserve fertility. Radical trachelectomy can be performed with a vaginal, abdominal, or laparoscopic/robotic approach. Vaginal radical trachelectomy (VRT) is generally not offered to patients with tumors 2cm or larger because of a high recurrence rate. There are no conclusive recommendations regarding the safety of abdominal radical trachelectomy (ART) or laparoscopic radical trachelectomy (LRT) in such patients. Several investigators have used neoadjuvant chemotherapy in patients with tumors 2 to 4cm to reduce tumor size so that fertility preservation may be offered. However, to our knowledge, no published study has compared outcomes between patients with cervical tumors 2cm or larger who underwent immediate radical trachelectomy and those who underwent neoadjuvant chemotherapy followed by radical trachelectomy. We conducted a literature review to compare outcomes with these 2 approaches. Our main endpoints for evaluation were oncological and obstetrical outcomes. The fertility preservation rate was 82.7%, 85.1%, 89%; and 91.1% for ART (tumors larger than >2cm), ART (all sizes), NACT followed by surgery and VRT (all sizes); respectively. The global pregnancy rate was 16.2%, 24% and 30.7% for ART, VRT, and NACT followed by surgery; respectively. The recurrence rate was 3.8%, 4.2%, 6%, 7.6% and 17% for ART (all sizes), VRT (all sizes), ART (tumors>2cm), NACT followed by surgery, and VRT (tumors>2cm). These outcomes must be considered when offering a fertility sparing technique to patients with a tumor larger than 2cm.

  17. 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.

  18. 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

  19. [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.

  20. The Role of GOLPH3L in the Prognosis and NACT response in Cervical Cancer

    PubMed Central

    Feng, Yanling; He, Fan; Yan, Shumei; Huang, He; Huang, Qidan; Deng, Ting; Wu, Huini; Gao, Bei; Liu, Jihong

    2017-01-01

    Background: We previously reported GOLPH3L is a novel oncogene associated with ovarian cancer. The role of GOLPH3L in cervical cancer and its cellular functions has not been determined. This study investigated clinical significance of GOLPH3L and potential proteins and pathways associated with GOLPH3L in cervical squamous cell carcinoma. Methods: Immunohistochemistry and western blot were used to examine the expression of GOLPH3L in cervical squamous cell carcinoma tissue specimens and adjacent non-cancerous tissues. The clinical and prognostic significance of GOLPH3L expression was statistically analyzed. Cell proliferation rate, cell cycle progression, apoptosis and cisplatin response in GOLPH3L silenced SiHa and HeLa cells were also examined. Phospho-antibody array was used to identify changes in protein phosphorylation and the corresponding signaling pathways associated with these changes. Results: GOLPH3L overexpressed in cervical cancer tissue specimens compared with normal adjacent non-cancerous tissues. Increased GOLPH3L expression was associated with FIGO staging (P=0.033), cervical stromal invasion (P=0.037), cervical canal stromal invasion (P=0.027), lymph node metastasis (P=0.016) and positive surgical margins (P=0.015). Patients with lower expression of GOLPH3L demonstrated longer progression-free survival and overall survival compared with those with higher expression. The tissue samples from patients who poorly responded to neoadjuvant chemotherapy (NACT) exhibited increased GOLPH3L expression levels compared with tissue samples from patients who achieved a pathologic complete response (pCR). Patients with lower GOLPH3L expression level, poorer tumor differentiation, shorter NACT treatment intervals and smaller tumor sizes were more likely to achieve a pCR after NACT. Knockdown GOLPH3L in cells was associated with an induction of cell cycle arrest, increased apoptosis and cisplatin sensitivity, and a reduction in cellular viability. Phospho

  1. 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.

  2. Correlation between the expression of S100A4 and the efficacy of TAC neoadjuvant chemotherapy in breast cancer.

    PubMed

    Li, Wen-Lei; Zhang, Yang; Liu, Bao-Guo; DU, Qian; Zhou, Chang-Xin; Tian, Xing-Song

    2015-11-01

    The aim of this study was to investigate the correlation between the expression of S100A4 and the efficacy of neoadjuvant chemotherapy in breast cancer. A total of 65 patients with invasive breast cancer were treated with neoadjuvant chemotherapy using the TAC regimen. The expression of S100A4 was detected by an immunohistochemical two-step method prior to treatment, after 2 cycles of chemotherapy and after 4 cycles of chemotherapy. Pathological evaluations of the chemotherapy were performed using the Miller and Payne (MP) grading system and their correlation with the changes of S100A4 expression during and after the treatment were explored. Between pre-neoadjuvant chemotherapy and 4 cycles post-chemotherapy, there was a significant difference in the expression of S100A4 (P<0.05); S100A4 expression was associated with neoadjuvant chemotherapy. However, between pre-neoadjuvant chemotherapy and 2 cycles post-chemotherapy, there was no significant difference in the expression of S100A4 (P>0.05). The intensity and changes of S100A4 expression were positively correlated with the efficacy of neoadjuvant chemotherapy (r=0.259, P<0.05). When patients with an MP grade of I or II following the second cycle of neoadjuvant chemotherapy were continually treated with the original chemotherapy for another 2 cycles, the desired effect was generally not achieved. S100A4 may be used as a predictor of the efficacy of neoadjuvant chemotherapy in breast cancer, guiding the formulation of individualized programs to improve the effectiveness of the treatment. For patients with an MP grade level of I or II after 2 cycles of neoadjuvant chemotherapy, the use of alternative chemotherapy regimens should be considered.

  3. 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

  4. Prognostic value of persistent node involvement after neoadjuvant chemotherapy in patients with operable breast cancer

    PubMed Central

    Pierga, J-Y; Mouret, E; Diéras, V; Laurence, V; Beuzeboc, P; Dorval, T; Palangié, T; Jouve, M; Vincent-Salomon, A; Scholl, S; Extra, J-M; Asselain, B; Pouillart, P

    2000-01-01

    Neoadjuvant chemotherapy is able to reduce the size of the majority of breast tumours and down-stage axillary-node status. The aim of this study was to assess the prognostic value of persistent node involvement after neoadjuvant chemotherapy. A total of 488 patients with T2–T3, N0–N1 breast cancer treated by neoadjuvant chemotherapy followed by tumour excision and axillary lymph-node dissection between 1981 and 1992 were selected from the Institut Curie database. Median follow-up was 7 years. Overall objective response rate before local treatment was 52% and breast tumour size was reduced in 83% of patients. No pathologic nodal involvement was observed in 46.5% of patients. Patients with ≥ eight positive nodes had a very poor median disease-free survival of only 20 months. Their 10-year disease-free survival rate was 7%, while the 10-year disease-free survival rate for patients with no node involvement was 64%. Median survival for patients with ≥ eight nodes positive was 48 months and the 10-year survival rate was 26% (P < 0.0001). On multivariate analysis, outcome was strongly correlated with pathological nodal status, tumour grade, hormonal receptor status and clinical response of the tumour. In conclusion, patients with extensive nodal involvement after neoadjuvant chemotherapy have a very poor outcome. Second-line treatment should be considered in this population. © 2000 Cancer Research Campaign http://www.bjcancer.com PMID:11076657

  5. [Peculiarities of urinary bladder cancer tumor cells apoptosis response on neoadjuvant chemotherapy].

    PubMed

    Iatsyna, A I; Stakhovskiĭ, É A; Sheremet, Ia A; Spivak, S I; Stakhovskiĭ, A É; Gavriliuk, O N; Vitruk, Iu V; Emets, A I; Blium, Ia B

    2011-01-01

    Induced apoptosis in urinary bladder cancer tumor cells of patients was studied using TUNEL reaction. It was shown that increase in induced apoptosis value had a definite correlation between corresponding features of tumor reaction as a response on Gemcitabine-Cisplatin neoadjuvant chemotherapy application. It was found that evaluation of induced apoptosis in urinary bladder cancer tumor cells using TUNEL method allows forecasting the effectiveness of chemotherapy on the cellular level in patients with this type of cancer.

  6. 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).

  7. Successful treatment of gallbladder mixed adenoneuroendocrine carcinoma with neo-adjuvant chemotherapy

    PubMed Central

    2012-01-01

    Mixed adenoneuroendocrine carcinoma (MANEC) carcinomas rarely occur in the gallbladder. Here we reported a case of giant gallbladder unresectable mass with local liver invasion and omentum metastasis, which proved to be neuroendocrine carcinoma (NEC) by biopsy, received successful radical operation after neo-adjuvant chemotherapy plus somatostatin treatment. The patient showed good response as the neoplasm diminished dramatically and showed clear margin after 6 courses of treatment. A radical operation including cholecystectomy, hepatic wedge resection of the gallbladder fossa segment and lymph node of group 8a and 8p resection was performed successfully. Postoperative histopathological examination revealed neuroendocrine carcinoma mixed with adenocarcinoma in the gallbladder wall. Followed up showed no evidence of recurrence after 7 months of the operation. We suggest that neo-adjuvant chemotherapy may be beneficial to gallbladder mixed neuroendocrine carcinomas in an advanced stage which could also be advantageous to NEC of other organs. Virtual slides http://www.diagnosticpathology.diagnomx.eu/vs/2731892837743787 PMID:23186166

  8. Increased prevalence of vitamin D insufficiency in patients with breast cancer after neoadjuvant chemotherapy.

    PubMed

    Jacot, William; Pouderoux, Stéphane; Thezenas, Simon; Chapelle, Angélique; Bleuse, Jean-Pierre; Romieu, Gilles; Lamy, Pierre-Jean

    2012-07-01

    Patients with locally advanced breast cancer treated with neoadjuvant chemotherapy are at risk of cancer treatment-induced bone loss and consequently of increased skeletal morbidity. In addition, this situation could be worsened by the fact that only a minority of patients with breast cancer have sufficient vitamin D. A comprehensive evaluation of bone homeostasis is critical in this context. We retrospectively evaluated the serum levels of calcium, vitamin D, TRAIL, RANK ligand (RANKL), Osteoprotegerin (OPG), Bone TRAP, CrossLaps and DKK1 in 77 patients (median age: 50 years; range 25-74), with locally advanced breast cancer treated in our institute with anthracyclines-taxane neoadjuvant chemotherapy (7 cycles of 21 days/each) between March 2007 and August 2008. Serum samples were collected before the first (baseline) and the last treatment cycle. Variations and correlations between biomarker levels were evaluated. At baseline, 79.5 % of patients had vitamin D insufficiency (<30 ng/ml), increasing to 97.4 % at the end of the neoadjuvant chemotherapy (p < 0.0001). Calcium and RANKL serum concentrations were also significantly decreased, while OPG was significantly increased, resulting in lower RANKL/OPG ratio. Calcium and vitamin D, RANKL and vitamin D and RANKL and OPG levels were significantly correlated (Spearman's coefficient r = 0.2721, p = 0.0006; r = 0.1916, p = 0.002; and r = -0.179, p = 0.03, respectively). Nearly all included patients suffered from vitamin D insufficiency by the end of the neoadjuvant chemotherapy with changes in the calcium/RANKL/OPG axis that are evocative of deregulation of a functional regulatory mechanism. Further studies are needed to determine how drugs modulate this regulatory mechanism to preserve bone homeostasis in patients with breast cancer.

  9. Evaluation of overall tumor cellularity after neoadjuvant chemotherapy in patient with locally advanced hypopharyngeal cancer.

    PubMed

    Chitose, Shun-ichi; Chijiwa, Hideki; Maeda, Akiteru; Umeno, Hirohito; Nakashima, Tadashi; Kiyokawa, Kensuke; Hayabuchi, Naofumi; Fujita, Hiromasa

    2012-11-01

    The aim of this study is to clarify the prognostic value of the pathological overall tumor cellularity after neoadjuvant chemotherapy for locally advanced hypopharyngeal cancer. In consecutive series of 45 operable patients with locally advanced hypopharyngeal cancer, neoadjuvant chemotherapy by cisplatin and 5-fluorouracil was administered. Pathological image analysis was performed in 30 patients using the large cross-section specimen after total resection to evaluate the overall tumor cellularity. The chemotherapeutic responses were classified according to the pathological grading scale by dividing into four categories; more than 70% overall tumor cellularity in Grade 1, between an estimated 10 and 70% in Grade 2, less than 10% in Grade 3, and no identifiable malignant tumor cells in Grade 4. The pathological grades were taken into account for analysis of the survival. In 30 available patients, 40% had Grade 1 pathological response, 30% had Grade 2, and 30% had Grade 3. There was no Grade 4 patient. The overall 5-year survival rate for these 30 patients was 53.33%. The survival rate (61.66%) for patients with Grade 2 and 3 responses was significantly higher than that (27.78%) for patients with Grade 1 response (p = 0.009). Cox regression analysis revealed that the increasing pathological grade was an independent predictor of a better survival in patients undergoing neoadjuvant chemotherapy. We have shown that the prognosis of patients with locally advanced hypopharyngeal cancer, who had been treated by neoadjuvant chemotherapy followed by total resection, can be predicted by evaluation of pathological overall tumor cellularity from the large section specimen.

  10. Evaluation of biomarker changes after administration of various neoadjuvant chemotherapies in breast cancer

    PubMed Central

    Jin, Guangchao; Han, Yu; Liu, Cun; Chen, Liansheng; Ding, Butong; Xuan, Shijin; Liu, Xianqiang; Ma, Guohui; Gao, Jun; Tian, Xingsong

    2015-01-01

    To assess the changes in estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and Ki-67 expression in breast cancer patients after various neoadjuvant chemotherapies. Data from 138 locally advanced breast cancer patients with histological diagnoses were reviewed. Seventy patients (group 1) were given 4 cycles of 500 mg/m2 cyclophosphamide and 50 mg/m2 pirarubicin every 21 days. Sixty-eight patients (group 2) were given 4 cycles of 500 mg/m2 cyclophosphamide and 75 mg/m2 docetaxel every 21 days. The biomarker changes of the operated tumor tissues were compared with the initial core biopsies. ER, PR, HER2 and Ki-67 expression changed by 28.6%, 22.9%, 17.1% and 54.3%, respectively, after neoadjuvant chemotherapy in group 1 and 16.2%, 22.1%, 13.2% and 70.6%, respectively, after neoadjuvant chemotherapy in group 2. There were significant differences between the groups regarding ER and Ki-67 status changes, and these changes can be used to inform treatment strategies. PMID:25755795

  11. The attention network changes in breast cancer patients receiving neoadjuvant chemotherapy: Evidence from an arterial spin labeling perfusion study

    PubMed Central

    Chen, Xingui; He, Xiaoxuan; Tao, Longxiang; Cheng, Huaidong; Li, Jingjing; Zhang, Jingjie; Qiu, Bensheng; Yu, Yongqiang; Wang, Kai

    2017-01-01

    To investigate the neural mechanisms underlying attention deficits that are related to neoadjuvant chemotherapy in combination with cerebral perfusion. Thirty one patients with breast cancer who were scheduled to receive neoadjuvant chemotherapy and 34 healthy control subjects were included. The patients completed two assessments of the attention network tasks (ANT), neuropsychological background tests, and the arterial spin labeling scan, which were performed before neoadjuvant chemotherapy and after completing chemotherapy. After neoadjuvant chemotherapy, the patients exhibited reduced performance in the alerting and executive control attention networks but not the orienting network (p < 0.05) and showed significant increases in cerebral blood flow (CBF) in the left posterior cingulate gyrus, left middle occipital gyrus, bilateral precentral gyrus, inferior parietal gyrus, supramarginal gyrus, angular gyrus, precuneus, cuneus, superior occipital gyrus, calcarine cortex, and temporal gyrus (p < 0.01 corrected) when compared with patients before chemotherapy and healthy controls. A significant correlation was found between the decrease performance of ANT and the increase in CBF changes in some brain regions of the patients with breast cancer. The results demonstrated that neoadjuvant chemotherapy influences hemodynamic activity in different brain areas through increasing cerebral perfusion, which reduces the attention abilities in breast cancer patients. PMID:28209975

  12. Residual mucin and response after neoadjuvant chemotherapy (NAC) in breast cancer.

    PubMed

    Jove, Maria; Verghese, Eldo; Sharma, Nisha; Lane, Sally

    2016-05-06

    Neoadjuvant chemotherapy (NAC) is the standard of care for patients with breast cancer with inoperable disease or smaller tumours who might benefit from a conservative surgery after downstaging of their disease. Nevertheless, evidence shows that preoperative and postoperative chemotherapy are equivalent in terms of long-term survival. Response and histological changes after NAC have been widely studied in invasive ductal carcinoma not otherwise specified, but there is a paucity of characterisation of patterns of response to chemotherapy in less frequent histological types. We report extensive residual mucin deposits after chemotherapy in a woman with locally advanced breast cancer and a prominent mucinous component at diagnosis. Interestingly, residual mucin was co-located with the initial tumour, in the breast as well as in the axillary lymph nodes. The distribution of mucin may be a valuable marker of the extent of mucinous carcinomas prior to NAC.

  13. 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

  14. 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

  15. 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

  16. Immune contexture and histological response after neoadjuvant chemotherapy predict clinical outcome of lung cancer patients.

    PubMed

    Remark, Romain; Lupo, Audrey; Alifano, Marco; Biton, Jerome; Ouakrim, Hanane; Stefani, Alessandro; Cremer, Isabelle; Goc, Jeremy; Régnard, Jean-Francois; Dieu-Nosjean, Marie-Caroline; Damotte, Diane

    2016-01-01

    There is now growing evidence that the immune contexture influences cancer progression and clinical outcome of patients with non-small cell lung cancer (NSCLC). If chemotherapy is widely used to treat patients with advanced-stage NSCLC, it remains unclear how it could modify the immune contexture and impact its prognostic value. Here, we analyzed two retrospective cohorts, respectively composed of 122 stage III-N2 NSCLC patients treated with chemotherapy before surgery and 39 stage-matched patients treated by surgery only. In patients treated with neoadjuvant chemotherapy, the histological characteristics, the expression of PD-L1 protein, and the tumor immune microenvironment (CD8(+) T cells, DC-LAMP(+) mature dendritic cells, and CD68(+) macrophages) were evaluated and their prognostic value assessed together with standard clinical parameters. By analyzing pre- and post-treatment specimens, we did not find any changes in the PD-L1 expression. We also found that the tumor immune contexture in patients treated with neoadjuvant chemotherapy exhibited a similar pattern that the one found in chemotherapy-naive patients, with comparable densities of tumor-infiltrating CD8(+) and DC-LAMP(+) cells and a similar spatial organization. The percentage of residual viable tumor cells and the immune pattern (CD8(+) and DC-LAMP(+) cell densities) were significantly associated with the clinical outcome and allowed the identification of short- and long-term survivors, respectively. In multivariate analysis, the immune pattern was found to be the strongest independent prognostic factor. In conclusion, this study decrypts the complex interplay between cancer and immune cells in patients undergoing chemotherapy and supports potential beneficial synergistic effect of immunotherapy and chemotherapy.

  17. An Epigenomic Approach to Improving Response to Neoadjuvant Cisplatin Chemotherapy in Bladder Cancer.

    PubMed

    Xylinas, Evanguelos; Hassler, Melanie R; Zhuang, Dazhong; Krzywinski, Martin; Erdem, Zeynep; Robinson, Brian D; Elemento, Olivier; Clozel, Thomas; Shariat, Shahrokh F

    2016-09-02

    Bladder cancer is among the five most common cancers diagnosed in the Western world and causes significant mortality and morbidity rates in affected patients. Therapeutic options to treat the disease in advanced muscle-invasive bladder cancer (MIBC) include cystectomy and chemotherapy. Neoadjuvant cisplatin-based combination chemotherapy is effective in MIBC; however, it has not been widely adopted by the community. One reason is that many patients do not respond to neoadjuvant chemotherapy, and no biomarker currently exists to identify these patients. It is also not clear whether a strategy to sensitize chemoresistant patients may exist. We sought to identify cisplatin-resistance patterns in preclinical models of bladder cancer, and test whether treatment with the epigenetic modifier decitabine is able to sensitize cisplatin-resistant bladder cancer cell lines. Using a screening approach in cisplatin-resistant bladder cancer cell lines, we identified dysregulated genes by RNA sequencing (RNAseq) and DNA methylation assays. DNA methylation analysis of tumors from 18 patients receiving cisplatin-based chemotherapy was used to confirm in vitro results. Cisplatin-resistant bladder cancer cells were treated with decitabine to investigate epigenetic sensitization of resistant cell lines. Our results show that HOXA9 promoter methylation status is associated with response to cisplatin-based chemotherapy in bladder cancer cell lines and in metastatic bladder cancer. Bladder cancer cells resistant to cisplatin chemotherapy can be sensitized to cisplatin by the DNA methylation inhibitor decitabine. Our data suggest that HOXA9 promoter methylation could serve as potential predictive biomarker and decitabine might sensitize resistant tumors in patients receiving cisplatin-based chemotherapy.

  18. Increasing utilization of neoadjuvant chemotherapy for muscle-invasive bladder cancer in the United States.

    PubMed

    Keegan, Kirk A; Zaid, Harras B; Patel, Sanjay G; Chang, Sam S

    2014-04-01

    The treatment and management of advanced urothelial carcinoma of the bladder is a considerable therapeutic challenge. Prospective, randomized clinical trial data demonstrate a survival advantage for those patients who receive chemotherapy prior to radical cystectomy. Despite the overall survival benefits, results from both institutional and administrative datasets suggest that historical use of a neoadjuvant chemotherapy paradigm is remarkably low. This review will evaluate the recent trends in pre-operative chemotherapy utilization that suggest small, but progressively increased use-currently on the order of 20 % of radical cystectomy patients. Additionally, this analysis will explore the various processes and structural barriers that preclude its receipt such as patient age and comorbidity, as well as physician preference, delay to potentially curable surgery, geographic region, distance to treatment facility, and socioeconomic status.

  19. 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

  20. Management of Inflammatory Breast Cancer After Neoadjuvant Chemotherapy

    SciTech Connect

    Abrous-Anane, Soumya; Savignoni, Alexia; Daveau, Caroline; Pierga, Jean-Yves; Gautier, Chantal; Reyal, Fabien; Dendale, Remi; Campana, Francois; Kirova, Youlia M.; Fourquet, Alain; Bollet, Marc A.

    2011-03-15

    Purpose: To assess the benefit of breast surgery for inflammatory breast cancer (IBC). Methods and Materials: This retrospective series was based on 232 patients treated for IBC. All patients received primary chemotherapy followed by either exclusive radiotherapy (118 patients; 51%) or surgery with or without radiotherapy (114 patients; 49%). The median follow-up was 11 years. Results: The two groups were comparable apart from fewer tumors <70 mm (43% vs. 33%, p = 0.003), a higher rate of clinical stage N2 (15% vs. 5%, p = 0.04), and fewer histopathologic Grade 3 tumors (46% vs. 61%, p <0.05) in the no-surgery group. The addition of surgery was associated with a significant improvement in locoregional disease control (p = 0.04) at 10 years locoregional free interval 78% vs. 59% but with no significant difference in overall survival rates or disease-free intervals. Late toxicities were not significantly different between the two treatment groups except for a higher rate of fibrosis in the no-surgery group (p <0.0001) and more lymphedema in the surgery group (p = 0.002). Conclusion: Our data suggest an improvement in locoregional control in patients treated by surgery, in conjunction with chemotherapy and radiotherapy, for IBC. Efforts must be made to improve overall survival.

  1. 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.

  2. 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

  3. Real-world outcomes in young women with breast cancer treated with neoadjuvant chemotherapy.

    PubMed

    Villarreal-Garza, Cynthia; Bargallo-Rocha, Juan Enrique; Soto-Perez-de-Celis, Enrique; Lasa-Gonsebatt, Federico; Arce-Salinas, Claudia; Lara-Medina, Fernando; Reynoso-Noverón, Nancy; Matus-Santos, Juan; Cabrera, Paula; Alvarado-Miranda, Alberto; Mohar, Alejandro

    2016-06-01

    Breast cancer in young women has been shown to have an aggressive behavior and worse prognosis. Studies evaluating young women enrolled in clinical trials of neoadjuvant chemotherapy have shown that age is a determinant factor in the achievement of a pathological complete response (pCR). In this study, we sought to analyze the outcomes of young patients treated with neoadjuvant chemotherapy at a single institution. 1639 patients treated with neoadjuvant chemotherapy were included. 316 patients ≤40 years were compared with 1323 patients aged >40 years regarding the achievement of a pCR (defined as no invasive residual tumor in the breast or lymph nodes). Disease-free survival (DFS) and overall survival were compared between groups according to pCR status and subtype, defined by hormone receptor (HR) and HER2 status. Young women were more likely to have a pCR than their older counterparts (37.4 vs. 26.3 %, P < 0.001). This difference was significant both for HR+/HER2- and triple-negative (TN) tumors. Young age and achieving less than pCR were associated with a greater chance of recurrence for the entire population. Age was not an independent factor for recurrence in TN and HER2+ disease. However, being younger than 40 increased recurrence risk in HR+/HER2- tumors. The achievement of a pCR was not associated with improved DFS in young women with HR+/HER2- tumors. Although young women have a high rate of pCR, they also have a worse prognosis. In a real-world clinical setting, the achievement of a pCR was an independently significant protective factor for recurrence across all subtypes and ages, except for HR+, HER2- disease in young women.

  4. [A pheochromocytoma of urinary bladder treated with neoadjuvant chemotherapy].

    PubMed

    Ibuki, Naokazu; Komura, Kazumasa; Koyama, Kouhei; Inamoto, Teruo; Segawa, Naoki; Tanimoto, Keiji; Tuji, Motomu; Azuma, Haruhito; Katsuoka, Yoji

    2009-12-01

    A 69-year-old female presented with hypertension and a solid mass in the bladder on ultrasonography. Cystoscopy revealed a submucosal tumor in the right lateral wall of the bladder. A transurethral resection was performed. Histologically, pathologic examination revealed a malignant pheochromocytoma. She refused surgical therapy and radiation therapy. She had no treatment for two years. She suddenly complained of gross hematuria. T2-weighted magnetic resonance imaging showed a bladder tumor of high intensity and extra-bladder invasion. She was treated with chemotherapy (CVD) for 26 cycles. Since the tumor size was reduced, she was referred to our hospital for operative indication. Partial cystectomy was performed. Histologically, the tumor was a pheochromocytoma of the urinary bladder. Ten months after the operation, she has no clinical evidence of recurrence.

  5. Correlating transcriptional networks with pathological complete response following neoadjuvant chemotherapy for breast cancer.

    PubMed

    Liu, Rong; Lv, Qiao-Li; Yu, Jing; Hu, Lei; Zhang, Li-Hua; Cheng, Yu; Zhou, Hong-Hao

    2015-06-01

    We aimed to investigate the association between gene co-expression modules and responses to neoadjuvant chemotherapy in breast cancer by using a systematic biological approach. The gene expression profiles and clinico-pathological data of 508 (discovery set) and 740 (validation set) patients with breast cancer who received neoadjuvant chemotherapy were analyzed. Weighted gene co-expression network analysis was performed and identified seven co-regulated gene modules. Each module and gene signature were evaluated with logistic regression models for pathological complete response (pCR). The association between modules and pCR in each intrinsic molecular subtype was also investigated. Two transcriptional modules were correlated with tumor grade, estrogen receptor status, progesterone receptor status, and chemotherapy response in breast cancer. One module that constitutes upregulated cell proliferation genes was associated with a high probability for pCR in the whole (odds ratio (OR) = 5.20 and 3.45 in the discovery and validation datasets, respectively), luminal B, and basal-like subtypes. The prognostic potentials of novel genes, such as MELK, and pCR-related genes, such as ESR1 and TOP2A, were identified. The upregulation of another gene co-expression module was associated with weak chemotherapy responses (OR = 0.19 and 0.33 in the discovery and validation datasets, respectively). The novel gene CA12 was identified as a potential prognostic indicator in this module. A systems biology network-based approach may facilitate the discovery of biomarkers for predicting chemotherapy responses in breast cancer and contribute in developing personalized medicines.

  6. Association of cytochrome P450 genetic polymorphisms with neoadjuvant chemotherapy efficacy in breast cancer patients

    PubMed Central

    2012-01-01

    Background The enzymes of the cytochrome P450 family (CYPs) play an important role in the metabolism of a great variety of anticancer agents; therefore, polymorphisms in genes encoding for metabolizing enzymes and drugs transporters can affect drug efficacy and toxicity. Methods The genetic polymorphisms of cytochrome P450 were studied in 395 patients with breast cancer by RLFP analysis. Results Here, we studied the association of functionally significant variant alleles of CYP3A4, CYP3A5, CYP2B6, CYP2C8, CYP2C9 and CYP2C19 with the clinical response to neoadjuvant chemotherapy in breast cancer patients. A significant correlation was observed between the CYP2C9*2 polymorphism and chemotherapy resistance (OR = 4.64; CI 95% = 1.01 – 20.91), as well as between CYP2C9*2 heterozygotes and chemotherapy resistance in women with nodal forms of breast cancer and a cancer hereditary load (OR = 15.50; CI 95% = 1.08 – 826.12) when the potential combined effects were examined. No significant association between chemotherapy resistance and the other examined genotypes and the potential combined clinical and tumour-related parameters were discovered. Conclusion In conclusion, CYP2C9*2 was associated with neoadjuvant chemotherapy resistance (OR = 4.64; CI 95% = 1.01 – 20.91) in the population of interest. PMID:22702493

  7. High Proliferation Predicts Pathological Complete Response to Neoadjuvant Chemotherapy in Early Breast Cancer

    PubMed Central

    Lluch, Ana; Ribelles, Nuria; Anton-Torres, Antonio; Sanchez-Rovira, Pedro; Albanell, Joan; Calvo, Lourdes; García-Asenjo, Jose Antonio Lopez; Palacios, Jose; Chacon, Jose Ignacio; Ruiz, Amparo; De la Haba-Rodriguez, Juan; Segui-Palmer, Miguel A.; Cirauqui, Beatriz; Margeli, Mireia; Plazaola, Arrate; Barnadas, Agusti; Casas, Maribel; Caballero, Rosalia; Carrasco, Eva; Rojo, Federico

    2016-01-01

    Background. In the neoadjuvant setting, changes in the proliferation marker Ki67 are associated with primary endocrine treatment efficacy, but its value as a predictor of response to chemotherapy is still controversial. Patients and Methods. We analyzed 262 patients with centralized basal Ki67 immunohistochemical evaluation derived from 4 GEICAM (Spanish Breast Cancer Group) clinical trials of neoadjuvant chemotherapy for breast cancer. The objective was to identify the optimal threshold for Ki67 using the receiver-operating characteristic curve method to maximize its predictive value for chemotherapy benefit. We also evaluated the predictive role of the defined Ki67 cutoffs for molecular subtypes defined by estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2). Results. A basal Ki67 cutpoint of 50% predicted pathological complete response (pCR). Patients with Ki67 >50% achieved a pCR rate of 40% (36 of 91) versus a pCR rate of 19% in patients with Ki67 ≤50% (33 of 171) (p = .0004). Ki67 predictive value was especially relevant in ER-HER2− and ER-HER2+ patients (pCR rates of 42% and 64%, respectively, in patients with Ki67 >50% versus 15% and 45%, respectively, in patients with Ki67 ≤50%; p = .0337 and .3238, respectively). Both multivariate analyses confirmed the independent predictive value of the Ki67 cutpoint of 50%. Conclusion. Basal Ki67 proliferation index >50% should be considered an independent predictive factor for pCR reached after neoadjuvant chemotherapy, suggesting that cell proliferation is a phenomenon closely related to chemosensitivity. These findings could help to identify a group of patients with a potentially favorable long-term prognosis. Implications for Practice: The use of basal Ki67 status as a predictive factor of chemotherapy benefit could facilitate the identification of a patient subpopulation with high probability of achieving pathological complete response when treated with primary chemotherapy, and thus

  8. Class III β-tubulin overexpression within the tumor microenvironment is a prognostic biomarker for poor overall survival in ovarian cancer patients treated with neoadjuvant carboplatin/paclitaxel.

    PubMed

    Roque, Dana M; Buza, Natalia; Glasgow, Michelle; Bellone, Stefania; Bortolomai, Ileana; Gasparrini, Sara; Cocco, Emiliano; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Rutherford, Thomas J; Schwartz, Peter E; Santin, Alessandro D

    2014-01-01

    Critics have suggested that neoadjuvant chemotherapy (NACT) followed by interval debulking may select for resistant clones or cancer stem cells when compared to primary cytoreduction. β-tubulins are chemotherapeutic targets of taxanes and epothilones. Class III β-tubulin overexpression has been linked to chemoresistance and hypoxia. Herein, we describe changes in class III β-tubulin in patients with advanced ovarian carcinoma in response to NACT, in relationship to clinical outcome, and between patients who underwent NACT versus primary debulking; we characterize in vitro chemosensitivity to paclitaxel/patupilone of cell lines established from this patient population, and class III β-tubulin expression following repeated exposure to paclitaxel. Using immunohistochemistry, we observed among 22 paired specimens obtained before/after NACT decreased expression of class III β-tubulin following therapy within stroma (p=0.07), but not tumor (p=0.63). Poor median overall survival was predicted by high levels of class III β-tubulin in both tumor (HR 3.66 [1.11,12.05], p=0.03) and stroma (HR 4.53 [1.28,16.1], p=0.02). Class III β-tubulin expression by quantitative-real-time-polymerase-chain-reaction was higher among patients who received NACT (n=12) compared to primary cytoreduction (n=14) (mean±SD fold-change: 491.2±115.9 vs. 224.1±55.66, p=0.037). In vitro subculture with paclitaxel resulted in class III β-tubulin upregulation, however, cell lines that overexpressed class III β-tubulin remained sensitive to patupilone. Overexpression of class III β-tubulin in patients dispositioned to NACT may thus identify an intrinsically aggressive phenotype, and predict poor overall survival and paclitaxel resistance. Decreases in stromal expression may represent normalization of the tumor microenvironment following therapy. Epothilones warrant study for patients who have received neoadjuvant carboplatin and paclitaxel.

  9. 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.

  10. Small cell neuroendocrine carcinoma of the urinary tract successfully managed with neoadjuvant chemotherapy.

    PubMed

    Ahsaini, Mustapha; Riyach, Omar; Tazi, Mohammed Fadl; El Fassi, Mohammed Jamal; Farih, My Hassan; Elfatmi, Hind; Amarti, Afaf

    2013-01-01

    Introduction. Small cell neuroendocrine carcinomas of the urinary tract is an extremely rare entity and very few cases have been reported in the literature. Small cell neuroendocrine carcinoma of the urinary tract (SCC-UT) is the association between bladder and urinary upper tract-small cell carcinoma (UUT-SCC). It characterized by an aggressive clinical course. The prognosis is poor due to local or distant metastases, and usually the muscle of the bladder is invaded. Case Presentation. We report a rare case of a 54-year-old Arab male native of moroccan; he is a smoker and was referred to our institution for intermittent hematuria. Following a diagnosis of small cell neuroendocrine carcinomas of the ureter and the bladder, thoracoabdominal-pelvic CT was done, and the staging of the tumor was done in the bladder (T2N0M0) and (T1N0M0) in the ureter. Neoadjuvant alternating doublet chemotherapy with ifosfamide/doxorubicin and etoposide/cisplatin was realized, and nephroureterectomy associated to a cystoprostatectomy was carried out. After 24 months of followup, no local or distant metastasis was detected. Conclusion. The purpose of this review is to present a rare case of pure small cell neuroendocrine carcinoma of the urinary tract and review the literature about the place of neoadjuvant chemotherapy in this rare tumors.

  11. Small Cell Neuroendocrine Carcinoma of the Urinary Tract Successfully Managed with Neoadjuvant Chemotherapy

    PubMed Central

    Ahsaini, Mustapha; Riyach, Omar; Tazi, Mohammed Fadl; El Fassi, Mohammed Jamal; Farih, My Hassan; Elfatmi, Hind; Amarti, Afaf

    2013-01-01

    Introduction. Small cell neuroendocrine carcinomas of the urinary tract is an extremely rare entity and very few cases have been reported in the literature. Small cell neuroendocrine carcinoma of the urinary tract (SCC-UT) is the association between bladder and urinary upper tract-small cell carcinoma (UUT-SCC). It characterized by an aggressive clinical course. The prognosis is poor due to local or distant metastases, and usually the muscle of the bladder is invaded. Case Presentation. We report a rare case of a 54-year-old Arab male native of moroccan; he is a smoker and was referred to our institution for intermittent hematuria. Following a diagnosis of small cell neuroendocrine carcinomas of the ureter and the bladder, thoracoabdominal-pelvic CT was done, and the staging of the tumor was done in the bladder (T2N0M0) and (T1N0M0) in the ureter. Neoadjuvant alternating doublet chemotherapy with ifosfamide/doxorubicin and etoposide/cisplatin was realized, and nephroureterectomy associated to a cystoprostatectomy was carried out. After 24 months of followup, no local or distant metastasis was detected. Conclusion. The purpose of this review is to present a rare case of pure small cell neuroendocrine carcinoma of the urinary tract and review the literature about the place of neoadjuvant chemotherapy in this rare tumors. PMID:24024065

  12. 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.

  13. Early Prediction of the Response of Breast Tumors to Neoadjuvant Chemotherapy using Quantitative MRI and Machine Learning

    PubMed Central

    Mani, Subramani; Chen, Yukun; Arlinghaus, Lori R.; Li, Xia; Chakravarthy, A. Bapsi; Bhave, Sandeep R.; Welch, E. Brian; Levy, Mia A.; Yankeelov, Thomas E.

    2011-01-01

    The ability to predict early in the course of treatment the response of breast tumors to neoadjuvant chemotherapy can stratify patients based on response for patient-specific treatment strategies. Currently response to neoadjuvant chemotherapy is evaluated based on physical exam or breast imaging (mammogram, ultrasound or conventional breast MRI). There is a poor correlation among these measurements and with the actual tumor size when measured by the pathologist during definitive surgery. We tested the feasibility of using quantitative MRI as a tool for early prediction of tumor response. Between 2007 and 2010 twenty consecutive patients diagnosed with Stage II/III breast cancer and receiving neoadjuvant chemotherapy were enrolled on a prospective imaging study. Our study showed that quantitative MRI parameters along with routine clinical measures can predict responders from non-responders to neoadjuvant chemotherapy. The best predictive model had an accuracy of 0.9, a positive predictive value of 0.91 and an AUC of 0.96. PMID:22195145

  14. 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

  15. 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

  16. 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

  17. A wearable optical device for continuous monitoring during neoadjuvant chemotherapy infusions

    NASA Astrophysics Data System (ADS)

    Teng, Fei; Cormier, Timothy; Sauer-Budge, Alexis; Roblyer, Darren M.

    2016-03-01

    We present a new continuous-wave (CW) wearable diffuse optical device aimed at investigating the hemodynamic response of locally advanced breast cancer patients during a patient's first neoadjuvant chemotherapy infusion. The system consists of a flexible substrate that supports an array of surface-mount LED and photodiode pairs (i.e. optodes). Probe performance was evaluated using solid tissue-simulating phantoms. Measurements revealed high SNR (65dB), low source-detector crosstalk (-59 dB), high measurement precision (0.17%), and good thermal stability (0.2% Vrms/°C). A cuff occlusion experiment was performed on the forearm of a healthy volunteer to demonstrate the ability to track rapid hemodynamic changes.

  18. Two cases of cisplatin-induced permanent renal failure following neoadjuvant chemotherapy for esophageal cancer

    PubMed Central

    Sasaki, Tomohiko; Motoyama, Satoru; Komatsuda, Atsushi; Shibata, Hiroyuki; Sato, Yusuke; Yoshino, Kei; Wakita, Akiyuki; Saito, Hajime; Anbai, Akira; Jin, Mario; Minamiya, Yoshihiro

    2016-01-01

    Introduction We experienced two esophageal cancer patients who developed severe acute renal failure after neoadjuvant chemotherapy with cisplatin and 5-fluorourasil. Presentation of case After administration of cisplatin, their serum creatinine increased gradually until they required hemodialysis and their renal failure was permanent. In both cases, renal biopsy examination indicated partial recovery of the proximal tubule, but renal function did not recover. After these events, one patient underwent definitive radiotherapy and the other underwent esophagectomy for their esophageal cancers, while continuing dialysis. Both patients are alive without cancer recurrence. Discussion In these two cases of cisplatin-induced renal failure, renal biopsy examination showed only slight disorder of proximal tubules and tendency to recover. Conclusion Although cisplatin-related nephrotoxicity is a well-recognized complication, there have been few reports of renal failure requiring hemodialysis in cancer patients. In this report, we present their clinical courses and the pathological findings of cisplatin-related renal failure. PMID:26851395

  19. Extramedullary haematopoiesis in axillary lymph nodes following neoadjuvant chemotherapy for locally advanced breast cancer.

    PubMed

    Takhar, Arunjit Singh; Ney, Alex; Patel, Meera; Sharma, Anup

    2013-05-22

    We report the case of a 53-year-old lady who presented with a lump in her left breast. Her initial investigations demonstrated a grade III invasive ductal carcinoma of the breast that was tethered to the pectoralis major; imaging and cytology also revealed metastatic nodes in the left axilla. After undergoing neoadjuvant chemotherapy with evidence of clinical and radiological tumour response, a wire-guided wide local excision and axillary node clearance was performed. When a histological analysis of the specimen was performed, there was no evidence of a viable metastatic tumour in the axillary lymph nodes, but there were several areas of extramedullary haematopoiesis. There are only two other reports in the literature of this finding. This could represent a potential source of false-positive diagnosis of axillary metastasis from breast cancer. It would be prudent to consider biopsy prior to clearance if there are megakaryocytes in axillary node cytology.

  20. Neoadjuvant Chemotherapy and Short-term Morbidity in Patients Undergoing Mastectomy With and Without Breast Reconstruction

    PubMed Central

    Abt, Nicholas B.; Flores, José M.; Baltodano, Pablo A.; Sarhane, Karim A.; Abreu, Francis M.; Cooney, Carisa M.; Manahan, Michele A.; Stearns, Vered; Makary, Martin A.; Rosson, Gedge D.

    2015-01-01

    IMPORTANCE Neoadjuvant chemotherapy (NC) is increasingly being used in patients with breast cancer, and evidence-based reports related to its independent effects on morbidity after mastectomy with immediate breast reconstruction are limited. OBJECTIVE To determine the effect of NC on 30-day postoperative morbidity in women undergoing mastectomy with or without immediate breast reconstruction. DESIGN, SETTING, AND PARTICIPANTS All women undergoing mastectomy with or without immediate breast reconstruction from January 1, 2005, through December 31, 2011, at university and private hospitals internationally were analyzed using the American College of Surgeons National Surgical Quality Improvement Program 2005-2011 databases. Patients who received NC were compared with those without a history of NC to estimate the relative odds of 30-day postoperative overall, systemic, and surgical site morbidity using model-wise multivariable logistic regression. EXPOSURE Neoadjuvant chemotherapy. MAIN OUTCOMES AND MEASURES Thirty-day postoperative morbidity (overall, systemic, and surgical site). RESULTS Of 85 851 women, 66 593 (77.6%) underwent mastectomy without breast reconstruction, with 2876 (4.3%) receiving NC; 7893 patients were excluded because of missing exposure data. The immediate breast reconstruction population included 19 258 patients (22.4%), with 820 (4.3%) receiving NC. After univariable analysis, NC was associated with a 20% lower odds of overall morbidity in the group undergoing mastectomy without breast reconstruction (odds ratio [OR], 0.80; 95% CI, 0.71-0.91) but had no significant effect in the immediate breast reconstruction group (OR, 0.98; 95% CI, 0.79-1.23). After adjustment for confounding, NC was independently associated with lower overall morbidity in the group undergoing mastectomy without breast reconstruction (OR, 0.61; 95% CI, 0.51-0.73) and the immediate tissue expander reconstruction subgroup (OR, 0.49; 95% CI, 0.30-0.84). Neoadjuvant chemotherapy

  1. Quantification of tumor changes during neoadjuvant chemotherapy with longitudinal breast DCE-MRI registration

    NASA Astrophysics Data System (ADS)

    Wu, Jia; Ou, Yangming; Weinstein, Susan P.; Conant, Emily F.; Yu, Ning; Hoshmand, Vahid; Keller, Brad; Ashraf, Ahmed B.; Rosen, Mark; DeMichele, Angela; Davatzikos, Christos; Kontos, Despina

    2015-03-01

    Imaging plays a central role in the evaluation of breast tumor response to neoadjuvant chemotherapy. Image-based assessment of tumor change via deformable registration is a powerful, quantitative method potentially to explore novel information of tumor heterogeneity, structure, function, and treatment response. In this study, we continued a previous pilot study to further validate the feasibility of an open source deformable registration algorithm DRAMMS developed within our group as a means to analyze spatio-temporal tumor changes for a set of 14 patients with DCE-MR imaging. Two experienced breast imaging radiologists marked landmarks according to their anatomical meaning on image sets acquired before and during chemotherapy. Yet, chemotherapy remarkably changed the anatomical structure of both tumor and normal breast tissue, leading to significant discrepancies between both raters for landmarks in certain areas. Therefore, we proposed a novel method to grade the manually denoted landmarks into different challenge levels based on the inter-rater agreement, where a high level indicates significant discrepancies and considerable amounts of anatomical structure changes, which would indeed impose giant problem for the following registration algorithm. It is interesting to observe that DRAMMS performed in a similar manner as the human raters: landmark errors increased as inter-rater differences rose. Among all selected six deformable registration algorithms, DRAMMS achieves the highest overall accuracy, which is around 5.5 mm, while the average difference between human raters is 3 mm. Moreover, DRAMMS performed consistently well within both tumor and normal tissue regions. Lastly, we comprehensively tuned the fundamental parameters of DRAMMS to better understand DRAMMS to guide similar works in the future. Overall, we further validated that DRAMMS is a powerful registration tool to accurately quantify tumor changes and potentially predict early tumor response to

  2. 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.

  3. Neoadjuvant chemotherapy for Patients with advanced epithelial ovarian cancer: A Meta-Analysis

    PubMed Central

    Zeng, Long-Jia; Xiang, Chun-Lin; Gong, Yi-Zhen; Kuang, Yan; Lu, Fang-Fang; Yi, Su-Yi; Zhang, Yue; Liao, Meng

    2016-01-01

    The value of neoadjuvant chemotherapy (NAC) has not yet been fully defined. We aimed to systematically evaluate the influence of neoadjuvant chemotherapy (NAC) on survival and complete cytoreduction after debulking surgery in advanced epithelial ovarian cancer (AEOC) patients. We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for the randomized controlled trials (RCTs) comparing NAC and primary debulking surgery (PDS) in AEOC patients. The last search date is February 25, 2016. Cochrane systematic evaluation was used to evaluate bias risk of included studies. RevMan 5.3 software was used for statistical analysis. A total of 4 RCTs involving 1922 patients were included. Compared with PDS, NAC may contribute to the completeness of debulking removal [no residual disease (RR: 2.37; 95%CI: 1.94–2.91; P<0.00001), residual disease ≤1 cm (RR: 1.28; 95%CI: 1.04–1.57; P = 0.02), optimal cytoreduction rate (RR: 1.76; 95%CI: 1.57–1.98; P<0.00001)], but there were no significant differences in both groups with regard to overall survival (HR: 0.94; 95%Cl: 0.81–1.08; P = 0.38) and progression-free survival (HR: 0.89; 95%Cl: 0.77–1.03; P = 0.12). This meta-analysis indicates that the higher rate of optimal debulking made NAC more favorable as a treatment option for AEOC patients with non-inferior survival compared with PDS. PMID:27804983

  4. 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

  5. Neoadjuvant chemotherapy for radioinduced osteosarcoma of the extremity: The Rizzoli experience in 20 cases

    SciTech Connect

    Bacci, Gaetano . E-mail: gaetano.bacci@ior.it; Longhi, Alessandra; Forni, Cristiana R.N.; Fabbri, Nicola; Briccoli, Antonio; Barbieri, Enza; Mercuri, Mario; Balladelli, Alba B.A.; Ferrari, Stefano; Picci, Piero

    2007-02-01

    Purpose: Evaluate treatment and outcome of 20 patients with radioinduced osteosarcoma (RIO). Because of previous primary tumor treatment, RIO protocols were different from others we used for non-RIO. Patients and Methods: Between 1983 and 1998, we treated 20 RIO patients, ages 4-36 years (mean 16 years), with chemotherapy (two cycles before surgery, three postoperatively). The first preoperative cycle consisted of high-dose Methotrexate (HDMTX)/Cisplatinum (CDP)/Adriamycin (ADM) and the second of HDMTX/CDP/Ifosfamide (IFO). The three postoperative treatments were performed with cycles of MTX/CDP; IFO was used as single agent per cycle repeated three times. Results: Two patients received palliative treatment because their osteosarcoma remained unresectable after preoperative chemotherapy. The remaining 18 patients had surgery (7 amputations, 11 resections); histologic response to preoperative chemotherapy was good in 8 patients, poor in 10. At a mean follow-up of 11 years (range, 7-22 years), 9 patients remained continuously disease-free, 10 died from osteosarcoma and 1 died from a third neoplasm (myeloid acute leukemia). These results are not significantly different from those achieved in 754 patients with conventional osteosarcoma treated in the same period with protocols used for conventional treatment. However, this later group had an 18% 3-year event-free survival after treatment of relapse vs. 0% in the RIO group. Conclusion: Treated with neoadjuvant chemotherapy RIO seem to have an outcome that is not significantly different from that of comparable patients with conventional primary high grade osteosarcoma (5-year event-free survival: 40% vs. 60%, p = NS; 5-year overall survival 40% vs. 67%, p < 0.00008.

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. AEG-1 as a predictor of sensitivity to neoadjuvant chemotherapy in advanced epithelial ovarian cancer

    PubMed Central

    Wang, Yao; Jin, Xin; Song, Hongtao; Meng, Fanling

    2016-01-01

    Objectives Astrocyte elevated gene-1 (AEG-1) plays a critical role in tumor progression and chemoresistance. The aim of the present study was to investigate the protein expression of AEG-1 in patients with epithelial ovarian cancer (EOC) who underwent debulking surgery after neoadjuvant chemotherapy (NAC). Materials and methods The protein expression of AEG-1 was analyzed using immunohistochemistry in 162 patients with EOC. The relationship between AEG-1 expression and chemotherapy resistance was assessed using univariate and multivariate logistic regression analyses with covariate adjustments. Results High AEG-1 expression was significantly associated with the International Federation of Gynecology and Obstetrics stage, age, serum cancer antigen-125 concentration, histological grade, the presence of residual tumor after the interval debulking surgery, and lymph node metastasis. Furthermore, AEG-1 expression was significantly higher in NAC-resistant disease than in NAC-sensitive disease (P<0.05). Multivariate analyses indicated that elevated AEG-1 expression predicted poor survival. Conclusion Our findings indicate that AEG-1 may be a potential new biomarker for predicting chemoresistance and poor prognoses in patients with EOC. PMID:27143933

  11. Wearable near-infrared optical probe for continuous monitoring during breast cancer neoadjuvant chemotherapy infusions

    NASA Astrophysics Data System (ADS)

    Teng, Fei; Cormier, Timothy; Sauer-Budge, Alexis; Chaudhury, Rachita; Pera, Vivian; Istfan, Raeef; Chargin, David; Brookfield, Samuel; Ko, Naomi Yu; Roblyer, Darren M.

    2017-01-01

    We present a new continuous-wave wearable diffuse optical probe aimed at investigating the hemodynamic response of locally advanced breast cancer patients during neoadjuvant chemotherapy infusions. The system consists of a flexible printed circuit board that supports an array of six dual wavelength surface-mount LED and photodiode pairs. The probe is encased in a soft silicone housing that conforms to natural breast shape. Probe performance was evaluated using tissue-simulating phantoms and in vivo normal volunteer measurements. High SNR (71 dB), low source-detector crosstalk (-60 dB), high measurement precision (0.17%), and good thermal stability (0.22% Vrms/°C) were achieved in phantom studies. A cuff occlusion experiment was performed on the forearm of a healthy volunteer to demonstrate the ability to track rapid hemodynamic changes. Proof-of-principle normal volunteer measurements were taken to demonstrate the ability to collect continuous in vivo breast measurements. This wearable probe is a first of its kind tool to explore prognostic hemodynamic changes during chemotherapy in breast cancer patients.

  12. 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.

  13. 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

  14. The prognostic impact of soluble and vesicular HLA-G and its relationship to circulating tumor cells in neoadjuvant treated breast cancer patients.

    PubMed

    König, Lisa; Kasimir-Bauer, Sabine; Hoffmann, Oliver; Bittner, Ann-Kathrin; Wagner, Bettina; Manvailer, Luis Felipe Santos; Schramm, Sabine; Bankfalvi, Agnes; Giebel, Bernd; Kimmig, Rainer; Horn, Peter A; Rebmann, Vera

    2016-09-01

    The non-classical human leukocyte antigen G (HLA-G) molecule and its soluble forms exert multiple immune suppressive regulatory functions in malignancy and in stem cells contributing to immune escape mechanisms. HLA-G can be secreted as free soluble HLA-G molecules or via extracellular vesicles (EVs). Here we evaluated these soluble HLA-G forms as prognostic marker for prediction of the clinical outcome of neoadjuvant chemotherapy (NACT) treated breast cancer (BC) patients. Plasma samples of BC patients procured before (n=142) and after (n=154) NACT were quantified for total soluble HLA-G (sHLA-Gtot) and HLA-G levels in ExoQuick™ derived EV fractions (sHLA-GEV) by ELISA. The corresponding increments were specified as free sHLA-G (sHLA-Gfree). Total and free sHLA-G were significantly increased in NACT treated BC patients compared to healthy controls (n=16). High sHLA-Gfree levels were exclusively associated to estrogen receptor expression before NACT. Importantly, high sHLA-GEV levels before NACT were related to disease progression and the detection of stem cell-like circulating tumor cells, but high sHLA-Gfree levels indicated an improved clinical outcome. Thus, this study demonstrates for the first time that the different sHLA-G subcomponents represent dissimilar qualitative prognostic impacts on the clinical outcome of NACT treated BC patients, whereas the total sHLA-G levels without separating into subcomponents are not related to clinical outcome.

  15. 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

  16. 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.

  17. Chromosome 17 Centromere Duplication and Responsiveness to Anthracycline-Based Neoadjuvant Chemotherapy in Breast Cancer12

    PubMed Central

    Tibau, Ariadna; López-Vilaró, Laura; Pérez-Olabarria, Maitane; Vázquez, Tania; Pons, Cristina; Gich, Ignasi; Alonso, Carmen; Ojeda, Belén; Ramón y Cajal, Teresa; Lerma, Enrique; Barnadas, Agustí; Escuin, Daniel

    2014-01-01

    Human epidermal growth factor receptor 2 (HER2) and topoisomerase II alpha (TOP2A) genes have been proposed as predictive biomarkers of sensitivity to anthracycline chemotherapy. Recently, chromosome 17 centromere enumeration probe (CEP17) duplication has also been associated with increased responsiveness to anthracyclines. However, reports are conflicting and none of these tumor markers can yet be considered a clinically reliable predictor of response to anthracyclines. We studied the association of TOP2A gene alterations, HER2 gene amplification, and CEP17 duplication with response to anthracycline-based neoadjuvant chemotherapy in 140 patients with operable or locally advanced breast cancer. HER2 was tested by fluorescence in situ hybridization and TOP2A and CEP17 by chromogenic in situ hybridization. Thirteen patients (9.3%) achieved pathologic complete response (pCR). HER2 amplification was present in 24 (17.5%) of the tumors. TOP2A amplification occurred in seven tumors (5.1%). CEP17 duplication was detected in 13 patients (9.5%). CEP17 duplication correlated with a higher rate of pCR [odds ratio (OR) 6.55, 95% confidence interval (95% CI) 1.25-34.29, P = .026], and analysis of TOP2A amplification showed a trend bordering on statistical significance (OR 6.97, 95% CI 0.96-50.12, P = .054). TOP2A amplification and CEP17 duplication combined were strongly associated with pCR (OR 6.71, 95% CI 1.66-27.01, P = .007). HER2 amplification did not correlate with pCR. Our results suggest that CEP17 duplication predicts pCR to primary anthracycline-based chemotherapy. CEP17 duplication, TOP2A amplifications, and HER2 amplifications were not associated with prognosis. PMID:25379022

  18. Clonal expansion of antitumor T cells in breast cancer correlates with response to neoadjuvant chemotherapy

    PubMed Central

    Park, Jae-Hyun; Jang, Miran; Tarhan, Yunus Emre; Katagiri, Toyomasa; Sasa, Mitsunori; Miyoshi, Yasuo; Kalari, Krishna R.; Suman, Vera J.; Weinshilboum, Richard; Wang, Liewei; Boughey, Judy C.; Goetz, Matthew P.; Nakamura, Yusuke

    2016-01-01

    The immune microenvironment of tumor plays a critical role in therapeutic responses to chemotherapy. Cancer tissues are composed of a complex network between anti-tumor and pro-tumor immune cells and molecules; therefore a comprehensive analysis of the tumor immune condition is imperative for better understanding of the roles of the immune microenvironment in anticancer treatment response. In this study, we performed T cell receptor (TCR) repertoire analysis of tumor infiltrating T cells (TILs) in cancer tissues of pre- and post-neoadjuvant chemotherapy (NAC) from 19 breast cancer patients; five cases showed CR (complete response), ten showed PR (partial response), and four showed SD/PD (stable disease/progressive disease) to the treatment. From the TCR sequencing results, we calculated the diversity index of the TCRβ chain and found that clonal expansion of TILs could be detected in patients who showed CR or PR to NAC. Noteworthy, the diversity of TCR was further reduced in the post-NAC tumors of CR patients. Our quantitative RT-PCR also showed that expression ratio of CD8/Foxp3 was significantly elevated in the post-NAC tumors of CR cases (p=0.0032), indicating that antitumor T cells were activated and enriched in these tumors. Collectively, our findings suggest that the clonal expansion of antitumor T cells may be a critical factor associated with response to chemotherapy and that their TCR sequences might be applicable for the development of TCR-engineered T cells treatment for individual breast cancer patients when their tumors relapse. PMID:27278091

  19. Chromosome 17 centromere duplication and responsiveness to anthracycline-based neoadjuvant chemotherapy in breast cancer.

    PubMed

    Tibau, Ariadna; López-Vilaró, Laura; Pérez-Olabarria, Maitane; Vázquez, Tania; Pons, Cristina; Gich, Ignasi; Alonso, Carmen; Ojeda, Belén; Ramón y Cajal, Teresa; Lerma, Enrique; Barnadas, Agustí; Escuin, Daniel

    2014-10-01

    Human epidermal growth factor receptor 2 (HER2) and topoisomerase II alpha (TOP2A) genes have been proposed as predictive biomarkers of sensitivity to anthracycline chemotherapy. Recently, chromosome 17 centromere enumeration probe (CEP17) duplication has also been associated with increased responsiveness to anthracyclines. However, reports are conflicting and none of these tumor markers can yet be considered a clinically reliable predictor of response to anthracyclines. We studied the association of TOP2A gene alterations, HER2 gene amplification, and CEP17 duplication with response to anthracycline-based neoadjuvant chemotherapy in 140 patients with operable or locally advanced breast cancer. HER2 was tested by fluorescence in situ hybridization and TOP2A and CEP17 by chromogenic in situ hybridization. Thirteen patients (9.3%) achieved pathologic complete response (pCR). HER2 amplification was present in 24 (17.5%) of the tumors. TOP2A amplification occurred in seven tumors (5.1%). CEP17 duplication was detected in 13 patients (9.5%). CEP17 duplication correlated with a higher rate of pCR [odds ratio (OR) 6.55, 95% confidence interval (95% CI) 1.25-34.29, P = .026], and analysis of TOP2A amplification showed a trend bordering on statistical significance (OR 6.97, 95% CI 0.96-50.12, P = .054). TOP2A amplification and CEP17 duplication combined were strongly associated with pCR (OR 6.71, 95% CI 1.66-27.01, P = .007). HER2 amplification did not correlate with pCR. Our results suggest that CEP17 duplication predicts pCR to primary anthracycline-based chemotherapy. CEP17 duplication, TOP2A amplifications, and HER2 amplifications were not associated with prognosis.

  20. Effects of Neoadjuvant Intraperitoneal/Systemic Chemotherapy (Bidirectional Chemotherapy) for the Treatment of Patients with Peritoneal Metastasis from Gastric Cancer

    PubMed Central

    Yonemura, Yutaka; Elnemr, Ayman; Endou, Yoshio; Ishibashi, Haruaki; Mizumoto, Akiyoshi; Miura, Masahiro; Li, Yan

    2012-01-01

    Novel multidisciplinary treatment combined with neoadjuvant intraperitoneal-systemic chemotherapy protocol (NIPS) and peritonectomy was developed. Ninety-six patients were enrolled. Peritoneal wash cytology was performed before and after NIPS through a port system. Patients were treated with 60 mg/m2 of oral S-1 for 21 days, followed by a 1-week rest. On days 1, 8, and 15, 30 mg/m2 of Taxotere and 30 mg/m2 of cisplatin with 500 mL of saline were introduced through the port. NIPS is done 2 cycles before surgery. Three weeks after NIPS, 82 patients were eligible to intend cytoreductive surgery (CRS) by gastrectomy + D2 dissection + periotnectomy to achieve complete cytoreduction. Sixty-eight patients showed positice cytology before NIPS, and the positive cytology results became negative in 47 (69%) patients after NIPS. Complete pathologic response on PC after NIPS was experienced in 30 (36.8%) patients. Stage migration was experienced in 12 patients (14.6%). Complete cytoreduction was achieved in 58 patients (70.7%). By the multivariate analysis, complete cytoreduction and pathologic response became a significantly good survival. However the high morbidity and mortality, stringent patient selection is important. The best indications of the therapy are patients with good pathologic response and PCI ≤ 6, which are supposed to be removed completely by peritonectomy. PMID:22900159

  1. Body Composition as a Prognostic Factor of Neoadjuvant Chemotherapy Toxicity and Outcome in Patients with Locally Advanced Gastric Cancer

    PubMed Central

    Velho, Sónia; Agostinho, Lisa; Branco, Francisco; Santos, Marta; Santos, Maria Pia Costa; Oliveira, Maria Helena; Strecht, João; Maio, Rui; Cravo, Marília; Baracos, Vickie E.

    2017-01-01

    Purpose Neoadjuvant chemotherapy has been shown to improve survival in locally advanced gastric cancer, but it is associated with significant toxicity. Sarcopenia and sarcopenic obesity have been studied in several types of cancers and have been reported to be associated with higher chemotherapy toxicity and morbi-mortality. The aim of this study was to assess the prevalence of sarcopenia/sarcopenic obesity in patients with gastric cancer, as well as its association with chemotherapy toxicity and long-term outcomes. Materials and Methods A retrospective analysis was performed using an academic cancer center patient cohort diagnosed with locally advanced gastric cancer between January 2012 and December 2014 and treated with neoadjuvant chemotherapy. We analyzed body composition (skeletal muscle and visceral fat index) in axial computed tomography images. Results A total of 48 patients met the inclusion criteria. The mean age was 68±10 years, and 33 patients (69%) were men. Dose-limiting toxicity was observed in 22 patients (46%), and treatment was terminated early owing to toxicity in 17 patients (35%). Median follow-up was 17 months. Sarcopenia and sarcopenic obesity were found at diagnosis in 23% and 10% of patients, respectively. We observed an association between termination of chemotherapy and both sarcopenia (P=0.069) and sarcopenic obesity (P=0.004). On multivariate analysis, the odds of treatment termination were higher in patients with sarcopenia (odds ratio=4.23; P=0.050). Patients with sarcopenic obesity showed lower overall survival (median survival of 6 months [95% confidence interval {CI}=3.9–8.5] vs. 25 months [95% CI=20.2–38.2]; log-rank test P=0.000). Conclusions Sarcopenia and sarcopenic obesity were associated with early termination of neoadjuvant chemotherapy in patients with gastric cancer; additionally, sarcopenic obesity was associated with poor survival. PMID:28337365

  2. 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.

  3. Multicenter Assessment of Neoadjuvant Chemotherapy for Muscle-invasive Bladder Cancer

    PubMed Central

    Zargar, Homayoun; Espiritu, Patrick N.; Fairey, Adrian S.; Mertens, Laura S.; Dinney, Colin P.; Mir, Maria C.; Krabbe, Laura-Maria; Cookson, Michael S.; Jacobsen, Niels-Erik; Gandhi, Nilay; Griffin, Joshua; Montgomery, Jeffrey S.; Vasdev, Nikhil; Yu, Evan Y.; Youssef, David; Xylinas, Evanguelos; Campain, Nicholas J.; Kassouf, Wassim; Dall’Era, Marc A.; Seah, Jo-An; Ercole, Cesar E.; Horenblas, Simon; Sridhar, Srikala S.; McGrath, Jonathan S.; Aning, Jonathan; Shariat, Shahrokh F.; Wright, Jonathan L.; Thorpe, Andrew C.; Morgan, Todd M.; Holzbeierlein, Jeff M.; Bivalacqua, Trinity J.; North, Scott; Barocas, Daniel A.; Lotan, Yair; Garcia, Jorge A.; Stephenson, Andrew J.; Shah, Jay B.; van Rhijn, Bas W.; Daneshmand, Siamak; Spiess, Philippe E.; Black, Peter C.

    2016-01-01

    Background The efficacy of neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (BCa) was established primarily with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), with complete response rates (pT0) as high as 38%. However, because of the comparable efficacy with better tolerability of gemcitabine and cisplatin (GC) in patients with metastatic disease, GC has become the most commonly used regimen in the neoadjuvant setting. Objective We aimed to assess real-world pathologic response rates to NAC with different regimens in a large, multicenter cohort. Design, setting, and participants Data were collected retrospectively at 19 centers on patients with clinical cT2–4aN0M0 urothelial carcinoma of the bladder who received at least three cycles of NAC, followed by radical cystectomy (RC), between 2000 and 2013. Intervention NAC and RC Outcome measurements and statistical analysis The primary outcome was pathologic stage at cystectomy. Univariable and multivariable analyses were used to determine factors predictive of pT0N0 and ≤pT1N0 stages. Results and limitations Data were collected on 935 patients who met inclusion criteria. GC was used in the majority of the patients (n = 602; 64.4%), followed by MVAC (n = 183; 19.6%) and other regimens (n = 144; 15.4%). The rates of pT0N0 and ≤pT1N0 pathologic response were 22.7% and 40.8%, respectively. The rate of pT0N0 disease for patients receiving GC was 23.9%, compared with 24.5% for MVAC (p = 0.2). There was no difference between MVAC and GC in pT0N0 on multivariable analysis (odds ratio: 0.89 [95% confidence interval, 0.61–1.34]; p = 0.6). Conclusions Response rates to NAC were lower than those reported in prospective randomized trials, and we did not discern a difference between MVAC and GC. Without any evidence from randomized prospective trials, the best NAC regimen for invasive BCa remains to be determined. Patient summary There was no apparent difference in the response rates to the

  4. Early decrements in bone density after completion of neoadjuvant chemotherapy in pediatric bone sarcoma patients

    PubMed Central

    2010-01-01

    Background Bone mineral density (BMD) accrual during childhood and adolescence is important for attaining peak bone mass. BMD decrements have been reported in survivors of childhood bone sarcomas. However, little is known about the onset and development of bone loss during cancer treatment. The objective of this cross-sectional study was to evaluate BMD in newly diagnosed Ewing's and osteosarcoma patients by means of dual-energy x-ray absorptiometry (DXA) after completion of neoadjuvant chemotherapy. Methods DXA measurements of the lumbar spine (L2-4), both femora and calcanei were performed perioperatively in 46 children and adolescents (mean age: 14.3 years, range: 8.6-21.5 years). Mean Z-scores, areal BMD (g/cm2), calculated volumetric BMD (g/cm3) and bone mineral content (BMC, g) were determined. Results Lumbar spine mean Z-score was -0.14 (95% CI: -0.46 to 0.18), areal BMD was 1.016 g/cm2 (95% CI: 0.950 to 1.082) and volumetric BMD was 0.330 g/cm3 (95% CI: 0.314 to 0.347) which is comparable to healthy peers. For patients with a lower extremity tumor (n = 36), the difference between the affected and non-affected femoral neck was 12.1% (95% CI: -16.3 to -7.9) in areal BMD. The reduction of BMD was more pronounced in the calcaneus with a difference between the affected and contralateral side of 21.7% (95% CI: -29.3 to -14.0) for areal BMD. Furthermore, significant correlations for femoral and calcaneal DXA measurements were found with Spearman-rho coefficients ranging from ρ = 0.55 to ρ = 0.80. Conclusions The tumor disease located in the lower extremity in combination with offloading recommendations induced diminished BMD values, indicating local osteopenia conditions. However, the results revealed no significant decrements of lumbar spine BMD in pediatric sarcoma patients after completion of neoadjuvant chemotherapy. Nevertheless, it has to be taken into account that bone tumor patients may experience BMD decrements or secondary osteoporosis in later life

  5. [A CASE OF UROTHELIAL CARCINOMA OF THE URINARY BLADDER WITH SQUAMOUS DIFFERENTIATION RESPONDING TO PACLITAXEL AND CARBOPLATIN NEOADJUVANT CHEMOTHERAPY].

    PubMed

    Banno, Eri; Nishino, Aki; Nagai, Yasuharu; Yasuda, Muneo; Tahara, Hideo; Kino, Shigeo; Kanno, Norihumi

    2015-07-01

    A 42-year-old man was referred to our hospital for macrohematuria. Computer tomography and magnetic resonance imaging revealed right hydronephrosis and a retroperitoneal mass, located next to right side of the bladder. Cystoscopy showed a protruded lesion covered with normal mucosa at the right lateral wall. The patient underwent transurethral resection of the bladder tumor and biopsies of the bladder wall. Histological examination showed squamous cell carcinoma. Neoadjuvant chemotherapy using paclitaxel and carboplatin (TC) was performed. A total cystectomy, right nephroureterectomy and construction of the ileal conduit were performed after one course of systemic chemotherapy. Histological examination showed urothelial carcinoma with squamous cell differentiation. Unexpectedly, a small amount of CIS was detected only in the vicinity of the TUR scar. The patient received 2 cycles of TC chemotherapy as adjuvant chemotherapy. Unfortunately, 11 months later, local recurrence and liver metastasis were detected. He died 17 months after the surgery.

  6. CKD-EPI and cockcroft-gault equations identify similar candidates for neoadjuvant chemotherapy in muscle-invasive bladder cancer.

    PubMed

    Pal, Sumanta K; Ruel, Nora; Villegas, Sergio; Chang, Mark; DeWalt, Kara; Wilson, Timothy G; Vogelzang, Nicholas J; Yuh, Bertram E

    2014-01-01

    Clinical guidelines suggest neoadjuvant cisplatin-based chemotherapy prior to cystectomy in the setting of muscle-invasive bladder cancer (MIBC). A creatinine clearance (CrCl) >60 mL/min is frequently used to characterize cisplatin-eligible patients, and use of the CKD-EPI equation to estimate CrCl has been advocated. From a prospectively maintained institutional database, patients with MIBC who received cystectomy were identified and clinicopathologic information was ascertained. CrCl prior to surgery was computed using three equations: (1) Cockcroft-Gault (CG), (2) CKD-EPI, and (3) MDRD. The primary objective was to determine if the CG and CKD-EPI equations identified a different proportion of patients who were cisplatin-eligible, based on an estimated CrCl of >60 mL/min. Cisplatin-eligibility was also assessed in subsets based on age, CCI score and race. Actuarial rates of neoadjuvant cisplatin-based chemotherapy use were also reported. Of 126 patients, 70% and 71% of patients were found to be cisplatin-eligible by the CKD-EPI and CG equations, respectively (P = 0.9). The MDRD did not result in significantly different characterization of cisplatin-eligibility as compared to the CKD-EPI and CG equations. In the subset of patients age >80, the CKD-EPI equation identified a much smaller proportion of cisplatin-eligible patients (25%) as compared to the CG equation (50%) or the MDRD equation (63%). Only 34 patients (27%) received neoadjuvant cisplatin-based chemotherapy. Of the 92 patients who did not receive neoadjuvant chemotherapy, 64% had a CrCl >60 mL/min by CG. In contrast to previous reports, the CKD-EPI equation does not appear to characterize a broader span of patients as cisplatin-eligible. Older patients (age >80) may less frequently be characterized as cisplatin-eligible by CKD-EPI. The discordance between actual rates of neoadjuvant chemotherapy use and rates of cisplatin eligibility suggest that other factors (e.g., patient and physician preference

  7. Neoadjuvant chemotherapy adaptation and serial MRI response monitoring in ER-positive HER2-negative breast cancer

    PubMed Central

    Rigter, L S; Loo, C E; Linn, S C; Sonke, G S; van Werkhoven, E; Lips, E H; Warnars, H A; Doll, P K; Bruining, A; Mandjes, I A; Vrancken Peeters, M J; Wesseling, J; Gilhuijs, K G; Rodenhuis, S

    2013-01-01

    Background: Changing the neoadjuvant chemotherapy regimen in insufficiently responding breast cancer is not a standard policy. We analysed a series of patients with ‘luminal'-type breast cancer in whom the second half of neoadjuvant chemotherapy was selected based on the response to the first half. Methods: Patients with oestrogen receptor-positive (ER+) human epidermal growth factor receptor 2-negative (HER2−) breast cancer received three courses of neoadjuvant dose-dense doxorubicin and cyclophosphamide (ddAC). Three further courses of ddAC were administered in case of a ‘favourable response' on the interim magnetic resonance imaging (MRI) and a switch to docetaxel and capecitabine (DC) was made in case of an ‘unfavourable response', using previously published response criteria. The efficacy of this approach was evaluated by tumour size reductions on serial contrast-enhanced MRI, pathologic response and relapse-free survival. Results: Two hundred and forty-six patients received three courses of ddAC. One hundred and sixty-four patients (67%) had a favourable response at the interim MRI, with a mean tumour size reduction of 31% after the first three courses and 34% after the second three courses. Patients with unfavourable responsive tumours had a mean tumour size reduction of 12% after three courses and received three courses of DC rather than ddAC. This led to a mean shrinkage of 27%. Conclusion: The tumour size reduction of initially less responsive tumours after treatment adaptation adds further evidence that a response-adapted strategy may enhance the efficacy of neoadjuvant chemotherapy. PMID:24149178

  8. 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

  9. Neoadjuvant Chemotherapy of Ovarian Cancer Results in Three Patterns of Tumor-Infiltrating Lymphocyte Response with Distinct Implications for Immunotherapy.

    PubMed

    Lo, Charlotte S; Sanii, Sanaz; Kroeger, David R; Milne, Katy; Talhouk, Aline; Chiu, Derek S; Rahimi, Kurosh; Shaw, Patricia A; Clarke, Blaise A; Nelson, Brad H

    2017-02-15

    Purpose: Some forms of chemotherapy can enhance antitumor immunity through immunogenic cell death, resulting in increased T-cell activation and tumor infiltration. Such effects could potentially sensitize tumors to immunotherapies, including checkpoint blockade. We investigated whether platinum- and taxane-based chemotherapy for ovarian cancer induces immunologic changes consistent with this possibility.Experimental Design: Matched pre- and post-neoadjuvant chemotherapy tumor samples from 26 high-grade serous carcinoma (HGSC) patients were analyzed by immunohistochemistry (IHC) for a large panel of immune cells and associated factors. The prognostic significance of post-chemotherapy TIL patterns was assessed in an expanded cohort (n = 90).Results: Neoadjuvant chemotherapy was associated with increased densities of CD3(+), CD8(+), CD8(+) TIA-1(+), PD-1(+) and CD20(+) TIL. Other immune subsets and factors were unchanged, including CD79a(+) CD138(+) plasma cells, CD68(+) macrophages, and MHC class I on tumor cells. Immunosuppressive cell types were also unchanged, including FoxP3(+) PD-1(+) cells (putative regulatory T cells), IDO-1(+) cells, and PD-L1(+) cells (both macrophages and tumor cells). Hierarchical clustering revealed three response patterns: (i) TIL(high) tumors showed increases in multiple immune markers after chemotherapy; (ii) TIL(low) tumors underwent similar increases, achieving patterns indistinguishable from the first group; and (iii) TIL(negative) cases generally remained negative. Despite the dramatic increases seen in the first two patterns, post-chemotherapy TIL showed limited prognostic significance.Conclusions: Chemotherapy augments pre-existing TIL responses but fails to relieve major immune-suppressive mechanisms or confer significant prognostic benefit. Our findings provide rationale for multipronged approaches to immunotherapy tailored to the baseline features of the tumor microenvironment. Clin Cancer Res; 23(4); 925-34. ©2016 AACR.

  10. Breast Cancer Spatial Heterogeneity in Near-Infrared Spectra and the Prediction of Neoadjuvant Chemotherapy Response

    NASA Astrophysics Data System (ADS)

    Santoro, Ylenia

    Breast cancer accounts for more than 20% of all female cancers. Many of these patients receive neoadjuvant chemotherapy (NAC) to reduce the size of the tumor before surgery and to anticipate the efficacy of treatments for after the procedure. Breast cancer is a heterogeneous disease that comes in several clinical and histological forms. The prediction of the efficacy of chemotherapy would potentially select good candidates who would respond while excluding poor candidates who would not benefit from treatment. In this work we investigate the possibility of noninvasively predicting chemotherapy response prior to treatment based on optical biomarkers obtained from tumor spatial heterogeneities of spectral features measured using Diffuse Optical Spectroscopy. We describe an algorithm to calculate an index that characterizes spatial differences in broadband near-infrared absorption spectra of tumor-containing breast tissue. Patient-specific tumor spatial heterogeneities are visualized through a Heterogeneity Spectrum (HS). HS is a biomarker that can be attributed to different molecular distributions within the tumor. To classify lesion heterogeneities, we built a Heterogeneity Index (HI) from the HS by weighing specific absorption bands. It has been shown that NAC response is potentially related to tumor heterogeneity. Therefore, we correlate the HI obtained prior to treatment with the final response to NAC. In this thesis we also present a novel digital parallel frequency domain system for tissue imaging. The systems employs a supercontinuum laser with high brightness, and a photomultiplier with a large detection area, both allowing a deep penetration with extremely low power on the sample. The digital parallel acquisition is performed through the use of the Flimbox and it decreases the time required for standard serial systems that need to scan through all modulation frequencies. The all-digital acquisition removes analog noise, avoids the analog mixer and it does not

  11. Is Radiotherapy an Option for Early Breast Cancers With Complete Clinical Response After Neoadjuvant Chemotherapy?

    SciTech Connect

    Daveau, Caroline; Savignoni, Alexia; Abrous-Anane, Soumya; Pierga, Jean-Yves; Reyal, Fabien; Gautier, Chantal; Kirova, Youlia M.; Dendale, Remi; Campana, Francois; Fourquet, Alain; Bollet, Marc A.

    2011-04-01

    Purpose: To determine whether the exclusive use of radiotherapy (ERT) could be a treatment option after complete clinical response (cCR) to neoadjuvant chemotherapy (NCT) for early breast cancer (EBC). Methods and Materials: Between 1985 and 1999, 1,477 patients received NCT for EBC considered too large for primary conservative surgery. Of 165 patients with cCR, 65 patients were treated with breast surgery (with radiotherapy) and 100 patients were treated with ERT. Results: The two groups were comparable in terms of baseline characteristics, except for larger initial tumor sizes in the ERT group. There were no significant differences in overall, disease-free and metastasis-free survival rates. Five-year and 10-year overall survival rates were 91% and 77% in the no-surgery group and 82% and 79% in the surgery group, respectively (p = 0.9). However, a nonsignificant trend toward higher locoregional recurrence rates (LRR) was observed in the no-surgery group (31% vs. 17% at 10 years; p = 0.06). In patients with complete responses on mammography and/or ultrasound, LRR were not significantly different (p = 0.45, 10-year LRR: 21% in surgery vs. 26% in ERT). No significant differences were observed in terms of the rate of cutaneous, cardiac, or pulmonary toxicities. Conclusions: Surgery is a key component of locoregional treatment for breast cancers that achieved cCR to NCT.

  12. [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.

  13. 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; Ranger, Bryan; West, Erik; Szczepanski, Amy; Rama, Olsi; Bey-Knight, Lisa; Myc, Lukasz

    2010-03-01

    The purpose of this study was to correlate changes in biomechanical properties of breast cancer lesions in response to neoadjuvant chemotherapy. Nine patients were examined repeatedly throughout their treatment, using an experimental prototype based on the principles of ultrasound tomography. The study was HIPAA compliant, approved by the Institutional Review Board, and performed after obtaining the requisite informed consent. 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 tumor properties could be measured in all cases. Furthermore, changes in sound speed were found to vary strongly from patient to patient. A comparison of the sound speed response curves with pathological findings suggests that complete responders exhibit distinctly different responses as measured by sound speed. These preliminary results were used to define a cut-point for predicting response. Subsequently, a prospective prediction of the treatment response of a new patient was made correctly. We hypothesize that changes in the biomechanical properties of breast cancers, as measured by sound speed, can predict response. Future studies will focus on testing this hypothesis and defining and quantifying markers of response.

  14. Effect of Imaging Parameter Thresholds on MRI Prediction of Neoadjuvant Chemotherapy Response in Breast Cancer Subtypes

    PubMed Central

    Jones, Ella F.; Newitt, David C.; Kornak, John; Wilmes, Lisa J.; Esserman, Laura J.; Hylton, Nola M.

    2016-01-01

    The purpose of this study is to evaluate the predictive performance of magnetic resonance imaging (MRI) markers in breast cancer patients by subtype. Sixty-four patients with locally advanced breast cancer undergoing neoadjuvant chemotherapy were enrolled in this study. Each patient received a dynamic contrast-enhanced (DCE-MRI) at baseline, after 1 cycle of chemotherapy and before surgery. Functional tumor volume (FTV), the imaging marker measured by DCE-MRI, was computed at various thresholds of percent enhancement (PEt) and signal-enhancement ratio (SERt). Final FTV before surgery and percent changes of FTVs at the early and final treatment time points were used to predict patients’ recurrence-free survival. The full cohort and each subtype defined by the status of hormone receptor and human epidermal growth factor receptor 2 (HR+/HER2-, HER2+, triple negative) were analyzed. Predictions were evaluated using the Cox proportional hazard model when PEt changed from 30% to 200% in steps of 10% and SERt changed from 0 to 2 in steps of 0.2. Predictions with high hazard ratios and low p-values were considered as strong. Different profiles of FTV as predictors for recurrence-free survival were observed in each breast cancer subtype and strong associations with survival were observed at different PEt/SERt combinations that resulted in different FTVs. Findings from this retrospective study suggest that the predictive performance of imaging markers based on FTV may be improved with enhancement thresholds being optimized separately for clinically-relevant subtypes defined by HR and HER2 receptor expression. PMID:26886725

  15. Conservative treatment of retinoblastoma: a prospective phase II randomized trial of neoadjuvant chemotherapy followed by local treatments and chemothermotherapy

    PubMed Central

    Lumbroso-Le Rouic, L; Aerts, I; Hajage, D; Lévy-Gabriel, C; Savignoni, A; Algret, N; Cassoux, N; Bertozzi, A-I; Esteve, M; Doz, F; Desjardins, L

    2016-01-01

    Purpose Intraocular retinoblastoma treatments often combine chemotherapy and focal treatments. A first prospective protocol of conservative treatments in our institution showed the efficacy of the use of two courses of chemoreduction with etoposide and carboplatin, followed by chemothermotherapy using carboplatin as a single agent and diode laser. In order to decrease the possible long-term toxicity of chemotherapy due to etoposide, a randomized neoadjuvant phase II protocol was conducted using vincristine–carboplatin vs etoposide–carboplatin. Patients and methods The study was proposed when initial tumor characteristics did not allow front-line local treatments. Patients included in this phase II noncomparative randomized study of neoadjuvant chemotherapy received vincristin–carboplatin (new arm) vs etoposide–carboplatin (our reference arm). They were subsequently treated by local treatments and chemothermotherapy. Primary end point was the need for secondary enucleation or external beam radiotherapy (EBRT) not exceeding 40% at 2 years. Results A total of 65 eyes in 55 children were included in the study (May 2004 to August 2009). Of these, 32 eyes (27 children) were treated in the arm etoposide–carboplatin and 33 eyes (28 children) in the arm vincristin–carboplatin. At 2 years after treatment, 23/33 (69.7%) eyes were treated and salvaged without EBRT or enucleation in the arm vincristin–carboplatin and 26/32 (81.2%) in the arm etoposide–carboplatin. Conclusion Even if the two treatment arms could be considered as sufficiently active according to the study decision rules, neoadjuvant chemotherapy by two cycles of vincristine–carboplatin followed by chemothermotherapy appear to offer less optimal local control than the etoposide–carboplatin combination. PMID:26427984

  16. Multispectral and phase-contrast diffuse optical tomography of breast cancer during neoadjuvant chemotherapy: a case study

    NASA Astrophysics Data System (ADS)

    Liang, Xiaoping; Zhang, Qizhi; Staal, Stephen; Grobmyer, Stephen; Jiang, Huabei

    2009-02-01

    Multispectral and phase-contrast diffuse optical tomography are used to track treatment progress in a patient with locally advanced invasive carcinoma of the breast cancer during neoadjuvant chemotherapy. Two types of chemotherapy treatment including four cycles of Adriamycin/Cytoxin (AC cycles) and twelve cycles of Taxol/Herceptin (TH cycles) were applied to patient. A total of eight optical exams were performed before and within the chemotherapy. Images of tissue refractive index, and absorption and scattering coefficients, as well as oxy-hemoglobin and deoxy-hemoglobin concentrations along with scattering particle volume fraction and mean diameter of cellular components were all obtained. The tumor was identified through absorption and scattering images. Tumor shrinkage was observed during the course of chemotherapy from all the optical images. Our results show that oxy-hemoglobin, deoxy-hemoglobin and total hemoglobin in tumor decreased after chemotherapy compared to that of before chemotherapy. Significant changes in tumor refractive index along with tumor cellular morphology during the entire chemotherapy are also observed.

  17. [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.

  18. Predicting Response to Neoadjuvant Chemotherapy with PET Imaging Using Convolutional Neural Networks

    PubMed Central

    Ypsilantis, Petros-Pavlos; Siddique, Musib; Sohn, Hyon-Mok; Davies, Andrew; Cook, Gary; Goh, Vicky; Montana, Giovanni

    2015-01-01

    Imaging of cancer with 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) has become a standard component of diagnosis and staging in oncology, and is becoming more important as a quantitative monitor of individual response to therapy. In this article we investigate the challenging problem of predicting a patient’s response to neoadjuvant chemotherapy from a single 18F-FDG PET scan taken prior to treatment. We take a “radiomics” approach whereby a large amount of quantitative features is automatically extracted from pretherapy PET images in order to build a comprehensive quantification of the tumor phenotype. While the dominant methodology relies on hand-crafted texture features, we explore the potential of automatically learning low- to high-level features directly from PET scans. We report on a study that compares the performance of two competing radiomics strategies: an approach based on state-of-the-art statistical classifiers using over 100 quantitative imaging descriptors, including texture features as well as standardized uptake values, and a convolutional neural network, 3S-CNN, trained directly from PET scans by taking sets of adjacent intra-tumor slices. Our experimental results, based on a sample of 107 patients with esophageal cancer, provide initial evidence that convolutional neural networks have the potential to extract PET imaging representations that are highly predictive of response to therapy. On this dataset, 3S-CNN achieves an average 80.7% sensitivity and 81.6% specificity in predicting non-responders, and outperforms other competing predictive models. PMID:26355298

  19. Axillary and internal mammary sentinel lymph node biopsy in breast cancer after neoadjuvant chemotherapy

    PubMed Central

    Cao, Xiao-Shan; Li, Hui-Juan; Cong, Bin-Bin; Sun, Xiao; Qiu, Peng-Fei; Liu, Yan-Bing; Wang, Chun-Jian; Wang, Yong-Sheng

    2016-01-01

    With the improvement of neoadjuvant chemotherapy (NAC), the proportion of pathological complete response (pCR) in the breast and axillary lymph node (ALN) is increasing. The evaluation of pCR does not include the status of internal mammary lymph node (IMLN). This study is to evaluate the roles of both axillary sentinel lymph node biopsy (ASLNB) and internal mammary sentinel lymph node biopsy (IM-SLNB) in breast cancer patients after NAC. There were 74 patients enrolled into this study. IM-SLNB was performed on patients with radioactive internal mammary sentinel lymph node (IM-SLN). Patients (n = 8) with cN0 and ycN0 received ASLNB, and axillary lymph node dissection (ALND) in cases of positive axillary sentinel lymph node (ASLN). Patients (n = 48) with cN+ but ycN0 received ASLNB and ALND. Patients (n = 18) with ycN+ received ALND without ASLNB. The visualization rate of IM-SLN was 56.8% (42/74). The success rate of IM-SLNB was 97.6% (41/42) and the metastasis rate of IM-SLN was 7.3% (3/41). The success rate of ASLNB was 100% (56/56). The false negative rate (FNR) of ASLNB was 17.2% (5/29). The FNR in patients with 1, 2 and ≥ 3ASLNs examined was 27.3% (3/11), 20.0% (2/10) and 0% (0/8) respectively. ASLNB could be performed on ycN0 after NAC, and ALND should be performed on initially ALN-positive patients. IM-SLNB should be considered after NAC, especially for patients with clinically positive axillary nodes before NAC, which might help make clear of the pathological nodal staging of both ALN and IMLN, improve the definition of nodal pCR, and guide the individual adjuvant regional and systemic therapy. PMID:27738336

  20. Axillary and internal mammary sentinel lymph node biopsy in breast cancer after neoadjuvant chemotherapy.

    PubMed

    Cao, Xiao-Shan; Li, Hui-Juan; Cong, Bin-Bin; Sun, Xiao; Qiu, Peng-Fei; Liu, Yan-Bing; Wang, Chun-Jian; Wang, Yong-Sheng

    2016-11-08

    With the improvement of neoadjuvant chemotherapy (NAC), the proportion of pathological complete response (pCR) in the breast and axillary lymph node (ALN) is increasing. The evaluation of pCR does not include the status of internal mammary lymph node (IMLN). This study is to evaluate the roles of both axillary sentinel lymph node biopsy (ASLNB) and internal mammary sentinel lymph node biopsy (IM-SLNB) in breast cancer patients after NAC. There were 74 patients enrolled into this study. IM-SLNB was performed on patients with radioactive internal mammary sentinel lymph node (IM-SLN). Patients (n = 8) with cN0 and ycN0 received ASLNB, and axillary lymph node dissection (ALND) in cases of positive axillary sentinel lymph node (ASLN). Patients (n = 48) with cN+ but ycN0 received ASLNB and ALND. Patients (n = 18) with ycN+ received ALND without ASLNB. The visualization rate of IM-SLN was 56.8% (42/74). The success rate of IM-SLNB was 97.6% (41/42) and the metastasis rate of IM-SLN was 7.3% (3/41). The success rate of ASLNB was 100% (56/56). The false negative rate (FNR) of ASLNB was 17.2% (5/29). The FNR in patients with 1, 2 and ≥ 3ASLNs examined was 27.3% (3/11), 20.0% (2/10) and 0% (0/8) respectively. ASLNB could be performed on ycN0 after NAC, and ALND should be performed on initially ALN-positive patients. IM-SLNB should be considered after NAC, especially for patients with clinically positive axillary nodes before NAC, which might help make clear of the pathological nodal staging of both ALN and IMLN, improve the definition of nodal pCR, and guide the individual adjuvant regional and systemic therapy.

  1. Predicting Response to Neoadjuvant Chemotherapy with PET Imaging Using Convolutional Neural Networks.

    PubMed

    Ypsilantis, Petros-Pavlos; Siddique, Musib; Sohn, Hyon-Mok; Davies, Andrew; Cook, Gary; Goh, Vicky; Montana, Giovanni

    2015-01-01

    Imaging of cancer with 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) has become a standard component of diagnosis and staging in oncology, and is becoming more important as a quantitative monitor of individual response to therapy. In this article we investigate the challenging problem of predicting a patient's response to neoadjuvant chemotherapy from a single 18F-FDG PET scan taken prior to treatment. We take a "radiomics" approach whereby a large amount of quantitative features is automatically extracted from pretherapy PET images in order to build a comprehensive quantification of the tumor phenotype. While the dominant methodology relies on hand-crafted texture features, we explore the potential of automatically learning low- to high-level features directly from PET scans. We report on a study that compares the performance of two competing radiomics strategies: an approach based on state-of-the-art statistical classifiers using over 100 quantitative imaging descriptors, including texture features as well as standardized uptake values, and a convolutional neural network, 3S-CNN, trained directly from PET scans by taking sets of adjacent intra-tumor slices. Our experimental results, based on a sample of 107 patients with esophageal cancer, provide initial evidence that convolutional neural networks have the potential to extract PET imaging representations that are highly predictive of response to therapy. On this dataset, 3S-CNN achieves an average 80.7% sensitivity and 81.6% specificity in predicting non-responders, and outperforms other competing predictive models.

  2. 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

  3. Do amount of variant differentiation and mitotic rate in bladder cancer change with neoadjuvant chemotherapy?

    PubMed

    Shen, Helen M; D'Souza, Amber M; Green, Ian F; Pohar, Kamal S; Mortazavi, Amir; Zynger, Debra L

    2015-09-01

    Neoadjuvant chemotherapy (NAC) is currently recommended to all candidate patients with muscularis propria-invasive bladder cancer. However, NAC is effective in only a subset of patients, and predictors of response are lacking. Our study aimed to characterize tumoral changes with NAC usage and to identify features at bladder biopsy/transurethral resection (Bx/TUR) that may predict response. A retrospective search was performed to identify patients with bladder cancer that were pT2 at Bx/TUR upon whom a radical cystectomy (RC) was performed from 2007 to 2010. A blinded slide review of the Bx/TUR and RC was conducted. Presence, type, percent of tumor variant morphology, and tumoral mitotic rate were assessed. Ninety RC patients with slides available were identified (46 NAC, 44 non-NAC). In NAC-treated patients, there was a significantly higher percentage of nonurothelial variant differentiation in the RC compared with Bx/TUR, whereas there was no difference in the non-NAC subgroup. Percent variant differentiation at Bx/TUR was not a predictor of response. There was a significant decrease in mitotic rate between Bx/TUR and RC in NAC patients, whereas there was no difference in the non-NAC subgroup, although mitotic rate was not a predictor of response. In conclusion, percent variant differentiation and mitotic rate changed significantly from Bx/TUR to RC with NAC usage, although neither predicted response. Pathologists should be aware that variant differentiation is common in bladder cancer, with increased presence after NAC, in order to improve recognition and documentation of these findings.

  4. Concurrent chemo-radiotherapy following neoadjuvant chemotherapy in locally advanced breast cancer

    PubMed Central

    Alvarado-Miranda, Alberto; Arrieta, Oscar; Gamboa-Vignolle, Carlos; Saavedra-Perez, David; Morales-Barrera, Rafael; Bargallo-Rocha, Enrique; Zinser-Sierra, Juan; Perez-Sanchez, Victor; Ramirez-Ugalde, Teresa; Lara-Medina, Fernando

    2009-01-01

    Background Despite broad advances in multimodal treatment of locally advanced breast cancer (LABC), 30 to 40% of patients develop loco-regional relapse. The aim of this study was to analyze in a retrospective manner the effectiveness of concurrent chemo-radiotherapy (CCRTh) after neoadjuvant chemotherapy (NCT) in patients with LABC. Methods One hundred twelve patients with LABC (stage IIB-IIIB) were treated with NCT (5-fluorouracil 500 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2 (FAC), or doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 (AC) IV in four 21-day courses) followed by CCRTh (60 Gy breast irradiation and weekly mitomycin 5 mg/m2, 5-fluorouracil 500 mg/m2, and dexamethasone 16 mg, or cisplatin 30 mg/m2, gemcitabine 100 mg/m2 and dexamethasone 16 mg), and 6–8 weeks later, surgery and two additional courses of FAC, AC, or paclitaxel 90 mg/m2 weekly for 12 weeks, and in case of estrogen-receptor positive patients, hormonal therapy. Results Stages IIB, IIIA and -B were 21.4, 42.9, and 35.7%, respectively. Pathological complete response (pCR) in the breast was 42% (95% CI, 33.2–50.5%) and, 29.5% (95% CI, 21.4–37.5%) if including both the breast and the axillary nodes. Multivariate analysis showed that the main determinant of pCR was negative estrogen-receptor status (HR = 3.8; 95% CI, 1.5–9; p = 0.016). The 5-year disease-free survival (DFS) was 76.9% (95% CI, 68.2–84.7%). No relationship between pCR and DFS was found. Multivariate analysis demonstrated that the main DFS determinant was clinical stage (IIB and IIIA vs. IIIB, HR = 3.1; 95% CI, 1.02–9.74; p = 0.04). Only one patient had local recurrence. Five-year overall survival was 84.2% (95% CI, 75–93.2%). The toxicity profile was acceptable. Conclusion This non-conventional multimodal treatment has good loco-regional control for LABC. Randomized clinical trials of preoperative CCRTh following chemotherapy, in patients with LABC are warranted. PMID:19591689

  5. A portable and compact near-infrared spectral tomography system for predicting breast tumor response to neoadjuvant chemotherapy

    NASA Astrophysics Data System (ADS)

    Zhao, Yan; El-Ghussein, Fadi; Zhang, Ziqi; Pogue, Brian W.; Paulsen, Keith D.; Jiang, Shudong

    2015-03-01

    A portable hybrid frequency domain (FD)-continuous wave (CW) Near-Infrared spectroscopy NIRS system has been developed for quantifying changes in total hemoglobin, oxygen saturation and water content in the breast during neoadjuvant chemotherapy. Simultaneous acquisition of two sets of 3 FD channels and 3 CW channels could be completed within 1 min. System calibration and homogeneous phantom measurement show phase variation less than 3% when PMT gain from 0.7 to 1.1 was used. The study of integrating this system into the workflow of clinical oncology practice is ongoing.

  6. TP53 mutations are associated with higher rates of pathologic complete response to anthracycline/cyclophosphamide-based neoadjuvant chemotherapy in operable primary breast cancer.

    PubMed

    Wang, Yuxia; Xu, Ye; Chen, Jiuan; Ouyang, Tao; Li, Jinfeng; Wang, Tianfeng; Fan, Zhaoqing; Fan, Tie; Lin, Benyao; Xie, Yuntao

    2016-01-15

    The role of TP53 mutations in predicting response to neoadjuvant chemotherapy in breast cancer remains controversial. The aims of this study were to investigate whether TP53 mutations were associated with response and survival in breast cancer patients who received neoadjuvant chemotherapy. Therefore, we identified TP53 mutations in the core-needle biopsy tumor samples obtained before the neoadjuvant chemotherapy from 351 operable primary breast cancer patients who either received anthracycline/cyclophosphamide-based (n = 252) or paclitaxel (n = 99) neoadjuvant chemotherapy. We found that 41.0% (144 of 351) of patients harbored TP53 mutations, and 14.8% of patients achieved a pCR (pathologic complete response) after neoadjuvant chemotherapy. Among patients treated with anthracycline/cyclophosphamide (n = 252), patients with TP53 mutations had a significantly higher pCR rate than those with wild-type (28.6 vs.7.1%; p < 0.001), and TP53 mutation was an independent favorable predictor of pCR [odds ratio (OR) = 3.41; 95% confidence interval (CI) 1.50-7.77; p = 0.003] in this group; moreover, patients with TP53 mutation had a better distant recurrence-free survival (DRFS) than those with wild-type [unadjusted hazard ratio (HR) = 0.43; 95% CI 0.20-0.94; p = 0.030] in this group. Among patients treated with paclitaxel (n = 99), no significant difference in pCR rates was observed between patients with or without TP53 mutations (15.2 vs. 11.3%; p = 0.57). Our results suggested that patients with TP53 mutations are more likely to respond to anthracycline/ cyclophosphamide-based neoadjuvant chemotherapy and have a favorable survival.

  7. 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.

  8. Differences in the recurrence pattern after neoadjuvant chemotherapy compared to surgery alone in patients with muscle-invasive bladder cancer.

    PubMed

    Koie, Takuya; Ohyama, Chikara; Yamamoto, Hayato; Imai, Atsushi; Hatakeyama, Shingo; Yoneyama, Takahiro; Hashimoto, Yasuhiro; Yoneyama, Tohru; Tobisawa, Yuki

    2015-01-01

    In patients with muscle-invasive bladder cancer (MIBC), neoadjuvant chemotherapy (NAC) confers a survival benefit compared to radical cystectomy (RC) alone. Recurrence is observed in many cases and is the most common cause of death in MIBC patients. However, the rate and pattern of recurrence after NAC in MIBC patients remain unclear. We retrospectively reviewed the charts of 348 consecutive patients who underwent RC and bilateral pelvic node dissection between May 1994 and July 2012. Our study focused on patients with MIBC who had histologically confirmed stage T2-T4a urothelial carcinoma of the bladder without lymph node or distant metastasis. Accordingly, 265 patients were included in this analysis, of whom 130 received NAC and 135 underwent RC alone. Propensity score matching was used to adjust for potential selection biases associated with treatment type. Recurrence was defined as local recurrence and distant metastasis, according to site. Propensity score matching analysis identified 130 matched pairs from the two groups. For the neoadjuvant gemcitabine and carboplatin (GCarbo) and RC alone groups, the 5-year overall survival rates were 89.2 and 51.4 %, respectively (P < 0.0001), and the recurrence-free survival rates were 85.4 and 57.0 %, respectively (P < 0.0001). However, the total number of local recurrences was markedly lower in the neoadjuvant GCarbo group than in the RC alone group. Neoadjuvant GCarbo was associated with improved oncological outcomes and a different recurrence pattern in MIBC patients compared to RC alone.

  9. Accumulation of ALDH1-positive cells after neoadjuvant chemotherapy predicts treatment resistance and prognosticates poor outcome in ovarian cancer.

    PubMed

    Ayub, Tiyasha H; Keyver-Paik, Mignon-Denise; Debald, Manuel; Rostamzadeh, Babak; Thiesler, Thore; Schröder, Lars; Barchet, Winfried; Abramian, Alina; Kaiser, Christina; Kristiansen, Glen; Kuhn, Walther; Kübler, Kirsten

    2015-06-30

    Although ovarian cancer is a highly chemosensitive disease, it is only infrequently cured. One of the major reasons lies in the presence of drug-resistant cancer stem-like cells, sufficient to fuel recurrence. We phenotyped cancer stem-like cells by flow cytometry and immunohistochemistry in 55 matched samples before and after taxane/platinum-based neoadjuvant chemotherapy. All used markers of stemness (ALDH1, CD24, CD117, CD133) isolated low frequencies of malignant cells. ALDH1 was the most valuable marker for tracking stemness in vivo. The enrichment of ALDH1 expression after treatment was associated with a poor response to chemotherapy, with platinum resistance and independently prognosticated unfavorable outcome. Our results suggest that increased ALDH1 expression after treatment identifies patients with aggressive tumor phenotypes.

  10. [Effect of neoadjuvant chemotherapy on complications in patients undergoing surgical treatment for non small cell lung cancer].

    PubMed

    Tomaszewski, Dariusz; Zajac-Lenczewska, Ina; Plichta, Lukasz; Lapiński, Mariusz; Murawski, Maciej; Sternau, Adam; Skokowski, Jan

    2004-01-01

    Neoadjuvant chemotherapy before resection is being the standard of care for stage IIIA non-small cell lung cancer in many institutions. The risk of complications in patients undergoing thoracotomy after induction chemotherapy remain controversial. We reviewed our experience. From 1998 to 2003, 29 patients underwent pulmonary resection after induction chemotherapy for advanced non-small cell lung cancer. Pneumonectomies were performed for 16 (55.2%) patients (2 right sleeve pneumonectomy and 1 pneumonectomy with wedge excision of tracheal carina), lobectomies for 11 (37.9%) patients (3 right upper sleeve lobectomy), segmentectomies for 1 (3.45%) patient and explorative thoracotomy for 1 (3.45%) patient. There were 3 (10.3%) postoperative deaths, all after right pneumonectomy; 2 caused by pneumonia of the left lung, 1 caused by pulmonary embolism in patient after re-thoracotomy for hemothorax. The postoperative complications included pneumonia in 2 patients, postoperative bleeding in 2, hemothorax in 1, prolonged intubation in 1, vocal cord paralysis in 2, cardiac arrhythmia in 2, atelectasis in 1 and residual air space in 1, resulting in 41,4% morbidity. Most of complications occurred after right pneumonectomy (45.5%). The mortality of patients who had received induction chemotherapy was higher than that of a comparative group of 1529 who underwent lung resection or only exploration without induction chemotherapy during the same period, and the difference was significant (10.3% vs 4.1%; p = 0.01). Morbidity differences were. not significant (p = 0.94).

  11. 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.

  12. 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

  13. Low expression of NQO1 predicts pathological complete response to neoadjuvant chemotherapy in breast cancer patients treated with TAC regimen.

    PubMed

    Grim, J; Jandík, P; Slánská, I; Doležalová-Brčáková, E; Fuksa, L; Ryška, A; Knížek, J; Petera, J; Mičuda, S; Hornychová, H

    2012-01-01

    The aim of this study was to evaluate preoperative tumour expression of NAD(P)H:quinone oxidoreductase 1 (NQO1) along with other biological markers as potential predictors of pathological complete response (pCR) to neoadjuvant docetaxel, doxorubicin, and cyclophosphamide-containing (TAC) chemotherapy in patients with primary breast cancer. Sixty-one patients who received neoadjuvant chemotherapy (NCT) with TAC regimen were enrolled in this prospective study. The pre- and post- NCT expression of oestrogen receptor (ER), progesterone receptor (PR), epidermal growth factor receptor 1 and 2 (EGFR and HER2), NQO1, Ki-67 proliferation index, multidrug resistance protein 1 (MDR1), p53 and BCL2 were evaluated by immunohistochemistry. The pCR was reached in 14 patients (23 % of the study group). Multivariate analysis demonstrated that patients with ER-, PR-, NQO1- negative, and Ki-67-positive tumours had a significantly higher chance to achieve pCR. Within the biological subtypes, the highest pCR rate (50 %) was seen in triple-negative (i.e. ER-, PR-, HER2-) tumours. Post-operative evaluation showed that in comparison to pre-operative tissue samples, NQO1 expression was significantly increased, while Ki-67 and HER2 decreased, in the residual tissue after NCT. In conclusion, the present data suggests that NQO1 expression may be a novel diagnostic biomarker for the prediction of positive response to NCT in patients with breast cancer.

  14. 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

  15. Tumor infiltrating lymphocytes in triple negative breast cancer receiving neoadjuvant chemotherapy

    PubMed Central

    Castaneda, Carlos A; Mittendorf, Elizabeth; Casavilca, Sandro; Wu, Yun; Castillo, Miluska; Arboleda, Patricia; Nunez, Teresa; Guerra, Henry; Barrionuevo, Carlos; Dolores-Cerna, Ketty; Belmar-Lopez, Carolina; Abugattas, Julio; Calderon, Gabriela; De La Cruz, Miguel; Cotrina, Manuel; Dunstan, Jorge; Gomez, Henry L; Vidaurre, Tatiana

    2016-01-01

    AIM To determine influence of neoadjuvant-chemotherapy (NAC) over tumor-infiltrating-lymphocytes (TIL) in triple-negative-breast-cancer (TNBC). METHODS TILs were evaluated in 98 TNBC cases who came to Instituto Nacional de Enfermedades Neoplasicas from 2005 to 2010. Immunohistochemistry staining for CD3, CD4, CD8 and FOXP3 was performed in tissue microarrays (TMA) sections. Evaluation of H/E in full-face and immunohistochemistry in TMA sections was performed in pre and post-NAC samples. STATA software was used and P value < 0.05 was considered statistically significant. RESULTS Higher TIL evaluated in full-face sections from pre-NAC tumors was associated to pathologic-complete-response (pCR) (P = 0.0251) and outcome (P = 0.0334). TIL evaluated in TMA sections showed low level of agreement with full-face sections (ICC = 0.017-0.20) and was not associated to pCR or outcome. TIL in post-NAC samples were not associated to response or outcome. Post-NAC lesions with pCR had similar TIL levels than those without pCR (P = 0.6331). NAC produced a TIL decrease in full-face sections (P < 0.0001). Percentage of TIL subpopulations was correlated with their absolute counts. Higher counts of CD3, CD4, CD8 and FOXP3 in pre-NAC samples had longer disease-free-survival (DFS). Higher counts of CD3 in pre-NAC samples had longer overall-survival. Higher ratio of CD8/CD4 counts in pre-NAC was associated with pCR. Higher ratio of CD4/FOXP3 counts in pre-NAC was associated with longer DFS. Higher counts of CD4 in post-NAC samples were associated with pCR. CONCLUSION TIL in pre-NAC full-face sections in TNBC are correlated to longer survival. TIL in full-face differ from TMA sections, absolute count and percentage analysis of TIL subpopulation closely related. PMID:27777881

  16. BRCAness and Prognosis in Triple-Negative Breast Cancer Patients Treated with Neoadjuvant Chemotherapy

    PubMed Central

    Kosaka, Yoshimasa; Nishimiya, Hiroshi; Tanaka, Youko; Minatani, Naoko; Kikuchi, Mariko; Shida, Akiko; Waraya, Mina; Katoh, Hiroshi; Enomoto, Takumo; Sengoku, Norihiko; Kajita, Sabine; Hoffman, Robert M.; Watanabe, Masahiko

    2016-01-01

    BRCAness is defined as the set of traits in which BRCA1 dysfunction, arising from gene mutation, methylation or deletion, results in DNA repair deficiency. In the present study, we addressed BRCAness, therapeutic efficacy, recurrence, and survival in patients with triple negative breast cancer (TNBC) who were treated with neoadjuvant chemotherapy at Kitasato University Hospital, Japan, between April 2006 and October 2012. BRCAness was determined by preoperative core needle biopsy (CNB) specimens and surgical specimens. Assay was performed using Multiplex Ligation-dependent Probe Amplification (MLPA) with P376-B2 BRCA1ness probemix (MRC-Holland, Amsterdam, The Netherlands). The relative copy number ratio of each sample was compared to Human Genomic DNA (Promega, Madison, WI, USA) as reference samples was calculated with Coffalyser.NET default settings. The BRCAness score was calculated with the relative copy number ratio of various DNA sequences. Values of 0.5 or more were determined as the BRCA1-like Type (BRCAness) and those of less than 0.5 as the Sporadic Type to analyze pathological complete response (pCR) rate, recurrence, and survival. pCR (ypT0/Tis/N0) was observed in 15 patients (pCR rate: 37.5%). These patients had no recurrence. Twelve patients recurred, 8 died from breast cancer. The BRCA1-like Type were 22 and Sporadic Type were 18 in CNB specimens. No major differences were observed between the BRCA1-like Type and Sporadic Type with pCR rate, recurrence rate and survival. Twenty four surgical specimens of non-pCR patients were available and 9 were BRCA1-like Type, who had more recurrences (7/9 vs. 5/15), and their relapse-free survival was also lower (p<0.05) than that of Sporadic Type. Seven BRCA1-like Type patients remained BRCA1-like Type in surgical specimens, were worse in recurrence (p<0.01) and survival (p<0.05) compared with 6 patients whose BRCA status in surgical specimens turned to Sporadic Type. New clinical trials assessing the true

  17. 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.

  18. 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.

  19. Altered glycometabolism affects both clinical features and prognosis of triple-negative and neoadjuvant chemotherapy-treated breast cancer.

    PubMed

    Dong, Tieying; Kang, Xinmei; Liu, Zhaoliang; Zhao, Shu; Ma, Wenjie; Xuan, Qijia; Liu, Hang; Wang, Zhipeng; Zhang, Qingyuan

    2016-06-01

    Glycometabolism is a distinctive aspect of energy metabolism in breast cancer, and key glycometabolism enzymes/pathways (glycolysis, hexosamine biosynthetic pathway, and pentose phosphate pathway) may directly or indirectly affect the clinical features. In this study, we analyzed the particular correlation between the altered glycometabolism and clinical features of breast cancer to instruct research and clinical treatment. Tissue microarrays containing 189 hollow needle aspiration samples and 295 triple-negative breast cancer tissues were used to test the expression of M2 isoform of pyruvate kinase (PKM2), glutamine-fructose-6-phosphate transaminase 1 (GFPT1), glucose-6-phosphate dehydrogenase (G6PD), and p53 by immunohistochemistry and the intensity of these glycometabolism-related protein was evaluated. Chi-square test, Kaplan-Meier estimates, and Cox proportional hazards model were used to analyze the relationship between the expression of these factors and major clinical features. PKM2, GFPT1, and G6PD affect the pathologic complete response rate of neoadjuvant chemotherapy patients in different ways; pyruvate kinase muscle isozyme 2 (PKM2) and G6PD are closely associated with the molecular subtypes, whereas GFPT1 is correlated with cancer size. All these three factors as well as p53 have impacts on the progression-free survival and overall survival of triple-negative breast cancer patients. Cancer size shows significant association with PKM2 and GFPT1 expression, while the pN stage and grade are associated with PKM2 and G6PD expression. Our study support that clinical characteristics are reflections of specific glycometabolism pathways, so their relationships may shed light on the orientation of research or clinical treatment. The expression of PKM2, GFPT1, and G6PD are hazardous factors for prognosis: high expression of these proteins predict worse progression-free survival and overall survival in triple-negative breast cancer, as well as worse pathologic

  20. 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.

  1. Pathological Complete Response and Long-Term Survival in a Very Elderly Patient after Neoadjuvant Chemotherapy for Locally Advanced, Unresectable Gastric Cancer

    PubMed Central

    Kobayashi, Mitsuyoshi; Mori, Hirohito; Ebara, Kazuo

    2014-01-01

    We address the pathological complete response and long-term survival of elderly patients after neoadjuvant chemotherapy in locally advanced, unresectable gastric cancer. An 83-year-old man was hospitalized for upper abdominal pain. Gastrointestinal endoscopy showed a large tumor spanning from the gastric angle to the antrum, and extending to the duodenum. Histological analysis of the biopsy specimen revealed a poorly differentiated adenocarcinoma. Computed tomography images showed thickening of the gastric wall and invasion of the body and head of the pancreas, but did not show distant metastases. The patient was diagnosed with unresectable gastric cancer, and was treated with neoadjuvant chemotherapy using S-1 (80 mg/m2) and paclitaxel (60 mg/m2). After the third course of chemotherapy, gastrointestinal endoscopy and abdominal computed tomography revealed a remarkable reduction in tumor size. This reduction allowed distal gastrectomy to be conducted. Histological examination of the specimen revealed no cancer cells in the primary lesion or lymph nodes. The patient was treated with adjuvant chemotherapy of oral tegafur-uracil (300 mg/day) for one year after surgery. He lived for five years after surgery without recurrence. Neoadjuvant chemotherapy using S-1 and paclitaxel is a potent strategy for improving survival in very elderly patients with unresectable gastric cancer. PMID:25298899

  2. Prospective cohort study of febrile neutropenia in breast cancer patients with neoadjuvant and adjuvant chemotherapy: CSPOR-BC FN study.

    PubMed

    Ishikawa, Takashi; Sakamaki, Kentaro; Narui, Kazutaka; Kaise, Hiroshi; Tsugawa, Koichiro; Ichikawa, Yasushi; Mukai, Hirofumi

    2016-07-01

    With the increasing use of adjuvant chemotherapy for treating early breast cancer, febrile neutropenia management has become crucial. Guidelines for febrile neutropenia management are mostly based on a Caucasian population survey although ethnic differences are reported in terms of adverse events. We survey the current status of febrile neutropenia and risk factors in Japanese female breast cancer patients receiving neoadjuvant and adjuvant chemotherapy regimens potential for febrile neutropenia. Subsequently, we plan to conduct a multicenter prospective cohort study involving 1000 patients with operable breast cancer. With the current state of oral antibiotics being routinely prescribed without hematology tests, we survey febrile neutropenia based on two different definitions, namely, true febrile neutropenia: ≥37.5°C and Grade 4 neutropenia, and surrogate febrile neutropenia: ≥37.5°C and oral antibiotic and antipyretic intake. The comparison of true febrile neutropenia and surrogate febrile neutropenia incidences is anticipated to provide information on the safety and feasibility of chemotherapy management without performing blood tests.

  3. The effect of molecular subtype and body mass index on neo-adjuvant chemotherapy in breast cancer patients.

    PubMed

    Iwase, Toshiaki; Nakamura, Rikiya; Yamamoto, Naohito; Yoshi, Atushi; Itami, Makiko; Miyazaki, Masaru

    2014-06-01

    The aim of the present study was to analyze the effect of subtype and body mass index (BMI) on neo-adjuvant chemotherapy (NAC) and postoperative prognosis. Two-hundred and forty nine patients who underwent surgery after NAC were included. A multivariate analysis and survival analysis were used to clarify the relationship between BMI, subtype, and NAC. In the logistic regression model, the pCR rate had a significant relationship with the subtype and tumor stage. In the non-pCR group, more overweight patients had significantly a worse disease-free survival (DFS) compared to normal range patients (Log lank test, p < 0.05). In the Cox proportional hazards model, subtype and tumor stage were significantly associated with decreased DFS. In conclusion, patients with the ER (+), HER (-) type and a high BMI had a high risk for recurrence when they achieved non-pCR after NAC.

  4. Evaluation of Neoadjuvant Chemotherapy Response with Dynamic Contrast Enhanced Breast Magnetic Resonance Imaging in Locally Advanced Invasive Breast Cancer

    PubMed Central

    Gezer, Naciye Sinem; Orbay, Özge; Balcı, Pınar; Durak, Merih Guray; Demirkan, Binnaz; Saydam, Serdar

    2014-01-01

    Objective The reliability of traditional methods such as physical examination, ultrasonography (US) and mammography is limited in determining the type of treatment response in patients with neoadjuvant chemotherapy (NAC) application for locally advanced breast cancer (LABC). Dynamic contrast-enhanced magnetic resonance imaging (MRI) is gaining popularity in the evaluation of NAC response. This study aimed to compare NAC response as determined by dynamic contrast-enhanced breast MRI in patients with LABC to histopathology that is the gold standard; and evaluate the compatibility of MRI, mammography and US with response types. Materials and Methods The US, mammography and MRI findings of 38 patients who received NAC with a diagnosis of locally advanced breast cancer and surgical treatment were retrospectively analyzed and compared to histopathology results. Type of response to treatment was determined according to the “Criteria in Solid Tumors Response Evolution 1.1” by mammography, US and MRI criteria. The relationship between response types as defined by all three imaging modalities and histopathology were evaluated, and the correlation of response type as detected by MRI and pathological response and histopathological type of breast cancer was further determined. For statistical analysis, the chi-square, paired t test, correlation and kappa tests were used. Results There is a statistical moderate positive correlation between response type according to pathology and MRI (kappa: 0.63). There was a weak correlation between response type according to mammography or US and according to pathology (kappa: 0.2). When the distribution of treatment response by MRI is stratified according to histopathological types, partial response was higher in all histopathological types similar to the type of pathologic response. When compared with pathology MRI detected treatment response accurately in 84.2% of the patients. Conclusion Dynamic contrast-enhanced breast MRI appears to

  5. Diffuse Optical Spectroscopy Evaluation of Treatment Response in Women with Locally Advanced Breast Cancer Receiving Neoadjuvant Chemotherapy1

    PubMed Central

    Falou, Omar; Soliman, Hany; Sadeghi-Naini, Ali; Iradji, Sara; Lemon-Wong, Sharon; Zubovits, Judit; Spayne, Jacqueline; Dent, Rebecca; Trudeau, Maureen; Boileau, Jean Francois; Wright, Frances C; Yaffe, Martin J.; Czarnota, Gregory J

    2012-01-01

    The aim of this study was to investigate the potential of diffuse optical spectroscopy for monitoring of patients with locally advanced breast cancer (LABC) undergoing neoadjuvant chemotherapy. Fifteen women receiving treatment for LABC had the affected breast scanned before; 1 week, 4 weeks, and 8 weeks after treatment initiation; and before surgery. Optical properties related to tissue microstructure and biochemical composition were obtained. Clinical and pathologic tumor response was evaluated using whole-mount pathology after mastectomy. Patients who responded to treatment demonstrated an initial increase followed by a drop in optical parameters measured in the whole breast, whereas nonresponding patients demonstrated only a drop in the same parameters 1 week after treatment initiation. Responding patients demonstrated a significant increase of 17% ± 7%, 8% ± 8%, 10% ± 7%, 11% ± 11%, and 16% ± 15% in deoxygenated hemoglobin, oxygenated hemoglobin, total hemoglobin concentrations, water percentage, and tissue optical index, 1 week after treatment initiation, respectively. In contrast, nonresponding patients had a decrease of 14% ± 9%, 18% ± 7%, 17% ± 7%, 29% ± 7%, and 32% ± 9% in their corresponding optical parameters. Deoxygenated hemoglobin concentration (with 100% sensitivity, 83% specificity) and water percentage (with 75% sensitivity, 100% specificity) were found to be the best predictors of treatment response at 1 week after starting treatment. The results of this study suggest that optical parameters can be potentially used to predict and monitor patients' responses to neoadjuvant chemotherapy and can form a basis for the customization of treatments in which inefficacious treatments can be switched to more efficacious therapies. PMID:22937175

  6. Results of a conservative treatment combining induction (neoadjuvant) and consolidation chemotherapy, hormonotherapy, and external and interstitial irradiation in 98 patients with locally advanced breast cancer (IIIA-IIIB)

    SciTech Connect

    Jacquillat, C.; Baillet, F.; Weil, M.; Auclerc, G.; Housset, M.; Auclerc, M.; Sellami, M.; Jindani, A.; Thill, L.; Soubrane, C.

    1988-05-15

    Ninety-eight patients with locally advanced breast cancer (Stage IIIA-IIIB) were entered into a pilot study combining intensive induction (neoadjuvant) chemotherapy (VTMFAP) with or without hormonochemotherapy, external and interstitial radiotherapy, and consolidation chemotherapy with or without hormonochemotherapy. Tumor regression over 50% was observed in 91% patients after chemotherapy, and complete clinical remission occurred in 100% patients after irradiation. The rate of local relapse is 13%. The 3-year disease-free survival is 62% and 3-year global survival is 77%. Initial chemotherapeutic tumor regression greater than 75% is the main predictive factor for disease-free survival.

  7. 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

  8. Effect of Neoadjuvant Chemotherapy on Renal Function following Radical Cystectomy: Is there a Meaningful Impact?

    PubMed Central

    Chandrasekar, Thenappan; Pugashetti, Neil; Durbin-Johnson, Blythe; Dall’Era, Marc A.; Evans, Christopher P.; deVere White, Ralph W.; Yap, Stanley A.

    2016-01-01

    Objective: To evaluate the patterns of impact of neoadjuvant chemotherapy (NAC) on renal function across the initial year following treatment for muscle-invasive bladder cancer (MIBC) with radical cystectomy (RC). Methods: We reviewed the charts of 241 patients who underwent RC for urothelial carcinoma of the bladder between 2003-14 at our institution. Renal function was evaluated at multiple time points (pre-chemotherapy, pre-operatively, post-operatively, 6–12 months follow-up), and then classified by CKD staging. Univariable and multivariable logistic regression analyses were performed to determine relationship between NAC and change in CKD stage. Results: Of the 241 patients who underwent RC for urothelial carcinoma of the bladder, 66 (27%) received NAC and 175 (73%) did not. In multivariable analysis, NAC was significantly associated with a decrease of at least one CKD stage from baseline to post-op (p = 0.009), but not to the 6–12 months follow-up time point (p = 0.050). The loss of GFR in the NAC cohort occurs up-front with chemotherapy, but the peri-operative course is similar to those who underwent cystectomy alone. Of the 15 NAC patients (26.8%) who were Stage 3 CKD prior to chemotherapy, none progressed to a higher stage CKD. Conclusion: NAC is associated with an initial decline in GFR, which then remains stable through the first year following RC. Despite an initial insult, patients receiving NAC are not vulnerable to further deterioration. When appropriately selected, NAC does not appear to result in a clinically significant deterioration of renal function. PMID:28035325

  9. Assessing the TP53 marker type in patients treated with or without neoadjuvant chemotherapy for resectable colorectal liver metastases: a p53 Research Group study.

    PubMed

    Pilat, N; Grünberger, T; Längle, F; Mittlböck, M; Perisanidis, B; Kappel, S; Wolf, B; Starlinger, P; Kührer, I; Mühlbacher, F; Kandioler, D

    2015-05-01

    The type of a biomarker - whether it is prognostic or predictive - is frequently not known, although such information is crucial for assessing the clinical value of a marker. In order to evaluate the type of marker TP53 is, we identified a cohort of 76 patients with colorectal liver metastases (CLM), homogeneously staged as resectable, who had been treated either with or without fluorouracil-based neoadjuvant chemotherapy. The TP53 genotype was assessed retrospectively from paraffin-embedded, diagnostic tumour biopsies using a standardised, p53 gene-specific sequencing protocol (mark53(®) kit). The overall median survival was 44.2 months, and the overall TP53 mutation frequency was 55%. A significant interaction was observed between chemotherapy and TP53 status (P = 0.045). To illustrate this effect, the 51 patients with and the 25 patients without neoadjuvant chemotherapy were described separately. In patients with neoadjuvant chemotherapy, mutated TP53 was significantly associated with poor survival (P = 0.0025), resulting in five-year survival rates of 22%, compared to 60% in patients with normal TP53. The hazard ratio was 3.12 (95% confidence intervals (CI): 1.46-6.95) to the disadvantage of TP53-mutated patients and 5.49 (P = 0.0001; 95% CI: 2.28-13.24) after adjustment for known prognostic factors. In patients treated with surgery alone, a mutated TP53 did not have a negative effect on survival (P = 0.54). A mutated TP53 status independently predicted survival disadvantage in CLM patients in the presence, but not in the absence, of neoadjuvant chemotherapy. Our data suggest that TP53 might be a pure predictive marker.

  10. 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

  11. 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

  12. Does neoadjuvant chemotherapy affect morbidity, mortality, reoperations, or readmissions in patients undergoing lumpectomy or mastectomy for breast cancer?

    PubMed Central

    Bennie, Barbara; Bray, Mallory S.; Vang, Choua A.; Linebarger, Jared H.

    2017-01-01

    Background The influence of neoadjuvant chemotherapy (NAC) prior to breast cancer surgery on postoperative complications is unclear. Our objective was to determine whether NAC was associated with postoperative outcomes in patients undergoing lumpectomy or mastectomy without reconstruction. Methods Patients meeting inclusion criteria were identified from the National Surgical Quality Improvement Program (NSQIP) database participant user files from 2005 through 2012, after which NSQIP discontinued the NAC variable. Primary outcome measures included a composite measure of morbidity and mortality (M&M) and reoperations and readmissions within 30 days of the index procedure. Rates of postoperative complications stratified by receipt of NAC were compared by χ2. A logistic regression model was then built that included confounding factors for M&M. Results There were 30,309 patients meeting inclusion criteria. NAC was not associated with any postoperative outcomes from 2005 through 2012, but it was associated with higher M&M in lumpectomy patients during 2011 to 2012 [P=0.011, odds ratio (OR) 2.579; 95% confidence interval (CI), 1.239–5.368]. Conclusions The finding that NAC was associated with higher M&M in lumpectomy patients during 2011 to 2012 warrants further investigation. Therefore, we recommend that the NSQIP database reinstitute the NAC variable to allow monitoring during anticipated changes in chemotherapy agents and protocols. PMID:28210548

  13. Neoadjuvant and adjuvant chemotherapy combined with anatomical resection of feline injection-site sarcoma: results in 21 cats.

    PubMed

    Bray, J; Polton, G

    2016-06-01

    This study assesses the outcome of two combined treatment strategies for the treatment of feline injection-site sarcoma (FISS). Twenty-one cats with primary or recurrent FISS received 3 cycles of neoadjuvant chemotherapy with epirubicin (25 mg m(-2) ), then an anatomical resection of the entire muscle compartment containing the tumour was performed based on the findings of co-axial imaging. Cats then received a further 3 cycles of adjuvant chemotherapy. Follow-up was performed by telephone contact with a median follow-up time of 1072 days. Three cats (14%) developed local tumour recurrence at days 264, 664 and 1573 after surgery. A median survival time could not be calculated as over 80% of the study population remained alive or were censored due to death from other causes. When compared to historical controls, the results of this study demonstrate superior rates of tumour-free survival and disease-free interval.

  14. Sentinel lymph node biopsy after neo-adjuvant chemotherapy in patients with breast cancer: Are the current false negative rates acceptable?

    PubMed

    Patten, D K; Zacharioudakis, K E; Chauhan, H; Cleator, S J; Hadjiminas, D J

    2015-08-01

    The advent of sentinel lymph node biopsy has revolutionised surgical management of axillary nodal disease in patients with breast cancer. Patients undergoing neo-adjuvant chemotherapy for large breast primary tumours may experience complete pathological response on a previously positive sentinel node whilst not eliminating the tumour from the other lymph nodes. Results from 2 large prospective cohort studies investigating sentinel lymph node biopsy after neo-adjuvant chemotherapy demonstrate a combined false negative rate of 12.6-14.2% and identification rate of 80-89% with the minimal acceptable false negative rate and identification rate being set at 10% and 90%, respectively. A false negative rate of 14% would have been classified as unacceptable when compared to the figures obtained by the pioneers of sentinel lymph node biopsy which was 5% or less.

  15. Modulation of circulating angiogenic factors and tumor biology by aerobic training in breast cancer patients receiving neoadjuvant chemotherapy.

    PubMed

    Jones, Lee W; Fels, Diane R; West, Miranda; Allen, Jason D; Broadwater, Gloria; Barry, William T; Wilke, Lee G; Masko, Elisabeth; Douglas, Pamela S; Dash, Rajesh C; Povsic, Thomas J; Peppercorn, Jeffrey; Marcom, P Kelly; Blackwell, Kimberly L; Kimmick, Gretchen; Turkington, Timothy G; Dewhirst, Mark W

    2013-09-01

    Aerobic exercise training (AET) is an effective adjunct therapy to attenuate the adverse side-effects of adjuvant chemotherapy in women with early breast cancer. Whether AET interacts with the antitumor efficacy of chemotherapy has received scant attention. We carried out a pilot study to explore the effects of AET in combination with neoadjuvant doxorubicin-cyclophosphamide (AC+AET), relative to AC alone, on: (i) host physiology [exercise capacity (VO2 peak), brachial artery flow-mediated dilation (BA-FMD)], (ii) host-related circulating factors [circulating endothelial progenitor cells (CEP) cytokines and angiogenic factors (CAF)], and (iii) tumor phenotype [tumor blood flow ((15)O-water PET), tissue markers (hypoxia and proliferation), and gene expression] in 20 women with operable breast cancer. AET consisted of three supervised cycle ergometry sessions/week at 60% to 100% of VO2 peak, 30 to 45 min/session, for 12 weeks. There was significant time × group interactions for VO2 peak and BA-FMD, favoring the AC+AET group (P < 0.001 and P = 0.07, respectively). These changes were accompanied by significant time × group interactions in CEPs and select CAFs [placenta growth factor, interleukin (IL)-1β, and IL-2], also favoring the AC+AET group (P < 0.05). (15)O-water positron emission tomography (PET) imaging revealed a 38% decrease in tumor blood flow in the AC+AET group. There were no differences in any tumor tissue markers (P > 0.05). Whole-genome microarray tumor analysis revealed significant differential modulation of 57 pathways (P < 0.01), including many that converge on NF-κB. Data from this exploratory study provide initial evidence that AET can modulate several host- and tumor-related pathways during standard chemotherapy. The biologic and clinical implications remain to be determined.

  16. Platelet–Lymphocyte Ratio as a Useful Predictor of the Therapeutic Effect of Neoadjuvant Chemotherapy in Breast Cancer

    PubMed Central

    Asano, Yuka; Kashiwagi, Shinichiro; Noda, Satoru; Kawajiri, Hidemi; Takashima, Tsutomu; Ohsawa, Masahiko; Kitagawa, Seiichi

    2016-01-01

    Background The peripheral blood platelet–lymphocyte ratio (PLR) has been proposed as an indicator for evaluating systemic inflammatory responses in cancer-bearing patients. While some reports suggest a correlation between PLR and prognosis, few studies have examined the relationship between PLR and sensitivity to chemotherapy. We conducted a study on whether PLR could serve as a predictor of the therapeutic effects of neoadjuvant chemotherapy (NAC). Methods PLR was evaluated in 177 breast cancer patients treated with the NAC 5-fluorouracil, epirubicin and cyclophosphamide, followed by weekly paclitaxel and subsequent curative surgery. The correlation between PLR and prognosis, and between PLR and the efficacy of NAC, were evaluated retrospectively. Results The low PLR group had significantly more patients > 56 years old (p = 0.001) and postmenopausal women (p = 0.001) than the high PLR group. The low PLR group also had a higher pathologic complete response (pCR) rate (p = 0.019). On examining the correlation with prognosis, the low-PLR group was found to have significantly longer disease-free survival (p = 0.004) and overall survival (p = 0.032) than the high PLR group. Multivariate analysis also revealed that lymph node metastasis (p = 0.043, hazard ratio = 4.40) and a high PLR (p = 0.005, hazard ratio = 2.84) were independent, unfavorable prognostic factors. Conclusions For patients with breast cancer treated with NAC, a low PLR indicated high chemotherapy sensitivity, suggesting that PLR could serve as a predictive marker of the therapeutic effect of NAC. PMID:27472762

  17. Effect of Postmastectomy Radiotherapy in Patients <35 Years Old With Stage II-III Breast Cancer Treated With Doxorubicin-Based Neoadjuvant Chemotherapy and Mastectomy

    SciTech Connect

    Garg, Amit K.; Oh, Julia L. Oswald, Mary Jane; Huang, Eugene; Strom, Eric A.; Perkins, George H.; Woodward, Wendy A.; Yu, T. Kuan; Tereffe, Welela; Meric-Bernstam, Funda; Hahn, Karin; Buchholz, Thomas A.

    2007-12-01

    Purpose: Postmastectomy radiotherapy (PMRT) improves locoregional control (LRC) in patients with high-risk features after mastectomy. Young age continues to evolve as a potentially important risk factor. The objective of this study was to assess the benefits of PMRT in patients <35 years old treated with doxorubicin-based neoadjuvant chemotherapy for Stage II-III breast cancer. Patients and Methods: We retrospectively analyzed 107 consecutive breast cancer patients <35 years old with Stage IIA-IIIC disease treated at our institution with doxorubicin-based neoadjuvant chemotherapy and mastectomy, with or without PMRT. The treatment groups were compared in terms of LRC and overall survival. Results: Despite more advanced disease stages, the patients who received PMRT (n = 80) had greater rates of LRC (5-year rate, 88% vs. 63%, p = 0.001) and better overall survival (5-year rate, 67% vs. 48%, p = 0.03) than patients who did not receive PMRT (n = 27). Conclusion: Among breast cancer patients <35 years old at diagnosis, the use of PMRT after doxorubicin-based neoadjuvant chemotherapy and mastectomy led to a statistically greater rate of LRC and overall survival compared with patients without PMRT. The benefit seen for PMRT in young patients provides valuable data to better tailor adjuvant, age-specific treatment decisions after mastectomy.

  18. 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

  19. 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

  20. 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

  1. Sentinel lymph node biopsy and neoadjuvant chemotherapy in breast cancer patients.

    PubMed

    Benson, John R; Jatoi, Ismail

    2014-03-01

    Patient selection and timing of sentinel lymph node (SLN) in the context of primary chemotherapy continues to evolve; there is some evidence that primary chemotherapy may modify lymphatic drainage patterns and cause differential downstaging between SLNs and non-SLNs. SLN biopsy undertaken prior to chemotherapy will minimize the risk of a false-negative result, may allow more accurate initial staging and provides important information on prognostication which can guide decisions about adjuvant radiotherapy. However, quantification of regional metastatic load is incomplete and some advocate SLN biopsy after primary chemotherapy to take advantage of nodal downstaging and avoidance of axillary dissection in up to 40% of patients. Initial reports on false-negative rates for SLN biopsy after primary chemotherapy in patients who had proven axillary node metastases at presentation based on needle core biopsy were relatively high and a cause for clinical concern. However, more recent data suggest that SLN biopsy is as accurate when performed post- as pre-neochemotherapy and current practice incorporates both approaches.

  2. Effectiveness of evaluating tumor vascularization using 3D power Doppler ultrasound with high-definition flow technology in the prediction of the response to neoadjuvant chemotherapy for T2 breast cancer: a preliminary report

    NASA Astrophysics Data System (ADS)

    Shia, Wei-Chung; Chen, Dar-Ren; Huang, Yu-Len; Wu, Hwa-Koon; Kuo, Shou-Jen

    2015-10-01

    The aim of this study was to evaluate the effectiveness of advanced ultrasound (US) imaging of vascular flow and morphological features in the prediction of a pathologic complete response (pCR) and a partial response (PR) to neoadjuvant chemotherapy for T2 breast cancer. Twenty-nine consecutive patients with T2 breast cancer treated with six courses of anthracycline-based neoadjuvant chemotherapy were enrolled. Three-dimensional (3D) power Doppler US with high-definition flow (HDF) technology was used to investigate the blood flow in and morphological features of the tumors. Six vascularity quantization features, three morphological features, and two vascular direction features were selected and extracted from the US images. A support vector machine was used to evaluate the changes in vascularity after neoadjuvant chemotherapy, and pCR and PR were predicted on the basis of these changes. The most accurate prediction of pCR was achieved after the first chemotherapy cycle, with an accuracy of 93.1% and a specificity of 85.5%, while that of a PR was achieved after the second cycle, with an accuracy of 79.31% and a specificity of 72.22%. Vascularity data can be useful to predict the effects of neoadjuvant chemotherapy. Determination of changes in vascularity after neoadjuvant chemotherapy using 3D power Doppler US with HDF can generate accurate predictions of the patient response, facilitating early decision-making.

  3. Histologic changes associated with neoadjuvant chemotherapy are predictive of nodal metastases in patients with high-risk prostate cancer.

    PubMed

    O'Brien, Catherine; True, Lawrence D; Higano, Celestia S; Rademacher, Brooks L S; Garzotto, Mark; Beer, Tomasz M

    2010-04-01

    Clinical trials are evaluating the effect of neoadjuvant chemotherapy on men with high-risk prostate cancer. Little is known about the clinical significance of postchemotherapy tumor histopathologic features. We assessed the prognostic and predictive value of histologic features (intraductal carcinoma, vacuolated cell morphologic features, inconspicuous glands, cribriform architecture, and inconspicuous cancer cells) observed in 50 high-risk prostate cancers treated with preprostatectomy docetaxel and mitoxantrone. At a median follow-up of 65 months, the overall relapse-free survival (RFS) rates at 2 and 5 years were 65% and 49%, respectively. In univariate analyses (using the Kaplan-Meier method and log-rank tests), intraductal (P = .001) and cribriform (P = .014) histologic features were associated with shorter RFS. In multivariate analyses, using the Cox proportional hazards regression, baseline prostate-specific antigen (P = .004), lymph node metastases (P < .001), and cribriform histologic features (P = .007) were associated with shorter RFS. In multivariable logistic regression analysis, only intraductal pattern (P = .007) predicted lymph node metastases. Intraductal and cribriform histologic features apparently predict postchemotherapy outcome.

  4. Role of vascular density and normalization in response to neoadjuvant bevacizumab and chemotherapy in breast cancer patients

    PubMed Central

    Tolaney, Sara M.; Boucher, Yves; Duda, Dan G.; Martin, John D.; Seano, Giorgio; Ancukiewicz, Marek; Barry, William T.; Goel, Shom; Lahdenrata, Johanna; Isakoff, Steven J.; Yeh, Eren D.; Jain, Saloni R.; Golshan, Mehra; Brock, Jane; Snuderl, Matija; Winer, Eric P.; Krop, Ian E.; Jain, Rakesh K.

    2015-01-01

    Preoperative bevacizumab and chemotherapy may benefit a subset of breast cancer (BC) patients. To explore potential mechanisms of this benefit, we conducted a phase II study of neoadjuvant bevacizumab (single dose) followed by combined bevacizumab and adriamycin/cyclophosphamide/paclitaxel chemotherapy in HER2-negative BC. The regimen was well-tolerated and showed a higher rate of pathologic complete response (pCR) in triple-negative (TN)BC (11/21 patients or 52%, [95% confidence interval (CI): 30,74]) than in hormone receptor-positive (HR)BC [5/78 patients or 6% (95%CI: 2,14)]. Within the HRBCs, basal-like subtype was significantly associated with pCR (P = 0.007; Fisher exact test). We assessed interstitial fluid pressure (IFP) and tissue biopsies before and after bevacizumab monotherapy and circulating plasma biomarkers at baseline and before and after combination therapy. Bevacizumab alone lowered IFP, but to a smaller extent than previously observed in other tumor types. Pathologic response to therapy correlated with sVEGFR1 postbevacizumab alone in TNBC (Spearman correlation 0.610, P = 0.0033) and pretreatment microvascular density (MVD) in all patients (Spearman correlation 0.465, P = 0.0005). Moreover, increased pericyte-covered MVD, a marker of extent of vascular normalization, after bevacizumab monotherapy was associated with improved pathologic response to treatment, especially in patients with a high pretreatment MVD. These data suggest that bevacizumab prunes vessels while normalizing those remaining, and thus is beneficial only when sufficient numbers of vessels are initially present. This study implicates pretreatment MVD as a potential predictive biomarker of response to bevacizumab in BC and suggests that new therapies are needed to normalize vessels without pruning. PMID:26578779

  5. Reproducibility of Residual Cancer Burden For Prognostic Assessment of Breast Cancer After Neoadjuvant Chemotherapy

    PubMed Central

    Peintinger, Florentia; Sinn, Bruno; Hatzis, Christos; Albarracin, Constance; Downs-Kelly, Erinn; Morkowski, Jerzy; Gould, Rebekah; Symmans, W. Fraser

    2016-01-01

    The residual cancer burden index was developed as a method to quantify residual disease ranging from pathological complete response to extensive residual disease. The aim of this study was to evaluate the inter-pathologist reproducibility in the residual cancer burden index score and category, and in their long-term prognostic utility. Pathology slides and pathology reports from 100 cases selected at random from patients treated in a randomized neoadjuvant trial were reviewed independently by five pathologists at M.D Anderson Cancer Center without prior coaching. Size of tumor bed, average percent overall tumor cellularity, average percent of the in situ cancer within the tumor bed, size of largest axillary metastasis and number of involved nodes were assessed separately by each pathologist and residual cancer burden categories were assigned to each case following calculation of the numerical residual cancer burden index score. Inter-pathologist agreement in the assessment of the continuous residual cancer burden score and its components and agreement in the residual cancer burden category assignments were evaluated and analyzed. The overall concordance correlation coefficient for the agreement in residual cancer burden score among all five pathologists was 0.931 (95% Confidence Interval 0.908 – 0.949). Overall accuracy of the residual cancer burden score determination was 0.989. The kappa coefficient for overall agreement in the residual cancer burden category assignments was 0.583 (95% Confidence Interval 0.539 – 0.626), indicating good overall inter-pathologist agreement. The metastatic component of the residual cancer burden index showed stronger concordance between pathologists (overall concordance correlation coefficient = 0.980; 95% Confidence Interval 0.954 – 0.992), than the primary component (overall concordance correlation coefficient = 0.795; 95% Confidence Interval 0.716 – 0.853). At a median follow-up of 12 years residual cancer burden

  6. Microvessel density and endothelial cell proliferation levels in colorectal liver metastases from patients given neo-adjuvant cytotoxic chemotherapy and bevacizumab.

    PubMed

    Eefsen, Rikke Løvendahl; Engelholm, Lars; Willemoe, Gro L; Van den Eynden, Gert G; Laerum, Ole Didrik; Christensen, Ib Jarle; Rolff, Hans Christian; Høyer-Hansen, Gunilla; Osterlind, Kell; Vainer, Ben; Illemann, Martin

    2016-04-01

    The treatment of patients with colorectal liver metastasis has improved significantly and first line therapy is often combined chemotherapy and bevacizumab, although it is unknown who responds to this regimen. Colorectal liver metastases grow in different histological growth patterns showing differences in angiogenesis. To identify possible response markers, histological markers of angiogenesis were assessed. Patients who underwent resection of colorectal liver metastasis at Rigshospitalet, Copenhagen, Denmark from 2007 to 2011 were included (n = 254) including untreated and patients treated with chemotherapy or chemotherapy plus bevacizumab. The resected liver metastases were characterised with respect to growth pattern, endothelial and tumour cell proliferation as well as microvessel density and tumour regression. Tumour regression grade of liver metastases differed significantly between untreated/chemotherapy treated patients in comparison to chemotherapy plus bevacizumab treated patients (both p < 0.0001). Microvessel density was decreased in liver metastases from patients treated with bevacizumab in comparison to those from untreated/chemotherapy-treated patients (p = 0.006/p = 0.002). Tumour cell proliferation assessed by Ki67 expression correlated to a shorter recurrence free survival in the total patient cohort. In conclusion, liver metastases from patients treated with neo-adjuvant chemotherapy and bevacizumab had significantly lower microvessel densities and tumour regression grades when compared to liver metastases from untreated or chemotherapy treated patients. This may indicate that bevacizumab treatment results in altered vascular biology and tumour viability, with possible tumour reducing effect.

  7. Accuracy of MRI for prediction of response to neo-adjuvant chemotherapy in triple negative breast cancer compared to other subtypes of breast cancer

    PubMed Central

    Bansal, Gaurav J; Santosh, Divya

    2016-01-01

    Purpose: The aim of this study was to compare the accuracy of magnetic resonance imaging (MRI) for the prediction of response to neo-adjuvant chemotherapy in triple negative (TN) breast cancer, with respect to other subtypes. Materials and Methods: There were a total of 1610 breast cancers diagnosed between March 2009 and August 2014, out of which 82 patients underwent MRI before and after neo-adjuvant chemotherapy but just before surgery. TN cancers were analyzed with respect to others subtypes. Accuracy of MRI for prediction of pathological complete response was compared between different subtypes by obtaining receiver operating characteristic (ROC) curves. The Statistical Package for the Social Sciences version 21 was used for all data analysis, with P value of 0.05 as statistically significant. Results: Out of 82 patients, 29 were luminal (HR+/HER2−), 23 were TN (HR−, HER2−), 11 were HER2 positive (HR−, HER2+), and 19 were of hybrid subtype (HR+/HER2+). TN cancers presented as masses on the pre-chemotherapy MRI scan, were grade 3 on histopathology, and showed concentric shrinkage following chemotherapy. TN cancers were more likely to have both imaging and pathological complete response following chemotherapy (P = 0.055) in contrast to luminal cancers, which show residual cancer. ROC curves were constructed for the prediction of pathological complete response with MRI. For the TN subgroup, MR had a sensitivity of 0.745 and specificity of 0.700 (P = 0.035), with an area under curve of 0.745 (95% confidence interval: 0.526–0.965), which was significantly better compared to other subtypes. Conclusion: TN breast cancers present as masses and show concentric shrinkage following chemotherapy. MRI is most accurate in predicting response to chemotherapy in the TN group, compared to others subtypes. MRI underestimates residual disease in luminal cancers. PMID:28104942

  8. The calpain system is associated with survival of breast cancer patients with large but operable inflammatory and non-inflammatory tumours treated with neoadjuvant chemotherapy.

    PubMed

    Storr, Sarah J; Zhang, Siwei; Perren, Tim; Lansdown, Mark; Fatayer, Hiba; Sharma, Nisha; Gahlaut, Renu; Shaaban, Abeer; Martin, Stewart G

    2016-07-26

    The calpains are a family of intracellular cysteine proteases that function in a variety of important cellular functions, including cell signalling, motility, apoptosis and survival. In early invasive breast cancer expression of calpain-1, calpain-2 and their inhibitor, calpastatin, have been associated with clinical outcome and clinicopathological factors.The expression of calpain-1, calpain-2 and calpastatin was determined using immunohistochemistry on core biopsy samples, in a cohort of large but operable inflammatory and non-inflammatory primary breast cancer patients treated with neoadjuvant chemotherapy. Information on treatment and prognostic variables together with long-term clinical follow-up was available for these patients. Diagnostic pre-chemotherapy core biopsy samples and surgically excised specimens were available for analysis.Expression of calpastatin, calpain-1 or calpain-2 in the core biopsies was not associated with breast cancer specific survival in the total patient cohort; however, in patients with non-inflammatory breast cancer, high calpastatin expression was significantly associated with adverse breast cancer-specific survival (P=0.035), as was low calpain-2 expression (P=0.031). Low calpastatin expression was significantly associated with adverse breast cancer-specific survival of the inflammatory breast cancer patients (P=0.020), as was low calpain-1 expression (P=0.003).In conclusion, high calpain-2 and low calpastatin expression is associated with improved breast cancer-specific survival in non-inflammatory large but operable primary breast cancer treated with neoadjuvant chemotherapy. In inflammatory cases, high calpain-1 and high calpastatin expression is associated with improved breast cancer-specific survival. Determining the expression of these proteins may be of clinical relevance. Further validation, in multi-centre cohorts of breast cancer patients treated with neoadjuvant chemotherapy, is warranted.

  9. Surgical outcome after docetaxel-based neoadjuvant chemotherapy in locally-advanced gastric cancer

    PubMed Central

    Biffi, Roberto; Fazio, Nicola; Luca, Fabrizio; Chiappa, Antonio; Andreoni, Bruno; Zampino, Maria Giulia; Roth, Arnaud; Schuller, Jan Christian; Fiori, Giancarla; Orsi, Franco; Bonomo, Guido; Crosta, Cristiano; Huber, Olivier

    2010-01-01

    AIM: To investigate feasibility, morbidity and surgical mortality of a docetaxel-based chemotherapy regimen randomly administered before or after gastrectomy in patients suffering from locally-advanced resectable gastric cancer. METHODS: Patients suffering from locally-advanced (T3-4 any N M0 or any T N1-3 M0) gastric carcinoma, staged with endoscopic ultrasound, bone scan, computed tomography, and laparoscopy, were assigned to receive four 21 d/cycles of TCF (docetaxel 75 mg/m2 day 1, cisplatin 75 mg/m2 day 1, and fluorouracil 300 mg/m2 per day for days 1-14), either before (Arm A) or after (Arm B) gastrectomy. Operative morbidity, overall mortality, and severe adverse events were compared by intention-to-treat analysis. RESULTS: From November 1999 to November 2005, 70 patients were treated. After preoperative TCF (Arm A), thirty-two (94%) resections were performed, 85% of which were R0. Pathological response was complete in 4 patients (11.7%), and partial in 18 (55%). No surgical mortality and 28.5% morbidity rate were observed, similar to those of immediate surgery arm (P = 0.86). Serious chemotherapy adverse events tended to be more frequent in arm B (23% vs 11%, P = 0.07), with a single death per arm. CONCLUSION: Surgery following docetaxel-based chemotherapy was safe and with similar morbidity to immediate surgery in patients with locally-advanced resectable gastric carcinoma. PMID:20143466

  10. 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

  11. Reproducibility of residual cancer burden for prognostic assessment of breast cancer after neoadjuvant chemotherapy.

    PubMed

    Peintinger, Florentia; Sinn, Bruno; Hatzis, Christos; Albarracin, Constance; Downs-Kelly, Erinn; Morkowski, Jerzy; Gould, Rebekah; Symmans, W Fraser

    2015-07-01

    The residual cancer burden index was developed as a method to quantify residual disease ranging from pathological complete response to extensive residual disease. The aim of this study was to evaluate the inter-Pathologist reproducibility in the residual cancer burden index score and category, and in their long-term prognostic utility. Pathology slides and pathology reports of 100 cases from patients treated in a randomized neoadjuvant trial were reviewed independently by five pathologists. The size of tumor bed, average percent overall tumor cellularity, average percent of the in situ cancer within the tumor bed, size of largest axillary metastasis, and number of involved nodes were assessed separately by each pathologist and residual cancer burden categories were assigned to each case following calculation of the numerical residual cancer burden index score. Inter-Pathologist agreement in the assessment of the continuous residual cancer burden score and its components and agreement in the residual cancer burden category assignments were analyzed. The overall concordance correlation coefficient for the agreement in residual cancer burden score among pathologists was 0.931 (95% confidence interval (CI) 0.908-0.949). Overall accuracy of the residual cancer burden score determination was 0.989. The kappa coefficient for overall agreement in the residual cancer burden category assignments was 0.583 (95% CI 0.539-0.626). The metastatic component of the residual cancer burden index showed stronger concordance between pathologists (overall concordance correlation coefficient=0.980; 95% CI 0.954-0.992), than the primary component (overall concordance correlation coefficient=0.795; 95% CI 0.716-0.853). At a median follow-up of 12 years residual cancer burden determined by each of the pathologists had the same prognostic accuracy for distant recurrence-free and survival (overall concordance correlation coefficient=0.995; 95% CI 0.989-0.998). Residual cancer burden

  12. 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

  13. Background Parenchymal Enhancement of the Contralateral Normal Breast: Association with Tumor Response in Breast Cancer Patients Receiving Neoadjuvant Chemotherapy1

    PubMed Central

    Chen, Jeon Hor; Yu, Hon J.; Hsu, Christine; Mehta, Rita S.; Carpenter, Philip M.; Su, Min Ying

    2015-01-01

    PURPOSE: This study investigated the association between background parenchymal enhancement (BPE) and pathologic response to neoadjuvant chemotherapy (NAC). METHODS: A total of 46 patients diagnosed with invasive breast cancer were analyzed. Each patient had three magnetic resonance imaging (MRI) studies, one pre-treatment and two follow-up (F/U) MRI studies. BPE was measured as the averaged enhancement of the whole fibroglandular tissues. The pre-treatment BPE and the changes in the F/U MRI were compared between patients achieving pathologic complete response (pCR) versus those not. Subgroup analyses based on age, estrogen receptor (ER), and human epidermal growth factor receptor 2 (HER2) status of their cancers were also performed. RESULTS: The pre-treatment BPE was higher in the pCR group than that in the non-pCR group. Compared to baseline, BPE at F/U-1 was significantly decreased in the pCR group but not in the non-pCR group. In subgroup analysis based on age, these results were seen only in the younger group (< 55 years old), not in the older group (≥ 55 years old). Older patients had a significantly lower pre-treatment BPE than younger patients. In analysis based on molecular biomarkers, a significantly decreased BPE at F/U-1 was only found in the ER-negative pCR group but not in the non-pCR, nor in the ER-positive groups. CONCLUSIONS: A higher pre-treatment BPE showing a significant decrease early after starting NAC was related to pCR in pre/peri-menopausal patients. PMID:26055178

  14. Dynamic contrast-enhanced magnetic resonance imaging for prediction of response to neoadjuvant chemotherapy in breast cancer

    NASA Astrophysics Data System (ADS)

    Fu, Juzhong; Fan, Ming; Zheng, Bin; Shao, Guoliang; Zhang, Juan; Li, Lihua

    2016-03-01

    Breast cancer is the second leading cause of women death in the United States. Currently, Neoadjuvant Chemotherapy (NAC) has become standard treatment paradigms for breast cancer patients. Therefore, it is important to find a reliable non-invasive assessment and prediction method which can evaluate and predict the response of NAC on breast cancer. The Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) approach can reflect dynamic distribution of contrast agent in tumor vessels, providing important basis for clinical diagnosis. In this study, the efficacy of DCE-MRI on evaluation and prediction of response to NAC in breast cancer was investigated. To this end, fifty-seven cases of malignant breast cancers with MRI examination both before and after two cycle of NAC were analyzed. After pre-processing approach for segmenting breast lesions and background regions, 126-dimensional imaging features were extracted from DCE-MRI. Statistical analyses were then performed to evaluate the associations between the extracted DCE-MRI features and the response to NAC. Specifically, pairwise t test was used to calculate differences of imaging features between MRI examinations before-and-after NAC. Moreover, the associations of these image features with response to NAC were assessed using logistic regression. Significant association are found between response to NAC and the features of lesion morphology and background parenchymal enhancement, especially the feature of background enhancement in normal side of breast (P=0.011). Our study indicate that DCE-MRI features can provide candidate imaging markers to predict response of NAC in breast cancer.

  15. Locoregional Recurrence of Breast Cancer in Patients Treated With Breast Conservation Surgery and Radiotherapy Following Neoadjuvant Chemotherapy

    SciTech Connect

    Min, Sun Young; Lee, Seung Ju; Shin, Kyung Hwan; Park, In Hae; Jung, So-Youn; Lee, Keun Seok; Ro, Jungsil; Lee, Seeyoun; Kim, Seok Won; Kim, Tae Hyun; Kang, Han-Sung; Cho, Kwan Ho

    2011-12-01

    Purpose: Breast conservation surgery (BCS) and radiotherapy (RT) following neoadjuvant chemotherapy (NCT) have been linked with high locoregional recurrence (LRR) rates and ipsilateral breast tumor recurrence (IBTR) rates. The purpose of this study was to analyze clinical outcomes in patients who exhibited LRR and IBTR after being treated by BCS and RT following NCT. Methods and Materials: In total, 251 breast cancer patients treated with BCS and RT following NCT between 2001 and 2006 were included. All patients had been shown to be clinically node-positive. Clinical stage at diagnosis (2003 AJCC) was II in 68% of patients and III in 32% of patients. Of those, 50%, 35%, and 15% of patients received anthracycline-based, taxane-based, and combined anthracycline-taxane NCT, respectively. All patients received RT. Results: During follow-up (median, 55 months), 26 (10%) patients had LRR, 19 of these patients had IBTR. Five-year actuarial rates of IBTR-free and LRR-free survival were 91% and 89%, respectively. In multivariate analyses, lack of hormone suppression therapy was found to increase both LRR and IBTR rates. Hazard ratios were 7.99 (p < 0.0001) and 4.22 (p = 0.004), respectively. Additionally, pathology stage N2 to N3 increased LRR rate (hazard ratio, 4.22; p = 0.004), and clinical AJCC stage III IBTR rate (hazard ratio, 9.05; p = 0.034). Achievement of pathological complete response and presence of multifocal tumors did not affect LRR or IBTR. Conclusions: In patients with locally advanced disease, who were clinically node-positive at presentation, BCS after NCT resulted in acceptably low rates of IBTR and LRR. Mastectomy should be considered as an option in patients who present with clinical stage III tumors or who are not treated with adjuvant hormone suppression therapy, because they exhibit high IBTR rates after NCT and BCS.

  16. Quality of pathologic response and surgery correlate with survival for completely resected bladder cancer following neoadjuvant chemotherapy

    PubMed Central

    Sonpavde, Guru; Goldman, Bryan H.; Speights, V.O.; Lerner, Seth P.; Wood, David P.; Vogelzang, Nicholas J.; Trump, Donald L.; Natale, Ronald B.; Grossman, H. Barton; Crawford, E. David

    2010-01-01

    BACKGROUND In a retrospective study of SWOG-S8710/INT-0080 (radical cystectomy [RC] alone vs 3 cycles of MVAC neoadjuvant chemotherapy [NC] before RC for bladder cancer), factors associated with improved overall survival (OS) included pathologic complete response (pCR) defined as P0, treatment with NC, completion of RC with negative margins and ≥10 pelvic lymph nodes (LNs) removed. METHODS We used stratified Cox regression to retrospectively study the association of quality of pathologic response post-RC with OS in the subset of S8710 patients that received NC and RC with negative margins. RESULTS Of 154 patients who received NC, 68 (44.2%) were

  17. Stent placement above the sphincter of Oddi permits implementation of neoadjuvant chemotherapy in patients with initially unresectable Klatskin tumor

    PubMed Central

    Kubota, Kensuke; Hasegawa, Sho; Iwasaki, Akito; Sato, Takamitsu; Fujita, Yuji; Hosono, Kunihiro; Nakajima, Atsushi; Mori, Ryutaro; Matsuyama, Ryusei; Endo, Itaru

    2016-01-01

    Background and study aims: Neoadjuvant chemotherapy (NAC) may lead to a successful margin-negative resection in patients with initially unresectable locally advanced Klatskin tumor (IULAKT). Use of removable plastic stents is preferable for the safe implementation of NAC in patients with IULAKT to reduce the risk of recurrent cholangitis. Our aim was to evaluate the efficacy associated with the use of plastic stents placed across the stenosis and above the papilla (above stent) during NAC. Patients and methods: In this study, we stratified the patients into two groups chronologically with respect to the period of stent placement: above stent group (n = 17) and across stent group (n = 23) (plastic stent across the sphincter of Oddi). Results: The median stent patency period was 99 days in the above stent group and 31 days in the across stent group (P < 0.0001). The number of stents (P = 0.017) and the rate of emerging undrained cholangitis areas (P = 0.025) were significantly reduced in the above stent group than the counterpart. Regarding time to recurrent biliary obstruction, the above stent group had a longer duration than the across stent group (log rank test, P = 0.004). Length of hospital stay was significantly shorter for the above stent group than the across stent group (P = 0.0475). Multivariate analysis revealed that above stent placement (odds ratio = 33.638, P = 0.0048) was significantly associated with stent patency over a period of 90 days. Conclusions: Above stent placement should be considered for the relief of biliary obstruction and potentially reduces the cost for patients with IULAKT scheduled to receive NAC. PMID:27092322

  18. Loco-regional control after neo-adjuvant chemotherapy and conservative treatment for locally advanced breast cancer patients.

    PubMed

    Levy, Antonin; Borget, Isabelle; Bahri, Manel; Arnedos, Monica; Rivin, Eleonor; Vielh, Philippe; Balleyguier, Corinne; Rimareix, Françoise; Bourgier, Céline

    2014-01-01

    Breast-conserving treatment (BCT) has been validated for breast cancer patients receiving adjuvant chemotherapy. Our objective was to evaluate the difference in loco-regional recurrence (LRR) rates between BCT and mastectomy in patients receiving radiation therapy after neo-adjuvant chemotherapy (NCT). A retrospective data base was used to identify all patients with breast cancer undergoing NCT from 2002 to 2007. Patients with initial metastatic disease were excluded from this analysis. LRR was compared between those undergoing BCT and mastectomy. Individual variables associated with LRR were evaluated. Two hundred eighty-four patients were included, 111 (39%) underwent BCT and 173 (61%) mastectomy. Almost all patients (99%) in both groups received postoperative radiation. Pathologic complete response was seen in 37 patients, of which 28 underwent BCT (p < 0.001). Patients receiving mastectomy had more invasive lobular carcinoma (p = 0.007) and a higher American Joint Committee on Cancer (AJCC) stage (p < 0.001) at diagnosis than those with BCT. At a median follow-up of 6.3 years, the loco-regional control rate was 91% (95% CI: 86-94%). The 10-year LRR rate was similar in the BCT group (9.2% [95% CI: 4.9-16.7%]) and in the mastectomy group (10.7% [95% CI: 5.9-15.2%]; p = 0.8). Ten-year overall survival (OS) rates (63% [95% CI: 46-79%] in the BCT group; 60% [95% CI: 47-73%] in the mastectomy group, p = 0.8) were not statistically different between the two patient populations. Multivariate analysis showed that AJCC stage ≥ III (HR: 2.6; 95% CI: 1.2-5.8; p = 0.02), negative PR (HR: 6; 95% CI: 1.2-30.6, p = 0.03), and number of positive lymph nodes ≥3 (HR: 2.5; 95% CI: 1.1-5.9; p = 0.03) were independent predictors of LRR. Ten-year OS was similar in the BCT and in the mastectomy group (p = 0.1). The rate of LRR was low and did not significantly differ between the BCT and the mastectomy group after NCT. Randomized trials assessing whether mastectomy can be safely

  19. ERCC1 and telomere status in breast tumours treated with neoadjuvant chemotherapy and their association with patient prognosis

    PubMed Central

    Gay‐Bellile, Mathilde; Romero, Pierre; Cayre, Anne; Véronèse, Lauren; Privat, Maud; Singh, Shalini; Combes, Patricia; Kwiatkowski, Fabrice; Abrial, Catherine; Bignon, Yves‐Jean; Vago, Philippe; Penault‐Llorca, Frédérique

    2016-01-01

    Abstract Dysfunctional telomeres and DNA damage repair (DDR) play important roles in cancer progression. Studies have reported correlations between these factors and tumour aggressiveness and clinical outcome in breast cancer. We studied the characteristics of telomeres and expression of ERCC1, a protein involved in a number of DNA repair pathways and in telomere homeostasis, to assess their prognostic value, alone or in combination, in 90 residual breast tumours after treatment with neoadjuvant chemotherapy (NCT). ERCC1 status was investigated at different molecular levels (protein and gene expression and gene copy‐number variations) by immunohistochemistry, qRT‐PCR and quantitative multiplex fluorescent‐PCR (QMF‐PCR). A comprehensive analysis of telomere characteristics was performed using qPCR for telomere length and qRT‐PCR for telomerase (hTERT), tankyrase 1 (TNKS) and shelterin complex (TRF1, TRF2, POT1, TPP1, RAP1 and TIN2) gene expression. Short telomeres, high hTERT and TNKS expression and low ERCC1 protein expression were independently associated with worse survival outcome. Interestingly, ERCC1 gains and losses correlated with worse disease‐free (p = 0.026) and overall (p = 0.043) survival as compared to survival of patients with normal gene copy‐numbers. Unsupervised hierarchical clustering of all ERCC1 and telomere parameters identified four subgroups with distinct prognosis. In particular, a cluster combining low ERCC1, ERCC1 gene alterations, dysfunctional telomeres and high hTERT and a cluster with high TNKS and shelterin expression correlated with poor disease‐free (HR= 5.41, p= 0.0044) and overall survival (HR= 6.01, p= 0.0023) irrespective of tumour stage and grade. This comprehensive study demonstrates that telomere dysfunction and DDR can contribute synergistically to tumour progression and chemoresistance. These parameters are predictors of clinical outcome in breast cancer patients treated with NCT and could be useful

  20. High TFAP2C/low CD44 expression is associated with an increased rate of pathologic complete response following neoadjuvant chemotherapy in breast cancer

    PubMed Central

    Spanheimer, Philip M.; Askeland, Ryan W.; Kulak, Mikhail V.; Wu, Tong; Weigel, Ronald J.

    2013-01-01

    Background In luminal breast cancer cell lines, TFAP2C regulates expression of key genes in the estrogen receptor–associated cluster and represses basal-associated genes including CD44. We examined the effect of TFAP2C overexpression in a basal cell line and characterized the expression of TFAP2C and CD44 in breast cancer specimens to determine if expression was associated with clinical response. Methods MDA-MB-231 breast cancer cells were treated with a TFAP2C-containing plasmid and evaluated for effects on CD44 expression. Pretreatment biopsy cores from patients receiving neoadjuvant chemotherapy for breast cancer were evaluated for TFAP2A, p53, TFAP2C, and CD44 expression by immunohistochemistry. Results Overexpression of TFAP2C in MDA-MB-231 cells resulted in decreased expression of CD44 mRNA and protein, P< 0.05. A pathologic complete response (pCR) following neoadjuvant chemotherapy was achieved in 17% of patients (4/23). Average expression for TFAP2C by immunohistochemistry in patients with a pCR was 93%, compared with 46% in patients with residual disease, P= 0.016; and in tumors that stained at ≥80% for TFAP2C, 4 of 9 (44%) achieved pCR, compared with 0 of 14 below 80%, P= 0.01. Additionally, in tumors that stained ≤80% for CD44, 4 of 10 (40%) achieved pCR, compared with 0 of 13 >80%, P = 0.02. In tumors that stained high for TFAP2C (≥80%) and low for CD44 (≥80%), 4 of 7 (57%) achieved pCR, compared with 0 of 16 in all other groups (P= 0.004). Conclusions TFAP2C repressed CD44 expression in basal-derived breast cancer. In primary breast cancer specimens, high TFAP2C and low CD44 expression were associated with pCR after neoadjuvant chemotherapy and could be predictive of tumors that have improved response to neoadjuvant chemotherapy. PMID:23764310

  1. Impact of neoadjuvant single or dual HER2 inhibition and chemotherapy backbone upon pathological complete response in operable and locally advanced breast cancer: Sensitivity analysis of randomized trials.

    PubMed

    Bria, Emilio; Carbognin, Luisa; Furlanetto, Jenny; Pilotto, Sara; Bonomi, Maria; Guarneri, Valentina; Vicentini, Cecilia; Brunelli, Matteo; Nortilli, Rolando; Pellini, Francesca; Sperduti, Isabella; Giannarelli, Diana; Pollini, Giovanni Paolo; Conte, Pierfranco; Tortora, Giampaolo

    2014-08-01

    The role of the dual HER2 inhibition, and the best chemotherapy backbone for neoadjuvant chemotherapy still represent an issue for clinical practice. A literature-based meta-analysis exploring single versus dual HER2 inhibition in terms of pathological complete response (pCR, breast plus axilla) rate and testing the interaction according to the chemotherapy (anthracyclines-taxanes or taxanes) was conducted. In addition, an event-based pooled analysis by extracting activity and safety events and deriving 95% confidence intervals (CI) was accomplished. Fourteen trials (4149 patients) were identified, with 6 trials (1820 patients) included in the meta-analysis and 31 arms (14 trials, 3580 patients) in the event-based pooled analysis. The dual HER2 inhibition significantly improves pCR rate, in the range of 16-19%, regardless of the chemotherapy backbone (relative risk 1.37, 95% CI 1.23-1.53, p<0.0001); pCR was significantly higher in the hormonal receptor negative population, regardless of the HER2 inhibition and type of chemotherapy. pCR and the rate of breast conserving surgery was higher when anthracyclines were added to taxanes, regardless of the HER2 inhibition. Severe neutropenia was higher with the addition of anthracyclines to taxanes, with an absolute difference of 19.7%, despite no differences in febrile neutropenia. While no significant differences according to the HER2 inhibition were found in terms of cardiotoxicity, a slightly difference for grade 3-4 (1.2%) against the addition of anthracyclines was calculated. The dual HER2 inhibition for the neoadjuvant treatment of HER2-positive breast cancer significantly increases pCR; the combination of anthracyclines, taxanes and anti-Her2 agents should be currently considered the standard of care.

  2. 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.

  3. 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.

  4. [A case of bladder cancer producing granulocyte colony-stimulating factor and interleukin-6 causing respiratory failure treated with neoadjuvant systemic chemotherapy along with sivelestat].

    PubMed

    Matsuzaki, Kyosuke; Okumi, Masayoshi; Kishimoto, Nozomu; Yazawa, Koji; Miyagawa, Yasushi; Uchida, Kinya; Nonomura, Norio

    2013-07-01

    A 67-year-old man visited an urological clinic with a chief complaint of urination pain. Cystourethroscopy and magnetic resonance imaging (MRI) examination revealed a bladder tumor (cT3bN0M0). Marked leukocytosis and respiratory distress with pleural effusion appeared. Pulse steroid therapy improved the general condition partially. The patient was sent to our hospital for further examination. Serum granulocyte colony-stimulating factor (G-CSF) and interleukin-6 (IL-6) were high and the pathological findings of bladder tumor obtained by transurethral resection (TUR) revealed an urothelial carcinoma that produced G-CSF and IL-6. Neoadjuvant systemic chemotherapy was performed along with use of steroid and sivelestat, which ameliorated the respiratory distress. After three courses of systemic chemotherapy, serum G-CSF and IL-6 normalized and cystoprostatectomy was performed. The patient has been in good health at 20 months after the surgery with no evidence of recurrence.

  5. Dihydropyrimidine dehydrogenase mutation in neoadjuvant chemotherapy in head and neck cancers: Myth or reality?

    PubMed Central

    Patil, Vijay M.; Noronha, Vanita; Joshi, Amit; Zanwar, Saurabh; Ramaswamy, Anant; Arya, Supreeta; Mahajan, Abhishek; Bhattacharjee, Atanu; Prabhash, Kumar

    2016-01-01

    Purpose: The docetaxel, 5-fluorouracil (5-FU), and cisplatin (TPF) regimen in India is associated with high percentages of Grade 3–4 toxicity. This analysis was planned to evaluate the incidence of dihydropyrimidine dehydrogenase (DPD) mutation in patients with severe gastrointestinal toxicity, to assess whether the mutation could be predicted by a set of clinical criteria and whether it has any impact on postneoadjuvant chemotherapy response. Methods: All consecutive patients who received TPF regimen in head and neck cancers between January 2015 and April 2015 were selected. Patients who had predefined set of toxicities in Cycle 1 were selected for DPD mutation testing. Depending on the results, C2 doses were modified. Postcompletion of two cycles, patients underwent radiological response assessment. Descriptive statistics has been performed. The normally distributed continuous variables were compared by unpaired Student's t-test, whereas variables which were not normally distributed by Wilcoxon sum rank test. For noncontinuous variables, comparison was performed by Fisher's exact test. Results: Out of 34 patients, who received TPF, 12 were selected for DPD testing, and 11 (32.4%, 95% confidence interval [95% CI]: 19.1–49.3%) had DPD mutation. The predictive accuracy of the criteria for the tested DPD mutations was 81.3% (95% CI: 62.1–100%). Of the 11 DPD mutation positive patients, except for one patient, all others received the second cycle of TPF. The dose adjustments done in 5-FU were 50% dose reduction in 9 patients and no dose reduction in one patient. The response rate in DPD mutated patients was 27.3% (3/11) and that in DPD nonmutated/nontested was 39.1% (9/23) (P = 0.70). Conclusion: In this small study, it seems that the incidence of DPD mutation is more common in Indian then it's in the Caucasian population. Clinical toxicity criteria can accurately predict for DPD mutation. Postdose adjustments of 5-FU from C2 onward, TPF can safely be delivered

  6. Patterns of local-regional management following neoadjuvant chemotherapy in breast cancer: Results from ACOSOG Z1071 (Alliance)

    PubMed Central

    Haffty, Bruce G.; McCall, Linda M.; Ballman, Karla V.; McLaughlin, Sarah; Jagsi, Reshma; Ollila, David W.; Hunt, Kelly K.; Buchholz, Thomas A.; Boughey, Judy C.

    2015-01-01

    Purpose/Objective(s) AXXXXX ZXXXX was a prospective trial evaluating the false negative rate of sentinel node (SLN) surgery after neoadjuvant chemotherapy (NAC) in breast cancer patients with initial node-positive disease. Radiation therapy (RT) decisions were at the discretion of treating physicians, providing an opportunity to evaluate variability in practice patterns following NAC. Methods and Materials Of 756 patients enrolled from July 2009 to June 2011, 685 met all eligibility requirements. Surgical approach, RT, ,and radiation field design were analyzed based on presenting clinical and pathologic factors. Results Of 401 node-positive patients, mastectomy was performed in 148 (36.9%), mastectomy with immediate reconstruction in 107 (26.7%), and breast-conserving surgery (BCS) in 146 (36.4%). Of the 284 pathologically node-negative patients, mastectomy was performed in 84 (29.6%), mastectomy with immediate reconstruction in 69 (24.3%) and BCS in 131 (46.1%). Bilateral mastectomy rates were higher in women undergoing reconstruction compared to those without (66.5% vs 32.2%, p<0.0001). Usage of internal mammary RT was low (7.8%–11.2%) and did not differ between surgical approaches. Supraclavicular-RT rate ranged from 46.6% to 52.2% and did not differ between surgical approaches but was omitted in 193/408 (47.3%) of node-positive patients. Rate of Axillary-RT was more frequent in patients who remained node-positive (p=0.002). However, 22% of patients who converted to node-negative still received Axillary RT. Post-mastectomy RT was more frequently omitted after reconstruction compared to mastectomy (23.9% vs 12.1%, p=0.002), and was omitted in 19 of 107 (17.8%) patients with residual node-positive disease in the reconstruction group. Conclusion The majority of clinically node-positive patients treated with NAC undergoing mastectomy receive RT. RT was less common in patients undergoing reconstruction. There is wide variability in RT fields. These practice

  7. Outcomes of Positron Emission Tomography-Staged Clinical N3 Breast Cancer Treated With Neoadjuvant Chemotherapy, Surgery, and Radiotherapy

    SciTech Connect

    Park, Hae Jin; Shin, Kyung Hwan; Cho, Kwan Ho; Park, In Hae; Lee, Keun Seok; Ro, Jungsil; Jung, So-Youn; Lee, Seeyoun; Kim, Seok Won; Kang, Han-Sung; Chie, Eui Kyu; Ha, Sung Whan

    2011-12-01

    Purpose: To evaluate the treatment outcome and efficacy of regional lymph node irradiation after neoadjuvant chemotherapy (NCT) and surgery in positron emission tomography (PET)-positive clinical N3 (cN3) breast cancer patients. Methods and Materials: A total of 55 patients with ipsilateral infraclavicular (ICL), internal mammary (IMN), or supraclavicular (SCL) lymph node involvement in the absence of distant metastases, as revealed by an initial PET scan, were retrospectively analyzed. The clinical nodal stage at diagnosis (2002 AJCC) was cN3a in 14 patients (26%), cN3b in 12 patients (22%), and cN3c in 29 patients (53%). All patients were treated with NCT, followed by mastectomy or breast-conserving surgery and subsequent radiotherapy (RT) with curative intent. Results: At the median follow-up of 38 months (range, 9-80 months), 20 patients (36%) had developed treatment failures, including distant metastases either alone or combined with locoregional recurrences that included one ipsilateral breast recurrence (IBR), six regional failures (RF), and one case of combined IBR and RF. Only 3 patients (5.5%) exhibited treatment failure at the initial PET-positive clinical N3 lymph node. The 5-year locoregional relapse-free survival, disease-free survival (DFS), and overall survival rates were 80%, 60%, and 79%, respectively. RT delivered to PET-positive IMN regions in cN3b patients and at higher doses ({>=}55 Gy) to SCL regions in cN3c patients was not associated with improved 5-year IMN/SCL relapse-free survival or DFS. Conclusion: NCT followed by surgery and RT, including the regional lymph nodes, resulted in excellent locoregional control for patients with PET-positive cN3 breast cancer. The primary treatment failure in this group was due to distant metastasis rather than RF. Neither higher-dose RT directed at PET-positive SCL nodes nor coverage of PET-positive IMN nodes was associated with additional gains in locoregional control or DFS.

  8. Impact of immunohistochemistry-based molecular subtype on chemosensitivity and survival in Hispanic breast cancer patients following neoadjuvant chemotherapy

    PubMed Central

    Gómez, Rodolfo; Ossa, Carlos Andrés; Montoya, María Elvira; Echeverri, Carolina; Ángel, Gonzalo; Ascuntar, Johana; Borrero, Mauricio; Gil, Mónica; Herrera, Sabrina; Gutiérrez, Eduardo; Herazo, Fernando; Jiménez, Alejo; Madrid, Jorge; Reyes, Pedro Alejandro; Zuluaga, Lina; García, Héctor

    2015-01-01

    Background Neoadjuvant chemotherapy (NAC) is the standard treatment for patients with locally advanced breast cancer, showing improvement in disease-free survival (DFS) and overall survival (OS) rates in patients achieving pathological complete response (pCR). The relationship between immunohistochemistry-based molecular subtyping (IMS), chemo sensitivity and survival is currently a matter of interest. We explore this relationship in a Hispanic cohort of breast cancer patients treated with NAC. Methods A retrospective survival analysis was performed on Colombian females with breast cancer treated at Instituto de Cancerología-Clinica Las Américas between January 2009 and December 2011. Patients were classified according to immunohistochemistry-based subtyping into the following five groups: Luminal A, Luminal B, Luminal B/HER 2+, HER2-enriched, and triple-negative breast cancer. Demographic characteristics, recurrence pattern, and survival rate were reviewed by bivariate and multivariate analysis. Results A total of 328 patients fulfilled the study’s inclusion parameters and the distribution of subtypes were as follows: Luminal A: 73 (22.3%), Luminal B/HER2−: 110 (33.5%), Luminal B/HER2+: 75 (22.9%), HER2-enriched: 30 (9.1%), and triple-negative: 40 (12.2%). The median follow-up was 41 months (interquartile range: 31–52). Pathological response to NAC was as follows: complete pathological response (pCR) in 28 (8.5%) patients, partial 247 (75.3%); stable disease 47 (14.3%), and progression 6 (1.8%) patients. The presence of pCR had a significant DFS and OS in the entire group (p = 0.01) but subtypes had different DFS in Luminal B (p = 0.01) and triple negative (p = 0.02) and also OS in Luminal B (p = 0.01) and triple negative (p = 0.01). Conclusions pCR is associated with an improved overall survival and disease-free survival rates in this group of Hispanics patients. Advanced stages, Luminal B subtypes, triple-negative tumours and non-pCR showed lower DFS

  9. Predictive Factors and Value of ypN+ after Neoadjuvant Chemotherapy in Clinically Lymph Node-Negative Breast Cancer

    PubMed Central

    Fukada, Ippei; Araki, Kazuhiro; Kobayashi, Kokoro; Shibayama, Tomoko; Takahashi, Shunji; Horii, Rie; Akiyama, Futoshi; Iwase, Takuji; Ohno, Shinji; Hatake, Kiyohiko; Hozumi, Yasuo; Sata, Naohiro; Ito, Yoshinori

    2016-01-01

    Background Pathological complete response (pCR) with neoadjuvant chemotherapy (NAC) has been regarded as a surrogate endpoint for disease-free survival (DFS) and overall survival (OS) of patients with breast cancer. No consensus regarding the definition of pCR has been established; there are several definitions according to a variety of classifications. Eradication of cancer cells in both breast and lymph nodes has been better associated with improved prognosis than in the breast alone. Even in patients diagnosed as having clinically node-negative cancer before NAC, postoperative pathological examination often shows axillary lymph node metastases. Patients and Methods Of the 771 patients with breast cancer who underwent NAC in the Cancer Institute Hospital between January 2000 and May 2009, 146 patients preoperatively diagnosed as having node-negative breast cancer were retrospectively evaluated. We have made the definition of clinically lymph node-negative (N0) as follows: first, ultrasonography before NAC did not show any lymphadenopathy. Second, a cytological procedure confirmed negative study for each patient when ultrasonography suggested lymphadenopathy. Results The median observation period was 79.7 months, and the median age of the subjects was 51 years. Pathological examination at the time of the surgery showed lymph node metastases (ypN+) in 46 patients (31.5%). Histological therapeutic effects revealed ypT0/is in 9 patients (6.2%) and ypTinv in 137 (93.8%). Multivariate analysis demonstrated that younger age (49>), large tumor size, NG3, and ypN+ were significant poor prognostic factors for DFS (p = 0.020, p = 0.008, P = 0.022 and p = 0.010, respectively). Moreover, ypN+ was the only significant poor prognostic factor for OS (p = 0.022). The predictive factors of ypN+ in clinically lymph node–negative breast cancer were ypTinv (p = 0.036) and the luminal type (HR+ and HER2-) (p = 0.029). Conclusion The prognosis of clinically lymph node negative breast

  10. Utility of [18F] Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG PET/CT) in the Initial Staging and Response Assessment of Locally Advanced Breast Cancer Patients Receiving Neoadjuvant Chemotherapy.

    PubMed

    Hulikal, Narendra; Gajjala, Sivanath Reddy; Kalawat, Teck Chand; Kottu, Radhika; Amancharla Yadagiri, Lakshmi

    2015-12-01

    In India up to 50 % of breast cancer patients still present as locally advanced breast cancer (LABC). The conventional methods of metastatic work up include physical examination, bone scan, chest & abdominal imaging, and biochemical tests. It is likely that the conventional staging underestimates the extent of initial spread and there is a need for more sophisticated staging procedure. The PET/CT can detect extra-axillary and occult distant metastases and also aid in predicting response to chemotherapy at an early point in time. To evaluate the utility of FDG PET/CT in initial staging and response assessment of patients with LABC receiving NACT. A prospective study of all biopsy confirmed female patients diagnosed with LABC receiving NACT from April 2013 to May 2014. The conventional work up included serum chemistry, CECT chest and abdomen and bone scan. A baseline whole body PET/CT was done in all patients. A repeat staging evaluation and a whole body PET/CT was done after 2/3rd cycle of NACT in non-responders and after 3/4 cycles in clinical responders. The histopathology report of the operative specimen was used to document the pathological response. The FDG PET/CT reported distant metastases in 11 of 38 patients, where as conventional imaging revealed metastases in only 6. Almost all the distant lesions detected by conventional imaging were detected with PET/CT, which showed additional sites of metastasis in 3 patients. In 2 patients, PET/CT detected osteolytic bone metastasis which were not detected by bone scan. In 5 patients PET CT detected N3 disease which were missed on conventional imaging. A total of 14 patients had second PET/CT done to assess the response to NACT and 11 patients underwent surgery. Two patients had complete pathological response. Of these 1 patient had complete metabolic and morphologic response and other had complete metabolic and partial morphologic response on second PET/CT scan. The 18 FDG PET/CT can detect more number of

  11. Prognostic value of tumor-infiltrating lymphocytes on residual disease after primary chemotherapy for triple-negative breast cancer: a retrospective multicenter study

    PubMed Central

    Dieci, M. V.; Criscitiello, C.; Goubar, A.; Viale, G.; Conte, P.; Guarneri, V.; Ficarra, G.; Mathieu, M. C.; Delaloge, S.; Curigliano, G.; Andre, F.

    2014-01-01

    Background There is a need to develop surrogates for treatment efficacy in the neoadjuvant setting to speed-up drug development and stratify patients according to outcome. Preclinical studies showed that chemotherapy induces an antitumor immune response. In order to develop new surrogates for drug efficacy, we assessed the prognostic value of tumor-infiltrating lymphocytes (TIL) on residual disease after neoadjuvant chemotherapy (NACT) in patients with triple-negative breast cancer (TNBC). Patients and methods Three hundred four TNBC patients with residual disease after NACT were retrospectively identified in three different hospitals. Hematoxylin and eosin-stained slides from surgical postchemotherapy specimens were evaluated for intratumoral (It-TIL) and stromal (Str-TIL) TIL. Cases were classified as High-TIL if It-TIL and/or Str-TIL >60%. Results TIL were assessable for 278 cases. Continuous It-TIL and Str-TIL variables were strong prognostic factors in the multivariate model, both for metastasis-free [hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.77–0.96, P = 0.01 and HR 0.85, 95% CI 0.75–0.98, P = 0.02 for Str-TIL and It-TIL, respectively] and overall survival (HR 0.86, 95% CI 0.77–0.97, P = 0.01 and HR 0.86, 95% CI 0.75–0.99, P = 0.03 for Str-TIL and It-TIL, respectively). The 5-year overall survival rate was 91% (95% CI 68% to 97%) for High-TIL patients (n = 27) and 55% (95% CI 48% to 61%) for Low-TIL patients (HR 0.19, 95% CI 0.06–0.61, log-rank P = 0.0017). The major prognostic impact of TIL was seen for patients with large tumor burden following NACT (residual tumor >2 cm and/or node metastasis). In all but one High-TIL case, It-TIL and Str-TIL values were lower on the prechemotherapy sample. Conclusions The presence of TIL in residual disease after NACT is associated with better prognosis in TNBC patients. This parameter may represent a new surrogate of drug efficacy to test investigational agents in the neoadjuvant setting and a new

  12. Changes and predictive and prognostic value of the mitotic index, Ki-67, cyclin D1, and cyclo-oxygenase-2 in 710 operable breast cancer patients treated with neoadjuvant chemotherapy.

    PubMed

    Penault-Llorca, Frédérique; Abrial, Catherine; Raoelfils, Inès; Chollet, Philippe; Cayre, Anne; Mouret-Reynier, Marie-Ange; Thivat, Emilie; Mishellany, Florence; Gimbergues, Pierre; Durando, Xavier

    2008-12-01

    The current study expands upon previous work using a database of 710 patients treated with neoadjuvant chemotherapy. First, we studied phenotypic characteristics of tumors before and after chemotherapy using the following factors: the mitotic index of the Scarff-Bloom-Richardson grade, Ki-67, cyclin D1, and cyclo-oxygenase-2. Second, the predictive value of these factors on response was assessed. Third, we measured the prognostic impact of these markers post-therapy in comparison with clinical and pathological responses according to the Chevallier and Sataloff classifications. Patients were treated using different neoadjuvant chemotherapy combinations, mainly in successive prospective phase II trials. They received a median number of six cycles (range, 1-9). After neoadjuvant chemotherapy, patients underwent surgery and radiotherapy. In cases of important residual disease, some received additional courses of chemotherapy. In addition, menopausal patients with hormone receptor-positive tumors received tamoxifen for 5 years. According to our analysis, we found significant variations before and after neoadjuvant chemotherapy only for cyclin D1 and the mitotic index. Concerning the predictive value of biomarkers for response, Ki-67 and the mitotic index were predictive on univariate analysis, both for objective clinical and pathological complete responses. Because these two factors were correlated, no multivariate analyses were conducted. We then assessed the prognostic impact of the biopathological factors. When the factors were measured before chemotherapy, all were prognostic. When evaluated after chemotherapy, the mitotic index, objective clinical response, and pathological complete response were prognostic. Because these factors were correlated, no multivariate model was done. The main clinical fact is that there were significant correlations between clinical and pathological responses and variations in the biological factors studied.

  13. 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.

  14. Grade of chemotherapy-induced necrosis as a predictor of local and systemic control in 881 patients with non-metastatic osteosarcoma of the extremities treated with neoadjuvant chemotherapy in a single institution.

    PubMed

    Bacci, Gaetano; Mercuri, Mario; Longhi, Alessandra; Ferrari, Stefano; Bertoni, Franco; Versari, Michela; Picci, Piero

    2005-09-01

    To determine whether necrosis induced by pre-operative chemotherapy correlates with the rate of systemic and local relapse, may change the pattern of relapse and/or may modify the chance of success of post-relapse treatments, we evaluated 881 patients with non-metastatic osteosarcoma of the extremities treated with five different protocols of neoadjuvant chemotherapy and surgery at the same institution between 1983 and 1999. The 5-year disease-free survival (DFS) and overall survival (OS) correlated significantly with the histological response to chemotherapy. Five-year DFS and OS in good and poor responders were 67.9% versus 51.3% (P < 0.0001) and 78.4% versus 63.7% (P < 0.0001), respectively. The prognostic value of the histological response was valid only for osteoblastic and telangiectatic osteosarcoma subtypes. Nonetheless, since they represent more than 70% of all osteosarcomas, we conclude that chemotherapy-induced necrosis has a significant prognostic value, regardless of the type of chemotherapy performed after surgery.

  15. The Impact of Skin-Sparing Mastectomy With Immediate Reconstruction in Patients With Stage III Breast Cancer Treated With Neoadjuvant Chemotherapy and Postmastectomy Radiation

    SciTech Connect

    Prabhu, Roshan; Godette, Karen; Carlson, Grant; Losken, Albert; Gabram, Sheryl; Fasola, Carolina; O'Regan, Ruth; Zelnak, Amelia; Torres, Mylin

    2012-03-15

    Purpose: The safety and efficacy of skin-sparing mastectomy (SSM) with immediate reconstruction (IR) in patients with locally advanced breast cancer are unclear. The purpose of this study is to compare the outcomes of women with noninflammatory Stage III SSM with IR vs. non-SSM-treated women who underwent neoadjuvant chemotherapy and adjuvant radiation therapy (XRT). Methods and Materials: Between October 1997 and March 2010, 100 consecutive patients (40 SSM with IR vs. 60 non-SSM) with Stage III breast cancer received anthracycline- and/or taxane-based neoadjuvant chemotherapy, mastectomy, and adjuvant XRT. Clinical stage (SSM with IR vs. for non-SSM) was IIIA (75% vs. 67%), IIIB (8% vs. 18%), and IIIC (8% vs. 8%). Tumors greater than 5 cm were found in 74% vs. 69%; 97% of patients in both groups were clinically node positive; and 8% vs. 18% had T4b disease. Results: The time from initial biopsy to XRT was prolonged for SSM-IR patients (274 vs. 254 days, p = 0.04), and there was a trend toward XRT delay of more than 8 weeks (52% vs. 31%, p = 0.07) after surgery. The rate of complications requiring surgical intervention was higher in the SSM-IR group (37.5% vs. 5%, p < 0.001). The 2-year actuarial locoregional control, breast cancer-specific survival, and overall survival rates for SSM with IR vs. non-SSM were 94.7% vs. 97.4%, 91.5% vs. 86.3%, and 87.4% vs. 84.8%, respectively (p = not significant). Conclusions: In our small study with limited follow-up, SSM with IR prolonged overall cancer treatment time and trended toward delaying XRT but did not impair oncologic outcomes. Complication rates were significantly higher in this group. Longer follow-up is needed.

  16. Impact of lymph node evaluation in adjuvant and neoadjuvant chemotherapy settings on survival outcomes in Wilms tumour: a review of 185 cases from a single institution.

    PubMed

    Nanda, Ronica H; Shehata, Bahig M; Khoshnam, Nasim; Durham, Megan; Kim, Sungjin; Selwanes, Wasim; Chen, Zhengjia; Zhang, Chao; Esiashvili, Natia

    2017-01-01

    It is unclear if lymph node sampling in Wilms tumour, though critical for staging purposes, affects survival outcomes. The value of lymph node sampling in patients treated with neoadjuvant chemotherapy (NAC) is even more uncertain. We reviewed our institutional data to determine the impact of lymph node sampling on survival, as well as its role in the context of NAC. A total of 185 patients with Wilms tumour treated at our institution were included in this analysis. The number of nodes sampled (≤7, or >7), lymph node status (unknown, negative, or positive), pathological stage, and use of neoadjuvant chemotherapy were analysed for survival outcomes. Covariates were evaluated with chi-square test or Fisher's exact test where appropriate. All analyses were performed using SAS 9.3 and R package version 2.15.2 with a significant level of 0.05. Median follow-up for all patients was 7.1 years. The number of lymph nodes sampled was significantly related to lymph node status (p<0.001). Lymph node involvement portended worse overall survival after controlling for stage and histology. Patients treated with NAC had higher rates of 'unknown' lymph node status (p<0.001) and worse overall survival than their counterparts (p=0.002); within this group, patients with 'unknown' lymph node status had significantly worse survival than those with negative or positive lymph node. Our data support the available evidence that sampling of more than seven lymph nodes is necessary for adequate staging of Wilms tumour. This is especially critical in patients treated with NAC, who had worse overall survival, likely due to understaging and undertreatment. These findings should be confirmed prospectively to provide proper guidelines to physicians caring for patients with Wilms tumour.

  17. 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

  18. ABCC2-24C > T polymorphism is associated with the response to platinum/5-Fu-based neoadjuvant chemotherapy and better clinical outcomes in advanced gastric cancer patients

    PubMed Central

    Shan, Fei; Li, Shuangxi; Li, Zhongwu; Xiao, Aitang; Xing, Zhaodong; Xue, Kan; Li, Zhemin; Hu, Ying; Jia, Yongning; Miao, Rulin; Zhang, Lianhai; Bu, Zhaode; Wu, Aiwen; Ji, Jiafu

    2016-01-01

    Several studies have evaluated the efficacy of neoadjuvant treatment using oxaliplatin and fluoropyrimidines in advanced gastric cancer (GC). However, preoperative biomarkers predictive of clinical outcome remain lacking. We examined polymorphisms in the MTHFR, DPYD, UMPS, ABCB1, ABCC2, GSTP1, ERCC1, and XRCC1 genes to evaluate their usefulness as pharmacogenetic markers in a cohort of 103 GC patients treated with preoperative chemotherapy. DNA was extracted from peripheral blood cells, and the genotypes were analyzed using a SNaPShotTM assay, polymerase chain reaction amplification, and sequencing. The ABCC2-24C > T (rs717620) genotype was associated with pathologic response to neoadjuvant chemotherapy. Patients with the TT and TC genotypes responded to neoadjuvant chemotherapy 3.80 times more often than those with the CC genotype (95% CI: 1.27–11.32). Patients with the CC genotype also had poorer outcomes than those with other genotypes. Thus, ABCC2-24C > T polymorphism may help to predict the response to preoperative chemotherapy in GC patients. PMID:27487151

  19. Predictive significance of DNA damage and repair biomarkers in triple-negative breast cancer patients treated with neoadjuvant chemotherapy: An exploratory analysis

    PubMed Central

    Ercolani, Cristiana; Pizzuti, Laura; Lauro, Luigi Di; Sergi, Domenico; Sperati, Francesca; Terrenato, Irene; Dattilo, Rosanna; Botti, Claudio; Fabi, Alessandra; Ramieri, Maria Teresa; Mentuccia, Lucia; Marinelli, Camilla; Iezzi, Laura; Gamucci, Teresa; Natoli, Clara; Vitale, Ilio; Barba, Maddalena; Mottolese, Marcella; De Maria, Ruggero; Maugeri-Saccà, Marcello

    2015-01-01

    Response of cancer cells to chemotherapy-induced DNA damage is regulated by the ATM-Chk2 and ATR-Chk1 pathways. We investigated the association between phosphorylated H2AX (γ-H2AX), a marker of DNA double-strand breaks that trigger the ATM-Chk2 cascade, and phosphorylated Chk1 (pChk1), with pathological complete response (pCR) in triple-negative breast cancer (TNBC) patients treated with neoadjuvant chemotherapy. γ-H2AX and pChk1 were retrospectively assessed by immunohistochemistry in a series of pretreatment biopsies related to 66 patients. In fifty-three tumors hormone receptor status was negative in both the diagnostic biopsies and residual cancers, whereas in 13 cases there was a slight hormone receptor expression that changed after chemotherapy. Internal validation was carried out. In the entire cohort elevated levels of γ-H2AX, but not pChk1, were associated with reduced pCR rate (p = 0.009). The association tested significant in both uni- and multivariate logistic regression models (OR 4.51, 95% CI: 1.39–14.66, p = 0.012, and OR 5.07, 95% CI: 1.28–20.09, p = 0.021, respectively). Internal validation supported the predictive value of the model. The predictive ability of γ-H2AX was further confirmed in the multivariate model after exclusion of tumors that underwent changes in hormone receptor status during chemotherapy (OR 7.07, 95% CI: 1.39–36.02, p = 0.018). Finally, in residual diseases a significant decrease of γ-H2AX levels was observed (p < 0.001). Overall, γ-H2AX showed ability to predict pCR in TNBC and deserves larger, prospective studies. PMID:26544894

  20. Predictive significance of DNA damage and repair biomarkers in triple-negative breast cancer patients treated with neoadjuvant chemotherapy: An exploratory analysis.

    PubMed

    Vici, Patrizia; Di Benedetto, Anna; Ercolani, Cristiana; Pizzuti, Laura; Di Lauro, Luigi; Sergi, Domenico; Sperati, Francesca; Terrenato, Irene; Dattilo, Rosanna; Botti, Claudio; Fabi, Alessandra; Ramieri, Maria Teresa; Mentuccia, Lucia; Marinelli, Camilla; Iezzi, Laura; Gamucci, Teresa; Natoli, Clara; Vitale, Ilio; Barba, Maddalena; Mottolese, Marcella; De Maria, Ruggero; Maugeri-Saccà, Marcello

    2015-12-15

    Response of cancer cells to chemotherapy-induced DNA damage is regulated by the ATM-Chk2 and ATR-Chk1 pathways. We investigated the association between phosphorylated H2AX (γ-H2AX), a marker of DNA double-strand breaks that trigger the ATM-Chk2 cascade, and phosphorylated Chk1 (pChk1), with pathological complete response (pCR) in triple-negative breast cancer (TNBC) patients treated with neoadjuvant chemotherapy. γ-H2AX and pChk1 were retrospectively assessed by immunohistochemistry in a series of pretreatment biopsies related to 66 patients. In fifty-three tumors hormone receptor status was negative in both the diagnostic biopsies and residual cancers, whereas in 13 cases there was a slight hormone receptor expression that changed after chemotherapy. Internal validation was carried out. In the entire cohort elevated levels of γ-H2AX, but not pChk1, were associated with reduced pCR rate (p = 0.009). The association tested significant in both uni- and multivariate logistic regression models (OR 4.51, 95% CI: 1.39-14.66, p = 0.012, and OR 5.07, 95% CI: 1.28-20.09, p = 0.021, respectively). Internal validation supported the predictive value of the model. The predictive ability of γ-H2AX was further confirmed in the multivariate model after exclusion of tumors that underwent changes in hormone receptor status during chemotherapy (OR 7.07, 95% CI: 1.39-36.02, p = 0.018). Finally, in residual diseases a significant decrease of γ-H2AX levels was observed (p < 0.001). Overall, γ-H2AX showed ability to predict pCR in TNBC and deserves larger, prospective studies.

  1. MicroRNA-21 links epithelial-to-mesenchymal transition and inflammatory signals to confer resistance to neoadjuvant trastuzumab and chemotherapy in HER2-positive breast cancer patients

    PubMed Central

    Nuciforo, Paolo G.; Di Tommaso, Luca; Giovannetti, Elisa; Peg, Vicente; Losurdo, Agnese; Pérez-Garcia, José; Masci, Giovanna; Corsi, Fabio; Cortés, Javier; Seoane, Joan; Calin, George A.; Santarpia, Libero

    2015-01-01

    Patients with primary HER2-positive breast cancer benefit from HER2-targeted therapies. Nevertheless, a significant proportion of these patients die of disease progression due to mechanisms of drug resistance. MicroRNAs (miRNAs) are emerging as critical core regulators of drug resistance that act by modulating the epithelial- to-mesenchymal transition (EMT) and cancer-related immune responses. In this study, we investigated the association between the expression of a specific subset of 14 miRNAs involved in EMT processes and immune functions and the response to neoadjuvant trastuzumab and chemotherapy in 52 patients with HER2-overexpressing breast tumors. The expression of only a single miRNA, miR-21, was significantly associated with residual disease (p = 0.030) and increased after trastuzumab-chemotherapy (p = 0.012). A target prediction analysis coupled with in vitro and in vivo validations revealed that miR-21 levels inversely correlated with the expression of PTEN (rs = −0.502; p = 0.005) and PDCD4 (rs = −0.426; p = 0.019), which differentially influenced the drug sensitivity of HER2-positive breast cancer cells. However, PTEN expression was only marginally associated with residual disease. We further demonstrated that miR-21 was able to affect the response to both trastuzumab and chemotherapy, triggering an IL-6/STAT3/NF-κB-mediated signaling loop and activating the PI3K pathway. Our findings support the ability of miR-21 signaling to sustain EMT and shape the tumor immune microenvironment in HER2-positive breast cancer. Collectively, these data provide a rationale for using miR-21 expression as a biomarker to select trastuzumab-chemotherapy-resistant HER2-positive breast cancer patients who may benefit from treatments containing PI3K inhibitors or immunomodulatory drugs. PMID:26452030

  2. Effects of neo-adjuvant chemotherapy for oesophago-gastric cancer on neuro-muscular gastric function.

    PubMed

    Sung, E Z H; Arasaradnam, R P; Jarvie, E M; James, S; Goodyear, S J; Borman, R A; Snead, D; Sanger, G J; Nwokolo, C U

    2012-12-01

    Delayed gastric emptying symptoms are often reported after chemotherapy. This study aims to characterise the effects of chemotherapy on gastric neuro-muscular function. Patients undergoing elective surgery for oesophago-gastric cancer were recruited. Acetylcholinesterase, nNOS, ghrelin receptor and motilin expressions were studied in gastric sections from patients receiving no chemotherapy (n = 3) or oesophageal (n = 2) or gastric (n = 2) chemotherapy. A scoring system quantified staining intensity (0-3; no staining to strong). Stomach sections were separately suspended in tissue baths for electrical field stimulation (EFS) and exposure to erythromycin or carbachol; three patients had no chemotherapy; four completed cisplatin-based chemotherapy within 6 weeks prior to surgery. AChE expression was markedly decreased after chemotherapy (scores 2.3 ± 0.7, 0.5 ± 0.2 and 0 ± 0 in non-chemotherapy, oesophageal- and gastric-chemotherapy groups (p < 0.03 each) respectively. Ghrelin receptor and motilin expression tended to increase (ghrelin: 0.7 ± 0.4 vs 2.0 ± 0.4 and 1.2 ± 0.2 respectively; p = 0.04 and p = 0.2; motilin: 0.7 ± 0.5 vs 2.2 ± 0.5 and 2.0 ± 0.7; p = 0.06 and p = 0.16). Maximal contraction to carbachol was 3.7 ± 0.7 g and 1.9 ± 0.8 g (longitudinal muscle) and 3.4 ± 0.4 g and 1.6 ± 0.6 (circular) in non-chemotherapy and chemotherapy tissues respectively (p < 0.05 each). There were loss of AChE and reduction in contractility to carbachol. The tendency for ghrelin receptors to increase suggests an attempt to upregulate compensating systems. Our study offers a mechanism by which chemotherapy markedly alters neuro-muscular gastric function.

  3. Chemotherapy

    MedlinePlus

    ... the cancer cells. This is called palliative chemotherapy. Chemotherapy for conditions other than cancer Some chemotherapy drugs ... you'll receive. Side effects that occur during chemotherapy treatment Common side effects of chemotherapy drugs include: ...

  4. Molecular characterization of patients with pathologic complete response or early failure after neoadjuvant chemotherapy for locally advanced breast cancer using next generation sequencing and nCounter assay

    PubMed Central

    Jung, Hae Hyun; Do, In-Gu; Lee, Kwang Hee; Ahn, TaeJin; Kil, Won Ho; Kim, Seok Won; Lee, Jeong Eon; Nam, Seok Jin; Kim, Duk-Hwan; Ahn, Jin Seok; Im, Young-Hyuck; Park, Yeon Hee

    2015-01-01

    Neoadjuvant chemotherapy (NAC) has the added advantage of increasing breast conservation rates with equivalent survival outcomes compared with adjuvant chemotherapy. A subset of breast cancer patients who received NAC experienced early failure (EF) during the course of therapy or within a short period after curative breast surgery. In contrast, patients with pathological complete response (pCR) were reported to have markedly favorable outcomes. This study was performed to identify actionable mutation(s) and to explain refractoriness and responsiveness to NAC. Included in this analysis were 76 patients among 397 with locally advanced breast cancer for whom a preoperative fresh-frozen paraffin-embedded tumor block was available for next-generation sequencing using AmpliSeq. The incidence of missense mutations in KRAS was much higher in patients with EF than in other groups (p < 0.01). In contrast, polymorphisms of the cMET gene were found in patients with pCR exclusively (p < 0.01). PMID:26009992

  5. A phase III, multicenter randomized controlled trial of neo-adjuvant chemotherapy paclitaxel plus cisplatin versus surgery alone for stage IIA–IIIB esophageal squamous cell carcinoma

    PubMed Central

    Zheng, Yan; Liu, Xianben; Zhang, Ruixiang; Wang, Zongfei; Sun, Haibo; Liu, Shilei

    2017-01-01

    Background The survival benefits of neoadjuvant chemotherapy (NAC) for esophagus squamous cell carcinoma (ESCC) remains controversial. The surgical procedure was not well defined in NAC strategy, in past trials. The different surgical procedure and different levels of lymphadenectomy may decrease the survival benefits from NAC. The new chemotherapy regimen with paclitaxel is promising. The purpose of this study is to confirm the superiority of paclitaxel, cisplatin and McKeown esophagectomy with total two-field lymphadenectomy compared with surgery alone for ESCC. Methods A two-arm phase III trial was launched in June 2015. A total of 528 patients will be recruited from eight Chinese institutions within 2.5 years. The overall survival (OS) is the primary endpoint, and the secondary endpoints include disease-free survival (DFS), R0 resection rate, complication rate, perioperation mortality, days of hospitalization, quality of life (QOL), NAC response rate, pathologic response rate, toxicities of NAC, prognostic factors, predictive factors, progression-free survival (PFS), and adverse events. Discussion The study will provide the final conclusion of NAC for ESCC in China. Trial registration NCT02442440 (https://register.clinicaltrials.gov/). PMID:28203424

  6. Phase II Trial Assessing the Ability of Neoadjuvant Chemotherapy With or Without Second-Look Surgery to Eliminate Measurable Disease for Nongerminomatous Germ Cell Tumors: A Children's Oncology Group Study

    PubMed Central

    Goldman, Stewart; Bouffet, Eric; Fisher, Paul G.; Allen, Jeffrey C.; Robertson, Patricia L.; Chuba, Paul J.; Donahue, Bernadine; Kretschmar, Cynthia S.; Zhou, Tianni; Buxton, Allen B.; Pollack, Ian F.

    2015-01-01

    Purpose This phase II trial evaluated the effect of neoadjuvant chemotherapy with or without second-look surgery before craniospinal irradiation on response rates and survival outcomes in children with newly diagnosed nongerminomatous germ cell tumors. Patients and Methods Induction chemotherapy consisted of six cycles of carboplatin/etoposide alternating with ifosfamide/etoposide. Patients demonstrating less than complete response after induction chemotherapy were encouraged to undergo second-look surgery. Patients who did not achieve complete response or partial response after chemotherapy with or without second-look surgery proceeded to high-dose chemotherapy with thiotepa and etoposide and autologous peripheral blood stem-cell rescue before craniospinal irradiation. Results The study included 102 patients treated between January 2004 and July 2008. Median age was 12 years, and 76% were male; 53.9% had pineal region masses, and 23.5% had suprasellar lesions. Sixty-nine percent of patients achieved complete response or partial response with neoadjuvant chemotherapy. At 5 years, event-free survival was 84% ± 4% (SE) and overall survival was 93% ± 3%. During the median follow-up of 5.1 years, 16 patients recurred or progressed, with seven deaths after relapse. No deaths were attributed to therapy-related toxicity. Relapse occurred at the site of primary disease in 10 patients, at a distant site in three patients, or both in one patient. In two patients, progression was detected by marker increase alone. Increased serum α-fetoprotein was a negative prognostic variable. Histologic subtype and increase of beta-human chorionic gonadotropin were not significantly correlated with worse outcomes. Conclusion Neoadjuvant chemotherapy with or without second-look surgery achieved high response rates contributing to excellent survival outcomes in children with newly diagnosed nongerminomatous germ cell tumors. This regimen should be included as a backbone for further

  7. 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

  8. Balancing activity and tolerability of neoadjuvant paclitaxel- and docetaxel-based chemotherapy for HER2-positive early stage breast cancer: sensitivity analysis of randomized trials.

    PubMed

    Carbognin, Luisa; Sperduti, Isabella; Nortilli, Rolando; Brunelli, Matteo; Vicentini, Cecilia; Pellini, Francesca; Pollini, Giovanni Paolo; Giannarelli, Diana; Tortora, Giampaolo; Bria, Emilio

    2015-03-01

    Paclitaxel and docetaxel represent the most adopted taxanes in the neoadjuvant treatment of HER2-positive breast cancer. Questions still remain with regard to their difference in terms of activity and tolerability. Events for pathological complete response (pCR), severe and febrile neutropenia (FN), and severe neurotoxicity were pooled by adopting a fixed- and random-effect model. A sensitivity analysis to test for the interaction between paclitaxel and docetaxel was accomplished. Absolute differences with 95% confidence intervals (CIs) and the number of patients needed to treat/harm (NNT/NNH) were calculated to derive the Likelihood of being Helped or Harmed (LHH). Data from 15 trials (3601 patients) were included. Paclitaxel significantly increases pCR rate by 6.8% in comparison with docetaxel (43.4%, 95% CI 41.1-45.7% versus 36.6%, 95% CI 34.3-39.0%, p=0.0001), regardless of the chemotherapy backbone, with an absolute difference of 9% and 9.2% for anthracycline-based or free-regimens. Paclitaxel significantly improves pCR versus docetaxel with a single HER2-inhibition by 6.7% (p=0.0012), with no difference if combined with a dual HER2-inhibition. Severe neutropenia and FN are significantly lower with paclitaxel, with an absolute difference of 32.4% (p<0.0001) and 2.5% (p=0.0059), respectively. Conversely, severe neurotoxicity is slightly higher with paclitaxel (3%, p=0.0001). The LHH ratio calculated for pCR and severe neutropenia is 2.0 and 0.7 for paclitaxel and docetaxel. Although the activity of neoadjuvant paclitaxel and docetaxel HER2-positive breast cancer is considered similar, the slight advantage in pCR, the significantly lower neutropenia and FN, do favor paclitaxel (in the weekly fashion) over docetaxel, despite the slightly worst neurotoxicity.

  9. Can Positron Emission Tomography/Computed Tomography with the Dual Tracers Fluorine-18 Fluoroestradiol and Fluorodeoxyglucose Predict Neoadjuvant Chemotherapy Response of Breast Cancer? ----A Pilot Study

    PubMed Central

    Yang, Zhongyi; Sun, Yifei; Xue, Jing; Yao, Zhifeng; Xu, Junyan; Cheng, Jingyi; Shi, Wei; Zhu, Beiling; Zhang, Yongping; Zhang, Yingjian

    2013-01-01

    Objective To assess the clinical value of dual tracers Positron emission tomography/computed tomography (PET/CT) 18F-fluoroestradiol (18F-FES) and 18F-fluorodeoxyglucose (18F-FDG) in predicting neoadjuvant chemotherapy response (NAC) of breast cancer. Methods Eighteen consecutive patients with newly diagnosed, non-inflammatory, stage II and III breast cancer undergoing NAC were included. Before chemotherapy, they underwent both 18F-FES and 18F-FDG PET/CT scans. Surgery was performed after three to six cycles of chemotherapy. Tumor response was graded and divided into two groups: the responders and non-responders. We used the maximum standardized uptake value (SUVmax) to qualify each primary lesion. Results Pathologic analysis revealed 10 patients were responders while the other 8 patients were non-responders. There was no statistical difference of SUVmax-FDG and tumor size between these two groups (P>0.05). On the contrary, SUVmax-FES was lower in responders (1.75±0.66 versus 4.42±1.14; U=5, P=0.002); and SUVmax-FES/FDG also showed great value in predicting outcome (0.16±0.06 versus 0.54±0.22; U=5, P=0.002). Conclusions Our study showed 18F-FES PET/CT might be feasible to predict response of NAC. However, whether the use of dual tracers 18F-FES and 18F-FDG has complementary value should be further studied. PMID:24205151

  10. Deletions of multidrug resistance gene loci in breast cancer leads to the down-regulation of its expression and predict tumor response to neoadjuvant chemotherapy

    PubMed Central

    Litviakov, Nikolai V.; Cherdyntseva, Nadezhda V.; Tsyganov, Matvey M.; Slonimskaya, Elena M.; Ibragimova, Marina K.; Kazantseva, Polina V.; Kzhyshkowska, Julia; Choinzonov, Eugeniy L.

    2016-01-01

    Neoadjuvant chemotherapy (NAC) is intensively used for the treatment of primary breast cancer. In our previous studies, we reported that clinical tumor response to NAC is associated with the change of multidrug resistance (MDR) gene expression in tumors after chemotherapy. In this study we performed a combined analysis of MDR gene locus deletions in tumor DNA, MDR gene expression and clinical response to NAC in 73 BC patients. Copy number variations (CNVs) in biopsy specimens were tested using high-density microarray platform CytoScanTM HD Array (Affymetrix, USA). 75%–100% persons having deletions of MDR gene loci demonstrated the down-regulation of MDR gene expression. Expression of MDR genes was 2–8 times lower in patients with deletion than in patients having no deletion only in post-NAC tumors samples but not in tumor tissue before chemotherapy. All patients with deletions of ABCB1 ABCB 3 ABCC5 gene loci – 7q21.1, 6p21.32, 3q27 correspondingly, and most patients having deletions in ABCC1 (16p13.1), ABCC2 (10q24), ABCG1 (21q22.3), ABCG2 (4q22.1), responded favorably to NAC. The analysis of all CNVs, including both amplification and deletion showed that the frequency of 13q14.2 deletion was 85% among patients bearing tumor with the deletion at least in one MDR gene locus versus 9% in patients with no deletions. Differences in the frequency of 13q14.2 deletions between the two groups were statistically significant (p = 2.03 ×10−11, Fisher test, Bonferroni-adjusted p = 1.73 × 10−8). In conclusion, our study for the first time demonstrates that deletion MDR gene loci can be used as predictive marker for tumor response to NAC. PMID:26799285

  11. HER2 and ESR1 mRNA expression levels and response to neoadjuvant trastuzumab plus chemotherapy in patients with primary breast cancer

    PubMed Central

    2013-01-01

    Introduction Recent data suggest that benefit from trastuzumab and chemotherapy might be related to expression of HER2 and estrogen receptor (ESR1). Therefore, we investigated HER2 and ESR1 mRNA levels in core biopsies of HER2-positive breast carcinomas from patients treated within the neoadjuvant GeparQuattro trial. Methods HER2 levels were centrally analyzed by immunohistochemistry (IHC), silver in situ hybridization (SISH) and qRT-PCR in 217 pretherapeutic formalin-fixed, paraffin-embedded (FFPE) core biopsies. All tumors had been HER2-positive by local pathology and had been treated with neoadjuvant trastuzumab/ chemotherapy in GeparQuattro. Results Only 73% of the tumors (158 of 217) were centrally HER2-positive (cHER2-positive) by IHC/SISH, with cHER2-positive tumors showing a significantly higher pCR rate (46.8% vs. 20.3%, P <0.0005). HER2 status by qRT-PCR showed a concordance of 88.5% with the central IHC/SISH status, with a low pCR rate in those tumors that were HER2-negative by mRNA analysis (21.1% vs. 49.6%, P <0.0005). The level of HER2 mRNA expression was linked to response rate in ESR1-positive tumors, but not in ESR1-negative tumors. HER2 mRNA expression was significantly associated with pCR in the HER2-positive/ESR1-positive tumors (P = 0.004), but not in HER2-positive/ESR1-negative tumors. Conclusions Only patients with cHER2-positive tumors - irrespective of the method used - have an increased pCR rate with trastuzumab plus chemotherapy. In patients with cHER2-negative tumors the pCR rate is comparable to the pCR rate in the non-trastuzumab treated HER-negative population. Response to trastuzumab is correlated to HER2 mRNA levels only in ESR1-positive tumors. This study adds further evidence to the different biology of both subsets within the HER2-positive group. Introduction The human epidermal growth factor receptor 2 (HER2) is the prototype of a predictive biomarker for targeted treatment [1-8]. International initiatives have established the

  12. Chemotherapy

    MedlinePlus

    Cancer chemotherapy; Cancer drug therapy; Cytotoxic chemotherapy ... Philadelphia, PA: Elsevier Saunders; 2016:chap 179. National Cancer Institute. Chemotherapy and you: support for people who have cancer. ...

  13. Intraoperative molecular analysis of sentinel lymph nodes following neoadjuvant chemotherapy in patients with clinical node negative breast cancer: An institutional study.

    PubMed

    Parada, David; Peña, Karla B; Riu, F Francesc; Aguilar, A Esther; Cohan, Sebastian

    2016-11-01

    Sentinel lymph node biopsy (SLNB) is an accurate, safe method for determining the axillary lymph node status. However, insufficient evidence exists to support the recommendation of SLNB in patients who have had neoadjuvant chemotherapy (NAC) to downsize tumours and allow for breast conservation surgery. The present study aimed to use molecular approaches to evaluate the feasibility and accuracy of SLNB in patients treated with NAC prior to SLN mapping and surgery. A total of 50 consecutive patients with operable invasive breast carcinomas who had received prior NAC were assessed using the one-step nucleic acid amplification (OSNA) method. The rate of SLN identification was 100%. The OSNA assay showed that 29 patients (58%) were negative for SLN and 21 patients (42%) were positive. In 19 of these 21 patients (90.48%), the SLN was the only positive lymph node. No axillary lymph nodes metastases were observed in patients with isolated tumour cells or with micrometastases. The OSNA assay is a highly sensitive, specific and reproducible diagnostic technique that can be used to analyse SLNs following NAC. The total tumoral load may assist with predicting additional non-SLN metastases.

  14. Intraoperative molecular analysis of sentinel lymph nodes following neoadjuvant chemotherapy in patients with clinical node negative breast cancer: An institutional study

    PubMed Central

    Parada, David; Peña, Karla B.; Riu, F. Francesc; Aguilar, A. Esther; Cohan, Sebastian

    2016-01-01

    Sentinel lymph node biopsy (SLNB) is an accurate, safe method for determining the axillary lymph node status. However, insufficient evidence exists to support the recommendation of SLNB in patients who have had neoadjuvant chemotherapy (NAC) to downsize tumours and allow for breast conservation surgery. The present study aimed to use molecular approaches to evaluate the feasibility and accuracy of SLNB in patients treated with NAC prior to SLN mapping and surgery. A total of 50 consecutive patients with operable invasive breast carcinomas who had received prior NAC were assessed using the one-step nucleic acid amplification (OSNA) method. The rate of SLN identification was 100%. The OSNA assay showed that 29 patients (58%) were negative for SLN and 21 patients (42%) were positive. In 19 of these 21 patients (90.48%), the SLN was the only positive lymph node. No axillary lymph nodes metastases were observed in patients with isolated tumour cells or with micrometastases. The OSNA assay is a highly sensitive, specific and reproducible diagnostic technique that can be used to analyse SLNs following NAC. The total tumoral load may assist with predicting additional non-SLN metastases. PMID:27882235

  15. Circulating oxidative stress parameters in pre- and post-menopausal healthy women and in women suffering from breast cancer treated or not with neoadjuvant chemotherapy.

    PubMed

    Ramírez-Expósito, María Jesús; Sánchez-López, Estefanía; Cueto-Ureña, Cristina; Dueñas, Basilio; Carrera-González, Pilar; Navarro-Cecilia, Joaquín; Mayas, María Dolores; Arias de Saavedra, José M; Sánchez-Agesta, Rafael; Martínez-Martos, José M

    2014-10-01

    We evaluate here the redox status in pre- and post-menopausal healthy women and in women with breast cancer in order to understand the consequences of the hormonal alterations of menopause for the oxidative stress status, its modifications with breast cancer and the influence of neoadjuvant chemotherapy (NC). To that, serum oxidative stress parameters (total antioxidant capacity, lipid peroxidation and protein oxidation), non-enzyme antioxidant defenses (total glutathione, uric acid and bilirubin) and enzyme antioxidant defenses (superoxide dismutase, catalase and glutathione peroxidase activities) were measured in healthy women and in women with breast cancer divided according to their menopausal status and that received or not NC. Circulating estradiol, progesterone, FSH and LH were also analyzed. We found that menopause itself modifies the redox status of healthy women, being most of these differences also reflected in women with breast cancer. However, several changes occur as a consequence of the disease. Furthermore, NC increases oxidative damage, decreases antioxidant defenses and eliminates the differences found in menopause. We conclude that the normal redox balance is disrupted by breast cancer but is also affected by the hormonal status promoted by menopause. In fact, NC nullifies the differences found between pre- and postmenopausal women in several antioxidant defense systems.

  16. Complete resection of a primitive neuroectodermal tumour arising in the bladder of a 31-year-old female after neoadjuvant chemotherapy

    PubMed Central

    Lam, Cameron J.; Shayegan, Bobby

    2016-01-01

    Primitive neuroectodermal tumours (PNET) that arise in the urinary bladder are an extremely rare occurrence. Very few cases have been reported so far in the literature1–13 and we report another case here in a 31-year-old-female. The patient presented with polyuria, gross hematuria, followed by development of anuria, and was discovered to have a 9.4 cm mass arising in the posterolateral aspect of the bladder. Histologically, the tumour showed small, round, blue cells. Further analysis using break-apart fluorescent in situ hybridization (FISH) revealed non-random chromosomal translocations of the ews gene suggestive of Ewing sarcoma (ES)/PNET. The patient completed seven cycles of neoadjuvant chemotherapy, which significantly reduced the size of the lesion. Due to the location of the lesion, surgical resection of the entire bladder and urethra with use of a continent cutaneous reservoir was performed. Here, the management of a 31-year-old female with ES/PNET arising from the bladder is reported. PMID:28255420

  17. Effect of MR Imaging Contrast Thresholds on Prediction of Neoadjuvant Chemotherapy Response in Breast Cancer Subtypes: A Subgroup Analysis of the ACRIN 6657/I-SPY 1 TRIAL

    PubMed Central

    Li, Wen; Arasu, Vignesh; Newitt, David C.; Jones, Ella F.; Wilmes, Lisa; Gibbs, Jessica; Kornak, John; Joe, Bonnie N.; Esserman, Laura J.; Hylton, Nola M.

    2016-01-01

    Functional tumor volume (FTV) measurements by dynamic contrast-enhanced magnetic resonance imaging can predict treatment outcomes for women receiving neoadjuvant chemotherapy for breast cancer. Here, we explore whether the contrast thresholds used to define FTV could be adjusted by breast cancer subtype to improve predictive performance. Absolute FTV and percent change in FTV (ΔFTV) at sequential time-points during treatment were calculated and investigated as predictors of pathologic complete response at surgery. Early percent enhancement threshold (PEt) and signal enhancement ratio threshold (SERt) were varied. The predictive performance of resulting FTV predictors was evaluated using the area under the receiver operating characteristic curve. A total number of 116 patients were studied both as a full cohort and in the following groups defined by hormone receptor (HR) and HER2 receptor subtype: 45 HR+/HER2−, 39 HER2+, and 30 triple negatives. High AUCs were found at different ranges of PEt and SERt levels in different subtypes. Findings from this study suggest that the predictive performance to treatment response by MRI varies by contrast thresholds, and that pathologic complete response prediction may be improved through subtype-specific contrast enhancement thresholds. A validation study is underway with a larger patient population. PMID:28066808

  18. HER-2/Neu overexpression does not predict response to neoadjuvant chemotherapy or prognosticate survival in patients with locally advanced breast cancer.

    PubMed

    Tulbah, Asma M; Ibrahim, Ezzeldin M; Ezzat, Adnan A; Ajarim, Dahish S; Rahal, Mohammed M; El Weshi, Amr N; Sorbris, Ralph

    2002-01-01

    Data about the prognostic and predictive value of HER-2/neu overexpression in patients with locally advanced breast cancer (LABC) treated with primary chemotherapy is limited. Therefore, this retrospective study was performed to examine this issue. Fifty-four consecutive patients with LABC were prospectively managed using a uniform multimodality approach. Response to neoadjuvant chemotherapy and survival were examined against HER-2/neu overexpression as determined by an immunohistochemistry method on formalin-fixed, paraffin-embedded samples of breast cancer using the commercially available, United States Food and Drug Administration-approved kit HercepTest (Dako Corp, Carpinteria, CA). The number of patients in each HercepTest immunostaining group were as follows; 0 in 12 patients (22%), 1+ in 8 (15%), 2+ in 12 (22%), and 3+ in 22 (41%). None of the clinical variables was significantly associated with HER-2/neu expression. After primary therapy, 22% of patients attained clinical complete response and an additional 70% achieved clinical partial response with an overall response rate of 92% (95% confidence interval: 100% to 79%). There was no significant correlation between clinical response and HercepTest positivity (p = 0.85). Of 52 patients with complete pathological data, there was no significant difference in HercepTest status between those who attained complete pathological response (46%) and those who did not (38%) (p = 0.74). Moreover, there was no significant difference in disease-free survival (75% vs 84%, [p = 0.26]) or overall survival (81% vs 84% [p = 0.31]) between those who overexpressed HER-2/neu and those with negative HercepTest, respectively. In patients with LABC, HER-2/neu overexpression determined using HercepTest assay and according to the manufacturer's approved guidelines failed to demonstrate a predictive or a prognostic role.

  19. CapOX as neoadjuvant chemotherapy for locally advanced operable colon cancer patients: a prospective single-arm phase II trial

    PubMed Central

    Liu, Fangqi; Yang, Li; Wu, Yuchen; Li, Cong; Zhao, Jiang; Keranmu, Adili; Zheng, Hongtu; Huang, Dan; Wang, Lei; Tong, Tong; Xu, Junyan; Zhu, Ji; Cai, Sanjun; Xu, Ye

    2016-01-01

    Objective The aim of this prospective, single-arm phase II trial was to confirm the safety and efficacy of neoadjuvant chemotherapy (NAC) using oxaliplatin plus capecitabine (CapOX) for patients with operable locally advanced colon cancer (CC). Methods Patients with computed tomography-defined T4 or lymph node-positive CCs were enrolled. After radiological staging, patients were treated with at least 2 cycles of NAC consisting of 130 mg/m2 oxaliplatin on d 1, plus 1,000 mg/m2 capecitabine twice daily for 14 d every 3 weeks, followed by surgery, and then with the rest cycles of adjuvant chemotherapy. Radiological response was evaluated after 2 cycles of NAC. Tumor response, treatment toxicity, and surgical complications were recorded. The pathological response to therapy was evaluated according to the tumor regression grade (TRG) score. The primary endpoint was pathologic tumor response. This trial is registered in ClinicalTrials.gov (No: NCT02415829). Results Forty-seven patients were enrolled in the study. Forty-two patients completed the planned treatments. The total radiological response rate was 68% (32/47), including complete and partial response rates of 2% (1/47) and 66% (31/47), respectively. Stable disease was observed in 32% (15/47) and progressive disease was observed in none. Complete pathologic response, major regression, and at least moderate regression were achieved in 1 (2%), 2 (4%), and 29 (62%) patients, respectively. Four patients developed grade 3 treatment toxicities. One patient with wound infection occurred after operation (1/47, 2%). There was no treatment-related death. Conclusions Our results suggest that NAC with CapOX is an effective and safe treatment option for patients with locally advanced CCs. PMID:28174487

  20. Expression status of CD44 and CD133 as a prognostic marker in esophageal squamous cell carcinoma treated with neoadjuvant chemotherapy followed by radical esophagectomy.

    PubMed

    Okamoto, Koichi; Ninomiya, Itasu; Ohbatake, Yoshinao; Hirose, Atsushi; Tsukada, Tomoya; Nakanuma, Shinichi; Sakai, Seisho; Kinoshita, Jun; Makino, Isamu; Nakamura, Keishi; Hayashi, Hironori; Oyama, Katsunobu; Inokuchi, Masafumi; Nakagawara, Hisatoshi; Miyashita, Tomoharu; Hidehiro, Tajima; Takamura, Hiroyuki; Fushida, Sachio; Ohta, Tetsuo

    2016-12-01

    Cancer stem cells (CSCs) have self-renewal and pluripotency capabilities and contribute to cancer progression and chemoresistance. It has been proposed that the treatment resistance and heterogeneity of CSCs are deeply involved in the prognosis of patients with esophageal squamous cell carcinoma (ESCC). The objective of this study was to identify the influence of the expression status of the CSC markers CD44 and CD133 on chemotherapeutic efficacy and prognosis in ESCC patients who underwent radical esophagectomy after neoadjuvant chemotherapy (NAC). Endoscopically biopsied specimens taken before NAC and surgically resected specimens after NAC were immunohistochemically assessed for CD44 and CD133 expression for 47 ESCC patients who underwent NAC followed by radical esophagectomy. The correlation between CD44 and CD133 expression status and clinicopathological findings and the prognosis of ESCC patients after NAC followed by esophagectomy were analyzed. The percentages of CD44-positive cells and CD133-positive cells in specimens were increased after NAC. CD44 and CD133 expression status before NAC did not correlate with the degree of tumor progression and had no impact on the chemotherapeutic effect. However, strong expression of CD44 or CD133 and a high proportion of CD133-expressing cells before NAC were significantly associated with poorer esophageal cancer-specific survival. Patients with strong expression of CD44 or CD133 and those with a high ratio of CD133-positive tumor cells showed significantly poor prognosis regardless of the effect of chemotherapy. Multivariate analysis showed that simultaneous strong expression of CD44 and CD133 before NAC, a high rate of CD133-positive tumor cells before NAC, and primary tumor remission assessed by preoperative endoscopy were significant independent prognostic factors for ESCC. Our data indicate that CD44 and CD133 expression status prior to treatment dictates the malignant potential of ESCC and may be a novel

  1. Neoadjuvant chemotherapy in the management of muscle-invasive bladder cancer: bridging the gap between evidence and practice.

    PubMed

    Sfakianos, John P; Galsky, Matthew D

    2015-05-01

    Although cisplatin-based chemotherapy followed by radical cystectomy is the standard treatment of muscle-invasive bladder cancer, population-based studies reveal that only a small fraction of patients actually receive such treatment. A comprehensive understanding of the reasons for this gap between efficacy and effectiveness is necessary to increase the likelihood of cure of all patients with muscle-invasive bladder cancer. These reasons include systems-, provider-, and patient-level barriers that are not amenable to a single solution. Tackling each barrier will ultimately be necessary to bridge the disconnect between what is achievable and what is actually achieved.

  2. A combination of Nottingham prognostic index and IHC4 score predicts pathological complete response of neoadjuvant chemotherapy in estrogen receptor positive breast cancer

    PubMed Central

    Jia, Weijuan; Liang, Gehao; Xie, Xinhua; Zheng, Wenbo; Song, Erwei; Su, Fengxi; Gong, Chang

    2016-01-01

    Pathologic complete response (pCR) prediction after neoadjuvant chemotherapy (NAC) is important for clinical decision-making in breast cancer. This study investigated the predictive value of Nottingham prognostic index (NPI), Immunohistochemical four (IHC4) score and a new predictive index combined with them in estrogen-positive (ER+) breast cancer following NAC. We retrospectively gathered clinical data of 739 ER+ breast cancer patients who received NAC from two cancer centers. We developed a new predictive biomarker named NPI+IHC4 to predict pCR in ER+ breast cancer in a training set (n=443) and validated it in an external validation set (n=296). The results showed that a lower IHC4 score, NPI and NPI+IHC4 were significantly associated a high pCR rate in the entire cohort. In the study set, NPI+IHC4 showed a better sensitivity and specificity for pCR prediction (AUC 0.699, 95% CI 0.626-0.772) than IHC4 score (AUC 0.613, 95% CI 0.533-0.692), NPI (AUC 0.576, 95% CI 0.494-0.659), tumor size (AUC 0.556, 95% CI 0.481-0.631) and TNM stage (AUC 0.521, 95% CI 0.442-0.601). In the validation set, NPI+IHC4 had a better predictive value for pCR (AUC 0.665, 95% CI 0.579-0.751) than IHC4 score or NPI alone. In addition, ER+ patients with lower IHC4, NPI and NPI+IHC4 scores had significantly better DFS in both study and validation sets. In summary, NPI+IHC4 can predict pCR following NAC and prognosis in ER+ breast cancer, which is cost-effect and potentially more useful in guiding decision-making regarding NAC in clinical practice. Further validation is needed in prospective clinical trials with larger cohorts of patients. PMID:27894097

  3. The Effect of Molecular Subtype and Residual Disease on Locoregional Recurrence in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy and Postmastectomy Radiation

    PubMed Central

    Yang, T. Jonathan; Morrow, Monica; Modi, Shanu; Zhang, Zhigang; Krause, Kate; Siu, Chun; McCormick, Beryl; Powell, Simon N.; Ho, Alice Y.

    2016-01-01

    Background The relative contribution of biologic subtype to locoregional recurrence (LRR) in patients who have been treated with neoadjuvant chemotherapy (NAC), mastectomy and postmastectomy radiotherapy (PMRT) is not clearly defined. Methods 233 patients with Stage II-III breast cancer received NAC, mastectomy and PMRT between 2000-2009: 53% (n=123) had HR+ (ER or PR+/HER2−), 23% (n=53) had HER2+ (HER2+/HR+ or HR−), and 24% (n=57) had triple negative disease (TN: HR−/HER2−). The 5-year LRR rates were estimated by Kaplan-Meier methods. Cox regression analysis was performed to evaluate covariates associated with LRR. Results Median follow-up was 62 months. A pathologic complete response (pCR) was seen in 14% of patients. The 5-year LRR rate was 8% in the entire cohort. The LRR rate was 0% in patients with a pCR versus 9% in patients without a pCR (p=0.05). TN disease (HR=4.4, p=0.003) and pathologic node positivity (HR=9.8, p=0.03) were associated with LRR. Patients with TN disease had a higher LRR rate compared to patients with HER2+ and HR+ disease (20% versus 6% and 4%, p=0.005). In patients without a pCR, TN subtype was associated with increased LRR (26% versus 7% HER+ and 4% HR+, p<0.001). Conclusions Patients with TN breast cancer had the highest LRR rate after NAC, mastectomy and PMRT. While no LRR was observed in TN patients with pCR, TN patients with residual disease had significantly higher LRR risk. Patients with HR+ and HER2+ breast cancer had favorable LRR rates, regardless of NAC response, likely due to receipt of adjuvant systemic targeted therapies. PMID:26130454

  4. Predicting response before initiation of neoadjuvant chemotherapy in breast cancer using new methods for the analysis of dynamic contrast enhanced MRI (DCE MRI) data

    NASA Astrophysics Data System (ADS)

    DeGrandchamp, Joseph B.; Whisenant, Jennifer G.; Arlinghaus, Lori R.; Abramson, V. G.; Yankeelov, Thomas E.; Cárdenas-Rodríguez, Julio

    2016-03-01

    The pharmacokinetic parameters derived from dynamic contrast enhanced (DCE) MRI have shown promise as biomarkers for tumor response to therapy. However, standard methods of analyzing DCE MRI data (Tofts model) require high temporal resolution, high signal-to-noise ratio (SNR), and the Arterial Input Function (AIF). Such models produce reliable biomarkers of response only when a therapy has a large effect on the parameters. We recently reported a method that solves the limitations, the Linear Reference Region Model (LRRM). Similar to other reference region models, the LRRM needs no AIF. Additionally, the LRRM is more accurate and precise than standard methods at low SNR and slow temporal resolution, suggesting LRRM-derived biomarkers could be better predictors. Here, the LRRM, Non-linear Reference Region Model (NRRM), Linear Tofts model (LTM), and Non-linear Tofts Model (NLTM) were used to estimate the RKtrans between muscle and tumor (or the Ktrans for Tofts) and the tumor kep,TOI for 39 breast cancer patients who received neoadjuvant chemotherapy (NAC). These parameters and the receptor statuses of each patient were used to construct cross-validated predictive models to classify patients as complete pathological responders (pCR) or non-complete pathological responders (non-pCR) to NAC. Model performance was evaluated using area under the ROC curve (AUC). The AUC for receptor status alone was 0.62, while the best performance using predictors from the LRRM, NRRM, LTM, and NLTM were AUCs of 0.79, 0.55, 0.60, and 0.59 respectively. This suggests that the LRRM can be used to predict response to NAC in breast cancer.

  5. Is Regional Lymph Node Irradiation Necessary in Stage II to III Breast Cancer Patients With Negative Pathologic Node Status After Neoadjuvant Chemotherapy?

    SciTech Connect

    Daveau, Caroline; Stevens, Denise; Brain, Etienne

    2010-10-01

    Purpose: Neoadjuvant chemotherapy (NAC) generally induces significant changes in the pathologic extent of disease. This potential down-staging challenges the standard indications of adjuvant radiation therapy. We assessed the utility of lymph node irradiation (LNI) in breast cancer (BC) patients with pathologic N0 status (pN0) after NAC and breast-conserving surgery (BCS). Methods and Materials: Among 1,054 BC patients treated with NAC in our institution between 1990 and 2004, 248 patients with clinical N0 or N1 to N2 lymph node status at diagnosis had pN0 status after NAC and BCS. Cox regression analysis was used to identify factors influencing locoregional recurrence-free survival (LRR-FS), disease-free survival (DFS), and overall survival (OS). Results: All 248 patients underwent breast irradiation, and 158 patients (63.7%) also received LNI. With a median follow-up of 88 months, the 5-year LRR-FS and OS rates were respectively 89.4% and 88.7% with LNI and 86.2% and 92% without LNI (no significant difference). Survival was poorer among patients who did not have a pathologic complete primary tumor response (hazard ratio, 3.05; 95% confidence interval, 1.17-7.99) and in patients with N1 to N2 clinical status at diagnosis (hazard ratio = 2.24; 95% confidence interval, 1.15-4.36). LNI did not significantly affect survival. Conclusions: Relative to combined breast and local lymph node irradiation, isolated breast irradiation does not appear to be associated with a higher risk of locoregional relapse or death among cN0 to cN2 breast cancer patients with pN0 status after NAC. These results need to be confirmed in a prospective study.

  6. 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.

  7. The Feasibility and Accuracy of Sentinel Lymph Node Biopsy in Initially Clinically Node-Negative Breast Cancer after Neoadjuvant Chemotherapy: A Systematic Review and Meta-Analysis

    PubMed Central

    Geng, Chong; Chen, Xiao; Pan, Xiaohua; Li, Jiyu

    2016-01-01

    Background With the increased use of neoadjuvant chemotherapy (NAC) in breast cancer, the timing of sentinel lymph node biopsy (SLNB) has become increasingly important. In this study, we aimed to evaluate the feasibility and accuracy of SLNB for initially clinically node-negative breast cancer after NAC by conducting a systematic review and meta-analysis. Methods We searched PubMed, Embase, and the Cochrane Library from January 1, 1993 to November 30, 2015 for studies on initially clinically node-negative breast cancer patients who underwent SLNB after NAC followed by axillary lymph node dissection (ALND). Results A total of 1,456 patients from 16 studies were included in this review. The pooled identification rate (IR) for SLNB was 96% [95% confidence interval (CI): 95%-97%], and the false negative rate (FNR) was 6% (95% CI: 3%-8%). The pooled sensitivity, negative predictive value (NPV) and accuracy rate (AR) were 94% (95% CI: 92%-97%, I2 = 27.5%), 98% (95% CI: 98%-99%, I2 = 42.7%) and 99% (95% CI: 99%-100%, I2 = 32.6%), respectively. In the subgroup analysis, no significant differences were found in either the IR of an SLNB when different mapping methods were used (P = 0.180) or in the FNR between studies with and without immunohistochemistry (IHC) staining (P = 0.241). Conclusion Based on current evidence, SLNB is technically feasible and accurate enough for axillary staging in initially clinically node-negative breast cancer patients after NAC. PMID:27606623

  8. 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.

  9. Chemotherapy

    Cancer.gov

    Chemotherapy is a type of cancer treatment that uses drugs to kill cancer cells. Learn how chemotherapy works against cancer, why it causes side effects, and how it is used with other cancer treatments.

  10. Chemotherapy

    MedlinePlus

    ... to Know Central Venous Catheters Track Your Chemotherapy Side Effects [PDF] Common Concerns About Chemotherapy Get information about common concerns people have when getting chemotherapy, and learn more about related topics. Is It Safe to Keep My Pet While I’m Being Treated for ... Drug Use ...

  11. A retrospective study of neoadjuvant chemotherapy plus radical hysterectomy versus radical hysterectomy alone in patients with stage II cervical squamous cell carcinoma presenting as a bulky mass

    PubMed Central

    Takatori, Eriko; Shoji, Tadahiro; Takada, Anna; Nagasawa, Takayuki; Omi, Hideo; Kagabu, Masahiro; Honda, Tatsuya; Miura, Fumiharu; Takeuchi, Satoshi; Sugiyama, Toru

    2016-01-01

    Objective In order to evaluate the usefulness of neoadjuvant chemotherapy (NAC) for stage II cervical squamous cell carcinoma with a bulky mass, we retrospectively compared patients receiving NAC followed by radical hysterectomy (RH; NAC group) with patients who underwent RH without NAC (Ope group). Patients and methods The study period was from June 2002 to March 2014. The subjects were 28 patients with a stage II bulky mass in the NAC group and 17 such patients in the Ope group. The chi-square test was used to compare operative time, volume of intraoperative blood loss, use of blood transfusion, and time from surgery to discharge between the two groups. Moreover, the log-rank test using the Kaplan–Meier method was performed to compare disease-free survival (DFS) and overall survival (OS) between the groups. Results There were no statistically significant differences between the two groups in operative time, volume of intraoperative blood loss, or use of blood transfusion. However, the time from surgery to discharge was 18 days (14–25 days) in the NAC group and 25 days (21–34 days) in the Ope group; the patients in the NAC group were discharged earlier (P=0.032). The hazard ratio for DFS in the NAC group as compared with that in the Ope group was 0.36 (95% CI 0.08–0.91), and the 3-year DFS rates were 81.2% and 41.0%, respectively (P=0.028). Moreover, the hazard ratio for OS was 0.39 (95% CI 0.11–1.24), and the 3-year OS rates were 82.3% and 66.4%, respectively (P=0.101). Conclusion NAC with cisplatin and irinotecan was confirmed to prolong DFS as compared with RH alone. The results of this study suggest that NAC might be a useful adjunct to surgery in the treatment of stage II squamous cell carcinoma presenting as a bulky mass. PMID:27695343

  12. 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.

  13. Beyond Axillary Lymph Node Metastasis, BMI and Menopausal Status Are Prognostic Determinants for Triple-Negative Breast Cancer Treated by Neoadjuvant Chemotherapy

    PubMed Central

    Bonsang-Kitzis, Hélène; Chaltier, Léonor; Belin, Lisa; Savignoni, Alexia; Rouzier, Roman; Sablin, Marie-Paule; Lerebours, Florence; Bidard, François-Clément; Cottu, Paul; Sastre-Garau, Xavier; Laé, Marick; Pierga, Jean-Yves; Reyal, Fabien

    2015-01-01

    Background Triple-negative breast cancers (TNBC) are a specific subtype of breast cancers with a particularly poor prognosis. However, it is a very heterogeneous subgroup in terms of clinical behavior and sensitivity to systemic treatments. Thus, the identification of risk factors specifically associated with those tumors still represents a major challenge. A therapeutic strategy increasingly used for TNBC patients is neoadjuvant chemotherapy (NAC). Only a subset of patients achieves a pathologic complete response (pCR) after NAC and have a better outcome than patients with residual disease. Purpose The aim of this study is to identify clinical factors associated with the metastatic-free survival in TNBC patients who received NAC. Methods We analyzed 326 cT1-3N1-3M0 patients with ductal infiltrating TNBC treated by NAC. The survival analysis was performed using a Cox proportional hazard model to determine clinical features associated with prognosis on the whole TNBC dataset. In addition, we built a recursive partitioning tree in order to identify additional clinical features associated with prognosis in specific subgroups of TNBC patients. Results We identified the lymph node involvement after NAC as the only clinical feature significantly associated with a poor prognosis using a Cox multivariate model (HR = 3.89 [2.42–6.25], p<0.0001). Using our recursive partitioning tree, we were able to distinguish 5 subgroups of TNBC patients with different prognosis. For patients without lymph node involvement after NAC, obesity was significantly associated with a poor prognosis (HR = 2.64 [1.28–5.55]). As for patients with lymph node involvement after NAC, the pre-menopausal status in grade III tumors was associated with poor prognosis (HR = 9.68 [5.71–18.31]). Conclusion This study demonstrates that axillary lymph node status after NAC is the major prognostic factor for triple-negative breast cancers. Moreover, we identified body mass index and menopausal status as

  14. Utility of Clinical Risk Stratification in the Selection of Muscle-Invasive Bladder Cancer Patients for Neoadjuvant Chemotherapy: A Retrospective Cohort Study.

    PubMed

    von Rundstedt, Friedrich-Carl; Mata, Douglas A; Kryvenko, Oleksandr N; Shah, Anup A; Jhun, Iny; Lerner, Seth P

    2017-01-27

    Introduction: Level I evidence supports the use of cisplatin-based neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer prior to radical cystectomy (RC). On average, 30-40% of patients achieve a complete pathologic response (i.e., stage pT0) after receiving NAC. Some centers risk-stratify patients, suggesting that there may be a higher-risk population that would derive the most benefit from NAC. Recently, a risk-stratification model developed at M.D. Anderson Cancer Center (MDACC) specified criteria for clinical staging and patient selection for NAC. We applied this model to our own RC patient cohort and evaluated our own experience with clinical risk stratification and the effect of NAC on post treatment risk categories. Methods: We retrospectively reviewed the charts of consecutive patients who underwent RC at two institutions between 2004 and 2014 and noted whether or not they received NAC. We determined the clinical stage by reviewing the exam under anesthesia, transurethral resection biopsy (TURBT) pathology, and preoperative imaging. Patients with cT2-T4a node-negative disease were included. Those with sarcomatoid features or adenocarcinoma were excluded. Patients were classified as high risk if they had tumor-associated hydronephrosis, clinical stage≥T3b-T4a disease, variant histology (i.e., micropapillary or small cell), or lymphovascular invasion (LVI), as specified by the MDACC model. Variables were examined for associations with cancer-specific survival (CSS), overall survival (OS), and risk-category reclassification. Results: We identified 166 patients with a median follow-up time of 22.2 months. In all, 117 patients (70.5%) did not receive NAC, 68 (58.1%) of whom we classified as high risk. Among patients not receiving NAC, CSS and OS were significantly decreased in high-risk patients (log-rank test p = 0.01 for both comparisons). The estimated age-adjusted hazard ratios of high-risk classification for cancer-specific and overall

  15. Utility of Clinical Risk Stratification in the Selection of Muscle-Invasive Bladder Cancer Patients for Neoadjuvant Chemotherapy: A Retrospective Cohort Study

    PubMed Central

    von Rundstedt, Friedrich-Carl; Mata, Douglas A.; Kryvenko, Oleksandr N.; Shah, Anup A.; Jhun, Iny; Lerner, Seth P.

    2016-01-01

    Introduction: Level I evidence supports the use of cisplatin-based neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer prior to radical cystectomy (RC). On average, 30–40% of patients achieve a complete pathologic response (i.e., stage pT0) after receiving NAC. Some centers risk-stratify patients, suggesting that there may be a higher-risk population that would derive the most benefit from NAC. Recently, a risk-stratification model developed at M.D. Anderson Cancer Center (MDACC) specified criteria for clinical staging and patient selection for NAC. We applied this model to our own RC patient cohort and evaluated our own experience with clinical risk stratification and the effect of NAC on post treatment risk categories. Methods: We retrospectively reviewed the charts of consecutive patients who underwent RC at two institutions between 2004 and 2014 and noted whether or not they received NAC. We determined the clinical stage by reviewing the exam under anesthesia, transurethral resection biopsy (TURBT) pathology, and preoperative imaging. Patients with cT2-T4a node-negative disease were included. Those with sarcomatoid features or adenocarcinoma were excluded. Patients were classified as high risk if they had tumor-associated hydronephrosis, clinical stage≥T3b-T4a disease, variant histology (i.e., micropapillary or small cell), or lymphovascular invasion (LVI), as specified by the MDACC model. Variables were examined for associations with cancer-specific survival (CSS), overall survival (OS), and risk-category reclassification. Results: We identified 166 patients with a median follow-up time of 22.2 months. In all, 117 patients (70.5%) did not receive NAC, 68 (58.1%) of whom we classified as high risk. Among patients not receiving NAC, CSS and OS were significantly decreased in high-risk patients (log-rank test p = 0.01 for both comparisons). The estimated age-adjusted hazard ratios of high-risk classification for cancer-specific and overall

  16. Chemotherapy

    MedlinePlus

    ... needs plenty of rest to recover from chemotherapy. Scale back on strenuous stuff, and make time to ... teeth very gently to avoid bleeding. Once you've finished chemo, it's still important to visit the ...

  17. Better pathologic complete response and relapse-free survival after carboplatin plus paclitaxel compared with epirubicin plus paclitaxel as neoadjuvant chemotherapy for locally advanced triple-negative breast cancer: a randomized phase 2 trial

    PubMed Central

    Yin, Yi; Mo, Hongnan; Zhang, Bailin; Wang, Xiang; Li, Qing; Yuan, Peng; Wang, Jiayu; Zheng, Shan; Cai, Ruigang; Ma, Fei; Fan, Yin

    2016-01-01

    Background: No standard chemotherapy is used as neoadjuvant therapy in triple negative breast cancer (TNBC). This study has compared carboplatin plus paclitaxel with commonly used epirubicin plus paclitaxel as neoadjuvant chemotherapy (NAC) in TNBC. Results: 91 patients with a median age of 47 years (PC 47 patients, EP 44 patients) were enrolled. 65% of the patients were premenopausal. While the objective response rate was similar in the PC and EP arm (89.4% vs. 79.5%, P = 0.195), the pCR rate in the PC arm was significantly higher (38.6% vs. 14.0%, P = 0.014). The median follow-up time was 55.0 months. 5-year RFS were 77.6% and 56.2%, significantly higher in the PC arm, P = 0.043. No significant difference in OS was observed between the two arms (P = 0.350). Adverse events were similar, except for more thrombocytopenia in the PC arm (P = 0.001). Methods: Patients with stage II/III TNBC were randomized to receive either paclitaxel (175 mg/m2, day1) plus carboplatin (Area Under the Curve = 5, day2) (PC) or epirubicin (75mg/m2, day1) plus paclitaxel (175 mg/m2, day2) (EP) as NAC every three weeks for 4-6 cycles. The primary endpoint was rate of pathologic complete response (pCR).The secondary endpoints included relapse-free survival (RFS), overall survival (OS) and safety. Conclusions:This study suggested that the addition of carboplatin to paclitaxel was superior to the regimen of epirubicin plus paclitaxel as NAC for TNBC in terms of improving pCR rate and RFS. Further phase 3 study has already started. PMID:27447966

  18. Breast-conserving surgery in locally advanced breast cancer submitted to neoadjuvant chemotherapy. Safety and effectiveness based on ipsilateral breast tumor recurrence and long-term follow-up

    PubMed Central

    Carrara, Guilherme Freire Angotti; Scapulatempo-Neto, Cristovam; Abrahão-Machado, Lucas Faria; Brentani, Maria Mitzi; Nunes, João Soares; Folgueira, Maria Aparecida Azevedo Koike; da Costa Vieira, René Aloisio

    2017-01-01

    OBJECTIVE: To evaluate ipsilateral breast tumor recurrence after breast-conserving surgery for locally advanced breast cancer. METHODS: A retrospective observational cohort study was performed in patients with locally advanced breast cancer submitted to breast-conserving surgery after neoadjuvant chemotherapy based on an adriamycin-cyclophosphamide-paclitaxel regimen. We evaluated the clinical, pathologic, immunohistochemistry, and surgical factors that contribute to ipsilateral breast tumor recurrence and locoregional recurrence. A Kaplan-Meier analysis and Cox model were used to evaluate the main factors related to disease-free survival. RESULTS: Of the 449 patients who received neoadjuvant chemotherapy, 98 underwent breast-conserving surgery. The average diameter of the tumors was 5.3 cm, and 87.2% reached a size of up to 3 cm. Moreover, 86.7% were classified as clinical stage III, 74.5% had T3-T4 tumors, 80.5% had N1-N2 axilla, and 89.8% had invasive ductal carcinoma. A pathologic complete response was observed in 27.6% of the tumors, and 100.0% of samples had free margins. The 5-year actuarial overall survival rate was 81.2%, and the mean follow-up was 72.8 months. The rates of ipsilateral breast tumor recurrence and locoregional recurrence were 11.2% and 15.3%, respectively. Multifocal morphology response was the only factor related to ipsilateral breast tumor recurrence disease-free survival (p=0.04). A multivariate analysis showed that the pathologic response evaluation criteria in solid tumors (RECIST)-breast cutoff was the only factor related to locoregional recurrence disease-free survival (p=0.01). CONCLUSIONS: Breast-conserving surgery is a safe and effective therapy for selected locally advanced breast tumors. PMID:28355358

  19. 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

  20. Role of miR-196 and its target gene HoxB8 in the development and proliferation of human colorectal cancer and the impact of neoadjuvant chemotherapy with FOLFOX4 on their expression

    PubMed Central

    Shen, Songfei; Pan, Jie; Lu, Xingrong; Chi, Pan

    2016-01-01

    The present study aimed to investigate the interaction between miR-196 and its target gene homeobox B8 (HoxB8) in colorectal cancer (CRC) cells, and the sensitivity of miR-196 and HoxB8 to fluorouracil, leucovorin and oxaliplatin (FOLFOX4) chemotherapy (1,200 mg/m2 fluorouracil, 200 mg/m2 leucovorin and 85 mg/m2 oxaliplatin). In total, 80 tissue samples were collected in the present study. In total, 50 patients undergoing preoperative chemotherapy completed at least 3 cycles (2 weeks per cycle) of 85 mg/m2 oxaliplatin (day 1) combined with a 2 h injection of 200 mg/m2 leucovorin (days 1 and 2), a bolus injection of 400 mg/m2 and 44 h continuous intravenous infusion of 1,200 mg/m2 fluorouracil. Complete response and partial response were included in the chemotherapy sensitive group (25 patients), and stable disease and progressive disease were included in the chemotherapy resistant group (25 patients). In addition, 30 patients without preoperative chemotherapy were examined for mRNA and protein expression of miR-196 and HoxB8. The expression of the mRNA and protein of miR-196 and HoxB8 was analyzed in 30 CRC and normal mucosa tissue samples. In addition, the expression of the mRNA and protein of miR-196 and HoxB8 was measured in 50 tissue samples obtained from patients that had received FOLFOX4 neoadjuvant chemotherapy. The expression levels of miR-196 and HoxB8 mRNA in CRC tissues were significantly increased compared with the corresponding normal mucosa tissue (P<0.05). The miR-196 mRNA was significantly correlated with lymph node metastasis, tumor stage and distant metastasis (P<0.05). miR-196 was indicated to be negatively correlated with HoxB8 mRNA expression (r=−0.458; P<0.05). The relative amount of miR-196 in the chemotherapy-sensitive group of patients was 0.949±0.691, which was increased compared with the chemotherapy-resistant group (0.345±0.536; P<0.01). The relative level of HoxB8 mRNA in the chemotherapy-sensitive group was 0.490±0.372, which was

  1. Discovery and characterization of novel inhibitors of the sodium-coupled citrate transporter (NaCT or SLC13A5)

    PubMed Central

    Huard, Kim; Brown, Janice; Jones, Jessica C.; Cabral, Shawn; Futatsugi, Kentaro; Gorgoglione, Matthew; Lanba, Adhiraj; Vera, Nicholas B.; Zhu, Yimin; Yan, Qingyun; Zhou, Yingjiang; Vernochet, Cecile; Riccardi, Keith; Wolford, Angela; Pirman, David; Niosi, Mark; Aspnes, Gary; Herr, Michael; Genung, Nathan E.; Magee, Thomas V.; Uccello, Daniel P.; Loria, Paula; Di, Li; Gosset, James R.; Hepworth, David; Rolph, Timothy; Pfefferkorn, Jeffrey A.; Erion, Derek M.

    2015-01-01

    Citrate is a key regulatory metabolic intermediate as it facilitates the integration of the glycolysis and lipid synthesis pathways. Inhibition of hepatic extracellular citrate uptake, by blocking the sodium-coupled citrate transporter (NaCT or SLC13A5), has been suggested as a potential therapeutic approach to treat metabolic disorders. NaCT transports citrate from the blood into the cell coupled to the transport of sodium ions. The studies herein report the identification and characterization of a novel small dicarboxylate molecule (compound 2) capable of selectively and potently inhibiting citrate transport through NaCT, both in vitro and in vivo. Binding and transport experiments indicate that 2 specifically binds NaCT in a competitive and stereosensitive manner, and is recognized as a substrate for transport by NaCT. The favorable pharmacokinetic properties of 2 permitted in vivo experiments to evaluate the effect of inhibiting hepatic citrate uptake on metabolic endpoints. PMID:26620127

  2. Chemotherapy

    MedlinePlus

    ... cell death (apoptosis). Types There are two main types of chemotherapy drugs: Cytostatic: These drugs prevent cells from reproducing. They include: Anti-angiogenesis agents/Angiogenesis inhibitors—These drugs prevent the development of blood vessels around the tumor that provide it with ...

  3. 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

  4. 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

  5. Prechemotherapy neutrophil : lymphocyte ratio is superior to the platelet : lymphocyte ratio as a prognostic indicator for locally advanced esophageal squamous cell cancer treated with neoadjuvant chemotherapy.

    PubMed

    Ji, W H; Jiang, Y H; Ji, Y L; Li, B; Mao, W M

    2016-07-01

    The study aimed to evaluate the prognostic significance of prechemotherapy neutrophil to lymphocyte ratio and platelet to lymphocyte ratio, and preoperative neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in locally advanced esophageal squamous cell cancer. We analyzed retrospectively locally advanced esophageal squamous cell cancer patients who had received neoadjuvant chemotherapy before undergoing a radical esophagectomy between 2009 and 2012. Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio before chemotherapy and before the surgery were calculated. Univariate analyses showed that prechemotherapy neutrophil to lymphocyte ratio >5 (P = 0.048, hazard ratio = 2.86; 95% confidence interval: 1.01-8.12) and prechemotherapy platelet to lymphocyte ratio >130 (P = 0.025, hazard ratio = 5.50; 95% confidence interval: 1.23-24.55) were associated significantly with overall survival (OS), and prechemotherapy platelet to lymphocyte ratio >130 (P = 0.026, hazard ratio = 3.18; 95% confidence interval: 1.15-8.85) was associated significantly with progression-free survival. However, only prechemotherapy neutrophil to lymphocyte ratio >5 (P = 0.024, hazard ratio = 3.50; 95% confidence interval: 1.18-10.40) remained significantly associated with OS in multivariate analyses. Neither preoperative neutrophil to lymphocyte ratio nor platelet to lymphocyte ratio was associated with OS or progression-free survival. The prechemotherapy neutrophil to lymphocyte ratio >5 to preoperative neutrophil to lymphocyte ratio ≤5 group showed significantly worse OS than the prechemotherapy neutrophil to lymphocyte ratio ≤5 to preoperative neutrophil to lymphocyte ratio ≤5 group (P = 0.050). The prechemotherapy platelet to lymphocyte ratio >130 to preoperative platelet to lymphocyte ratio ≤130 group (P = 0.016) and platelet to lymphocyte ratio >130 to preoperative platelet to lymphocyte ratio >130 group (P = 0.042) showed significantly worse OS than the

  6. Comparison of the effectiveness and toxicity of neoadjuvant chemotherapy regimens, capecitabine/epirubicin/cyclophosphamide vs 5-fluorouracil/epirubicin/cyclophosphamide, followed by adjuvant, capecitabine/docetaxel vs docetaxel, in patients with operable breast cancer

    PubMed Central

    Zhang, Minmin; Wei, Wei; Liu, Jianlun; Yang, Huawei; Jiang, Yi; Tang, Wei; Li, Qiuyun; Liao, Xiaoming

    2016-01-01

    The aim of this study was to compare the effectiveness and toxicity of neoadjuvant chemotherapy regimens, xeloda/epirubicin/cyclophosphamide (XEC) vs 5-fluorouracil/epirubicin/cyclophosphamide (FEC), followed by adjuvant chemotherapy regimens, capecitabine/taxotere (XT) vs taxotere (T), in axillary lymph node (LN)-positive early-stage breast cancer. In this randomized, Phase III trial, 137 patients with operable primary breast cancer (T2-0, N0-1) who were tested axillary LN positive through aspiration biopsy of axillary LNs were randomized (1:1) to four 3-weekly cycles of XEC or FEC. Patients underwent surgery within 4–6 weeks after the fourth cycle, followed by four adjuvant cycles of 3-weekly XT or T. The primary end point was tumor pathological complete response. Toxicity profiles were secondary objectives. In total, 131 patients had clinical and radiological evaluation of response and underwent surgery. Treatment with XEC led to an increased rate of pathological complete response in primary tumor (18% vs 6%, respectively, P=0.027) and objective remission rate (87% vs 73%, P=0.048) compared to FEC. Clinical complete response occurred in 20% and 7% for XEC and FEC, respectively. Compared to FEC, XEC was associated with more hand-foot syndrome (57% vs 11%, P<0.001) and 3/4 grade nausea/vomiting/diarrhea (30% vs 14%, P=0.034) but less phlebitis (3% vs 14%, P=0.035). XT and T adjuvant chemotherapy regimens were well tolerated: treatment-related 3/4 grade adverse events occurred in 28% and 17% of patients receiving XT and T, respectively. PMID:27354816

  7. MMP2 and MMP9 serum levels are associated with favorable outcome in patients with inflammatory breast cancer treated with bevacizumab-based neoadjuvant chemotherapy in the BEVERLY-2 study

    PubMed Central

    Tabouret, Emeline; Bertucci, François; Pierga, Jean-Yves; Petit, Thierry; Levy, Christelle; Ferrero, Jean-Marc; Campone, Mario; Gligorov, Joseph; Lerebours, Florence; Roché, Henri; Bachelot, Thomas; van Laere, Steven; Ueno, Naoto T.; Toiron, Yves; Finetti, Pascal; Birnbaum, Daniel; Borg, Jean-Paul; Viens, Patrice

    2016-01-01

    Purpose Addition of bevacizumab to trastuzumab-based neoadjuvant chemotherapy in HER2-positive inflammatory breast cancer (IBC) was associated with favorable outcome in the BEVERLY-2 phase II trial. Circulating levels of matrix metalloproteinases (MMP) 2 and 9 were correlated to high response rate and prolonged survival in high-grade glioma treated with bevacizumab. We examined the prognostic impact of MMP2 and MMP9 serum levels in BEVERLY-2 patients. Experimental design MMP2 and MMP9 serum levels were assessed using ELISA at baseline and before surgery in 45/52 available samples. Correlations were tested with pathological complete response (pCR), disease-free survival (DFS) and overall survival (OS). Results Baseline (b) MMP2 and MMP9 serum levels were independent from patient characteristics and circulating tumor or endothelial cells, and were not correlated to pCR. High bMMP2 was correlated to better DFS (p=0.001) and OS (p=0.032), while low bMMP9 was correlated to better OS (p=0.022) and tended to be associated with longer DFS (p=0.071). In multivariate analyses, bMMP2 (p=0.003, Hazard Ratio [HR]: 0.115) and bMMP9 (p=0.041, HR: 3.511) remained correlated to DFS. As continuous variables, bMMP2 was associated with relapse (p=0.002) and death (p=0.049), while bMMP9 was associated with death (p=0.035). During treatment, significant increase in MMP2 and decrease in MMP9 levels (p<0.001 for both) were observed in 100% and 87% of patients respectively. Conclusions High bMMP2 and low bMMP9 serum levels were associated with better survival in HER2-positive IBC patients treated with bevacizumab- and trastuzumab-based neoadjuvant chemotherapy. Their predictive value of bevacizumab benefit should be evaluated in a randomized trial. PMID:26921265

  8. Neoadjuvant chemotherapy shows similar response in patients with inflammatory or locally advanced breast cancer when compared with operable breast cancer: a secondary analysis of the GeparTrio trial data.

    PubMed

    Costa, Serban Dan; Loibl, Sibylle; Kaufmann, Manfred; Zahm, Dirk-Michael; Hilfrich, Jörn; Huober, Jens; Eidtmann, Holger; du Bois, Andreas; Blohmer, Jens-Uwe; Ataseven, Beyhan; Weiss, Erich; Tesch, Hans; Gerber, Bernd; Baumann, Klaus H; Thomssen, Christoph; Breitbach, Georg Peter; Ibishi, Shaip; Jackisch, Christian; Mehta, Keyur; von Minckwitz, Gunter

    2010-01-01

    PURPOSE Neoadjuvant chemotherapy followed by mastectomy is the treatment of choice in patients with inflammatory breast cancer (IBC) or locally advanced breast cancer (LABC), but it is considered less effective in these diseases than in operable breast cancer (OBC). We report a prospective comparison of the GeparTrio trial of patients with IBC (cT4 days) or LABC (cT4a-c or cN3; stage IIIB or IIIC) and patients with OBC (cT2-3). PATIENTS AND METHODS Participants were stratified by stage and were randomly assigned to six or eight cycles of docetaxel/doxorubicin/cyclophosphamide (TAC) or to two cycles of TAC followed by four cycles of vinorelbine/capecitabine. We present results of a secondary aim of the study, which was to compare pathologic complete response (pCR; ie, no remaining invasive/noninvasive tumor in breast and lymph nodes) in different stage groups. Results A total of 287 patients with IBC (n = 93) or LABC (n = 194) and 1,777 patients with OBC were entered onto the trial. At baseline, parameters were as follows for the three types of cancer, respectively: median tumor sizes: 8.0 cm, 7.0 cm, and 4.0 cm (P < .001); multiple lesions: 31.2%, 27.3%, and 19.6% (P < .001); nodal involvement: 86.6%, 71.2%, and 51.6% (P < .001); grade 3: 44.4%, 30.4%, and 39.9% (P = .178); lobular-invasive type: 7.5%, 17.5%, and 13.3% (P = .673); negative hormone receptor status: 38.0%, 20.0%, and 36.4% (P = .008); and positive human growth factor receptor 2 status: 45.1%, 38.9%, and 35.7% (P = .158). Response rates for IBC, LABC, and OBC, respectively, were 8.6%, 11.3%, and 17.7% for pCR (P = .002); 71.0%, 69.6%, and 83.4% for overall response by physical or sonographic examination (P < .001); and 12.9%, 33.0%, and 69.9% for breast conservation (P < .001). All P values were for IBC and LABC versus OBC. However, tumor stage itself was not an independent predictor for pCR in multivariable analysis (odds ratio, 1.51; 95% CI, 0.88 to 2.59; P = .13). CONCLUSION No evidence of a

  9. 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.

  10. Use of Cox's Cure Model to Establish Clinical Determinants of Long-Term Disease-Free Survival in Neoadjuvant-Chemotherapy-Treated Breast Cancer Patients without Pathologic Complete Response.

    PubMed

    Asano, Junichi; Hirakawa, Akihiro; Hamada, Chikuma; Yonemori, Kan; Hirata, Taizo; Shimizu, Chikako; Tamura, Kenji; Fujiwara, Yasuhiro

    2013-01-01

    In prognostic studies for breast cancer patients treated with neoadjuvant chemotherapy (NAC), the ordinary Cox proportional-hazards (PH) model has been often used to identify prognostic factors for disease-free survival (DFS). This model assumes that all patients eventually experience relapse or death. However, a subset of NAC-treated breast cancer patients never experience these events during long-term follow-up (>10 years) and may be considered clinically "cured." Clinical factors associated with cure have not been studied adequately. Because the ordinary Cox PH model cannot be used to identify such clinical factors, we used the Cox PH cure model, a recently developed statistical method. This model includes both a logistic regression component for the cure rate and a Cox regression component for the hazard for uncured patients. The purpose of this study was to identify the clinical factors associated with cure and the variables associated with the time to recurrence or death in NAC-treated breast cancer patients without a pathologic complete response, by using the Cox PH cure model. We found that hormone receptor status, clinical response, human epidermal growth factor receptor 2 status, histological grade, and the number of lymph node metastases were associated with cure.

  11. Parameterizing the Logistic Model of Tumor Growth by DW-MRI and DCE-MRI Data to Predict Treatment Response and Changes in Breast Cancer Cellularity during Neoadjuvant Chemotherapy1

    PubMed Central

    Atuegwu, Nkiruka C; Arlinghaus, Lori R; Li, Xia; Chakravarthy, A Bapsi; Abramson, Vandana G; Sanders, Melinda E; Yankeelov, Thomas E

    2013-01-01

    Diffusion-weighted and dynamic contrast-enhanced magnetic resonance imaging (MRI) data of 28 patients were obtained pretreatment, after one cycle, and after completion of all cycles of neoadjuvant chemotherapy (NAC). For each patient at each time point, the tumor cell number was estimated using the apparent diffusion coefficient and the extravascular extracellular (ve) and plasma volume (vp) fractions. The proliferation/death rate was obtained using the number of tumor cells from the first two time points in conjunction with the logistic model of tumor growth, which was then used to predict tumor cellularity at the conclusion of NAC. The Pearson correlation coefficient between the predicted and the experimental number of tumor cells measured at the end of NAC was 0.81 (P = .0043). The proliferation rate estimated after the first cycle of therapy was able to separate patients who went on to achieve pathologic complete response from those who did not (P = .021) with a sensitivity and specificity of 82.4% and 72.7%, respectively. These data provide preliminary results indicating that incorporating readily available quantitative MRI data into a simple model of tumor growth can lead to potentially clinically relevant information for predicting an individual patient's response to NAC. PMID:23730404

  12. Crucial Contributions by T Lymphocytes (Effector, Regulatory, and Checkpoint Inhibitor) and Cytokines (TH1, TH2, and TH17) to a Pathological Complete Response Induced by Neoadjuvant Chemotherapy in Women with Breast Cancer

    PubMed Central

    Verma, Chandan; Eremin, Jennifer M.; Cowley, Gerard; Ilyas, Mohammed; Eremin, Oleg

    2016-01-01

    The tumour microenvironment consists of malignant cells, stroma, and immune cells. Prominent tumour-infiltrating lymphocytes (TILs) in breast cancer are associated with a good prognosis and are predictors of a pathological complete response (pCR) with neoadjuvant chemotherapy (NAC). The contribution of different T effector/regulatory cells and cytokines to tumour cell death with NAC requires further characterisation and was investigated in this study. Breast tumours from 33 women with large and locally advanced breast cancers undergoing NAC were immunohistochemically (intratumoural, stromal) assessed for T cell subsets and cytokine expression using labelled antibodies, employing established semiquantitative methods. Prominent levels of TILs and CD4+, CD8+, and CTLA-4+ (stromal) T cells and CD8+ : FOXP3+ ratios were associated with a significant pCR; no association was seen with FOXP3+, CTLA-4+ (intratumoural), and PD-1+ T cells. NAC significantly reduced CD4+, FOXP3+, CTLA-4+ (stromal) (concurrently blood FOXP3+, CTLA-4+ Tregs), and PD-1+ T cells; no reduction was seen with CD8+ and CTLA-4+ (intratumoural) T cells. High post-NAC tumour levels of FOXP3+ T cells, IL-10, and IL-17 were associated with a failed pCR. Our study has characterised further the contribution of T effector/regulatory cells and cytokines to tumour cell death with NAC. PMID:27777963

  13. Identification of SNPs associated with response of breast cancer patients to neoadjuvant chemotherapy in the EORTC-10994 randomized phase III trial.

    PubMed

    Le Morvan, V; Litière, S; Laroche-Clary, A; Ait-Ouferoukh, S; Bellott, R; Messina, C; Cameron, D; Bonnefoi, H; Robert, J

    2015-02-01

    Using cell line panels we identified associations between single-nucleotide polymorphisms (SNPs) and chemosensitivity. To validate these findings in clinics, we genotyped a subset of patients included in a neoadjuvant breast cancer trial to explore the relationship between genotypes and clinical outcome according to treatment received and p53 status. We genotyped 384 selected SNPs in the germline DNA extracted from formalin-fixed paraffin-embedded non-invaded lymph nodes of 243 patients. The polymorphisms of five selected genes were first studied, and then all 384 SNPs were considered. Correction for multiple testing was applied. CYP1B1 polymorphism was significantly associated with pathological complete response (pCR) in patients who had received DNA-damaging agents. MDM2, MDM4 and TP53BP1 polymorphisms were significantly associated with pCR in patients harboring a p53-positive tumor. In the complete SNP panel, there was a significant association between overall survival (OS) and a SNP of ADH1C, R272Q (P=0.0023). By multivariate analysis, only ADH1C genotype and p53 status were significantly associated with OS.

  14. Association of Body Mass Index Changes during Neoadjuvant Chemotherapy with Pathologic Complete Response and Clinical Outcomes in Patients with Locally Advanced Breast Cancer.

    PubMed

    Kogawa, Takahiro; Fouad, Tamer M; Wei, Caimiao; Masuda, Hiroko; Kai, Kazuharu; Fujii, Takeo; El-Zein, Randa; Chavez-MacGregor, Mariana; Litton, Jennifer K; Brewster, Abenaa; Alvarez, Ricardo H; Hortobagyi, Gabriel N; Valero, Vicente; Theriault, Richard; Ueno, Naoto T

    2015-01-01

    The purpose of this study was to determine the association between body mass index (BMI) measurements (baseline BMI and changes in BMI during neoadjuvant systemic treatment [NST]) and clinical efficacy (pathologic complete response [pCR] rate and survival outcomes) in locally advanced breast cancer (LABC). We hypothesized that high baseline BMI and increases in BMI during NST are associated with lower pCR rates and poorer clinical outcomes in LABC. We retrospectively reviewed the medical records of 1002 patients, 204 with primary inflammatory breast cancer (IBC) and 798 with stage III non-IBC, who underwent standard NST and definitive surgery between November 1, 2006, and December 31, 2012. The median follow-up time for the survivors was 19.6 months (0.4 - 67.8 months). The pCR rates of patients whose BMI increased or decreased were 23.2% and 18.1%, respectively, (p=0.048). The unadjusted overall survival (OS) was significantly better in the group with increased BMI (p=0.006). However, increased BMI was not an independent predictor of pCR and clinical outcomes (recurrence-free survival and OS) after adjusting for other clinical variables. In subset analyses, increased BMI as a continuous variable was an independent predictor of higher pCR rates in the normal BMI/underweight group (odds ratio [OR]=1.35, 95% confidence interval [CI]: 1.06-0.71, p=0.015). Increased BMI (BMI change ≥0 vs. <0) was also an independent predictor of pCR (OR=1.65, 95% CI: 1.00-2.72, p=0.049) in the postmenopausal group. Our results show that increasing BMI shows improved clinical outcome in terms of better pCR rates in normal BMI/underweight group and in the postmenopausal group. These results contradict previously reported findings on the association between high BMI and poor clinical efficacy regarding pCR rate and survival outcomes in early-stage breast cancer. Thus, the role of BMI in breast cancer may depend on patients' clinical characteristics such as advanced stage.

  15. Metastatic recurrence in a pancreatic cancer patient derived orthotopic xenograft (PDOX) nude mouse model is inhibited by neoadjuvant chemotherapy in combination with fluorescence-guided surgery with an anti-CA 19-9-conjugated fluorophore.

    PubMed

    Hiroshima, Yukihiko; Maawy, Ali; Zhang, Yong; Murakami, Takashi; Momiyama, Masashi; Mori, Ryutaro; Matsuyama, Ryusei; Katz, Matthew H G; Fleming, Jason B; Chishima, Takashi; Tanaka, Kuniya; Ichikawa, Yasushi; Endo, Itaru; Hoffman, Robert M; Bouvet, Michael

    2014-01-01

    The aim of this study is to determine the efficacy of neoadjuvant chemotherapy (NAC) with gemcitabine (GEM) in combination with fluorescence-guided surgery (FGS) on a pancreatic cancer patient derived orthotopic xenograft (PDOX) model. A PDOX model was established from a CA19-9-positive, CEA-negative tumor from a patient who had undergone a pancreaticoduodenectomy for pancreatic adenocarcinoma. Mice were randomized to 4 groups: bright light surgery (BLS) only; BLS+NAC; FGS only; and FGS+NAC. An anti-CA19-9 or anti-CEA antibody conjugated to DyLight 650 was administered intravenously via the tail vein of mice with the pancreatic cancer PDOX 24 hours before surgery. The PDOX was brightly labeled with fluorophore-conjugated anti-CA19-9, but not with a fluorophore-conjugated anti-CEA antibody. FGS was performed using the fluorophore-conjugated anti-CA19-9 antibody. FGS had no benefit over BLS to prevent metastatic recurrence. NAC in combination with BLS did not convey an advantage over BLS to prevent metastatic recurrence. However, FGS+NAC significantly reduced the metastatic recurrence frequency to one of 8 mice, compared to FGS only after which metastasis recurred in 6 out of 8 mice, and BLS+NAC with metastatic recurrence in 7 out of 8 mice (p = 0.041). Thus NAC in combination with FGS can reduce or even eliminate metastatic recurrence of pancreatic cancer sensitive to NAC. The present study further emphasizes the power of the PDOX model which enables metastasis to occur and thereby identify the efficacy of NAC in combination with FGS on metastatic recurrence.

  16. The role of postmastectomy radiotherapy in clinically node-positive, stage II-III breast cancer patients with pathological negative nodes after neoadjuvant chemotherapy: an analysis from the NCDB

    PubMed Central

    Jiang, Shuai; Jiang, Wen; Chen, Kai; Kim, Betty Y.S.; Liu, Qiang; Jacobs, Lisa K.

    2016-01-01

    Purpose The role of postmastectomy radiotherapy (PMRT) in clinically node-positive, stage II-III breast cancer patients with pathological negative nodes (ypN0) after neoadjuvant chemotherapy (NAC) remains controversial. Methods A total of 1560 clinically node-positive, stage II-III breast cancer patients treated with NAC and mastectomy who achieved ypN0 between 1998 and 2009 in the National Cancer Database were analyzed. The effects of PMRT on overall survival (OS) for the entire cohort and multiple subgroups were evaluated. Imputation and propensity score matching were used as sensitivity analyses to minimize biases. Results Of the entire 1560 eligible patients, 903 (57.9%) received PMRT and 657 (42.1%) didn’t. At a median follow-up of 56.0 months, no statistical difference was observed for OS between two groups by univariate and multivariate analyses (P = 0.120; HR 1.571, 95% CI 0.839-2.943). On subgroup analyses, PMRT significantly improved OS in patients with clinical stage IIIB/IIIC disease, T3/T4 tumor, or residual invasive breast cancer after NAC (P < 0.05). This improvement in OS remained significant after sensitivity analyses for the propensity score-matched patients. Conclusions This study demonstrated that PMRT showed a heterogeneous effect in clinically node-positive, stage II-III breast cancer patients with ypN0 following NAC. PMRT improved OS for patients with clinical stage IIIB/IIIC disease, T3/T4 tumor, or residual invasive breast tumor after NAC. In the absence of definitive conclusions from prospective studies, including the ongoing NSABP B-51 trial, our findings may help identify specific groups of women with clinically node-positive, stage II-III breast cancers who could benefit from PMRT after NAC. PMID:26709538

  17. Identification and resection of the clipped node decreases the false negative rate of sentinel lymph node surgery in patients presenting with node positive breast cancer (T0-T4, N1-2) who receive neoadjuvant chemotherapy – results from ACOSOG Z1071 (Alliance)

    PubMed Central

    Boughey, Judy C.; Ballman, Karla V.; Le-Petross, Huong T.; McCall, Linda M.; Mittendorf, Elizabeth A.; Ahrendt, Gretchen M.; Wilke, Lee G.; Taback, Bret; Feliberti, Eric C.; Hunt, Kelly K.

    2015-01-01

    Background The American College of Surgeons Oncology Group Z1071 trial reported a false negative rate (FNR) of 12.6% with sentinel lymph node (SLN) surgery after neoadjuvant chemotherapy in women presenting with node-positive breast cancer. One proposed method to decrease the FNR is clip placement in the positive node at initial diagnosis with confirmation of clipped node resection at surgery. Methods Z1071 was a multi-institutional trial in which women with clinical T0-4,N1-2,M0 breast cancer underwent SLN surgery and axillary dissection (ALND) after neoadjuvant chemotherapy. In cases with a clip placed in the node, the clip location at surgery (SLN or ALND) was evaluated. Results A clip was placed at initial node biopsy in 203 patients. In the 170 (83.7%) patients with cN1 disease and at least 2 SLNs resected, clip location was confirmed in 141 cases. In 107 (75.9%) patients where the clipped node was within the SLN specimen, the FNR was 6.8% (CI:1.9–16.5%). In 34 (24.1%) cases where the clipped node was in the ALND specimen, the FNR was 19.0% (CI:5.4–41.9%). In cases without a clip placed (n=355) and those where clipped node location was not confirmed at surgery (n=29), the FNR was 13.4% and 14.3%, respectively. Conclusion Clip placement at diagnosis of node-positive disease with removal of the clipped node during SLN surgery reduces the FNR of SLN surgery after neoadjuvant chemotherapy. Clip placement in the biopsy-proven node at diagnosis and evaluation of resected specimens for the clipped node should be considered when performing SLN surgery in this setting. PMID:26649589

  18. 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

  19. A Stromal Immune Module Correlated with the Response to Neoadjuvant Chemotherapy, Prognosis and Lymphocyte Infiltration in HER2-Positive Breast Carcinoma Is Inversely Correlated with Hormonal Pathways

    PubMed Central

    Lae, Marick; Moarii, Matahi; Sadacca, Benjamin; Pinheiro, Alice; Galliot, Marion; Abecassis, Judith; Laurent, Cecile; Reyal, Fabien

    2016-01-01

    Introduction HER2-positive breast cancer (BC) is a heterogeneous group of aggressive breast cancers, the prognosis of which has greatly improved since the introduction of treatments targeting HER2. However, these tumors may display intrinsic or acquired resistance to treatment, and classifiers of HER2-positive tumors are required to improve the prediction of prognosis and to develop novel therapeutic interventions. Methods We analyzed 2893 primary human breast cancer samples from 21 publicly available datasets and developed a six-metagene signature on a training set of 448 HER2-positive BC. We then used external public datasets to assess the ability of these metagenes to predict the response to chemotherapy (Ignatiadis dataset), and prognosis (METABRIC dataset). Results We identified a six-metagene signature (138 genes) containing metagenes enriched in different gene ontologies. The gene clusters were named as follows: Immunity, Tumor suppressors/proliferation, Interferon, Signal transduction, Hormone/survival and Matrix clusters. In all datasets, the Immunity metagene was less strongly expressed in ER-positive than in ER-negative tumors, and was inversely correlated with the Hormonal/survival metagene. Within the signature, multivariate analyses showed that strong expression of the “Immunity” metagene was associated with higher pCR rates after NAC (OR = 3.71[1.28–11.91], p = 0.019) than weak expression, and with a better prognosis in HER2-positive/ER-negative breast cancers (HR = 0.58 [0.36–0.94], p = 0.026). Immunity metagene expression was associated with the presence of tumor-infiltrating lymphocytes (TILs). Conclusion The identification of a predictive and prognostic immune module in HER2-positive BC confirms the need for clinical testing for immune checkpoint modulators and vaccines for this specific subtype. The inverse correlation between Immunity and hormone pathways opens research perspectives and deserves further investigation. PMID:28005906

  20. 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.

  1. Retrospective analysis of 119 Chinese noninflammatory locally advanced breast cancer cases treated with intravenous combination of vinorelbine and epirubicin as a neoadjuvant chemotherapy: a median follow-up of 63.4 months

    PubMed Central

    2009-01-01

    Background This study is a retrospective evaluation of the efficacy of neoadjuvant chemotherapy (NC) with a vinorelbine (V) and epirubicin (E) intravenous combination regimen and is aimed at identification of predictive markers for the long-term outcome in noninflammatory locally advanced breast cancer (NLABC). Methods One-hundred-and-nineteen patients with NLABC were identified from September 2001 to May 2006. Analysis was performed in March 2008, with a median follow-up of 63.4 months (range, 9-76 months). All patients were diagnosed with invasive breast cancer using 14 G core needle biopsy and treated with three cycles of VE before surgery. Local-regional radiotherapy was offered to all patients after the completion of chemotherapy followed by hormonal therapy according to hormone receptor status. Tissue sections cut from formalin-fixed paraffin-embedded blocks from biopsy specimens and postoperative tumor tissues were stained for the presence of estrogen receptor (ER), progesterone receptor (PgR), HER-2 (human epidermal growth factor receptor-2), and MIB-1(Ki-67). Results Patients characteristics were median age 52 years (range: 25-70 years); clinical TNM stage, stage IIB (n = 32), stage IIIA (n = 56), stage IIIB (n = 22) and stage IIIC (n = 9). All patients were evaluable for response: clinically complete response was documented in 27 patients (22.7%); 78 (65.6%) obtained partial response; stable disease was observed in 13 (10.9%); 1 patient (0.8%) had progressive disease. Pathological complete response was found in 22 cases (18.5%). Seventy-five patients were alive with no recurrence after a median follow-up of 63.4 months, the 5-year rates for disease-free survival and overall survival were 58.7% and 71.3%, respectively, after the start of NC. On multivariate analysis, the independent variables associated with increased risk of relapse and death were high pre-Ki-67(p = 0.012, p = 0.017, respectively), high post-Ki-67 expression (p = 0.045, p = 0

  2. Mutations in the Na+/Citrate Cotransporter NaCT (SLC13A5) in Pediatric Patients with Epilepsy and Developmental Delay

    PubMed Central

    Klotz, Jenna; Porter, Brenda E; Colas, Claire; Schlessinger, Avner; Pajor, Ana M

    2016-01-01

    Mutations in the SLC13A5 gene that codes for the Na+/citrate cotransporter, NaCT, are associated with early onset epilepsy, developmental delay and tooth dysplasia in children. In this study, we identify additional SLC13A5 mutations in nine epilepsy patients from six families. To better characterize the syndrome, families with affected children answered questions about the scope of illness and the treatment strategies. Currently, there are no effective treatments, but some antiepileptic drugs targeting the γ-aminobutyric acid system reduce seizure frequency. Acetazolamide, a carbonic anhydrase inhibitor and atypical antiseizure medication, decreases seizures in four patients. In contrast to previous reports, the ketogenic diet and fasting resulted in worsening of symptoms. The effects of the mutations on NaCT transport function and protein expression were examined by transient transfections of COS-7 cells. There was no transport activity from any of the mutant transporters, although some of the mutant transporter proteins were present on the plasma membrane. The structural model of NaCT suggests that these mutations can affect helix packing or substrate binding. We tested various treatments, including chemical chaperones and low temperatures, but none improved transport function in the NaCT mutants. Interestingly, coexpression of NaCT and the mutants results in decreased protein expression and activity of the wild-type transporter, indicating functional interaction. In conclusion, this study has identified additional SLC13A5 mutations in patients with chronic epilepsy starting in the neonatal period, with the mutations producing inactive Na+/citrate transporters. PMID:27261973

  3. 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.

  4. 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.

  5. A Phase II Study of 3′-Deoxy-3′-18F-Fluorothymidine PET in the Assessment of Early Response of Breast Cancer to Neoadjuvant Chemotherapy: Results from ACRIN 6688

    PubMed Central

    Kostakoglu, Lale; Duan, Fenghai; Idowu, Michael O.; Jolles, Paul R.; Bear, Harry D.; Muzi, Mark; Cormack, Jean; Muzi, John P.; Pryma, Daniel A.; Specht, Jennifer M.; Hovanessian-Larsen, Linda; Miliziano, John; Mallett, Sharon; Shields, Anthony F.; Mankoff, David A.

    2016-01-01

    Our objective was to determine whether early change in standardized uptake values (SUVs) of 3′deoxy-3′-18F-fluorothymidine (18F-FLT) using PET with CT could predict pathologic complete response (pCR) of primary breast cancer to neoadjuvant chemotherapy (NAC). The key secondary objective was to correlate SUV with the proliferation marker Ki-67 at baseline and after NAC. Methods This prospective, multicenter phase II study did not specify the therapeutic regimen, thus, NAC varied among centers. All evaluable patients underwent 18F-FLT PET/CT at baseline (FLT1) and after 1 cycle of NAC (FLT2); 43 patients were imaged at FLT1, FLT2, and after NAC completion (FLT3). The percentage change in maximum SUV (%ΔSUVmax) between FLT1 and FLT2 and FLT3 was calculated for the primary tumors. The predictive value of ΔSUVmax for pCR was determined using receiver-operating-characteristic curve analysis. The correlation between SUVmax and Ki-67 was also assessed. Results Fifty-one of 90 recruited patients (median age, 54 y; stage IIA–IIIC) met the eligibility criteria for the primary objective analysis, with an additional 22 patients totaling 73 patients for secondary analyses. A pCR in the primary breast cancer was achieved in 9 of 51 patients. NAC resulted in a significant reduction in %SUVmax (mean Δ, 39%; 95% confidence interval, 31–46). There was a marginal difference in %ΔSUVmax_FLT1-FLT2 between pCR and no-pCR patient groups (Wilcoxon 1-sided P = 0.050). The area under the curve for ΔSUVmax in the prediction of pCR was 0.68 (90% confidence interval, 0.50–0.83; Delong 1-sided P = 0.05), with slightly better predictive value for percentage mean SUV (P = 0.02) and similar prediction for peak SUV (P = 0.04). There was a weak correlation with pretherapy SUVmax and Ki-67 (r = 0.29, P = 0.04), but the correlation between SUVmax and Ki-67 after completion of NAC was stronger (r = 0.68, P < 0.0001). Conclusion 18F-FLT PET imaging of breast cancer after 1 cycle of NAC

  6. 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

  7. Impact of the Addition of Carboplatin and/or Bevacizumab to Neoadjuvant Once-per-Week Paclitaxel Followed by Dose-Dense Doxorubicin and Cyclophosphamide on Pathologic Complete Response Rates in Stage II to III Triple-Negative Breast Cancer: CALGB 40603 (Alliance)

    PubMed Central

    Sikov, William M.; Berry, Donald A.; Perou, Charles M.; Singh, Baljit; Cirrincione, Constance T.; Tolaney, Sara M.; Kuzma, Charles S.; Pluard, Timothy J.; Somlo, George; Port, Elisa R.; Golshan, Mehra; Bellon, Jennifer R.; Collyar, Deborah; Hahn, Olwen M.; Carey, Lisa A.; Hudis, Clifford A.; Winer, Eric P.

    2015-01-01

    Purpose One third of patients with triple-negative breast cancer (TNBC) achieve pathologic complete response (pCR) with standard neoadjuvant chemotherapy (NACT). CALGB 40603 (Alliance), a 2 × 2 factorial, open-label, randomized phase II trial, evaluated the impact of adding carboplatin and/or bevacizumab. Patients and Methods Patients (N = 443) with stage II to III TNBC received paclitaxel 80 mg/m2 once per week (wP) for 12 weeks, followed by doxorubicin plus cyclophosphamide once every 2 weeks (ddAC) for four cycles, and were randomly assigned to concurrent carboplatin (area under curve 6) once every 3 weeks for four cycles and/or bevacizumab 10 mg/kg once every 2 weeks for nine cycles. Effects of adding these agents on pCR breast (ypT0/is), pCR breast/axilla (ypT0/isN0), treatment delivery, and toxicities were analyzed. Results Patients assigned to either carboplatin or bevacizumab were less likely to complete wP and ddAC without skipped doses, dose modification, or early discontinuation resulting from toxicity. Grade ≥ 3 neutropenia and thrombocytopenia were more common with carboplatin, as were hypertension, infection, thromboembolic events, bleeding, and postoperative complications with bevacizumab. Employing one-sided P values, addition of either carboplatin (60% v 44%; P = .0018) or bevacizumab (59% v 48%; P = .0089) significantly increased pCR breast, whereas only carboplatin (54% v 41%; P = .0029) significantly raised pCR breast/axilla. More-than-additive interactions between the two agents could not be demonstrated. Conclusion In stage II to III TNBC, addition of either carboplatin or bevacizumab to NACT increased pCR rates, but whether this will improve relapse-free or overall survival is unknown. Given results from recently reported adjuvant trials, further investigation of bevacizumab in this setting is unlikely, but the role of carboplatin could be evaluated in definitive studies, ideally limited to biologically defined patient subsets most likely

  8. 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.

  9. 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.

  10. Staging and evaluation of neoadjuvant chemotherapy response with ¹⁸F-FDG PET/CT in NUT-midline carcinoma in a child: a case report and review of the literature.

    PubMed

    Ciftci, E; Demirsoy, U; Anik, Y; Gorur, G; Corapcioglu, F; Demir, H

    2015-01-01

    NUT midline carcinoma (NMC) is a newly defined and lethal cancer with aggressive course. It mostly affects children and young adults. Diagnosis is confirmed with the evidence of BRD4-NUT mutation on the chromosome 15q14 by fluorescence in situ hybridization. Use of (18)F-FDG PET/CT in NMC patients is very limited in the literature. In this report, we describe a 7-year-old boy with the diagnosis of NMC who was scanned with (18)F-FDG PET/CT for staging and treatment response evaluation after the chemotherapy. It was disseminated and had moderate FDG avidity in the initial scan and showed progression after 4 cycles of chemotherapy. We also reviewed the literature related to (18)F-FDG PET/CT in staging and assessment of chemotherapy response of NMC.

  11. 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.

  12. Activation of Inflammatory Responses Correlate With Hedgehog Activation and Precede Expansion of Cancer Stem-Like Cells in an Animal Model of Residual Triple Negative Breast Cancer after Neoadjuvant Chemotherapy.

    PubMed

    Arnold, Kimberly M; Flynn, Nicole J; Sims-Mourtada, Jennifer

    2015-01-01

    Triple Negative Breast Cancer (TNBC) is characterized as a lack of expression of the hormonal receptors, estrogen and progesterone, and Human epidermal growth factor receptor 2 (HER2) and as such is unresponsive to current targeted therapy. Resistance of breast cancers to treatment is thought to be due to a sub-population of tumor cells called Breast Cancer Stem Cells (BCSCs) and contributes to poor prognosis and increased risk of recurrence. Previously, we have shown that hedgehog activation is induced by chemotherapy and promotes expansion of a stem-like population in breast cancer cell lines. In addition, chemotherapy can induce an inflammatory response and inflammatory factors can lead to activation of Hedgehog (HH) at sites of tissue injury. Therefore, we wanted to investigate how chemotherapy altered hedgehog signaling and correlated with the release of inflammatory cytokines in a mouse model of breast cancer. Patient derived triple negative breast tumor bearing mice were treated with weekly doses of docetaxel. Following treatment, tumor volume decreased reaching a nadir around 15 days after the start of treatment and increased back to pre-treatment size 35-39 days post treatment. Immunohistochemical staining of mice tumors revealed that Sonic hedgehog and nuclear Gli-1 expression transiently increased following docetaxel treatment, reached peak expression at day 8, and subsequently decreased to almost pre-treatment levels following regrowth of the tumor. Similarly, Interleukin 6 (IL-6) and Interleukin 8 (IL-8) expression transiently increased, peaked around day 8, and decreased upon tumor regrowth, however, remained above pre-treatment levels. Expression of the stem cell marker ALDH1A3 proceeded activation of hedgehog signaling and expression of inflammatory cytokines, increasing around day 15 post treatment and continued to be elevated during tumor regrowth. Thus, chemotherapy treatment resulted in activation of the hedgehog pathway and release of

  13. Neoadjuvant chemoradiotherapy and surgery as treatment for oral maxillary squamous cell carcinoma in a dog.

    PubMed

    Mestrinho, L A; Bernardo, E; Niza, M M R E; Lloret, A; Buracco, P

    2012-07-01

    A gingival maxillary squamous cell carcinoma was diagnosed in a 12-year-old male Yorkshire Terrier. After a complete diagnostic work-up, including a computed tomography scan, the tumour was staged as T3bN1aM0 and considered non-resectable at presentation. The combination of neoadjuvant megavoltage radiotherapy and neoadjuvant and adjuvant chemotherapy with carboplatin and doxorubicin decreased the size of the tumour, allowing for surgery. The dog was free from local disease for 421 days after which it was euthanased at the owners' request.

  14. 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.

  15. 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.

  16. Chemotherapy in Retinoblastoma: Current Approaches

    PubMed Central

    Yanık, Özge; Gündüz, Kaan; Yavuz, Kıvılcım; Taçyıldız, Nurdan; Ünal, Emel

    2015-01-01

    Retinoblastoma (RB) is the most common childhood malignant intraocular tumor. Although enucleation and external beam radiotherapy have been historically used, today the most commonly used eye-sparing approach is chemotherapy. Chemotherapy can be used in both intraocular and extraocular RB cases. Chemotherapeutic agents may be applied in different ways, including systemic, subconjunctival, intra-arterial and intravitreal routes. The main purposes of application of systemic therapy are to reduce the tumor size for local treatment (chemoreduction), or to reduce the risk of metastasis after enucleation surgery (adjuvant therapy). Intra-arterial chemotherapy with the current name “super-selective intra-arterial infusion therapy” could be applied as primary therapy in tumors confined to the retina or as a secondary method in tumor recurrence. The most important advantage of intra-arterial therapy is the prevention of systemic chemotherapy complications. Intravitreal chemotherapy is administered in the presence of persistent or recurrent vitreous seeding. The term “extraocular RB” includes orbital invasion and metastatic disease. Current treatment for orbital invasion is neoadjuvant chemotherapy followed by surgical enucleation and adjuvant chemotherapy and radiotherapy after surgery. In metastatic disease, regional lymph node involvement, distant metastases, and/or central nervous system (CNS) involvement may occur. Among them, CNS involvement has the worst prognosis, remaining at almost 100% mortality. In metastatic disease, high-dose salvage chemotherapy and autologous hematopoietic stem cell rescue therapy are the possible treatment options; radiotherapy could also be added to the protocol according to the side of involvement. PMID:27800245

  17. Chemotherapy and novel therapeutics before radical prostatectomy for high-risk clinically localized prostate cancer.

    PubMed

    Cha, Eugene K; Eastham, James A

    2015-05-01

    Although both surgery and radiation are potential curative options for men with clinically localized prostate cancer, a significant proportion of men with high-risk and locally advanced disease will demonstrate biochemical and potentially clinical progression of their disease. Neoadjuvant systemic therapy before radical prostatectomy (RP) is a logical strategy to improve treatment outcomes for men with clinically localized high-risk prostate cancer. Furthermore, delivery of chemotherapy and other systemic agents before RP affords an opportunity to explore the efficacy of these agents with pathologic end points. Neoadjuvant chemotherapy, primarily with docetaxel (with or without androgen deprivation therapy), has demonstrated feasibility and safety in men undergoing RP, but no study to date has established the efficacy of neoadjuvant chemotherapy or neoadjuvant chemohormonal therapies. Other novel agents, such as those targeting the vascular endothelial growth factor receptor, epidermal growth factor receptor, platelet-derived growth factor receptor, clusterin, and immunomodulatory therapeutics, are currently under investigation.

  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. 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.

  20. 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

  1. Tumour-infiltrating regulatory T cell density before neoadjuvant chemoradiotherapy for rectal cancer does not predict treatment response.

    PubMed

    McCoy, Melanie J; Hemmings, Chris; Anyaegbu, Chidozie C; Austin, Stephanie J; Lee-Pullen, Tracey F; Miller, Timothy J; Bulsara, Max K; Zeps, Nikolajs; Nowak, Anna K; Lake, Richard A; Platell, Cameron F

    2017-02-03

    Neoadjuvant (preoperative) chemoradiotherapy (CRT) decreases the risk of rectal cancer recurrence and reduces tumour volume prior to surgery. However, response to CRT varies considerably between individuals and factors associated with response are poorly understood. Foxp3+ regulatory T cells (Tregs) inhibit anti-tumour immunity and may limit any response to chemotherapy and radiotherapy. We have previously reported that a low density of Tregs in the tumour stroma following neoadjuvant CRT for rectal cancer is associated with improved tumour regression. Here we have examined the association between Treg density in pre-treatment diagnostic biopsy specimens and treatment response, in this same patient cohort. We aimed to determine whether pre-treatment tumour-infiltrating Treg density predicts subsequent response to neoadjuvant CRT. Foxp3+, CD8+ and CD3+ cell densities in biopsy samples from 106 patients were assessed by standard immunohistochemistry (IHC) and evaluated for their association with tumour regression grade and survival. We found no association between the density of any T cell subset pre-treatment and clinical outcome, indicating that tumour-infiltrating Treg density does not predict response to neoadjuvant CRT in rectal cancer. Taken together with the findings of the previous study, these data suggest that in the context of neoadjuvant CRT for rectal cancer, the impact of chemotherapy and/or radiotherapy on anti-tumour immunity may be more important than the state of the pre-existing local immune response.

  2. 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

  3. [Clinical and histopathological results after the neo-adjuvant treatment of advanced rectal tumors].

    PubMed

    Varga, László; Baradnay, Gellért; Hohn, József; Simonka, Zsolt; Hideghéthy, Katalin; Maráz, Anikó; Nikolényi, Alíz; Veréb, Blanka; Tiszlavicz, László; Németh, István; Mán, Eszter; Lázár, György

    2010-06-01

    The role of the surgical intervention is decisive in treating colorectal tumors. The neo-adjuvant radio-chemotherapy has improved the efficacy of the treatment of advanced rectum tumors. In order to decrease the size and stage of advanced rectal carcinoma and to increase the rate of resecability, we introduced neoadjuvant radio-chemotherapy. We carried out neo-adjuvant and surgical treatment in case of 67 patients with rectal adenocarcinoma (T 2-4 N 1-2 M 0 ) between June 1, 2005 and July 31, 2008. The average age of the patients was 61.2 years, the division according to sex was 44 males/23 females. Regarding the local stage of the rectal process or the proximity to the sphincter, we applied radio-chemotherapy (radiotherapy 25 times altogether 45 Gy and on the first and last week for 5-5 days they received 350 mg/m 2 /day 5-FU and 20 mg/m 2 /day leucovorin chemotherapy, recently complemented with 3 x 1.8 Gy advanced boost radiation aiming at the macroscopic tumor site with security zone). Patients underwent surgery 8 weeks on average after restaging examinations. Thirty-eight patients underwent anterior rectal resection with double stapler procedure; there were 18 abdominoperineal rectal extirpations, 7 Hartmann operations and 4 per annum excisions. Compared to the preoperative staging, the histological evaluation of the resected specimens showed total remission (pT 0 N 0 ) in 11% and partial remission in 43%. The morbidity necessitating reoperation was 5.9%, without mortality and suture insufficiency. The long-term neo-adjuvant oncological treatment led to down-staging of rectal tumors in most cases and increased the resecability and rate of resection operations.

  4. 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

  5. Subharmonic Imaging and Pressure Estimation for Monitoring Neoadjuvant Chemotherapy

    DTIC Science & Technology

    2015-11-01

    range for human studies). For these optimization experiments, the dogs’ kidneys were imaged (transcutaneously), because this is the most vascular...imaging sites. We will also acquire simultaneous measurements of pressure in the kidneys with a Logiq 9 ultrasound scanner modified to obtain...obtained in maximum intensity projection (MIP) mode (as part of the optimization algorithm) can be seen in Figure 1 for the left kidney . The

  6. Tracked Ultrasound Elastography for Neo-adjuvant Chemotherapy Monitoring

    DTIC Science & Technology

    2011-05-01

    in the size of the resolution cell . Also, uniform force can be applied to the tissue due to the flat surface of the probe. This is an important...E=F>B=@ QF9f;9BFQR;BQDL9B<gF=BW9B;=E@:B= N9 ;I9hAQRE;O=>;I99RQJ;EDE;OE@QY9JG;I9:B=:=J9W@9;I=WJ9R9D;JQ>9dE@eQY9:QEBJJADI;IQ;EF9QDI:QEB;I9RQ;9BQRQFW=A;e...BQDLEFYJOJ;9@J=>9R9D;B=@QYF9;EDjkSlQFW=:;EDQR;BQDL9B<MJEFY:IQF;=@QFWmnopqprQFE@QR9f:9BE@9F;JGd9JI=d;IQ;;I9:B=:=J9W;9DIFEhA9JJEYFEsDQF;ROE@:B= N9 ;I99RQJ

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. Practical use of perioperative chemotherapy for muscle-invasive bladder cancer: summary of session at the Society of Urologic Oncology annual meeting.

    PubMed

    Apolo, Andrea B; Grossman, Herbert Barton; Bajorin, Dean; Steinberg, Gary; Kamat, Ashish M

    2012-01-01

    At the 11th annual meeting of the Society of Urologic Oncology, an expert panel was convened to discuss the practical use of perioperative chemotherapy for muscle-invasive bladder cancer. The discussion was structured as a case-based debate among the panelists. The topics included: neoadjuvant chemotherapy with a focus on T2 disease, pros and cons, survival data, tolerability of cisplatin-based therapy, can we avoid radical cystectomy in complete responders, limitations and alternatives to cisplatin-based therapy, management of 'suboptimal' chemotherapy, residual disease after neoadjuvant chemotherapy, adjuvant chemotherapy, and key aspects of radical cystectomy and lymph-node dissection in multimodal therapy. The presentations were derived from published literature. The panelists agreed that patients with muscle-invasive bladder cancer should be managed with a multidisciplinary team, including urologist and medical oncologist. Cisplatin-based neoadjuvant chemotherapy has demonstrated improved survival and should be incorporated into the management of all eligible patients with muscle-invasive bladder cancer. However, in some centers, neoadjuvant chemotherapy is reserved for patients with >T2 disease or high-risk features. There are no data for the administration of non-cisplatin-based neoadjuvant chemotherapy, such as carboplatin-combinations. Cisplatin-ineligible patients should proceed directly to surgical extirpation with adjuvant cisplatin-based chemotherapy considered based on pathologic findings. However, the data for adjuvant chemotherapy is less compelling. As our refinement of the selection process continues, we may be able to better identify subsets of patients who may be spared chemotherapy, but much work remains to be done in this arena. The current standard for muscle-invasive bladder cancer patients is cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy and pelvic lymph-node dissection.

  12. Adjuvant gemcitabine versus NEOadjuvant gemcitabine/oxaliplatin plus adjuvant gemcitabine in resectable pancreatic cancer: a randomized multicenter phase III study (NEOPAC study)

    PubMed Central

    2011-01-01

    Background Despite major improvements in the perioperative outcome of pancreas surgery, the prognosis of pancreatic cancer after curative resection remains poor. Adjuvant chemotherapy increases disease-free and overall survival, but this treatment cannot be offered to a significant proportion of patients due to the surgical morbidity. In contrast, almost all patients can receive (neo)adjuvant chemotherapy before surgery. This treatment is safe and effective, and has resulted in a median survival of 26.5 months in a recent phase II trial. Moreover, neoadjuvant chemotherapy improves the nutritional status of patients with pancreatic cancer. This multicenter phase III trial (NEOPAC) has been designed to explore the efficacy of neoadjuvant chemotherapy. Methods/Design This is a prospective randomized phase III trial. Patients with resectable cytologically proven adenocarcinoma of the pancreatic head are eligible for this study. All patients must be at least 18 years old and must provide written informed consent. An infiltration of the superior mesenteric vein > 180° or major visceral arteries are considered exclusion criteria. Eligible patients will be randomized to surgery followed by adjuvant gemcitabine (1000 mg/m2) for 6 months or neoadjuvant chemotherapy (gemcitabine 1000 mg/m2, oxaliplatin 100 mg/m2) followed by surgery and the same adjuvant treatment. Neoadjuvant chemotherapy is given four times every two weeks. The staging as well as the restaging protocol after neoadjuvant chemotherapy include computed tomography of chest and abdomen and diagnostic laparoscopy. The primary study endpoint is progression-free survival. According to the sample size calculation, 155 patients need to be randomized to each treatment arm. Disease recurrence will be documented by scheduled computed tomography scans 9, 12, 15, 21 and thereafter every 6 months until disease progression. For quality control, circumferential resection margins are marked intraoperatively, and

  13. [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

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. Cancer Chemotherapy

    MedlinePlus

    ... controlled way. Cancer cells keep growing without control. Chemotherapy is drug therapy for cancer. It works by killing the cancer ... It depends on the type and amount of chemotherapy you get and how your body reacts. Some ...

  19. 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.

  20. 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

  1. Inhaled chemotherapy in lung cancer: future concept of nanomedicine

    PubMed Central

    Zarogoulidis, Paul; Chatzaki, Ekaterini; Porpodis, Konstantinos; Domvri, Kalliopi; Hohenforst-Schmidt, Wolfgang; Goldberg, Eugene P; Karamanos, Nikos; Zarogoulidis, Konstantinos

    2012-01-01

    Regional chemotherapy was first used for lung cancer 30 years ago. Since then, new methods of drug delivery and pharmaceuticals have been investigated in vitro, and in animals and humans. An extensive review of drug delivery systems, pharmaceuticals, patient monitoring, methods of enhancing inhaled drug deposition, safety and efficacy, and also additional applications of inhaled chemotherapy and its advantages and disadvantages are presented. Regional chemotherapy to the lung parenchyma for lung cancer is feasible and efficient. Safety depends on the chemotherapy agent delivered to the lungs and is dose-dependent and time-dependent. Further evaluation is needed to provide data regarding early lung cancer stages, and whether regional chemotherapy can be used as neoadjuvant or adjuvant treatment. Finally, inhaled chemotherapy could one day be administered at home with fewer systemic adverse effects. PMID:22619512

  2. Inhaled chemotherapy in lung cancer: future concept of nanomedicine.

    PubMed

    Zarogoulidis, Paul; Chatzaki, Ekaterini; Porpodis, Konstantinos; Domvri, Kalliopi; Hohenforst-Schmidt, Wolfgang; Goldberg, Eugene P; Karamanos, Nikos; Zarogoulidis, Konstantinos

    2012-01-01

    Regional chemotherapy was first used for lung cancer 30 years ago. Since then, new methods of drug delivery and pharmaceuticals have been investigated in vitro, and in animals and humans. An extensive review of drug delivery systems, pharmaceuticals, patient monitoring, methods of enhancing inhaled drug deposition, safety and efficacy, and also additional applications of inhaled chemotherapy and its advantages and disadvantages are presented. Regional chemotherapy to the lung parenchyma for lung cancer is feasible and efficient. Safety depends on the chemotherapy agent delivered to the lungs and is dose-dependent and time-dependent. Further evaluation is needed to provide data regarding early lung cancer stages, and whether regional chemotherapy can be used as neoadjuvant or adjuvant treatment. Finally, inhaled chemotherapy could one day be administered at home with fewer systemic adverse effects.

  3. Exploring circulating micro-RNA in the neoadjuvant treatment of breast cancer.

    PubMed

    Casey, Máire-Caitlín; Sweeney, Karl J; Brown, James Andrew Lawrence; Kerin, Michael J

    2016-07-01

    Breast cancer is the most frequently diagnosed malignancy amongst females worldwide. In recent years the management of this disease has transformed considerably, including the administration of chemotherapy in the neoadjuvant setting. Aside from increasing rates of breast conserving surgery and enabling surgery via tumour burden reduction, use of chemotherapy in the neoadjuvant setting allows monitoring of in vivo tumour response to chemotherapeutics. Currently, there is no effective means of identifying chemotherapeutic responders from non-responders. Whilst some patients achieve complete pathological response (pCR) to chemotherapy, a good prognostic index, a proportion of patients derive little or no benefit, being exposed to the deleterious effects of systemic treatment without any knowledge of whether they will receive benefit. The identification of predictive and prognostic biomarkers could confer multiple benefits in this setting, specifically the individualization of breast cancer management and more effective administration of chemotherapeutics. In addition, biomarkers could potentially expedite the identification of novel chemotherapeutic agents or increase their efficacy. Micro-RNAs (miRNAs) are small non-coding RNA molecules. With their tissue-specific expression, correlation with clinicopathological prognostic indices and known dysregulation in breast cancer, miRNAs have quickly become an important avenue in the search for novel breast cancer biomarkers. We provide a brief history of breast cancer chemotherapeutics and explore the emerging field of circulating (blood-borne) miRNAs as breast cancer biomarkers for the neoadjuvant treatment of breast cancer. Established molecular markers of breast cancer are outlined, while the potential role of circulating miRNAs as chemotherapeutic response predictors, prognosticators or potential therapeutic targets is discussed.

  4. Neoadjuvant cisplatin plus temozolomide versus standard treatment in patients with unresectable glioblastoma or anaplastic astrocytoma: a differential effect of MGMT methylation.

    PubMed

    Capdevila, Laia; Cros, Sara; Ramirez, Jose-Luis; Sanz, Carolina; Carrato, Cristina; Romeo, Margarita; Etxaniz, Olatz; Hostalot, Cristina; Massuet, Ana; Cuadra, Jose Luis; Villà, Salvador; Balañà, Carmen

    2014-03-01

    Patients with unresectable glioblastoma or anaplastic astrocytoma have a dismal prognosis. The role of neoadjuvant chemotherapy prior to irradiation in these patients has been studied primarily in non-randomized studies. We have compared the effect of neoadjuvant chemotherapy plus radiotherapy versus concomitant radiotherapy plus temozolomide in a retrospective analysis of two consecutive series of patients in whom surgery consisted of biopsy only. From 2003 to 2005, 23 patients received two cycles of temozolomide plus cisplatin followed by radiotherapy (Cohort 1), and from 2006 to 2010, 23 additional patients received concomitant radiotherapy and temozolomide followed by adjuvant temozolomide (Cohort 2). In Cohort 1, 91.3 % of patients received all planned chemotherapy cycles. Progression-free and overall survival were 3.3 and 8.5 months, respectively. In Cohort 2, progression-free and overall survival were 5.1 and 11.2 months, respectively. No differences between the two groups were observed in rate of completion of radiotherapy, progression-free or overall survival. MGMT methylation was assessed in 91.3 % of patients. In Cohort 1, patients without MGMT methylation showed a trend towards shorter progression-free survival (P = 0.09), while in Cohort 2, patients without MGMT methylation had longer progression-free survival (P = 0.04). In the overall patient population, neoadjuvant temozolomide plus cisplatin had neither a positive nor negative influence on outcome. However, our findings indicate that patients with methylated MGMT may derive greater benefit from neoadjuvant temozolomide than those with unmethylated MGMT.

  5. 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.

  6. 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.

  7. 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

  8. [Place of the pathologist in the management of primary bone tumors (osteosarcoma and Ewing's family tumors after neoadjuvant treatment)].

    PubMed

    Gomez-Brouchet, Anne; Bouvier, Corinne; Decouvelaere, Anne-Valérie; Larousserie, Frédérique; Aubert, Sébastien; Leroy, Xavier; Guinebretière, Jean-Marc; Coulomb, Aurore; Cassagnau, Elisabeth; de Muret, Anne; Audard, Virginie; Marie, Béatrice; de Pinieux, Gonzague

    2011-12-01

    The survival of osteosarcoma and Ewing family tumours has been improved by the introduction of neoadjuvant chemotherapy. The response to preoperative chemotherapy is evaluated on the microscopic analysis of the surgical resection, by the percentage of tumour necrosis according to the Huvos and Rosen's grading. It remains the only reliable prognostic factor for patients and is used to guide the choice of post-operative chemotherapy. The macroscopic and microscopic management of the surgical resection (cf. supra) is essential and is the subject of a specific protocol. Several studies have been conducted to identify news factors able to predict the response to chemotherapy, the tumour aggressiveness and its ability to develop metastases. Inhibitors of mTOR and/or regulators of the balance RANKL/OPG are promising therapeutics. The study's expression of these new factors could be performed on the biopsy and will offer new therapeutic strategy.

  9. 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.

  10. 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.

  11. 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.

  12. Chemotherapy in Early Breast Cancer: When, How and Which One?

    PubMed Central

    Schmidt, Marcus

    2014-01-01

    Summary The efficacy of chemotherapy depends on the level of risk of the individual patient. Because of this, careful estimation of the risk level is mandatory. In addition to well-established clinicopathological factors, validated gene expression signatures might be useful in selected patients if all other criteria are inconclusive for therapeutic decision-making. If indicated, chemotherapy can be used either after surgery (adjuvant) or before surgery (neoadjuvant). Both approaches lead to comparable long-term survival. The neoadjuvant setting offers the additional opportunity for elaborate translational studies to develop and validate predictive biomarkers and to discover mechanisms of resistance to therapy. If possible, chemotherapy regimens should include both anthracyclines and taxanes. Docetaxel should be used every 3 weeks; better tolerability with equivalent efficacy favors the concurrent over the sequential approach. Paclitaxel, on the other hand, should be administered sequentially, either weekly or every 2 weeks. Especially, intense dose-dense sequential chemotherapy with granulocyte colony-stimulating factor support is very effective in high-risk breast cancer patients. In order to decrease toxicities, anthracycline-free regimens or a shortening of the duration of adjuvant chemotherapy are potential options that should be further explored. PMID:25177256

  13. 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.

  14. Metronomic chemotherapy.

    PubMed

    Mutsaers, Anthony J

    2009-08-01

    Chemotherapy drugs are usually administered at doses that are high enough to result in an obligatory break period to allow for the observation of potential side effects and institution of supportive care, if required. In recent years, efforts to administer chemotherapy on a more continuous basis, with a much shorter break period, or none at all, have received increased interest, and the practice has come to be known as metronomic chemotherapy. The basis for success with this currently investigational approach may be rooted in continuous drug exposure to susceptible cancer cells, inhibition of tumor blood vessel growth-a process known as tumor angiogenesis, and/or alterations in tumor immunology. Increased benefit also appears to occur when metronomic chemotherapy is used in combination with newer, targeted antiangiogenic agents, and therefore represents a promising approach to combination therapy, particularly as targeted oncology drugs make their way into veterinary oncology applications. There is still much to be learned in this field, especially with regard to optimization of the proper drugs, dose, schedule, and tumor applications. However, the low cost, ease of administration, and acceptable toxicity profiles potentially associated with this therapeutic strategy make metronomic chemotherapy protocols attractive and suitable to veterinary applications. Preliminary clinical trial results have now been reported in both human and veterinary medicine, including adjuvant treatment of canine splenic hemangiosarcoma and incompletely resected soft tissue sarcoma, and, further, more powerful studies are currently ongoing.

  15. Metronomic chemotherapy

    PubMed Central

    Maiti, Rituparna

    2014-01-01

    Toxic effects and chemoresistance are major hurdles in chemotherapy and to avoid these problems caused by traditional chemotherapeutic regimens, a new modality of drug administration called “metronomic chemotherapy” has emerged. Such regimen involves the frequent administration of conventional chemotherapeutic agents at very low doses to target activated endothelial cells in tumors, the advantages of which include minimal adverse effects and a rare chance of developing acquired drug resistance. Previously it was thought that they act by targeting angiogenesis, but recently additional mechanisms have been discovered which has established metronomic chemotherapy as a type of multi-targeted therapy. The knowledge gained from the preclinical studies of metronomic chemotherapy, along with clinical experience, will help to design better therapeutic protocols against cancer. Detailed pharmacogenomic and pharmacoproteomic studies on tumor endothelial cells and large multi-centered clinical trials, integrating bio-marker analyzes, are needed to investigate and validate the best treatment combinations for each tumor type and patient population. PMID:25210398

  16. Intracavitary chemotherapy

    SciTech Connect

    Markman, M.

    1985-01-01

    Pharmacokinetic modeling has suggested, and clinical investigations have confirmed, that intracavitary drug administration can result in a much greater drug exposure for the cavity into which the agent is instilled compared to the plasma. Both the safety and the efficacy of several agents administered individually or in combination have now been demonstrated. Several malignancies, in particular ovarian carcinoma and malignant mesothelioma, which remain confined to body cavities for much of their natural history, might be most rationally treated by the intracavitary treatment approach. Early clinical trials have demonstrated significant activity of intracavitary chemotherapy in both of these malignancies. Optimal drugs and dosages as well as appropriate scheduling for the various tumors involving body cavities remain to be defined. Whether or not combination intracavitary chemotherapy will significantly improve survival of patients with malignant disease confined to body cavities must await carefully controlled clinical trials comparing this treatment approach to standard systemically administered chemotherapy. 144 references.

  17. A Direct Synergistic Effect of Immunotherapy and Chemotherapy as a New Paradigm in Treatment of Breast Cancer

    DTIC Science & Technology

    2008-04-01

    breast cancer (LABC) have a poor prognosis when treated with surgery and radiotherapy. Preoperative (neo-adjuvant) chemotherapy has been developed...between induction of immunity to the universal tumor antigen CYP1B1 and response to next therapy. Clin Cancer Res 2005;11(12):4430-6. 6. Wheeler CJ

  18. An overview of randomised controlled trials of adjuvant chemotherapy in head and neck cancer.

    PubMed Central

    Munro, A. J.

    1995-01-01

    Meta-analysis of the published results from 54 randomised controlled trials of adjuvant chemotherapy in head and neck cancer suggests that chemotherapy might increase absolute survival by 6.5% (95% confidence interval 3.1-9.9%). The odds ratio in favour of chemotherapy is 1.37 (95% confidence interval 1.24-1.5). Single-agent chemotherapy given synchronously with radiotherapy increased survival by 12.1% (95% confidence interval 5-19%). The benefit from neoadjuvant chemotherapy was less: a rate difference of 3.7% (95% confidence interval 0.9-6.5%). The results suggest that the investigation of optimal agents and scheduling for synchronous radiotherapy and chemotherapy might still be important in clinical trials in head and neck cancer. PMID:7819055

  19. Oral Chemotherapy: What You Need to Know

    MedlinePlus

    ... How Is Chemotherapy Used to Treat Cancer? How Chemotherapy Drugs Work Getting Chemotherapy Questions to Ask About Chemotherapy Chemotherapy ... How Is Chemotherapy Used to Treat Cancer? How Chemotherapy Drugs Work Getting Chemotherapy Questions to Ask About Chemotherapy Chemotherapy ...

  20. 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.

  1. 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

  2. Chemotherapy-induced monoamine oxidase expression in prostate carcinoma functions as a cytoprotective resistance enzyme and associates with clinical outcomes.

    PubMed

    Gordon, Ryan R; Wu, Mengchu; Huang, Chung-Ying; Harris, William P; Sim, Hong Gee; Lucas, Jared M; Coleman, Ilsa; Higano, Celestia S; Gulati, Roman; True, Lawrence D; Vessella, Robert; Lange, Paul H; Garzotto, Mark; Beer, Tomasz M; Nelson, Peter S

    2014-01-01

    To identify molecular alterations in prostate cancers associating with relapse following neoadjuvant chemotherapy and radical prostatectomy patients with high-risk localized prostate cancer were enrolled into a phase I-II clinical trial of neoadjuvant chemotherapy with docetaxel and mitoxantrone followed by prostatectomy. Pre-treatment prostate tissue was acquired by needle biopsy and post-treatment tissue was acquired by prostatectomy. Prostate cancer gene expression measurements were determined in 31 patients who completed 4 cycles of neoadjuvant chemotherapy. We identified 141 genes with significant transcript level alterations following chemotherapy that associated with subsequent biochemical relapse. This group included the transcript encoding monoamine oxidase A (MAOA). In vitro, cytotoxic chemotherapy induced the expression of MAOA and elevated MAOA levels enhanced cell survival following docetaxel exposure. MAOA activity increased the levels of reactive oxygen species and increased the expression and nuclear translocation of HIF1α. The suppression of MAOA activity using the irreversible inhibitor clorgyline augmented the apoptotic responses induced by docetaxel. In summary, we determined that the expression of MAOA is induced by exposure to cytotoxic chemotherapy, increases HIF1α, and contributes to docetaxel resistance. As MAOA inhibitors have been approved for human use, regimens combining MAOA inhibitors with docetaxel may improve clinical outcomes.

  3. Chemotherapy-Induced Monoamine Oxidase Expression in Prostate Carcinoma Functions as a Cytoprotective Resistance Enzyme and Associates with Clinical Outcomes

    PubMed Central

    Huang, Chung-Ying; Harris, William P.; Sim, Hong Gee; Lucas, Jared M.; Coleman, Ilsa; Higano, Celestia S.; Gulati, Roman; True, Lawrence D.; Vessella, Robert; Lange, Paul H.; Garzotto, Mark; Beer, Tomasz M.; Nelson, Peter S.

    2014-01-01

    To identify molecular alterations in prostate cancers associating with relapse following neoadjuvant chemotherapy and radical prostatectomy patients with high-risk localized prostate cancer were enrolled into a phase I-II clinical trial of neoadjuvant chemotherapy with docetaxel and mitoxantrone followed by prostatectomy. Pre-treatment prostate tissue was acquired by needle biopsy and post-treatment tissue was acquired by prostatectomy. Prostate cancer gene expression measurements were determined in 31 patients who completed 4 cycles of neoadjuvant chemotherapy. We identified 141 genes with significant transcript level alterations following chemotherapy that associated with subsequent biochemical relapse. This group included the transcript encoding monoamine oxidase A (MAOA). In vitro, cytotoxic chemotherapy induced the expression of MAOA and elevated MAOA levels enhanced cell survival following docetaxel exposure. MAOA activity increased the levels of reactive oxygen species and increased the expression and nuclear translocation of HIF1α. The suppression of MAOA activity using the irreversible inhibitor clorgyline augmented the apoptotic responses induced by docetaxel. In summary, we determined that the expression of MAOA is induced by exposure to cytotoxic chemotherapy, increases HIF1α, and contributes to docetaxel resistance. As MAOA inhibitors have been approved for human use, regimens combining MAOA inhibitors with docetaxel may improve clinical outcomes. PMID:25198178

  4. 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

  5. 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

  6. (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.

  7. 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

  8. 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.

  9. 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

  10. 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

  11. Types of chemotherapy

    MedlinePlus

    ... medlineplus.gov/ency/patientinstructions/000910.htm Types of chemotherapy To use the sharing features on this page, ... or on cancer cells. How Doctors Choose Your Chemotherapy The type and dose of chemotherapy your doctor ...

  12. Chemoprevention, chemotherapy, and chemoresistance in colorectal cancer.

    PubMed

    Marin, Jose J G; Sanchez de Medina, Fermin; Castaño, Beatriz; Bujanda, Luis; Romero, Marta R; Martinez-Augustin, Olga; Moral-Avila, Rosario Del; Briz, Oscar

    2012-05-01

    Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death in industrialized countries. Chemoprevention is a promising approach, but studies demonstrating their usefulness in large populations are still needed. Among several compounds with chemopreventive ability, cyclooxygenase inhibitors have received particular attention. However, these agents are not without side effects, which must be weighed against their beneficial actions. Early diagnosis is critical in the management of CRC patients, because, in early stages, surgery is curative in >90% of cases. If diagnosis occurs at stages II and III, which is often the case, neoadjuvant chemotherapy and radiotherapy before surgery are, in a few cases, recommended. Because of the high risk of recurrence in advanced cancers, chemotherapy is maintained after tumor resection. Chemotherapy is also indicated when the patient has metastases and in advanced cancer located in the rectum. In the last decade, the use of anticancer drugs in monotherapy or in combined regimens has markedly increased the survival of patients with CRC at stages III and IV. Although the rate of success is higher than in other gastrointestinal tumors, adverse effects and development of chemoresistance are important limitations to pharmacological therapy. Genetic profiling regarding mechanisms of chemoresistance are needed to carry out individualized prediction of the lack of effectiveness of pharmacological regimens. This would minimize side effects and prevent the selection of aggressive, cross-resistant clones, as well as avoiding undesirable delays in the use of the most efficient therapeutic approaches to treat these patients.

  13. Preoperative Chemotherapy for Gastric Cancer: Personal Interventions and Precision Medicine

    PubMed Central

    Xu, Wei; Beeharry, Maneesh K.; Yan, Min; Zhu, Zhenggang

    2016-01-01

    In spite of the declining incidence of gastric cancer (GC) in recent years, the mortality rate is still high. The asymptomatic nature and nonspecific clinical manifestations combined with the lack of efficient screening programs delay the diagnosis of GC. Therefore, the prevalence of advanced gastric cancer (AGC) has prompted the need for aggressive and intensive treatment options. Among the various treatment options for AGC, surgery is still the mainstay. However, the efficacy of surgery alone is not established. Results from multiple randomized controlled trials suggest that preoperative chemotherapy is promising intervention for the treatment and management of AGC. The main objective of neoadjuvant chemotherapy is to downstage or control micrometastasis in resectable tumor before surgery. On the other hand, conversion chemotherapy refers to surgical treatment aiming at R0 resection after chemotherapy for originally nonresectable or marginally resectable tumors. Nevertheless, preoperative chemoradiotherapy is considered beneficial for AGC patients. Over the last few decades, the combination of chemotherapy and targeted therapy prior to surgery demonstrated great results for the treatment of AGC. The rapid developments in genomics and proteomics have heralded the era of precision medicine. The combination of preoperative chemotherapy and precision medicine may enhance survival in AGC patients. PMID:28105420

  14. Tumor deposits: markers of poor prognosis in patients with locally advanced rectal cancer following neoadjuvant chemoradiotherapy

    PubMed Central

    Zhang, Lu-Ning; Xiao, Wei-Wei; Xi, Shao-Yan; OuYang, Pu-Yun; You, Kai-Yun; Zeng, Zhi-Fan; Ding, Pei-Rong; Zhang, Hui-Zhong; Pan, Zhi-Zhong; Xu, Rui-Hua; Gao, Yuan-Hong

    2016-01-01

    Background Tumor deposits (TDs) were reported to be poor prognoses in colorectal carcinoma, but the significance in locally advanced rectal cancer (LARC) (T3-4/N+) following neoadjuvant chemoradiotherapy (neo-CRT) and surgery is unclear. Since adjuvant chemotherapy showed no benefit for LARC following neo-CRT, it is of great value to investigate whether TDs can identify the subgroup of patients who may benefit from adjuvant chemotherapy. Methods Between 2004 and 2012, 310 LARC patients following neo-CRT and surgery were retrospectively reviewed. Overall survival (OS), disease-free survival (DFS), distant metastasis free survival (DMFS) and local recurrence free survival (LRFS) were evaluated by Kaplan-Meier method, log-rank test and Cox models. Results TDs-positive patients showed adverse OS, DFS and DMFS (all P≤0.001), but not LRFS (P = 0.273). In multivariate analysis, TDs continued to be associated with poor OS (HR = 2.44, 95% CI 1.32-4.4, P = 0.004) and DFS (HR = 1.99, 95% CI 1.21-3.27, P = 0.007), but not DMFS (HR = 1.77, 95% CI 0.97-3.20, P = 0.061) or LRFS (HR = 1.85, 95% CI 0.58-5.85, P = 0.298). Among TDs-positive patients, adjuvant chemotherapy significantly improved OS (P = 0.045) and DMFS (P = 0.026), but not DFS (P = 0.127) or LRFS (P = 0.862). Conclusions TDs are predictive of poor survival in LARC after neo-CRT. Fortunately, TDs-positive patients appear to benefit from adjuvant chemotherapy. PMID:26695441

  15. 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

  16. 18F-FLT and 18F-FDG PET/CT in Predicting Response to Chemoradiotherapy in Nasopharyngeal Carcinoma: Preliminary Results

    PubMed Central

    Qi, Shi; Zhongyi, Yang; Yingjian, Zhang; Chaosu, Hu

    2017-01-01

    The purpose of this study was to explore the feasibility of 18F-Fluorothymidine (18F-FLT) and 18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in predicting treatment response of nasopharyngeal carcinoma (NPC). Patients with NPC of Stage II-IVB were prospectively enrolled, receiving 2 cycles of neoadjuvant chemotherapy (NACT), followed by concurrent chemoradiotherapy. Each patient underwent pretreatment and post-NACT FLT PET/CT and FDG PET/CT. Standard uptake values (SUV) and tumor volume were measured. Tumor response to NACT was evaluated before radiotherapy by MRI (magnetic resonance imaging), and tumor regression at the end of radiotherapy was evaluated at 55 Gy, according to RECIST 1.1 Criteria. Finally, 20 patients were consecutively enrolled. At the end of radiotherapy, 7 patients reached complete regression while others were partial regression. After 2 cycles of NACT both FLT and FDG parameters declined remarkably. Parameters of FDG PET were more strongly correlated to tumor regression than those of FLT PET.70% SUVmax was the best threshold to define contouring margin around the target. Some residual lesions after NACT showed by MRI were negative in PET/CT. Preliminary results showed both 18F-FDG and 18F-FLT PET have the potential to monitor and predict tumor regression. PMID:28091565

  17. Ewing sarcoma/primitive neuroectodermal tumor of the kidney treated with chemotherapy including ifosfamide.

    PubMed

    Yoshihara, Hiroki; Kamiya, Takahiro; Hosoya, Yosuke; Hasegawa, Daisuke; Ogawa, Chitose; Asanuma, Hiroshi; Mizuno, Ryuichi; Hosoya, Ryota; Manabe, Atsushi

    2016-08-01

    Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET) of the kidney is extremely rare, and is usually diagnosed after nephrectomy without neoadjuvant chemotherapy. Although ifosfamide and etoposide improve survival to a great extent in ES/PNET, the use of nephrotoxic agent, particularly ifosfamide, is a concern after nephrectomy. We describe the case of a 14-year-old female patient with abdominal mass who was diagnosed with ES/PNET of the right kidney after nephrectomy. Adjuvant chemotherapy including ifosfamide and etoposide were given. The estimated glomerular filtration rate decreased to 75% after the end of therapy. There was no evidence of recurrence 70 months after initial diagnosis.

  18. Breakthrough therapy for peritoneal carcinomatosis of gastric cancer: Intraperitoneal chemotherapy with taxanes

    PubMed Central

    Yamaguchi, Hironori; Kitayama, Joji; Ishigami, Hironori; Kazama, Shinsuke; Nozawa, Hiroaki; Kawai, Kazushige; Hata, Keisuke; Kiyomatsu, Tomomichi; Tanaka, Toshiaki; Tanaka, Junichiro; Nishikawa, Takeshi; Otani, Kensuke; Yasuda, Koji; Ishihara, Soichiro; Sunami, Eiji; Watanabe, Toshiaki

    2015-01-01

    The effect of chemotherapy on peritoneal carcinomatosis (PC) of gastric cancer remains unclear. Recently, the intraperitoneal (IP) administration of taxanes [e.g., paclitaxel (PTX) and docetaxel (DOC)] during the perioperative period has shown promising results. Herein, we summarized the rationale and methodology for using IP chemotherapy with taxanes and reviewed the clinical results. IP administered taxanes remain in the IP space at an extremely high concentration for 48-72 h. The drug directly infiltrates peritoneal metastatic nodules from the surface and then produces antitumor effects, making it ideal for IP chemotherapy. There are two types of perioperative IP chemotherapy with taxanes: neoadjuvant intraperitoneal and systemic chemotherapy and sequential perioperative intraperitoneal chemotherapy (SPIC). In SPIC, patients receive neoadjuvant IP chemotherapy and the same regimen of IP chemotherapy after cytoreductive surgery (CRS) until disease progression. Usually, a taxane dissolved in 500-1000 mL of saline at ordinary temperature is administered through an IP access port on an outpatient basis. According to phase I studies, the recommended doses (RD) are as follows: IP DOC, 45-60 mg/m2; IP PTX [without intravenous (IV) PTX], 80 mg/m2; and IP PTX (with IV PTX), 20 mg/m2. Phase II studies have reported a median survival time of 14.4-24.6 mo with a 1-year overall survival of 67%-78%. A phase III study comparing S-1 in combination with IP and IV PTX to S-1 with IV cisplatin started in 2011. The prognosis of patients who underwent CRS was better than that of those who did not; however, this was partly due to selection bias. Although several phase II studies have shown promising results, a randomized controlled study is needed to validate the effectiveness of IP chemotherapy with taxanes for PC of gastric cancer. PMID:26600928

  19. Quality of life during chemotherapy in lung cancer patients: results across different treatment lines

    PubMed Central

    Wintner, L M; Giesinger, J M; Zabernigg, A; Sztankay, M; Meraner, V; Pall, G; Hilbe, W; Holzner, B

    2013-01-01

    Background: Most lung cancer patients are diagnosed at an advanced disease stage and predominantly receive palliative treatment, which increasingly consists of several chemotherapy lines. We report on patients' quality of life (QOL) to gain knowledge on QOL during and across multiple lines of chemotherapy. This includes patients with (neo)adjuvant therapy up to 3rd or above line palliative chemotherapy. Methods: Lung cancer patients receiving outpatient chemotherapy at the Kufstein County Hospital completed an electronic version of the EORTC QLQ-C30. Linear mixed models were used for statistical analysis. Results: One hundred and eighty seven patients were included in the study. Surprisingly, irrespective of the chemotherapy line patients reported stable QOL scores during treatment. None of the calculated monthly change rates attained clinical significance, referring to established guidelines that classify a small clinical meaningful change as 5 to 10 points. According to treatment line, 3rd or above line palliative chemotherapy was associated with the worst QOL scores, whereas patients undergoing (neo)adjuvant or 1st line palliative chemotherapy reported fairly comparable QOL. Conclusion: The essential finding of our study is that all QOL aspects of the EORTC QLQ-C30 questionnaire remained unchanged during each chemotherapy line in an unselected population of lung cancer patients. Between treatment lines pronounced differences were found, indicating that later palliative chemotherapy lines are associated with higher QOL impairments. These changes in QOL may not primarily be related to the treatment, but rather refer to impairments due to disease progression and may be partly due to a consequence of the prior therapies. PMID:24091620

  20. The role of chemotherapy in early non-small-cell lung cancer management.

    PubMed

    Rosell, R; Felip, E; Maestre, J; Sanchez, J M; Sanchez, J J; Manzano, J L; Astudillo, J; Taron, M; Monzo, M

    2001-12-01

    Great advances have been made in chemotherapy in advanced and metastatic non-small-cell lung cancer (NSCLC), and a major milestone was reached with the administration of neoadjuvant chemotherapy in stage IIIA N2 disease. The systemic nature of lung cancer has been confirmed by many genetic analyses documenting micrometastases in negative lymph nodes and bone marrow, and mRNA gene overexpression as a surrogate of cancer cells has been identified in peripheral blood. Furthermore, serum or plasma cell-free tumor DNA has been observed even in tumors with a diameter of less than 2 cm. Pharmacogenetic screening can lead to tailored chemotherapy even in patients with early disease through the use of a genetic tool kit that will allow us to optimize the use of chemotherapy by using serial measurements of serum DNA that can help to detect residual disease and re-assess the chemosensitivity of sub-clinical micrometastatic disease. The ongoing (neo)adjuvant taxol/carboplatin hope (NATCH) trial is testing the value of three cycles of chemotherapy given pre- or post-operatively compared with surgery alone and will analyze genetic abnormalities in serum DNA at three different points during patient follow-up. Our major concern in this review is to analyze the pros and cons of chemotherapy in NSCLC. Although this review is not a formal meta-analysis, we have discussed the most relevant published studies in this field. We conclude that not only is there no evidence of detrimental effects of chemotherapy, in fact, there are many indications that chemotherapy induces response in up to 80% of patients and downgrades N2 disease in up to 50% of patients. This translates into significantly better survival when accompanied by complete resection. Since at least 50% of patients with stage IB disease develop distant metastases, it seems logical to explore the role of chemotherapy in early disease.

  1. 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.

  2. 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

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

    PubMed Central

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

    2002-01-01

    and toxicity and cost before making treatment decisions. Recommendations After surgical resection, patients whose tumours have penetrated the muscularis propria or involve regional lymph nodes should be considered for adjuvant combined chemoradiotherapy. The current standard protocol consists of 1 cycle of 5-fluorouracil (5-FU) (425 mg/m2 daily) and leucovorin (20 mg/m2 daily) administered daily for 5 days, followed 1 month later by 45 Gy (1.8 Gy/d) of radiation given with 5-FU (400 mg/m2 daily) and leucovorin (20 mg/m2 daily) on days 1 through 4 and the last 3 days of radiation. One month after completion of radiation, 2 cycles of 5-FU (425 mg/m2 daily) and leucovorin (20 mg/m2 daily) in a daily regimen for 5 days are given at monthly intervals. There is no evidence on which to make a recommendation for patients with node-negative tumours that have not penetrated the muscularis propria. For patients unable to undergo radiation, adjuvant chemotherapy alone may be of benefit, particularly for those with lymph-node metastases. The optimal regimen remains to be defined. There is insufficient evidence from randomized trials to recommend neoadjuvant chemotherapy, or neoadjuvant or adjuvant radiotherapy or immunotherapy, either alone or in combination, outside a clinical trial. Validation A draft version of this document was circulated to 166 clinicians using a 21-item feedback questionnaire. Ninety-nine (63%) returned the questionnaire, and 74 of these indicated that the guideline was relevant to their clinical practice and completed the survey. Of the 74 clinicians, 52 (70%) agreed that the document should be approved as a practice guideline. Sponsors The CCOPGI is supported by Cancer Care Ontario and the Ontario Ministry of Health and Long-Term Care. PMID:12500920

  4. Influence of Chemotherapy on EGFR Mutation Status Among Patients With Non–Small-Cell Lung Cancer

    PubMed Central

    Bai, Hua; Wang, Zhijie; Chen, Keneng; Zhao, Jun; Lee, J. Jack; Wang, Shuhang; Zhou, Qinghua; Zhuo, Minglei; Mao, Li; An, Tongtong; Duan, Jianchun; Yang, Lu; Wu, Meina; Liang, Zhen; Wang, Yuyan; Kang, Xiaozheng; Wang, Jie

    2012-01-01

    Purpose EGFR mutation is a predictor of epidermal growth factor receptor–tyrosine kinase inhibitor treatment response in patients with non–small-cell lung cancer (NSCLC). However, it remains unclear whether chemotherapy affects EGFR mutation status in NSCLC. We investigated the influence of chemotherapy on EGFR mutations in plasma and tumor tissues from patients with NSCLC. Patients and Methods Samples were derived from three cohorts: one, 264 patients with advanced NSCLC who received first-line chemotherapy with matched pre- and postchemotherapy blood samples; two, 63 patients with stages IIb to IIIb disease with pre– and post–neoadjuvant chemotherapy tumor tissues; and three, 79 patients with advanced NSCLC who underwent palliative surgery. EGFR mutation status was determined and analyzed to reveal potential impact of chemotherapy. Results In the first cohort, EGFR mutations were detected in 34.5% of the prechemotherapy plasma samples (91 of 264) but in only 23.1% of the postchemotherapy plasma samples (61 of 264). The decrease in EGFR mutation rate was statistically significant (P < .001). Patients whose EGFR mutations switched from positive to negative after chemotherapy had a better partial response (PR) than patients with a reverse change (P = .037). A similar decrease in EGFR mutation rate was observed in tissues after neoadjuvant chemotherapy in the second cohort (34.9% [22 of 63] v 19.0% [12 of 63]; P = .013). In the third cohort, 38.0% of the tumors (30 of 79) showed an intratumor heterogeneity of EGFR mutation, whereas 62.0% (49 of 79) were homogeneous, either with EGFR mutation or no mutation. Conclusion Our results suggest that chemotherapy may reduce EGFR mutation frequency in patients with NSCLC, likely the result of a preferential response of subclones with EGFR mutations in tumors with heterogeneous tumor cell populations. PMID:22826274

  5. Radio-chemotherapy for bladder cancer: Contribution of chemotherapy on local control

    PubMed Central

    Plataniotis, George A; Dale, Roger G

    2013-01-01

    The purpose of this study was to review the magnitude of contribution of chemotherapy (CT) in the local control of muscle invasive bladder carcinoma in the studies where a combined radio-chemotherapy (RCT) was used (how much higher local control rates are obtained with RCT compared to RT alone). Studies on radiotherapy (RT) and combined RCT, neo-adjuvant, concurrent, adjuvant or combinations, reported after 1990 were reviewed. The mean complete response (CR) rates were significantly higher for the RCT studies compared to RT-alone studies: 75.9% vs 64.4% (Wilcoxon rank-sum test, P = 0.001). Eleven of the included RCT studies involved 2-3 cycles of neo-adjuvant CT, in addition to concurrent RCT. The RCT studies included the one-phase type (where a full dose of RCT was given and then assessment of response and cystectomy for non-responders followed) and the two-phase types (where an assessment of response was undertaken after an initial RCT course, followed 6 wk later by a consolidation RCT for those patients with a CR). CR rates between the two subgroups of RCT studies were 79.6% (one phase) vs 71.6% (two-phase) (P = 0.015). The average achievable tumour control rates, with an acceptable rate of side effects have been around 70%, which may represent a plateau. Further increase in CR response rates demands for new chemotherapeutic agents, targeted therapies, or modified fractionation in various combinations. Quantification of RT and CT contribution to local control using radiobiological modelling in trial designs would enhance the potential for both improved outcomes and the estimation of the potential gain. PMID:24003352

  6. [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.

  7. 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.

  8. Assessment of the Radiation-Equivalent of Chemotherapy Contributions in 1-Phase Radio-chemotherapy Treatment of Muscle-Invasive Bladder Cancer

    SciTech Connect

    Plataniotis, George A.; Dale, Roger G.

    2014-03-15

    Purpose: To estimate the radiation equivalent of the chemotherapy contribution to observed complete response rates in published results of 1-phase radio-chemotherapy of muscle-invasive bladder cancer. Methods and Materials: A standard logistic dose–response curve was fitted to data from radiation therapy-alone trials and then used as the platform from which to quantify the chemotherapy contribution in 1-phase radio-chemotherapy trials. Two possible mechanisms of chemotherapy effect were assumed (1) a fixed radiation-independent contribution to local control; or (2) a fixed degree of chemotherapy-induced radiosensitization. A combination of both mechanisms was also considered. Results: The respective best-fit values of the independent chemotherapy-induced complete response (CCR) and radiosensitization (s) coefficients were 0.40 (95% confidence interval −0.07 to 0.87) and 1.30 (95% confidence interval 0.86-1.70). Independent chemotherapy effect was slightly favored by the analysis, and the derived CCR value was consistent with reports of pathologic complete response rates seen in neoadjuvant chemotherapy-alone treatments of muscle-invasive bladder cancer. The radiation equivalent of the CCR was 36.3 Gy. Conclusion: Although the data points in the analyzed radio-chemotherapy studies are widely dispersed (largely on account of the diverse range of chemotherapy schedules used), it is nonetheless possible to fit plausible-looking response curves. The methodology used here is based on a standard technique for analyzing dose-response in radiation therapy-alone studies and is capable of application to other mixed-modality treatment combinations involving radiation therapy.

  9. Squamous Cell Carcinoma of the Pancreas in a Patient with Germline BRCA2 Mutation-Response to Neoadjuvant Radiochemotherapy

    PubMed Central

    Schultheis, Anne M.; Nguyen, Gia Phuong; Ortmann, Monika; Kruis, Wolfgang; Büttner, Reinhard; Schildhaus, Hans-Ulrich; Markiefka, Birgid

    2014-01-01

    Primary squamous cell carcinoma of the pancreas is a rare malignant neoplasia, accounting for approximately 0.5–2% of all malignant pancreatic tumors. These lesions are characterized by poor prognosis. Here we report on a case of a 57-year-old female patient with known BRCA2 germline mutation presenting with primary squamous cell carcinoma of the pancreas as the only malignancy. The tumor was locally advanced at the first presentation but responded almost completely to neoadjuvant radio-chemotherapy. Our case highlights the facts (i) that pancreatic carcinomas belong to the tumor spectrum of patients with the BRCA2-associated hereditary breast and ovarian cancer syndrome (HBOC) and (ii) that tumors of the pancreas can represent the first or even the only manifestation of HBOC. Furthermore, this case of a nonkeratinizing squamous cell carcinoma indicates that HBOC-associated carcinomas of the pancreas might be characterized by a broader morphological spectrum than was previously thought. Since BRCA mutations cause deficiency of DNA double-strand breakage repair in tumors, neoadjuvant treatment regimens might become a reasonable option in HBOC-associated pancreatic carcinomas. To our knowledge, this is the first reported case of a primary pancreatic squamous cell carcinoma in a patient with this particular genetic background of BRCA2-associated HBOC. PMID:24959366

  10. Less than 12 lymph nodes in the surgical specimen after neoadjuvant chemo-radiotherapy: an indicator of tumor regression in locally advanced rectal cancer?

    PubMed Central

    Gurawalia, Jaiprakash; Nayak, Sandeep P.; Kurpad, Vishnu; Pandey, Arun

    2016-01-01

    Background The number of lymph node retrieved in the surgical specimen is important for tumor staging and has paramount impact on prognosis in colorectal cancer and imitates the adequacy of lymph node surgical clearance. The paucity of lymph node yields in patients undergoing resection after preoperative chemo radiotherapy (CRT) in rectal cancer has seen. Lower total number of lymph nodes in the total mesoractal excision (TME) specimen after CRT, could a marker of better tumor response. Methods We retrospectively reviewed the prospectively managed data of patients underwent excision for rectal cancer, who treated by neoadjuvant radiotherapy with or without chemotherapy in locally advanced rectal cancer. From 2010 to 2014, 364 patients underwent rectal cancer surgery, of which ninety-one treated with neoadjuvant treatment. Standard surgical and pathological protocols were followed. Patients were categorized into two groups based on the number of total harvested lymph nodes with group 1, having 12 or more nodes harvested, and group 2 including patients who had <12 lymph nodes harvested. The total number of lymph nodes retrieved from the surgical specimen was correlated with grade of tumor regression with neoadjuvant treatment. Results Out of 91 patients, 38 patients (42%) had less than 12 lymph nodes examined in specimen. The difference in median number of lymph nodes was observed significantly as 9 (range, 2–11) versus 16 (range, 12–32), in group 2 and 1, respectively (P<0.01). Patients with fewer lymph node group were comparable with respect to age, BMI, pre-operative staging, neoadjuvant treatment. Pathological complete response in tumor pCR was seen with significantly higher rate (40% vs. 26%, P<0.05) in group 2. As per Mandard criteria, there was significant difference in tumor regression grade (TRG) between both the groups (P<0.05). Among patients with metastatic lymph nodes, median LNR was lower in <12 lymph nodes group at 0.167 (range, 0.09–0.45) versus

  11. Chemotherapy | Smokefree.gov

    Cancer.gov

    Chemotherapy works by killing cancer cells, but healthy cells get attacked too. Damage to healthy cells can cause uncomfortable side effects. Use this action deck to get information on common chemotherapy side effects and learn how to manage them.

  12. Chemotherapy for Thyroid Cancer

    MedlinePlus

    ... Stage Thyroid Cancer Treating Thyroid Cancer Chemotherapy for Thyroid Cancer Chemotherapy (chemo) uses anti-cancer drugs that are ... Thyroid Cancer, by Type and Stage More In Thyroid Cancer About Thyroid Cancer Causes, Risk Factors, and Prevention ...

  13. Chemotherapy for cholangiocarcinoma: An update.

    PubMed

    Ramírez-Merino, Natalia; Aix, Santiago Ponce; Cortés-Funes, Hernán

    2013-07-15

    tumor effects. Nowadays, no neoadjuvant therapy can be considered a standard approach for the treatment of patients with cholangiocarcinoma. There are promising results and randomized trials are needed in patients with a metastatic cholangiocarcinoma. In systemic therapy, no single drug or combination has consistently increased median survival beyond the expected 8-12 mo. It is always recommended that patients enrol in clinical trials. Clinical trials have shown that the more standard chemotherapy for a first line regimen of gemcitabine plus cisplatin (or oxaliplatin as a potentially better tolerated agent) is superior to gemcitabine alone. Leucovorin-modulated 5-fluorouracil, capecitabine monotherapy or single agent gemcitabine are reasonable options for patients with a borderline performance status. After progression in patients with an adequate performance status, active regimens that could be considered include gemcitabine plus capecitabine, or erlotinib plus bevacizumab, for second line treatment.

  14. Chemotherapy for cholangiocarcinoma: An update

    PubMed Central

    Ramírez-Merino, Natalia; Aix, Santiago Ponce; Cortés-Funes, Hernán

    2013-01-01

    tumor effects. Nowadays, no neoadjuvant therapy can be considered a standard approach for the treatment of patients with cholangiocarcinoma. There are promising results and randomized trials are needed in patients with a metastatic cholangiocarcinoma. In systemic therapy, no single drug or combination has consistently increased median survival beyond the expected 8-12 mo. It is always recommended that patients enrol in clinical trials. Clinical trials have shown that the more standard chemotherapy for a first line regimen of gemcitabine plus cisplatin (or oxaliplatin as a potentially better tolerated agent) is superior to gemcitabine alone. Leucovorin-modulated 5-fluorouracil, capecitabine monotherapy or single agent gemcitabine are reasonable options for patients with a borderline performance status. After progression in patients with an adequate performance status, active regimens that could be considered include gemcitabine plus capecitabine, or erlotinib plus bevacizumab, for second line treatment. PMID:23919111

  15. [Chemotherapy-induced alopecia].

    PubMed

    Spaëth, Dominique; Rosso, Nathalie; Clivot, Laetitia

    2006-11-30

    Chemotherapy-induced alopecia is frequent with most chemotherapy regimens; mechanisms, evolution and small prevention tools are described. Scalp cooling (helmets or continuous cooling systems) can avoid or diminish hair loss in selected chemotherapy regimens but tolerance can be fair and long harmlessness needs to be confirmed by prospective studies. Drug prevention is only in the first steps of research.

  16. 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

  17. 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,

  18. Clinical efficacy of preoperative chemotherapy with or without ifosfamide in patients with osteosarcoma of the extremity: meta-analysis of randomized controlled trials.

    PubMed

    Su, Wenmei; Lai, Zhennan; Wu, Fenping; Lin, Yanming; Mo, Yanli; Yang, Zhixiong; Wu, Jiayuan

    2015-02-01

    Ifosfamide has been used in neoadjuvant chemotherapy since the mid-1980s. Although several studies have been conducted, the results remain controversial. Randomized controlled trials have an improved balance of confounding factors and reliable results. Thus, we performed a meta-analysis based on randomized controlled trials to gather more evidence of the effect of ifosfamide on neoadjuvant chemotherapy for patients with osteosarcoma of the extremity. An electronic search was conducted via the Internet retrieval system to identify eligible trials until September 2014. Odds ratios (ORs) and 95 % confidence interval (CI) were calculated to compare the results of ifosfamide and ifosfamide-free therapies. Four trials with a total of 1,378 patients were eligible for our meta-analysis. Overall, compared with neoadjuvant chemotherapy without ifosfamide, the use of ifosfamide had no advantage in terms of histological response to chemotherapy (cHR; OR 1.36; 95 % CI 0.90-2.03, P = 0.140), 5-year event-free survival (EFS; OR 1.16; 95 % CI 0.789-1.75, P = 0.464), and 5-year overall survival (OS; OR 1.06; 95 % CI 0.70-1.59, P = 0.794). However, improvement was noted in the rate of limb salvage (OR 4.06; 95 % CI 2.04-8.10, P < 0.001). Neoadjuvant chemotherapy with ifosfamide for patients with extremity osteosarcoma might not increase the cHR and exhibited no significant effect on either EFS or OS. However, ifosfamide therapy could significantly increase the rate of limb salvage for osteosarcoma of the extremity, which suggests that the preoperative use of ifosfamide could increase the success rate of limb salvage operation.

  19. Design of a rectal probe for diffuse optical spectroscopy imaging for chemotherapy and radiotherapy monitoring

    NASA Astrophysics Data System (ADS)

    van de Giessen, Martijn; Santoro, Ylenia; Mirzaei Zarandi, Soroush; Pigazzi, Alessio; Cerussi, Albert E.; Tromberg, Bruce J.

    2014-03-01

    Diffuse optical spectroscopy imaging (DOSI) has shown great potential for the early detection of non-responding tumors during neoadjuvant chemotherapy in breast cancer, already one day after therapy starts. Patients with rectal cancer receive similar chemotherapy treatment. The rectum geometry and tissue properties of healthy and tumor tissue in the rectum and the requirement of surface contact impose constraints on the probe design. In this work we present the design of a DOSI probe with the aim of early chemotherapy/radiotherapy effectiveness detection in rectal tumors. We show using Monte Carlo simulations and phantom measurements that the colon tissue can be characterized reliably using a source-detector separation in the order of 10 mm. We present a design and rapid prototype of a probe for DOSI measurements that can be mounted on a standard laparoscope and that fits through a standard rectoscope. Using predominantly clinically approved components we aim at fast clinical translation.

  20. 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.

  1. 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

  2. Decorin in human oral cancer: A promising predictive biomarker of S-1 neoadjuvant chemosensitivity

    SciTech Connect

    Kasamatsu, Atsushi; Uzawa, Katsuhiro; Minakawa, Yasuyuki; Ishige, Shunsaku; Kasama, Hiroki; Endo-Sakamoto, Yosuke; Ogawara, Katsunori; Shiiba, Masashi; Takiguchi, Yuichi; Tanzawa, Hideki

    2015-01-30

    Highlights: • DCN is significantly up-regulated in chemoresistant cancer cell lines. • DCN is a key regulator for chemoresistant mechanisms in vitro and in vivo. • DCN predicts the clinical responses to S-1 NAC for patients with oral cancer. - Abstract: We reported previously that decorin (DCN) is significantly up-regulated in chemoresistant cancer cell lines. DCN is a small leucine-rich proteoglycan that exists and functions in stromal and epithelial cells. Accumulating evidence suggests that DCN affects the biology of several types of cancer by directly/indirectly targeting the signaling molecules involved in cell growth, survival, metastasis, and angiogenesis, however, the molecular mechanisms of DCN in chemoresistance and its clinical relevance are still unknown. Here we assumed that DCN silencing cells increase chemosusceptibility to S-1, consisted of tegafur, prodrug of 5-fluorouracil. We first established DCN knockdown transfectants derived from oral cancer cells for following experiments including chemosusceptibility assay to S-1. In addition to the in vitro data, DCN knockdown zenografting tumors in nude mice demonstrate decreasing cell proliferation and increasing apoptosis with dephosphorylation of AKT after S-1 chemotherapy. We also investigated whether DCN expression predicts the clinical responses of neoadjuvant chemotherapy (NAC) using S-1 (S-1 NAC) for oral cancer patients. Immunohistochemistry data in the preoperative biopsy samples was analyzed to determine the cut-off point for status of DCN expression by receiver operating curve analysis. Interestingly, low DCN expression was observed in five (83%) of six cases with complete responses to S-1 NAC, and in one (10%) case of 10 cases with stable/progressive disease, indicating that S-1 chemosensitivity is dramatically effective in oral cancer patients with low DCN expression compared with high DCN expression. Our findings suggest that DCN is a key regulator for chemoresistant mechanisms, and

  3. 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.

  4. 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

  5. Keratin 5 overexpression is associated with serous ovarian cancer recurrence and chemotherapy resistance.

    PubMed

    Ricciardelli, Carmela; Lokman, Noor A; Pyragius, Carmen E; Ween, Miranda P; Macpherson, Anne M; Ruszkiewicz, Andrew; Hoffmann, Peter; Oehler, Martin K

    2017-01-27

    This study investigated the clinical significance of keratin 5 and 6 expression in serous ovarian cancer progression and chemotherapy resistance. KRT5 and KRT6 (KRT6A, KRT6B & KRT6C) gene expression was assessed in publically available serous ovarian cancer data sets, ovarian cancer cell lines and primary serous ovarian cancer cells. Monoclonal antibodies which detect both K5/6 or only K5 were used to assess protein expression in ovarian cancer cell lines and a cohort of high grade serous ovarian carcinomas at surgery (n = 117) and after neoadjuvant chemotherapy (n = 21). Survival analyses showed that high KRT5 mRNA in stage III/IV serous ovarian cancers was significantly associated with reduced progression-free (HR 1.38, P < 0.0001) and overall survival (HR 1.28, P = 0.013) whilst high KRT6 mRNA was only associated with reduced progression-free survival (HR 1.2, P = 0.031). Both high K5/6 (≥ 10%, HR 1.78 95% CI; 1.03-2.65, P = 0.017) and high K5 (≥ 10%, HR 1.90, 95% CI; 1.12-3.19, P = 0.017) were associated with an increased risk of disease recurrence. KRT5 but not KRT6C mRNA expression was increased in chemotherapy resistant primary serous ovarian cancer cells compared to chemotherapy sensitive cells. The proportion of serous ovarian carcinomas with high K5/6 or high K5 immunostaining was significantly increased following neoadjuvant chemotherapy. K5 can be used to predict serous ovarian cancer prognosis and identify cancer cells that are resistant to chemotherapy. Developing strategies to target K5 may therefore improve serous ovarian cancer survival.

  6. Chemotherapy Studies on Schistosomiasis.

    DTIC Science & Technology

    Schistosoma mansoni, *Chemotherapy, *Prophylaxis, Preventive medicine, Mice, Drugs, Brazil , Laboratory tests, Snails, Cercariae, Tropical medicine, Selection, Parasitology, Schistosomiasis, Chemotherapeutic agents, Medical research

  7. 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.

  8. 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

  9. Chemotherapy for Soft Tissue Sarcomas

    MedlinePlus

    ... Stage Soft Tissue Sarcoma Treating Soft Tissue Sarcomas Chemotherapy for Soft Tissue Sarcomas Chemotherapy (chemo) is the use of drugs given into ... Depending on the type and stage of sarcoma, chemotherapy may be given as the main treatment or ...

  10. Personalized chemotherapy selection for breast cancer using gene expression profiles

    PubMed Central

    Yu, Kaixian; Sang, Qing-Xiang Amy; Lung, Pei-Yau; Tan, Winston; Lively, Ty; Sheffield, Cedric; Bou-Dargham, Mayassa J.; Liu, Jun S.; Zhang, Jinfeng

    2017-01-01

    Choosing the optimal chemotherapy regimen is still an unmet medical need for breast cancer patients. In this study, we reanalyzed data from seven independent data sets with totally 1079 breast cancer patients. The patients were treated with three different types of commonly used neoadjuvant chemotherapies: anthracycline alone, anthracycline plus paclitaxel, and anthracycline plus docetaxel. We developed random forest models with variable selection using both genetic and clinical variables to predict the response of a patient using pCR (pathological complete response) as the measure of response. The models were then used to reassign an optimal regimen to each patient to maximize the chance of pCR. An independent validation was performed where each independent study was left out during model building and later used for validation. The expected pCR rates of our method are significantly higher than the rates of the best treatments for all the seven independent studies. A validation study on 21 breast cancer cell lines showed that our prediction agrees with their drug-sensitivity profiles. In conclusion, the new strategy, called PRES (Personalized REgimen Selection), may significantly increase response rates for breast cancer patients, especially those with HER2 and ER negative tumors, who will receive one of the widely-accepted chemotherapy regimens. PMID:28256629

  11. Evaluation of breast cancer chemotherapy efficacy with multifractal spectrum analysis of magnetic resonance image.

    PubMed

    Li, Li; Hu, Wen-yong; Liu, Li-zhi; Pang, Ya-chun; Shao, Yuan-zhi

    2014-01-01

    Multifractal spectrum analysis of dynamic contrast enhanced (DCE) breast MR images was used to establish a new quantitative analysis method for solid tumor blood perfusion and to explore its applicability in evaluating efficacy of breast cancer chemotherapy. Five randomly selected patients suffering from newly diagnosed malignant breast nodule lesions were enrolled in this study, and four of them were treated with neoadjuvant chemotherapy. Their DCE breast MR images were collected before and after treatment. Chemotherapeutic efficacy was analyzed using international response evaluation criteria for solid tumors (RECIST). Sandbox method for statistical number density was employed to measure and calculate multifractal spectra of DCE breast MR images with spatiotemporal characteristics. Multifractal spectral data of malignant lesions before and after chemotherapy were compared. Multifractal spectra of malignant lesions show an asymmetric bell-shape. Chemotherapy efficacy was assessed to be partial remission (PR) for three patients and their multifractal spectral width significantly increased after chemotherapy while to be stable disease (SD) for other patient and of her changed slightly. Multifractal spectral width correlates with blood-supply condition of tumor lesion before and after chemotherapy, providing a potential suitable characteristic parameter for evaluating chemotherapeutic efficacy quantitatively.

  12. Pediatric and Young Adult Nasopharyngeal Carcinoma Patients Treated With Preradiation Cisplatin and Docetaxel Chemotherapy

    SciTech Connect

    Varan, Ali Ozyar, Enis; Corapcioglu, Funda; Koeksal, Yavuz; Aydin, Burca; Yazici, Nalan; Akyuez, Canan; Bueyuekpamukcu, Muenevver

    2009-03-15

    Purpose: To evaluate treatment results for pediatric and young adult (aged <21 years) patients with nonmetastatic nasopharyngeal carcinoma treated with neoadjuvant cisplatin + docetaxel and radiotherapy. Methods and Materials: Ten patients with nasopharyngeal carcinoma who received diagnoses between 2004 and 2007 were treated with four cycles of cisplatin 100 mg/m{sup 2} + docetaxel 75 mg/m{sup 2} on Day 1 with premedication every 3 weeks. All patients were treated with fractionated external beam radiotherapy after chemotherapy to a median dose of 59.4 Gy (range, 54-59.4 Gy) to the primary disease and 40 Gy to the supraclavicular field with the clavicles shielded. Five children were monitored with serum EBV DNA quantification at diagnosis, after each cycle of chemotherapy, before radiotherapy, and at follow-up. Results: The median age of the patients was 14 years (range, 9-20 years), with a male:female ratio of 6:4. Stage distribution was as follows: 2 patients had Stage IIb disease, 2 had Stage III, 4 had Stage IVa, and 2 had Stage IVb disease. After cisplatin+docetaxel chemotherapy 1 patient had a complete response, 5 had a partial response, 3 had stable disease, and 1 had disease progression. The 2-year overall survival rate in our series was 90% and the event-free survival rate was 70%. No major chemotherapy toxicity was observed. The EBV DNA titers were higher in 2 of the 5 monitored patients at the time of diagnosis. Conclusion: As neoadjuvant chemotherapy before radiotherapy, the cisplatin+docetaxel combination is safe for use in the treatment of childhood nasopharyngeal carcinoma.

  13. High expression of intratumoral stromal proteins is associated with chemotherapy resistance in breast cancer

    PubMed Central

    Wang, Tingting; Srivastava, Supriya; Hartman, Mikael; Buhari, Shaik Ahmad; Chan, Ching-Wan; Iau, Philip; Khin, Lay Wai; Wong, Andrea; Tan, Sing-Huang; Goh, Boon-Cher; Lee, Soo-Chin

    2016-01-01

    We studied the changes of intratumoral stromal proteins including THBS1, TNC, FN, SPARC and α-SMA, following neoadjuvant chemotherapy. The underlying mechanisms by which THBS1 and TNC regulated resistance to docetaxel were further studied using functional studies. 100 patients with newly diagnosed breast cancer were treated with alternating sequential doxorubicin and docetaxel. Immunohistochemistry (IHC) staining for stromal proteins was performed on pre- and post-treatment core biopsies respectively. THBS1 and TNC were further validated with IHC in an independent cohort of 31 patients. A high baseline combined expression score of the 5 stromal proteins predicted independently for poor progression-free (HRadjusted 2.22, 95% CI 1.06–4.64) and overall survival (HRadjusted 5.94, 95% CI 2.25–15.71). After 1–2 cycles of chemotherapy, increased expression of THBS1, TNC, FN, SPARC and α-SMA was seen in patients with subsequent pathological lymph node involvement at surgery. Increased expression of THBS1 and TNC compared to baseline was also seen in intrinsically resistant tumors, but not in sensitive ones. Both THBS1 and TNC-associated chemoresistance were confirmed in an independent validation cohort. Exogenous THBS1 and TNC protected MCF-7 cells against proliferation inhibition induced by docetaxel through activating integrin β1/mTOR pathway. Thus, up-regulation of THBS1, TNC, FN, SPARC and α-SMA following neoadjuvant chemotherapy was associated with chemotherapy resistance in breast cancer patients. Functional studies showed THBS1 and TNC to mediate chemoresistance through the integrin β1/mTOR pathway, suggesting that therapies targeting integrin β1/mTOR pathway may be a promising strategy to overcome chemotherapy resistance. PMID:27487140

  14. 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

  15. Chemotherapy of colorectal liver metastases induces a rapid rise in intermediate blood monocytes which predicts treatment response

    PubMed Central

    Schauer, Dominic; Starlinger, Patrick; Alidzanovic, Lejla; Zajc, Philipp; Maier, Thomas; Feldman, Alexandra; Padickakudy, Robin; Buchberger, Elisabeth; Elleder, Vanessa; Spittler, Andreas; Stift, Judith; Pop, Lorand; Gruenberger, Birgit; Gruenberger, Thomas; Brostjan, Christine

    2016-01-01

    ABSTRACT We have previously reported that intermediate monocytes (CD14++/CD16+) were increased in colorectal cancer (CRC) patients, while the subset of pro-angiogenic TIE2-expressing monocytes (TEMs) was not significantly elevated. This study was designed to evaluate changes in frequency and function of intermediate monocytes and TEMs during chemotherapy and anti-angiogenic cancer treatment and their relation to treatment response. Monocyte populations were determined by flow cytometry in 60 metastasized CRC (mCRC) patients who received neoadjuvant chemotherapy with or without bevacizumab. Blood samples were taken before treatment, after two therapy cycles, at the end of neoadjuvant therapy and immediately before surgical resection of liver metastases. Neoadjuvant treatment resulted in a significant increase in circulating intermediate monocytes which was most pronounced after two cycles and positively predicted tumor response (AUC = 0.875, p = 0.005). With a cut-off value set to 1% intermediate monocytes of leukocytes, this parameter showed a predictive sensitivity and specificity of 75% and 88%. Anti-angiogenic therapy with bevacizumab had no impact on monocyte populations including TEMs. In 15 patients and six healthy controls, the gene expression profile and the migratory behavior of monocyte subsets was evaluated. The profile of intermediate monocytes suggested functions in antigen presentation, inflammatory cytokine production, chemotaxis and was remarkably stable during chemotherapy. Intermediate monocytes showed a preferential migratory response to tumor-derived signals in vitro and correlated with the level of CD14+/CD16+ monocytic infiltrates in the resected tumor tissue. In conclusion, the rapid rise of intermediate monocytes during chemotherapy may offer a simple marker for response prediction and a timely change in regimen. PMID:27471631

  16. Neoadjuvant cisplatin and etoposide, with or without tamoxifen, prior to radiotherapy in high-grade gliomas: a single-center experience.

    PubMed

    Díaz, Roberto; Jordá, María V; Reynés, Gaspar; Aparicio, Jorge; Segura, Angel; Amador, Román; Calderero, Verónica; Beltrán, Andrés

    2005-03-01

    Neoadjuvant chemotherapy (CT), prior to radical radiotherapy (RT), in the treatment of high-grade gliomas may offer several advantages over standard adjuvant CT. The addition of tamoxifen, which can circumvent P-glycoprotein (P-gp)-mediated chemo-resistance, also merits attention. We have evaluated the neoadjuvant regimen of cisplatin and etoposide after surgery of grade III-IV gliomas and prior to radical RT, with regard to response rates (RRs), overall survival (OS) and time to progression (TTP). The synergistic activity between etoposide and tamoxifen was also studied. Forty-four patients were included. CT regime: cisplatin 100 mg/m2 on day +1 and etoposide 100 mg/m2 on days +1 to +3 every 3 weeks for 3 cycles. The initial 24 were also treated with high-dose tamoxifen, 275 mg/m2 on days -3 to +3. An immunohistochemical analysis of P-gp, p53, vascular endothelial growth factor, Ki67 and bcl-2 was also performed. Median follow-up was 11.57 months. In the 16 patients with measurable disease after surgery, a RR of 12.5% was seen, with 37.5% of disease stabilizations and 31.25% of progressions. The median OS and TTP were 11.3 and 5.7 months. Excluding the three deaths possibly related to tamoxifen, grade 3-4 was low, mainly emesis. Favorable prognostic factors were age less than 60 years, extent of surgery, absence of measurable disease, and the absence of radiological necrosis and ring enhancement. Only high p53 expression was associated with better OS. We conclude that neoadjuvant cisplatin and etoposide is a feasible regime, although any real advantage over standard adjuvant CT is dubious. Short-course high-dose tamoxifen should not be used alongside primary CT.

  17. Chemotherapy (For Parents)

    MedlinePlus

    ... road, children and teens treated for cancer often go on to lead long, healthy, and happy lives. Reviewed by: Lisa Wray, MD Date ... Center Side Effects of Chemotherapy and Radiation Late Effects of Cancer and Cancer Treatment Effects ...

  18. Chemotherapy in metastatic retinoblastoma.

    PubMed

    Kingston, J E; Hungerford, J L; Plowman, P N

    1987-03-01

    Eleven children with metastatic retinoblastoma diagnosed during the period 1970-1984 were treated with chemotherapy. Short-term complete responses were observed in three children treated with a four-drug combination which included cisplatinum, and in one child treated with vincristine and cyclophosphamide. The median duration of survival of the 11 children receiving chemotherapy was nine months, whilst the median survival of 13 children with metastatic retinoblastoma who were not given chemotherapy was only 2.3 months (p = 0.06). This suggests that retinoblastoma is a chemosensitive tumour and therefore adjuvant chemotherapy may have a role in children with retinoblastoma who at diagnosis are thought to be at high risk of developing metastatic disease.

  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. 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

  1. Sclerosing Epithelioid Fibrosarcoma of the Bone: A Case Report of High Resistance to Chemotherapy and a Survey of the Literature

    PubMed Central

    Grunewald, Thomas G. P.; von Luettichau, Irene; Weirich, Gregor; Wawer, Angela; Behrends, Uta; Prodinger, Peter M.; Jundt, Gernot; Bielack, Stefan S.; Gradinger, Reiner; Burdach, Stefan

    2010-01-01

    Sclerosing epithelioid fibrosarcoma (SEF) is a rare soft tissue sarcoma mostly occurring in extraosseous sites. SEF represents a clinically challenging entity especially because no standardized treatment regimens are available. Intraosseous localization is an additional challenge with respect to the therapeutical approach. We report on a 16-year-old patient with SEF of the right proximal tibia. The patient underwent standardized neoadjuvant chemotherapy analogous to the EURAMOS-1 protocol for the treatment of osteosarcoma followed by tumor resection and endoprosthetic reconstruction. Histopathological analysis of the resected tumor showed >90% vital tumor cells suggesting no response to chemotherapy. Therefore, therapy was reassigned to the CWS 2002 High-Risk protocol for the treatment of soft tissue sarcoma. To date (22 months after diagnosis), there is no evidence of relapse or metastasis. Our data suggest that SEF may be resistant to a chemotherapy regimen containing Cisplatin, Doxorubicin, and Methotrexate, which should be considered in planning treatment for patients with SEF. PMID:20396630

  2. Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy

    PubMed Central

    Choi, Woonyoung; Porten, Sima; Kim, Seungchan; Willis, Daniel; Plimack, Elizabeth R.; Hoffman-Censits, Jean; Roth, Beat; Cheng, Tiewei; Tran, Mai; Lee, I-Ling; Melquist, Jonathan; Bondaruk, Jolanta; Majewski, Tadeusz; Zhang, Shizhen; Pretzsch, Shanna; Baggerly, Keith; Siefker-Radtke, Arlene; Czerniak, Bogdan; Dinney, Colin P.N.; McConkey, David J.

    2014-01-01

    Summary Muscle-invasive bladder cancers (MIBCs) are biologically heterogeneous and have widely variable clinical outcomes and responses to conventional chemotherapy. We discovered 3 molecular subtypes of MIBC that resembled established molecular subtypes of breast cancer. Basal MIBCs shared biomarkers with basal breast cancers and were characterized by p63 activation, squamous differentiation, and more aggressive disease at presentation. Luminal MIBCs contained features of active PPARγ and estrogen receptor (ER) transcription and were enriched with activating FGFR3 mutations and potentially FGFR inhibitor sensitivity. p53-like MIBCs were consistently resistant to neoadjuvant MVAC chemotherapy, and all chemoresistant tumors adopted a p53-like phenotype after therapy. Our observations have important implications for prognostication, the future clinical development of targeted agents, and disease management with conventional chemotherapy. PMID:24525232

  3. Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy.

    PubMed

    Choi, Woonyoung; Porten, Sima; Kim, Seungchan; Willis, Daniel; Plimack, Elizabeth R; Hoffman-Censits, Jean; Roth, Beat; Cheng, Tiewei; Tran, Mai; Lee, I-Ling; Melquist, Jonathan; Bondaruk, Jolanta; Majewski, Tadeusz; Zhang, Shizhen; Pretzsch, Shanna; Baggerly, Keith; Siefker-Radtke, Arlene; Czerniak, Bogdan; Dinney, Colin P N; McConkey, David J

    2014-02-10

    Muscle-invasive bladder cancers (MIBCs) are biologically heterogeneous and have widely variable clinical outcomes and responses to conventional chemotherapy. We discovered three molecular subtypes of MIBC that resembled established molecular subtypes of breast cancer. Basal MIBCs shared biomarkers with basal breast cancers and were characterized by p63 activation, squamous differentiation, and more aggressive disease at presentation. Luminal MIBCs contained features of active PPARγ and estrogen receptor transcription and were enriched with activating FGFR3 mutations and potential FGFR inhibitor sensitivity. p53-like MIBCs were consistently resistant to neoadjuvant methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy, and all chemoresistant tumors adopted a p53-like phenotype after therapy. Our observations have important implications for prognostication, the future clinical development of targeted agents, and disease management with conventional chemotherapy.

  4. 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

  5. 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

  6. Tumor RNA disruption predicts survival benefit from breast cancer chemotherapy.

    PubMed

    Parissenti, Amadeo M; Guo, Baoqing; Pritzker, Laura B; Pritzker, Kenneth P H; Wang, Xiaohui; Zhu, Mu; Shepherd, Lois E; Trudeau, Maureen E

    2015-08-01

    In a prior substudy of the CAN-NCIC-MA.22 clinical trial (ClinicalTrials.gov identifier NCT00066443), we observed that neoadjuvant chemotherapy reduced tumor RNA integrity in breast cancer patients, a phenomenon we term "RNA disruption." The purpose of the current study was to assess in the full patient cohort the relationship between mid-treatment tumor RNA disruption and both pCR post-treatment and, subsequently, disease-free survival (DFS) up to 108 months post-treatment. To meet these objectives, we developed the RNA disruption assay (RDA) to quantify RNA disruption and stratify it into 3 response zones of clinical importance. Zone 1 is a level of RNA disruption inadequate for pathologic complete response (pCR); Zone 2 is an intermediate level, while Zone 3 has high RNA disruption. The same RNA disruption cut points developed for pCR response were then utilized for DFS. Tumor RDA identified >fourfold more chemotherapy non-responders than did clinical response by calipers. pCR responders were clustered in RDA Zone 3, irrespective of tumor subtype. DFS was about 2-fold greater for patients with tumors in Zone 3 compared to Zone 1 patients. Kaplan-Meier survival curves corroborated these findings that high tumor RNA disruption was associated with increased DFS. DFS values for patients in zone 3 that did not achieve a pCR were similar to that of pCR recipients across tumor subtypes, including patients with hormone receptor positive tumors that seldom achieve a pCR. RDA appears superior to pCR as a chemotherapy response biomarker, supporting the prospect of its use in response-guided chemotherapy.

  7. Surgical treatment pattern and outcomes in epithelial ovarian cancer patients from a cancer institute in Kerala, India

    PubMed Central

    Georgeena, P; Rajanbabu, Anupama; Vijaykumar, DK; Pavithran, K; Sundaram, KR; Deepak, KS; Sanal, MR

    2016-01-01

    Objective To evaluate the treatment and survival pattern of patients with advanced epithelial ovarian cancer. Methods and results Retrospective study of all advanced epithelial ovarian cancer patients treated in the department of gynaecologic oncology from an academic centre, in a four year period from 1 January 2008–31 December 2011. Selection criteria All patients with advanced epithelial ovarian cancer (stage III and IV) who underwent surgery from 2008–2011and had a follow-up of at least three months after completion of treatment were included. The decision on whether primary surgery or neoadjuvant chemotherapy (NACT) in advanced ovarian cancer was based on age, performance status, clinical and imaging findings. Results A total of 178 cases of epithelial ovarian cancer were operated on during this four year period. Among them 28 patients were recurrent cases, 22 had early stages of ovarian cancer, and the rest 128 had stage III and IV ovarian cancer. In these 128 patients, 50(39.1%) underwent primary surgery and 78(60.9%) had NACT followed by surgery. In the primary surgery group 36(72.0%) patients had optimal debulking while in the NACT group 59(75.6%) patient had optimal debulking. With a median follow-up of 34 months, the median overall survival (OS) and progression free survival (PFS) was 53 and 49 months respectively. Patients who underwent primary surgery had better median PFS than patients who had NACT (56 months versus 39 months, p = 0.002). In stage III C the difference median PFS was significant for those treated with primary surgery when compared with NACT (55 months versus 39 months, p = 0.012). In patients who had optimal debulking to no residual disease (n = 90), primary surgery gave a significant improved PFS (59 months versus 38 months, p = 0.001) when compared with NACT. In univariate analysis, NACT was associated with increased risk of death (HR: 0.350; CI: 0.177–0.693). Conclusion In advanced epithelial ovarian cancer, primary surgery

  8. Adjuvant chemotherapy in soft tissue sarcomas…Conflicts, consensus, and controversies.

    PubMed

    Bajpai, Jyoti; Susan, Deepa

    2016-01-01

    Soft tissue sarcomas (STSs) are an uncommon and diverse group of more than 50 mesenchymal malignancies. Each of these histologic subtypes represents a unique disease with distinct biologic behavior and varying sensitivity to chemotherapy. The judicious use of adjuvant/neoadjuvant chemotherapy along with surgery and radiation in the treatment of localized STS has a role in improving patient outcomes by decreasing local and distant recurrences. There is evidence that the use of adjuvant chemotherapy to a mixed cohort of chemo sensitive and insensitive sarcoma subtypes results in limited benefit. Therefore, it is of paramount importance to identify the subpopulation with high metastatic potential and to identify effective histology-specific treatment options to these patients. Present perspective, will focus on the rationale for adjuvant chemotherapy in sarcoma, with emphasis on the histology driven chemotherapy. It will outline key therapeutic opportunities and hurdles in adjuvant medical treatment of sarcoma, focusing on specific subtypes that are on the verge of new breakthroughs, as well as those in which promise has not lived up to expectations.

  9. Response to chemotherapy is not related to chromosome instability in synovial sarcoma

    PubMed Central

    Chakiba, C.; Lagarde, P.; Pissaloux, D.; Neuville, A.; Brulard, C.; Pérot, G.; Coindre, J. M.; Terrier, P.; Ranchere-Vince, D.; Ferrari, A.; Collini, P.; Suurmeijer, A. J. H.; Blay, J. Y.; Terrisse, S. A.; Piperno-Neumann, S.; Averous, G.; Bui, B.; Orbach, D.; Italiano, A.; Chibon, F.

    2014-01-01

    Background Synovial sarcoma (SS) is an aggressive soft-tissue tumor. Despite being considered as a chemosensitive disease, the real impact of perioperative chemotherapy on metastasis-free survival (MFS) is controversial. We have shown that metastatic relapse of SS is strongly associated with genomic complexity. There are no data regarding the potential correlation between genomic complexity and response to chemotherapy. Patients and methods The study population included 65 SS patients diagnosed between 1991 and 2013 and with available tissue material. Genomic profiling was carried out by using array-CGH. Forty-five SS out of the 65 patients were treated with neoadjuvant anthracycline/ifosfamide-based chemotherapy. Radiological response was assessed according to RECIST criteria. Histological response was defined by the percentage of recognizable tumor cells on the surgical specimen. Results Genomic complexity was significantly associated with MFS. However, there was no statistically significant association between radiological or histological response and genomic complexity. Conclusion The absence of significant association between response to chemotherapy and genomic complexity suggests that the prognostic value of chromosome instability in SS is independent of response to chemotherapy; mechanisms leading to metastatic relapse of SS are intrinsic to the biology of the tumor and current cytotoxic drugs are only poorly efficient to prevent it. PMID:25070544

  10. Sensor-controlled scalp cooling to prevent chemotherapy-induced alopecia in female cancer patients

    PubMed Central

    Fehr, M.K.; Welter, J.; Sell, W.; Jung, R.; Felberbaum, R.

    2016-01-01

    Background Scalp cooling has been used since the 1970s to prevent chemotherapy-induced alopecia, one of the most common and psychologically troubling side effects of chemotherapy. Currently available scalp cooling systems demonstrate varying results in terms of effectiveness and tolerability. Methods For the present prospective study, 55 women receiving neoadjuvant, adjuvant, or palliative chemotherapy were enrolled. The aim was to assess the effectiveness of a sensor-controlled scalp cooling system (DigniCap: Sysmex Europe GmbH, Norderstedt, Germany) to prevent chemotherapy-induced alopecia in breast or gynecologic cancer patients receiving 1 of 7 regimens. Clinical assessments, satisfaction questionnaires, and alopecia evaluations [World Health Organization (who) grading for toxicity] were completed at baseline, at each cycle, and at completion of chemotherapy. Results Of the 55 patients, 78% underwent scalp cooling until completion of chemotherapy. In multivariate analysis, younger women and those receiving paclitaxel weekly or paclitaxel–carboplatin experienced less alopecia. The compound successful outcome (“no head covering” plus “who grade 0/1”) was observed in all patients 50 years of age and younger receiving 4 cycles of docetaxel–cyclophosphamide or 6 cycles of paclitaxel–carboplatin. Conversely, alopecia was experienced by all women receiving triplet polychemotherapy (6 cycles of docetaxel–doxorubicin–cyclophosphamide). For women receiving sequential polychemotherapy regimens (3 cycles of fluorouracil–epirubicin–cyclophosphamide followed by 3 cycles of docetaxel or 4 cycles of doxorubicin–cyclophosphamide followed by 4 cycles of docetaxel), the subgroup 50 years of age and younger experienced a 43% success rate compared with a 10% rate for the subgroup pf older women receiving the same regimens. Conclusions The ability of scalp cooling to prevent chemotherapy-induced alopecia varies with the chemotherapy regimen and the age of the

  11. A germline predictive signature of response to platinum chemotherapy in esophageal cancer.

    PubMed

    Rumiato, Enrica; Boldrin, Elisa; Malacrida, Sandro; Battaglia, Giorgio; Bocus, Paolo; Castoro, Carlo; Cagol, Matteo; Chiarion-Sileni, Vanna; Ruol, Alberto; Amadori, Alberto; Saggioro, Daniela

    2016-05-01

    Platinum-based neoadjuvant therapy is the standard treatment for esophageal cancer (EC). At present, no reliable response markers exist, and patient therapeutic outcome is variable and very often unpredictable. The aim of this study was to understand the contribution of host constitutive DNA polymorphisms in discriminating between responder and nonresponder patients. DNA collected from 120 EC patients treated with platinum-based neoadjuvant chemotherapy was analyzed using drug metabolism enzymes and transporters (DMET) array platform that interrogates polymorphisms in 225 genes of drug metabolism and disposition. Four gene variants of DNA repair machinery, 2 in ERCC1 (rs11615; rs3212986), and 2 in XPD (rs1799793; rs13181) were also studied. Association analysis was performed with pTest software and corrected by permutation test. Predictive models of response were created using the receiver-operating characteristics curve approach and adjusted by the bootstrap procedure. Sixteen single nucleotide polymorphisms (SNPs) of the DMET array resulted significantly associated with either good or poor response; no association was found for the 4 variants mapping in DNA repair genes. The predictive power of 5 DMET SNPs mapping in ABCC2, ABCC3, CYP2A6, PPARG, and SLC7A8 genes was greater than that of clinical factors alone (area under the curve [AUC] = 0.74 vs 0.62). Interestingly, their combination with the clinical variables significantly increased the predictivity of the model (AUC = 0.78 vs 0.62, P = 0.0016). In conclusion, we identified a genetic signature of response to platinum-based neoadjuvant chemotherapy in EC patients. Our results also disclose the potential benefit of combining genetic and clinical variables for personalized EC management.

  12. 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.

  13. 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.

  14. Computer-aided breast MR image feature analysis for prediction of tumor response to chemotherapy

    SciTech Connect

    Aghaei, Faranak; Tan, Maxine; Liu, Hong; Zheng, Bin; Hollingsworth, Alan B.; Qian, Wei

    2015-11-15

    Purpose: To identify a new clinical marker based on quantitative kinetic image features analysis and assess its feasibility to predict tumor response to neoadjuvant chemotherapy. Methods: The authors assembled a dataset involving breast MR images acquired from 68 cancer patients before undergoing neoadjuvant chemotherapy. Among them, 25 patients had complete response (CR) and 43 had partial and nonresponse (NR) to chemotherapy based on the response evaluation criteria in solid tumors. The authors developed a computer-aided detection scheme to segment breast areas and tumors depicted on the breast MR images and computed a total of 39 kinetic image features from both tumor and background parenchymal enhancement regions. The authors then applied and tested two approaches to classify between CR and NR cases. The first one analyzed each individual feature and applied a simple feature fusion method that combines classification results from multiple features. The second approach tested an attribute selected classifier that integrates an artificial neural network (ANN) with a wrapper subset evaluator, which was optimized using a leave-one-case-out validation method. Results: In the pool of 39 features, 10 yielded relatively higher classification performance with the areas under receiver operating characteristic curves (AUCs) ranging from 0.61 to 0.78 to classify between CR and NR cases. Using a feature fusion method, the maximum AUC = 0.85 ± 0.05. Using the ANN-based classifier, AUC value significantly increased to 0.96 ± 0.03 (p < 0.01). Conclusions: This study demonstrated that quantitative analysis of kinetic image features computed from breast MR images acquired prechemotherapy has potential to generate a useful clinical marker in predicting tumor response to chemotherapy.

  15. Hepatic Artery Infusion Chemotherapy

    PubMed Central

    Schüller, J.; Kroiss, A.; Dinstl, K.

    1990-01-01

    Hepatic artery chemotherapy was given to 36 patients, using totally implantable devices consisting of a port and external pump. Twenty-seven patients had inoperable liver metastases of colorectal origin. The infusion system was inserted by laparotomy into the hepatic artery via the gastroduodenal artery. There was no operative mortality. Thirteen infusion systems could not be used for chemotherapy due to dislodgement, early death and lack of follow-up. FUdR was infused every two weeks. There were minor local complications like thrombosis of the system and dislodgement of the port. Toxic effects could be managed by reducing the dose. Response to chemotherapy was evaluated by survival, clinical condition, CEA, ultrasound and CT six months after onset of arterial chemotherapy. Ten/twenty-three patients (43%) responded to therapy, eight of them died on the average 19 months after initial chemotherapy. Six patients were non-responders, seven had stable disease. Five/ten patients developed extrahepatic metastases. Mean survival time was 13.1 months, mean interval until relapse 10.6 months. PMID:2149279

  16. 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.

  17. Long-term survival of advanced triple-negative breast cancers with a dose-intense cyclophosphamide/anthracycline neoadjuvant regimen

    PubMed Central

    Giacchetti, S; Porcher, R; Lehmann-Che, J; Hamy, A-S; de Roquancourt, A; Cuvier, C; Cottu, P-H; Bertheau, P; Albiter, M; Bouhidel, F; Coussy, F; Extra, J-M; Marty, M; de Thé, H; Espié, M

    2014-01-01

    Background: Triple-negative (TN) breast cancers exhibit major initial responses to neoadjuvant chemotherapy, but generally have a poor outcome. Because of the lack of validated drug targets, chemotherapy remains an important therapeutic tool in these cancers. Methods: We report the survival of two consecutive series of 267 locally advanced breast cancers (LABC) treated with two different neoadjuvant regimens, either a dose-dense and dose-intense cyclophosphamide–anthracycline (AC) association (historically called SIM) or a conventional sequential association of cyclophosphamide and anthracycline, followed by taxanes (EC-T). We compared pathological responses and survival rates of these two groups and studied their association with tumours features. Results: Although the two regimens showed equivalent pathological complete response (pCR) in the whole population (16 and 12%), the SIM regimen yielded a non-statistically higher pCR rate than EC-T (48% vs 24%, P=0.087) in TN tumours. In the SIM protocol, DFS was statistically higher for TN than for non-TN patients (P=0.019), although we showed that the TN status was associated with an increased initial risk of recurrence in both regimens. This effect gradually decreased and after 2 years, TN was associated with a significantly decreased likelihood of relapse in SIM-treated LABC (hazard ratio (HR)=0.25 (95% CI: 0.07–0.86), P=0.028). Conclusions: AC dose intensification treatment is associated with a very favourable long-term survival rate in TN breast cancers. These observations call for a prospective assessment of such dose-intense AC-based regimens in locally advanced TN tumours. PMID:24569467

  18. 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.

  19. 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

  20. Managing Chemotherapy Side Effects: Pain

    MedlinePlus

    ... ational C ancer I nstitute Managing Chemotherapy Side Effects Pain It’s important to treat pain. If you ... to pay for pain medicine. Managing Chemotherapy Side Effects: Pain Keep track of the pain. Each day, ...

  1. 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.

  2. 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.

  3. Low stromal Foxp3+ regulatory T-cell density is associated with complete response to neoadjuvant chemoradiotherapy in rectal cancer

    PubMed Central

    McCoy, M J; Hemmings, C; Miller, T J; Austin, S J; Bulsara, M K; Zeps, N; Nowak, A K; Lake, R A; Platell, C F

    2015-01-01

    Background: Foxp3+ regulatory T cells (Tregs) play a vital role in preventing autoimmunity, but also suppress antitumour immune responses. Tumour infiltration by Tregs has strong prognostic significance in colorectal cancer, and accumulating evidence suggests that chemotherapy and radiotherapy efficacy has an immune-mediated component. Whether Tregs play an inhibitory role in chemoradiotherapy (CRT) response in rectal cancer remains unknown. Methods: Foxp3+, CD3+, CD4+, CD8+ and IL-17+ cell density in post-CRT surgical samples from 128 patients with rectal cancer was assessed by immunohistochemistry. The relationship between T-cell subset densities and clinical outcome (tumour regression and survival) was evaluated. Results: Stromal Foxp3+ cell density was strongly associated with tumour regression grade (P=0.0006). A low stromal Foxp3+ cell density was observed in 84% of patients who had a pathologic complete response (pCR) compared with 41% of patients who did not (OR: 7.56, P=0.0005; OR: 5.27, P=0.006 after adjustment for presurgery clinical factors). Low stromal Foxp3+ cell density was also associated with improved recurrence-free survival (HR: 0.46, P=0.03), although not independent of tumour regression grade. Conclusions: Regulatory T cells in the tumour microenvironment may inhibit response to neoadjuvant CRT and may represent a therapeutic target in rectal cancer. PMID:26645238

  4. Computer-aided global breast MR image feature analysis for prediction of tumor response to chemotherapy: performance assessment

    NASA Astrophysics Data System (ADS)

    Aghaei, Faranak; Tan, Maxine; Hollingsworth, Alan B.; Zheng, Bin; Cheng, Samuel

    2016-03-01

    Dynamic contrast-enhanced breast magnetic resonance imaging (DCE-MRI) has been used increasingly in breast cancer diagnosis and assessment of cancer treatment efficacy. In this study, we applied a computer-aided detection (CAD) scheme to automatically segment breast regions depicting on MR images and used the kinetic image features computed from the global breast MR images acquired before neoadjuvant chemotherapy to build a new quantitative model to predict response of the breast cancer patients to the chemotherapy. To assess performance and robustness of this new prediction model, an image dataset involving breast MR images acquired from 151 cancer patients before undergoing neoadjuvant chemotherapy was retrospectively assembled and used. Among them, 63 patients had "complete response" (CR) to chemotherapy in which the enhanced contrast levels inside the tumor volume (pre-treatment) was reduced to the level as the normal enhanced background parenchymal tissues (post-treatment), while 88 patients had "partially response" (PR) in which the high contrast enhancement remain in the tumor regions after treatment. We performed the studies to analyze the correlation among the 22 global kinetic image features and then select a set of 4 optimal features. Applying an artificial neural network trained with the fusion of these 4 kinetic image features, the prediction model yielded an area under ROC curve (AUC) of 0.83+/-0.04. This study demonstrated that by avoiding tumor segmentation, which is often difficult and unreliable, fusion of kinetic image features computed from global breast MR images without tumor segmentation can also generate a useful clinical marker in predicting efficacy of chemotherapy.

  5. Biopsy proportion of tumour predicts pathological tumour response and benefit from chemotherapy in resectable oesophageal carcinoma: results from the UK MRC OE02 trial

    PubMed Central

    Hale, Matthew D.; Nankivell, Matthew; Hutchins, Gordon G.; Stenning, Sally P.; Langley, Ruth E.; Mueller, Wolfram; West, Nicholas P.; Wright, Alexander I.; Treanor, Darren; Hewitt, Lindsay C.; Allum, William H.; Cunningham, David; Hayden, Jeremy D.; Grabsch, Heike I.

    2016-01-01

    Background Neoadjuvant chemotherapy followed by surgery is the standard of care for UK patients with locally advanced resectable oesophageal carcinoma (OeC). However, not all patients benefit from multimodal treatment and there is a clinical need for biomarkers which can identify chemotherapy responders. This study investigated whether the proportion of tumour cells per tumour area (PoT) measured in the pre-treatment biopsy predicts chemotherapy benefit for OeC patients. Patients and methods PoT was quantified using digitized haematoxylin/eosin stained pre-treatment biopsy slides from 281 OeC patients from the UK MRC OE02 trial (141 treated by surgery alone (S); 140 treated by 5-fluorouracil/cisplatin followed by surgery (CS)). The relationship between PoT and clinicopathological data including tumour regression grade (TRG), overall survival and treatment interaction was investigated. Results PoT was associated with chemotherapy benefit in a non-linear fashion (test for interaction, P=0.006). Only patients with a biopsy PoT between 40% and 70% received a significant survival benefit from neoadjuvant chemotherapy (N=129; HR (95%CI):1.94 (1.39-2.71), unlike those with lower or higher PoT (PoT<40%, N=39, HR:1.25 (0.66-2.35); PoT>70% (N=28, HR:0.65 (0.36-1.18)). High pre-treatment PoT was related to lack of primary tumour regression (TRG 4 or 5), P=0.0402. Conclusions This is the first study to identify in a representative subgroup of OeC patients from a large randomized phase III trial that the proportion of tumour in the pre-chemotherapy biopsy predicts benefit from chemotherapy and may be a clinically useful biomarker for patient treatment stratification. PMID:27769054

  6. Histopathologic tumor response after induction chemotherapy and stereotactic body radiation therapy for borderline resectable pancreatic cancer

    PubMed Central

    Chuong, Michael D.; Frakes, Jessica M.; Figura, Nicholas; Hoffe, Sarah E.; Shridhar, Ravi; Mellon, Eric A.; Hodul, Pamela J.; Malafa, Mokenge P.; Springett, Gregory M.

    2016-01-01

    Background While clinical outcomes following induction chemotherapy and stereotactic body radiation therapy (SBRT) have been reported for borderline resectable pancreatic cancer (BRPC) patients, pathologic response has not previously been described. Methods This single-institution retrospective review evaluated BRPC patients who completed induction gemcitabine-based chemotherapy followed by SBRT and surgical resection. Each surgical specimen was assigned two tumor regression grades (TRG), one using the College of American Pathologists (CAP) criteria and one using the MD Anderson Cancer Center (MDACC) criteria. Overall survival (OS) and progression free survival (PFS) were correlated to TRG score. Results We evaluated 36 patients with a median follow-up of 13.8 months (range, 6.1-24.8 months). The most common induction chemotherapy regimen (82%) was GTX (gemcitabine, docetaxel, capecitabine). A median SBRT dose of 35 Gy (range, 30-40 Gy) in 5 fractions was delivered to the region of vascular involvement. The margin-negative resection rate was 97.2%. Improved response according to MDACC grade trended towards superior PFS (P=061), but not OS. Any neoadjuvant treatment effect according to MDACC scoring (IIa-IV vs. I) was associated with improved OS and PFS (both P=0.019). We found no relationship between CAP score and OS or PFS. Conclusions These data suggest that the increased pathologic response after induction chemotherapy and SBRT is correlated with improved survival for BRPC patients. PMID:27034789

  7. Stability of the HER2 gene after primary chemotherapy in advanced breast cancer.

    PubMed

    Varga, Zsuzsanna; Caduff, Rosmarie; Pestalozzi, Bernhard

    2005-02-01

    We investigated whether alterations of the Her2 gene could be detected in breast cancer samples following primary chemotherapy in advanced breast cancer. The prospective study involved 23 patients with stage-II, -III or -IV breast cancer. All patients were treated with two to six cycles of fluorouracil-epirubicin and/or cyclophosphamid/epi-docetaxel. The Her2 protein and gene were assessed both on core needle biopsies prior to and on surgical specimens after completing chemotherapy using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) methods. Estrogen and progesterone receptors (ER/PR) were also determined on both samples using IHC. Her2 status was modified in eight patients using IHC (35%) and in three patients using FISH (13%). Changes in ER/PR expression were detected in seven patients (30%). Our data suggest that alterations of the Her2 gene can occur, although not usually after primary or neoadjuvant chemotherapy. However, changes in ER/PR status seem to be a more common event; thus, both can lead to different therapeutic options. Intratumoral heterogeneity as well as sampling variations can contribute to modification of the Her2 status after primary chemotherapy.

  8. Chemotherapy-induced endometrial pathology: mimicry of malignancy and viral endometritis

    PubMed Central

    Kim, Eun Kyung; Yoon, Gun; Kim, Hyun-Soo

    2016-01-01

    Chemotherapy is a common type of preoperative neoadjuvant treatment and postoperative adjuvant or palliative therapy for many different types of malignancies. Certain chemotherapeutic agents can induce bizarre epithelial atypia that mimics malignancy. Unfamiliarity with these changes could potentially cause confusion with a neoplastic or infectious process. The endometrium is one of the few sites where chemotherapy-induced epithelial atypia has not been appreciated. We identified four patients with marked cytologic atypia of the endometrial glandular epithelium from the surgical pathology files of Severance Hospital. The histopathologic features, immunostaining results and medical records of these patients were reviewed. All patients underwent hysteroscopic examination with endometrial curettage for investigation of vaginal bleeding. They had previously undergone chemotherapy for uterine cervical cancer (n=1), rectal cancer (n=2) and myelodysplastic syndrome (n=1). The chemotherapy regimens included alkylating agents (busulfan, cyclophosphamide, ifosfamide, cisplatin, and oxaliplatin), pyrimidine antagonists (capecitabine, decitabine, and 5-fluorouracil), taxanes (paclitaxel), and topoisomerase inhibitors (irinotecan and etoposide). On histopathological examination, the atypical epithelial changes included marked nuclear enlargement and pleomorphism, a degenerative-looking chromatin pattern, abundant microvacuolated cytoplasm, and preservation of the nuclear/cytoplasmic ratio. This study demonstrates that certain chemotherapeutic agents may cause bizarre, reactive atypia of the endometrial glandular epithelium. These changes should not be interpreted as neoplastic or infectious in nature. An awareness of prior exposure to cytotoxic agents and a familiarity with the nature and distribution of these bizarre alterations is essential to avoid misinterpretation of the morphologic features and prevent unnecessary treatment. PMID:27347355

  9. Long-Term Follow-Up of Dose-Adapted and Reduced-Field Radiotherapy With or Without Chemotherapy for Central Nervous System Germinoma

    SciTech Connect

    Jensen, Ashley W.; Issa Laack, Nadia N.; Buckner, Jan C.; Schomberg, Paula J.; Wetmore, Cynthia J.; Brown, Paul D.

    2010-08-01

    Purpose: To update our institutional experience with neoadjuvant chemotherapy and minimized radiotherapy vs. radiation monotherapy for intracranial germinoma. Methods and Materials: We retrospectively reviewed records of 59 patients with diagnosis of primary intracranial germinoma between 1977 and 2007. Treatment was irradiation alone or neoadjuvant platinum-based chemotherapy and local irradiation (initial tumor plus margin) for patients with localized complete response and reduced-dose craniospinal irradiation for others. Results: For the chemoradiotherapy group (n = 28), median follow-up was 7 years. No patient died. The freedom from progression (FFP) rate was 88% at 5 years and 80% at 10 years. In 4 patients, disease recurred 1.1 to 6.8 years after diagnosis. All were young male patients who received 30.6 Gy to local fields after complete response to chemotherapy. The FFP rate was 88% for local irradiation vs. 100% for more extensive fields (p = .06). For the radiotherapy-alone group (n = 31), median follow-up was 15 years. Overall and disease-free survival rates were 93% and 93% at 5 years and 90% and 87% at 15 years. In 5 patients, disease recurred 1.1 to 4.9 years after diagnosis. Most patients in this group were young men 18 to 23 years of age with suprasellar primary disease treated with about 50 Gy to local fields. The FFP rate was 44% for local irradiation vs. 100% for more extensive fields (p < .01). Conclusions: The addition of neoadjuvant chemotherapy to local-field radiotherapy reduced central nervous system cancer recurrence when high-risk patients were excluded by thorough pretreatment staging. There was trend toward improved central nervous system tumor control when larger fields (whole brain, whole ventricle, or craniospinal axis) were used.

  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. Chemotherapy in pregnancy.

    PubMed

    Ngu, Siew-Fei; Ngan, Hextan Y S

    2016-05-01

    Cancer diagnosed during pregnancy is uncommon, complicating between 0.02% and 0.1% of all pregnancies. Nonetheless, due to increasing age of childbearing, the incidence of cancer during pregnancy is likely to increase due to higher incidence of several age-dependent malignancies. The most common malignancies include breast cancer, cervical cancer, malignant melanoma and lymphoma. One of the key challenges in the management of cancer in pregnancy is treating the women with standard chemotherapy regimen, without compromising the safety of the developing foetus. Exposure of chemotherapy in the first trimester is associated with an increased risk of major birth defects, whereas use in the second and third trimesters is associated with intrauterine growth restriction, low birthweight and stillbirth. In this article, we review available data regarding the use of chemotherapeutic agents in pregnancy, and we summarise the neonatal outcomes, including malformations, perinatal complications and long-term follow-up. In addition, the management plan during pregnancy is also discussed.

  12. Chemotherapy of Leishmaniasis.

    DTIC Science & Technology

    1978-12-01

    NOTES 1S. KEY WORDS (Continue on reverse side linscoeawy and identiIIy by block number) LEISHMANIA LEISHMANIASIS CHEMOTHERAPY ANTILEISHMANIAL PENTOSTAM...number of compounds was supplied by WRAIR for testing on four strains of Leishmania in December 1977. Preliminary data were supplied to WRAIR by the...1 Visceral leishmaniasis The laboratory model used for the investigation of drug activity against visceral infection in this laboratory is L. donovani

  13. Chemotherapy of Cutaneous Leishmaniasis

    DTIC Science & Technology

    2012-10-01

    bacterial emerging diseases. 43rd Annual Commonwealth Caribbean Medical Research Council Meeting. Ocho Rios, Jamaica, April, 1998. Palmer, C.J., J...1 Award Number: W81XWH-10-2-0196 TITLE: CHEMOTHERAPY OF CUTANEOUS LEISHMANIASIS PRINCIPAL INVESTIGATOR: DR. ARBA AGER CONTRACTING ...Respondents should be aware that notwithstanding any other provision of law , no person shall be subject to any penalty for failing to comply with a

  14. Neoadjuvant Sequential Docetaxel Followed by High‐Dose Epirubicin in Combination With Cyclophosphamide Administered Concurrently With Trastuzumab. The DECT Trial

    PubMed Central

    Pizzuti, Laura; Barba, Maddalena; Giannarelli, Diana; Sergi, Domenico; Botti, Claudio; Marchetti, Paolo; Anzà, Michele; Maugeri‐Saccà, Marcello; Natoli, Clara; Di Filippo, Simona; Catenaro, Teresa; Tomao, Federica; Amodio, Antonella; Carpano, Silvia; Perracchio, Letizia; Mottolese, Marcella; Di Lauro, Luigi; Sanguineti, Giuseppe; Di Benedetto, Anna; Giordano, Antonio

    2016-01-01

    To report the results of the DECT trial, a phase II study of locally advanced or operable HER2‐positive breast cancer (BC) treated with taxanes and concurrent anthracyclines and trastuzumab. Eligible patients (stage IIA‐IIIB HER2‐positive BC, 18–75 years, normal organ functions, ECOG ≤1, and left ventricular ejection fraction (LVEF) ≥55%) received four cycles of neoadjuvant docetaxel, 100 mg/m2 intravenously, plus trastuzumab 6 mg/kg (loading dose 8 mg/kg) every 3 weeks, followed by four 3‐weekly cycles of epirubicin 120 mg/m2 and cyclophosphamide, 600 mg/m2, plus trastuzumab. Primary objective was pathologic complete response (pCR) rate, defined as ypT0/is ypN0 at definitive surgery. We enrolled 45 consecutive patients. All but six patients (13.3%) completed chemotherapy and all underwent surgery. pCR was observed in 28 patients (62.2%) overall and in 6 (66.7%) from the inflammatory subgroup. The classification and regression tree analysis showed a 100% pCR rate in patients with BMI ≥25 and with hormone negative disease. The median follow up was 46 months (8–78). Four‐year recurrence‐free survival was 74.7% (95%CI, 58.2–91.2). Seven patients (15.6%) recurred and one died. Treatment was well tolerated, with limiting toxicity being neutropenia. No clinical cardiotoxicity was observed. Six patients (13.4%) showed a transient LVEF decrease (<10%). In one patient we observed a ≥10% asymptomatic LVEF decrease persisting after surgery. Notwithstanding their limited applicability due to the current guidelines, our findings support the efficacy of the regimen of interest in the neoadjuvant setting along with a fairly acceptable toxicity profile, including cardiotoxicity. Results on BMI may invite further assessment in future studies. J. Cell. Physiol. 231: 2541–2547, 2016. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. PMID:27187274

  15. Integrating Chemotherapy in the Management of Cervical Cancer: A Critical Appraisal.

    PubMed

    Kumar, Lalit; Gupta, Sudeep

    2016-01-01

    The management of locally advanced cervix cancer has undergone a paradigm shift during the last decade. Concurrent chemoradiation (CCRT) (with cisplatin alone or in combination) is currently the standard treatment approach. CCRT results in a 5-year overall survival rate of 66% and a disease-free survival of 58%. About 30-40% of patients with locally advanced cervical cancer fail to achieve complete response to CCRT; alternative approaches are needed to improve the outcome for such patients. Weekly paclitaxel and carboplatin for 4-6 weeks as dose-dense chemotherapy prior to CCRT could be one such potential approach. The role of adjuvant chemotherapy after CCRT in patients with positive lymph nodes, larger tumor volume and stage III-IVA disease needs further exploration. Adjuvant chemotherapy is also being investigated for early-stage (stages IA2, IB1 or IIA) cervical cancer with presence of risk factors such as lymph node metastasis, lymphovascular space invasion and invasion depth of more than 10 mm, microscopic parametrial invasion, non-squamous histology and positive surgical margins. For patients with early-stage disease (IA2-IIA), short-course chemotherapy prior to surgery is associated with an improved outcome in many studies. Neo-adjuvant chemotherapy followed by fertility preservation surgery is feasible in carefully selected young patients with bulky stage IB1 disease. Recently, a number of molecular pathways have been identified as potential therapeutic targets. Bevacizumab - an inhibitor of vascular endothelial growth factor - is associated with improved survival in patients with recurrent/metastatic cervical cancer. Whether bevacizumab and other similar novel agents targeting molecular pathways could be used in front-line treatment along with cytotoxic chemotherapy is likely to be an area of research in future studies.

  16. Death by bleomycin pulmonary toxicity in ovarian dysgerminoma with pathologic complete response to chemotherapy. A case report.

    PubMed

    Calzas Rodríguez, Julia; Carmen Juarez Morales, María Del; Casero, Miguel Angel Racionero

    2016-01-01

    With cisplatin-based chemotherapy, most patients with ovarian dysgerminoma will survive long-term. Bleomycin is an important part of ovarian germ cell tumors (OGCT) treatment, and its dose-limiting toxicity is the development of pulmonary toxicity and it is increased in patients older than 40 years. We report the case of an elderly patient with an unresectable ovarian dysgerminoma who received neoadjuvant chemotherapy and who developed fatal bleomycin pulmonary toxicity (BPT) after surgery. A monitoring of pulmonary function is not routinely recommended for detecting BPT, although together with carefully assessment for symptoms or signs suggestive of pulmonary toxicity is the best way to reduce the risk of BPT. The frequency of pulmonary events in older patients makes us to think about the possibility of either reduce the dose of bleomycin or removing it from the BEP in ovarian GCT.

  17. 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

  18. 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.

  19. Secondary malignancies following cancer chemotherapy.

    PubMed

    Boffetta, P; Kaldor, J M

    1994-01-01

    Many agents used in cancer chemotherapy are known carcinogens. However, few secondary malignancies have been definitely linked to chemotherapy, since studies on this problem are complicated by methodological problems. A causal relationship has been established between alkylating agents and leukaemia and between cyclophosphamide and bladder cancer. The risk of leukaemia peaks at 5-10 years after beginning of chemotherapy and declines steadily after its end. The interaction between chemotherapy and radiotherapy has not been fully clarified, nor has the leukaemogenic potency of individual drugs, although combinations without nitrogen mustard seem to entail a lower risk. Other tumours reported at increased incidence, in particular among Hodgkin's disease patients, for whom a carcinogenic effect of chemotherapy seems plausible, are non-Hodgkin's lymphoma and lung cancer. Other secondary solid tumors have also been reported, but for none of them an independent effect of chemotherapy has been demonstrated.

  20. MiRNA-621 sensitizes breast cancer to chemotherapy by suppressing FBXO11 and enhancing p53 activity

    PubMed Central

    Xue, J; Chi, Y; Chen, Y; Huang, S; Ye, X; Niu, J; Wang, W; Pfeffer, L M; Shao, Z-m; Wu, Z-H; Wu, J

    2016-01-01

    MicroRNAs (miRNAs) have been demonstrated to have critical roles in regulating cancer cell proliferation, survival and sensitivity to chemotherapy. The potential application of using miRNAs to predict therapeutic response to cancer treatment holds high promise, but miRNAs with predictive value remain to be identified and underlying mechanisms have not been completely understood. Here, we show a strong correlation between miR-621 expression and chemosensitivity to paclitaxel plus carboplatin (PTX/CBP) regimen, an effective neoadjuvant chemotherapy for breast cancer patients. High level of miR-621 predicts better response to PTX/CBP regimen neoadjuvant chemotherapy in breast cancer patients, who also tend to achieve pathological complete response. Ectopic overexpression of miR-621 promoted apoptosis and increased chemosensitivity to PTX and CBP both in cultured breast cancer cells and in xenograft tumor model. We further show that FBXO11 is a direct functional target of miR-621 and miR-621 level is negatively correlated with FBXO11 expression in breast cancer patients. Ectopic expression of FBXO11 attenuated increased apoptosis in breast cancer cells overexpressing miR-621 upon PTX or CBP treatment. Consistently, high FBXO11 expression significantly correlated with poor survival in breast cancer patients. Mechanistically, we found in breast cancer cells FBXO11 interacts with p53 and promotes its neddylation, which suppressed the p53 transactivity. Accordingly, miR-621-dependent FBXO11 suppression enhanced p53 activity and increased apoptosis in breast cancer cells exposed to chemotherapeutics. Taken together, our data suggest that miR-621 enhances chemosensitivity of breast cancer cells to PTX/CBP chemotherapy by suppressing FBXO11-depedent inhibition of p53. miR-621 may serve as a predictive biomarker and a potential therapeutic target in breast cancer treatment. PMID:25867061

  1. Chemotherapy of Rodent Malaria.

    DTIC Science & Technology

    1985-07-01

    15 ML W_____ 1 .5 1.25 1-4 1. j . .. .... AD CHEMOTHERAPY OF RODENT MALARIA /I ’ IFINAL REPORT 00 WALLACE PETERS MD DSc I!JULY 1985 Supported by US...Table 15 and detailed report sheets are appended as Tables 16 through 21. 3.1.1 WR 251855 AA This lepidine, an analogue of primaquine, is very active...in our 15 preliminary test. The remaining three compounds also exhibited toxicity in varying degrees at this dose and, consequently, even the low level

  2. 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