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Sample records for advanced rectal cancer

  1. Locally advanced rectal cancer: management challenges

    PubMed Central

    Kokelaar, RF; Evans, MD; Davies, M; Harris, DA; Beynon, J

    2016-01-01

    Between 5% and 10% of patients with rectal cancer present with locally advanced rectal cancer (LARC), and 10% of rectal cancers recur after surgery, of which half are limited to locoregional disease only (locally recurrent rectal cancer). Exenterative surgery offers the best long-term outcomes for patients with LARC and locally recurrent rectal cancer so long as a complete (R0) resection is achieved. Accurate preoperative multimodal staging is crucial in assessing the potential operability of advanced rectal tumors, and resectability may be enhanced with neoadjuvant therapies. Unfortunately, surgical options are limited when the tumor involves the lateral pelvic sidewall or high sacrum due to the technical challenges of achieving histological clearance, and must be balanced against the high morbidity associated with resection of the bony pelvis and significant lymphovascular structures. This group of patients is usually treated palliatively and subsequently survival is poor, which has led surgeons to seek innovative new solutions, as well as revisit previously discarded radical approaches. A small number of centers are pioneering new techniques for resection of beyond-total mesorectal excision tumors, including en bloc resections of the sciatic notch and composite resections of the first two sacral vertebrae. Despite limited experience, these new techniques offer the potential for radical treatment of previously inoperable tumors. This narrative review sets out the challenges facing the management of LARCs and discusses evolving management options. PMID:27785074

  2. Predictive Biomarkers to Chemoradiation in Locally Advanced Rectal Cancer

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  4. Advances and Challenges in Treatment of Locally Advanced Rectal Cancer

    PubMed Central

    Smith, J. Joshua; Garcia-Aguilar, Julio

    2015-01-01

    Dramatic improvements in the outcomes of patients with rectal cancer have occurred over the past 30 years. Advances in surgical pathology, refinements in surgical techniques and instrumentation, new imaging modalities, and the widespread use of neoadjuvant therapy have all contributed to these improvements. Several questions emerge as we learn of the benefits or lack thereof for components of the current multimodality treatment in subgroups of patients with nonmetastatic locally advanced rectal cancer (LARC). What is the optimal surgical technique for distal rectal cancers? Do all patients need postoperative chemotherapy? Do all patients need radiation? Do all patients need surgery, or is a nonoperative, organ-preserving approach warranted in selected patients? Answering these questions will lead to more precise treatment regimens, based on patient and tumor characteristics, that will improve outcomes while preserving quality of life. However, the idea of shifting the treatment paradigm (chemoradiotherapy, total mesorectal excision, and adjuvant therapy) currently applied to all patients with LARC to a more individually tailored approach is controversial. The paradigm shift toward organ preservation in highly selected patients whose tumors demonstrate clinical complete response to neoadjuvant treatment is also controversial. Herein, we highlight many of the advances and resultant controversies that are likely to dominate the research agenda for LARC in the modern era. PMID:25918296

  5. Refining Preoperative Therapy for Locally Advanced Rectal Cancer

    Cancer.gov

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

  6. 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

  7. Chemotherapy, Radiation Therapy, and Surgery in Treating Patients With Locally Advanced Rectal Cancer

    ClinicalTrials.gov

    2013-01-09

    Adenocarcinoma of the Rectum; Mucinous Adenocarcinoma of the Rectum; Signet Ring Adenocarcinoma of the Rectum; Stage IIA Rectal Cancer; Stage IIB Rectal Cancer; Stage IIC Rectal Cancer; Stage IIIA Rectal Cancer; Stage IIIB Rectal Cancer; Stage IIIC Rectal Cancer

  8. Locally advanced rectal cancer: The importance of a multidisciplinary approach

    PubMed Central

    Berardi, Rossana; Maccaroni, Elena; Onofri, Azzurra; Morgese, Francesca; Torniai, Mariangela; Tiberi, Michela; Ferrini, Consuelo; Cascinu, Stefano

    2014-01-01

    Rectal cancer accounts for a relevant part of colorectal cancer cases, with a mortality of 4-10/100000 per year. The development of locoregional recurrences and the occurrence of distant metastases both influences the prognosis of these patients. In the last two decades, new multimodality strategies have improved the prognosis of locally advanced rectal cancer with a significant reduction of local relapse and an increase in terms of overall survival. Radical surgery still remains the principal curative treatment and the introduction of total mesorectal excision has significantly achieved a reduction in terms of local recurrence rates. The employment of neoadjuvant treatment, delivered before surgery, also achieved an improved local control and an increased sphincter preservation rate in low-lying tumors, with an acceptable acute and late toxicity. This review describes the multidisciplinary management of rectal cancer, focusing on the effectiveness of neoadjuvant chemoradiotherapy and of post-operative adjuvant chemotherapy both in the standard combined modality treatment programs and in the ongoing research to improve these regimens. PMID:25516638

  9. Locally advanced rectal cancer: the importance of a multidisciplinary approach.

    PubMed

    Berardi, Rossana; Maccaroni, Elena; Onofri, Azzurra; Morgese, Francesca; Torniai, Mariangela; Tiberi, Michela; Ferrini, Consuelo; Cascinu, Stefano

    2014-12-14

    Rectal cancer accounts for a relevant part of colorectal cancer cases, with a mortality of 4-10/100000 per year. The development of locoregional recurrences and the occurrence of distant metastases both influences the prognosis of these patients. In the last two decades, new multimodality strategies have improved the prognosis of locally advanced rectal cancer with a significant reduction of local relapse and an increase in terms of overall survival. Radical surgery still remains the principal curative treatment and the introduction of total mesorectal excision has significantly achieved a reduction in terms of local recurrence rates. The employment of neoadjuvant treatment, delivered before surgery, also achieved an improved local control and an increased sphincter preservation rate in low-lying tumors, with an acceptable acute and late toxicity. This review describes the multidisciplinary management of rectal cancer, focusing on the effectiveness of neoadjuvant chemoradiotherapy and of post-operative adjuvant chemotherapy both in the standard combined modality treatment programs and in the ongoing research to improve these regimens.

  10. Locally advanced rectal cancer: Preliminary results of rectal preservation after neoadjuvant chemoradiotherapy.

    PubMed

    Vaccaro, Carlos Alberto; Yazyi, Federico Julio; Ojra Quintana, Guillermo; Santino, Juan Pablo; Sardi, Mabel Edith; Beder, Damián; Tognelli, Joaquin; Bonadeo, Fernando; Lastiri, José María; Rossi, Gustavo Leandro

    2016-05-01

    The standard treatment for locally advanced rectal cancer is total mesorectal excision. However, organ preservation has been proposed for tumors with good response to neoadjuvant treatment. The aim of this study was to evaluate the oncologic results of this strategy. This is a retrospective cohort study (2005-2014) including a consecutive series of patients with rectal adenocarcinoma with complete or almost complete clinical response after preoperative chemo-radiotherapy, that were treated according to a strategy of preservation of the rectum. A total of 204 patients with rectal cancer received neoadjuvant therapy. Thirty (14.7%) had a good response and were treated with rectal preservation (23 «Watch and Wait» and 7 local resections). Median follow-up was 46 months (interquartile range: 30-68). In the group of «Watch & Wait», 4 patients had local recurrence before 12 months (actuarial local recurrence rate=18.5%). All of them underwent salvage surgery (2 with radical surgery and 2 local resections) without any further recurrence. Disease-free survival actuarial rate at 3 years follow-up was 94.1% (95% CI 82.9-100). None of the 7 patients that were treated by local excision had local recurrence. The organ preservation rate for the whole group was 93%. The strategy of organ preservation in locally advanced rectal cancer is feasible in cases with good response to neoadjuvant therapy. When implemented in a highly selected group of patients this strategy is associated with satisfactory oncologic results. Copyright © 2016 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Immunoscore in Rectal Cancer

    ClinicalTrials.gov

    2017-06-13

    Cancer of the Rectum; Neoplasms, Rectal; Rectal Cancer; Rectal Tumors; Rectal Adenocarcinoma; Melanoma; Breast Cancer; Renal Cell Cancer; Lung Cancer; Bladder Cancer; Head and Neck Cancer; Ovarian Cancer; Thyroid Cancer

  12. Locally advanced rectal cancer: time for precision therapeutics.

    PubMed

    Weiser, Martin R; Zhang, Zhen; Schrag, Deborah

    2015-01-01

    The year 2015 marks the 30th anniversary of the publication of NSABP-R01, a landmark trial demonstrating the benefit of adding pelvic radiation to the treatment regimen for locally advanced rectal cancer with a resultant decrease in local recurrence from 25% to 16%. These results ushered in the era of multimodal therapy for rectal cancer, heralding modern treatment and changing the standard of care in the United States. We have seen many advances over the past 3 decades, including optimization of the administration and timing of radiation, widespread adoption of total mesorectal excision (TME), and the implementation of more effective systemic chemotherapy. The current standard is neoadjuvant chemoradiation with 5-fluorouracil (5-FU) and a radiosensitizer, TME, and adjuvant chemotherapy including 5-FU and oxaliplatin. The results of this regimen have been impressive, with a reported local recurrence rate of less than 10%. However, the rates of distant relapse remain 30% to 40%, indicating room for improvement. In addition, trimodality therapy is arduous and many patients are unable to complete the full course of treatment. In this article we discuss the current standard of care and alternative strategies that have evolved in an attempt to individualize therapy according to risk of recurrence.

  13. Recent advances in robotic surgery for rectal cancer.

    PubMed

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

    2015-08-01

    Robotic technology, which has recently been introduced to the field of surgery, is expected to be useful, particularly in treating rectal cancer where precise manipulation is necessary in the confined pelvic cavity. Robotic surgery overcomes the technical drawbacks inherent to laparoscopic surgery for rectal cancer through the use of multi-articulated flexible tools, three-dimensional stable camera platforms, tremor filtering and motion scaling functions, and greater ergonomic and intuitive device manipulation. Assessments of the feasibility and safety of robotic surgery for rectal cancer have reported similar operation times, blood loss during surgery, rates of postoperative morbidity, and circumferential resection margin involvement when compared with laparoscopic surgery. Furthermore, rates of conversion to open surgery are reportedly lower with increased urinary and male sexual functions in the early postoperative period compared with laparoscopic surgery, demonstrating the technical advantages of robotic surgery for rectal cancer. However, long-term outcomes and the cost-effectiveness of robotic surgery for rectal cancer have not been fully evaluated yet; therefore, large-scale clinical studies are required to evaluate the efficacy of this new technology.

  14. Neoadjuvant Treatment Strategies for Locally Advanced Rectal Cancer.

    PubMed

    Gollins, S; Sebag-Montefiore, D

    2016-02-01

    Improved surgical technique plus selective preoperative radiotherapy have decreased rectal cancer pelvic local recurrence from, historically, 25% down to about 5-10%. However, this improvement has not reduced distant metastatic relapse, which is the main cause of death and a key issue in rectal cancer management. The current standard is local pelvic treatment (surgery ± preoperative radiotherapy) followed by adjuvant chemotherapy, depending on resection histology. For circumferential resection margin (CRM)-threatened cancer on baseline magnetic resonance imaging, downstaging long-course preoperative chemoradiation (LCPCRT) is generally used. However, for non-CRM-threatened disease, varying approaches are currently adopted in the UK, including straight to surgery, short-course preoperative radiotherapy and LCPCRT. Clinical trials are investigating intensification of concurrent chemoradiation. There is also increasing interest in investigating preoperative neoadjuvant chemotherapy (NAC) as a way of exposing micro-metastatic disease to full-dose systemic chemotherapy as early as possible and potentially reducing metastatic relapse. Phase II trials suggest that this strategy is feasible, with promising histological response and low rates of tumour progression during NAC. Phase III trials are needed to determine the benefit of NAC when added to standard therapy and also to determine if it can be used instead of neoadjuvant radiotherapy-based schedules. Although several measures of neoadjuvant treatment response assessment based on imaging or pathology are promising predictive biomarkers for long-term survival, none has been validated in prospective phase III studies. The phase III setting will enable this, also providing translational opportunities to examine molecular predictors of response and survival. Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  15. Preoperative Chemoradiotherapy in Elderly Patients with Locally Advanced Rectal Cancer

    PubMed Central

    Musio, Daniela; Izzo, Luciano; Pugliese, Federico; Izzo, Paolo; Bolognese, Antonio

    2013-01-01

    Purpose. To evaluate the treatment tolerance and clinical outcomes in patients aged 70 and older with locally advanced rectal carcinoma treated with multimodality approach. Methods and Materials. We retrospectively analysed 20 consecutive elderly patients, with histologically proven rectal adenocarcinoma, staged T3-4, and/or node-positive tumour, who received chemoradiotherapy and proceeded to surgical approach. Performance status score and adult comorbidity evaluation-27 score were calculated, and their influence on treatment tolerance and clinical outcomes was analysed. Results. All patients completed programmed chemoradiotherapy treatment. Gastrointestinal toxicity was the most common acute side effects: proctitis in 70% of patients and diarrhoea in 55%, classified as Grade 3 in 3 patients only. Radiation dermatitis was reported in 7 patients (35%) and it was graded G3 in one patient. There was no haematological toxicity. Eighteen patients out of 20 underwent surgery. Sphincter preservation was assured in 13 patients. Comorbidity index was related to higher severe acute toxicity (P = 0.015) but no influenced treatment outcomes. Conclusion. Treatment tolerance with combined modality is good in elderly patients. Due to age, no dose reduction for radiation therapy and chemotherapy should be considered. PMID:24392453

  16. Genetic Mutations in Blood and Tissue Samples in Predicting Response to Treatment in Patients With Locally Advanced Rectal Cancer Undergoing Chemoradiation

    ClinicalTrials.gov

    2017-09-08

    Mucinous Adenocarcinoma of the Rectum; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Rectum; Stage IIA Rectal Cancer; Stage IIB Rectal Cancer; Stage IIC Rectal Cancer; Stage IIIA Rectal Cancer; Stage IIIB Rectal Cancer; Stage IIIC Rectal Cancer

  17. Tegafur-uracil (UFT) plus folinic acid in advanced rectal cancer.

    PubMed

    Sanchiz, F; Milla, A

    1994-12-01

    We previously reported positive results to Tegafur-Uracil (UFT) chemotherapy in a group of patients with advanced rectal cancer. We have continued the study and now report the effectiveness of UFT plus folinic acid (FA) in 52 patients with advanced rectal cancer. The therapeutic schedule was UFT, 600 mg/m2/day x 14 days p.o. + FA, 90 mg/m2/day x 14 days p.o. Fifty-two out of a total of 56 patients were evaluated for response and toxicity. A higher incidence of positive responses in patients without previous chemotherapy was appreciated. Twenty-one of the 52 evaluated patients showed a partial response (PR). Responses were strongly correlated with previous chemotherapy (14/20; 70% PR of cases without previous chemotherapy vs 7/32; 22% of cases with previous chemotherapy). All responding patients came forward with a median time to progression of 8.2 months (19.6 months for patients without previous chemotherapy vs 7.7 months for patients with previous chemotherapy, P < 0.01). We concluded that the UFT plus FA could be a treatment of choice for patients with advanced rectal cancer.

  18. Akt Inhibitor MK2206 in Treating Patients With Previously Treated Colon or Rectal Cancer That is Metastatic or Locally Advanced and Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2016-12-13

    Colon Mucinous Adenocarcinoma; Colon Signet Ring Cell Adenocarcinoma; Rectal Mucinous Adenocarcinoma; Rectal Signet Ring Cell Adenocarcinoma; Recurrent Colon Carcinoma; Recurrent Rectal Carcinoma; Stage IIIA Colon Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

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

    SciTech Connect

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

    2013-01-01

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

  20. Advances in radiotherapy and targeted therapies for rectal cancer

    PubMed Central

    Sermeus, Alexandra; Leonard, Wim; Engels, Benedikt; De Ridder, Mark

    2014-01-01

    The last decade witnessed a significant progress in understanding the biology and immunology of colorectal cancer alongside with the technical innovations in radiotherapy. The stepwise implementation of intensity-modulated and image-guided radiation therapy by means of megavolt computed tomography and helical tomotherapy enabled us to anatomically sculpt dose delivery, reducing treatment related toxicity. In addition, the administration of a simultaneous integrated boost offers excellent local control rates. The novel challenge is the development of treatment strategies for medically inoperable patient and organ preserving approaches. However, distant control remains unsatisfactory and indicates an urgent need for biomarkers that predict the risk of tumor spread. The expected benefit of targeted therapies that exploit the tumor genome alone is so far hindered by high cost techniques and pharmaceuticals, hence hardly justifying rather modest improvements in patient outcomes. On the other hand, the immune landscape of colorectal cancer is now better clarified with regard to the immunosuppressive network that promotes immune escape. Both N2 neutrophils and myeloid-derived suppressor cells (MDSC) emerge as useful clinical biomarkers of poor prognosis, while the growing list of anti-MDSC agents shows promising ability to boost antitumor T-cell immunity in preclinical settings. Therefore, integration of genetic and immune biomarkers is the next logical step towards effective targeted therapies in the context of personalized cancer treatment. PMID:24415852

  1. Current concepts in rectal cancer.

    PubMed

    Fleshman, James W; Smallwood, Nathan

    2015-03-01

    The history of rectal cancer management informs current therapy and points us in the direction of future improvements. Multidisciplinary team management of rectal cancer will move us to personalized treatment for individuals with rectal cancer in all stages.

  2. Magnetic resonance imaging of rectal cancer.

    PubMed

    Dewhurst, Catherine E; Mortele, Koenraad J

    2013-01-01

    This article aims to discuss the anatomy of the anorectum, the MRI protocol parameters required to optimize diagnosis of rectal cancer, and the diagnostic MRI criteria essential to stage rectal cancer accurately, using the TNM staging classification. A brief review of more emerging important aspects of rectal cancer staging, such as the circumferential resection margin, extramural vascular invasion, and the staging of low rectal cancers, will also be provided. Finally, the authors will touch upon the evaluation of tumor response to neoadjuvant chemoradiation therapy in the setting of locally advanced rectal cancer. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Progress in the treatment of locally advanced clinically resectable rectal cancer.

    PubMed

    Minsky, Bruce D

    2011-12-01

    There have been significant developments in the adjuvant treatment of locally advanced clinically resectable (T3 and/or N+) rectal cancer. Postoperative systemic chemotherapy plus concurrent pelvic irradiation (chemoradiation) significantly improves local control and survival compared with surgery alone. The German Rectal Cancer Trial confirmed that when chemoradiation is delivered preoperatively there is a significant decrease in acute and late toxicity and a corresponding increase in local control and sphincter preservation. Despite these advances, controversies remain. Among these controversies are the role of short-course radiation, whether postoperative adjuvant chemotherapy is necessary for all patients, and if the type of surgery after chemoradiation can be modified based on tumor response. Are there more accurate imaging techniques and/or molecular markers to help identify patients with positive pelvic nodes with the goal of reducing the chance of overtreatment with preoperative therapy. Will more effective systemic agents both improve outcome and modify the need for pelvic irradiation? This review examines the advances in chemoradiation as well as addresses these and other opportunities for improvement.

  4. Application of Laparoscopic Extralevator Abdominoperineal Excision in Locally Advanced Low Rectal Cancer

    PubMed Central

    Wang, Yan-Lei; Dai, Yong; Jiang, Jin-Bo; Yuan, Hui-Yang; Hu, San-Yuan

    2015-01-01

    Background: When compared with conventional abdominoperineal resection (APR), extralevator abdominoperineal excision (ELAPE) has been demonstrated to reduce the risk of local recurrence for the treatment of locally advanced low rectal cancer. Combined with the laparoscopic technique, laparoscopic ELAPE (LELAPE) has the potential to reduce invasion and hasten postoperative recovery. In this study, we aim to investigate the advantages of LELAPE in comparison with conventional APR. Methods: From October 2010 to February 2013, 23 patients with low rectal cancer (T3–4N0–2M0) underwent LELAPE; while during the same period, 25 patients were treated with conventional APR. The patient characteristics, intraoperative data, postoperative complications, and follow-up results were retrospectively compared and analyzed. Results: The basic patient characteristics were similar; but the total operative time for the LELAPE was longer than that of the conventional APR group (P = 0.014). However, the operative time for the perineal portion was comparable between the two groups (P = 0.328). The LELAPE group had less intraoperative blood loss (P = 0.022), a lower bowel perforation rate (P = 0.023), and a positive circumferential margin (P = 0.028). Moreover, the patients, who received the LELAPE, had a lower postoperative Visual Analog Scale, quicker recovery of bowel function (P = 0.001), and a shorter hospital stay (P = 0.047). However, patients in the LELAPE group suffered more chronic perineal pain (P = 0.002), which may be related to the coccygectomy (P = 0.033). Although the metastasis rate and mortality rate were similar between the two groups, the local recurrence rate of the LELAPE group was statistically improved (P = 0.047). Conclusions: When compared with conventional APR, LELAPE has the potential to reduce the risk of local recurrence, and decreases operative invasion for the treatment of locally advanced low rectal cancer. PMID:25963355

  5. Current perspectives on preoperative integrated treatments for locally advanced rectal cancer: a review of agreement and controversies.

    PubMed

    Cellini, Francesco; Valentini, Vincenzo

    2012-08-01

    The optimal approach to the diagnosis and treatment of locally advanced rectal cancer involves multidisciplinary, integrated management. In the past 30 years, survival and freedom from disease have increased, but the ideal multidisciplinary management remains to be determined. The preferred integrated treatment modality is preoperative radio(chemo)therapy followed by total mesorectal excision. Certain aspects of this standard are still debated, and the European and American approaches vary. The chief recommendations per international guidelines are summarized, and the next generation of integrated treatments for locally advanced rectal cancer is discussed.

  6. High-dose-rate intraluminal brachytherapy during preoperative chemoradiation for locally advanced rectal cancers

    PubMed Central

    Tunio, Mutahir Ali; Rafi, Mansoor; Hashmi, Altaf; Mohsin, Rehan; Qayyum, Abdul; Hasan, Mujahid; Sattar, Amjad; Mubarak, Muhammad

    2010-01-01

    AIM: To determine the feasibility and safety of high dose rate intraluminal brachytherapy (HDR-ILBT) boost during preoperative chemoradiation for rectal cancer. METHODS: Between 2008 and 2009, thirty-six patients with locally advanced rectal cancer (≥ T3 or N+), were treated initially with concurrent capecitabine (825 mg/m2 oral twice daily) and pelvic external beam radiotherapy (EBRT) (45 Gy in 25 fractions), then were randomized to group A; HDR-ILBT group (n = 17) to receive 5.5-7 Gy × 2 to gross tumor volume (GTV) and group B; EBRT group (n = 19) to receive 5.4 Gy × 3 fractions to GTV with EBRT. All patients underwent total mesorectal excision. RESULTS: Grade 3 acute toxicities were registered in 12 patients (70.6%) in group A and in 8 (42.1%) in group B. Complete pathologic response of T stage (ypT0) in group A was registered in 10 patients (58.8%) and in group B, 3 patients (15.8%) had ypT0 (P < 0.0001). Sphincter preservation was reported in 6/9 patients (66.7%) in group A and in 5/10 patients (50%) in group B (P < 0.01). Overall radiological response was 68.15% and 66.04% in Group A and B, respectively. During a median follow up of 18 mo, late grade 1 and 2 sequelae were registered in 3 patients (17.6%) and 4 patients (21.1%) in the groups A and B, respectively. CONCLUSION: HDR-ILBT was found to be effective dose escalation technique in preoperative chemoradiation for rectal cancers, with higher response rates, downstaging and with manageable acute toxicities. PMID:20845511

  7. Advances in management of adjuvant chemotherapy in rectal cancer: Consequences for clinical practice.

    PubMed

    Netter, Jeanne; Douard, Richard; Durdux, Catherine; Landi, Bruno; Berger, Anne; Taieb, Julien

    2016-11-01

    More than half the patients with rectal cancer present with locally advanced rectal disease at diagnosis with a high risk of recurrence. Preoperative chemoradiotherapy and standardized radical surgery with total mesorectal excision have been established as the 'gold standard' for treating these patients. Pathological staging using the ypTNM classification system to decide on adjuvant chemotherapy (ACT) is widely used in clinical practice, but the delivery of ACT is still controversial, as many discrepancies persist in the conclusions of different trials, due to heterogeneity of the inclusion criteria between studies, lack of statistical power, and variations in preoperative and adjuvant regimens. In 2014, a meta-analysis of four randomized phase-III trials (EORTC 22921, I-CNR-RT, PROCTOR-SCRIPT, CHRONICLE) failed to demonstrate any statistical efficacy of fluorouracil (5FU)-based ACT. Three recent randomized trials aimed to compare 5FU with 5FU plus oxaliplatin-based chemotherapy. Two of them (ADORE, CAO/ARO/AIO-04) appeared to find a disease-free survival benefit for patients treated with the combination therapy. Thus, while awaiting new data, it can be said that, as of 2015, patients with yp stage I tumors or histological complete response derived no benefit from adjuvant therapy. On the other hand, the FOLFOX chemotherapy regimen should be proposed for yp stage III patients, and may be considered for yp stage II tumors in fit patients with high-risk factors. Nevertheless, well-designed and sufficiently powered clinical trials dedicated to adjuvant treatments for rectal cancer remain justified in future to achieve a high level of proof in keeping with evidence-based medical standards. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  8. Restaging locally advanced rectal cancer by different imaging modalities after preoperative chemoradiation: a comparative study

    PubMed Central

    2013-01-01

    Background To compare the accuracy of different imaging modalities, alone and in combination in predicting findings at surgery after preoperative chemoradiation for locally advanced rectal cancer. Methods Following chemoradiation, tumors were reclassified on the basis of findings on pelvic computed tomography (CT) (94 patients), endorectal ultrasonography (EUS) (138 patients) alone or by both CT and EUS (80 patients). The ability of the imaging modalities, to predict the pathologic T status, N status, and TNM stage at surgery was evaluated and compared. Results Mean age of the patients was 64.5 years (range 28–88 years); 55% were male. CT and EUS combined had a positive predictive value of 20% for pathologic pT1 stage, 29% for pT1, 29% for pT2, and 58% for pT3. Predictive values for the operative TNM stage were 50% for stage I, 45% for stage II, and 31% for stage III. These values did not exceed those for each modality alone. Conclusion The performance of preoperative CT and EUS in predicting the T and TNM stage of rectal cancer at surgery is poor. Neither modality alone nor the two combined is sufficiently accurate to serve as the basis for decisions regarding treatment modification. PMID:24286200

  9. The best timing for administering systemic chemotherapy in patients with locally advanced rectal cancer

    PubMed Central

    Shimodaira, Yusuke; Harada, Kazuto; Lin, Quan

    2016-01-01

    Over the past several decades, outcomes for patients with rectal cancer have improved considerably. However, several questions have emerged as survival times have lengthened and quality of life has improved for these patients. Currently patients with locally advanced rectal cancer (LARC) are often recommended multimodality therapy with fluoropyrimidine-based chemotherapy (CT) and radiation followed by total mesorectal excision (TME), with consideration given to FOLFOX before chemoradiotherapy (CRT). Recently, Garcia-Aguilar and colleagues reported in Lancet Oncology that the addition of mFOLFOX6 administered between CRT and surgery affected the number of patients achieving pathologic complete response (pathCR), which is of great interest from the standpoint of pursuit of optimal timing of systemic CT delivery. This was a multicenter phase II study consisting of 4 sequential treatment groups of patients with LARC, and they reported that patients given higher number CT cycles between CRT and surgery achieved higher rates of pathCR than those given standard treatment. There was no association between response improvement and tumor progression, increased technical difficulty, or surgical complications. Ongoing phase III clinical trial further assessing this strategy might result in a paradigm shift. PMID:26889491

  10. The best timing for administering systemic chemotherapy in patients with locally advanced rectal cancer.

    PubMed

    Shimodaira, Yusuke; Harada, Kazuto; Lin, Quan; Ajani, Jaffer A

    2016-01-01

    Over the past several decades, outcomes for patients with rectal cancer have improved considerably. However, several questions have emerged as survival times have lengthened and quality of life has improved for these patients. Currently patients with locally advanced rectal cancer (LARC) are often recommended multimodality therapy with fluoropyrimidine-based chemotherapy (CT) and radiation followed by total mesorectal excision (TME), with consideration given to FOLFOX before chemoradiotherapy (CRT). Recently, Garcia-Aguilar and colleagues reported in Lancet Oncology that the addition of mFOLFOX6 administered between CRT and surgery affected the number of patients achieving pathologic complete response (pathCR), which is of great interest from the standpoint of pursuit of optimal timing of systemic CT delivery. This was a multicenter phase II study consisting of 4 sequential treatment groups of patients with LARC, and they reported that patients given higher number CT cycles between CRT and surgery achieved higher rates of pathCR than those given standard treatment. There was no association between response improvement and tumor progression, increased technical difficulty, or surgical complications. Ongoing phase III clinical trial further assessing this strategy might result in a paradigm shift.

  11. Response to chemoradiotherapy and lymph node involvement in locally advanced rectal cancer

    PubMed Central

    García-Flórez, Luis J; Gómez-Álvarez, Guillermo; Frunza, Ana M; Barneo-Serra, Luis; Fresno-Forcelledo, Manuel F

    2015-01-01

    AIM: To establish the association between lymph node involvement and the response to neoadjuvant therapy in locally advanced rectal cancer. METHODS: Data of 130 patients with mid and low locally advanced rectal adenocarcinoma treated with neoadjuvant chemoradiation followed by radical surgery over a 5-year period were reviewed. Tumor staging was done by endorectal ultrasound and/or magnetic resonance imaging. Tumor response to neoadjuvant therapy was determined by T-downstaging and tumor regression grading (TRG). Pathologic complete response (pCR) is defined as the absence of tumor cells in the surgical specimen (ypT0N0). The varying degrees TRG were classified according to Mandard’s scoring system. The evaluation of the response is based on the comparison between previous clinico-radiological staging and the results of pathological evaluation. χ2 and Spearman’s correlation tests were used for the comparison of variables. RESULTS: Pathologic complete response (pCR, ypT0N0, TRG1) was observed in 19 cases (14.6%), and other 18 (13.8%) had only very few residual malignant cells in the rectal wall (TRG2). T-downstaging was found in 63 (48.5%). Mean lymph node retrieval was 9.4 (range 0-38). In 37 cases (28.5%) more than 12 nodes were identified in the surgical specimen. Preoperative lymph node involvement was seen in 77 patients (59.2%), 71 N1 and 6 N2. Postoperative lymph node involvement was observed in 41 patients (31.5%), 29 N1 and 12 N2, while the remaining 89 were N0 (68.5%). In relation to ypT stage, we found nodal involvement of 9.4% in ypT0-1, 22.2% in ypT2 and 43.7% in ypT3-4. Of the 37 patients considered “responders” to neoadjuvant therapy (TRG1 and 2), there were only 4 N+ (10.8%) and the remainder N0 (89.2%). In the “non responders” group (TRG 3, 4 and 5), 37 cases were N+ (39.8%) and 56 (60.2%) were N0 (P < 0.001). CONCLUSION: Response to neoadjuvant chemoradiation in rectal cancer is associated with lymph node involvement. PMID:26425268

  12. Long-term results after neoadjuvant radiochemotherapy for locally advanced resectable extraperitoneal rectal cancer.

    PubMed

    Coco, Claudio; Valentini, Vincenzo; Manno, Alberto; Mattana, Claudio; Verbo, Alessandro; Cellini, Numa; Gambacorta, Maria Antonietta; Covino, Marcello; Mantini, Giovanna; Miccichè, Francesco; Pedretti, Giorgio; Petito, Luigi; Rizzo, Gianluca; Cosimelli, Maurizio; Impiombato, Fabrizio Ambesi; Picciocchi, Aurelio

    2006-03-01

    This study was designed to evaluate long-term outcome in locally advanced resectable extraperitoneal rectal cancer treated by preoperative radiochemotherapy. Eighty-three consecutive patients who developed locally advanced resectable extraperitoneal rectal cancer underwent preoperative concomitant radiochemotherapy followed by surgery, including total mesorectal excision. Median follow-up was 108 (range, 10-169) months. The living patients underwent complete follow-up of, at least, nine years. Fourteen patients developed local recurrence. The time to detection was longer than two years in eight cases and longer than five years in four. Twenty-one patients developed metastases, 19 within the first five years from surgery. At the univariate analysis, clinical stage at presentation, lymph node involvement at clinical restaging after neoadjuvant therapy, and pT and pN stage were found positively correlated to the incidence of metastases. At the multivariate analysis, the only factors which confirmed a positive correlation were pT stage and pN stage. The actuarial overall survival at five, seven, and ten years was 75.5, 67.8, and 60.4 percent, respectively. The same figures for cancer-related survival were 77.9, 70, and 65.8 percent. At the univariate analysis, factors directly correlated with worse survival were: TNM stage at clinical restaging after neoadjuvant therapy (in particular lymph node involvement) pTNM, pT, and pN. At the multivariate analysis the only factors that confirmed a correlation with worse survival were pTNM, pT, and pN. Long- term follow-up allows to individuate 28 percent of all local relapses after the first five years from surgery. Postoperative stage is highly predictive of prognosis.

  13. Local advanced rectal cancer perforation in the midst of preoperative chemoradiotherapy: A case report and literature review

    PubMed Central

    Takase, Nobuhisa; Yamashita, Kimihiro; Sumi, Yasuo; Hasegawa, Hiroshi; Yamamoto, Masashi; Kanaji, Shingo; Matsuda, Yoshiko; Matsuda, Takeru; Oshikiri, Taro; Nakamura, Tetsu; Suzuki, Satoshi; Koma, Yu-Ichiro; Komatsu, Masato; Sasaki, Ryohei; Kakeji, Yoshihiro

    2017-01-01

    Standard chemoradiotherapy (CRT) for local advanced rectal cancer (LARC) rarely induce rectal perforation. Here we report a rare case of rectal perforation in a patient with LARC in the midst of preoperative CRT. A 56-year-old male was conveyed to our hospital exhibiting general malaise. Colonoscopy and imaging tests resulted in a clinical diagnosis of LARC with direct invasion to adjacent organs and regional lymphadenopathy. Preoperative 5-fluorouracil-based CRT was started. At 25 d after the start of CRT, the patient developed a typical fever. Computed tomography revealed rectal perforation, and he underwent emergency sigmoid colostomy. At 12 d after the surgery, the remaining CRT was completed according to the original plan. The histopathological findings after radical operation revealed a wide field of tumor necrosis and fibrosis without lymph node metastasis. We share this case as important evidence for the treatment of LARC perforation in the midst of preoperative CRT. PMID:28138443

  14. Rectal cancer: a review

    PubMed Central

    Fazeli, Mohammad Sadegh; Keramati, Mohammad Reza

    2015-01-01

    Rectal cancer is the second most common cancer in large intestine. The prevalence and the number of young patients diagnosed with rectal cancer have made it as one of the major health problems in the world. With regard to the improved access to and use of modern screening tools, a number of new cases are diagnosed each year. Considering the location of the rectum and its adjacent organs, management and treatment of rectal tumor is different from tumors located in other parts of the gastrointestinal tract or even the colon. In this article, we will review the current updates on rectal cancer including epidemiology, risk factors, clinical presentations, screening, and staging. Diagnostic methods and latest treatment modalities and approaches will also be discussed in detail. PMID:26034724

  15. [A Case of Advanced Rectal Cancer Resected Successfully after Induction Chemotherapy with Modified FOLFOX6 plus Panitumumab].

    PubMed

    Yukawa, Yoshimi; Uchima, Yasutake; Kawamura, Minori; Takeda, Osami; Hanno, Hajime; Takayanagi, Shigenori; Hirooka, Tomoomi; Dozaiku, Toshio; Hirooka, Takashi; Aomatsu, Naoki; Hirakawa, Toshiki; Iwauchi, Takehiko; Nishii, Takafumi; Morimoto, Junya; Nakazawa, Kazunori; Takeuchi, Kazuhiro

    2016-05-01

    We report a case of advanced colon cancer that was effectively treated with mFOLFOX6 plus panitumumab combination chemotherapy. The patient was a 54-year-old man who had type 2 colon cancer of the rectum. An abdominal CT scan demonstrated rectal cancer with bulky lymph node metastasis and 1 hepatic node (rectal cancer SI [bladder retroperitoneum], N2M0H1P0, cStage IV). He was treated with mFOLFOX6 plus panitumumab as neoadjuvant chemotherapy. After 4 courses of chemotherapy, CT revealed that the primary lesion and regional metastatic lymph nodes had reduced in size (rectal cancer A, N1H1P0M0, cStage IV). Anterior rectal resection with D3 nodal dissection and left lateral segmentectomy of the liver was performed. The histological diagnosis was tubular adenocarcinoma (tub2-1), int, INF a, pMP, ly0, v0, pDM0, pPM0, R0. He was treated with 4 courses of mFOLFOX6 after surgery. The patient has been in good health without a recurrence for 2 years and 5 months after surgery. This case suggests that induction chemotherapy with mFOLFOX6 plus panitumumab is a potentially effective regimen for advanced colon cancer.

  16. Advanced rectal cancer in a long-term Hartmann's pouch: a forgotten organ revisited.

    PubMed

    Al Maksoud, Ahmed Mahmoud Abd El Aziz; Ahmed, Iftikhar

    2016-01-28

    Hartmann's procedure is widely performed as a first-stage operation in cases of left colon emergencies when a one stage management is judged to be unsafe. Forty per cent of patients with Hartmann's procedure never get their stoma reversed, ending with a permanent stoma. The distal excluded Hartmann's pouch is usually forgotten compared to the proximal functioning colon. A 70-year-old man with Hartmann's procedure carried out previously for complicated diverticular disease presented with bleeding per rectum. Invasive adenocarcinoma was confirmed on histology. Subsequent staging revealed a locally advanced rectal cancer. The tumour progressed despite a course of neoadjuvant chemoradiation. The general condition of the patient deteriorated with development of renal failure. The patient died a few weeks later. By reporting this case, we are revisiting the long forgotten Hartmann's pouch to highlight the potential pathologies in the distal stump and to emphasise that a distal stump should not be forgotten even in asymptomatic patients. 2016 BMJ Publishing Group Ltd.

  17. Definitive high-dose radiotherapy with concurrent chemotherapy for locally advanced rectal cancer

    PubMed Central

    Kim, Min-Jeong; Kim, Eun Seok; Yeo, Seung-Gu

    2016-01-01

    Abstract Background: Standard management for locally advanced rectal cancer (LARC) involves preoperative chemoradiotherapy (CRT) and radical surgery. However, this level of treatment may be unnecessary for a subgroup of LARC patients. Previous reports have shown that approximately 20% of LARC patients experience a complete tumor response to preoperative CRT. Post-CRT nonoperative management of these patients may prevent morbidities associated with radical surgery. To our knowledge, this case report firstly presents the favorable long-term outcomes of a LARC patient who underwent definitive aim CRT. Methods: The patient was 73 years’ old, and staging workups revealed T3N2bM0 rectal adenocarcinoma. He agreed to receive CRT, but refused surgery. A radiotherapy (RT) dose of 64.8 Gy was prescribed, which was higher than conventional (50.4 Gy) preoperative aim RT. The regimen of concurrent chemotherapy was the same as that used in preoperative aim CRT: 2 cycles of 5-fluorouracil and leucovorin. Results: Three months after CRT completion, a complete tumor response was identified clinically. Colonoscopic biopsy after 1 year showed no tumor cells. This patient is alive after 4 years with no evidence of recurrence or severe toxicity. Conclusion: The long-term outcomes of this case indicate the feasibility of definitive high-dose RT with concurrent chemotherapy for LARC. PMID:27749573

  18. Comparison of 5-fluorouracil/leucovorin and capecitabine in preoperative chemoradiotherapy for locally advanced rectal cancer

    SciTech Connect

    Kim, Dae Yong; Jung, Kyung Hae . E-mail: khjung@ncc.re.kr; Kim, Tae Hyun; Kim, Duck-Woo; Chang, Hee Jin; Jeong, Jun Yong; Kim, Young Hoon; Son, Seok-Hyun; Yun, Tak; Hong, Chang Won; Sohn, Dae Kyung; Lim, Seok-Byung; Choi, Hyo Seong; Jeong, Seung-Yong; Park, Jae-Gahb

    2007-02-01

    Purpose: To describe our experience with a bolus injection of 5-fluorouracil and leucovorin (FL) vs. capecitabine in terms of radiologic and pathologic findings in preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer. Methods: The study enrolled 278 patients scheduled for preoperative CRT using two protocols with different chemotherapeutic regimens. Pelvic radiotherapy (50.4 Gy) was delivered concurrently with FL (n = 145) or capecitabine (n = 133). Surgery was performed 6 weeks after CRT completion. Tumor responses to CRT were measured using both radiologic and pathologic examination. Magnetic resonance volumetry was performed at the initial workup and just before surgery after completion of preoperative CRT. Post-CRT pathology tests were used to determine tumor stage and regression. Results: Radiologic examination showed that tumor volume decreased by 68.2% {+-} 20.5% in the FL group and 68.3% {+-} 22.3% in the capecitabine group (p = 0.970). Postoperative pathologic T stage determination showed that downstaging occurred in 44.3% of FL and 49.9% of capecitabine patients (p = 0.571). The tumor regression grades after CRT were Grade 1 (minimal response) in 22.6% and 21.0%, Grade 2 (moderate response) in 53.2% and 50.0%, Grade 3 (near-complete response) in 12.9% and 12.9%, and Grade 4 (complete response) in 11.3% and 16.1% of the FL and capecitabine groups, respectively (p = 0.758). Conclusion: In the present study, the radiologic and pathologic findings did not reveal significant differences in short-term tumor responses between preoperative FL and capecitabine CRT for locally advanced rectal cancer. Long-term results and a prospective randomized trial are needed.

  19. Preoperative chemoradiation for locally advanced rectal cancer: comparison of three radiation dose and fractionation schedules

    PubMed Central

    Park, Shin-Hyung; Kim, Jae-Chul

    2016-01-01

    Purpose: The standard radiation dose for patients with locally rectal cancer treated with preoperative chemoradiotherapy is 45–50 Gy in 25–28 fractions. We aimed to assess whether a difference exists within this dose fractionation range. Materials and Methods: A retrospective analysis was performed to compare three dose fractionation schedules. Patients received 50 Gy in 25 fractions (group A), 50.4 Gy in 28 fractions (group B), or 45 Gy in 25 fractions (group C) to the whole pelvis, as well as concurrent 5-fluorouracil. Radical resection was scheduled for 8 weeks after concurrent chemoradiotherapy. Results: Between September 2010 and August 2013, 175 patients were treated with preoperative chemoradiotherapy at our institution. Among those patients, 154 were eligible for analysis (55, 50, and 49 patients in groups A, B, and C, respectively). After the median follow-up period of 29 months (range, 5 to 48 months), no differences were found between the 3 groups regarding pathologic complete remission rate, tumor regression grade, treatment-related toxicity, 2-year locoregional recurrence-free survival, distant metastasis-free survival, disease-free survival, or overall survival. The circumferential resection margin width was a prognostic factor for 2-year locoregional recurrence-free survival, whereas ypN category was associated with distant metastasis-free survival, disease-free survival, and overall survival. High tumor regression grading score was correlated with 2-year distant metastasis-free survival and disease-free survival in univariate analysis. Conclusion: Three different radiation dose fractionation schedules, within the dose range recommended by the National Comprehensive Cancer Network, had no impact on pathologic tumor regression and early clinical outcome for locally advanced rectal cancer. PMID:27306773

  20. 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.

  1. Does chronomodulated radiotherapy improve pathological response in locally advanced rectal cancer?

    PubMed

    Squire, Tim; Buchanan, Grant; Rangiah, David; Davis, Ian; Yip, Desmond; Chua, Yu Jo; Rich, Tyvin; Elsaleh, Hany

    2017-01-01

    tumour distance from the anal verge. Females were less likely to exhibit several of the above responses. Neoadjuvant radiotherapy for locally advanced rectal cancer performed later in the day coupled with a longer time period to surgical resection may improve pathological tumour response rates and nodal downstaging. A prospective study in chronomodulated radiotherapy in this disease is warranted.

  2. Discriminating cancer-related and cancer-unrelated chemoradiation-response genes for locally advanced rectal cancers

    PubMed Central

    Guo, You; Cheng, Jun; Ao, Lu; Li, Xiangyu; Guan, Qingzhou; Zhang, Juan; Yan, Haidan; Cai, Hao; Gao, Qiao; Jiang, Weizhong; Guo, Zheng

    2016-01-01

    For patients with locally advanced rectal cancer (LARC) treated with preoperation chemoradiation (pCRT), identifying differentially expressed (DE) genes between non-responders and responders is a common approach for investigating mechanisms of chemoradiation resistance. However, some of such DE genes might be irrelevant to cancer itself but simply reflect the pharmacokinetic differences of the normal tissues. In this study, we adopted the RankComp algorithm to identify DE genes for each of LARC sample compared with its own normal state. Then, we identified genes with significantly different deregulation frequencies between the non-responders and responders, defined as cancer-related pCRT-response genes. Pathway enrichment and protein-protein interaction analyses showed that these genes specifically and intensively interacted with currently known effective genes of pCRT, involving in DNA replication, cell cycle and DNA repair. In contrast, after excluding the cancer-related pCRT-response genes, the other DE genes between non-responders and responders were enriched in many pathways of drug and protein metabolisms and transports, and interacted with both the known effective genes and pharmacokinetic genes. Hence, these two types of DE genes should be distinguished for investigating mechanisms of pCRT response in LARCs. PMID:27845363

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

    SciTech Connect

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

    2010-03-01

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

  4. Rectal imaging and cancer.

    PubMed

    Vining, D J

    1998-09-01

    Rectal imaging has evolved substantially during the past 25 years and now offers surgeons exquisite anatomic detail and physiologic information. Dynamic cystoproctography, helical computed tomography, endoscopic ultrasonography, endorectal magnetic resonance imaging, and immunoscintigraphy have become standards for the diagnosis of rectal disease, staging of neoplasia, and survey of therapeutic results. The indications, limitations, and relative costs of current imaging methods are reviewed, and advances in imaging technology that promise future benefits to colorectal surgeons are introduced.

  5. Chemoradiation of rectal cancer.

    PubMed

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

    2013-02-01

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

  6. The Role of Robotic Surgery for Rectal Cancer: Overcoming Technical Challenges in Laparoscopic Surgery by Advanced Techniques.

    PubMed

    Park, Seungwan; Kim, Nam Kyu

    2015-07-01

    The conventional laparoscopic approach to rectal surgery has several limitations, and therefore many colorectal surgeons have great expectations for the robotic surgical system as an alternative modality in overcoming challenges of laparoscopic surgery and thus enhancing oncologic and functional outcomes. This review explores the possibility of robotic surgery as an alternative approach in laparoscopic surgery for rectal cancer. The da Vinci® Surgical System was developed specifically to compensate for the technical limitations of laparoscopic instruments in rectal surgery. The robotic rectal surgery is associated with comparable or better oncologic and pathologic outcomes, as well as low morbidity and mortality. The robotic surgery is generally easier to learn than laparoscopic surgery, improving the probability of autonomic nerve preservation and genitourinary function recovery. Furthermore, in very complex procedures such as intersphincteric dissections and transabdominal transections of the levator muscle, the robotic approach is associated with increased performance and safety compared to laparoscopic surgery. The robotic surgery for rectal cancer is an advanced technique that may resolve the issues associated with laparoscopic surgery. However, high cost of robotic surgery must be addressed before it can become the new standard treatment.

  7. Association Between the Cytogenetic Profile of Tumor Cells and Response to Preoperative Radiochemotherapy in Locally Advanced Rectal Cancer

    PubMed Central

    González-González, María; Garcia, Jacinto; Alcazar, José A.; Gutiérrez, María L.; Gónzalez, Luis M.; Bengoechea, Oscar; Abad, María M.; Santos-Briz, Angel; Blanco, Oscar; Martín, Manuela; Rodríguez, Ana; Fuentes, Manuel; Muñoz-Bellvis, Luis; Orfao, Alberto; Sayagues, Jose M.

    2014-01-01

    Abstract Neoadjuvant radiochemotherapy to locally advanced rectal carcinoma patients has proven efficient in a high percentage of cases. Despite this, some patients show nonresponse or even disease progression. Recent studies suggest that different genetic alterations may be associated with sensitivity versus resistance of rectal cancer tumor cells to neoadjuvant therapy. We investigated the relationship between intratumoral pathways of clonal evolution as assessed by interphase fluorescence in situ hybridization (51 different probes) and response to neoadjuvant radiochemotherapy, evaluated by Dworak criteria in 45 rectal cancer tumors before (n = 45) and after (n = 31) treatment. Losses of chromosomes 1p (44%), 8p (53%), 17p (47%), and 18q (38%) and gains of 1q (49%) and 13q (75%) as well as amplification of 8q (38%) and 20q (47%) chromosomal regions were those specific alterations found at higher frequencies. Significant association (P < 0.05) was found between alteration of 1p, 1q, 11p, 12p, and 17p chromosomal regions and degree of response to neoadjuvant therapy. A clear association was observed between cytogenetic profile of the ancestral tumor cell clone and response to radiochemotherapy; cases presenting with del(17p) showed a poor response to neoadjuvant treatment (P = 0.03), whereas presence of del(1p) was more frequently observed in responder patients (P = 0.0002). Moreover, a significantly higher number of copies of chromosomes 8q (P = 0.004), 13q (P = 0.003), and 20q (P = 0.002) were found after therapy versus paired pretreatment rectal cancer samples. Our results point out the existence of an association between tumor cytogenetics and response to neoadjuvant therapy in locally advanced rectal cancer. Further studies in larger series of patients are necessary to confirm our results. PMID:25474426

  8. Complete pathological response to bevacizumab and chemoradiation in advanced rectal cancer

    PubMed Central

    Willett, Christopher G; Duda, Dan G; di Tomaso, Emmanuelle; Boucher, Yves; Czito, Brian G; Vujaskovic, Zeljko; Vlahovic, Gordana; Bendell, Johanna; Cohen, Kenneth S; Hurwitz, Herbert I; Bentley, Rex; Lauwers, Gregory Y; Poleski, Martin; Wong, Terence Z; Paulson, Erik; Ludwig, Kirk A; Jain, Rakesh K

    2009-01-01

    SUMMARY Background Localized rectal cancer responds well to 5-fluorouracil and radiation-based regimens. A phase I–II trial is currently testing the efficacy of adding bevacizumab, a VEGF-specific antibody, to standard chemoradiotherapy. The case presented here is a complete pathological response seen in a patient with extensive and locally invasive carcinoma after receiving this combined treatment. Investigations Physical examination, rectal ultrasound, PET–CT scan, laboratory tests, proctoscopic examination, chest radiograph, rectal forcep biopsies with immunohistochemistry, and protein and flow cytometric analyses. Diagnosis Large, invasive, ultrasound stage T4 carcinoma of the rectum, which was positive for survivin. Management One 2-week cycle of bevacizumab alone, followed by 3 cycles of bevacizumab with continuous 5-fluorouracil infusion, and external-beam radiation therapy given 5 days per week to the pelvis, abdominoperineal resection with posterior vaginectomy, hysterectomy and bilateral salpingo-oophorectomy. PMID:17464339

  9. Pseudocirrhosis caused by regorafenib in an advanced rectal cancer patient with multiple liver metastases

    PubMed Central

    Kumamoto, Kensuke; Endo, Shungo; Isohata, Noriyuki; Nirei, Azuma; Nemoto, Daiki; Utano, Kenichi; Saito, Takuro; Togashi, Kazutomo

    2017-01-01

    A 70-year-old man who was diagnosed with unresectable advanced rectal cancer with multiple liver metastases, received oxaliplatin-based treatment with bevacizumab as first-line chemotherapy and irinotecan-based treatment with bevacizumab as second-line chemotherapy for a total of 17 months. The patient was treated with regorafenib (160 mg/day for 3 weeks) as third-line chemotherapy. Following completion of one course of regorafenib treatment, the patient complained of abdominal distension. Computed tomography (CT) examination identified liver atrophy and massive ascites, while no such symptoms were observed prior to the regorafenib treatment. Blood testing revealed increases in the aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) levels. The patient was admitted to the Aizu Medical Center (Aizuwakamatsu, Japan). Approximately 2,000 ml of ascitic fluid were aspirated daily for 1 week by abdominal puncture. The patient was administered oral diuretics, including 20 mg/day of furosemide and 25 mg/day of spironolactone. Albumin was administered to correct the albumin deficit. The levels of AST, ALT and ALP were decreased from the peak value reported on admission and the patient was discharged from our hospital 16 days following treatment initiation. The CT examination after 1 month revealed that the volume of the liver had been restored and the ascites had disappeared. Furthermore, almost all the liver metastases were reduced in size. The carcinoembryonic antigen level, which was elevated prior to regorafenib treatment, also decreased to normal. PMID:28123730

  10. Locally advanced rectal cancer: predicting non-responders to neoadjuvant chemoradiotherapy using apparent diffusion coefficient textures.

    PubMed

    Liu, Ming; Lv, Han; Liu, Li-Heng; Yang, Zheng-Han; Jin, Er-Hu; Wang, Zhen-Chang

    2017-07-01

    The purpose of the study is to evaluate whether apparent diffusion coefficient (ADC) textures could identify patient with locally advanced rectal cancer (LARC) who would not respond to neoadjuvant chemoradiotherapy (NCRT). Twenty-six patients who underwent MRI including diffusion-weighted imaging at a 3.0 T system before NCRT were enrolled. Texture analysis of pre-therapy ADC mapping was carried out, and a total of 133 ADC textures as well as routine mean ADC value of the primary tumor were extracted for each patient. Texture parameters and mean ADC were compared between responsive group and non-responsive group. Logistic regression was used to determine the independent predictors for non-responders. Receiver operating characteristic curve (ROC) was performed to evaluate the predictive performance of the significant parameters. Eighteen of the 133 texture parameters significantly differed between responsive and non-responsive groups (p < 0.05). Further, energy variance and SdGa47 were identified as independent predictors for non-responders to NCRT; this logistic model achieved an area under the curve (AUC) of 0.908. Texture analysis based on pre-therapy ADC mapping could potentially be helpful to identify patients with LARC who would not respond to NCRT.

  11. Clinical implications of preoperative chemoradiotherapy prior to laparoscopic surgery for locally advanced low rectal cancer

    PubMed Central

    Kondo, Keisaku; Shimbo, Taiju; Tanaka, Keitaro; Yamamoto, Masashi; Narumi, Yoshifumi; Okuda, Junji; Uchiyama, Kazuhisa

    2017-01-01

    The present study aimed to evaluate whether preoperative chemoradiotherapy (CRT) has any adverse effects on laparoscopic surgery (LS) for locally advanced low rectal cancer (LARC). The study was performed at the Osaka Medical College Hospital, and included patients who were operated on between July 2006 and December 2013. The short-term outcomes in 156 patients who underwent surgery for LARC following CRT were evaluated, of whom 152 underwent LS. Among the patients who were followed for >40 months, 77 patients (the CRT group) were compared with 39 patients who underwent LS without CRT (the surgery-alone group) for long-term outcomes. The total number of patients who received sphincter-preserving surgery was 74%. No positive longitudinal resection margins were identified, and only 1.3% had identifiable positive circumferential resection margins. The complication rate was 14%, and no serious complications occurred. There were no significant differences between the CRT and the surgery-alone groups in terms of the 5-year relapse-free survival rate (70.1 vs. 61.5%; P=0.81) or the 5-year overall survival rate (88.3 vs. 69.2%; P=0.06). However, the 5-year local recurrence-free survival rate was significantly improved in the CRT group patients (96.1 vs. 79.5%; P=0.009). In conclusion, our results have demonstrated that LS with preoperative CRT appears to be feasible and safe, and may have beneficial effects on local recurrence. PMID:28123724

  12. Best MRI predictors of complete response to neoadjuvant chemoradiation in locally advanced rectal cancer.

    PubMed

    Sathyakumar, Kirthi; Chandramohan, Anuradha; Masih, Dipti; Jesudasan, Mark Ranjan; Pulimood, Anna; Eapen, Anu

    2016-01-01

    To identify the MRI parameters which best predict complete response (CR) to neoadjuvant chemoradiotherapy (CRT) in patients with locally advanced rectal cancer (LARC) and to assess their diagnostic performance. This was a prospective study of pre- and post-CRT MRI and diffusion-weighted imaging (DWI) of 64 patients with LARC who underwent neoadjuvant CRT and subsequent surgery. Histopathological tumour regression grade was the reference standard. Multivariate regression analysis was performed to identify the best MRI predictors of CR to neoadjuvant CRT, and their diagnostic performance was assessed. The study cohort comprised 48 males and 16 females (n = 64), with mean age of 49.48 ± 14.3 years, range of 23-74 years. 11 patients had pathological complete response. The following factors predicted CR on univariate analysis: low initial (pre-CRT) tumour volume on T2 weighted high-resolution (HR) images and DWI, tumour volume-reduction rate (TVRR) of >95% on DWI and CR on post-CRT DWI (ydwiT0) as assessed by the radiologist. However, the best MRI predictors of CR on multivariate regression analysis were CR on post-CRT DWI (ydwiT0) as assessed by the radiologist and TVRR of >95% on DWI, and these parameters had an area under the curve (95% confidence interval) of 0.881 (0.74-1.0) and 0.843 (0.7-0.98), respectively. The sensitivity, specificity, positive-predictive value, negative-predictive value and accuracy of DWI in predicting CR was 81.8%, 94.3%, 75%, 96.1% and 76%; the sensitivity, specificity and accuracy of TVRR of >95% as a predictor of CR was 80%, 84.1% and 64.1%, respectively; however, this difference was not statistically significant. The interobserver agreement was substantial for ydwiT0. Visual assessment of CR on post-CRT DWI and TVRR of >95% on DWI were the best predictors of CR after neoadjuvant CRT in patients with LARC, and the former being more practical can be used in daily practice. In rectal cancer, ydwiT0 as assessed by the radiologist

  13. Transanal endoscopic microsurgery after neoadjuvant radiochemotherapy for locally advanced extraperitoneal rectal cancer.

    PubMed

    Rizzo, G; Zaccone, G; Magnocavallo, M; Mattana, C; Pafundi, D P; Gambacorta, M A; Valentini, V; Coco, C

    2017-08-01

    The aim of this study is to provide a prospective analysis of post-operative and oncological outcomes in patients affected by locally advanced rectal cancer (LARC), who obtained a major/complete clinical response after pre-operative radio-chemotherapy (RCT) and were treated with local excision (LE) by trans-anal endoscopic microsurgery (TEM) to confirm a pathological complete response (pCR) after to neo-adjuvant RCT. All patients with LARC treated by pre-operative RCT and full-thickness LE by TEM (2000-2014) were included in the study. If the pathological analysis confirmed near complete or pCR, intensive follow up was proposed. If the pathological response was incomplete, a radical resection with TME was proposed. Post-operative (according to Clavien's classification), functional and long-term oncological outcome were analyzed. 36 patients were treated by TEM. The median post-operative hospital stay was 5 days. The post-operative morbidity was 41.6% (no grade ≥3). At pathological analysis, 23 specimens were ypT0 TRG1, and 4 were ypT1 TRG2. In 9 cases (ypT>1 and/or TRG>2), radical surgery with TME was proposed but 3 refused it. Median follow-up was 68 months. One local recurrence and 4 distant metastases occurred. The 5-yr actuarial local control, overall survival and disease-free survival were 96.0%, 92.0% and 82.8%. In case of major or complete clinical response of LARC after pre-operative RCT, LE by TEM can be used to confirm the pathological response. This avoids the necessity of radical surgery and, in our experience, this approach seems to guarantee oncological safety with the functional advantages of an organ-sparing procedure. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  14. Locally Advanced Rectal Cancer Patients Receiving Radio-Chemotherapy: A Novel Clinical-Pathologic Score Correlates With Global Outcome

    SciTech Connect

    Berardi, Rossana; Mantello, Giovanna; Scartozzi, Mario; Del Prete, Stefano; Luppi, Gabriele; Martinelli, Roberto; Fumagalli, Marco; Grillo-Ruggieri, Filippo; Bearzi, Italo; Mandolesi, Alessandra; Marmorale, Cristina; Cascinu, Stefano

    2009-12-01

    Purpose: To determine the importance of downstaging of locally advanced rectal cancer after neoadjuvant treatment. Methods and Materials: The study included all consecutive patients with locally advanced rectal cancer who underwent neoadjuvant treatment (chemotherapy and/or radiotherapy) in different Italian centers from June 1996 to December 2003. A novel score was used, calculated as the sum of numbers obtained by giving a negative or positive point, respectively, to each degree of increase or decrease in clinical to pathologic T and N status. Results: A total of 317 patients were eligible for analysis. Neoadjuvant treatments performed were as follows: radiotherapy alone in 75 of 317 patients (23.7%), radiotherapy plus chemotherapy in 242 of 317 patients (76.3%). Worse disease-free survival was observed in patients with a lower score (Score 1 = -3 to +3 vs. Score 2 = +4 to +7; p = 0.04). Conclusions: Our results suggest that a novel score, calculated from preoperative and pathologic tumor and lymph node status, could represent an important parameter to predict outcome in patients receiving neoadjuvant treatment for rectal cancer. The score could be useful to select patients for adjuvant chemotherapy after neoadjuvant treatment and surgery.

  15. Epidermal growth factor receptor as a predictor of tumor downstaging in locally advanced rectal cancer patients treated with preoperative chemoradiotherapy

    SciTech Connect

    Kim, Jun-Sang . E-mail: k423j@cnu.ac.kr; Kim, Jin-Man; Li, Shengjin; Yoon, Wan-Hee; Song, Kyu-Sang; Kim, Ki-Hwan; Yeo, Seung-Gu; Nam, Ji Sook; Cho, Moon-June

    2006-09-01

    Purpose: To examine retrospectively whether levels of epidermal growth factor receptor (EGFR) expression can predict tumor downstaging after preoperative chemoradiotherapy in patients with locally advanced rectal cancer. Methods and Materials: A total of 183 patients with rectal cancer (cT3-T4 or N+) were enrolled in this study. Preoperative chemoradiotherapy consisted of 50.4 Gy of pelvic radiation with concurrent 5-fluorouracil and leucovorin bolus intravenous chemotherapy in 94 patients or oral capecitabine and leucovorin in 89 patients. EGFR expression in pretreatment paraffin-embedded tumor biopsy specimens was assessed by immunohistochemistry. EGFR expression was determined from the intensity and extent of staining. Tumor downstaging was defined as a reduction of at least one T-stage level. Results: Tumor downstaging occurred in 97 patients (53%), and the tumors showed a pathologic complete response in 27 patients (15%). Positive EGFR expression was observed in 140 (76%) of 183 patients. EGFR expression levels were low in 113 patients (62%) and high in 70 patients (38%). On logistic regression analysis, the significant predictive factor for increased tumor downstaging was a low level of EGFR expression and preoperative chemotherapy using oral capecitabine (odds ratio, 0.437; p 0.012 vs. odds ratio, 3.235; p < 0.001, respectively). Conclusion: A high level of EGFR expression may be a significant predictive molecular marker for decreased tumor downstaging after preoperative chemoradiotherapy in locally advanced rectal cancer.

  16. Future of therapy for rectal cancer.

    PubMed

    Minsky, Bruce D

    2013-06-01

    Since 2004, the standard of care for patients with cT3 and/or N+ rectal cancer has been preoperative chemoradiation followed by surgery and postoperative adjuvant chemotherapy. A number of advances have occurred and are defining the future of rectal cancer therapy. Among these are short course radiation, the impact of postoperative adjuvant chemotherapy, selective radiation and selective surgery, and new chemoradiation regimens with novel agents. This review will examine these developments and assess their impact on the future therapy of rectal cancer.

  17. Rectal cancer. Treatment advances that reduce recurrence rates and lengthen survival.

    PubMed

    Sexe, R; Miedema, B W

    1993-07-01

    The risk of malignant disease arising in rectal mucosa is high. Surgery is the most effective form of treatment but results in cure in only 50% of patients. Adjuvant preoperative radiation therapy reduces the likelihood of local recurrence but does not improve survival rates. Fluorouracil is the most effective agent for adjuvant chemotherapy and slightly improves survival when given after surgery. Combining radiation therapy with chemotherapy appears to have a synergistic effect, and recent studies show that providing this combination after surgery improves survival. Future trends in the treatment of rectal cancer are expected to include expanded use of local excision to preserve anal sphincter function, preoperative use of a combination of radiation therapy and chemotherapy, perioperative use of chemotherapy combined with immunostimulating therapy, and use of tumor antibodies for diagnostic and therapeutic purposes.

  18. Panitumumab as a radiosensitizing agent in KRAS wild-type locally advanced rectal cancer.

    PubMed

    Mardjuadi, Feby Ingriani; Carrasco, Javier; Coche, Jean-Charles; Sempoux, Christine; Jouret-Mourin, Anne; Scalliet, Pierre; Goeminne, Jean-Charles; Daisne, Jean-François; Delaunoit, Thierry; Vuylsteke, Peter; Humblet, Yves; Meert, Nicolas; van den Eynde, Marc; Moxhon, Anne; Haustermans, Karin; Canon, Jean-Luc; Machiels, Jean-Pascal

    2015-09-01

    Our goal was to optimize the radiosensitizing potential of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies, when given concomitantly with preoperative radiotherapy in KRAS wild-type locally advanced rectal cancer (LARC). Based on pre-clinical studies conducted by our group, we designed a phase II trial in which panitumumab (6 mg/kg/q2 weeks) was combined with preoperative radiotherapy (45 Gy in 25 fractions) to treat cT3-4/N + KRAS wild-type LARC. The primary endpoint was complete pathologic response (pCR) (H0 = 5%, H1 = 17%, α = 0.05, β = 0.2). From 19 enrolled patients, 17 (89%) were evaluable for pathology assessment. Although no pCR was observed, seven patients (41%) had grade 3 Dworak pathological tumor regression. The regimen was safe and was associated with 95% of sphincter-preservation rate. No NRAS, BRAF, or PI3KCA mutation was found in this study, but one patient (5%) showed loss of PTEN expression. The quantification of plasma EGFR ligands during treatment showed significant upregulation of plasma TGF-α and EGF following panitumumab administration (p < 0.05). At surgery, patients with important pathological regression (grade 3 Dworak) had higher plasma TGF-α (p = 0.03) but lower plasma EGF (p = 0.003) compared to those with grade 0-2 Dworak. Our study suggests that concomitant panitumumab and preoperative radiotherapy in KRAS wild-type LARC is feasible and results in some tumor regression. However, pCR rate remained modest. Given that the primary endpoint of our study was not reached, we remain unable to recommend the use of panitumumab as a radiosensitizer in KRAS wild-type LARC outside a research setting.

  19. 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

  20. Capecitabine Initially Concomitant to Radiotherapy Then Perioperatively Administered in Locally Advanced Rectal Cancer

    SciTech Connect

    Zampino, Maria Giulia Magni, Elena; Leonardi, Maria Cristina; Petazzi, Elena; Santoro, Luigi; Luca, Fabrizio; Chiappa, Antonio; Petralia, Giuseppe; Trovato, Cristina; Fazio, Nicola; Orecchia, Roberto; Nole, Franco; Braud, Filippo de

    2009-10-01

    Purpose: To evaluate the impact of neoadjuvant capecitabine, concomitant to radiotherapy, followed by capecitabine monotherapy, in operable locally advanced rectal cancer (LARC) by measuring pathologic response and conservative surgery rate, toxicity profile, and disease-free survival (DFS). Methods and Materials: From October 2002 to July 2006, a total of 51 patients affected by LARC (T3-T4 or any node positive tumor), received capecitabine (825 mg/m{sup 2}, orally, twice daily continuously) concomitant to radiotherapy on the pelvis (50.4 Gy/ 28 fractions), followed by two cycles of capecitabine (1,250 mg/m{sup 2}, orally, twice daily, 14 days on 7 days off) up until 2 weeks before surgery. Tailored adjuvant systemic treatment was discussed according to pathologic stage. Results: Of 51 patients, (median age 61 years, range 38-82 years; 19 women and 32 men; ECOG performance status 0/1/2: 46/4/1), 50 were evaluable for response: 18% complete pathologic remission; 12% T-downstaging, and 30% N-downstaging. One patient died before surgery from mesenteric stroke. Grade 3 acute toxicities were 2% diarrhea, 8% dermatitis, 2% liver function test elevation, and 2% hand-foot syndrome. Sphincter preservation rates for tumors {<=}6 cm from the anal verge were 62% and 80% for the whole population. Median follow up was 43.0 months (range 0.8-68.6 months). Five-years DFS was 85.4% (95% CI = 75.3-95.4%). Conclusions: Based on our study results, we conclude that this regimen is well tolerated and active and compares favorably with existing capecitabine-based approaches.

  1. Tumor Volume Reduction Rate After Preoperative Chemoradiotherapy as a Prognostic Factor in Locally Advanced Rectal Cancer

    SciTech Connect

    Yeo, Seung-Gu; Kim, Dae Yong; Park, Ji Won; Oh, Jae Hwan; Kim, Sun Young; Chang, Hee Jin; Kim, Tae Hyun; Kim, Byung Chang; Sohn, Dae Kyung; Kim, Min Ju

    2012-02-01

    Purpose: To investigate the prognostic significance of tumor volume reduction rate (TVRR) after preoperative chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC). Methods and Materials: In total, 430 primary LARC (cT3-4) patients who were treated with preoperative CRT and curative radical surgery between May 2002 and March 2008 were analyzed retrospectively. Pre- and post-CRT tumor volumes were measured using three-dimensional region-of-interest MR volumetry. Tumor volume reduction rate was determined using the equation TVRR (%) = (pre-CRT tumor volume - post-CRT tumor volume) Multiplication-Sign 100/pre-CRT tumor volume. The median follow-up period was 64 months (range, 27-99 months) for survivors. Endpoints were disease-free survival (DFS) and overall survival (OS). Results: The median TVRR was 70.2% (mean, 64.7% {+-} 22.6%; range, 0-100%). Downstaging (ypT0-2N0M0) occurred in 183 patients (42.6%). The 5-year DFS and OS rates were 77.7% and 86.3%, respectively. In the analysis that included pre-CRT and post-CRT tumor volumes and TVRR as continuous variables, only TVRR was an independent prognostic factor. Tumor volume reduction rate was categorized according to a cutoff value of 45% and included with clinicopathologic factors in the multivariate analysis; ypN status, circumferential resection margin, and TVRR were significant prognostic factors for both DFS and OS. Conclusions: Tumor volume reduction rate was a significant prognostic factor in LARC patients receiving preoperative CRT. Tumor volume reduction rate data may be useful for tailoring surgery and postoperative adjuvant therapy after preoperative CRT.

  2. Phase II study of preoperative bevacizumab, capecitabine and radiotherapy for resectable locally-advanced rectal cancer.

    PubMed

    García, Margarita; Martinez-Villacampa, Mercedes; Santos, Cristina; Navarro, Valentin; Teule, Alex; Losa, Ferran; Pisa, Aleydis; Cambray, Maria; Soler, Gemma; Lema, Laura; Kreisler, Esther; Figueras, Agnes; Juan, Xavier San; Viñals, Francesc; Biondo, Sebastiano; Salazar, Ramon

    2015-02-26

    To evaluate whether the addition of bevacizumab (BVZ) to capecitabine-based chemoradiotherapy in the preoperative treatment of locally advanced rectal cancer (LARC) improves efficacy measured by the pathological complete response (pCR) rate. A phase II two-step design was performed. Patients received four cycles of therapy consisting of: BVZ 10 mg/kg in first infusion on day 1 and 5 mg/kg on days 15, 29, 43, capecitabine 1800 mg/m(2)/day 5 days per week during radiotherapy, which consisted of external-beam irradiation (45 Gy in 1.8 Gy dose per session over 5 sessions/week for 5 weeks). Six to eight weeks after completion of all therapies surgery was undergone. To profile the biological behaviour during BVZ treatment we measured molecular biomarkers before treatment, during BVZ monotherapy, and during and after combination therapy. Microvessel density (MVD) was measured after surgery. Forty-three patients were assessed and 41 were included in the study. Three patients achieved a pathological complete response (3/40: 7.5%) and 27 (67.5%) had a pathological partial response, (overall pathological response rate of 75%). A further 8 patients (20%) had stable disease, giving a disease control rate of 95%. Downstaging occurred in 31 (31/40: 77.5%) of the patients evaluated. This treatment resulted in an actuarial 4-year disease-free and overall survival of 85.4 and 92.7% respectively. BVZ with chemoradiotherapy showed acceptable toxicity. No correlations were observed between biomarker results and efficacy variables. BVZ with capecitabine and radiotherapy seem safe and active and produce promising survival results in LARC. ClinicalTrials.gov Identifier NCT00847119 . Trial registration date: February 18, 2009.

  3. Spontaneous rupture of the renal pelvis presenting as an urinoma in locally advanced rectal cancer

    PubMed Central

    Garg, Pankaj Kumar; Mohanty, Debajyoti; Rathi, Vinita; Jain, Bhupendra Kumar

    2014-01-01

    A 29-year-old gentleman underwent a transverse colostomy for intestinal obstruction caused by advanced rectal carcinoma. On the 5th postoperative day, the patient developed a painful swelling on the right side of the abdomen. The contrast enhanced computed tomography of the abdomen revealed a right sided hydronephrosis, a large rent in the renal pelvis, and a large retroperitoneal fluid collection on the right side. Percutaneous nephrostomy and pigtail catheter drainage of the urinoma led to resolution of abdominal swelling. Development of a urinoma as a consequence of rectal carcinoma is highly unusual. Prompt imaging for confirmation of diagnosis, decompression of the renal pelvicalyceal system, and drainage of the urinoma limits morbidity. PMID:24749123

  4. Clinical factors of post-chemoradiotherapy as valuable indicators for pathological complete response in locally advanced rectal cancer

    PubMed Central

    Peng, Jianhong; Lin, Junzhong; Qiu, Miaozhen; Wu, Xiaojun; Lu, Zhenhai; Chen, Gong; Li, Liren; Ding, Peirong; Gao, Yuanhong; Zeng, Zhifan; Zhang, Huizhong; Wan, Desen; Pan, Zhizhong

    2016-01-01

    OBJECTIVES: Pathological complete response has shown a better prognosis for patients with locally advanced rectal cancer after preoperative chemoradiotherapy. However, correlations between post-chemoradiotherapy clinical factors and pathologic complete response are not well confirmed. The aim of the current study was to identify post-chemoradiotherapy clinical factors that could serve as indicators of pathologic complete response in locally advanced rectal cancer. METHODS: This study retrospectively analyzed 544 consecutive patients with locally advanced rectal cancer treated at Sun Yat-sen University Cancer Center from December 2003 to June 2014. All patients received preoperative chemoradiotherapy followed by surgery. Univariate and multivariate regression analyses were performed to identify post-chemoradiotherapy clinical factors that are significant indicators of pathologic complete response. RESULTS: In this study, 126 of 544 patients (23.2%) achieved pathological complete response. In multivariate analyses, increased pathological complete response rate was significantly associated with the following factors: post-chemoradiotherapy clinical T stage 0-2 (odds ratio=2.098, 95% confidence interval=1.023-4.304, p=0.043), post-chemoradiotherapy clinical N stage 0 (odds ratio=2.011, 95% confidence interval=1.264-3.201, p=0.003), interval from completion of preoperative chemoradiotherapy to surgery of >7 weeks (odds ratio=1.795, 95% confidence interval=1.151-2.801, p=0.010) and post-chemoradiotherapy carcinoembryonic antigen ≤2 ng/ml (odds ratio=1.579, 95% confidence interval=1.026-2.432, p=0.038). CONCLUSIONS: Post-chemoradiotherapy clinical T stage 0-2, post-chemoradiotherapy clinical N stage 0, interval from completion of chemoradiotherapy to surgery of >7 weeks and post-chemoradiotherapy carcinoembryonic antigen ≤2 ng/ml were independent clinical indicators for pathological complete response. These findings demonstrate that post-chemoradiotherapy clinical

  5. Phase I Study of Neoadjuvant Radiotherapy With 5-Fluorouracil for Rectal Cancer

    ClinicalTrials.gov

    2017-09-14

    Mucinous Adenocarcinoma of the Rectum; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Rectum; Rectal Adenocarcinoma; Stage IIA Rectal Cancer; Stage IIB Rectal Cancer; Stage IIC Rectal Cancer; Stage IIIA Rectal Cancer; Stage IIIB Rectal Cancer; Stage IIIC Rectal Cancer

  6. XRCC2 as a predictive biomarker for radioresistance in locally advanced rectal cancer patients undergoing preoperative radiotherapy

    PubMed Central

    Qin, Chang-Jiang; Song, Xin-Ming; Chen, Zhi-Hui; Ren, Xue-Qun; Xu, Kai-Wu; Jing, Hong; He, Yu-Long

    2015-01-01

    XRCC2 has been shown to increase the radioresistance of some cancers. Here, XRCC2 expression was investigated as a predictor of preoperative radiotherapy (PRT) treatment response in locally advanced rectal cancer (LARC). XRCC2 was found to be overexpressed in rectal cancer tissues resected from patients who underwent surgery without PRT. In addition, overall survival for LARC patients was improved in XRCC2-negative patients compared with XRCC2-positive patients after treatment with PRT (P < 0.001). XRCC2 expression was also associated with an increase in LARC radioresistance. Conversely, XRCC2-deficient cancer cells were more sensitive to irradiation in vitro, and a higher proportion of these cells underwent cell death induced by G2/M phase arrest and apoptosis. When XRCC2 was knocked down, the repair of DNA double-strand breaks caused by irradiation was impaired. Therefore, XRCC2 may increases LARC radioresistance by repairing DNA double-strand breaks and preventing cancer cell apoptosis. Moreover, the present data suggest that XRCC2 is a useful predictive biomarker of PRT treatment response in LARC patients. Thus, inhibition of XRCC2 expression or activity represents a potential therapeutic strategy for improving PRT response in LARC patients. PMID:26320178

  7. Do all locally advanced rectal cancers require radiation? A review of literature in the modern era.

    PubMed

    Vonk, David T; Hazard, Lisa J

    2010-09-01

    Potentially curable rectal cancer is primarily treated with surgical resection. Adjuvant or neoadjuvant radiotherapy is often utilized for patients deemed to be at unacceptable risk for local recurrence. The purpose of this article is to review the pertinent literature and elucidate the role of radiotherapy in patients with an intermediate risk of local recurrence. The addition of chemoradiotherapy is recommended in the majority of patients with transmural or node positive rectal cancer. However, some patients with favorable characteristics may have only a small incremental benefit from the addition of radiotherapy. The decision to treat or not to treat should take into consideration the patient and physician tolerance of risk of recurrence and risk of treatment related toxicity. The primary factors identified for determining low risk patients are circumferential radial margin (CRM), location within the rectum, and nodal status. Patients at lowest risk have widely negative CRM (>2mm), proximal lesions (>10cm from the anal verge), and no nodal disease. Patients with all three low risk factors have an absolute reduction in local recurrence that is <5% and may be eligible to forego radiotherapy. Additional factors identified which may impact local recurrence risk are elevated serum CEA level, lymphovascular space invasion, pathologic grade, and extramural space invasion.

  8. The evaluation of the oxidative stress for patients receiving neoadjuvant chemoradiotherapy for locally advanced rectal cancer

    PubMed Central

    Serbanescu, GL; Gruia, MI; Bara, M; Anghel, RM

    2017-01-01

    Hypothesis: Nowadays, rectal cancer is an important healthcare challenge that affects many thousands of people each year worldwide, being diagnosed especially after the age of 50 years. Objective: This study attempted to evaluate the oxidative stress in patients with rectal cancer. Methods and results: 30 patients from the “Prof. Dr. Al. Trestioreanu” Institute of Oncology in Bucharest were treated with neoadjuvant radiochemotherapy during 2014 and 2016 and were included in the clinical study. Blood samples were obtained in dynamics during the treatment. From the blood samples, the serum was separated and used to identify the biochemical oxidative stress parameters. Results: Regarding the determination of lipid peroxides, albumin thiols, the cuprum oxidase activity of ceruloplasmin, the values registered in the dynamic of the treatment highlighted their increase to a maximum at the treatment’s endpoint due to an important oxidative stress. Regarding the serum values for total antioxidants, the results pointed out the activation of the natural protection systems, which in time were overwhelmed, due to the installed oxidative stress. Conclusion: Part of the cytotoxic effect of radiotherapy was due to the production of oxidative stress. The cell was constantly exposed to the cytotoxic action of the reactive oxygen species. The obtained results indicated the dual relation to which the tumoral cell exposed itself and the installed oxidative stress, respectively, the oxidative stress being a cause or a consequence of the malign transformation. Abbreviations: CT = computed tomography, MRI = magnetic resonance imaging, ESMO = European Society for Medical Oncology, ECOG = performance status scale PMID:28255388

  9. The evaluation of the oxidative stress for patients receiving neoadjuvant chemoradiotherapy for locally advanced rectal cancer.

    PubMed

    Serbanescu, G L; Gruia, M I; Bara, M; Anghel, R M

    2017-01-01

    Hypothesis: Nowadays, rectal cancer is an important healthcare challenge that affects many thousands of people each year worldwide, being diagnosed especially after the age of 50 years. Objective: This study attempted to evaluate the oxidative stress in patients with rectal cancer. Methods and results: 30 patients from the "Prof. Dr. Al. Trestioreanu" Institute of Oncology in Bucharest were treated with neoadjuvant radiochemotherapy during 2014 and 2016 and were included in the clinical study. Blood samples were obtained in dynamics during the treatment. From the blood samples, the serum was separated and used to identify the biochemical oxidative stress parameters. Results: Regarding the determination of lipid peroxides, albumin thiols, the cuprum oxidase activity of ceruloplasmin, the values registered in the dynamic of the treatment highlighted their increase to a maximum at the treatment's endpoint due to an important oxidative stress. Regarding the serum values for total antioxidants, the results pointed out the activation of the natural protection systems, which in time were overwhelmed, due to the installed oxidative stress. Conclusion: Part of the cytotoxic effect of radiotherapy was due to the production of oxidative stress. The cell was constantly exposed to the cytotoxic action of the reactive oxygen species. The obtained results indicated the dual relation to which the tumoral cell exposed itself and the installed oxidative stress, respectively, the oxidative stress being a cause or a consequence of the malign transformation. Abbreviations: CT = computed tomography, MRI = magnetic resonance imaging, ESMO = European Society for Medical Oncology, ECOG = performance status scale.

  10. Combined radiotherapy, 5-fluorouracil continuous infusion and weekly oxaliplatin in advanced rectal cancer: a phase I study.

    PubMed

    François, Eric; Ychou, Marc; Ducreux, Michel; Bertheault-Cvitkovic, Frédérique; Giovannini, Marc; Conroy, Thierry; Lemanski, Claire; Thomas, Olivier; Magnin, Valérie

    2005-12-01

    The aim of this study was to determine the maximum-tolerated dose (MTD) of weekly oxaliplatin combined with 5-fluorouracil (5FU) continuous infusion administered concomitantly with fractionated radiotherapy in patients presenting advanced rectal cancer. Forty-three patients with rectal cancer (stage T3/T4 (n = 24), metastatic (n = 17) and 2 with local recurrence), were included. The radiotherapy dose delivered was 45 Gy over 5 weeks (1.8 Gy/fraction/day, 5 days per week). The initial weekly oxaliplatin dosage was 30 mg/m2 and the 5FU dosage 150 mg/m2/d. The oxaliplatin and 5FU doses were escalated. Eight dose levels were tested. At dose level 8 (oxaliplatin 80 mg/m2, 5FU 225 mg/m2/d), 2 patients out of 4 presented dose-limiting toxicity (severe diarrhoea with dehydration and fatal shock, rectovesical fistula). At dose level 7, 2 further patients presented with grade 3 diarrhoea. The main toxicity of the combination was diarrhoea. The hematological and neurological toxicities were not severe and were not dose-limiting. Out of the 30 patients undergoing surgery, 4 (13.3%) presented with pathological complete response and 4 (13.3%) only presented with microscopic residual disease. The results from this study enabled determination of the recommended weekly oxaliplatin dose (60 mg/m2) combined with 5FU continuous infusion (225 mg/m2) and fractionated radiotherapy (45 Gy) in the pre-operative treatment of advanced rectal cancer. The good safety profile of the regimen, associated with promising results in terms of histological response, suggest that the regimen could be developed in future phase II/III studies.

  11. Prognostic and Predictive Value of Baseline and Posttreatment Molecular Marker Expression in Locally Advanced Rectal Cancer Treated With Neoadjuvant Chemoradiotherapy

    SciTech Connect

    Bertolini, Federica . E-mail: bertolini.federica@policlinico.mo.it; Bengala, Carmelo; Losi, Luisa; Pagano, Maria; Iachetta, Francesco; Dealis, Cristina; Jovic, Gordana; Depenni, Roberta; Zironi, Sandra; Falchi, Anna Maria; Luppi, Gabriele; Conte, Pier Franco

    2007-08-01

    Purpose: To evaluate expression of a panel of molecular markers, including p53, p21, MLH1, MSH2, MIB-1, thymidylate synthase, epidermal growth factor receptor (EGFR), and tissue vascular endothelial growth factor (VEGF), before and after treatment in patients treated with neoadjuvant chemoradiotherapy for locally advanced rectal cancer, to correlate the constitutive profile and dynamics of expression with pathologic response and outcome. Methods and Materials: Expression of biomarkers was evaluated by immunohistochemistry in tumor samples from 91 patients with clinical Stage II and III rectal cancer treated with preoperative pelvic radiotherapy (50 Gy) plus concurrent 5-fluorouracil by continuous intravenous infusion. Results: A pathologic complete remission was observed in 14 patients (15.4%). Patients with MLH1-positive tumors had a higher pathologic complete response rate (24.3% vs. 9.4%; p = 0.055). Low expression of constitutive p21, absence of EGFR expression after chemoradiotherapy, and high Dworak's tumor regression grade (TRG) were significantly associated with improved disease-free survival and overall survival. A high MIB-1 value after chemoradiotherapy was significantly associated with worse overall survival. Multivariate analysis confirmed the prognostic value of constitutive p21 expression as well as EGFR expression and MIB-1 value after chemoradiotherapy among patients not achieving TRG 3-4. Conclusions: In our study, we observed the independent prognostic value of EGFR expression after chemoradiotherapy on disease-free survival. Moreover, our study suggests that a constitutive high p21 expression and a high MIB-1 value after neoadjuvant chemoradiotherapy treatment could predict worse outcome in locally advanced rectal cancer.

  12. Transanal endoscopic microsurgery after neoadjuvant radiochemotherapy for locally advanced extraperitoneal rectal cancer: short-term morbidity and functional outcome.

    PubMed

    Coco, C; Rizzo, G; Mattana, C; Gambacorta, M A; Verbo, A; Barbaro, B; Vecchio, F M; Pafundi, D P; Mastromarino, M G; Valentini, V

    2013-08-01

    Transanal endoscopic microsurgery (TEM) after radiochemotherapy (RCT) has been reported in selected cases of locally advanced rectal cancer as an alternative to traditional radical resection with total mesorectal excision with a curative intent or as diagnostic tool to confirm a pathological complete response of the primary tumor. No study has evaluated functional outcome after TEM in preoperatively irradiated patients. This study was designed to evaluate short-term morbidity (according to Clavien's classifications) and establish (by a questionnaire) continence and evacuative function after RCT and TEM, at 1 year from surgery, analyzing the impact of RCT on postoperative outcomes. Patients with locally advanced rectal cancer treated by RCT and TEM (group 1) or with early T1 or adenomas treated only by TEM (group 2) entered this cohort comparative study. Twenty-two patients entered the study as group 1 and 25 as group 2. No postoperative mortality occurred. The morbidity rate was 36.4 % in group 1 vs. 16 % in group 2 (p = 0.114). The rate of suture dehiscence was 22.7 % in group 1 vs. 4 % in group 2 (p = 0.068). No grade III complications, reoperation, or hospital readmission within 30 days was recorded in either group. One year after surgery, continence and evacuative scores in group 1 were 1.05 ± 1.25 and 24.72 ± 2.79, respectively, which were similar to group 2 (p = 0.081 and 0.288, respectively). TEM after RCT in selected rectal cancer patients has an acceptable morbidity and functional results at 1 year from surgery. Preoperative irradiation could increase postoperative short-term morbidity, but it does not seem to influence evacuative or sphincter function after 1 year from surgery.

  13. Multidisciplinary management in rectal cancer.

    PubMed

    Hervás Morón, Asunción; García de Paredes, María Luisa; Lobo Martínez, Eduardo

    2010-12-01

    The treatment of rectal cancer has evolved over the last few decades from surgery alone to treatments with trimodal therapy for high-risk patients. The involvement of a multidisciplinary team of radiologists, pathologists, surgeons, radiotherapists and medical oncologists is now fundamental for decision-making and outcomes. The evolution of different diagnostic and therapeutic techniques has optimised the therapeutic rate. Future studies will determine the optimal regimen for inducing complete responses in locally advanced disease and whether the intensification of local treatments could enable the use of more conservative treatments, as for other tumour locations. The study of biomarkers will be essential in this respect.

  14. Impact of chemotherapy on eosinophilia-associated advanced rectal cancer: A case report and review of the literature

    PubMed Central

    Inoue, Maki; Kadono, Jun; Sugita, Hiroshi; Nakazono, Toshihiro; Motoi, Shunsuke; Kitazono, Iwao; Goto, Yuko; Fukukura, Yoshihiko; Yoshimitsu, Makoto; Misaka, Takaharu; Imoto, Yutaka

    2016-01-01

    The present study reports a case of eosinophilia-associated rectal cancer that was successfully stabilized using chemotherapy, and reviews the mechanisms of eosinophilia and the importance of chemotherapy. A 65-year-old man, who had previously been diagnosed with suspected rectal cancer, presented with the chief complaint of melena. Eosinophilia, abnormal blood coagulation, and elevated carcinoembryonic antigen and carbohydrate antigen 19–9 tumor marker levels were observed, and the patient was subsequently diagnosed with advanced rectal cancer accompanied by multiple lymph node metastases that extended from the para-aortic lymph nodes to the left axillary lymph nodes. The complication of deep vein thrombosis was also observed. Tumor hemorrhage was exacerbated, and thus, Hartmann's procedure was performed. Pathological findings included poorly- to moderately-differentiated adenocarcinoma; however, no eosinophil infiltration was observed within the tumor. Following surgery, the eosinophilia and lymph node metastasis were exacerbated, and an oxaliplatin plus capecitabine chemotherapy regimen was initiated. The patient's eosinophil count and tumor marker levels normalized, and the lymph nodes decreased in size; however, re-enlargement of the lymph nodes was observed 6 months after surgery. The patient was then administered a chemotherapeutic regimen of irinotecan/fluorouracil/folinic acid + bevacizumab, and stable disease was maintained until pleural and peritoneal dissemination were observed at 22 months post-surgery. Following a rapid deterioration in condition, the patient succumbed to the disease at 23 months post-surgery. The present case indicates that although eosinophilia-associated colon cancer exhibits a poor prognosis, early chemotherapeutic intervention may improve this. PMID:28105235

  15. Indication of pre-surgical radiochemotherapy enhances psychosocial morbidity among patients with resectable locally advanced rectal cancer.

    PubMed

    Bencova, V; Krajcovicova, I; Svec, J

    2016-01-01

    Patients with cancer experience stress-determined psychosocial comorbidities and behavioural alterations. Patients expectation to be cured by the first line surgery and their emotional status can be negatively influenced by the decision to include neoadjuvant long-course radiotherapy prior to surgical intervention. From the patient's perspective such treatment algorithmindicates incurability of the disease. The aim of this study was to analyse the extent and dynamics of stress and related psychosocial disturbances among patients with resectable rectal cancer to whom the neoadjuvant radiochemotherapy before surgery has been indicated.Three standardised assessment tools evaluating psychosocial morbidity of rectal cancer patients have been implemented: The EORTC QLQ C30-3, the EORTC QLQ CR29 module and the HADS questionnaires previously tested for internal consistency were answered by patients before and after long-course radiotherapy and after surgery and the scores of clinical and psychosocial values were evaluated by means of the EORTC and HADS manuals. The most profound psychosocial distress was experienced by patients after the decision to apply neoadjuvant radiotherapy and concomitant chemotherapy before surgical intervention. The involvement of pre-surgical radiotherapy into the treatment algorithm increased emotional disturbances (anxiety, feelings of hopelessness) and negatively influenced patient's treatment adherence and positive expectations from the healing process. The negative psychosocial consequences appeared to be more enhanced in female patients. Despite provided information about advances of neoadjuvant radiotherapy onto success of surgical intervention, the emotional and cognitive disorders improved only slightly. The results clearly indicate that addressed communication and targeted psychosocial support has to find place before pre-surgical radiochemotherapy and as a standard part through the trajectory of the entire multimodal rectal cancer

  16. Implications for determining the optimal treatment for locally advanced rectal cancer in elderly patients aged 75 years and older.

    PubMed

    Wan, Jue-feng; Zhu, Ji; Li, Gui-chao; Sun, Wen-jie; Zhang, Zhen

    2015-10-06

    Patients were excluded if they were older than 75 years of age in most clinical trials. Thus, the optimal treatment strategies in elderly patients with locally advanced rectal cancer (LARC) are still controversial. We designed our study to specifically evaluate the cancer specific survival of four subgroups of patients according to four different treatment modalities: surgery only, radiation (RT) only, neoadjuvant RT and adjuvant RT by analyzing the Surveillance, Epidemiology, and End Results (SEER)-registered database. The results showed that the 5-year cancer specific survival (CSS) was 52.1% in surgery only, 27.7% in RT only, 70.4% in neoadjuvant RT and 60.4% in adjuvant RT, which had significant difference in univariate log-rank test (P < 0.001) and multivariate Cox regression (P < 0.001). Thus, the neoadjuvant RT and surgery may be the optimal treatment pattern in elderly patients, especially for patients who are medically fit for the operation.

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

    SciTech Connect

    Jakobsen, Anders . E-mail: andjac@vgs.vejleamt.dk; Mortensen, John P.; Bisgaard, Claus; Lindebjerg, Jan; Hansen, Johnny W.; Rafaelsen, Soren R.

    2006-02-01

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

  18. Predicting response to neoadjuvant chemoradiation therapy in locally advanced rectal cancer: diffusion-weighted 3 Tesla MR imaging.

    PubMed

    Jung, Se Hee; Heo, Suk Hee; Kim, Jin Woong; Jeong, Yong Yeon; Shin, Sang Soo; Soung, Min-Gyu; Kim, Heong Rok; Kang, Heoung Keun

    2012-01-01

    To evaluate the efficacy of diffusion-weighted imaging (DWI) on 3 Tesla (T) MR imaging to predict the tumor response to neoadjuvant chemoradiation therapy (CRT) in patients with locally advanced rectal cancer. Thirty-five patients who underwent neoadjuvant CRT and subsequent surgical resection were included. Tumor volume was measured on T2-weighted MR images before and after neoadjuvant CRT and the percentage of tumor volume reduction was calculated. The apparent diffusion coefficient (ADC) value was measured on the DWI before and after neoadjuvant CRT, and the change of ADC (Δ ADC) was calculated. The histopathologic response was categorized either as a responder to CRT or as a nonresponder. The relationship between the ADC parameters and the percentage of tumor volume reduction or histopathologic response was then evaluated. There was a significant correlation between tumor volume reduction and pre-CRT ADC and Δ ADC, respectively (r = -0.352, r = 0.615). Pre-CRT ADC of the histopathologic responders was significantly lower than that of the histopathologic nonresponders (P = 0.034). Δ ADC of the histopathologic responders was significantly higher than that of the histopathologic nonresponders (P < 0.005). DWI on 3T MR imaging may be a promising technique for helping to predict and monitor the treatment response to neoadjuvant CRT in patients with locally advanced rectal cancer. Copyright © 2011 Wiley Periodicals, Inc.

  19. Selecting Patients With Locally Advanced Rectal Cancer for Neoadjuvant Treatment Strategies

    PubMed Central

    Dewdney, Alice; Cunningham, David

    2013-01-01

    Rectal cancer remains a significant problem worldwide. Outcomes vary significantly according to the stage of disease and prognostic factors, including the distance of the tumor from the circumferential resection margin. Accurate staging, including high-resolution magnetic resonance imaging, allows stratification of patients into low-, moderate-, and high-risk disease; this information can be used to inform multidisciplinary team decisions regarding the role of neoadjuvant therapy. Both neoadjuvant short-course radiotherapy and long-course chemoradiation reduce the risk of local recurrence compared with surgery alone, but they have little impact on survival. Although there remains a need to reduce overtreatment of those patients at moderate risk, evaluation of intensified regimens for those with high-risk disease is still required to reduce distant failure rates and improve survival in these patients with an otherwise poor prognosis. PMID:23821325

  20. Prospective phase II trial of nimotuzumab in combination with radiotherapy and concurrent capecitabine in locally advanced rectal cancer.

    PubMed

    Jin, Ting; Zhu, Yuan; Luo, Jia-Lin; Zhou, Ning; Li, De-Chuan; Ju, Hai-Xin; Fan, Yong-Tian; Liu, Yong; Zhu, Yu-Ping; Feng, Hai-Yang; Liu, Lu-Ying

    2015-03-01

    The aim of the study was to evaluate the safety and efficacy of adding concurrent nimotuzumab to preoperative radiotherapy with concurrent capecitabine in locally advanced rectal cancer. Patients with rectal cancer (clinical stage T3/4 or N+) were scheduled to receive weekly nimotuzumab (400 mg; days -6, 1, 8, 15, 22, and 29). Capecitabine (825 mg/m(2)) was delivered orally twice daily for the duration of radiotherapy. Radiotherapy was administered at 50.4 Gy (45 + 5.4 Gy). The main endpoint was the pathologic complete response (pCR) rate. Twenty-one patients with T3 or T4 disease were enrolled; 66.7 % were nodal-positive; the median distance from the anal verge was 5.5 cm. A pCR was achieved in four patients (19.0 %); 71.4 % patients obtained moderate or good tumor regression (Grade 2 and 3). Downstaging occurred in 15/21 (71.4 %) patients by T stage and 11/14 (78.6 %) by N stage. The actual dose intensities (median/mean, %) were nimotuzumab (100, 100) and capecitabine (100, 99.5). The most frequent Grade 1/2 toxicities were radiation dermatitis (57.1 %), nausea/vomiting (52.4 %), leukocytopenia (47.6 %), diarrhea (47.6 %), and proctitis (38.1 %). Grade 3 diarrhea was observed in 9.5 % of patients and Grade 3 leukocytopenia in 4.8 %. These preliminary results indicate that nimotuzumab can be safely combined with radiotherapy plus concurrent capecitabine. The efficacy of this regimen (pCR = 19.0 %) was significantly higher than that observed in previous phase II trials of preoperative radiotherapy with concurrent capecitabine and cetuximab in rectal cancer. Further investigation of concurrent nimotuzumab with radiotherapy plus capecitabine is warranted.

  1. Clinical Trial of Oral Nelfinavir Before and During Radiation Therapy for Advanced Rectal Cancer

    PubMed Central

    Hill, Esme J.; Roberts, Corran; Franklin, Jamie M.; Enescu, Monica; West, Nicholas; MacGregor, Thomas P.; Chu, Kwun-Ye; Boyle, Lucy; Blesing, Claire; Wang, Lai-Mun; Mukherjee, Somnath; Anderson, Ewan M.; Brown, Gina; Dutton, Susan; Love, Sharon B.; Schnabel, Julia A.; Quirke, Phil; Muschel, Ruth; McKenna, William G.; Partridge, Michael; Sharma, Ricky A.

    2016-01-01

    Purpose Nelfinavir, a PI3-kinase pathway inhibitor, is a radiosensitizer which increases tumor blood flow in preclinical models. We conducted an early-phase study to demonstrate the safety of nelfinavir combined with hypofractionated radiotherapy (RT) and to develop biomarkers of tumor perfusion and radiosensitization for this combinatorial approach. Patients and Methods Ten patients with T3-4 N0-2 M1 rectal cancer received 7 days of oral nelfinavir (1250 mg bd) and a further 7 days of nelfinavir during pelvic RT (25 Gy/5 fractions/7 days). Perfusion CT (p-CT) and DCE-MRI scans were performed pre-treatment, after 7 days of nelfinavir and prior to last fraction of RT. Biopsies taken pre-treatment and 7 days after the last fraction of RT were analysed for tumor cell density (TCD). Results There were 3 drug-related grade 3 adverse events: diarrhea, rash, lymphopenia. On DCE-MRI, there was a mean 42% increase in median Ktrans, and a corresponding median 30% increase in mean blood flow on p-CT during RT in combination with nelfinavir. Median TCD decreased from 24.3% at baseline to 9.2% in biopsies taken 7 days after RT (P=0.01). Overall, 5/9 evaluable patients exhibited good tumor regression on MRI assessed by Tumor Regression Grade (mrTRG). Conclusions This is the first study to evaluate nelfinavir in combination with RT without concurrent chemotherapy. It has shown that nelfinavir-RT is well tolerated and is associated with increased blood flow to rectal tumors. The efficacy of nelfinavir-RT versus RT alone merits clinical evaluation, including measurement of tumor blood flow. PMID:26861457

  2. Irradiation with protons for the individualized treatment of patients with locally advanced rectal cancer: a planning study with clinical implications.

    PubMed

    Wolff, Hendrik Andreas; Wagner, Daniela Melanie; Conradi, Lena-Christin; Hennies, Steffen; Ghadimi, Michael; Hess, Clemens Friedrich; Christiansen, Hans

    2012-01-01

    Ongoing clinical trials aim to improve local control and overall survival rates by intensification of therapy regimen for patients with locally advanced rectal cancer. It is well known that whenever treatment is intensified, risk of therapy-related toxicity rises. An irradiation with protons could possibly present an approach to solve this dilemma by lowering the exposure to the organs-at-risk (OAR) without compromising tumor response. Twenty five consecutive patients were treated from 04/2009 to 5/2010. For all patients, four different treatment plans including protons, RapidArc, IMRT and 3D-conformal-technique were retrospectively calculated and analyzed according to dosimetric aspects. Detailed DVH-analyses revealed that protons clearly reduced the dose to the OAR and entire normal tissue when compared to other techniques. Furthermore, the conformity index was significantly better and target volumes were covered consistent with the ICRU guidelines. Planning results suggest that treatment with protons can improve the therapeutic tolerance for the irradiation of rectal cancer, particularly for patients scheduled for an irradiation with an intensified chemotherapy regimen and identified to be at high risk for acute therapy-related toxicity. However, clinical experiences and long-term observation are needed to assess tumor response and related toxicity rates. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  3. Escalated radiation dose alone vs. concurrent chemoradiation for locally advanced and unresectable rectal cancers: results from phase II randomized study.

    PubMed

    Engineer, Reena; Mohandas, K M; Shukla, P J; Shrikhande, S V; Mahantshetty, U; Chopra, S; Goel, M; Mehta, S; Patil, P; Ramadwar, M; Deodhar, K; Arya, S; Shrivastava, Shyam Kishore

    2013-07-01

    This trial was undertaken to compare the rates of resectability between patients treated with neoadjuvant concurrent chemoradiation vs. boosted radiotherapy alone. Patients with clinically unresectable rectal cancer were randomized to receive external beam radiation therapy (EBRT) to pelvis (45 Gy) with concurrent oral Capecitabine (CRT group; Arm 1) or EBRT to pelvis (45 Gy) alone followed by 20 Gy dose of localized radiotherapy boost to the primary tumor site (RT with boost group, Arm 2). All patients were assessed for resectability after 6 weeks by clinical examination and by CT scan and those deemed resectable underwent surgery. A total of 90 patients were randomized, 46 to Arm 1 and 44 to Arm 2. Eighty seven patients (44 in Arm 1 and 41 in Arm 2) completed the prescribed treatment protocol. Overall resectability rate was low in both the groups; R0 resection was achieved in 20 (43 %) patients in Arm 1 vs. 15 (34 %) in Arm 2. Adverse factors that significantly affected the resectability rate in both the groups were extension of tumor to pelvic bones and signet ring cell pathology. Complete pathological response was seen in 7 and 11 %, respectively. There was greater morbidity such as wound infection and delayed wound healing in Arm 2 (16 vs. 40 %; p = 0.03). Escalated radiation dose without chemotherapy does not achieve higher complete (R0) tumor resectability in locally advanced inoperable rectal cancers, compared to concurrent chemoradiation.

  4. Clinical and Oncological Outcomes of Laparoscopic Lateral Pelvic Lymph Node Dissection in Advanced Lower Rectal Cancer: Single-institution Experience.

    PubMed

    Nonaka, Takashi; Fukuda, Akiko; Maekawa, Kyoichiro; Nagayoshi, Shigeki; Tokunaga, Takayuki; Takatsuki, Mitsutoshi; Kitajima, Tomoo; Taniguchi, Ken; Fujioka, Hikaru

    2017-09-01

    The aim of this study was to compare the clinical outcomes of laparoscopic versus open surgery for total mesorectal excision (TME) with lateral pelvic lymph node dissection (LPLD) in advanced lower rectal cancer. Forty-four patients who underwent TME with LPLD for lower rectal cancer (pStage II/III) between January 2008 and December 2014 were divided into two groups according to the type of surgical approach as follows: open LPLD group (OLD, n=17) and laparoscopic LPLD group (LLD, n=27). Operative time was comparable between the groups (p=0.15), whereas intraoperative blood loss and complication rates were significantly less in LLD than in OLD. Postoperative hospital stay was shorter in LLD than in OLD. Overall survival and local recurrence-free survival were similar in the two groups. Disease-free survival was better in LLD than in OLD, although the difference was not significant. Laparoscopic TME with LPLD is safe and feasible. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  5. Bevacizumab in the pre-operative treatment of locally advanced rectal cancer: A systematic review

    PubMed Central

    Fornaro, Lorenzo; Caparello, Chiara; Vivaldi, Caterina; Rotella, Virginia; Musettini, Gianna; Falcone, Alfredo; Baldini, Editta; Masi, Gianluca

    2014-01-01

    Despite advances in the management of patients with locally advanced, non-metastatic rectal adenocarcinoma (LARC), prognosis remains largely unsatisfactory due to a high rate of distant relapse. In fact, currently available neoadjuvant protocols, represented by fluoropyrimidine-based chemo-radiotherapy (CT-RT) or short-course RT, together with improved surgical techniques, have largely reduced the risk of local relapse, with limited impact on distant recurrence. Available results of phase III trials with additional cytotoxic agents combined with standard CT-RT are disappointing, as no significant reduction in the risk of recurrence has been demonstrated. In order to improve the control of micrometastatic disease, integrating targeted agents into neoadjuvant treatment protocols thus offers a rational approach. In particular, the antiangiogenic agent bevacizumab has demonstrated synergistic activity with both CT and RT in pre-clinical and clinical models, and thus may represent a suitable companion in the neoadjuvant treatment of LARC. Preliminary results of phase I-II clinical studies are promising and suggest potential clinical parameters and molecular predictive biomarkers useful for patient selection: treatment personalization is indeed the key in order to maximize the benefit while reducing the risk of more complex neoadjuvant treatment schedules. PMID:24876730

  6. [Sacral resection in surgical treatment of locally advanced primary and recurrent rectal and anal cancer: short-term outcomes].

    PubMed

    Tsarkov, P V; Efetov, S K; Sidorova, L V; Tulina, I A

    2017-01-01

    To assess safety of rectum removal with distal sacral resection. The short-term results of surgical treatment of primary and recurrent locally advanced rectal and anal cancer with sacral fixation have been analyzed. 32 patients underwent combined operations with sacral resection at the level of S2-S5. In 12 patients only one point of tumor fixation (F1) was revealed, 10 patients had two points of fixation (F2), three patients had three fixation points (F3) and in 7 cases the tumor was fixed to four points (F4) of fixation to different pelvic structures. Mean intraoperative blood loss and surgery time was 551±81 ml and 320±20 min in cases of sacral fixation only that was significantly lower compared with F2 cases - 1278±551 ml and 433±45 min, F3 cases - 2200±600 ml and 620±88 min, F4 cases - 2157±512.5 ml and 519±52,3 min, respectively (р<0.05). Complications requiring surgical intervention occurred in 9% patients (n=3). Among 23 patients with intact bladder and ureters urinary disorders occurred in 42% (n=10). Resection margin was negative along posterior surface of the specimen in all cases. Advanced surgery with distal sacral resection is advisable for radical removal of locally advanced and recurrent rectal and anal canal cancer fixed to the sacrum with negative resection margin. These operations are feasible in specialized centers and should be performed by specially trained oncological or colorectal surgeon.

  7. Novel radiation techniques for rectal cancer

    PubMed Central

    2014-01-01

    The concepts for management of rectal cancer have changed drastically over the past few years. Through national bowel cancer screening programmes in the Western countries and the increasing use of endoscopic procedures as diagnostic tool, there is increase in detection of rectal cancer in early stages. There is increase in ageing population worldwide but more so in Western countries. In addition, there is realisation of harm from extirpative surgical procedures which are directed towards managing advanced rectal cancer in the past. Increase in cost of health care burden has also led the investigators to seek alternative treatment options which are effective, safe and cost effective. There are several modern radiation techniques which fits this bill and we need to be aware of newer novel radiation techniques to fulfil this gap. PMID:24982769

  8. The impact of body mass index on rectal dose in locally advanced cervical cancer treated with high-dose-rate brachytherapy.

    PubMed

    Lim, Jihoon; Durbin-Johnson, Blythe; Valicenti, Richard; Mathai, Matthew; Stern, Robin L; Mayadev, Jyoti

    2013-01-01

    The impact of body mass index (BMI) on rectal dose in brachytherapy for cervical cancer is unknown. We assessed the association of BMI on rectal dose and lower gastrointestinal (GI) toxicity. Between 2007 and 2010, 51 patients with 97 brachytherapy planning images were reviewed. Volumetric measurements of the maximum percentage, mean percentage, dose to 2cc (D2cc), and dose to 1cc (D1cc) of the rectum, and the Internal Commission on Radiation Units and Measurement (ICRU) rectal point were recorded. Linear mixed effect models, analysis of variance, and regression analyses were used to determine the correlation between multiple observations or to detect a difference in the mean. The GI acute and late toxicity were prospectively recorded and retrospectively analyzed. The average BMI (kg/m(2)) was 27.7 with a range of 17.4-46.6. Among the patients, 8% were morbidly obese, 25% obese, 25% overweight, 40% normal weight, and 2% underweight. The mean D1cc, D2cc, mean rectal dose (%), maximum rectal dose (%), and ICRU rectum was 3.03 Gy, 2.78 Gy, 20%, 60%, and 2.99 Gy, respectively. On multivariate analysis, there was a significant decrease in the D1cc and D2cc rectal dose (p=0.016), ICRU rectal point dose (p=0.022), and mean rectal dose percentage (p=0.021) with an increase in BMI. There was, however, no statistically significant relationship between BMI and GI toxicity. Obesity decreases the rectal dose given in high-dose-rate brachytherapy for locally advanced cervical cancer because of an increase in fatty tissue in the recto-uterine space. There is no significant correlation between BMI and acute or late GI toxicity. Published by Elsevier Inc.

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

    PubMed Central

    Hadaki, Maher; Harrison, Mark

    2013-01-01

    Radiotherapy has a longstanding and well-defined role in the treatment of resectable rectal cancer to reduce the historically high risk of local recurrence. In more advanced borderline or unresectable cases, where the circumferential resection margin (CRM) is breached or threatened according to magnetic resonance imaging (MRI), despite optimized local multimodality treatment and the gains achieved by modern high quality total mesorectal excision (TME), at least half the patients fail to achieve sufficient downstaging with current schedules. Many do not achieve an R0 resection. In less locally advanced cases, even if local control is achieved, this confers only a small impact on distant metastases and a significant proportion of patients (30-40%) still subsequently develop metastatic disease. In fact, distant metastases have now become the predominant cause of failure in rectal cancer. Therefore, increasing the intensity and efficacy of chemotherapy and chemoradiotherapy by integrating additional cytotoxics and biologically targetted agents seems an appealing strategy to explore—with the aim of enhancing curative resection rates and improving distant control and survival. However, to date, we lack validated biomarkers for these biological agents apart from wild-type KRAS. For cetuximab, the appearance of an acneiform rash is associated with response, but low levels of magnesium appear more controversial. There are no molecular biomarkers for bevacizumab. Although some less invasive clinical markers have been proposed for bevacizumab, such as circulating endothelial cells (CECS), circulating levels of VEGF and the development of overt hypertension, these biomarkers have not been validated and are observed to emerge only after a trial of the agent. We also lack a simple method of ongoing monitoring of ‘on target’ effects of these biological agents, which could determine and pre-empt the development of resistance, prior to radiological and clinical assessessments

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

    PubMed

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

    2013-09-01

    Radiotherapy has a longstanding and well-defined role in the treatment of resectable rectal cancer to reduce the historically high risk of local recurrence. In more advanced borderline or unresectable cases, where the circumferential resection margin (CRM) is breached or threatened according to magnetic resonance imaging (MRI), despite optimized local multimodality treatment and the gains achieved by modern high quality total mesorectal excision (TME), at least half the patients fail to achieve sufficient downstaging with current schedules. Many do not achieve an R0 resection. In less locally advanced cases, even if local control is achieved, this confers only a small impact on distant metastases and a significant proportion of patients (30-40%) still subsequently develop metastatic disease. In fact, distant metastases have now become the predominant cause of failure in rectal cancer. Therefore, increasing the intensity and efficacy of chemotherapy and chemoradiotherapy by integrating additional cytotoxics and biologically targetted agents seems an appealing strategy to explore-with the aim of enhancing curative resection rates and improving distant control and survival. However, to date, we lack validated biomarkers for these biological agents apart from wild-type KRAS. For cetuximab, the appearance of an acneiform rash is associated with response, but low levels of magnesium appear more controversial. There are no molecular biomarkers for bevacizumab. Although some less invasive clinical markers have been proposed for bevacizumab, such as circulating endothelial cells (CECS), circulating levels of VEGF and the development of overt hypertension, these biomarkers have not been validated and are observed to emerge only after a trial of the agent. We also lack a simple method of ongoing monitoring of 'on target' effects of these biological agents, which could determine and pre-empt the development of resistance, prior to radiological and clinical assessessments or

  11. 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

  12. 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.

  13. Preoperative Chemoradiotherapy with Capecitabine and Oxaliplatin in Locally Advanced Rectal Cancer. A Phase I–II Multicenter Study of the Dutch Colorectal Cancer Group

    PubMed Central

    Punt, Cornelis J. A.; Tesselaar, Margot E.; Cats, Annemieke; Havenga, Klaas; Leer, Jan W. H.; Marijnen, Corrie A.; Jansen, Edwin P.; Van Krieken, Han H. J. M.; Wiggers, Theo; Van de Velde, Cornelis J. H.; Mulder, Nanno H.

    2007-01-01

    Background We studied the maximum tolerated dose (MTD) and efficacy of oxaliplatin added to capecitabine and radiotherapy (Capox-RT) as neoadjuvant therapy for rectal cancer. Methods T3-4 rectal cancer patients received escalating doses of oxaliplatin (day 1 and 29) with a fixed dose of capecitabine of 1000 mg/m2 twice daily (days 1–14, 25–38) added to RT with 50.4 Gy and surgery after 6–8 weeks. The MTD, determined during phase I, was used in the subsequent phase II, in which R0 resection rate (a negative circumferential resection margin) was the primary end point. Results Twenty-one patients were evaluable. In the phase I part, oxaliplatin at 85 mg/m2 was established as MTD. In phase II, the main toxicity was grade III diarrhea (18%). All patients underwent surgery, and 20 patients had a resectable tumor. An R0 was achieved in 17/21 patients, downstaging to T0-2 in 7/21 and a pCR in 2/21. Conclusion Combination of Capox-RT has an acceptable acute toxicity profile and a high R0 resection rate of 81% in locally advanced rectal cancer. However the pCR rate was low. PMID:17653805

  14. Laparoscopic versus robotic rectal resection for rectal cancer in a veteran population.

    PubMed

    Fernandez, Ramiro; Anaya, Daniel A; Li, Linda T; Orcutt, Sonia T; Balentine, Courtney J; Awad, Samir A; Berger, David H; Albo, Daniel A; Artinyan, Avo

    2013-10-01

    Robotic rectal cancer resection remains controversial. We compared the safety and efficacy of laparoscopic vs robotic rectal cancer resection in a high-risk Veterans Health Administration population. Patients who underwent minimally invasive rectal cancer resection were identified from an institutional colorectal cancer database. Baseline characteristics and outcomes were compared between robotic and laparoscopic groups. The robotic group (n = 13) did not differ significantly from the laparoscopic group (n = 59) with respect to baseline characteristics except for a higher rate of previous abdominal surgery. Robotic patients had significantly lower tumors, more advanced disease, a higher rate of preoperative chemoradiation, and were more likely to undergo abdominoperineal resection. Robotic rectal resection was associated with longer operative time. There were no differences in blood loss, conversion rates, postoperative morbidity, lymph nodes harvested, margin positivity, or specimen quality between groups. The robotic approach for rectal cancer resection is safe with similar postoperative and oncologic outcomes compared with laparoscopy. Published by Elsevier Inc.

  15. The Value of Restaging With Chest and Abdominal CT/MRI Scan After Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer.

    PubMed

    Liu, Guo-Chen; Zhang, Xu; Xie, E; An, Xin; Cai, Pei-Qiang; Zhu, Ying; Tang, Jing-Hua; Kong, Ling-Heng; Lin, Jun-Zhong; Pan, Zhi-Zhong; Ding, Pei-Rong

    2015-11-01

    Little was known with regard to the value of preoperative systemic restaging for patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (CRT). This study was designed to evaluate the role of chest and abdominal computed tomography (CT) scan or magnetic resonance imaging (MRI) on preoperative restaging in LARC after neoadjuvant CRT and to assess the impact on treatment strategy.Between January 2007 and April 2013, 386 newly diagnosed consecutive patients with LARC who underwent neoadjuvant CRT and received restaging with chest and abdominal CT/MRI scan were included. Imaging results before and after CRT were analyzed.Twelve patients (3.1%) (6 liver lesions, 2 peritoneal lesions, 2 distant lymph node lesions, 1 lung lesions, 1 liver and lung lesions) were diagnosed as suspicious metastases on the restaging scan after radiotherapy. Seven patients (1.8%) were confirmed as metastases by pathology or long-term follow-up. The treatment strategy was changed in 5 of the 12 patients as a result of restaging CT/MRI findings. Another 10 patients (2.6%) who present with normal restaging imaging findings were diagnosed as metastases intra-operatively. The sensitivity, specificity accuracy, negative predictive value, and positive predictive values of restaging CT/MRI was 41.4%, 98.6%, 58.3%, and 97.3%, respectively.The low incidence of metastases and minimal consequences for the treatment plan question the clinical value of routine restaging of chest and abdomen after neoadjuvant CRT. Based on this study, a routine restaging CT/MRI of chest and abdomen in patients with rectal cancer after neoadjuvant CRT is not advocated, carcino-embryonic antigen (CEA) -guided CT/MRI restaging might be an alternative.

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

    SciTech Connect

    Kim, Sun Young; Hong, Yong Sang; Kim, Dae Yong; Kim, Tae Won; Kim, Jee Hyun; Im, Seok Ah; Lee, Keun Seok; Yun, Tak; Jeong, Seung-Yong; Choi, Hyo Seong; Lim, Seok-Byung; Chang, Hee Jin; Jung, Kyung Hae

    2011-11-01

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

  17. Prognostic Role of Neutrophil-to-Lymphocyte Ratio in Locally Advanced Rectal Cancer Treated with Neoadjuvant Chemoradiotherapy

    PubMed Central

    Shen, Jinwen; Zhu, Yuan; Wu, Wei; Zhang, Lingnan; Ju, Haixing; Fan, Yongtian; Zhu, Yuping; Luo, Jialin; Liu, Peng; Zhou, Ning; Lu, Ke; Zhang, Na; Li, Dechuan; Liu, Luying

    2017-01-01

    Background Increasing evidence suggests that cancer-associated inflammation is associated with poorer outcomes. The neutrophil-to-lymphocyte ratio (NLR), considered as a systemic inflammation marker, is thought to predict prognoses in colorectal cancer. In this study, we explored the association between the NLR and prognoses following neoadjuvant chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC). Material/Methods From February 2002 to December 2012, a group of 202 patients diagnosed with LARC and receiving neoadjuvant CRT followed by radical surgery was included in our retrospective study. The associations between the pre-CRT NLR and clinicopathological characteristics, as well as the predictive value of pre-CRT NLR against survival outcomes, were analyzed. Results The average NLR was 2.7±1.5 (median 2.4, range 0.6–12.8). There were 63 (31.2%) patients with NLR ≥3.0, and 139 (68.8%) patients with NLR <3.0. Correlation analyses showed that no clinicopathological characteristics except age were associated with NLR. We did not find an association between NLR and survival outcomes. In multivariate Cox model analyses, the R1/R2 resection, lymph node ratio ≥0.1, and perineural/lymphovascular invasion were independently associated with worse disease-free survival and overall survival. Conclusions In our cohort, the NLR did not correlate with survival outcomes in LARC patients undergoing neoadjuvant CRT. The prognostic value of NLR should be validated in large-scale prospective studies. PMID:28100902

  18. Down-staging following neoadjuvant chemo-radiotherapy for locally advanced rectal cancer: Does timing of surgery really matter?

    PubMed Central

    Sirohi, Bhawna; Barreto, Savio George; Patkar, Shraddha; Gupta, Alok; DeSouza, Ashwin; Talole, Sanjay; Deodhar, Kedar; Shetty, Nitin; Engineer, Reena; Goel, Mahesh; Shrikhande, Shailesh V.

    2014-01-01

    Background: Neoadjuvant chemoradiotherapy (NACTRT) improves local recurrence rate in locally advanced (LA) rectal cancer with no survival benefit. Pathological complete response (pCR) post-NACTRT is associated with improved outcome. Debate is ongoing as to when would be the opportune time to operate. Aim: To determine if greater down-staging can be achieved by a longer time interval from NACTRT to surgery (tumor regression score [TRS]) and whether this would impact sphincter saving surgery rates and early relapse rates. Materials and Methods: A retrospective analysis of a prospectively maintained database of patients with LA rectal adenocarcinoma treated from January 2012 to August 2013 was carried out. One hundred and ten patients who completed NACTRT (50 Gy/25 fractions with capecitabine 825 mg/m2 twice daily) followed by surgical resection were included. For response evaluation patients were divided into two groups, Group 1 (TRS ≤60 days, n = 42) and 2 (TRS >60 days, n = 68). Tumor down-staging, pCR rate, tumor regression grade (TRG) post-NACTRT and relapse rates were correlated with TRS. Results: Of 110 patients (median age: 49 years (21-73), 71% males; 18 (16.5%) with signet ring histology) 96% patients underwent an R0 resection. Post-NACTRT, CR was attained in 5 (4.5%), partial response in 98 (89%) and stable disease in 7 (6.4%) patients. Median time from completion of NACTRT to surgery was 64.5 days (6-474). Median lymph nodes harvested were 10 (1-50). Overall, 22 (20%) patients achieved pCR. 26 (62%) patients in Group 1 compared to 36 (53%) in Group 2 underwent sphincter sparing surgery (SSS) (P = 0.357). Six patients (14%) in Group 1 and 16 (24%) in Group 2 achieved pCR (P = 0.24). Median TRG in both groups was three. Conclusion: Timing of surgery following NACTRT for LA rectal cancer does not influence pathological response, ability to perform SSS or disease-free survival. There is no incremental benefit of delaying the surgery though this needs to be

  19. ACR Appropriateness Criteria on Resectable Rectal Cancer

    SciTech Connect

    Suh, W. Warren; Konski, Andre A.; Mohiuddin, Mohammed; Poggi, Matthew M.; Regine, William F.; Cosman, Bard C.; Saltz, Leonard; Johnstone, Peter A.S.

    2008-04-01

    The American College of Radiology (ACR) Appropriateness Criteria on Resectable Rectal Cancer was updated by the Expert Panel on Radiation Oncology-Rectal/Anal Cancer, based on a literature review completed in 2007.

  20. Prevalence and clinical significance of acellular mucin in locally advanced rectal cancer patients showing pathologic complete response to preoperative chemoradiotherapy.

    PubMed

    Lim, Seok-Byung; Hong, Seung-Mo; Yu, Chang Sik; Hong, Yong Sang; Kim, Tae Won; Park, Jin-hong; Kim, Jong Hoon; Kim, Jin Cheon

    2013-01-01

    Occasionally, patients with locally advanced rectal adenocarcinoma who receive preoperative chemoradiotherapy (CRT) show acellular mucin in resection specimens that had shown pathologic complete response (pCR), but the clinical and prognostic significance of this finding has been controversial. This study analyzed data from 217 consecutive patients showing pCR to preoperative CRT followed by resection to evaluate the clinicopathologic features and prognostic significance of acellular mucin. Patients were categorized according to the presence of acellular mucin, as identified by pathologic analysis. The clinicopathologic findings and oncologic results were compared. Acellular mucins were identified in 35 (16.1%) of 217 pCR patients. Acellular mucins were found predominantly in male patients (20.8% vs. 9.8%, P=0.039) and in those with mucinous/signet ring cell differentiation (66.7% vs. 15.1%, P=0.008). The presence of acellular mucin was more frequent in patients with a shorter (<42 d) CRT-operation interval (22.6% vs. 10.3%, P=0.017). With a mean follow-up of 41 months (range, 2 to 119 mo), the 3-year overall survival (96.8% with mucin vs. 95.9% without mucin, P=0.314) and the 3-year disease-free survival (97.0% with mucin vs. 93.0% without mucin, P=0.131) did not differ between the groups. The presence of acellular mucin in rectal cancer patients showing pCR to preoperative CRT is associated with male sex and mucinous differentiation and does not have a significant impact on oncologic outcomes. Acellular mucins are also associated with the CRT-operation interval as a phenomenon of time-dependent response to CRT.

  1. The impact of metabolic syndrome on outcome and response to neoadjuvant chemoradiation in locally advanced rectal cancer patients.

    PubMed

    Anderson, Brandon J; Wahlquist, Amy E; Hill, Elizabeth G; Marshall, David T; Kimchi, Eric T; Staveley O'Carroll, Kevin F; Camp, E Ramsay

    2016-09-01

    Metabolic syndrome (MetS) is a constellation of cardiovascular risk factors shown to increase the risk of developing various malignancies, as well as diminish tumor response to conventional therapies. The effects of MetS and its individual components on therapeutic response and treatment-related outcomes were examined in patients with locally advanced rectal cancer (LARC). Data was retrospectively collected on LARC patients treated with neoadjuvant chemoradiation (nCRT) and surgery. Medical records were reviewed for patient characteristics, staging, treatment plan, and outcomes. One hundred two patients were included in the study. Patients with HTN had a significantly decreased nCRT response and were four times more likely to experience a poor response to treatment compared to patients without HTN. Additionally, HTN was found to significantly increase the rate of surgical complications. Neither DM nor obesity exhibited any significant effect on therapeutic response or complication rates, either individually or in combination with another risk factor. This study demonstrates the importance of considering underlying MetS risk factors, especially HTN, when predicting tumor response in LARC patients undergoing nCRT followed by radical surgery. The results provide support for an increased focus on pre-treatment risk factor control to optimize cancer therapy outcomes. Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

  2. Oncologic and Functional Hazards of Obesity Among Patients With Locally Advanced Rectal Cancer Following Neoadjuvant Chemoradiation Therapy.

    PubMed

    Park, In J; You, Y Nancy; Skibber, John M; Rodriguez-Bigas, Miguel A; Das, Prajnan; Eng, Cathy; Kopetz, Scott; Wolff, Robert A; Crane, Christopher H; Krishnan, Sunil; Minsky, Bruce; Hu, Chung-Yuan; Nguyen, Sa; Chang, George J

    2017-06-01

    Obesity is a major health concern and risk factor for colorectal cancer that may also impact cancer treatment and outcomes. Rectal cancer response to chemoradiotherapy (CXRT) is associated with long-term survival and sphincter preservation. The purpose of this study was to evaluate the impact of obesity on treatment outcomes after neoadjuvant CXRT for rectal cancer. A retrospective cohort study of patients diagnosed (1993 to 2010) with cT3-4 or cN+ (by endorectal ultrasound, computed tomography, or magnetic resonance imaging) rectal carcinoma and treated with CXRT and total mesorectal excision was performed. Patients were classified as obese (body mass index ≥30 kg/m) or nonobese (body mass index <30 kg/m), and by response to CXRT: complete (pCR) or incomplete (pIR). Associations between obesity, tumor response, and sphincter preservation were evaluated using multivariate logistic regression analysis and survival outcomes by Cox regression. A total of 753 patients met criteria and 28.7% (n=216) patients were obese. Obese and nonobese groups did not differ in age, sex, tumor location, grade, or number of examined lymph nodes. However, obesity was associated with a lower rate of pCR (ORmulti=0.60; 95% confidence interval, 0.38-0.94; P=0.04) and among mid to low rectal cancer patients, a lower rate of sphincter preservation (ORmulti=0.67; 95% confidence interval, 0.45-0.99). Among both obese and nonobese patients, CR was associated with more favorable recurrence-free survival than pIR. Considering the increasing obesity prevalence and its association with CXRT response, oncologic outcomes, and sphincter preservation, further study is needed regarding the impact of obesity on neoadjuvant treatment response. Moreover, obesity should be targeted as a modifiable risk factor for adverse outcomes following multimodality treatment for rectal cancer.

  3. Automatic segmentation software in locally advanced rectal cancer: READY (REsearch program in Auto Delineation sYstem)-RECTAL 02: prospective study.

    PubMed

    Gambacorta, Maria A; Boldrini, Luca; Valentini, Chiara; Dinapoli, Nicola; Mattiucci, Gian C; Chiloiro, Giuditta; Pasini, Danilo; Manfrida, Stefania; Caria, Nicola; Minsky, Bruce D; Valentini, Vincenzo

    2016-07-05

    To validate autocontouring software (AS) in a clinical practice including a two steps delineation quality assurance (QA) procedure.The existing delineation agreement among experts for rectal cancer and the overlap and time criteria that have to be verified to allow the use of AS were defined.Median Dice Similarity Coefficient (MDSC), Mean slicewise Hausdorff Distances (MSHD) and Total-Time saving (TT) were analyzed.Two expert Radiation Oncologists reviewed CT-scans of 44 patients and agreed the reference-CTV: the first 14 consecutive cases were used to populate the software Atlas and 30 were used as Test.Each expert performed a manual (group A) and an automatic delineation (group B) of 15 Test patients.The delineations were compared with the reference contours.The overlap between the manual and automatic delineations with MDSC and MSHD and the TT were analyzed.Three acceptance criteria were set: MDSC ≥ 0.75, MSHD ≤1mm and TT sparing ≥ 50%.At least 2 criteria had to be met, one of which had to be TT saving, to validate the system.The MDSC was 0.75, MSHD 2.00 mm and the TT saving 55.5% between group A and group B. MDSC among experts was 0.84.Autosegmentation systems in rectal cancer partially met acceptability criteria with the present version.

  4. Automatic segmentation software in locally advanced rectal cancer: READY (REsearch program in Auto Delineation sYstem)-RECTAL 02: prospective study

    PubMed Central

    Dinapoli, Nicola; Mattiucci, Gian C.; Chiloiro, Giuditta; Pasini, Danilo; Manfrida, Stefania; Caria, Nicola; Minsky, Bruce D.

    2016-01-01

    To validate autocontouring software (AS) in a clinical practice including a two steps delineation quality assurance (QA) procedure. The existing delineation agreement among experts for rectal cancer and the overlap and time criteria that have to be verified to allow the use of AS were defined. Median Dice Similarity Coefficient (MDSC), Mean slicewise Hausdorff Distances (MSHD) and Total-Time saving (TT) were analyzed. Two expert Radiation Oncologists reviewed CT-scans of 44 patients and agreed the reference-CTV: the first 14 consecutive cases were used to populate the software Atlas and 30 were used as Test. Each expert performed a manual (group A) and an automatic delineation (group B) of 15 Test patients. The delineations were compared with the reference contours. The overlap between the manual and automatic delineations with MDSC and MSHD and the TT were analyzed. Three acceptance criteria were set: MDSC ≥ 0.75, MSHD ≤1mm and TT sparing ≥ 50%. At least 2 criteria had to be met, one of which had to be TT saving, to validate the system. The MDSC was 0.75, MSHD 2.00 mm and the TT saving 55.5% between group A and group B. MDSC among experts was 0.84. Autosegmentation systems in rectal cancer partially met acceptability criteria with the present version. PMID:27302924

  5. MRI in local staging of rectal cancer: an update

    PubMed Central

    Tapan, Ümit; Özbayrak, Mustafa; Tatlı, Servet

    2014-01-01

    Preoperative imaging for staging of rectal cancer has become an important aspect of current approach to rectal cancer management, because it helps to select suitable patients for neoadjuvant chemoradiotherapy and determine the appropriate surgical technique. Imaging modalities such as endoscopic ultrasonography, computed tomography, and magnetic resonance imaging (MRI) play an important role in assessing the depth of tumor penetration, lymph node involvement, mesorectal fascia and anal sphincter invasion, and presence of distant metastatic diseases. Currently, there is no consensus on a preferred imaging technique for preoperative staging of rectal cancer. However, high-resolution phased-array MRI is recommended as a standard imaging modality for preoperative local staging of rectal cancer, with excellent soft tissue contrast, multiplanar capability, and absence of ionizing radiation. This review will mainly focus on the role of MRI in preoperative local staging of rectal cancer and discuss recent advancements in MRI technique such as diffusion-weighted imaging and dynamic contrast-enhanced MRI. PMID:25010367

  6. Circulating serum microRNA-345 correlates with unfavorable pathological response to preoperative chemoradiotherapy in locally advanced rectal cancer

    PubMed Central

    Yu, Jing; Li, Ning; Wang, Xin; Ren, Hua; Wang, Weihu; Wang, Shulian; Song, Yongwen; Liu, Yueping; Li, Yexiong; Zhou, Xuantong; Luo, Aiping; Liu, Zhihua; Jin, Jing

    2016-01-01

    Preoperative chemoradiotherapy (pre-CRT) has been represented as the standard treatment for locally advanced rectal cancer (LARC), but large variations of tumor radiation response to CRT have been reported in the clinic. To explore the function of microRNAs as potential therapeutic predictors of pre-CRT pathological response in LARC, we analyzed global miRNA expression in CRT-sensitive and CRT-resistant groups before treatment. MiR-345 was significantly elevated in the CRT-resistant group. Therefore, miR-345 was selected as a candidate for further analysis. We assessed the correlation between the miRNA signatures and the chemoradiotherapeutic response in 20 randomly selected LARC tissue samples (Validation set) and 87 serum samples (Training set) by qRT-PCR. Further, we validated the results in 42 randomly selected LARC serum samples (Validation set). High miR-345 expression was significantly correlated with unfavorable pre-CRT pathological response in tissue and serum. Moreover, low miR-345 levels predicted superior 3-year local recurrence free survival (LRFS). Taken together, circulating serum miR-345 correlates with unfavorable pre-CRT response and poor locoregional control in LARC. It might be a promising biomarker to facilitate patient stratification for personalized treatment. PMID:27572313

  7. MicroRNA-31 Emerges as a Predictive Biomarker of Pathological Response and Outcome in Locally Advanced Rectal Cancer.

    PubMed

    Caramés, Cristina; Cristobal, Ion; Moreno, Víctor; Marín, Juan P; González-Alonso, Paula; Torrejón, Blanca; Minguez, Pablo; Leon, Ana; Martín, José I; Hernández, Roberto; Pedregal, Manuel; Martín, María J; Cortés, Delia; García-Olmo, Damian; Fernández, María J; Rojo, Federico; García-Foncillas, Jesús

    2016-06-03

    Neoadjuvant chemoradiotherapy (CRT) followed by total mesorectal excision has emerged as the standard treatment for locally advanced rectal cancer (LARC) patients. However, many cases do not respond to neoadjuvant CRT, suffering unnecessary toxicities and surgery delays. Thus, identification of predictive biomarkers for neoadjuvant CRT is a current clinical need. In the present study, microRNA-31 expression was measured in formalin-fixed paraffin-embedded (FFPE) biopsies from 78 patients diagnosed with LARC who were treated with neoadjuvant CRT. Then, the obtained results were correlated with clinical and pathological characteristics and outcome. High microRNA-31 (miR-31) levels were found overexpressed in 34.2% of cases. Its overexpression significantly predicted poor pathological response (p = 0.018) and worse overall survival (OS) (p = 0.008). The odds ratio for no pathological response among patients with miR-31 overexpression was 0.18 (Confidence Interval = 0.06 to 0.57; p = 0.003). Multivariate analysis corroborated the clinical impact of miR-31 in determining pathological response to neoadjuvant CRT as well as OS. Altogether, miR-31 quantification emerges as a novel valuable clinical tool to predict both pathological response and outcome in LARC patients.

  8. MicroRNA-31 Emerges as a Predictive Biomarker of Pathological Response and Outcome in Locally Advanced Rectal Cancer

    PubMed Central

    Caramés, Cristina; Cristobal, Ion; Moreno, Víctor; Marín, Juan P.; González-Alonso, Paula; Torrejón, Blanca; Minguez, Pablo; Leon, Ana; Martín, José I.; Hernández, Roberto; Pedregal, Manuel; Martín, María J.; Cortés, Delia; García-Olmo, Damian; Fernández, María J.; Rojo, Federico; García-Foncillas, Jesús

    2016-01-01

    Neoadjuvant chemoradiotherapy (CRT) followed by total mesorectal excision has emerged as the standard treatment for locally advanced rectal cancer (LARC) patients. However, many cases do not respond to neoadjuvant CRT, suffering unnecessary toxicities and surgery delays. Thus, identification of predictive biomarkers for neoadjuvant CRT is a current clinical need. In the present study, microRNA-31 expression was measured in formalin-fixed paraffin-embedded (FFPE) biopsies from 78 patients diagnosed with LARC who were treated with neoadjuvant CRT. Then, the obtained results were correlated with clinical and pathological characteristics and outcome. High microRNA-31 (miR-31) levels were found overexpressed in 34.2% of cases. Its overexpression significantly predicted poor pathological response (p = 0.018) and worse overall survival (OS) (p = 0.008). The odds ratio for no pathological response among patients with miR-31 overexpression was 0.18 (Confidence Interval = 0.06 to 0.57; p = 0.003). Multivariate analysis corroborated the clinical impact of miR-31 in determining pathological response to neoadjuvant CRT as well as OS. Altogether, miR-31 quantification emerges as a novel valuable clinical tool to predict both pathological response and outcome in LARC patients. PMID:27271609

  9. Long-Term Results of a Randomized Trial in Locally Advanced Rectal Cancer: No Benefit From Adding a Brachytherapy Boost

    SciTech Connect

    Appelt, Ane L.; Vogelius, Ivan R.; Pløen, John; Rafaelsen, Søren R.; Lindebjerg, Jan; Havelund, Birgitte M.; Bentzen, Søren M.; Jakobsen, Anders

    2014-09-01

    Purpose/Objective(s): Mature data on tumor control and survival are presented from a randomized trial of the addition of a brachytherapy boost to long-course neoadjuvant chemoradiation therapy (CRT) for locally advanced rectal cancer. Methods and Materials: Between March 2005 and November 2008, 248 patients with T3-4N0-2M0 rectal cancer were prospectively randomized to either long-course preoperative CRT (50.4 Gy in 28 fractions, per oral tegafur-uracil and L-leucovorin) alone or the same CRT schedule plus a brachytherapy boost (10 Gy in 2 fractions). The primary trial endpoint was pathologic complete response (pCR) at the time of surgery; secondary endpoints included overall survival (OS), progression-free survival (PFS), and freedom from locoregional failure. Results: Results for the primary endpoint have previously been reported. This analysis presents survival data for the 224 patients in the Danish part of the trial. In all, 221 patients (111 control arm, 110 brachytherapy boost arm) had data available for analysis, with a median follow-up time of 5.4 years. Despite a significant increase in tumor response at the time of surgery, no differences in 5-year OS (70.6% vs 63.6%, hazard ratio [HR] = 1.24, P=.34) and PFS (63.9% vs 52.0%, HR=1.22, P=.32) were observed. Freedom from locoregional failure at 5 years were 93.9% and 85.7% (HR=2.60, P=.06) in the standard and in the brachytherapy arms, respectively. There was no difference in the prevalence of stoma. Explorative analysis based on stratification for tumor regression grade and resection margin status indicated the presence of response migration. Conclusions: Despite increased pathologic tumor regression at the time of surgery, we observed no benefit on late outcome. Improved tumor regression does not necessarily lead to a relevant clinical benefit when the neoadjuvant treatment is followed by high-quality surgery.

  10. Neoadjuvant capecitabine, radiotherapy, and bevacizumab (CRAB) in locally advanced rectal cancer: results of an open-label phase II study

    PubMed Central

    2011-01-01

    Background Preoperative capecitabine-based chemoradiation is a standard treatment for locally advanced rectal cancer (LARC). Here, we explored the safety and efficacy of the addition of bevacizumab to capecitabine and concurrent radiotherapy for LARC. Methods Patients with MRI-confirmed stage II/III rectal cancer received bevacizumab 5 mg/kg i.v. 2 weeks prior to neoadjuvant chemoradiotherapy followed by bevacizumab 5 mg/kg on Days 1, 15 and 29, capecitabine 825 mg/m2 twice daily on Days 1-38, and concurrent radiotherapy 50.4 Gy (1.8 Gy/day, 5 days/week for 5 weeks + three 1.8 Gy/day), starting on Day 1. Total mesorectal excision was scheduled 6-8 weeks after completion of chemoradiotherapy. Tumour regression grades (TRG) were evaluated on surgical specimens according to Dworak. The primary endpoint was pathological complete response (pCR). Results 61 patients were enrolled (median age 60 years [range 31-80], 64% male). Twelve patients (19.7%) had T3N0 tumours, 1 patient T2N1, 19 patients (31.1%) T3N1, 2 patients (3.3%) T2N2, 22 patients (36.1%) T3N2 and 5 patients (8.2%) T4N2. Median tumour distance from the anal verge was 6 cm (range 0-11). Grade 3 adverse events included dermatitis (n = 6, 9.8%), proteinuria (n = 4, 6.5%) and leucocytopenia (n = 3, 4.9%). Radical resection was achieved in 57 patients (95%), and 42 patients (70%) underwent sphincter-preserving surgery. TRG 4 (pCR) was recorded in 8 patients (13.3%) and TRG 3 in 9 patients (15.0%). T-, N- and overall downstaging rates were 45.2%, 73.8%, and 73.8%, respectively. Conclusions This study demonstrates the feasibility of preoperative chemoradiotherapy with bevacizumab and capecitabine. The observed adverse events of neoadjuvant treatment are comparable with those previously reported, but the pCR rate was lower. PMID:21880132

  11. Surgical and Survival Outcomes Following Pelvic Exenteration for Locally Advanced Primary Rectal Cancer: Results from an International Collaboration.

    PubMed

    2017-09-21

    The aim of the study was to analyze data from an international collaboration, and ascertain prognostic indicators that inform clinical decision-making and practices regarding the role of pelvic exenteration for locally advanced primary rectal cancer (LARC). With improved national screening programs fewer patients present with LARC. Despite this, select cohorts of patients require pelvic exenteration. To date, the majority of outcome data are from single-center series. Anonymized data from 14 countries on patients who had pelvic exenteration for LARC between 2004 and 2014 were accumulated. The primary endpoint was overall survival. The impact of resection margin, nodal status, bone resection, and use of neoadjuvant therapy (before exenteration) on survival was evaluated using multivariable analysis. Of 1291 patients, 778 (60.3%) were male with a median (range) age of 63 (18-90) years; 78.1% received neoadjuvant therapy. Bone resection en bloc was performed in 8.2% of patients (n = 106), and 22.6% (n = 292) had resection combined with flap reconstruction. Negative resection margin (R0 resection) was achieved in 79.9%. The 30-day postoperative mortality was 1.5%.The median overall survival following R0, R1, and R2 resection was 43, 21, and 10 months (P < 0.001) with a 3-year survival of 56.4%, 29.6%, and 8.1%, respectively (P < 0.001); 37.8% of patients experienced one or more major complication. Neoadjuvant therapy increased the risk of 30-day morbidity (P < 0.012). Multivariable analysis identified resection margin and nodal status as significant determinants of overall survival (other than advanced age). Attainment of negative resection margins (R0) is the key to survival. Neoadjuvant therapy may improve survival; however, it does so at the increased risk of postoperative morbidity.

  12. Changes in treatment patterns for patients with locally advanced rectal cancer in the United States over the past decade: An analysis from the National Cancer Data Base.

    PubMed

    Sineshaw, Helmneh M; Jemal, Ahmedin; Thomas, Charles R; Mitin, Timur

    2016-07-01

    In the United States, neoadjuvant chemoradiotherapy (NACRT) is widely accepted as the standard of care in the treatment of patients with locally advanced rectal cancer. In the current study, the authors attempted to examine patterns of treatment in the United States over the past decade. Using the National Cancer Data Base, a total of 66,197 patients who were diagnosed with American Joint Committee on Cancer stage II to III rectal adenocarcinoma and treated between 2004 and 2012 were identified. The authors described trends in the receipt of treatment for 3 time periods (2004-2006, 2007-2009, and 2010-2012) and analyzed 5-year overall survival probabilities for 28,550 patients treated between 2004 and 2007. Receipt of NACRT increased significantly from 42.9% between 2004 and 2006 to 50.0% between 2007 and 2009, and to 55.0% between 2010 and 2012 (P < .0001). In contrast, the use of adjuvant chemoradiotherapy (CRT) decreased from 16.7% between 2004 and 2006 to 10.5% between 2007 and 2009, and to 6.7% between 2010 and 2012 (P < .0001). Similarly, the use of surgery alone decreased from 13.1% between 2004 and 2006 to 8.7% between 2010 and 2012 (P < .0001). Older age, the presence of comorbidities, larger primary tumor size, lymph node involvement, not being of non-Hispanic white race/ethnicity, lack of private insurance, and treatment at a facility that did not have a high case volume were associated with a significantly lower possibility of receiving NACRT. The 5-year overall survival rates for patients treated with NACRT, surgery and adjuvant CRT, surgery alone, and definitive CRT were 72.4%, 70.9%, 44.9%, and 48.8%, respectively. The use of NACRT before surgery in US patients with rectal cancer has substantially increased over the past decade. However, only approximately one-half of patients currently receive this standard therapy, which could be explained in part by socioeconomic factors. Trimodality therapy is associated with the best outcomes for

  13. PET-MRI in Diagnosing Patients With Colon or Rectal Cancer

    ClinicalTrials.gov

    2015-11-25

    Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage IIA Colon Cancer; Stage IIA Rectal Cancer; Stage IIB Colon Cancer; Stage IIB Rectal Cancer; Stage IIC Colon Cancer; Stage IIC Rectal Cancer; Stage IIIA Colon Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

  14. Robotic surgery for rectal cancer.

    PubMed

    Nozawa, Hiroaki; Watanabe, Toshiaki

    2017-09-26

    Laparoscopic surgery has gained acceptance as a less invasive approach in the treatment of colon cancer. However, laparoscopic surgery for rectal cancer, particularly cancer of the lower rectum, is still challenging because of limited accessibility. Robotic surgery overcomes the limitations of laparoscopy associated with anatomy and offers certain advantages, including 3-D imaging, dexterity and ambidextrous capability, lack of tremors, motion scaling, and a short learning curve. Robotic rectal surgery has been reported to reduce conversion rates, particularly in low anterior resection, but it is associated with longer operative times than the conventional laparoscopic approach. Postoperative morbidities are similar between the robotic and conventional laparoscopic approaches, and oncological outcomes such as the quality of the mesorectum and the status of resection margins are also equivalent. The possible superiority of robotic surgery in terms of the preservation of autonomic function has yet to be established in research based on larger numbers of patients. Although robotic rectal surgery is safe, feasible, and appears to overcome some of the technical limitations associated with conventional laparoscopic surgery, the advantages provided by this technical innovation are currently limited. To justify its expensive cost, robotic surgery is more suitable for select patients, such as obese patients, men, those with cancer of the lower rectum, and those receiving preoperative chemoradiotherapy. © 2017 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and John Wiley & Sons Australia, Ltd.

  15. Phase II study of capecitabine and oxaliplatin given prior to and concurrently with preoperative pelvic radiotherapy in patients with locally advanced rectal cancer

    PubMed Central

    Koeberle, D; Burkhard, R; von Moos, R; Winterhalder, R; Hess, V; Heitzmann, F; Ruhstaller, T; Terraciano, L; Neuweiler, J; Bieri, G; Rust, C; Toepfer, M

    2008-01-01

    This multicentre phase II study evaluated the efficacy and safety of preoperative capecitabine plus oxaliplatin and radiotherapy (RT) in patients with locally advanced rectal cancer (T3/T4 rectal adenocarcinoma with or without nodal involvement). Treatment consisted of one cycle of XELOX (capecitabine 1000 mg m−2 bid on days 1–14 and oxaliplatin 130 mg m−2 on day 1), followed by RT (1.8 Gy fractions 5 days per week for 5 weeks) plus CAPOX (capecitabine 825 mg m−2 bid on days 22–35 and 43–56, and oxaliplatin 50 mg m−2 on days 22, 29, 43 and 50). Surgery was recommended 5 weeks after completion of chemoradiotherapy. The primary end point was pathological complete tumour response (pCR). Sixty patients were enrolled. In the intent-to-treat population, the pCR rate was 23% (95% CI: 13–36%). 58 patients underwent surgery; R0 resection was achieved in 57 (98%) patients, including all 5 patients with T4 tumours. Sphincter preservation was achieved in 49 (84%) patients. Tumour and/or nodal downstaging was observed in 39 (65%) patients. The most common grade 3/4 adverse events were diarrhoea (20%) and lymphocytopaenia (43%). Preoperative capecitabine, oxaliplatin and RT achieved encouraging rates of pCR, R0 resection, sphincter preservation and tumour downstaging in patients with locally advanced rectal cancer. PMID:18349837

  16. Phase II study of capecitabine and oxaliplatin given prior to and concurrently with preoperative pelvic radiotherapy in patients with locally advanced rectal cancer.

    PubMed

    Koeberle, D; Burkhard, R; von Moos, R; Winterhalder, R; Hess, V; Heitzmann, F; Ruhstaller, T; Terraciano, L; Neuweiler, J; Bieri, G; Rust, C; Toepfer, M

    2008-04-08

    This multicentre phase II study evaluated the efficacy and safety of preoperative capecitabine plus oxaliplatin and radiotherapy (RT) in patients with locally advanced rectal cancer (T3/T4 rectal adenocarcinoma with or without nodal involvement). Treatment consisted of one cycle of XELOX (capecitabine 1000 mg m(-2) bid on days 1-14 and oxaliplatin 130 mg m(-2) on day 1), followed by RT (1.8 Gy fractions 5 days per week for 5 weeks) plus CAPOX (capecitabine 825 mg m(-2) bid on days 22-35 and 43-56, and oxaliplatin 50 mg m(-2) on days 22, 29, 43 and 50). Surgery was recommended 5 weeks after completion of chemoradiotherapy. The primary end point was pathological complete tumour response (pCR). Sixty patients were enrolled. In the intent-to-treat population, the pCR rate was 23% (95% CI: 13-36%). 58 patients underwent surgery; R0 resection was achieved in 57 (98%) patients, including all 5 patients with T4 tumours. Sphincter preservation was achieved in 49 (84%) patients. Tumour and/or nodal downstaging was observed in 39 (65%) patients. The most common grade 3/4 adverse events were diarrhoea (20%) and lymphocytopaenia (43%). Preoperative capecitabine, oxaliplatin and RT achieved encouraging rates of pCR, R0 resection, sphincter preservation and tumour downstaging in patients with locally advanced rectal cancer.

  17. Dose-Effect Relationship in Chemoradiotherapy for Locally Advanced Rectal Cancer: A Randomized Trial Comparing Two Radiation Doses

    SciTech Connect

    Jakobsen, Anders; Ploen, John; Vuong, Te; Appelt, Ane; Lindebjerg, Jan; Rafaelsen, Soren R.

    2012-11-15

    Purpose: Locally advanced rectal cancer represents a major therapeutic challenge. Preoperative chemoradiation therapy is considered standard, but little is known about the dose-effect relationship. The present study represents a dose-escalation phase III trial comparing 2 doses of radiation. Methods and Materials: The inclusion criteria were resectable T3 and T4 tumors with a circumferential margin of {<=}5 mm on magnetic resonance imaging. The patients were randomized to receive 50.4 Gy in 28 fractions to the tumor and pelvic lymph nodes (arm A) or the same treatment supplemented with an endorectal boost given as high-dose-rate brachytherapy (10 Gy in 2 fractions; arm B). Concomitant chemotherapy, uftoral 300 mg/m{sup 2} and L-leucovorin 22.5 mg/d, was added to both arms on treatment days. The primary endpoint was complete pathologic remission. The secondary endpoints included tumor response and rate of complete resection (R0). Results: The study included 248 patients. No significant difference was found in toxicity or surgical complications between the 2 groups. Based on intention to treat, no significant difference was found in the complete pathologic remission rate between the 2 arms (18% and 18%). The rate of R0 resection was different in T3 tumors (90% and 99%; P=.03). The same applied to the rate of major response (tumor regression grade, 1+2), 29% and 44%, respectively (P=.04). Conclusions: This first randomized trial comparing 2 radiation doses indicated that the higher dose increased the rate of major response by 50% in T3 tumors. The endorectal boost is feasible, with no significant increase in toxicity or surgical complications.

  18. Phase II study of capecitabine (Xeloda (registered) ) and concomitant boost radiotherapy in patients with locally advanced rectal cancer

    SciTech Connect

    Krishnan, Sunil; Janjan, Nora A.; Skibber, John M.; Rodriguez-Bigas, Miguel A.; Wolff, Robert A.; Das, Prajnan; Delclos, Marc E.; Chang, George J.; Hoff, Paulo M.; Eng, Cathy; Brown, Thomas D.; Crane, Christopher H.; Feig, Barry W.; Morris, Jeffrey; Vadhan-Raj, Saroj; Hamilton, Stanley R.; Lin, Edward H. . E-mail: elin@u.washington.edu

    2006-11-01

    Purpose: The aim of this study was to determine the efficacy of capecitabine (Xeloda (registered) ), an oral fluoropyrimidine, as a radiosensitizer in the neoadjuvant treatment of locally advanced rectal cancer (LARC). Methods and Materials: We conducted a phase II study of capecitabine (825 mg/m{sup 2} orally, twice daily continuous) with radiotherapy (52.5 Gy/30 fractions to the primary tumor and perirectal nodes) in 54 patients with LARC (node-negative {>=}T3 or any node-positive tumor) staged by endoscopic ultrasound (EUS). The primary endpoint was pathologic response rate; secondary endpoints included toxicity profiles and survival parameters. Results: Of the 54 patients (median age, 56.7 years; range, 21.3-78.7 years; male:female ratio, 1.7; Eastern Cooperative Oncology Group performance status 0-1: 100%), 51 patients (94%) had T3N0 or T3N1 disease by EUS. Surgery was not performed in 3 patients; 2 of these patients had metastatic disease, and the third patient refused after a complete clinical response. Of the 51 patients evaluable for pathologic response, 9 patients (18%) achieved complete response, and 12 patients (24%) had microscopic residual disease (<10% viable cells). In addition, 26 patients of all 54 patients (51%) achieved T-downstaging, and 15 patients of 29 patients (52%) achieved N-downstaging. Grade 3/4 toxicities were radiation dermatitis (9%) and diarrhea (2%). Sphincter preservation rate for tumor {<=}5 cm from the anal verge was 67% (18/27). Conclusion: This regimen of radiotherapy plus capecitabine is well tolerated and is more convenient than protracted venous infusion of 5-FU. The pathologic response rate is comparable to our previous experience using protracted venous infusion 5-FU for LARC.

  19. A nomogram to predict distant metastasis after neoadjuvant chemoradiotherapy and radical surgery in patients with locally advanced rectal cancer.

    PubMed

    Sun, Yanwu; Lin, Huiming; Lu, Xingrong; Huang, Ying; Xu, Zongbin; Huang, Shenghui; Wang, Xiaojie; Chi, Pan

    2017-03-01

    To compare distant metastasis (DM) in locally advanced rectal cancer (LARC) patients treated with neoadjuvant chemoradiotherapy (nCRT) and surgery alone, and to develop a predictive nomogram for DM following nCRT. Propensity-scoring match analysis was performed to compare DM in LARC treated with nCRT (n = 375) and surgery alone (n = 375). Cox regression was performed to identify predictors of DM following nCRT. A nomogram was developed and validated by internal (n = 425) and external validation (n = 97). The 5-year local recurrence rate was significantly lower in the nCRT group (5.6% vs. 10.4%; P = 0.020). The 5-year DM rates (nCRT vs. surgery alone: 25.3% vs. 24.4%; P = 0.235) were similar between groups. Cox regression showed that the post-nCRT pathologic stage (ypTNM stage, OR = 2.022, P = 0.002), IMA nodal metastasis (OR = 2.171, P = 0.023), and CRM involvement (OR = 2.535, P = 0.016) were independently associated with DM following nCRT. A predictive nomogram was developed with a C-index of 0.70 on internal validation, and 0.71 on the external validation. NCRT improved local control, but not distant metastasis. A nomogram to predict 3- and 5-year DM rates, using clinicopathological parameters, was successfully developed. This prognostic tool could support decision-making in clinical practice and follow-up strategies. © 2017 Wiley Periodicals, Inc.

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

    SciTech Connect

    Hong, Yong Sang; Lee, Jae-Lyun; Park, Jin Hong; Kim, Jong Hoon; Yoon, Sang Nam; Lim, Seok-Byung; Yu, Chang Sik; Kim, Mi-Jung; Jang, Se-Jin; Lee, Jung Shin; Kim, Jin Cheon; Kim, Tae Won

    2011-03-01

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

  1. [A Case of Unresectable Advanced Rectal Cancer with a Pancreatic Tumor That Was Successfully Treated with FOLFIRINOX].

    PubMed

    Yabe, Nobushige; Murai, Shinji; Ozawa, Hiroki; Yokose, Takahiro; Oto, Ippei; Yoshikawa, Takahisa; Kitasato, Kenjiro; Shimizu, Hirotomo; Kojima, Kenji; Hasegawa, Hirotoshi; Kitagawa, Yuko

    2016-11-01

    A 72-year-old man was admitted to our hospital department in September 2014 because of a positive fecal occult blood test.Colonoscopy showed a type 2 tumor in half of the AV 15 cm rectosigmoid colon.Histology of the biopsy indicated a moderately differentiated adenocarcinoma, and the RAS gene test found wild type.On CT examination, there were multiple liver lung metastases and a 30mm diameter tumor with pancreatic duct extension to the pancreatic body.A PET-CT examination had a high SUVmax at the same site.Because of the location of the tumor EUS-FNA was not used.However, the possibility of pancreatic body cancer could not be denied after the CT examination.Treatment by radical resection was impossible because of the spread of the cancer so we selected chemotherapy.Undeniable pancreatic metastasis of rectal cancer, pancreatic cancer was used as a prognostic factor as double cancer of rectal cancer and pancreatic cancer, from that UGT1A1 test side effects appearance was a low-risk decision, was selected FOLFIRINOX in the treatment regimen.After 25 cycles, the pancreatic body tumor and liver metastases and also the primary tumor were reduced, the multiple lung metastases disappeared, and disease control was good.Side effects were diarrhea on the day of administration of irinotecan, but this was controllable by administering oral loperamide when starting the infusion.Grade 3 or more peripheral neuropathy has not developed, and this regimen is continuing.Pancreatic cancer is a solid cancer with a poor prognosis; if you do not reach the tissue diagnosis of metastatic pancreatic cancer, was a case in which no choice but to select a regimen to carcinoma of the prognostic.

  2. Rectal cancer with synchronous liver metastases: Do we have a clear direction?

    PubMed

    Pathak, S; Nunes, Q M; Daniels, I R; Smart, N J; Poston, G J; Påhlman, L

    2015-12-01

    Rectal cancer is a common entity and often presents with synchronous liver metastases. There are discrepancies in management guidelines throughout the world regarding the treatment of advanced rectal cancer, which are further compounded when it presents with synchronous liver metastases. The following article examines the evidence regarding treatment options for patients with synchronous rectal liver metastases and suggests potential treatment algorithms.

  3. A Specific miRNA Signature Correlates With Complete Pathological Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer

    SciTech Connect

    Della Vittoria Scarpati, Giuseppina; Falcetta, Francesca; Carlomagno, Chiara; Ubezio, Paolo; Marchini, Sergio; De Stefano, Alfonso; Singh, Vijay Kumar; D'Incalci, Maurizio; De Placido, Sabino; Pepe, Stefano

    2012-07-15

    Purpose: MicroRNAs (miRNAs) are small, noncoding RNA molecules that can be down- or upregulated in colorectal cancer and have been associated to prognosis and response to treatment. We studied miRNA expression in tumor biopsies of patients with rectal cancer to identify a specific 'signature' correlating with pathological complete response (pCR) after neoadjuvant chemoradiotherapy. Methods and Materials: A total of 38 T3-4/N+ rectal cancer patients received capecitabine-oxaliplatin and radiotherapy followed by surgery. Pathologic response was scored according to the Mandard TRG scale. MiRNA expression was analyzed by microarray and confirmed by real-time Reverse Transcription Polymerase Chain Reaction (qRT-PCR) on frozen biopsies obtained before treatment. The correlation between miRNA expression and TRG, coded as TRG1 (pCR) vs. TRG >1 (no pCR), was assessed by methods specifically designed for this study. Results: Microarray analysis selected 14 miRNAs as being differentially expressed in TRG1 patients, and 13 were confirmed by qRT-PCR: 11 miRNAs (miR-1183, miR-483-5p, miR-622, miR-125a-3p, miR-1224-5p, miR-188-5p, miR-1471, miR-671-5p, miR-1909 Asterisk-Operator , miR-630, miR-765) were significantly upregulated in TRG1 patients, 2 (miR-1274b, miR-720) were downexpressed. MiR-622 and miR-630 had a 100% sensitivity and specificity in selecting TRG1 cases. Conclusions: A set of 13 miRNAs is strongly associated with pCR and may represent a specific predictor of response to chemoradiotherapy in rectal cancer patients.

  4. Optimal Timing of Surgical Resection After Radiation in Locally Advanced Rectal Adenocarcinoma: An Analysis of the National Cancer Database.

    PubMed

    Huntington, Ciara R; Boselli, Danielle; Symanowski, James; Hill, Joshua S; Crimaldi, Anthony; Salo, Jonathan C

    2016-03-01

    In the treatment of rectal cancer, a longer radiation-surgery interval from the end of neoadjuvant radiation therapy to surgery has been associated with higher rates of complete pathologic response (pCR), but the optimal interval with respect to survival has not been established. Data from the National Cancer Database (NCDB) was used to evaluate the impact of radiation-surgery interval on oncologic outcomes. The NCDB was searched for patients diagnosed with nonmetastatic rectal cancer who underwent preoperative radiation followed by radical surgical resection. A Cox proportional hazards model was constructed to examine the influence of radiation-surgery interval while controlling for potential confounding factors. Sensitivity analysis was used to confirm the results of the model. A cohort of 6397 patients meeting all inclusion and exclusion criteria from 2004-2006 was identified, and the pCR rate for this cohort was 6.9%. Of those who experienced a pCR, 76.2% had done so by 60 days. Intervals greater than 60 days were associated with higher rates of positive surgical margins (6.7 vs. 4.8%, p = 0.009) and lower rates of sphincter-preserving surgery (64.9 vs. 68.9%, p = 0.007). An interval greater than 60 days was associated with significantly shorter survival (hazard ratio (HR), 1.314; 95% CI 1.191-1.449; p < 0.001). Radiation-surgery interval beyond 60 days is associated with increased rate of positive surgical margins, decreased rate of sphincter-preserving surgery, and decreased survival. Delay of surgery for rectal cancer beyond 60 days after the completion of neoadjuvant therapy should be done with caution.

  5. Endoscopic ultrasound for the characterization and staging of rectal cancer. Current state of the method. Technological advances and perspectives.

    PubMed

    Gersak, Mariana M; Badea, Radu; Graur, Florin; Hajja, Nadim Al; Furcea, Luminita; Dudea, Sorin M

    2015-06-01

    Endoscopic ultrasound is the most accurate type of examination for the assessment of rectal tumors. Over the years, the method has advanced from gray-scale examination to intravenous contrast media administration and to different types of elastography. The multimodal approach of tumors (transrectal, transvaginal) is adapted to each case. 3D ultrasound is useful for spatial representation and precise measurement of tumor formations, using CT/MR image reconstruction; color elastography is useful for tumor characterization and staging; endoscopic ultrasound using intravenous contrast agents can help study the amount of contrast agent targeted at the level of the tumor formations and contrast wash-in/wash-out time, based on the curves displayed on the device. The transvaginal approach often allows better visualization of the tumor than the transrectal approach. Performing the procedure with the rectal ampulla distended with contrast agent may be seen as an optimization of the examination methodology. All these aspects are additional methods for gray-scale endoscopic ultrasound, capable of increasing diagnostic accuracy. This paper aims at reviewing the progress of transrectal and transvaginal ultrasound, generically called endoscopic ultrasound, for rectal tumor diagnosis and staging, with emphasis on the current state of the method and its development trends.

  6. [Surgical treatment of rectal cancer].

    PubMed

    Vergara-Fernández, O; Salinas-Aragón, L E; Camacho-Mauries, D; Medina-Franco, H

    2010-01-01

    Rectal affection accounts for 30% of colorectal cancer. The standard of treatment is surgical resection, which often is curative. For superior and middle-rectal involvement, low anterior resection (LAR) is the preferred procedure. For tumors involving the lower portion of the rectum, abdominoperineal resection (APR) or LAR are the options of treatment, depending on sphincter involvement. The main surgical objective is to achieve a R0 resection with an appropriated total mesorrectal excision, greater number of lymph nodes and negative distal and radial margins. These surgical parameters have been used as quality indicators and have prognostic implications in terms of overall and disease-free survival. Total mesorectal excision with preservation of hypogastric nerves has shown a reduction in rates of sexual and bladder dysfunction as well as lower local recurrence. At specialized centers such procedures are performed by minimal invasive surgery; however the number of meta-analysis is scarce.

  7. Drugs Approved for Colon and Rectal Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for use in colon cancer and rectal cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  8. Metabolic and molecular relative percentage coreduction in patients with locally advanced rectal cancer treated with neoadjuvant therapy.

    PubMed

    Sole, Claudio V; Calvo, Felipe A; Alvarez, Emilio; Carreras, Jose L

    2016-07-01

    Vascular endothelial growth factor receptor-2 (VEGFR-2), epidermal growth factor receptor-1 (EGFR) and cyclooxygenase-2 (COX-2) stimulate key processes involved in tumour progression and are important targets for cancer therapeutics. (18)F-FDG maximum standardized uptake value (SUVmax) on PET/CT is a marker of tumour metabolic activity. The purpose of this study was to measure percentage reductions in SUVmax (∆SUVmax%), VEGFR-2 (∆VEGFR-2%), EGFR (∆EGFR%) and COX-2 (∆COX-2%) in patients with locally advanced rectal cancer (LARC) after preoperative treatment, and to correlate the changes in these markers of response with pathological response in terms of tumour regression grade (TRG) using Rödel's scale and long-term clinical outcome. VEGFR-2, EGFR and COX-2 were measured using a quantitative and qualitative compound immunohistochemistry analysis (immunoreactive score) of the pretreatment endoscopic biopsy and definitive surgical specimens. Composite indexes using ∆SUVmax% and the three molecules were developed to differentiate patients with metabolic and molecular responses from nonresponders. Cox proportional hazards model was used to explore associations between the tumour markers, disease-free survival (DFS) and overall survival (OS). The analysis included 38 patients with a median follow-up of 86 months (range 5 - 113 months). The ∆VEGFR-2%/∆SUVmax% index correctly identified 13 of 19 pathological responders (TRG 3 and 4) and 17 of 19 nonresponders (TRG 0 - 2) (sensitivity 68 %, specificity 89 %, accuracy 79 %, positive predictive value 87 %, negative predictive value 74 %). In multivariate analysis, only the ∆VEGFR-2%/∆SUVmax% index was associated with DFS (HR 0.11, p = 0.001) and OS (HR 0.15, p = 0.02). In patients with LARC the ∆VEGFR-2%/∆SUVmax% response index is associated with outcome. Determination of the optimal diagnostic cut-off level for this novel biomarker association should be explored. Evaluation in a

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

    PubMed

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

    2015-11-10

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

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

    PubMed Central

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

    2015-01-01

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

  11. 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

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

    SciTech Connect

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

    2013-05-01

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

  13. Value of diffusion-weighted MRI and apparent diffusion coefficient measurements for predicting the response of locally advanced rectal cancer to neoadjuvant chemoradiotherapy.

    PubMed

    Iannicelli, Elsa; Di Pietropaolo, Marco; Pilozzi, Emanuela; Osti, Mattia Falchetto; Valentino, Maria; Masoni, Luigi; Ferri, Mario

    2016-10-01

    The aim of our study was to assess the performance value of magnetic resonance imaging (MRI) in the restaging of locally advanced rectal cancer after neoadjuvant chemoradiotherapy (CRT) and in the identification of good vs. poor responders to neoadjuvant therapy. A total of 34 patients with locally advanced rectal cancer underwent MRI prior to and after CRT. T stage and tumor regression grade (TRG) on post-CRT MRI was compared with the pathological staging ypT and TRG. Tumor volume and the apparent diffusion coefficient (ADC) were measured using diffusion-weighted imaging (DWI) before and after neoadjuvant CRT; the percentage of tumor volume reduction and the change of ADC (ΔADC) was also calculated. ADC parameters and the percentage of tumor volume reduction were correlated to histopathological results. The diagnostic performance of ADC and volume reduction to assess tumor response was evaluated by calculating the area under the ROC curve and the optimal cut-off values. A significant correlation between the T stage and the TRG defined in DW-MRI after CRT and the ypT and the TRG observed on the surgical specimens was found (p = 0.001; p < 0.001). The mean post-CRT ADC and ΔADC in responder patients was significantly higher compared to non-responder ones (p = 0.001; p = 0.01). Furthermore, the mean post-CRT ADC values were significantly higher in tumors with T-downstage (p = 0.01). DW-MRI may have a significant role in the restaging and in the evaluation of post-CRT response of locally advanced rectal cancer. Quantitative analysis of DWI through ADC map may result in a promising noninvasive tool to evaluate the response to therapy.

  14. Preoperative Chemoradiation With Irinotecan and Capecitabine in Patients With Locally Advanced Resectable Rectal Cancer: Long-Term Results of a Phase II Study

    SciTech Connect

    Hong, Yong Sang; Kim, Dae Yong; Lim, Seok-Byung; Choi, Hyo Seong; Jeong, Seung-Yong; Jeong, Jun Yong; Sohn, Dae Kyung; Kim, Dae-Hyun; Chang, Hee Jin; Park, Jae-Gahb; Jung, Kyung Hae

    2011-03-15

    Purpose: Preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer has shown benefit over postoperative CRT; however, a standard CRT regimen has yet to be defined. We performed a prospective concurrent CRT Phase II study with irinotecan and capecitabine in patients with locally advanced rectal cancer to investigate the efficacy and safety of this regimen. Methods and Materials: Patients with locally advanced, nonmetastatic, and mid-to-lower rectal cancer were enrolled. Radiotherapy was delivered in 1.8-Gy daily fractions for a total of 45 Gy in 25 fractions, followed by a coned-down boost of 5.4 Gy in 3 fractions. Concurrent chemotherapy consisted of 40 mg/m{sup 2} of irinotecan per week for 5 consecutive weeks and 1,650 mg/m{sup 2} of capecitabine per day for 5 days per week (weekdays only) from the first day of radiotherapy. Total mesorectal excision was performed within 6 {+-} 2 weeks. The pathologic responses and survival outcomes were included for the study endpoints. Results: In total, 48 patients were enrolled; 33 (68.7%) were men and 15 (31.3%) were women, and the median age was 59 years (range, 32-72 years). The pathologic complete response rate was 25.0% (11 of 44; 95% confidence interval, 12.2-37.8) and 8 patients (18.2% [8 of 44]) showed near-total tumor regression. The 5-year disease-free and overall survival rates were 75.0% and 93.6%, respectively. Grade 3 toxicities included leukopenia (3 [6.3%]), neutropenia (1 [2.1%]), infection (1 [2.1%]), alanine aminotransferase elevation (1 [2.1%]), and diarrhea (1 [2.1%]). There was no Grade 4 toxicity or treatment-related death. Conclusions: Preoperative CRT with irinotecan and capecitabine with treatment-free weekends showed very mild toxicity profiles and promising results in terms of survival.

  15. Systematic review and meta-analysis of preoperative chemoradiotherapy with or without oxaliplatin in locally advanced rectal cancer

    PubMed Central

    Zheng, Jiabin; Feng, Xingyu; Hu, Weixian; Wang, Junjiang; Li, Yong

    2017-01-01

    Abstract Background: Preoperative chemoradiotherapy has become the current standard regimen for locally advanced rectal cancer (LARC). However, the additional benefit of oxaliplatin to preoperative chemotherapy was still controversial. On one hand, oxaliplatin may improve the tumor response rate of even prolong the survival time. On the other hand, it can bring a series of adverse effects. Opinions vary from studies to studies. We aim to perform a meta-analysis to evaluate the efficacy, safety, and long-term survival of oxaliplatin in preoperative chemoradiotherapy for LARC. Method: To identify clinical trials fusing oxaliplatin in preoperative chemoradiotherapy for LARC published until December 2015, we searched PubMed, the Cochrane Library, and the Springer Link databases by combining various key words. We also search for relevant ASCO conferences. Data were extracted from every study to perform a meta-analysis using STATA 12.0 software. Result: Eleven articles or ASCO abstracts from 8 studies with a total of 5597 patients were included. Adding oxaliplatin to preoperative chemoradiotherapy can significantly improve the ypCR rate [risk ratio (RR) = 1.208, 95% confidence interval (95% CI): 1.070–1.364, P = 0.002, I2 = 14.5%], and decrease the preoperative metastasis (RR = 0.494, 95% CI: 0.256–0.954, P = 0.036, I2 = 53.9%) and local recurrence rate (RR = 0.761, 95% CI: 0.616–0.941, P = 0.012, I2 = 26.1%). What's more, oxaliplatin can prolong the disease-free survival (DFS) [hazard ratio (HR) = 0.867, 95% CI: 0.741–0.992, P = 0.000, I2 = 16.3%]. However, oxaliplatin can increase the chemoradiotherapy-related toxicities (RR = 1.858, 95% CI 1.427–2.419, P = 0.000, I2 = 84.7%). There was no significant difference between the groups with and without oxaliplatin in operation rate, R0 resection rate, sphincter preservation rate, permanent stoma rate, postoperative complication, mortality, and overall

  16. Fournier gangrene: rare complication of rectal cancer.

    PubMed

    Ossibi, Pierlesky Elion; Souiki, Tarik; Ibn Majdoub, Karim; Toughrai, Imane; Laalim, Said Ait; Mazaz, Khalid; Tenkorang, Somuah; Farih, My Hassan

    2015-01-01

    Fournier's Gangrene is a rare complication of rectal cancer. Its discovery is often delayed. It's incidence is about 0.3/100,000 populations in Western countries. We report a patient with peritoneal perforation of rectal cancer revealed by scrotal and perineal necrotizing fasciitis.

  17. Delineation of Gross Tumor Volume (GTV) for Radiation Treatment Planning of Locally Advanced Rectal Cancer Using Information From MRI or FDG-PET/CT: A Prospective Study

    SciTech Connect

    Braendengen, Morten; Hansson, Karl; Radu, Calin; Siegbahn, Albert; Jacobsson, Hans; Glimelius, Bengt

    2011-11-15

    Purpose: Accurate delineation of target volumes is important to maximize radiation dose to the tumor and minimize it to nontumor tissue. Computed tomography (CT) and magnetic resonance imaging (MRI) are standard imaging modalities in rectal cancer. The aim was to explore whether functional imaging with F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET), combined with CT (FDG-PET/CT) gives additional information to standard pretreatment evaluation and changes the shape and size of the gross tumor volume (GTV). Methods and Materials: From 2007 to 2009, 77 consecutive patients with locally advanced rectal cancer were prospectively screened for inclusion in the study at two university hospitals in Sweden, and 68 patients were eligible. Standard GTV was delineated using information from clinical examination, CT, and MRI (GTV-MRI). Thereafter, a GTV-PET was defined in the fused PET-CT, and the target volume delineations were compared for total volume, overlap, and mismatch. Pathologic uptake suspect of metastases was also registered. Results: The median volume of GTV-MRI was larger than that of GTV-PET: 111 cm{sup 3} vs. 87 cm{sup 3} (p < 0.001). In many cases, the GTV-MRI contained the GTV defined on the PET/CT images as subvolumes, but when a GTV total was calculated after the addition of GTV-PET to GTV-MRI, the volume increased, with median 11% (range, 0.5-72%). New lesions were seen in 15% of the patients for whom PET/CT was used. Conclusions: FDG-PET/CT facilitates and adds important information to the standard delineation procedure of locally advanced rectal cancer, mostly resulting in a smaller GTV, but a larger total GTV using the union of GTV-MRI and GTV-PET. New lesions were sometimes seen, potentially changing the treatment strategy.

  18. Neoadjuvant Chemotherapy with Capecitabine, Oxaliplatin and Bevacizumab Followed by Concomitant Chemoradiation and Surgical Resection in Locally Advanced Rectal Cancer with High Risk of Recurrence - A Phase II Study.

    PubMed

    Eisterer, Wolfgang; Piringer, Gudrun; DE Vries, Alexander; Öfner, Dietmar; Greil, Richard; Tschmelitsch, Jörg; Samonigg, Hellmut; Sölkner, Lidija; Gnant, Michael; Thaler, Josef

    2017-05-01

    To evaluate feasibility and safety of neoadjuvant chemotherapy with capecitabine, oxaliplatin and bevacizumab followed by concomitant standard chemoradiation and surgical resection in patients with high-risk locally advanced rectal cancer. Magnetic resonance imaging (MRI)-defined high-risk cT3/4 rectal cancer patients were treated with 3 cycles of neoadjuvant chemotherapy with capecitabine (1,000 mg/m(2) twice daily days 1-14, 22-35, 43-56), oxaliplatin (130 mg/sqm on days 1, 22, 43) and bevacizumab (7.5 mg/kg on days 1, 22, 43) followed by capecitabine (825 mg/m(2) twice daily on radiotherapy days week 1-4) concomitantly with radiotherapy (1.8 Gy daily up to 45 Gy in 5 weeks) and surgical resection by total mesorectal excision. Feasibility, safety, response rate and postoperative morbidity were evaluated. Twenty-five patients were recruited. Median age was 62 years (range=24-78 years) and all patients had Eastern Cooperation Oncology Group (ECOG) performance status 0. From all patients, 79.2% finished neoadjuvant chemotherapy. Twenty patients underwent surgery. Pathologic complete remission rate, R0 resection and T-downstaging were achieved in 25%, 95% and 54.2% of the "intention to treat" (ITT) patients. The most common grade 3 adverse events (AEs) during neoadjuvant chemotherapy were diarrhea (16.6%) and mucositis (12.5%). In one patient, a grade 4 acute renal failure occurred (4.2%). During chemoradiation, skin reactions (5.3%) were the most common grade 3 AEs. Two major perioperative complications required re-intervention. Neoadjuvant chemotherapy with bevacizumab, capecitabine and oxaliplatin followed by concomitant standard chemoradiation is feasible in patients with high-risk locally advanced rectal cancer (LARC) and resulted in complete pathologic remission (pCR) rate of 25% and neoadjuvant chemotherapy completion rate of 80%. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  19. Carcinoembryonic Antigen as a Predictor of Pathologic Response and a Prognostic Factor in Locally Advanced Rectal Cancer Patients Treated With Preoperative Chemoradiotherapy and Surgery

    SciTech Connect

    Park, Ji Won; Lim, Seok-Byung Kim, Dae Yong; Jung, Kyung Hae; Hong, Yong Sang; Chang, Hee Jin; Choi, Hyo Seong; Jeong, Seung-Yong

    2009-07-01

    Purpose: To evaluate the role of serum carcinoembryonic antigen (CEA) as a predictor of response to preoperative chemoradiotherapy (CRT) and prognostic factor for rectal cancer. Materials and Methods: The study retrospectively evaluated 352 locally advanced rectal cancer patients who underwent preoperative CRT followed by surgery. Serum CEA levels were determined before CRT administration (pre-CRT CEA) and before surgery (post-CRT CEA). Correlations between pre-CRT CEA levels and rates of good response (Tumor regression grade 3/4) were explored. Patients were categorized into three CEA groups according to their pre-/post-CRT CEA levels (ng/mL) (Group A: pre-CRT CEA {<=} 3; B: pre-CRT CEA >3, post-CRT CEA {<=}3; C: pre- and post-CRT CEA >3 ng/mL), and their oncologic outcomes were compared. Results: Of 352 patients, good responses were achieved in 94 patients (26.7%). The rates of good response decreased significantly as the pre-CRT CEA levels became more elevated (CEA [ng/mL]: {<=}3, 36.4%; 3-6, 23.6%; 6-9, 15.6%; >9, 7.8%; p < 0.001). The rates of good response were significantly higher in Group A than in Groups B and C (36.4% vs. 17.3% and 14.3%, respectively; p < 0.001). The 3-year disease-free survival rate was significantly better in Groups A and B than in Group C (82% and 79% vs. 57%, respectively; p = 0.005); the CEA grouping was identified as an independent prognostic factor (p = 0.025). Conclusions: In locally advanced rectal cancer patients, CEA levels could be of clinical value as a predictor of response to preoperative CRT and as an independent prognostic factor after preoperative CRT and curative surgery.

  20. Bevacizumab, Fluorouracil, Leucovorin Calcium, and Oxaliplatin Before Surgery in Treating Patients With Stage II-III Rectal Cancer

    ClinicalTrials.gov

    2017-04-11

    Mucinous Adenocarcinoma of the Rectum; Signet Ring Adenocarcinoma of the Rectum; Stage IIA Rectal Cancer; Stage IIB Rectal Cancer; Stage IIC Rectal Cancer; Stage IIIA Rectal Cancer; Stage IIIB Rectal Cancer; Stage IIIC Rectal Cancer

  1. Progress in Rectal Cancer Treatment

    PubMed Central

    Ceelen, Wim P.

    2012-01-01

    The dramatic improvement in local control of rectal cancer observed during the last decades is to be attributed to attention to surgical technique and to the introduction of neoadjuvant therapy regimens. Nevertheless, systemic relapse remains frequent and is currently insufficiently addressed. Intensification of neoadjuvant therapy by incorporating chemotherapy with or without targeted agents before the start of (chemo)radiation or during the waiting period to surgery may present an opportunity to improve overall survival. An increasing number of patients can nowadays undergo sphincter preserving surgery. In selected patients, local excision or even a “wait and see” approach may be feasible following active neoadjuvant therapy. Molecular and genetic biomarkers as well as innovative imaging techniques may in the future allow better selection of patients for this treatment option. Controversy persists concerning the selection of patients for adjuvant chemotherapy and/or targeted therapy after neoadjuvant regimens. The currently available evidence suggests that in complete pathological responders long-term outcome is excellent and adjuvant therapy may be omitted. The results of ongoing trials will help to establish the ideal tailored approach in resectable rectal cancer. PMID:22970381

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

    SciTech Connect

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

    2013-01-01

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

  3. Matrix metalloproteinase-9 expression correlated with tumor response in patients with locally advanced rectal cancer undergoing preoperative chemoradiotherapy

    SciTech Connect

    Unsal, Diclehan . E-mail: diclehan@yahoo.com; Uner, Aytug; Akyurek, Nalan; Erpolat, Petek; Dursun, Ayse; Pak, Yucel

    2007-01-01

    Purpose: To analyze whether the expression of matrix metalloproteinases (MMPs) and their tissue inhibitors are associated with tumor response to preoperative chemoradiotherapy in rectal cancer patients. Methods and Materials: Forty-four patients who had undergone preoperative chemoradiotherapy were evaluated retrospectively. Treatment consisted of pelvic radiotherapy and two cycles of 5-fluorouracil plus leucovorin. Surgery was performed 6-8 weeks later. MMP-2, MMP-9, and tissue inhibitors of metalloproteinase-1 and -2 expression was analyzed by immunohistochemistry of the preradiation biopsy and surgical specimens. The intensity and extent of staining were evaluated separately, and a final score was calculated by multiplying the two scores. The primary endpoint was the correlation of expression with tumor response, with the secondary endpoint the effect of chemoradiotherapy on the expression. Results: Preoperative treatment resulted in downstaging in 20 patients (45%) and no clinical response in 24 (55%). The pathologic tumor response was complete in 11 patients (25%), partial in 23 (52%), and none in 10 (23%). Positive MMP-9 staining was observed in 20 tumors (45%) and was associated with the clinical nodal stage (p = 0.035) and the pathologic and clinical response (p < 0.0001). The staining status of the other markers was associated with neither stage nor response. The overall pathologic response rate was 25% in MMP-9-positive patients vs. 52% in MMP-9-negative patients (p = 0.001). None of the 11 patients with pathologic complete remission was MMP-9 positive. Conclusions: Matrix metalloproteinase-9 expression correlated with a poor tumor response to preoperative chemoradiotherapy in rectal carcinoma patients.

  4. Germ line polymorphisms as predictive markers for pre-surgical radiochemotherapy in locally advanced rectal cancer: a 5-year literature update and critical review.

    PubMed

    Pezzolo, Elisa; Modena, Yasmina; Corso, Barbara; Giusti, Pietro; Gusella, Milena

    2015-05-01

    Locally advanced rectal cancer is currently treated with pre-surgical radiotherapy and chemotherapy. Approximately one-half of patients obtain a relevant shrinkage/disappearance of tumour, with major clinical advantages. The remaining patients, in contrast, show no benefit and possibly need alternative treatment. To provide the best therapeutic option for each individual patient, predictive markers have been widely researched. This review was undertaken to evaluate recent progress made in this field. A systematic literature search was performed using PubMed and Scopus database, focused on germ line gene polymorphisms as biomarkers and response and toxicity as outcomes. Because an exhaustive previous review was available describing findings up to 2008, we restricted our analysis to the last 5 years. Ten original research articles were found, reporting promising results for some candidate genes in drug metabolism (TYMS, MTHFR), DNA repair (XRCC1, OGG1, CCND1) and inflammation (SOD2, TGFB1)/immunity (IL13) pathways, but with no firm conclusion. All the studies had small sample size and were defined as exploratory. This review highlights pivotal molecular, clinical, genetic and statistical issues in the investigation of genetic polymorphisms as outcome predictors for rectal cancer and offers suggestions for future development. What emerges is a clear need for new proposals, especially in view of the increasing evidence for tumour-host and gene-gene interactions during anticancer treatment, together with stronger adherence to proper methodological requirements.

  5. A comparative study of volumetric analysis, histopathologic downstaging, and tumor regression grade in evaluating tumor response in locally advanced rectal cancer following preoperative chemoradiation

    SciTech Connect

    Kim, Nam Kyu . E-mail: namkyuk@yumc.yonsei.ac.kr; Baik, Seung Hyuk; Min, Byung Soh; Pyo, Hong Ryull; Choi, Yun Jung; Kim, Hogeun; Seong, Jinsil; Keum, Ki Chang; Rha, Sun Young; Chung, Hyun Cheol

    2007-01-01

    Purpose: To compare tumor volume reduction rate, histopathologic downstaging, and tumor regression grade (TRG) among tumor responses in rectal cancer after preoperative chemoradiotherapy (CRT). Patients and Methods: Between 2002 and 2004, 30 patients with locally advanced rectal cancer underwent preoperative CRT, followed by surgical resection. Magnetic resonance volumetry was performed before and after CRT. Histopathologic tumor staging and tumor regression were reviewed. We compared pre- and post-CRT tumor volume and percent of volume reduction, according to histopathologic downstaging and TRG. Results: The tumor volume reduction rates ranged from 14.6% to 100%. Mean pre- and post-CRT tumor volumes were significantly smaller in patients who showed T downstaging than in those who did not (p 0.040, 0.014). The mean tumor volume reduction was 66.4% vs. 55.2% (p 0.361). However, the mean pre- and post-CRT tumor volume and mean tumor volume reduction rate between patients who showed N downstaging and those who did not were not statistically different (p = 0.176, 0.767, and 0.899). With respect to TRG, the mean pre- and post-CRT tumor volumes were not statistically significant (p = 0.108, 0.708, and 0.120). Conclusion: Tumor volume reduction rate does not correlate with histopathologic downstaging and TRG. It might be hazardous to evaluate tumor response with respect to volume reduction and to select the surgical method on this basis.

  6. Mechanical suture in rectal cancer.

    PubMed

    Cheregi, Cornel Dragos; Simon, Ioan; Fabian, Ovidiu; Maghiar, Adrian

    2017-01-01

    Colorectal cancer is one of the most frequent digestive malignancies, being the third cause of death by cancer, despite early diagnosis and therapeutic progress made over the past years. Standard treatment in these patients is to preserve the anal sphincter with restoration of intestinal function by mechanical colorectal anastomosis or coloanal anastomosis, and to maintain genitourinary function by preservation of hypogastric nerves. In order to emphasize the importance of this surgical technique in the Fourth Surgical Clinic of the CF Clinical Hospital Cluj-Napoca, we conducted a prospective observational interventional study over a 3-year period (2013-2016) in 165 patients hospitalized for rectal and rectosigmoid adenocarcinoma in various disease stages, who underwent Dixon surgery using the two techniques of manual and mechanical end-to-end anastomosis. For mechanical anastomosis, we used Covidien and Panther circular staplers. The patients were assigned to two groups, group A in which Dixon surgery with manual end-to-end anastomosis was performed (116 patients), and group B in which Dixon surgery with mechanical end-to-end anastomosis was carried out (49 patients). Mechanical anastomosis allowed to restore intestinal continuity following low anterior resection in 21 patients with lower rectal adenocarcinoma compared to 2 patients in whom intestinal continuity was restored by manual anastomosis, with a statistically significant difference (p<0.000001). The double-row mechanical suture technique is associated with a reduced duration of surgery (121.67 minutes for Dixon surgery with mechanical anastomosis, compared to 165.931 minutes for Dixon surgery with manual anastomosis, p<0.0001). The use of circular transanal staplers facilitates end-to-end anastomosis by double-row mechanical suture, allowing to perform low anterior resection in situations when the restoration of intestinal continuity by manual anastomosis is technically not possible, with the aim to

  7. The accuracy of endorectal ultrasonography in rectal cancer staging

    PubMed Central

    COTE, ADRIAN; GRAUR, FLORIN; LEBOVICI, ANDREI; MOIS, EMIL; AL HAJJAR, NADIM; MARE, CODRUTA; BADEA, RADU; IANCU, CORNEL

    2015-01-01

    . The accuracy of ERUS is higher in diagnosing rectal cancer in stages T1, T2 and even in stage T3 with malignant tumor which is not occlusive. ERUS is less accurate for T staging of locally advanced and stenotic tumours. PMID:26609269

  8. Clinical utility of integrated positron emission tomography/computed tomography imaging in the clinical management and radiation treatment planning of locally advanced rectal cancer.

    PubMed

    Whaley, Jonathan T; Fernandes, Annemarie T; Sackmann, Robert; Plastaras, John P; Teo, Boon-Keng; Grover, Surbhi; Perini, Rodolfo F; Metz, James M; Pryma, Daniel A; Apisarnthanarax, Smith

    2014-01-01

    The role of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT) in the staging and radiation treatment planning of locally advanced rectal cancer is ill defined. We studied the role of integrated PET/CT in the staging, radiation treatment planning, and use as an imaging biomarker in rectal cancer patients undergoing multimodality treatment. Thirty-four consecutive patients with T3-4N0-2M0-1 rectal adenocarcinoma underwent FDG-PET/CT scanning for staging and radiation treatment planning. Planned clinical management was compared before and after the addition of PET/CT information. Three radiation oncologists independently delineated CT-based gross tumor volumes (GTVCT) using clinical information and CT imaging data, as well as gradient autosegmented PET/CT-based GTVs (GTVPETCT). The mean GTV, interobserver concordance index (CCI), and proximal and distal margins were compared. The maximal standardized uptake value (SUVmax), metabolic tumor volume (MTV), and dual-time point PET parameters were correlated with clinicopathologic endpoints. Clinical management was altered by PET/CT in 18% (n = 6) of patients with clinical upstaging in 6 patients and radiation treatment planning altered in 5 patients. Of the 30 evaluable preoperative patients, the mean GTVPETCT was significantly smaller than the mean GTVCT volumes: 88.1 versus 102.8 cc (P = .03). PET/CT significantly increased interobserver CCI in contouring GTV compared with CT only-based contouring: 0.56 versus 0.38 (P < .001). The proximal and distal margins were altered by a mean of 0.4 ± 0.24 cm and -0.25 ± 0.18 cm, respectively. MTV was inversely associated with 2-year progression-free survival (PFS) and overall survival (OS): smaller MTVs (<33 cc) had superior 2-year PFS (86% vs 60%, P = .04) and OS (100% vs 45%, P < .01) compared with larger MTVs (>33 cc). SUVmax and dual-time point PET parameters did not correlate with any endpoints. FDG-PET/CT imaging impacts overall clinical

  9. Bupivacaine administered intrathecally versus rectally in the management of intractable rectal cancer pain in palliative care

    PubMed Central

    Zaporowska-Stachowiak, Iwona; Kowalski, Grzegorz; Łuczak, Jacek; Kosicka, Katarzyna; Kotlinska-Lemieszek, Aleksandra; Sopata, Maciej; Główka, Franciszek

    2014-01-01

    slower after rectal than after intrathecal administration (t½= 5.50 versus 2.02 hours, respectively). Limitations This study reports two cases only, and there could be inter-patient variation. Conclusion Bupivacaine in boluses administered intrathecally (0.25%, 2 mL) provided effective, safe analgesia in advanced cancer patients. Bupivacaine enema (100 mg·100 mL−1) was shown to be a valuable option for control of end-of-life tenesmoid cancer pain. PMID:25336967

  10. Magnetic resonance imaging-detected tumor response for locally advanced rectal cancer predicts survival outcomes: MERCURY experience.

    PubMed

    Patel, Uday B; Taylor, Fiona; Blomqvist, Lennart; George, Christopher; Evans, Hywel; Tekkis, Paris; Quirke, Philip; Sebag-Montefiore, David; Moran, Brendan; Heald, Richard; Guthrie, Ashley; Bees, Nicola; Swift, Ian; Pennert, Kjell; Brown, Gina

    2011-10-01

    To assess magnetic resonance imaging (MRI) and pathologic staging after neoadjuvant therapy for rectal cancer in a prospectively enrolled, multicenter study. In a prospective cohort study, 111 patients who had rectal cancer treated by neoadjuvant therapy were assessed for response by MRI and pathology staging by T, N and circumferential resection margin (CRM) status. Tumor regression grade (TRG) was also assessed by MRI. Overall survival (OS) was estimated by using the Kaplan-Meier product-limit method, and Cox proportional hazards models were used to determine associations between staging of good and poor responders on MRI or pathology and survival outcomes after controlling for patient characteristics. On multivariate analysis, the MRI-assessed TRG (mrTRG) hazard ratios (HRs) were independently significant for survival (HR, 4.40; 95% CI, 1.65 to 11.7) and disease-free survival (DFS; HR, 3.28; 95% CI, 1.22 to 8.80). Five-year survival for poor mrTRG was 27% versus 72% (P = .001), and DFS for poor mrTRG was 31% versus 64% (P = .007). Preoperative MRI-predicted CRM independently predicted local recurrence (LR; HR, 4.25; 95% CI, 1.45 to 12.51). Five-year survival for poor post-treatment pathologic T stage (ypT) was 39% versus 76% (P = .001); DFS for the same was 38% versus 84% (P = .001); and LR for the same was 27% versus 6% (P = .018). The 5-year survival for involved pCRM was 30% versus 59% (P = .001); DFS, 28 versus 62% (P = .02); and LR, 56% versus 10% (P = .001). Pathology node status did not predict outcomes. MRI assessment of TRG and CRM are imaging markers that predict survival outcomes for good and poor responders and provide an opportunity for the multidisciplinary team to offer additional treatment options before planning definitive surgery. Postoperative histopathology assessment of ypT and CRM but not post-treatment N status were important postsurgical predictors of outcome.

  11. Focusing the management of rectal cancer

    PubMed Central

    Dbeis, Rachel; Smart, Neil J.

    2016-01-01

    Rectal cancer treatment has undergone major changes over the last 15 years with a focus on individualized care based around MRI assessment of the relationship of the tumour to the mesorectal fascia, improved surgical techniques and targeted use of pre-operative oncological therapies in patients with locally advanced disease. The recognition that some tumours responded completely to pre-operative chemoradiotherapy, and the selective use of a non-operative policy has led to a quest to further identify those patients and their tumour in whom this approach could be used, irrespective of MRI stage. With no clear patient factors identified, the tumour and its gene expression has become a target for research to identify individual single-nucleotide polymorphisms, which may indicate a response to specific treatment, or not. To date some agents have been identified and trialed, such as cetuximab, with individual tumours being assessed for response allowing directed treatment. The reviewed paper by Sebio and colleagues report a study that links polymorphisms in the DNA repair gene XRCC1 with response to neoadjuvant 5-Fluorouracil treatment in rectal cancer patients. However, genetic heterogeneity alone may not explain the variations of drug response and environmental factors may lead to epigenetic effects and therefore alter responses. Therefore whilst this study demonstrates the impact of different single nucleotide polymorphisms (SNPs), it is only one step forward, but perhaps a step in the right direction. PMID:28149883

  12. Natural killer-like signature observed post therapy in locally advanced rectal cancer is a determinant of pathological response and improved survival.

    PubMed

    Alderdice, Matthew; Dunne, Philip D; Cole, Aidan J; O'Reilly, Paul G; McArt, Darragh G; Bingham, Vicky; Fuchs, Marc-Aurel; McQuaid, Stephen; Loughrey, Maurice B; Murray, Graeme I; Samuel, Leslie M; Lawler, Mark; Wilson, Richard H; Salto-Tellez, Manuel; Coyle, Vicky M

    2017-09-01

    Around 12-15% of patients with locally advanced rectal cancer undergo a pathologically complete response (tumor regression grade 4) to long-course preoperative chemoradiotherapy; the remainder exhibit a spectrum of tumor regression (tumor regression grade 1-3). Understanding therapy-related transcriptional alterations may enable better prediction of response as measured by progression-free and overall survival, in addition to aiding the development of improved strategies based on the underlying biology of the disease. To this end, we performed high-throughput gene expression profiling in 40 pairs of formalin-fixed paraffin-embedded rectal cancer biopsies and matched resections following long-course preoperative chemoradiotherapy (discovery cohort). Differential gene expression analysis was performed contrasting tumor regression grades in resections. Enumeration of the tumor microenvironment cell population was undertaken using in silico analysis of the transcriptional data, and real-time PCR validation of NCR1 undertaken. Immunohistochemistry and survival analysis was used to measure CD56+ cell populations in an independent cohort (n=150). Gene expression traits observed following long-course preoperative chemoradiotherapy in the discovery cohort suggested an increased abundance of natural killer cells in tumors that displayed a clinical response to CRT in a tumor regression grade-dependent manner. CD56+ natural killer-cell populations were measured by immunohistochemistry and found to be significantly higher in tumor regression grade 3 patients compared with tumor regression grade 1-2 in the validation cohort. Furthermore, it was observed that patients positive for CD56 cells after therapy had a better overall survival (HR=0.282, 95% CI=0.109-0.729, χ(2)=7.854, P=0.005). In conclusion, we have identified a novel post-therapeutic natural killer-like transcription signature in patients responding to long-course preoperative chemoradiotherapy. Furthermore, patients

  13. Prognosis of locally advanced rectal cancer can be predicted more accurately using pre- and post-chemoradiotherapy neutrophil-lymphocyte ratios in patients who received preoperative chemoradiotherapy

    PubMed Central

    Sung, SooYoon; Park, Eun Young; Kay, Chul Seung

    2017-01-01

    Purpose The neutrophil-lymphocyte ratio (NLR) has been suggested as an inflammation-related factor, but also as an indicator of systemic anti-tumor immunity. We aimed to evaluate the prognostic value of the NLR and to propose a proper cut-off value in patients with locally advanced rectal cancer who received preoperative chemoradiation (CRT) followed by curative total mesorectal excision (TME). Methods A total of 110 rectal cancer patients with clinical T3-4 or node-positive disease were retrospectively analyzed. The NLR value before preoperative CRT (pre-CRT NLR) and the NLR value between preoperative CRT and surgery (post-CRT NLR) were obtained. Using a maximally selected log-rank test, cut-off values were determined as 1.75 for the pre-CRT NLR and 5.14 for the post-CRT NLR. Results Patients were grouped as follows: group A, pre-CRT NLR ≤ 1.75 and post-CRT NLR ≤ 5.14 (n = 29); group B, pre-CRT NLR > 1.75 and post-CRT NLR ≤ 5.14, or pre-CRT NLR ≤ 1.75 and post-CRT NLR > 5.14 (n = 61); group C, pre-CRT NLR > 1.75 and post-CRT NLR > 5.14 (n = 20). The median follow-up time was 31.1 months. The 3-year disease-free survival (DFS) and overall survival (OS) rates showed significant differences between the NLR groups (3-year DFS rate: 92.7% vs. 73.0% vs. 47.3%, for group A, B, and C, respectively, p = 0.018; 3-year OS rate: 96.0% vs. 85.5% vs. 59.8%, p = 0.034). Multivariate analysis revealed that the NLR was an independent prognostic factor for DFS (p = 0.028). Conclusion Both the pre-CRT NLR and the post-CRT NLR have a predictive value for the prognosis of patients with locally advanced rectal cancer treated with preoperative CRT followed by curative TME and adjuvant chemotherapy. A persistently elevated post-CRT NLR may be an indicator of an increased risk of distant metastasis. PMID:28291841

  14. [A case of neoadjuvant chemotherapy for locally advanced rectal cancer, which had a invasion into the vagina followed by curative resection].

    PubMed

    Kimura, Kei; Kagawa, Yoshinori; Kato, Takeshi; Ishida, Tomo; Morimoto, Yoshihiro; Matusita, Katsunori; Kusama, Hiroki; Hashimoto, Tadayoshi; Katura, Yoshiteru; Nitta, Kanae; Takeno, Atushi; Nakahira, Shin; Okishiro, Masatsugu; Sakisaka, Hideki; Taniguchi, Hirokazu; Egawa, Chiyomi; Takeda, Yutaka; Tamura, Shigeyuki

    2014-11-01

    A-64-years-old woman with locally advanced rectal cancer, which had invaded the vagina, was referred to our hospital. She was administered neoadjuvant chemotherapy to reduce the tumor size. After 4 courses of chemotherapy consisting of folinic acid, fluorouracil, and oxaliplatin (mFOLFOX6), an enhanced computed tomography (CT) scan and magnetic resonance imaging (MRI) indicated marked tumor shrinkage. We performed a laparoscopically assisted low anterior resection, which included total mesorectal resection, resection of the vaginal posterior wall, and right lateral lymph node resection. The chemotherapy prevented us from having to create a permanent colostomy. The efficacy of the neoadjuvant chemotherapy was Grade 1b. We experienced a case of neoadjuvant chemotherapy followed by curative resection.

  15. Voiding Dysfunction after Total Mesorectal Excision in Rectal Cancer

    PubMed Central

    Kim, Jae Heon; Noh, Tae Il; Oh, Mi Mi; Park, Jae Young; Lee, Jeong Gu; Um, Jun Won; Min, Byung Wook

    2011-01-01

    Purpose The aim of this study was to assess the voiding dysfunction after rectal cancer surgery with total mesorectal excision (TME). Methods This was part of a prospective study done in the rectal cancer patients who underwent surgery with TME between November 2006 and June 2008. Consecutive uroflowmetry, post-voided residual volume, and a voiding questionnaire were performed at preoperatively and postoperatively. Results A total of 50 patients were recruited in this study, including 28 male and 22 female. In the comparison of the preoperative data with the postoperative 3-month data, a significant decrease in mean maximal flow rate, voided volume, and post-voided residual volume were found. In the comparison with the postoperative 6-month data, however only the maximal flow rate was decreased with statistical significance (P=0.02). In the comparison between surgical methods, abdominoperineal resection patients showed delayed recovery of maximal flow rate, voided volume, and post-voided residual volume. There was no significant difference in uroflowmetry parameters with advances in rectal cancer stage. Conclusions Voiding dysfunction is common after rectal cancer surgery but can be recovered in 6 months after surgery or earlier. Abdominoperineal resection was shown to be an unfavorable factor for postoperative voiding. Larger prospective study is needed to determine the long-term effect of rectal cancer surgery in relation to male and female baseline voiding condition. PMID:22087426

  16. Social isolation and cancer management - advanced rectal cancer with patient delay following the 2011 triple disaster in Fukushima, Japan: a case report.

    PubMed

    Ozaki, Akihiko; Leppold, Claire; Sawano, Toyoaki; Tsubokura, Masaharu; Tsukada, Manabu; Tanimoto, Tetsuya; Kami, Masahiro; Ohira, Hiromichi

    2017-05-16

    Little is known about the effects of social isolation in the elderly on their process of gaining health information and seeking health care. In March 2011, Fukushima, Japan experienced an earthquake, tsunami, and nuclear disaster, also known as Japan's triple disaster. In June 2016, an 80-year-old Japanese man, who lived alone after divorce at the age of 42, presented to our hospital with bloody stools and dizziness. Although his bloody stools initially occurred in May 2015, a year earlier, he did not pursue the possibility of malignancy. He was diagnosed as having stage IIIA rectal cancer. Detailed history taking revealed that he experienced social isolation after the disaster, due to the evacuation of his friends, losing his regular opportunities for socialization. He additionally reported that the current diagnosis of rectal cancer made him feel he had lost his health in addition to his social relationships. Although radical surgery was attempted, it failed to resect the lesion completely, and thereafter his disease gradually progressed. As support from family or friends was not available, he was not able to receive palliative radiation therapy or home-based care in his end-of-life period. He died at a long-term care facility in February 2017. This case suggests that intense social isolation after the Fukushima disaster was a likely contributor to the patient delay, poor treatment course, and poor outcome of an elderly patient with rectal cancer. Direct communication with family and friends may play an indispensable role in increasing health awareness and promoting health-seeking behaviors, and in the midst of social isolation, elderly patients with cancer may lose these opportunities and experience increased risk of patient delay. Although health care providers may be able to alleviate isolation-induced delay by promoting cancer knowledge and awareness widely among local residents, policy-led interventions at the community level may be essential to reducing

  17. Transanal endoscopic surgery in rectal cancer.

    PubMed

    Serra-Aracil, Xavier; Mora-Lopez, Laura; Alcantara-Moral, Manel; Caro-Tarrago, Aleidis; Gomez-Diaz, Carlos Javier; Navarro-Soto, Salvador

    2014-09-07

    Total mesorectal excision (TME) is the standard treatment for rectal cancer, but complications are frequent and rates of morbidity, mortality and genitourinary alterations are high. Transanal endoscopic microsurgery (TEM) allows preservation of the anal sphincters and, via its vision system through a rectoscope, allows access to rectal tumors located as far as 20 cm from the anal verge. The capacity of local surgery to cure rectal cancer depends on the risk of lymph node invasion. This means that correct preoperative staging of the rectal tumor is necessary. Currently, local surgery is indicated for rectal adenomas and adenocarcinomas invading the submucosa, but not beyond (T1). Here we describe the standard technique for TEM, the different types of equipment used, and the technical limitations of this approach. TEM to remove rectal adenoma should be performed in the same way as if the lesion were an adenocarcinoma, due to the high percentage of infiltrating adenocarcinomas in these lesions. In spite of the generally good results with T1, some authors have published surprisingly high recurrence rates; this is due to the existence of two types of lesions, tumors with good and poor prognosis, divided according to histological and surgical factors. The standard treatment for rectal adenocarcinoma T2N0M0 is TME without adjuvant therapy. In this type of adenocarcinoma, local surgery obtains the best results when complete pathological response has been achieved with previous chemoradiotherapy. The results with chemoradiotherapy and TEM are encouraging, but the scientific evidence remains limited at present.

  18. Surgical outcomes of post chemoradiotherapy unresectable locally advanced rectal cancers improve with interim chemotherapy, is FOLFIRINOX better than CAPOX?

    PubMed Central

    Engineer, Reena; Ramaswamy, Anant; Sahu, Arvind; Zanwar, Saurabh; Arya, Suprita; Chopra, Supriya; Bal, Munita; Patil, Prachi; Desouza, Ashwin; Saklani, Avanish

    2016-01-01

    Background Role of chemotherapy in patients who continue to have unresectable disease after pre-operative chemo-radiotherapy (CRT) remains largely unaddressed. Methods Patients with LA rectal cancer from January 2013 to June 2015 were evaluated. Post-CRT, patients, who were deemed unresectable, were considered for further interim chemotherapy (i-CT). Results Seventy six patients (15%) with median age of 38.5 years received i-CT after CRT. About 61.8% patients receiving i-CT managed to undergo a definitive surgery and the extent of surgery was reduced in 48.7% patients. With the median follow up of 19 months, the estimated 2-year event free survival (EFS) of 48% and OS was 56%. The estimated 2-year OS was 81% in mucinous tumors whereas it was 44.4% in signet ring pathology (P=0.045). The 2-year OS of 86% for whom surgery was done vs. 38% (2-year OS) in whom surgery was not done (P=0.011). Survival was better in conservative surgery group vs. total pelvic exenteration (TPE) vs. no surgery (2-year OS: 84% vs. 59.1% vs. 38%; P=0.033). In the CAPE-OX group, 71.4% (14/23) underwent surgery whereas 75.9% (29/47) in the 5-FU plus irinotecan plus oxaliplatin (FOLFIRINOX) group with EFS (P=0.570) and OS (P=0.120). In conservative surgery group, OS was better in FOLFIRINOX (2-year OS: 95.7%) vs. capecitabine plus oxaliplatin (CAPOX) (2-year OS: 70%) (P=0.012). Conclusions i-CT can lead to improved resection rates, improved survivals and downstaging with acceptable toxicity. FOLFIRINOX appears to better over CAPOX, specifically in whom conservative surgery is feasible. PMID:28078119

  19. Significance of Magnetic Resonance Imaging–Assessed Tumor Response for Locally Advanced Rectal Cancer Treated With Preoperative Long-Course Chemoradiation

    PubMed Central

    Fayaz, Mohamed Salah; Demian, Gerges Attia; Fathallah, Wael Moftah; Eissa, Heba El-Sayed; Abozlouf, Sadeq; George, Thomas; Samir, Suzanne Mona

    2016-01-01

    Purpose To study the predictive and prognostic value of magnetic resonance imaging (MRI)–assessed tumor response after long-course neoadjuvant therapy for locally advanced rectal cancer. Methods This study included 79 patients who had T3 or T4 and/or N+ rectal cancer treated with long-course neoadjuvant chemoradiation. MRI-assessed tumor regression grade (mrTRG) was assessed in 64 patients. MRIs were reviewed by the study radiologist. Surgical and pathologic reports for those who underwent surgery were reviewed. Disease-free survival (DFS) was estimated. Progression during therapy, local relapse, metastasis, and death resulting from the tumor were classified as events. Statistical significance was calculated. Results In 11 patients, the tumor completely disappeared on MRI; that is, it had an mrTRG of 1. All but one patient, who chose deferred surgery, had a complete pathologic response (pCR), with a positive predictive value of nearly 100%. Of the 20 patients who had an mrTRG of 2 on MRI, six had a pCR. mrTRG 3, mrTRG 4, and mrTRG 5 were detected in 24, six, and three patients, respectively, of whom only one patient had a pCR. The 2-year DFS was 77%. The mrTRG was significant for DFS. The 2-year DFS was 88% for patients with a good response versus 66% for those with a poor response (P = .046). Conclusion MRI-assessed complete tumor response was strongly correlated with pCR and, therefore, can be used as a surrogate marker to predict absence of viable tumor cells. Our results can be used to implement use of mrTRGs in larger prospective correlative studies as a tool to select patients for whom deferred surgery may be appropriate. Also, those with a poor response may be offered further treatment options before definitive surgery. PMID:28717704

  20. Significance of Magnetic Resonance Imaging-Assessed Tumor Response for Locally Advanced Rectal Cancer Treated With Preoperative Long-Course Chemoradiation.

    PubMed

    Fayaz, Mohamed Salah; Demian, Gerges Attia; Fathallah, Wael Moftah; Eissa, Heba El-Sayed; El-Sherify, Mustafa Shawki; Abozlouf, Sadeq; George, Thomas; Samir, Suzanne Mona

    2016-08-01

    To study the predictive and prognostic value of magnetic resonance imaging (MRI)-assessed tumor response after long-course neoadjuvant therapy for locally advanced rectal cancer. This study included 79 patients who had T3 or T4 and/or N+ rectal cancer treated with long-course neoadjuvant chemoradiation. MRI-assessed tumor regression grade (mrTRG) was assessed in 64 patients. MRIs were reviewed by the study radiologist. Surgical and pathologic reports for those who underwent surgery were reviewed. Disease-free survival (DFS) was estimated. Progression during therapy, local relapse, metastasis, and death resulting from the tumor were classified as events. Statistical significance was calculated. In 11 patients, the tumor completely disappeared on MRI; that is, it had an mrTRG of 1. All but one patient, who chose deferred surgery, had a complete pathologic response (pCR), with a positive predictive value of nearly 100%. Of the 20 patients who had an mrTRG of 2 on MRI, six had a pCR. mrTRG 3, mrTRG 4, and mrTRG 5 were detected in 24, six, and three patients, respectively, of whom only one patient had a pCR. The 2-year DFS was 77%. The mrTRG was significant for DFS. The 2-year DFS was 88% for patients with a good response versus 66% for those with a poor response (P = .046). MRI-assessed complete tumor response was strongly correlated with pCR and, therefore, can be used as a surrogate marker to predict absence of viable tumor cells. Our results can be used to implement use of mrTRGs in larger prospective correlative studies as a tool to select patients for whom deferred surgery may be appropriate. Also, those with a poor response may be offered further treatment options before definitive surgery.

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

    SciTech Connect

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

    2012-06-01

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

  2. [Rectal cancer: diagnosis, screening and treatment].

    PubMed

    Decanini-Terán, César Oscar; González-Acosta, Jorge; Obregón-Méndez, Jorge; Vega-de Jesús, Martín

    2011-01-01

    Rectal cancer is one of the primary malignant neoplasms occurring in Mexican patients of reproductive age. Unfortunately, randomized studies in rectal cancer do not exist as they do with well-recognized colon cancer. We must individualize the epidemiology, risk factors, diagnostic approach, staging and treatment because management is different in rectal cancers affecting the mid- and lower third of the rectum than in the upper third and in colon cancers. Histological staging is the primary prognostic factor. TNM staging (tumor, node, and metastasis) is used internationally by the American Joint Committee on Cancer (AJCC). Staging is done with the assistance of endorectal ultrasound, which is best used in early-stage cancer; however, there are certain disadvantages in detecting node involvement. Magnetic resonance, on the other hand, allows for the evaluation of stenotic tumors and node involvement. Once the correct diagnosis and staging have been made, the next step is correct treatment. Neoadjuvant treatment has demonstrated to be better than adjuvant treatment. Abdominoperineal resection is rarely practiced currently, with sphincter preservation being the preferred procedure. Laparoscopic approach has conferred the advantages of the approach itself when performed by experts in the procedure but there is insufficient evidence to make it the "gold standard." Rectal cancer is a complex pathology that must be considered totally different from colon cancer for diagnosis and treatment. The patient must be staged completely and appropriately for individualizing correct treatment. More long-term studies are needed for optimizing treatment modalities.

  3. The value of forceps biopsy and core needle biopsy in prediction of pathologic complete remission in locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy.

    PubMed

    Tang, Jing-Hua; An, Xin; Lin, Xi; Gao, Yuan-Hong; Liu, Guo-Chen; Kong, Ling-Heng; Pan, Zhi-Zhong; Ding, Pei-Rong

    2015-10-20

    Patients with pathological complete remission (pCR) after treated with neoadjuvant chemoradiotherapy (nCRT) have better long-term outcome and may receive conservative treatments in locally advanced rectal cancer (LARC). The study aimed to evaluate the value of forceps biopsy and core needle biopsy in prediction of pCR in LARC treated with nCRT. In total, 120 patients entered this study. Sixty-one consecutive patients received preoperative forceps biopsy during endoscopic examination. Ex vivo core needle biopsy was performed in resected specimens of another 43 consecutive patients. The accuracy for ex vivo core needle biopsy was significantly higher than forceps biopsy (76.7% vs. 36.1%; p < 0.001). The sensitivity for ex vivo core needle biopsy was significantly lower in good responder (TRG 3) than poor responder (TRG ≤ 2) (52.9% vs. 94.1%; p = 0.017). In vivo core needle biopsy was further performed in 16 patients with good response. Eleven patients had residual cancer cells in final resected specimens, among whom 4 (36.4%) patients were biopsy positive. In conclusion, routine forceps biopsy was of limited value in identifying pCR after nCRT. Although core needle biopsy might further identify a subset of patients with residual cancer cells, the accuracy was not substantially increased in good responders.

  4. Incidence and risk factors for rectal pain after laparoscopic rectal cancer surgery

    PubMed Central

    Lee, Jin Young; Kim, Hee Cheol; Huh, Jung Wook; Lim, Hyun Young; Lee, Eun Kyung; Park, Hui Gyeong; Bang, Yu Jeong

    2017-01-01

    Objective This study was performed to investigate the incidence of and potential risk factors for rectal pain after laparoscopic rectal cancer surgery. Methods We retrospectively analyzed data from 300 patients who underwent laparoscopic rectal cancer surgery. We assessed the presence of rectal pain and categorized patients into Group N (no rectal pain) or Group P (rectal pain). Results In total, 288 patients were included. Of these patients, 39 (13.5%) reported rectal pain and 14 (4.9%) had rectal pain that persisted for >3 months. Univariate analysis revealed that patients in Group P had more preoperative chemoradiotherapy, more ileostomies, longer operation times, more anastomotic margins of <2 cm from the anal verge, more anastomotic leakage, and longer hospital stays. Multivariate analysis identified an anastomotic margin of <2 cm from the anal verge and a long operation time as risk factors. The presence of diabetes mellitus was a negative predictor of rectal pain. Conclusions In this study, the incidence of rectal pain after laparoscopic rectal cancer surgery was 13.5%. An anastomotic margin of <2 cm from the anal verge and a long operation time were risk factors for rectal pain. The presence of diabetes mellitus was a negative predictor of rectal pain. Thus, the possibility of postoperative rectal pain should be discussed preoperatively with patients with these risk factors. PMID:28415928

  5. Preoperative staging of rectal cancer.

    PubMed

    Smith, Neil; Brown, Gina

    2008-01-01

    Detailed preoperative staging using high resolution magnetic resonance imaging (MRI) enables the selection of patients that require preoperative therapy for tumour regression. This information can be used to instigate neoadjuvant therapy in those patients with poor prognostic features prior to disturbing the tumour bed and potentially disseminating disease. The design of trials incorporating MR assessment of prognostic factors prior to therapy has been found to be of value in assessing treatment modalities and outcomes that are targeted to these preoperative prognostic subgroups and in providing a quantifiable assessment of the efficacy of particular chemoradiation treatment protocols by comparing pre-treatment MR staging with post therapy histology assessment. At present, we are focused on achieving clear surgical margins of excision (CRM) to avoid local recurrence. We recommend that all patients with rectal cancer should undergo pre-operative MRI staging. Of these, about half will have good prognosis features (T1-T3b, N0, EMVI negative, CRM clear) and may safely undergo primary total mesorectal excision. Of the remainder, those with threatened or involved margins will certainly benefit from pre-operative chemoradiotherapy with the aim of downstaging to permit safe surgical excision. In the future, our ability to recognise features predicting distant failure, such as extramural vascular invasion (EMVI) may be used to stratify patients for neo-adjuvant systemic chemotherapy in an effort to prevent distant relapse. The optimal pre-operative treatment regimes for these patients (radiotherapy alone, systemic chemotherapy alone or combination chemo-radiotherapy) is the subject of current and future trials.

  6. [Quality radiotherapy in rectal cancer].

    PubMed

    Capirci, C; Amichetti, M; De Renzis, C

    2001-01-01

    The quality of radiotherapy significantly impacts on the results of treatment, in patients with rectal carcinoma, especially in terms of acute and late toxicity. Based on this assumption, the Italian Association of Radiation Oncology (AIRO) formulated a document aimed to define the standards of radiation treatment for rectal carcinomas. Two different levels of standard were described: a first level, considered as "minimal requirement", and a second level, considered as "optimal treatment". A retrospective evaluation, based on a questionnaire, revealed that in 1996, in most Italian Centers, patients affected by rectal carcinoma received radiation treatment within the first level of proposed standards. A subsequent analysis concerned the evaluation of the level of treatments applied in 2000. In this paper the radiotherapy standards proposed by the AIRO are described in the different phases of the radiation treatment.

  7. Intraoperative Radiation Therapy Reduces Local Recurrence Rates in Patients With Microscopically Involved Circumferential Resection Margins After Resection of Locally Advanced Rectal Cancer

    SciTech Connect

    Alberda, Wijnand J.; Verhoef, Cornelis; Nuyttens, Joost J.; Meerten, Esther van; Rothbarth, Joost; Wilt, Johannes H.W. de; Burger, Jacobus W.A.

    2014-04-01

    Purpose: Intraoperative radiation therapy (IORT) is advocated by some for patients with locally advanced rectal cancer (LARC) who have involved or narrow circumferential resection margins (CRM) after rectal surgery. This study evaluates the potentially beneficial effect of IORT on local control. Methods and Materials: All surgically treated patients with LARC treated in a tertiary referral center between 1996 and 2012 were analyzed retrospectively. The outcome in patients treated with IORT with a clear but narrow CRM (≤2 mm) or a microscopically involved CRM was compared with the outcome in patients who were not treated with IORT. Results: A total of 409 patients underwent resection of LARC, and 95 patients (23%) had a CRM ≤ 2 mm. Four patients were excluded from further analysis because of a macroscopically involved resection margin. In 43 patients with clear but narrow CRMs, there was no difference in the cumulative 5-year local recurrence-free survival of patients treated with (n=21) or without (n=22) IORT (70% vs 79%, P=.63). In 48 patients with a microscopically involved CRM, there was a significant difference in the cumulative 5-year local recurrence-free survival in favor of the patients treated with IORT (n=31) compared with patients treated without IORT (n=17) (84 vs 41%, P=.01). Multivariable analysis confirmed that IORT was independently associated with a decreased local recurrence rate (hazard ratio 0.24, 95% confidence interval 0.07-0.86). There was no significant difference in complication rate of patients treated with or without IORT (65% vs 52%, P=.18) Conclusion: The current study suggests that IORT reduces local recurrence rates in patients with LARC with a microscopically involved CRM.

  8. Combination of three-gene immunohistochemical panel and magnetic resonance imaging-detected extramural vascular invasion to assess prognosis in non-advanced rectal cancer patients

    PubMed Central

    Li, Xiao-Fu; Jiang, Zheng; Gao, Ying; Li, Chun-Xiang; Shen, Bao-Zhong

    2016-01-01

    AIM To identify a small, clinically applicable immunohistochemistry (IHC) panel that could be combined with magnetic resonance imaging (MRI)-detected extramural vascular invasion (EMVI) for assessment of prognosis concerning the non-advanced rectal cancer patients prior to operation. METHODS About 329 patients with pathologically confirmed rectal carcinoma (RC) were screened in this research, all of whom had been examined via an MRI and were treatment-naïve from July 2011 to July 2014. The candidate proteins that were reported to be altered by RC were examined in tissues by IHC. All chosen samples were adopted from the fundamental cores of histopathologically confirmed carcinomas during the initial surgeries. RESULTS Of the three proteins that were tested, c-MYC, PCNA and TIMP1 were detected with relatively significant expression in tumors, 35.9%, 23.7% and 58.7% respectively. The expression of the three proteins were closely connected with prognosis (P = 0.032, 0.003, 0.021). The patients could be classified into different outcome groups according to an IHC panel (P < 0.01) via these three proteins. Taking into consideration known survival covariates, especially EMVI, the IHC panel served as an independent prognostic factor. The EMVI combined with the IHC panel could categorize patients into different prognostic groups with distinction (P < 0.01). CONCLUSION These studies argue that this three-protein panel of c-MYC, PCNA, coupled with TIMP1 combined with MRI-detected EMVI could offer extra prognostic details for preoperative treatment of RC. PMID:27784970

  9. Correlation between tumor regression grade and rectal volume in neoadjuvant concurrent chemoradiotherapy for rectal cancer

    PubMed Central

    Lee, Hong Seok; Choi, Doo Ho; Park, Hee Chul; Park, Won; Yu, Jeong Il; Chung, Kwangzoo

    2016-01-01

    Purpose To determine whether large rectal volume on planning computed tomography (CT) results in lower tumor regression grade (TRG) after neoadjuvant concurrent chemoradiotherapy (CCRT) in rectal cancer patients. Materials and Methods We reviewed medical records of 113 patients treated with surgery following neoadjuvant CCRT for rectal cancer between January and December 2012. Rectal volume was contoured on axial images in which gross tumor volume was included. Average axial rectal area (ARA) was defined as rectal volume divided by longitudinal tumor length. The impact of rectal volume and ARA on TRG was assessed. Results Average rectal volume and ARA were 11.3 mL and 2.9 cm². After completion of neoadjuvant CCRT in 113 patients, pathologic results revealed total regression (TRG 4) in 28 patients (25%), good regression (TRG 3) in 25 patients (22%), moderate regression (TRG 2) in 34 patients (30%), minor regression (TRG 1) in 24 patients (21%), and no regression (TRG0) in 2 patients (2%). No difference of rectal volume and ARA was found between each TRG groups. Linear correlation existed between rectal volume and TRG (p = 0.036) but not between ARA and TRG (p = 0.058). Conclusion Rectal volume on planning CT has no significance on TRG in patients receiving neoadjuvant CCRT for rectal cancer. These results indicate that maintaining minimal rectal volume before each treatment may not be necessary. PMID:27592514

  10. Transanal Approach to Rectal Polyps and Cancer

    PubMed Central

    Rai, Vinay; Mishra, Nitin

    2016-01-01

    A transanal approach to rectal polyp and cancer excision is often an appropriate alternative to conventional rectal resection, and has a lower associated morbidity. There has been a steady evolution in the techniques of transanal surgery over the past 30 years. It started with traditional transanal excision and was revolutionized by introduction of transanal endoscopic microsurgery in early 1980s. Introduction of transanal minimally invasive surgery made it more accessible to surgeons around the world. Now robotic platforms are being tried in certain institutions. Concerns have been raised about recurrence rates of cancers with transanal approach and success of subsequent salvage operations. PMID:26929754

  11. [Adjuvant chemotherapy for patients with rectal cancer].

    PubMed

    Qvortrup, Camilla; Mortensen, John Pløen; Pfeiffer, Per

    2013-09-09

    A new Cochrane meta-analysis evaluated adjuvant chemotherapy (5-fluorouracil (5FU)-based, not modern combination chemotherapy) in almost 10,000 patients with rectal cancer and showed a 17% reduction in mortality corresponding well to the efficacy observed in recent studies, which reported a reduction in mortality just about 20%. The authors recommend adjuvant chemotherapy which is in accordance with the Danish national guidelines where 5-FU-based chemotherapy is recommended for stage III and high-risk stage II rectal cancer.

  12. The curative management of synchronous rectal and prostate cancer

    PubMed Central

    Kavanagh, Dara O; Martin, Joseph; Small, Cormac; Joyce, Myles R; Faul, Clare M; Kelly, Paul J; O'Riordain, Michael; Gillham, Charles M; Armstrong, John G; Salib, Osama; McNamara, Deborah A; McVey, Gerard; O'Neill, Brian D P

    2016-01-01

    Objective: Neoadjuvant “long-course” chemoradiation is considered a standard of care in locally advanced rectal cancer. In addition to prostatectomy, external beam radiotherapy and brachytherapy with or without androgen suppression (AS) are well established in prostate cancer management. A retrospective review of ten cases was completed to explore the feasibility and safety of applying these standards in patients with dual pathology. To our knowledge, this is the largest case series of synchronous rectal and prostate cancers treated with curative intent. Methods: Eligible patients had synchronous histologically proven locally advanced rectal cancer (defined as cT3-4Nx; cTxN1-2) and non-metastatic prostate cancer (pelvic nodal disease permissible). Curative treatment was delivered to both sites simultaneously. Follow-up was as per institutional guidelines. Acute and late toxicities were reviewed, and a literature search performed. Results: Pelvic external beam radiotherapy (RT) 45–50.4 Gy was delivered concurrent with 5-fluorouracil (5FU). Prostate total dose ranged from 70.0 to 79.2 Gy. No acute toxicities occurred, excluding AS-induced erectile dysfunction. Nine patients proceeded to surgery, and one was managed expectantly. Three relapsed with metastatic colorectal cancer, two with metastatic prostate cancer. Five patients have no evidence of recurrence, and four remain alive with metastatic disease. With a median follow-up of 2.2 years (range 1.2–6.3 years), two significant late toxicities occurred; G3 proctitis in a patient receiving palliative bevacizumab and a G3 anastomotic stricture precluding stoma reversal. Conclusion: Patients proceeding to synchronous radical treatment of both primary sites should receive 45–50.4 Gy pelvic RT with infusional 5FU. Prostate dose escalation should be given with due consideration to the potential impact of prostate cancer on patient survival, as increasing dose may result in significant late morbidity

  13. Comparison of Adjuvant Chemotherapy Regimens in Treating Patients With Stage II or Stage III Rectal Cancer Who Are Receiving Radiation Therapy and Fluorouracil Before or After Surgery

    ClinicalTrials.gov

    2013-02-26

    Mucinous Adenocarcinoma of the Rectum; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Rectum; Stage IIA Rectal Cancer; Stage IIB Rectal Cancer; Stage IIC Rectal Cancer; Stage IIIA Rectal Cancer; Stage IIIB Rectal Cancer; Stage IIIC Rectal Cancer; Stage IVA Rectal Cancer; Stage IVB Rectal Cancer

  14. Rectal dose to prostate cancer patients treated with proton therapy with or without rectal spacer.

    PubMed

    Chung, Heeteak; Polf, Jerimy; Badiyan, Shahed; Biagioli, Matthew; Fernandez, Daniel; Latifi, Kujtim; Wilder, Richard; Mehta, Minesh; Chuong, Michael

    2017-01-01

    The purpose of this study was to evaluate whether a spacer inserted in the prerectal space could reduce modeled rectal dose and toxicity rates for patients with prostate cancer treated in silico with pencil beam scanning (PBS) proton therapy. A total of 20 patients were included in this study who received photon therapy (12 with rectal spacer (DuraSeal™ gel) and 8 without). Two PBS treatment plans were retrospectively created for each patient using the following beam arrangements: (1) lateral-opposed (LAT) fields and (2) left and right anterior oblique (LAO/RAO) fields. Dose volume histograms (DVH) were generated for the prostate, rectum, bladder, and right and left femoral heads. The normal tissue complication probability (NTCP) for ≥grade 2 rectal toxicity was calculated using the Lyman-Kutcher-Burman model and compared between patients with and without the rectal spacer. A significantly lower mean rectal DVH was achieved in patients with rectal spacer compared to those without. For LAT plans, the mean rectal V70 with and without rectal spacer was 4.19 and 13.5%, respectively. For LAO/RAO plans, the mean rectal V70 with and without rectal spacer was 5.07 and 13.5%, respectively. No significant differences were found in any rectal dosimetric parameters between the LAT and the LAO/RAO plans generated with the rectal spacers. We found that ≥ 9 mm space resulted in a significant decrease in NTCP modeled for ≥grade 2 rectal toxicity. Rectal spacers can significantly decrease modeled rectal dose and predicted ≥grade 2 rectal toxicity in prostate cancer patients treated in silico with PBS. A minimum of 9 mm separation between the prostate and anterior rectal wall yields the largest benefit.

  15. Neoadjuvant Treatment With Single-Agent Cetuximab Followed by 5-FU, Cetuximab, and Pelvic Radiotherapy: A Phase II Study in Locally Advanced Rectal Cancer

    SciTech Connect

    Bertolini, Federica Chiara, Silvana; Bengala, Carmelo; Antognoni, Paolo; Dealis, Cristina; Zironi, Sandra; Malavasi, Norma; Scolaro, Tindaro; Depenni, Roberta; Jovic, Gordana; Sonaglio, Claudia; Rossi, Aldo; Luppi, Gabriele; Conte, Pier Franco

    2009-02-01

    Purpose: Preoperative chemoradiotherapy followed by surgery represents the standard of care for locally advanced rectal cancer (LARC). Cetuximab has proved activity in advanced colorectal cancer, and its incorporation in preoperative treatment may increase tumor downstaging. Methods and Materials: After biopsy and staging, uT3/uT4 N0/+ LARC received single-agent cetuximab in three doses, followed by weekly cetuximab plus 5-fluorouracil (5-FU), concomitantly with RT. Sample size was calculated according to Bryant and Day test, a two-stage design with at least 10 pathologic complete remissions observed in 60 patients (pts) able to complete the treatment plan. Results: Forty pts with LARC were entered: male/female = 34/6; median age: 61 (range, 28-77); 12 uT3N0 Ed(30%); 25 uT3N1 (62%); 3 uT4N1 (8%); all Eastern Cooperative Oncology Group = 0. Thirty-five pts completed neoadjuvant treatment; 5 (12%) withdrew therapy after one cetuximab administration: three for hypersensitivity reactions, one for rapid progression, and one for purulent arthritis. They continued 5-FU in continuous infusion in association with RT. Thirty-one pts (77%) presented with acnelike rash; dose reduction/interruption of treatment was necessary in six pts (15%): two for Grade 3 acnelike rash, two for Grade 3 gastrointestinal toxicity, and two for refusal. Thirty-eight pts were evaluable for pathological response (one patient refused surgery, and one was progressed during neoadjuvant treatment). Pathological staging was: pT0N0 three pts (8%), pT1N0 1 pt (3%); pT2N0 13 pts (34%), and pT3 19 pts (50%) (N0:9, N1:5; N2:5); pT4 2 pts (5%). Conclusions: Preoperative treatment with 5-FU, cetuximab, and pelvic RT is feasible with acceptable toxicities; however, the rate of pathologic responses is disappointingly low.

  16. Phase I Trial of Preoperative Hypofractionated Intensity-Modulated Radiotherapy with Incorporated Boost and Oral Capecitabine in Locally Advanced Rectal Cancer

    SciTech Connect

    Freedman, Gary M. . E-mail: G_Freedman@FCCC.edu; Meropol, Neal J.; Sigurdson, Elin R.; Hoffman, John; Callahan, Elaine; Price, Robert; Cheng, Jonathan; Cohen, Steve; Lewis, Nancy; Watkins-Bruner, Deborah; Rogatko, Andre; Konski, Andre

    2007-04-01

    Purpose: To determine the safety and efficacy of preoperative hypofractionated radiotherapy using intensity-modulated radiotherapy (IMRT) and an incorporated boost with concurrent capecitabine in patients with locally advanced rectal cancer. Methods and Materials: The eligibility criteria included adenocarcinoma of the rectum, T3-T4 and/or N1-N2 disease, performance status 0 or 1, and age {>=}18 years. Photon IMRT and an incorporated boost were used to treat the whole pelvis to 45 Gy and the gross tumor volume plus 2 cm to 55 Gy in 25 treatments within 5 weeks. The study was designed to escalate the dose to the gross tumor volume in 5-Gy increments in 3-patient cohorts. Capecitabine was given orally 825 mg/m{sup 2} twice daily for 7 days each week during RT. The primary endpoint was the maximal tolerated radiation dose, and the secondary endpoints were the pathologic response and quality of life. Results: Eight patients completed RT at the initial dose level of 55 Gy. The study was discontinued because of toxicity-six Grade 3 toxicities occurred in 3 (38%) of 8 patients. All patients went on to definitive surgical resection, and no patient had a pathologically complete response. Conclusion: This regimen, using hypofractionated RT with an incorporated boost, had unacceptable toxicity despite using standard doses of capecitabine and IMRT. Additional research is needed to determine whether IMRT is able to reduce the side effects during and after pelvic RT with conventional dose fractionation.

  17. A scoring system basing pathological parameters to predict regional lymph node metastasis after preoperative chemoradiotherapy for locally advanced rectal cancer: implication for local excision

    PubMed Central

    Wang, Xiao-Jie; Chi, Pan; Lin, Hui-Ming; Lu, Xing-Rong; Huang, Ying; Xu, Zong-Bin; Huang, Sheng-Hui; Sun, Yan-Wu; Ye, Dao-Xiong; Yu, Qian

    2016-01-01

    Local excision is an alternative to radical surgery that is indicated in patients with locally advanced rectal cancer (LARC) who have a good response to chemoradiotherapy (CRT). Regional lymph node status is a major uncertainty during local excision of LARC following CRT. We retrospectively reviewed clinicopathologic variables for 244 patients with LARC who were treated at our institute between December 2000 and December 2013 in order to identify independent predictors of regional lymph node metastasis. Multivariate analysis of the training sample demonstrated that histopathologic type, tumor size, and the presence of lymphovascular invasion were significant predictors of regional nodal metastasis. These variables were then incorporated into a scoring system in which the total scores were calculated based on the points assigned for each parameter. The area under the curve in the receiver operating characteristic analysis was 0.750, and the cutoff value for the total score to predict regional nodal metastasis was 7.5. The sensitivity of our system was 73.2% and the specificity was 69.4%. The sensitivity was 77.8% and the specificity was 51.2% when the scoring system was applied to the testing sample. Using this system, we could accurately predict regional nodal metastases in LARC patients following CRT, which may be useful for stratifying patients in clinical trials and selecting potential candidates for organ-sparing surgery following CRT for LARC PMID:27489356

  18. SU-E-T-126: Dosimetric Comparisons of VMAT, IMRT and 3DCRT for Locally Advanced Rectal Cancer with Simultaneous Integrated Boost

    SciTech Connect

    Zhao, J; Wang, J; Zhang, Z; Hu, W

    2014-06-01

    Purpose: The purpose of this study is to compare the dosimetric differences among volumetric modulated arc therapy (VMAT), fixed-field intensity modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) for the preoperative locally advanced rectal cancer (LARC). Methods: Ten LARC patients treated in our department using the simultaneous escalate strategy were retrospectively analyzed in this study. All patients had T3 with N+/− and were treated with IMRT. Two additional VMAT and 3DCRT plans were created for each patient. Both IMRT and VMAT had similar optimization objectives. The prescription was 50Gy to the PTV and 55Gy to the GTV. The target coverage and organs at risk were compared for all the techniques.The paired, two-tailed Wilcoxcon signed-rank test was applied for statistical analysis. Results: IMRT and VMAT plans achieved comparable tumor response except for the conformality index (1.07 vs 1.19 and 1.08 vs 1.03 of IMRT vs VMAT for PTV-G and PTV-C respectively). Compared to VMAT, IMRT showed superior or similar dose sparing in the small bowel, bladder, femoral head. Both IMRT and VMAT had better organs at risk sparing and homogeneity index of PTV-G. Conclusion: All 3DCRT, IMRT and VMAT meet the prescript. The IMRT and VMAT provided comparable dosemitric parameters for target volume. IMRT shows better sparing for small bowel, bladder, femoral heads and normal tissue to 3DCRT and VMAT.

  19. The influence of the treatment response on the impact of resection margin status after preoperative chemoradiotherapy in locally advanced rectal cancer

    PubMed Central

    2013-01-01

    Background Circumferential resection margin (CRM) and distal resection margin (DRM) have different impact on clinical outcomes after preoperative chemoradiotherapy (CRT) followed by surgery. Effect and adequate length of resection margin as well as impact of treatment response after preoperative CRT was evaluated. Methods Total of 403 patients with rectal cancer underwent preoperative CRT followed by total mesorectal excision between January 2004 and December 2010. After applying the criterion of margin less than 0.5 cm for CRM or less than 1 cm for DRM, 151 cases with locally advanced rectal cancer were included as a study cohort. All patients underwent conventionally fractionated radiation with radiation dose over 50 Gy and concurrent chemotherapy with 5-fluorouracil or capecitabine. Postoperative chemotherapy was administered to 142 patients (94.0%). Median follow-up duration was 43.1 months. Results The 5-year overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS) rates, and locoregional control rates (LRC) were 84.5%, 72.8%, 74.2%, and 86.3%, respectively. CRM of 1.5 mm and DRM of 7 mm were cutting points showing maximal difference in a maximally selected rank method. In univariate analysis, CRM of 1.5 mm was significantly related with worse clinical outcomes, whereas DRM of 7 mm was not. In multivariate analysis, CRM of 1.5 mm, and ypN were prognosticators for all studied endpoints. However, CRM was not a significant prognostic factor for good responders, defined as patients with near total regression or T down-staging, which was found in 16.5% and 40.5% among studied patients, respectively. In contrast, poor responders demonstrated a significant difference according to the CRM status for all studied end-points. Conclusions Close CRM, defined as 1.5 mm, was a significant prognosticator, but the impact was only prominent for poor responders in subgroup analysis. Postoperative treatment strategy may be

  20. Preoperative bi-fractionated accelerated radiation therapy for combined treatment of locally advanced rectal cancer in a consectutive series of unselected patients

    PubMed Central

    Biffi, Roberto; Marsiglia, Hugo; Fossa, Barbara Jereczek; Leonardi, Maria Cristina; Cante, Domenico; Lazzari, Roberta; Chiappa, Antonio; Cenciarelli, Sabine; Andreoni, Bruno; Zampino, Maria Giulia; Orecchia, Roberto

    2007-01-01

    preoperative setting to patients bearing locally advanced rectal cancer is reliable and safe, as its immediate and late toxicity (mainly infectious) is acceptably low and long-term survivals are achievable. These findings support the increasing use of preoperative RT for treatment of this malignancy in experienced centres. Ongoing multicentric trials are expected to address still unsolved issues, including the benefit of CT adjunct to preoperative RT. PMID:17883838

  1. Development of the American Society of Colon & Rectal Surgeons (ASCRS) Rectal Cancer Surgery Checklist

    PubMed Central

    Glasgow, Sean C.; Morris, Arden M.; Baxter, Nancy N.; Fleshman, James W.; Alavi, Karim S.; Luchtefeld, Martin A.; Monson, John R. T.; Chang, George J.; Temple, Larissa K.

    2016-01-01

    Background There is excellent evidence that surgical safety checklists contribute to decreased morbidity and mortality. Objective To develop a surgical checklist comprising the key phases of care for rectal cancer patients. Design Consensus-oriented decision-making model involving iterative input from subject matter experts under the auspices of the American Society of Colon and Rectal Surgeons. Results The process generated a 25-item checklist covering the spectrum of care for rectal cancer patients undergoing surgery. Limitations Lack of prospective validation. Conclusions The American Society of Colon and Rectal Surgeons Rectal Cancer Surgery checklist comprises the essential elements of pre-, intra- and postoperative care that must be addressed during the surgical treatment of patients with rectal cancer. PMID:27270511

  2. Clinically relevant study end points in rectal cancer.

    PubMed

    Fernandez-Martos, Carlos; Guerrero, Angel; Minsky, Bruce

    2012-01-01

    In rectal cancer currently there are no clearly validated early end points which can serve as surrogates for long-term clinical outcome such as local control and survival. However, the use of a variety of response rates (i.e. pathological complete response, downsizing the primary tumor, tumor regression grade (TRG), radiological response) as endpoints in early (phase II) clinical trials is common since objective response to therapy is an early indication of activity. Disease-free survival (DFS) has been proposed as the most appropriate end point in adjuvant trials and is one of the most frequently used in newer rectal cancer trials. Due to the devastating nature of local recurrence in locally advanced rectal cancer, local control (which is itself a subset of the overall DFS endpoint) is still considered an important endpoint. Recently, circumferential resection margin (CRM) has been proposed as novel early end point because the CRM status can account for effects on DFS and overall survival after chemoradiation, radiation (RT), or surgery alone. Consensus is needed to define the most appropriate end points in both early and phase III trials in locally advanced cancer.

  3. KRAS and BRAF Mutations and PTEN Expression Do Not Predict Efficacy of Cetuximab-Based Chemoradiotherapy in Locally Advanced Rectal Cancer

    SciTech Connect

    Erben, Philipp; Stroebel, Philipp; Horisberger, Karoline; Popa, Juliana; Bohn, Beatrice; Hanfstein, Benjamin; Kaehler, Georg; Kienle, Peter; Post, Stefan; Wenz, Frederik; Hochhaus, Andreas

    2011-11-15

    Purpose: Mutations in KRAS and BRAF genes as well as the loss of expression of phosphatase and tensin homolog (PTEN) (deleted on chromosome 10) are associated with impaired activity of antibodies directed against epidermal growth factor receptor in patients with metastatic colorectal cancer. The predictive and prognostic value of the KRAS and BRAF point mutations as well as PTEN expression in patients with locally advanced rectal cancer (LARC) treated with cetuximab-based neoadjuvant chemoradiotherapy is unknown. Methods and Materials: We have conducted phase I and II trials of the combination of weekly administration of cetuximab and irinotecan and daily doses of capecitabine in conjunction with radiotherapy (45 Gy plus 5.4 Gy) in patients with LARC (stage uT3/4 or uN+). The status of KRAS and BRAF mutations was determined with direct sequencing, and PTEN expression status was determined with immunohistochemistry testing of diagnostic tumor biopsies. Tumor regression was evaluated by using standardized regression grading, and disease-free survival (DFS) was calculated according to the Kaplan-Meier method. Results: A total of 57 patients were available for analyses. A total of 31.6% of patients carried mutations in the KRAS genes. No BRAF mutations were found, while the loss of PTEN expression was observed in 9.6% of patients. Six patients achieved complete remission, and the 3-year DFS rate was 73%. No correlation was seen between tumor regression or DFS rate and a single marker or a combination of all markers. Conclusions: In the present series, no BRAF mutation was detected. The presence of KRAS mutations and loss of PTEN expression were not associated with impaired response to cetuximab-based chemoradiotherapy and 3-year DFS.

  4. A Phase II study of preoperative radiotherapy and concomitant weekly irinotecan in combination with protracted venous infusion 5-fluorouracil, for resectable locally advanced rectal cancer

    SciTech Connect

    Navarro, Matilde . E-mail: mnavarrogarcia@ico.scs.es; Dotor, Emma; Rivera, Fernando; Sanchez-Rovira, Pedro; Vega-Villegas, Maria Eugenia; Cervantes, Andres; Garcia, Jose Luis; Gallen, Manel; Aranda, Enrique

    2006-09-01

    Purpose: The aim of this study was to evaluate the efficacy and tolerance of preoperative chemoradiotherapy (CRT) with irinotecan (CPT-11) and 5-fluorouracil (5-FU) in patients with resectable rectal cancer. Methods and Materials: Patients with resectable T3-T4 rectal cancer and Eastern Cooperative Oncology Group performance status <2 were included. CPT-11 (50 mg/m{sup 2} weekly) and 5-FU (225 mg/m{sup 2}/day continuous infusion, 5 days/week) were concurrently administered with radiation therapy (RT) (45 Gy, 1.8 Gy/day, 5 days/week), during 5 weeks. Results: A total of 74 patients were enrolled: mean age, 59 years (20-74 years; SD, 11.7). Planned treatment was delivered to most patients (median relative dose intensity for both drugs was 100%). Grade 3/4 lymphocytopenia occurred in 35 patients (47%), neutropenia in 5 (7%), and anemia in 2 (3%). Main Grade 3 nonhematologic toxicities were diarrhea (14%), asthenia (9%), rectal mucositis (8%), and abdominal pain (8%). Of the 73 resected specimens, 13.7% (95% confidence interval [CI], 6.8-23.7) had a pathologic complete response and 49.3% (95% CI, 37.4-61.3) were downstaged. Additionally, 66.7% (95% CI, 51.1-80.0) of patients with ultrasound staged N1/N2 disease had no pathologic evidence of nodal involvement after CRT. Conclusions: This preoperative CRT schedule has been shown to be effective and feasible in a large population of patients with resectable rectal cancer.

  5. Transanal local excision of rectal cancer.

    PubMed

    Read, D R; Sokil, S; Ruiz-Salas, G

    1995-01-01

    Twenty-five patients with invasive rectal cancer treated by transanal excision between 1978-1989 are presented. Two patients had poorly differentiated tumours and were converted to abdominoperineal resection and one patient had extensive liver metastases documented preoperatively. The remaining twenty-two, mean age 64 years, fulfilled the criteria for local treatment. Eighty-two percent of tumours were T1 or T2 stage. There was no operative mortality. Six complications in five patients occurred, none requiring surgical intervention. Five patients died of unrelated causes without evidence of recurrence at 4, 4, 14, 26 and 58 months. The length of follow-up for the surviving group (17 patients) was 16 to 115 months (mean 63 months). Two patients developed local recurrence at 32 and 60 months. Transanal excision can be curative for selected rectal cancers.

  6. The importance of a multidisciplinary team in rectal cancer management.

    PubMed

    Bochis, Ovidiu Vasile; Fekete, Zsolt; Vlad, Catalin; Fetica, Bogdan; Leucuta, Daniel Corneliu; Busuioc, Constantin Ioan; Irimie, Alexandru

    2017-01-01

    The aim of this study was to evaluate the impact of the interval between surgery and adjuvant treatments regarding the overall survival and recurrence-free survival in patients from a developing country. For stages II and III rectal cancer, international guidelines recommend neoadjuvant chemoradiotherapy (CRT) regardless of the tumor location. In the developing countries there is a shortage of radiotherapy centers, specialists, which lead to long waiting lists for radiotherapy. These problems might lead to protocol deviations. We conducted a retrospective study on 161 patients with rectal cancer treated with surgery, postoperative CRT and with or without chemotherapy for a total of 6 months, at The Oncology Institute Cluj-Napoca between 2006-2010. All patients had 5 years of follow-up. A total of 161 patients were enrolled in this study. The majority of patients were locally advanced stages (89.44%). The well known prognostic factors, such as TNM stage, performance status, CEA serum level, perineural, vascular and lymphatic invasion, and node capsular effraction had a statistically significant influence on overall survival. In 21.12% of patients the first adjuvant treatment was started in the first 4 weeks after surgery. Only 13.04% of patients started the concomitant CRT within the limit of 6 weeks after surgery. Concerning the time between surgery and CRT, we did not observe a statistically significantly difference in OS if the radiotherapy started after the first 6 weeks (p=0.701). The OS rate for locally advanced rectal cancer patients was 69.44%. In rectal cancer, the importance of the first therapeutic act is crucial. Following international guidelines provides a survival advantage and a better quality of life. In case of adjuvant treatment, it is recommended to start this treatment as soon as the local infrastructure allows it.

  7. Fluorouracil-based neoadjuvant chemoradiotherapy with or without oxaliplatin for treatment of locally advanced rectal cancer: An updated systematic review and meta-analysis

    PubMed Central

    Li, Zhi-Wen; Zhao, Ling; Wu, Hong-Fen; Yue, Dan; Yang, Jin-Lei; Zhou, Zhi-Rui; Liu, Shi-Xin

    2016-01-01

    To measure the safety and efficacy of oxaliplatin (OX) application in neoadjuvant chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC), EMBASE, PubMed, Cochrane Library, and Web of Science were used for a literature search. Cochrane's risk of bias tool of randomized controlled trials (RCTs) was used for quality evaluation. The statistical analyses were performed using RevMan 5.3. In addition, 95% confidence intervals (CIs) and pooled risk ratios (RRs) were calculated. Seven RCTs were included in our meta-analysis. After adding OX to fluoropyrimidine (FU), a marginal significant improvement in disease-free survival was noted compared with FU alone (RR = 0.89, 95% CI: 0.78–1.00; P = 0.05). Neoadjuvant CRT with OX significantly decreased the distant metastasis rate (RR = 0.79, 95% CI: 0.67–0.94, P = 0.007). However, no improvement in the local recurrence rate (RR = 0.86, 95% CI: 0.68–1.08; P = 0.19) was noted. In addition, neoadjuvant CRT with OX also significantly increased the pathologic complete response (RR = 1.24, 95% CI: 1.02–1.51; P = 0.03). Grade 3–4 acute toxicity and grade 3–4 diarrhea was considerably higher for OX/FU compared with FU alone. In conclusion, the use of OX on the basis of FU/capecitabine in preoperative CRT is feasible. LARC patients are likely to benefit from CRT regimens with OX. PMID:27322422

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

    PubMed Central

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

    2015-01-01

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

  9. Circumferential resection margin positivity after preoperative chemoradiotherapy based on magnetic resonance imaging for locally advanced rectal cancer: implication of boost radiotherapy to the involved mesorectal fascia

    PubMed Central

    Kim, Kyung Hwan; Park, Min Jung; Lim, Joon Seok; Kim, Nam Kyu; Min, Byung Soh; Ahn, Joong Bae; Kim, Tae Il; Kim, Ho Geun; Koom, Woong Sub

    2016-01-01

    Objective To identify patients who are at a higher risk of pathologic circumferential resection margin involvement using preoperative magnetic resonance imaging. Methods Between October 2008 and November 2012, 165 patients with locally advanced rectal cancer (cT4 or cT3 with <2 mm distance from tumour to mesorectal fascia) who received preoperative chemoradiotherapy were analysed. The morphologic patterns on post-chemoradiotherapy magnetic resonance imaging were categorized into five patterns from Pattern A (most-likely negative pathologic circumferential resection margin) to Pattern E (most-likely positive pathologic circumferential resection margin). In addition, the location of mesorectal fascia involvement was classified as lateral, posterior and anterior. The diagnostic accuracy of the morphologic criteria was calculated using receiver operating characteristic curve analysis. Results Pathologic circumferential resection margin involvement was identified in 17 patients (10.3%). The diagnostic accuracy of predicting pathologic circumferential resection margin involvement was 0.73 using the five-scale magnetic resonance imaging pattern. The sensitivity, specificity, positive predictive value and negative predictive value for predicting pathologic circumferential resection margin involvement were 76.5, 65.5, 20.3 and 96.0%, respectively, when cut-off was set between Patterns C and D. On multivariate logistic regression, the magnetic resonance imaging patterns D and E (P= 0.005) and posterior or lateral mesorectal fascia involvement (P= 0.017) were independently associated with increased probability of pathologic circumferential resection margin involvement. The rate of pathologic circumferential resection margin involvement was 30.0% when the patient had Pattern D or E with posterior or lateral mesorectal fascia involvement. Conclusions Patients who are at a higher risk of pathologic circumferential resection margin involvement can be identified using preoperative

  10. A randomized phase II study of capecitabine-based chemoradiation with or without bevacizumab in resectable locally advanced rectal cancer: clinical and biological features.

    PubMed

    Salazar, Ramon; Capdevila, Jaume; Laquente, Berta; Manzano, Jose Luis; Pericay, Carles; Villacampa, Mercedes Martínez; López, Carlos; Losa, Ferran; Safont, Maria Jose; Gómez, Auxiliadora; Alonso, Vicente; Escudero, Pilar; Gallego, Javier; Sastre, Javier; Grávalos, Cristina; Biondo, Sebastiano; Palacios, Amalia; Aranda, Enrique

    2015-02-26

    Perioperatory chemoradiotherapy (CRT) improves local control and survival in patients with locally advanced rectal cancer (LARC). The objective of the current study was to evaluate the addition of bevacizumab (BEV) to preoperative capecitabine (CAP)-based CRT in LARC, and to explore biomarkers for downstaging. Patients (pts) were randomized to receive 5 weeks of radiotherapy 45 Gy/25 fractions with concurrent CAP 825 mg/m(2) twice daily 5 days per week and BEV 5 mg/kg once every 2 weeks (3 doses) (arm A), or the same schedule without BEV (arm B). The primary end point was pathologic complete response (ypCR: ypT0N0). Ninety pts were included in arm A (44) or arm B (46). Grade 3-4 treatment-related toxicity rates were 16% and 13%, respectively. All patients but one (arm A) proceeded to surgery. The ypCR rate was 16% in arm A and 11% in arm B (p =0.54). Fifty-nine percent vs 39% of pts achieved T-downstaging (arm A vs arm B; p =0.04). Serial samples for biomarker analyses were obtained for 50 out of 90 randomized pts (arm A/B: 22/28). Plasma angiopoietin-2 (Ang-2) levels decreased in arm A and increased in arm B (p <0.05 at all time points). Decrease in Ang-2 levels from baseline to day 57 was significantly associated with tumor downstaging (p =0.02). The addition of BEV to CAP-based preoperative CRT has shown to be feasible in LARC. The association between decreasing Ang-2 levels and tumor downstaging should be further validated in customized studies. Clinicaltrials.gov identifier NCT01043484. Trial registration date: 12/30/2009.

  11. Circumferential resection margin positivity after preoperative chemoradiotherapy based on magnetic resonance imaging for locally advanced rectal cancer: implication of boost radiotherapy to the involved mesorectal fascia.

    PubMed

    Kim, Kyung Hwan; Park, Min Jung; Lim, Joon Seok; Kim, Nam Kyu; Min, Byung Soh; Ahn, Joong Bae; Kim, Tae Il; Kim, Ho Geun; Koom, Woong Sub

    2016-04-01

    To identify patients who are at a higher risk of pathologic circumferential resection margin involvement using preoperative magnetic resonance imaging. Between October 2008 and November 2012, 165 patients with locally advanced rectal cancer (cT4 or cT3 with <2 mm distance from tumour to mesorectal fascia) who received preoperative chemoradiotherapy were analysed. The morphologic patterns on post-chemoradiotherapy magnetic resonance imaging were categorized into five patterns from Pattern A (most-likely negative pathologic circumferential resection margin) to Pattern E (most-likely positive pathologic circumferential resection margin). In addition, the location of mesorectal fascia involvement was classified as lateral, posterior and anterior. The diagnostic accuracy of the morphologic criteria was calculated using receiver operating characteristic curve analysis. Pathologic circumferential resection margin involvement was identified in 17 patients (10.3%). The diagnostic accuracy of predicting pathologic circumferential resection margin involvement was 0.73 using the five-scale magnetic resonance imaging pattern. The sensitivity, specificity, positive predictive value and negative predictive value for predicting pathologic circumferential resection margin involvement were 76.5, 65.5, 20.3 and 96.0%, respectively, when cut-off was set between Patterns C and D. On multivariate logistic regression, the magnetic resonance imaging patterns D and E (P= 0.005) and posterior or lateral mesorectal fascia involvement (P= 0.017) were independently associated with increased probability of pathologic circumferential resection margin involvement. The rate of pathologic circumferential resection margin involvement was 30.0% when the patient had Pattern D or E with posterior or lateral mesorectal fascia involvement. Patients who are at a higher risk of pathologic circumferential resection margin involvement can be identified using preoperative magnetic resonance imaging although

  12. A Retrospective Analysis on Two-week Short-course Pre-operative Radiotherapy in Elderly Patients with Resectable Locally Advanced Rectal Cancer

    PubMed Central

    Shi, Chen; Zhou, Hao; Li, Xiaofan; Cai, Yong

    2016-01-01

    To validate that a two-week short-course pre-operative radiotherapy regimen is feasible, safe, and effective for the management of elderly patients with locally advanced rectal cancer (LARC), we retrospectively analyzed 99 radiotherapy-naive patients ≥70 years of age with LARC. Patients received pelvic radiation therapy (3D-CRT 30Gy/10f/2w) followed by TME surgery; some patients received adjuvant chemotherapy. The primary endpoint was OS, while the secondary endpoints were DFS, safety and response rate. The median follow-up time was 5.1 years. The 5-year OS and DFS rates were 58.3% and 51.2%, respectively. The completion rate of radiotherapy (RT) was 99.0% (98 of 99). Grade 3 acute adverse events, which resulted from RT, occurred in only 1 patient (1.0%). In addition, no grade 4 acute adverse events induced by RT were observed. All 99 patients (100%) were able to undergo R0 surgical resection, and 68.6% of the patients received sphincter-sparing surgery. The rate of occurrence of clinically relevant post-operative complications was 12.1%. Three patients (3.0%) achieved pathologic complete responses, and forty-three patients (43.4%) achieved pathologic partial responses. The rates of T-downsizing and N-downstaging were 30.3% and 55.7%, respectively. Therefore, we believe that a two-week short-course pre-operative radiotherapy is feasible in elderly patients with resectable LARC. PMID:27886277

  13. Upfront Systemic Chemotherapy and Short-Course Radiotherapy with Delayed Surgery for Locally Advanced Rectal Cancer with Distant Metastases: Outcomes, Compliance, and Favorable Prognostic Factors

    PubMed Central

    Kim, Tae Hyung; Ahn, Joong Bae; Jung, Minkyu; Kim, Tae Il; Kim, Hoguen; Shin, Sang Joon; Kim, Nam Kyu

    2016-01-01

    Purpose/Objective(s) Optimal treatment for locally advanced rectal cancer (LARC) with distant metastasis remains elusive. We aimed to evaluate upfront systemic chemotherapy and short-course radiotherapy (RT) followed by delayed surgery for such patients, and to identify favorable prognostic factors. Materials/Methods We retrospectively reviewed 50 LARC patients (cT4 or cT3, <2 mm from the mesorectal fascia) with synchronous metastatic disease. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival, treatment-related toxicity, and compliance. We considered P values <0.05 significant. Results At 22 months median follow-up, the median PFS time was 16 months and the 2-year PFS rate was 34.8%. Thirty-five patients who received radical surgery for primary and metastatic tumors were designated the curable group. Six patients with clinical complete response (ypCR) of metastases who underwent radical surgery for only the primary tumor were classified as potentially curable. Nine patients who received no radical surgery (3 received palliative surgery) were deemed the palliative group. The ypCR rate among surgery patients was 13.6%. PFS rates for the curable or potentially curable groups were significantly longer than that of the palliative group (P<0.001). On multivariate analysis, solitary organ metastasis and R0 status were independent prognostic factors for PFS. Conclusions These findings demonstrated that a strong possibility that upfront chemotherapy and short-course RT with delayed surgery are an effective alternative treatment for LARC with potentially resectable distant metastasis, owing to achievement of pathologic down-staging, R0 resection, and favorable compliance and toxicity, despite the long treatment duration. PMID:27536871

  14. A proposed approach for the selection of the proper surgical therapy to obtain an adequate margin of resection in locally advanced ultra-low rectal cancer after modern preoperative CRX management.

    PubMed

    Echenique, Ignacio; Cabanillas, Fernando; Texidor, Vangie; Cáceres, Janice; Isenberg, Gerald; Claudio, Carlos; Ayala, Roberto; Madera, Frank

    2009-01-01

    We performed a retrospective review to identify objective factors that could facilitate the surgeon's decision regarding the feasibility of an adequate resection with a margin of< 2 cm from the dentate line. We could not find clear guidelines for clinicians regarding the use of close margins for sphincter saving surgery following chemoradiation (CRX). We proposed what state of the art imaging tools are potentially useful to identify tumor downstage following preoperative CRX and aid in the development of guidelines. Reviewed of the literature on the subject and performance of current diagnostic imaging studies useful in identifying rectal tumor downstaging after preoperative CRX. Without safe margins of resection an abdominoperineal resection (APR) is the operation of choice. All sphincter saving rectal cancer operations results for ultra-low tumors need to be as good as results from an APR. Performing frozen section for the ultralow rectal cancer margins is recommended. The Endorectal Ultrasonography (ERUS) data appear encouraging and suggest that we should evaluate TRUS earlier after CRX, before the desmoplastic reaction and scar tissue appears. It could turn out to be an objective and accurate method of evaluating tumor downstaging. Color Doppler evaluation has shown higher specificity than that of grey scale ultrasound in staging and differentiating scar from anal cancers. Similarly, PET scanning performed earlier and with modern PET-CT equipment is worth exploring. At this point with the information available from the literature, we suggest that patients with clinically advanced rectal cancer can have a distal margin resection of less than 2 cm if: 1- the tumor is not mucin producing, 2- the tumor is not high-grade, and 3- the response to preop CRX is adequate, however there exist no clear guidelines available to judge what is an excellent versus a moderate or poor response.

  15. Rectal cancer: An evidence-based update for primary care providers

    PubMed Central

    Gaertner, Wolfgang B; Kwaan, Mary R; Madoff, Robert D; Melton, Genevieve B

    2015-01-01

    Rectal adenocarcinoma is an important cause of cancer-related deaths worldwide, and key anatomic differences between the rectum and the colon have significant implications for management of rectal cancer. Many advances have been made in the diagnosis and management of rectal cancer. These include clinical staging with imaging studies such as endorectal ultrasound and pelvic magnetic resonance imaging, operative approaches such as transanal endoscopic microsurgery and laparoscopic and robotic assisted proctectomy, as well as refined neoadjuvant and adjuvant therapies. For stage II and III rectal cancers, combined chemoradiotherapy offers the lowest rates of local and distant relapse, and is delivered neoadjuvantly to improve tolerability and optimize surgical outcomes, particularly when sphincter-sparing surgery is an endpoint. The goal in rectal cancer treatment is to optimize disease-free and overall survival while minimizing the risk of local recurrence and toxicity from both radiation and systemic therapy. Optimal patient outcomes depend on multidisciplinary involvement for tailored therapy. The successful management of rectal cancer requires a multidisciplinary approach, with the involvement of enterostomal nurses, gastroenterologists, medical and radiation oncologists, radiologists, pathologists and surgeons. The identification of patients who are candidates for combined modality treatment is particularly useful to optimize outcomes. This article provides an overview of the diagnosis, staging and multimodal therapy of patients with rectal cancer for primary care providers. PMID:26167068

  16. [Neoadjuvant radiochemotherapy treatment in locally advanced rectal adenocarcinoma].

    PubMed

    Carau, B; Orrù, P; Orrù, S; Dessì, M; Nagliati, M; Lay, G; Maxia, V; Casula, G; Amichetti, M

    2003-01-01

    A prospective phase II study was conducted to evacuate toxicity and results of preoperative radiochemotherapy in locoregionally advanced rectal cancer (LARC). A total of 33 patients entered the study and received 45 Gy to the pelvis plus a supplemental boost of 5.4-9 Gy concurrently with 5 FU c.i. at a dose of 225-275 mg/m2. Thirty patients were operated after 5-7 weeks (20 anterior resection and 10 abdominoperineal excision). In 14 patients (47%) a downstaging was observed, 5 patients experienced a complete clearance of the primary tumor. After a median of 14 months (range, 5-27), 23 patients, are alive and well. And 8 patients experienced a disease progression (4 local-regional and 4 distant). Our results provide further evidence of the utility and effectiveness of preoperative radiochemotherapy in LARC.

  17. Adjuvant therapy of resectable rectal cancer.

    PubMed

    Minsky, Bruce D

    2002-08-01

    The two conventional treatments for clinically resectable rectal cancer are surgery followed by postoperative combined modality therapy and preoperative combined modality therapy followed by surgery and postoperative chemotherapy. Preoperative therapy (most commonly combined modality therapy) has gained acceptance as a standard adjuvant therapy. The potential advantages of the preoperative approach include decreased tumor seeding, less acute toxicity, increased radiosensitivity due to more oxygenated cells, and enhanced sphincter preservation. There are a number of new chemotherapeutic agents that have been developed for the treatment of patients with colorectal cancer. Phase I/II trials examining the use of new chemotherapeutic agents in combination with pelvic radiation therapy are in progress.

  18. Immunological Landscape and Clinical Management of Rectal Cancer

    PubMed Central

    Pérez-Ruiz, Elísabeth; Berraondo, Pedro

    2016-01-01

    The clinical management of rectal cancer and colon cancer differs due to increased local relapses in rectal cancer. However, the current molecular classification does not differentiate rectal cancer and colon cancer as two different entities. In recent years, the impact of the specific immune microenvironment in cancer has attracted renewed interest and is currently recognized as one of the major determinants of clinical progression in a wide range of tumors. In colorectal cancer, the density of lymphocytic infiltration is associated with better overall survival. Due to the need for biomarkers of response to conventional treatment with chemoradiotherapy in rectal tumors, the immune status of rectal cancer emerges as a useful tool to improve the management of patients. PMID:26941741

  19. [Current MRI staging of rectal cancer].

    PubMed

    Wietek, B M; Kratt, T

    2012-11-01

    Colorectal carcinoma is the second most prevalent cause for cancer, and has very variable outcomes. Advancements in surgery, the change from adjuvant to neo-adjuvant radio-chemo-therapies as well as in clinical diagnostics have improved the prognosis for patients in a multi-modal therapy concept. An accurate primary staging including a reliable prediction of the circumferential resection margin (CRM) has established MR Imaging (MRI) beside intraluminal endoscopic ultrasound (EUS). MRI facilitates the selection of patients likely to benefit from a preoperative therapy, especially in cases of unfavorable factors. Currently the relationship of the tumor to the mesorectal fascia has become a more important prognostic factor than the T-staging, particularly for surgical therapy. In addition further prognostic factors like the depth of infiltration into the perirectal fat and the extramural venous infiltration (EMVI) have important impact on therapy and prognosis. High resolution MRI has proved useful in clarifying the relationship between the tumor and the mesorectal fascia, which represents the CRM at the total mesorectal excision (TME) especially in the upper and middle third. Preoperative evaluation of the other prognostic factors as well as the nodal status is still difficult. It is used increasingly not only for primary staging but also progressively for the monitoring of neoadjuvant therapy. The addition of diffusion weighted imaging (DWI) is an interesting option for the improvement of response evaluation. The following overview provides an introduction of MRI diagnosis as well as its importance for the evaluation of the clinically relevant prognostic factors leading to an improvement of therapy and prognosis of patients with rectal carcinoma. © Georg Thieme Verlag KG Stuttgart · New York.

  20. GLUT-1 expression and response to chemoradiotherapy in rectal cancer.

    PubMed

    Brophy, Sarah; Sheehan, Katherine M; McNamara, Deborah A; Deasy, Joseph; Bouchier-Hayes, David J; Kay, Elaine W

    2009-12-15

    Preoperative chemoradiotherapy is used in locally advanced rectal cancer to reduce local recurrence and improve operability, however a proportion of tumors do not undergo significant regression. Identification of predictive markers of response to chemoradiotherapy would improve patient selection and may allow response modification by targeting of specific pathways. The aim of this study was to determine whether expression of glucose transporter-1 (GLUT-1) and p53 in pretreatment rectal cancer biopsies was predictive of tumor response to chemoradiotherapy. Immunohistochemical staining for GLUT-1 and p53 was performed on 69 pretreatment biopsies and compared to tumor response in the resected specimen as determined by the tumor regression grade (TRG) scoring system. GLUT-1 expression was significantly associated with reduced response to chemoradiotherapy and increasing GLUT expression correlated with poorer response (p=0.02). GLUT-1 negative tumors had a 70% probability of good response (TRG3/4) compared to a 31% probability of good response in GLUT-1 positive tumors. GLUT-1 may be a useful predictive marker of response to chemoradiotherapy in rectal cancer.

  1. An isolated vaginal metastasis from rectal cancer.

    PubMed

    Sadatomo, Ai; Koinuma, Koji; Horie, Hisanaga; Lefor, Alan K; Sata, Naohiro

    2016-02-01

    Isolated vaginal metastases from colorectal cancer are extremely rare. There are only a few reported cases in the English literature, and the characteristics of such cases of metastasis remain relatively unknown. We present a case of isolated vaginal metastasis from rectal cancer in a 78-year-old female patient. The patient had no symptoms related to vaginal tumor. Magnetic resonance imaging (MRI) showed thickening of the middle rectum and a vaginal tumor. Biopsy from the vaginal tumor showed adenocarcinoma, similar to the rectal lesion. Low anterior resection with ileostomy, hystero-oophorectomy, and transvaginal tumor resection was performed. After nineteen months, computed tomography scan revealed multiple lung metastases and recurrent tumor in the pelvis. The patient refused chemotherapy and is alive three months after developing recurrent disease. Most cases of primary vaginal carcinoma are squamous cell carcinoma. Other histologic types such as adenocarcinoma are usually metastatic lesions. Primary lesions associated with metastatic vaginal adenocarcinoma are most often the uterus, and are very rarely from the colon or rectum. We review previous case reports of isolated vaginal metastases from colorectal cancer and discuss their symptoms, treatments, and outcomes. We should keep the vagina within the field of view of pelvic MRI, which is one of the preoperative diagnostic tools for colorectal cancer. If female patients show gynecological symptoms, gynecological examination should be recommended. Isolated vaginal metastases are an indication for surgical resection, and adjuvant chemotherapy is also recommended.

  2. A novel strategy of radiofrequency hyperthermia (neothermia) in combination with preoperative chemoradiotherapy for the treatment of advanced rectal cancer: a pilot study

    PubMed Central

    Shoji, Hisanori; Motegi, Masahiko; Osawa, Kiyotaka; Okonogi, Noriyuki; Okazaki, Atsushi; Andou, Yoshitaka; Asao, Takayuki; Kuwano, Hiroyuki; Takahashi, Takeo; Ogoshi, Kyoji

    2015-01-01

    The safety of weekly regional hyperthermia performed with 8 MHz radiofrequency (RF) capacitive heating equipment has been established in rectal cancer. We aimed to standardize hyperthermia treatment for scientific evaluation and for assessing local tumor response to RF hyperthermia in rectal cancer. Forty-nine patients diagnosed with rectal adenocarcinoma were included in the study. All patients received chemoradiation with intensity-modulated radiation therapy 5 days/week (dose, 50 Gy/25 times) concomitant with 5 days/week for five times of capecitabine (1700 mg/m2 per day) and once a week for five times of 50 min irradiations by an 8 MHz RF capacitive heating device. Thirty-three patients underwent surgery 8 weeks after treatment. Three patients did not undergo surgery because of progressive disease (PD) and 13 refused. Eight (16.3%) patients had a pathological complete response (ypCR) after surgery. Among patients without surgery, 3 (6.1%) had clinical complete response (CR) and 3 (6.1%) had local CR but distant PD (CRPD). Ninety percent of ypCR + CR patients were shown in 6.21 W min−1 m−2/treatment or higher group of average total accumulated irradiation output with 429°C min−1 m−2 or higher group of total accumulated thermal output. However, a patient with CRPD was in the higher total accumulated thermal output group. We propose a new quantitative parameter for the hyperthermia and demonstrated that patients can benefit from mild irradiation with mild temperature. Using these parameters, the exact output, optimal thermal treatment, and contraindications or indications of this modality could be determined in a multi-institutional, future study. PMID:25664976

  3. Laparoscopic intersphincteric resection for low rectal cancer.

    PubMed

    Lim, Sang Woo; Huh, Jung Wook; Kim, Young Jin; Kim, Hyeong Rok

    2011-12-01

    Laparoscopic intersphincteric resection (ISR) after neoadjuvant chemoradiation is helpful in the management of patients with low rectal cancer. With the advent of this technique, the need for performance of abdominoperineal resection seems to have decreased in patients with very low rectal tumors. The aim of the present study was to evaluate the feasibility, the functional outcome, and the short-term oncologic outcomes of laparoscopic ISR for low rectal adenocarcinoma at our institution. We retrospectively reviewed the data of 111 consecutive patients who underwent laparoscopic ISR for low rectal adenocarcinoma between July 2005 and December 2009. Demographic status, surgical outcomes, functional outcome data, and oncologic outcome data were collected. The mean distance of the tumor from the anal verge was 3.4 cm (range: 1-5 cm). The mean operative time was 214.7 min (range, 150-450 min). The mean distal resection margin was 1.3 ± 1.1 cm. Morbidity occurred in 24 patients (21.6%), including anastomotic leakage in 2 patients (1.8%). The mean Wexner continence score after stoma repair was 7.5 ± 2.7 (range: 2 ~ 19), and 9.8 in total ISR, 7.3 in partial ISR (P = 0.071). The 3-year overall survival rate was 92.8%, and the 3-year disease-free survival rate was 73.0%. Local recurrence was noted in 6 of the 111 patients with TNM stage I to III (5.4%). The patients with lesions at 2 cm to the dentate line had a 7.07-fold greater risk of local recurrence, including a 13.42-fold greater risk of lateral pelvic wall recurrence and perineal recurrence (95% Confidence interval [CI], 1.141-158.006; P = 0.009) than in those who had lesions more than 2 cm from the anal verge (95% CI, 1.290-38.832; P = 0.011). Laparoscopic ISR after neoadjuvant chemoradiation can be recommended as a technically feasible, minimally invasive, and a sphincter-saving procedure with acceptable functional and short-term oncologic outcomes in patients with very low rectal cancer.

  4. Rectal and colon cancer: Not just a different anatomic site.

    PubMed

    Tamas, K; Walenkamp, A M E; de Vries, E G E; van Vugt, M A T M; Beets-Tan, R G; van Etten, B; de Groot, D J A; Hospers, G A P

    2015-09-01

    Due to differences in anatomy, primary rectal and colon cancer require different staging procedures, different neo-adjuvant treatment and different surgical approaches. For example, neoadjuvant radiotherapy or chemoradiotherapy is administered solely for rectal cancer. Neoadjuvant therapy and total mesorectal excision for rectal cancer might be responsible in part for the differing effect of adjuvant systemic treatment on overall survival, which is more evident in colon cancer than in rectal cancer. Apart from anatomic divergences, rectal and colon cancer also differ in their embryological origin and metastatic patterns. Moreover, they harbor a different composition of drug targets, such as v-raf murine sarcoma viral oncogene homolog B (BRAF), which is preferentially mutated in proximal colon cancers, and the epidermal growth factor receptor (EGFR), which is prevalently amplified or overexpressed in distal colorectal cancers. Despite their differences in metastatic pattern, composition of drug targets and earlier local treatment, metastatic rectal and colon cancer are, however, commonly regarded as one entity and are treated alike. In this review, we focused on rectal cancer and its biological and clinical differences and similarities relative to colon cancer. These aspects are crucial because they influence the current staging and treatment of these cancers, and might influence the design of future trials with targeted drugs.

  5. Combined modality therapy for rectal cancer.

    PubMed

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

    2010-01-01

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

  6. Determinants of survival following pelvic exenteration for primary rectal cancer.

    PubMed

    Radwan, R W; Jones, H G; Rawat, N; Davies, M; Evans, M D; Harris, D A; Beynon, J

    2015-09-01

    Pelvic exenteration is a potentially curative treatment for locally advanced primary rectal cancer. Previous studies have been limited by small sample sizes and heterogeneous data. A consecutive series of patients was studied to identify the clinicopathological determinants of survival. All patients undergoing pelvic exenterative surgery for primary rectal cancer (1992-2014) at this hospital were analysed. The primary outcome measure was 5-year overall survival. Secondary endpoints included length of hospital stay, complication rate, 30-day mortality and disease recurrence rate. Statistical analysis was performed using Kaplan-Meier and Cox regression analysis. A total of 174 patients with a median age of 65 (range 31-90) years were included. Ninety-six patients underwent posterior pelvic exenteration and 78 had total pelvic exenteration. Median follow-up was 48 (range 1-229) months. Two patients (1.1 per cent) died within 30 days of surgery and 16.1 per cent returned to the operating theatre. The 5-year survival rate following complete resection (R0) was 59.3 per cent. In univariable analysis, adverse survival was associated with advanced age (P = 0.003), metastatic disease (P = 0.001), pathological node status (P = 0.001), circumferential resection margin (P = 0.001), local recurrence (P = 0.015) and the need for neoadjuvant therapy (P = 0.039). Pelvic exenteration is an aggressive treatment option with a high morbidity rate that provides favourable long-term outcomes in patients with locally advanced primary rectal cancer. © 2015 BJS Society Ltd Published by John Wiley & Sons Ltd.

  7. SU-F-R-48: Early Prediction of Pathological Response of Locally Advanced Rectal Cancer Using Perfusion CT:A Prospective Clinical Study

    SciTech Connect

    Nie, K; Yue, N; Jabbour, S; Kim, S; Shi, L; Mao, T; Qian, L; Hu, X; Sun, X; Niu, T

    2016-06-15

    Purpose: To prospectively evaluate the tumor vascularity assessed by perfusion CT for prediction of chemo-radiation treatment (CRT) response in locally advanced rectal cancer (LARC). Methods: Eighteen consecutive patients (61.9±8.8 years, from March–June 2015) diagnosed with LARC who underwent 6–8 weeks CRT followed by surgery were included. The pre-treatment perfusion CT was acquired after a 5s delay of contrast agent injection for 45s with 1s interval. A total of 7-cm craniocaudal range covered the tumor region with 3-mm slice thickness. The effective radiation dose is around 15mSv, which is about 1.5 the conventional abdomen/pelvis CT dose. The parametric map of blood flow (BF), blood volume (BV), mean transit time (MTT), permeability (PMB), and maximum intensity map (MIP) were obtained from commercial software (Syngo-CT 2011A, Siemens). An experienced radiation oncologist outlined the tumor based on the pre-operative MR and pathologic residual region, but was blinded with regards to pathological tumor stage. The perfusion parameters were compared to histopathological response quantified by tumor regression grade as good-responder (GR, TRG 0-1) vs. non-good responder (non-GR). Furthermore, the predictive value for pathological complete response (pCR) was also investigated. Results: Both BV (p=0.02) and MTT (P=0.02) was significantly higher and permeambility was lower (p=0.004) in the good responders. The BF was higher in GR group but not statistically significant. Regarding the discrimination of pCR vs non-pCR, the BF was higher in the pCR group (p=0.08) but none of those parameters showed statistically significant differences. Conclusion: BV and MTT can discriminate patients with a favorable response from those that fail to respond well, potentially selecting high-risk patients with resistant tumors that may benefit from an aggressive preoperative treatment approach. However, future studies with more patient data are needed to verify the prognostic value

  8. Preoperative intensity-modulated radiotherapy with a simultaneous integrated boost combined with Capecitabine in locally advanced rectal cancer: short-term results of a multicentric study.

    PubMed

    Lupattelli, Marco; Matrone, Fabio; Gambacorta, Maria Antonietta; Osti, Mattia; Macchia, Gabriella; Palazzari, Elisa; Nicosia, Luca; Navarria, Federico; Chiloiro, Giuditta; Valentini, Vincenzo; Aristei, Cynthia; De Paoli, Antonino

    2017-08-22

    Preoperative radiotherapy (RT) in combination with fluoropyrimidine-based chemotherapy (CT) is the standard of care in patients with locally advanced, T3-T4 N0-2, rectal cancer (LARC). Given the correlation between RT dose-tumor response and the prognostic role of the tumor regression grade (TRG), treatment intensification represents an area of active investigation. The aim of the study was to analyze the role of RT dose-intensification in the preoperative treatment of LARC in terms of feasibility, efficacy and toxicity. We retrospectively analyzed patients with LARC treated with intensity-modulated radiotherapy (IMRT) and simultaneous integrated boost (SIB) at five Italian radiation oncology centers. Concurrent Capecitabine was administered. Treatment response was evaluated in terms of disease down-staging and TRG. Acute toxicity was evaluated according to the CTC-AE 4.0 scale. A total of 76 patients were identified for this analysis. A dose of 45 Gy was prescribed to the entire mesorectum and pelvic lymph nodes with a median SIB dose of 54 Gy (range 52.5-57.5) to the tumor and corresponding mesorectum. Overall, 74/76 (97.4%) patients completed the planned RT, whereas 64/76 (84.2%) patients completed the prescribed CT. Eight (10.5%) patients developed grade 3-4 acute toxicity. Overall, 72/76 patients underwent surgery. The tumor and nodal down-staging was documented in 51 (70.8%) and 43 (67%) patients, respectively. Twenty (27.8%) patients obtained a pathologic complete response. Surgical morbidity was reported in 13/72 patients (18.1%). Although retrospective in design, this study indicates that IMRT-SIB with a dose range of 52.5-57.5 Gy (median 54 Gy) and concomitant Capecitabine appears feasible, well tolerated and effective in terms of disease down-staging and pathological complete response. Long-term toxicity and the impact on disease control and patient survival will be evaluated with a longer follow-up time. NA.

  9. 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

  10. Combined value of apparent diffusion coefficient-standardized uptake value max in evaluation of post-treated locally advanced rectal cancer

    PubMed Central

    Ippolito, Davide; Fior, Davide; Trattenero, Chiara; Ponti, Elena De; Drago, Silvia; Guerra, Luca; Franzesi, Cammillo Talei; Sironi, Sandro

    2015-01-01

    AIM: To assess the clinical diagnostic value of functional imaging, combining quantitative parameters of apparent diffusion coefficient (ADC) and standardized uptake value (SUV)max, before and after chemo-radiation therapy, in prediction of tumor response of patients with rectal cancer, related to tumor regression grade at histology. METHODS: A total of 31 patients with biopsy proven diagnosis of rectal carcinoma were enrolled in our study. All patients underwent a whole body 18FDG positron emission tomography (PET)/computed tomography (CT) scan and a pelvic magnetic resonance (MR) examination including diffusion weighted (DW) imaging for staging (PET1, RM1) and after completion (6.6 wk) of neoadjuvant treatment (PET2, RM2). Subsequently all patients underwent total mesorectal excision and the histological results were compared with imaging findings. The MR scanning, performed on 1.5 T magnet (Philips, Achieva), included T2-weighted multiplanar imaging and in addition DW images with b-value of 0 and 1000 mm²/s. On PET/CT the SUVmax of the rectal lesion were calculated in PET1 and PET2. The percentage decrease of SUVmax (ΔSUV) and ADC (ΔADC) values from baseline to presurgical scan were assessed and correlated with pathologic response classified as tumor regression grade (Mandard’s criteria; TRG1 = complete regression, TRG5 = no regression). RESULTS: After completion of therapy, all the patients were submitted to surgery. According to the Mandard’s criteria, 22 tumors showed complete (TRG1) or subtotal regression (TRG2) and were classified as responders; 9 tumors were classified as non responders (TRG3, 4 and 5). Considering all patients the mean values of SUVmax in PET 1 was higher than the mean value of SUVmax in PET 2 (P < 0.001), whereas the mean ADC values was lower in RM1 than RM2 (P < 0.001), with a ΔSUV and ΔADC respectively of 60.2% and 66.8%. The best predictors for TRG response were SUV2 (threshold of 4.4) and ADC2 (1.29 × 10-3 mm2/s) with high

  11. Long-Term Follow-Up of Preoperative Pelvic Radiation Therapy and Concomitant Boost Irradiation in Locally Advanced Rectal Cancer Patients: A Multi-Institutional Phase II Study (KROG 04-01)

    SciTech Connect

    Lee, Jong Hoon; Kim, Dae Yong; Nam, Taek-Keun; Yoon, Sei-Chul; Lee, Doo Seok; Park, Ji Won; Oh, Jae Hwan; Chang, Hee Jin; Yoon, Mee Sun; Jeong, Jae-Uk; Jang, Hong Seok

    2012-11-15

    Purpose: To perform a prospective phase II study to investigate the efficacy and safety of preoperative pelvic radiation therapy and concomitant small-field boost irradiation with 5-fluorouracil and leucovorin for 5 weeks in locally advanced rectal cancer patients. Methods and Materials: Sixty-nine patients with locally advanced, nonmetastatic, mid-to-lower rectal cancer were prospectively enrolled. They had received preoperative chemoradiation therapy and total mesorectal excision. Pelvic radiation therapy of 43.2 Gy in 24 fractions plus concomitant boost radiation therapy of 7.2 Gy in 12 fractions was delivered to the pelvis and tumor bed for 5 weeks. Two cycles of 5-fluorouracil and leucovorin were administered for 3 days in the first and fifth week of radiation therapy. The pathologic response, survival outcome, and treatment toxicity were evaluated for the study endpoints. Results: Of 69 patients, 8 (11.6%) had a pathologically complete response. Downstaging rates were 40.5% for T classification and 68.1% for N classification. At the median follow-up of 69 months, 36 patients have been followed up for more than 5 years. The 5-year disease-free survival (DFS) and overall survival rates were 66.0% and 75.3%, respectively. Higher pathologic T (P = .045) and N (P = .032) classification were significant adverse prognostic factors for DFS, and high-grade histology was an adverse prognostic factor for both DFS (P = .025) and overall survival (P = .031) on the multivariate analysis. Fifteen patients (21.7%) experienced grade 3 or 4 acute toxicity, and 7 patients (10.1%) had long-term toxicity. Conclusion: Preoperative pelvic radiation therapy with concomitant boost irradiation with 5-fluorouracil and leucovorin for 5 weeks showed acceptable acute and long-term toxicities. However, the benefit of concomitant small-field boost irradiation for 5 weeks in rectal cancer patients was not demonstrated beyond conventional irradiation for 6 weeks in terms of tumor response and

  12. [Local diagnostics for rectal cancer. What is realistic?].

    PubMed

    Ptok, H; Gastinger, I; Lippert, H

    2012-05-01

    Accurate pretherapeutic staging of rectal cancer is crucial for further therapeutic management and important for prognosis. The most accurate diagnostic tools in the assessment of T and N categories of rectal cancer are endorectal ultrasound (EUS) and magnetic resonance imaging (MRI). Furthermore, MRI can accurately predict the distance of the tumor to the colorectal membrane (CRM) and computed tomography (CT) is more suitable for detecting distant metastases. In the routine care of rectal cancer EUS is the most frequently used diagnostic tool for local staging. The achieved accuracy for determining T category by EUS in routine clinical staging is lower than results reported in the literature. Furthermore, the accuracy of EUS depends on the experience of the examiner. Currently the frequency of using MRI for routine clinical staging of rectal cancer is low and in one out of five cases the local staging of rectal cancer is exclusively carried out by CT.

  13. Abdominosacral resection for locally recurring rectal cancer

    PubMed Central

    Belli, Filiberto; Gronchi, Alessandro; Corbellini, Carlo; Milione, Massimo; Leo, Ermanno

    2016-01-01

    AIM To investigate feasibility and outcome of abdominal-sacral resection for treatment of locally recurrent rectal adenocarcinoma. METHODS A population of patients who underwent an abdominal-sacral resection for posterior recurrent adenocarcinoma of the rectum at the National Cancer Institute of Milano, between 2005 and 2013, is considered. Retrospectively collected data includes patient characteristics, treatment and pathology details regarding the primary and the recurrent rectal tumor surgical resection. A clinical and instrumental follow-up was performed. Surgical and oncological outcome were investigated. Furthermore an analytical review of literature was conducted in order to compare our case series with other reported experiences. RESULTS At the time of abdomino-sacral resection, the mean age of patients was 55 (range, 38-64). The median operating time was 380 min (range, 270-480). Sacral resection was performed at S2/S3 level in 3 patients, S3/S4 in 3 patients and S4/S5 in 4 patients. The median operating time was 380 ± 58 min. Mean intraoperative blood loss was 1750 mL (range, 200-680). The median hospital stay was 22 d. Overall morbidity was 80%, mainly type II complication according to the Clavien-Dindo classification. Microscopically negative margins (R0) is obtained in all patients. Overall 5-year survival after first surgical procedure is 60%, with a median survival from the first surgery of 88 ± 56 mo. The most common site of re-recurrence was intrapelvic. CONCLUSION Sacral resection represents a feasible approach to posterior rectal cancer recurrence without evidence of distant spreading. An accurate staging is essential for planning the best therapy. PMID:28070232

  14. [Robotic total mesorectal excision for rectal cancer].

    PubMed

    Rossi, Gustavo; Alvarez, Fernando A; Mentz, Ricardo; Vaccaro, Carlos A; Im, Víctor; Quintana, Guillermo Ojea

    2013-06-01

    Laparoscopic total mesorectal excision (TME) has proven to be feasible and safe. However, it represents a major technical challenge, since it involves the dissection of the rectum in a confined space such as the bony pelvis using un-ergonomic surgical devices. This difficulty is accentuated in patients with distal tumors and high body mass index (BMI), in which the surgical margins and the hypogastric nerves may be affected. Therefore, robotic surgery aims to overcome these limitations that conspire against the mininvasive surgical approach of rectal cancer. We present an obese (BMI = 32 kg/m2) 82-year-old man with a history of smoking and prostate cancer that was recently diagnosed with a middle rectal adenocarcinoma at 9 cm from the anal verge. Rectal examination evidenced a mobile lesion. Computed tomography scan ruled out metastases and at the local staging by MRI, the tumor was considered as T3-N0 with free circumferential margins. Surgical treatment was decided and a hybrid technique was used combining an initial laparoscopic approach followed by the robotic TME. The patient had a full recovery and was discharged three days after surgery without complications. Pathological examination revealed a low-grade adenocarcinoma with mesorectal invasion, free circumferential and distal margins, and 24 negative lymph nodes (pT3-pN0-pM0/Stage II). Robotic TME was performed safely in an obese patient. It facilitated dissection maneuvers in a confined space with proper identification and preservation of the hypogastric nerves, allowing retrieving an intact mesorectum. Prospective randomized trials will define the role of this new technology.

  15. Preliminary report of a new treatment strategy for advanced pelvic malignancy: surgical resection and radiation therapy using afterloading catheters plus an inflatable displacement prosthesis in the treatment of advanced primary and recurrent rectal cancer

    SciTech Connect

    Edington, H.D.; Hancock, S.; Coe, F.L.; Sugarbaker, P.H.

    1986-09-01

    An unsolved problem in colon and rectal surgery involves the treatment of locally invasive primary and recurrent rectal cancer. An approach is described that uses intracavitary iridium-192 sources in combination with a pelvic displacement prosthesis to augment external beam radiation doses to sites of residual disease identified at surgery. This approach should permit administration of tumoricidal doses of radiation to positive surgical margins minimizing radiation toxicity to the small bowel. The radiation source and all prosthetic materials are removed at the bedside within 2 weeks of surgery, ensuring accurate radiation dosimetry, minimizing infectious complications, and sparing the patient the need for full high-dose pelvic irradiation.

  16. Rectal prolapse as initial clinical manifestation of colon cancer.

    PubMed

    Chen, C-W; Hsiao, C-W; Wu, C-C; Jao, S-W

    2008-04-01

    Rectal prolapse as the initial clinical manifestation of colorectal cancer is uncommon. We describe the case of a 75-year-old woman who was diagnosed as having adenocarcinoma of the sigmoid colon after presenting with complete rectal prolapse. The tumor caused rectosigmoid intussusception and then it prolapsed out through the anus. She underwent rectosigmoidectomy and rectopexy. The postoperative course was uneventful. The relationship between colorectal cancer and rectal prolapse has not been clearly established. This case report describes an unusual presentation of colorectal cancer. It suggests that rectal prolapse can present as the initial symptom of colorectal cancer and may also be a presenting feature of the occult intra-abdominal pathology. The importance of adequate investigation such as colonoscopy should be emphasized in patients who develop a new onset of rectal prolapse.

  17. Addition of Bevacizumab to XELOX Induction Therapy Plus Concomitant Capecitabine-Based Chemoradiotherapy in Magnetic Resonance Imaging–Defined Poor-Prognosis Locally Advanced Rectal Cancer: The AVACROSS Study

    PubMed Central

    Salud, Antonieta; Vicente, Pilar; Arriví, Antonio; Roca, José María; Losa, Ferran; Ponce, José; Safont, María José; Guasch, Inmaculada; Moreno, Isabel; Ruiz, Ana; Pericay, Carles

    2011-01-01

    Background. Concomitant chemoradiotherapy followed by total mesorectal excision is standard treatment for locally advanced rectal cancer. This approach, however, focuses on local disease control and delays systemic treatment. Induction chemotherapy has the advantage of earlier administration of systemic therapy and may improve distant control. The objective of the current study was to assess the efficacy and toxicity of adding bevacizumab to induction chemotherapy followed by preoperative bevacizumab-based chemoradiotherapy in patients with locally advanced rectal cancer. Patients and Methods. Eligible patients had high-risk rectal adenocarcinoma defined by magnetic resonance imaging criteria. Treatment consisted of four 21-day cycles of bevacizumab (7.5 mg/kg) and XELOX (capecitabine plus oxaliplatin), followed by concomitant radiotherapy (50.4 Gy) plus bevacizumab (5 mg/kg every 2 weeks) and capecitabine (825 mg/m2 twice daily on days 1–15). Surgery was scheduled for 6–8 weeks after chemoradiotherapy. The primary endpoint was pathologic complete response (pCR). Results. Between July 2007 and July 2008, 47 patients were recruited. Among 45 patients who underwent surgery, pCR was achieved in 16 patients (36%; 95% confidence interval: 22.29%–51.27%), and an additional 17 patients (38%) had Dworak tumor regression grade 3. R0 resection was performed in 44 patients (98%). Most grade 3/4 adverse events occurred during the induction phase and included diarrhea (11%), asthenia (4%), neutropenia (6%), and thrombocytopenia (4%). Eleven patients (24%) required surgical reintervention. Conclusions. Addition of bevacizumab to induction chemotherapy and chemoradiotherapy is feasible, with impressive activity and manageable toxicity. However, caution is recommended regarding surgical complications. PMID:21467148

  18. Addition of bevacizumab to XELOX induction therapy plus concomitant capecitabine-based chemoradiotherapy in magnetic resonance imaging-defined poor-prognosis locally advanced rectal cancer: the AVACROSS study.

    PubMed

    Nogué, Miguel; Salud, Antonieta; Vicente, Pilar; Arriví, Antonio; Roca, José María; Losa, Ferran; Ponce, José; Safont, María José; Guasch, Inmaculada; Moreno, Isabel; Ruiz, Ana; Pericay, Carles

    2011-01-01

    Concomitant chemoradiotherapy followed by total mesorectal excision is standard treatment for locally advanced rectal cancer. This approach, however, focuses on local disease control and delays systemic treatment. Induction chemotherapy has the advantage of earlier administration of systemic therapy and may improve distant control. The objective of the current study was to assess the efficacy and toxicity of adding bevacizumab to induction chemotherapy followed by preoperative bevacizumab-based chemoradiotherapy in patients with locally advanced rectal cancer. Eligible patients had high-risk rectal adenocarcinoma defined by magnetic resonance imaging criteria. Treatment consisted of four 21-day cycles of bevacizumab (7.5 mg/kg) and XELOX (capecitabine plus oxaliplatin), followed by concomitant radiotherapy (50.4 Gy) plus bevacizumab (5 mg/kg every 2 weeks) and capecitabine (825 mg/m2 twice daily on days 1-15). Surgery was scheduled for 6-8 weeks after chemoradiotherapy. The primary endpoint was pathologic complete response (pCR). Between July 2007 and July 2008, 47 patients were recruited. Among 45 patients who underwent surgery, pCR was achieved in 16 patients (36%; 95% confidence interval: 22.29%-51.27%), and an additional 17 patients (38%) had Dworak tumor regression grade 3. R0 resection was performed in 44 patients (98%). Most grade 3/4 adverse events occurred during the induction phase and included diarrhea (11%), asthenia (4%), neutropenia (6%), and thrombocytopenia (4%). Eleven patients (24%) required surgical reintervention. Addition of bevacizumab to induction chemotherapy and chemoradiotherapy is feasible, with impressive activity and manageable toxicity. However, caution is recommended regarding surgical complications.

  19. [A Case of Advanced Rectal Cancer in Which Combined Prostate Removal and ISR Using the da Vinci Surgical System with Preoperative Chemotherapy Allowed Curative Resection].

    PubMed

    Kawakita, Hideaki; Katsumata, Kenji; Kasahara, Kenta; Kuwabara, Hiroshi; Shigoka, Masatoshi; Matsudo, Takaaki; Enomoto, Masanobu; Ishizaki, Tetsuo; Hisada, Masayuki; Kasuya, Kazuhiko; Tsuchida, Akihiko

    2016-11-01

    A 53-year-old male presented with a chief complaint of dyschezia.Lower gastrointestinal endoscopy confirmed the presence of a type II tumor in the lower part of the rectum, and a biopsy detected a well-differentiated adenocarcinoma.As invasion of the prostate and levator muscle of the anus was suspected on diagnostic imaging, surgery was performed after preoperative chemotherapy.With no clear postoperative complications, the patient was discharged 26 days after surgery. After 24 months, the number of urination ranged from 1 to 6, with a Wexner score of 6 and a mild desire to urinate in the absence of incontinence.At present, the patient is alive without recurrence.When combined with chemotherapy, robotassisted surgery allows the curative resection of extensive rectal cancer involving the suspected invasion of other organs.In this respect, it is likely to be a useful method to conserve anal and bladder function.

  20. Technical feasibility of laparoscopic extended surgery beyond total mesorectal excision for primary or recurrent rectal cancer.

    PubMed

    Akiyoshi, Takashi

    2016-01-14

    Relatively little is known about the oncologic safety of laparoscopic surgery for advanced rectal cancer. Recently, large randomized clinical trials showed that laparoscopic surgery was not inferior to open surgery, as evidenced by survival and local control rates. However, patients with T4 tumors were excluded from these trials. Technological advances in the instrumentation and techniques used by laparoscopic surgery have increased the use of laparoscopic surgery for advanced rectal cancer. High-definition, illuminated, and magnified images obtained by laparoscopy may enable more precise laparoscopic surgery than open techniques, even during extended surgery for T4 or locally recurrent rectal cancer. To date, the quality of evidence regarding the usefulness of laparoscopy for extended surgery beyond total mesorectal excision has been low because most studies have been uncontrolled series, with small sample sizes, and long-term data are lacking. Nevertheless, laparoscopic extended surgery for rectal cancer, when performed by specialized laparoscopic colorectal surgeons, has been reported safe in selected patients, with significant advantages, including a clear visual field and less blood loss. This review summarizes current knowledge on laparoscopic extended surgery beyond total mesorectal excision for primary or locally recurrent rectal cancer.

  1. Preoperative Capecitabine and Pelvic Radiation in Locally Advanced Rectal Cancer-Is it Equivalent to 5-FU Infusion Plus Leucovorin and Radiotherapy?

    SciTech Connect

    Chan, Alexander K.; Wong, Alfred O.; Jenken, Daryl A.

    2010-04-15

    Purpose: The aim of this retrospective case-matching study was to compare the treatment outcomes and acute toxicity of preoperative radiotherapy (RT) with capecitabine vs. preoperative RT with intermittent 5-fluorouracil (5-FU) infusion, leucovorin, and mitomycin C in rectal cancer. Methods and Materials: We matched 34 patients who were treated with preoperative concurrent capecitabine and 50 Gy of RT by their clinical T stage (T3 or T4) and the tumor location (<=7 cm or >7 cm from the anal verge) with another 68 patients who were treated with preoperative intermittent 5-FU infusion, leucovorin, mitomycin C, and 50 Gy of RT for a comparison of the pathologic tumor response, local control, distant failure, and survival rates. Results: The pathologic complete response rate was 21% with capecitabine and 18% with 5-FU and leucovorin (p = 0.72). The rate of T downstaging after chemoradiation was 59% for both groups. The rate of sphincter-sparing resection was 38% after capecitabine plus RT and 43% after 5-FU plus RT (p = 0.67). At 3 years, there was no significant difference in the local control rate (93% for capecitabine and 92% for 5-FU and leucovorin), relapse-free rate (74% for capecitabine and 73% for 5-FU and leucovorin), or disease-specific survival rate (86% for capecitabine and 77% for 5-FU and leucovorin). The acute toxicity profile was comparable, with little Grade 3 and 4 toxicity. Conclusions: When administered with concurrent preoperative RT, both capecitabine and intermittent 5-FU infusion with leucovorin modulation provided comparable pathologic tumor response, local control, relapse-free survival, and disease-specific survival rates in rectal cancer.

  2. Current debate in the oncologic management of rectal cancer

    PubMed Central

    Millard, Trish; Kunk, Paul R; Ramsdale, Erika; Rahma, Osama E

    2016-01-01

    Despite the considerable amount of research in the field, the management of locally advanced rectal cancer remains a subject to debate. To date, effective treatment centers on surgical resection with the standard approach of total mesorectal resection. Radiation therapy and chemotherapy have been incorporated in order to decrease local and systemic recurrence. While it is accepted that a multimodality treatment regimen is indicated, there remains significant debate for how best to accomplish this in regards to order, dosing, and choice of agents. Preoperative radiation is the standard of care, yet remains debated with the option for chemoradiation, short course radiation, and even ongoing studies looking at the possibility of leaving radiation out altogether. Chemotherapy was traditionally incorporated in the adjuvant setting, but recent reports suggest the possibility of improved efficacy and tolerance when given upfront. In this review, the major studies in the management of locally advanced rectal cancer will be discussed. In addition, future directions will be considered such as the role of immunotherapy and ongoing trials looking at timing of chemotherapy, inclusion of radiation, and non-operative management. PMID:27795811

  3. Current debate in the oncologic management of rectal cancer.

    PubMed

    Millard, Trish; Kunk, Paul R; Ramsdale, Erika; Rahma, Osama E

    2016-10-15

    Despite the considerable amount of research in the field, the management of locally advanced rectal cancer remains a subject to debate. To date, effective treatment centers on surgical resection with the standard approach of total mesorectal resection. Radiation therapy and chemotherapy have been incorporated in order to decrease local and systemic recurrence. While it is accepted that a multimodality treatment regimen is indicated, there remains significant debate for how best to accomplish this in regards to order, dosing, and choice of agents. Preoperative radiation is the standard of care, yet remains debated with the option for chemoradiation, short course radiation, and even ongoing studies looking at the possibility of leaving radiation out altogether. Chemotherapy was traditionally incorporated in the adjuvant setting, but recent reports suggest the possibility of improved efficacy and tolerance when given upfront. In this review, the major studies in the management of locally advanced rectal cancer will be discussed. In addition, future directions will be considered such as the role of immunotherapy and ongoing trials looking at timing of chemotherapy, inclusion of radiation, and non-operative management.

  4. [Adjuvant radiotherapy in rectal cancer and total mesorectal excision].

    PubMed

    Coco, C; Valentini, V; Verbo, A

    2001-01-01

    Local recurrence (LR) after surgical resection for adenocarcinoma of the rectum still remains an unsolved problem. Local relapse often occurs when tumor spreads in perirectal fat (mesorectum) or along the lateral iliac lymph nodes also when surgery is considered radically. There is a close relationship between local recurrence rate and lymphatic involvement, local tumor extension and tumour grading. Total mesorectal excision (TME) appears to be associated with a reduced LR rate when resection of perirectal fat is done "en-bloc" and when a negative radial margins is obtained. TME allows autonomic nerve sparing and sphincter preservation too, but lateral nodes are not treated by TME. Extended lymphadenectomy with lateral dissection for advanced rectal cancer has been often associated with an increase rate of long term morbidity, particularly regarding urinary and sexual function. Concomitant preoperative chemo-radiation for advanced rectal cancer is a relatively safe procedure with an acceptable morbidity and mortality. This approach is associated with a considerable clinical and pathologic tumor downstaging. Tumor resectability is improved and lateral spreading is also better controlled. An improving in survival and a longer disease free period has been reported. More radical sphincter saving operations are also allowed.

  5. Neoadjuvant chemoradiation therapy and pathological complete response in rectal cancer

    PubMed Central

    Ferrari, Linda; Fichera, Alessandro

    2015-01-01

    The management of rectal cancer has evolved significantly in the last few decades. Significant improvements in local disease control were achieved in the 1990s, with the introduction of total mesorectal excision and neoadjuvant radiotherapy. Level 1 evidence has shown that, with neoadjuvant chemoradiation therapy (CRT) the rates of local recurrence can be lower than 6% and, as a result, neoadjuvant CRT currently represents the accepted standard of care. This approach has led to reliable tumor down-staging, with 15–27% patients with a pathological complete response (pCR)—defined as no residual cancer found on histological examination of the specimen. Patients who achieve pCR after CRT have better long-term outcomes, less risk of developing local or distal recurrence and improved survival. For all these reasons, sphincter-preserving procedures or organ-preserving options have been suggested, such as local excision of residual tumor or the omission of surgery altogether. Although local recurrence rate has been stable at 5–6% with this multidisciplinary management method, distal recurrence rates for locally-advanced rectal cancers remain in excess of 25% and represent the main cause of death in these patients. For this reason, more recent trials have been looking at the administration of full-dose systemic chemotherapy in the neoadjuvant setting (in order to offer early treatment of disseminated micrometastases, thus improving control of systemic disease) and selective use of radiotherapy only in non-responders or for low rectal tumors smaller than 5 cm. PMID:26290512

  6. Postoperative adjuvant chemotherapy in rectal cancer operated for cure.

    PubMed

    Petersen, Sune Høirup; Harling, Henrik; Kirkeby, Lene Tschemerinsky; Wille-Jørgensen, Peer; Mocellin, Simone

    2012-03-14

    Colorectal cancer is one of the most common types of cancer in the Western world. Apart from surgery - which remains the mainstay of treatment for resectable primary tumours - postoperative (i.e., adjuvant) chemotherapy with 5-fluorouracil (5-FU) based regimens is now the standard treatment in Dukes' C (TNM stage III) colon tumours i.e. tumours with metastases in the regional lymph nodes but no distant metastases. In contrast, the evidence for recommendations of adjuvant therapy in rectal cancer is sparse. In Europe it is generally acknowledged that locally advanced rectal tumours receive preoperative (i.e., neoadjuvant) downstaging by radiotherapy (or chemoradiotion), whereas in the US postoperative chemoradiotion is considered the treatment of choice in all Dukes' C rectal cancers. Overall, no universal consensus exists on the adjuvant treatment of surgically resectable rectal carcinoma; moreover, no formal systematic review and meta-analysis has been so far performed on this subject. We undertook a systematic review of the scientific literature from 1975 until March 2011 in order to quantitatively summarize the available evidence regarding the impact of postoperative adjuvant chemotherapy on the survival of patients with surgically resectable rectal cancer. The outcomes of interest were overall survival (OS) and disease-free survival (DFS). CCCG standard search strategy in defined databases with the following supplementary search. 1. Rect* or colorect* - 2. Cancer or carcinom* or adenocarc* or neoplasm* or tumour - 3. Adjuv* - 4. Chemother* - 5. Postoper* Randomised controlled trials (RCT) comparing patients undergoing surgery for rectal cancer who received no adjuvant chemotherapy with those receiving any postoperative chemotherapy regimen. Two authors extracted data and a third author performed an independent search for verification. The main outcome measure was the hazard ratio (HR) between the risk of event between the treatment arm (adjuvant chemotherapy

  7. Proforma-based reporting in rectal cancer.

    PubMed

    Taylor, F; Mangat, N; Swift, I R; Brown, G

    2010-10-04

    The improvements in outcomes associate with the use of preoperative therapy rather than postoperative treatment means that clinical teams are increasingly reliant on imaging to identify high-risk features of disease to determine treatment plans. For many solid tumours, including rectal cancer, validated techniques have emerged in identifying prognostic factors pre-operatively. In the MERCURY study, a standardised scanning technique and the use of reporting proformas enabled consistently accurate assessment and documentation of the prognostic factors. This is now an essential tool to enable our clinical colleagues to make treatment decisions. In this review, we describe the proforma-based reporting tool that enables a systematic approach to the interpretation of the magnetic resonance images, thereby enabling all the clinically relevant features to be adequately assessed.

  8. Chemoembolization Using Irinotecan in Treating Patients With Liver Metastases From Metastatic Colon or Rectal Cancer

    ClinicalTrials.gov

    2015-09-10

    Liver Metastases; Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage IV Colon Cancer; Stage IV Rectal Cancer

  9. Radiotherapy and local control in rectal cancer.

    PubMed

    Valentini, V; Rosetto, M E; Fares, C; Mantini, G; Salvi, G; Turriziani, A

    1998-01-01

    Recurrence is a stage in the natural history of rectal cancer. Preoperative radiotherapy or postoperative radiochemotherapy lower the rate of recurrence, improving local control. From 1980 to 1997, at the "Divisione di Radioterapia" of the "Università Cattolica del S. Cuore" of Rome 380 patients with rectal cancer of early clinical stage T2-3, candidates for surgery for cure, underwent radiation therapy. 119 patients underwent postoperative radiotherapy (45-50 Gy); 45 patients underwent "sandwich" radiotherapy (45 Gy:27 Gy before and 28 Gy after surgery), of whom 7 were treated with preoperative radiotherapy alone; 145 patients underwent preoperative concomitant radiochemotherapy according to 3 different protocols, radiotherapy (38 Gy) combined with mitomycin C and 5-FU; radiotherapy (50.4 Gy) combined with cisplatin and 5-FU; radiotherapy (45 Gy) combined with 5-FU and folinic acid. 71 patients were treated with preoperative radiotherapy (38 Gy) combined with IORT (10 Gy). Median follow-up was 6 years. Overall local control was 85% at 3 years, 83% at 5 years, 81% at 10 years. The rate of local control at 5 years was: 76% for postoperative radiotherapy, 83% for "sandwich" radiotherapy, 84% for preoperative radiochemotherapy and 93% for preoperative radiotherapy combined with IORT. Local control was shown to be significantly better with preoperative treatment as compared to postoperative treatment (p = 0.02). The incidence of metastases was 35% in the patients with local recurrence and 16% in those with local control. The difference in survival was highly significant in patients with local control as compared to those with local recurrence: at 5 years 87% and 32% respectively. Patients with local control showed a lower incidence of metastasis and a better survival.

  10. Phase I-II Trial of Concurrent Capecitabine and Oxaliplatin With Preoperative Intensity-Modulated Radiotherapy in Patients With Locally Advanced Rectal Cancer

    SciTech Connect

    Aristu, Jose Javier Arbea, Leire; Rodriguez, Javier; Hernandez-Lizoain, Jose Luis; Sola, Jesus Javier; Moreno, Marta M.D.; Azcona, Juan Diego; Diaz-Gonzalez, Juan Antonio; Garcia-Foncillas, Jesus Miguel; Martinez-Monge, Rafael

    2008-07-01

    Purpose: To identify the maximal tolerated dose level of preoperative intensity-modulated radiotherapy combined with capecitabine and oxaliplatin and to evaluate the efficacy. Patients and Methods: Patients with rectal T3-T4 and/or N0-N+ rectal cancer received capecitabine 825 mg/m{sup 2} twice daily Monday through Friday and oxaliplatin 60 mg/m{sup 2} intravenously on Days 1, 8, and 15, concurrently with intensity-modulated radiotherapy. The radiation dose was increased in 5.0-Gy steps in cohorts of 3 patients starting from 37.5 Gy in 15 fractions (dose level [DL] 1). DL2 and DL3 were designed to reach 42.5 Gy in 17 fractions and 47.5 Gy in 19 fractions, respectively. Results: No dose-limiting toxicity was observed at DL1 or DL2. Of the 3 patients treated at DL3, 1 presented with Grade 3 diarrhea, which was considered a dose-limiting toxicity, and 3 additional patients were added. Of the 6 patients treated at DL3, no new dose-limiting toxicities were observed, and DL3 was identified as the recommended dose in this study. Eight additional patients were treated at 47.5 Gy. Grade 2 proctitis was the most frequent adverse event (40%); Grade 3 diarrhea occurred in 2 patients (10%). All patients underwent surgery, and 17 patients (85%) underwent R0 resection. Four patients (20%) presented with a histologic response of Grade 4, 11 (55%) with Grade 3+, 2 (15%) with Grade 3, and 2 patients (10%) with Grade 2. Conclusion: The maximal tolerated dose in this study was 47.5 Gy. The high rates of pathologic response of Grade 3+ and 4 must be confirmed through the accrual of new patients in the Phase II study.

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

    PubMed Central

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

    2015-01-01

    Background: Neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery is the mainstay of treatment for locally advanced rectal cancer. Several heparin-binding associated proteins have been reported to play a critical role in cancer progression. However, the clinical relevancies of such proteins and their associations with CCRT response in rectal cancer have not yet to be fully elucidated. Methods: The analysis of a public transcriptome of rectal cancer indicated that thrombospondin 2 (THBS2) is a predictive factor for CCRT response. Immunohistochemical analyses were conducted to evaluate the expression of THBS2 in pretreatment biopsy specimens from rectal cancer patients without distant metastasis. Furthermore, the relationships between THBS2 expression and various clinicopathological factors or survival were analyzed. Results: Low expression of THBS2 was significantly associated with advanced pretreatment tumor (P<0.001) and nodal status (P=0.004), post-treatment tumor (P<0.001) and nodal status (P<0.001), increased vascular invasion (P=0.003), increased perineural invasion (P=0.023) and inferior tumor regression grade (P=0.015). In univariate analysis, low THBS2 expression predicted worse outcomes for disease-free survival, local recurrence-free survival and metastasis-free survival (all P<0.001). In multivariate analysis, low expression of THBS2 still served as a negative prognostic factor for disease-free survival (Hazard ratio=3.057, P=0.002) and metastasis-free survival (Hazard ratio=3.362, P=0.012). Conclusion: Low THBS2 expression was correlated with advanced disease status and low tumor regression after preoperative CCRT and that it acted as an independent negative prognostic factor in rectal cancer. THBS2 may represent a predictive biomarker for CCRT response in rectal cancer. PMID:26807188

  12. A familial component to human rectal cancer, independent of colon cancer risk

    PubMed Central

    Maul, John Scott; Burt, Randall W.; Cannon-Albright, Lisa A.

    2007-01-01

    Background & Aims: The Utah Population Database (UPDB) is unique; it links genealogy for over 2 million Utah individuals to a statewide Cancer Registry. We have investigated the familial nature of rectal cancer, considered independently from colon cancer. Methods: We estimated relative risks in relatives, and average relatedness among rectal cancer cases using matched controls from the UPDB. Results: There is a significant increased risk for rectal cancer in first-degree relatives of rectal cancer cases (Relative Risk = 1.97), equivalent to the risk for colon cancer (RR =2.11). The significant increased risk for rectal cancer extends to second- and third-degree relatives. The relative risk for rectal cancer among first-degree relatives of young-onset rectal cancer cases (< 55 years), is equivalent (RR = 3.34) to their risk of colon cancer (RR=3.35). Conclusions: The UPDB provides strong evidence for a familial component to rectal cancer that may include a genetic component in addition to shared environment. There is a significant increased risk of rectal cancer in the close and distant relatives of rectal cancer cases, which is even higher among relatives of young-onset cases. While it has been reported that relatives of colon cancer probands are at increased risk for colorectal cancer, the risk of large bowel cancer among relatives of rectal cancer patients has been less clear. Relatives of rectal cancer probands experience a risk of cancer of the large bowel that is at least as high as the risk previously reported for relatives of individuals with colon cancer. PMID:17625976

  13. Optimal Imaging Strategies for Rectal Cancer Staging and Ongoing Management.

    PubMed

    Balyasnikova, Svetlana; Brown, Gina

    2016-06-01

    Imaging determines the optimal treatment for rectal cancer patients. High-resolution magnetic resonance imaging (MRI) overcomes many of the known limitations of previous methods. When performed in accordance with the recommended standards, MRI enables accurate staging of both early and advanced rectal cancer, accurate response assessment, the delineation of recurrent disease and planning surgical treatment in a safe and effective manner. Tumour-related high-risk features with known adverse outcomes can be preoperatively identified and treated with neoadjuvant chemoradiotherapy. Further, MRI post-treatment tumour response assessment using TRG grading system also predicts the likely survival outcomes and in the future will be used to modify treatment further by stratification into good and poor responders. There is a paucity of literature with validated outcome data concerning use of diffusion-weighted imaging and positron emission tomography (PET)/computed tomography (CT), and in the absence of any validated methods and outcome data, their use in the initial assessment and restaging after treatment is limited to research protocols. Combination MRI and CT is essential for distant spread assessment and recurrent disease, and currently PET-CT is sometimes used in the workup of patients with recurrent and metastatic disease.

  14. Prognosis and value of preoperative radiotherapy in locally advanced rectal signet-ring cell carcinoma

    PubMed Central

    Ling, Chun-Run; Wang, Rui; Wang, Mo-Jin; Ping, Jie; Zhuang, Wen

    2017-01-01

    As well known, signet-ring cell carcinoma (SRCC) is a rare histological subtype of colorectal adenocarcinoma, which has been associated with poor prognosis and resistant to non-surgery therapy compared with common adenocarcinoma. In this study, we assessed the effect of preoperative radiotherapy (PRT) for locally advanced rectal SRCC in a large patient group from the Surveillance, Epidemiology, and End Results program (SEER, 1988–2011) database. SRCC was found in 0.9% (n = 622) rectal cancer (RC) patients in our study. In the PRT setting, SRCC had significantly worse cancer-specific survival than mucinous adenocarcinoma and nonmucinous adenocarcinoma patients (log-rank, P < 0.001). In terms of SRCC, stage III RC patients benefited from PRT (log-rank, P < 0.001) while stage II did not (P = 0.095). The multivariate Cox proportional hazard model showed that PRT was an independent benefit factor in stage III rectal SRCC patients (HR, 0.611; 95% CI, 0.407–0.919; P = 0.018). In conclusion, SRCC was an independent predictor of poor prognosis in stage III RC patients, but not in stage II. In the PRT setting of locally advanced RC, SRCC patients had significantly worse prognosis. PRT was an independent prognostic factor associated with improved survival in stage III rectal SRCC. PMID:28345614

  15. Fournier gangrene: first manifestation of occult rectal cancer.

    PubMed

    Ruiz-Tovar, J; Córdoba, L; Devesa, J M

    2011-01-01

    Fournier gangrene is a necrotizing fasciitis of the genital and perineal region. Diverse factors predispose to Fournier gangrene, such as diabetes mellitus, ethylism, liver dysfunction, haematological disorders, obesity or recent regional instrumentation. Rectal tumours can also predispose to Fournier gangrene; most of the reported cases are perforated or unresectable colorectal tumours, but some cases of anorectal cancer diagnosed after recovery from Fournier gangrene have also been reported. In these cases, the presence of a rectal tumour at the time of, or prior to, diagnosis of Fournier gangrene could not be ruled out. We present three cases of rectal cancer whose first manifestation was as Fournier gangrene.

  16. Combined-modality therapy for rectal cancer using irinotecan.

    PubMed

    Minsky, Bruce D

    2002-05-01

    Preoperative or postoperative pelvic radiation plus concurrent fluorouracil-based chemotherapy is standard adjuvant treatment for patients with T3 and/or N1/2 rectal cancer. Newer chemotherapeutic regimens have been developed for the treatment of patients with metastatic disease. Irinotecan (CPT-11, Camptosar)-based regimens have improved survival in patients with metastatic disease and are being actively investigated in combination with pelvic radiation therapy for patients with rectal cancer.

  17. [Peri-operative treatments for rectal cancer].

    PubMed

    Gérard, Jean-Pierre; Doyen, Jerome; Bénézery, Karen; Borens, Bruno; Hannoun-Levi, Jean-Michel; François, Éric

    2015-06-01

    Depending on its location or stage, rectal cancer may differ significantly. Before any treatment decision a careful work up is mandatory relying mainly on endoscopy and imaging (MRI). Surgery according to the TME principle is the cornerstone of treatment. Most of the time surgery is associated with external beam radiotherapy often combined with concurrent chemotherapy (capecitabine) according to the neoadjuvant regimen CAP 50 (5 weeks long). It is sometimes possible to escalate safely the dose of irradiation using contact X-ray brachytherapy 50 Kv or Iridium 192 interstitial brachytherapy. Adjuvant chemotherapy may be given in case of pejorative pathological findings but its benefit is not yet proven in contrast with colon cancer. Local recurrences are becoming unusual as is permanent APE surgery with permanent stoma. To reduce the risk of distant metastasis clinical trials are testing first line chemotherapy in T3-4 lesions. For early stage (T2-"small" T3) clinical trials try to achieve organ preservation. Intensification of CAP 50 either with more chemotherapy or radiation dose escalation using contact X-ray aim at achieving a clinical complete response followed by local excision or close surveillance.

  18. Patterns of metastasis in colon and rectal cancer

    PubMed Central

    Riihimäki, Matias; Hemminki, Akseli; Sundquist, Jan; Hemminki, Kari

    2016-01-01

    Investigating epidemiology of metastatic colon and rectal cancer is challenging, because cancer registries seldom record metastatic sites. We used a population based approach to assess metastatic spread in colon and rectal cancers. 49,096 patients with colorectal cancer were identified from the nationwide Swedish Cancer Registry. Metastatic sites were identified from the National Patient Register and Cause of Death Register. Rectal cancer more frequently metastasized into thoracic organs (OR = 2.4) and the nervous system (1.5) and less frequently within the peritoneum (0.3). Mucinous and signet ring adenocarcinomas more frequently metastasized within the peritoneum compared with generic adenocarcinoma (3.8 [colon]/3.2 [rectum]), and less frequently into the liver (0.5/0.6). Lung metastases occurred frequently together with nervous system metastases, whereas peritoneal metastases were often listed with ovarian and pleural metastases. Thoracic metastases are almost as common as liver metastases in rectal cancer patients with a low stage at diagnosis. In colorectal cancer patients with solitary metastases the survival differed between 5 and 19 months depending on T or N stage. Metastatic patterns differ notably between colon and rectal cancers. This knowledge should help clinicians to identify patients in need for extra surveillance and gives insight to further studies on the mechanisms of metastasis. PMID:27416752

  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. Do high radiation doses in locally advanced prostate cancer patients treated with 103Pd implant plus external beam irradiation cause increased urinary, rectal, and sexual morbidity?

    PubMed

    Stone, Nelson N; Cesaretti, Jamie A; Rosenstein, Barry; Stock, Richard G

    2010-01-01

    To investigate the morbidity of higher radiation doses in prostate cancer patients. Five hundred eighty-five men treated with seed implantation and external beam irradiation were followed a median of 5 years (range, 2-11). Hormonal therapy (HT) of 9 months duration was used in 504 (86.2%) patients. The biologic effective dose (BED) was calculated using an alpha/beta of 2. Urinary incontinence (UI) and symptoms (IPSS) were prospectively collected. Rectal morbidity was scored according to the Radiation Therapy Oncology Group (RTOG) scale. Two BED dose groups of 220 Gy (n=136) were used. Comparisons of means were made by Student's t test, and the associations were tested by chi-square analysis (Pearson). Urinary retention developed in 36 (6.2%) and was not associated with BED or IPSS. Retention occurred more often with prostate volume >50 cc (17%, p=0.001). The median change in urinary symptoms (IPSS) was 1. Sixty-one percent with high BED were more likely to have increased postimplant symptoms compared with 39% with lower BED (p=0.025; odds ratio [OR], 1.107; 95% confidence interval [CI], 1.10-1.21). UI occurred in 25 patients (4.3%) and was only associated with a postimplant transurethral resection of the prostate (TURP) (n=25), 16% vs. 2.3% for no TURP (p=0.001; OR, 8; 95% CI, 2.4-27). Of the 373 patients initially potent, 204 (54.7%) maintained potency. Impotence was only associated with age at implant (p=0.001) and HT (p=0.004). Sixty-two (10.6%) patients had Grade 1-2 and 4 patients had Grade 3-4 (0.7%, 2 ulcers and 2 fistulas) rectal complications. Three of the Grade 3/4 complications occurred with a dose 220 Gy does not seem to increase morbidity. (c) 2010 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  1. Extralevator abdominoperineal excision versus conventional surgery for low rectal cancer: a single surgeon experience

    PubMed Central

    Neşşar, Gürel; Demirbağ, Ali Eba; Celep, Bahadır; Elbir, Orhan Hayri; Kayaalp, Cüneyt

    2016-01-01

    Objective Extralevator abdominoperineal excision (ELAPE) reduces the risk of positive circumferential resection margin (CRM) and of intraoperative perforation (IOP), both of which are associated with high local recurrence rates and poor survival outcomes for rectal cancer. The aim of this study was to compare the results of ELAPE with conventional abdominoperineal excision (APE) for low rectal cancer. Material and Methods A total of 25 consecutive patients underwent ELAPE for low rectal cancer between November 2008 and September 2011. Fifty-six patients treated by conventional APE prior to 2008 were selected from our rectal cancer database for comparison as a historical cohort. Results The mean follow-up was 44.7 months in the ELAPE group, and 70.6 months in the APE group. Patients undergoing ELAPE had a lower CRM positivity and IOP rate than APE (12% vs. 20%, p=0,531; 4% vs. 8,9%, p=0,826; respectively). The ELAPE group was associated with higher perineal wound complications than the APE group (16.0% vs. 1.8%, p=0.030). Local recurrence rates for patients in both groups did not differ significantly (4.0% vs. 3.6%, p=1.0). Conclusion The results of this study suggest that ELAPE technique was associated with less CRM involvement and reduced rates of IOP but markedly higher rates of postoperative perineal complications occurred as compared to conventional surgery. ELAPE must be reserved for advanced low rectal cancers. PMID:28149119

  2. Phase II Study of Preoperative Capecitabine and Oxaliplatin-based Intensified Chemoradiotherapy With or Without Induction Chemotherapy in Patients With Locally Advanced Rectal Cancer and Synchronous Liver-limited Resectable Metastases

    PubMed Central

    Cho, Hyungwoo; Kim, Jeong Eun; Kim, Kyu-pyo; Yu, Chang Sik; Kim, Jin Cheon; Kim, Jong Hoon; Lee, Myung Ah; Jang, Hong Seok; Oh, Seong Taek; Kim, Sun Young; Oh, Jae Hwan; Kim, Dae Yong; Hong, Yong Sang

    2016-01-01

    Objectives: Controversy surrounds the management of patients with locally advanced rectal cancer with synchronous resectable liver metastases (LMs). This study was designed to improve both systemic and local control in these patients. Methods: Patients with locally advanced rectal cancer (cT3-4N0 or cTanyN1-2) and synchronous resectable liver-limited metastases (cM1a) were randomly assigned to receive either preoperative treatments of induction CapeOx, followed by chemoradiotherapy with CapeOx (CapeOx-RT) (arm A) or CapeOx-RT alone (arm B). Induction CapeOx consisted of oxaliplatin 130 mg/m2 on day 1 and capecitabine 1000 mg/m2 twice daily on days 1 to 14, every 3 weeks for 2 cycles; CapeOx-RT consisted of radiotherapy with 45 Gy/25 daily fractions±5.4 Gy/3 fractions, oxaliplatin 50 mg/m2 weekly for 5 weeks, and capecitabine 825 mg/m2 twice daily on days 1 to 38. Total mesorectal excision and simultaneous liver metastasectomy were planned within 6 weeks after completion of preoperative treatments. The primary endpoint was R0 resection rate of both the primary tumor and LMs. Results: Thirty-eight patients were randomly assigned to the present study, 18 to arm A and 20 to arm B. The overall R0 resection rate for both the primary tumor and LMs was 77.8% in arm A and 70.0% in arm B (P=0.72). The median progression-free survival was 14.2 versus 15.1 months (P=0.422) and the 3-year overall survival rate was 75.0% versus 88.8% (P=0.29), respectively. Conclusions: Both treatment strategies showed considerable R0 resection rates; however, further study will be warranted to apply these intensified strategies in clinical practice. PMID:27322695

  3. The effect of neoadjuvant chemoradiotherapy on whole-body physical fitness and skeletal muscle mitochondrial oxidative phosphorylation in vivo in locally advanced rectal cancer patients--an observational pilot study.

    PubMed

    West, Malcolm A; Loughney, Lisa; Lythgoe, Daniel; Barben, Christopher P; Adams, Valerie L; Bimson, William E; Grocott, Michael P W; Jack, Sandy; Kemp, Graham J

    2014-01-01

    In the United Kingdom, patients with locally advanced rectal cancer routinely receive neoadjuvant chemoradiotherapy. However, the effects of this on physical fitness are unclear. This pilot study is aimed to investigate the effect of neoadjuvant chemoradiotherapy on objectively measured in vivo muscle mitochondrial function and whole-body physical fitness. We prospectively studied 12 patients with rectal cancer who completed standardized neoadjuvant chemoradiotherapy, recruited from a large tertiary cancer centre, between October 2012 and July 2013. All patients underwent a cardiopulmonary exercise test and a phosphorus magnetic resonance spectroscopy quadriceps muscle exercise-recovery study before and after neoadjuvant chemoradiotherapy. Data were analysed and reported blind to patient identity and clinical course. Primary variables of interest were the two physical fitness measures; oxygen uptake at estimated anaerobic threshold and oxygen uptake at Peak exercise (ml.kg-1.min-1), and the post-exercise phosphocreatine recovery rate constant (min-1), a measure of muscle mitochondrial capacity in vivo. Median age was 67 years (IQR 64-75). Differences (95%CI) in all three primary variables were significantly negative post-NACRT: Oxygen uptake at estimated anaerobic threshold -2.4 ml.kg-1.min-1 (-3.8, -0.9), p = 0.004; Oxygen uptake at Peak -4.0 ml.kg-1.min-1 (-6.8, -1.1), p = 0.011; and post-exercise phosphocreatine recovery rate constant -0.34 min-1 (-0.51, -0.17), p<0.001. The significant decrease in both whole-body physical fitness and in vivo muscle mitochondrial function raises the possibility that muscle mitochondrial mechanisms, no doubt multifactorial, may be important in deterioration of physical fitness following neoadjuvant chemoradiotherapy. This may have implications for targeted interventions to improve physical fitness pre-surgery. Clinicaltrials.gov registration NCT01859442.

  4. The Effect of Neoadjuvant Chemoradiotherapy on Whole-Body Physical Fitness and Skeletal Muscle Mitochondrial Oxidative Phosphorylation In Vivo in Locally Advanced Rectal Cancer Patients – An Observational Pilot Study

    PubMed Central

    West, Malcolm A.; Loughney, Lisa; Lythgoe, Daniel; Barben, Christopher P.; Adams, Valerie L.; Bimson, William E.; Grocott, Michael P. W.; Jack, Sandy; Kemp, Graham J.

    2014-01-01

    Background In the United Kingdom, patients with locally advanced rectal cancer routinely receive neoadjuvant chemoradiotherapy. However, the effects of this on physical fitness are unclear. This pilot study is aimed to investigate the effect of neoadjuvant chemoradiotherapy on objectively measured in vivo muscle mitochondrial function and whole-body physical fitness. Methods We prospectively studied 12 patients with rectal cancer who completed standardized neoadjuvant chemoradiotherapy, recruited from a large tertiary cancer centre, between October 2012 and July 2013. All patients underwent a cardiopulmonary exercise test and a phosphorus magnetic resonance spectroscopy quadriceps muscle exercise-recovery study before and after neoadjuvant chemoradiotherapy. Data were analysed and reported blind to patient identity and clinical course. Primary variables of interest were the two physical fitness measures; oxygen uptake at estimated anaerobic threshold and oxygen uptake at Peak exercise (ml.kg−1.min−1), and the post-exercise phosphocreatine recovery rate constant (min−1), a measure of muscle mitochondrial capacity in vivo. Results Median age was 67 years (IQR 64–75). Differences (95%CI) in all three primary variables were significantly negative post-NACRT: Oxygen uptake at estimated anaerobic threshold −2.4 ml.kg−1.min−1 (−3.8, −0.9), p = 0.004; Oxygen uptake at Peak −4.0 ml.kg−1.min−1 (−6.8, −1.1), p = 0.011; and post-exercise phosphocreatine recovery rate constant −0.34 min−1 (−0.51, −0.17), p<0.001. Conclusion The significant decrease in both whole-body physical fitness and in vivo muscle mitochondrial function raises the possibility that muscle mitochondrial mechanisms, no doubt multifactorial, may be important in deterioration of physical fitness following neoadjuvant chemoradiotherapy. This may have implications for targeted interventions to improve physical fitness pre-surgery. Trial Registration Clinicaltrials

  5. Multiple differential expression networks identify key genes in rectal cancer.

    PubMed

    Li, Ri-Heng; Zhang, Ai-Min; Li, Shuang; Li, Tian-Yang; Wang, Lian-Jing; Zhang, Hao-Ran; Li, Ping; Jia, Xiong-Jie; Zhang, Tao; Peng, Xin-Yu; Liu, Min-Di; Wang, Xu; Lang, Yan; Xue, Wei-Lan; Liu, Jing; Wang, Yan-Yan

    2016-01-01

    Rectal cancer is an important contributor to cancer mortality. The objective of this paper is to identify key genes across three phenotypes (fungating, polypoid and polypoid & small-ulcer) of rectal cancer based on multiple differential expression networks (DENs). Differential interactions and non-differential interactions were evaluated according to Spearman correlation coefficient (SCC) algorithm, and were selected to construct DENs. Topological analysis was performed for exploring hub genes in largest components of DENs. Key genes were denoted as intersections between nodes of DENs and rectal cancer associated genes from Genecards. Finally, we utilized hub genes to classify phenotypes of rectal cancer on the basis of support vector machines (SVM) methodology. We obtained 19 hub genes and total 12 common key genes of three largest components of DENs, and EGFR was the common element. The SVM results revealed that hub genes could classify phenotypes, and validated feasibility of DEN methods. We have successfully identified significant genes (such as EGFR and UBC) across fungating, polypoid and polypoid & small-ulcer phenotype of rectal cancer. They might be potential biomarkers for classification, detection and therapy of this cancer.

  6. Adjuvant chemotherapy for rectal cancer: Is it needed?

    PubMed Central

    Milinis, Kristijonas; Thornton, Michael; Montazeri, Amir; Rooney, Paul S

    2015-01-01

    Adjuvant chemotherapy has become a standard treatment of advanced rectal cancer in the West. The benefits of adjuvant chemotherapy after surgery alone have been well established. However, controversy surrounds the use adjuvant chemotherapy in patients who received preoperative chemoradiotherapy, despite it being recommended by a number of international guidelines. Results of recent multicentre randomised control trials showed no benefit of adjuvant chemotherapy in terms of survival and rates of distant metastases. However, concerns exist regarding the quality of the studies including inadequate staging modalities, out-dated chemotherapeutic regimens and surgical approaches and small sample sizes. It has become evident that not all the patients respond to adjuvant chemotherapy and more personalised approach should be employed when considering the benefits of adjuvant chemotherapy. The present review discusses the strengths and weaknesses of the current evidence-base and suggests improvements for future studies. PMID:26677436

  7. [Quality standards in rectal cancer surgery].

    PubMed

    Pera, M; Pascual, M

    2005-01-01

    The results of surgery for rectal cancer have classically been measured through indicators such as morbidity, mortality, and length of hospital stay. In the last few years other parameters have been included that evaluate healthcare quality such as the functional results of the surgical technique employed and quality of life. Total resection of the mesorectum, performed by experienced surgeons, is the surgical technique of choice. Currently, the sphincter can be preserved in 70% of patients. Anastomotic dehiscence after anterior resection of the rectum is the most serious complication and the most important risk factor is the height of the anastomosis. The overall dehiscence rate should be less than 15% and operative mortality should be between 2% and 3%. The colonic reservoir improves functional outcome and consequently it is the procedure of choice to reconstruct transit after low anterior resection. Local recurrence should be less than 10% and 5-year survival should be between 70% and 80%. In general, quality of life is better after anterior resection of the rectum than after abdominoperineal amputation, despite the functional deterioration presented by some patients.

  8. What is being researched in rectal cancer?

    PubMed

    Reina Duarte, Angel; Ferrer Márquez, Manuel; Rubio Gil, Francisco A; Belda Lozano, Ricardo; Alvarez García, Antonio; Blesa Sierra, Isabel; Fuentes Porcel, Orlando; Vidaña Márquez, Elisa; Rosado Cobian, Rafael

    2014-11-25

    Clinical evidence has a more significant role in medical specialties than in surgery. Rectal cancer (CR) is no exception. This paper explores what CR-related subjects are being investigated at the present time in a quantitative and qualitative way and analyzes this information to know what possible answers clinical research could give us in the future. The data collection was carried out in April 2014 and was based on 3 sources: 2 institutional clinical trials registries -American (clinicaltrials.gov) and European (EU Clinical Trials Register)- and a survey given to members of the Asociación Española de Coloproctología (AECP). The obtained studies were exported to a database designed especially for this review, which included a number of descriptive elements that would allow the cataloging of the different studies. The AECP survey results were analyzed separately. There are currently 216 clinical trials ongoing related to CR. Two-thirds are primarily conducted by oncologists. Nearly a third are surgical. The research focuses on improving preoperative treatment: new drugs, new schemes of chemo-radiotherapy (usually induction or consolidation schemes) or optimization of radiotherapy and its effects. Surgical clinical trials are related to robotics, laparoscopy, stoma, low colorectal anastomosis, distal CR and local treatment. Most of the current clinical trials ongoing on CR are analyzing aspects of chemo-radiotherapy and its effects. A third focus on purely surgical issues. Copyright © 2014 AEC. Published by Elsevier Espana. All rights reserved.

  9. Predictive response biomarkers in rectal cancer neoadjuvant treatment.

    PubMed

    Agostini, Marco; Crotti, Sara; Bedin, Chiara; Cecchin, Erika; Maretto, Isacco; D'Angelo, Edoardo; Pucciarelli, Salvatore; Nitti, Donato

    2014-01-01

    Locally advanced rectal cancer (RC) treatment is a challenge, because RC has a high rate of local recurrence. To date preoperative chemoradiotherapy (pCRT) is widely accepted as standard protocol of care for middle-low RC, but complete tumour response rate ranges from 4 to 44% and 5-year local recurrence rate is 6%. Better understanding of molecular biology and carcinogenesis pathways could be used both for pre-neoplastic lesions and locally recurrence diagnosis, and for tumour response prediction to therapy. Circulating molecules, gene expression and protein signature are promising sources to biomarker discovery. Several studies have evaluated potential predictors of response and recently, cell-free Nucleic Acid levels have been associated to tumour response to neoadjuvant therapies. Alternative method is the serum or plasma proteome and peptidome analysis. It may be ideally suited for its minimal invasiveness and it can be repeated at multiple time points throughout the treatment in contrast to tissue-based methods which still remain the most reliable and specific approach. Many studies have analyzed preoperative rectal tissue prognostic factor, but data are controversial or not confirmed.

  10. Unique considerations in the patient with rectal cancer.

    PubMed

    Minsky, Bruce D

    2011-08-01

    In the past two decades, substantial progress has been made in the adjuvant management of colorectal cancer. Chemotherapy has improved overall survival in patients with node-positive (N+) disease. In contrast with colon cancer, which has a low incidence of local recurrence, patients with rectal cancer have a higher incidence requiring the addition of pelvic radiation therapy (chemoradiation). Patients with rectal cancer have a number of unique management considerations: for example, the role of short-course radiation, whether postoperative adjuvant chemotherapy is necessary for all patients, and if the type of surgery following chemoradiation should be based on the response rate. More accurate imaging techniques and/or molecular markers may help identify patients with positive pelvic nodes to reduce the chance of overtreatment with preoperative therapy. Will more effective systemic agents both improve the results of radiation as well as modify the need for pelvic radiation? This review will address these and other controversies specific to patients with rectal cancer.

  11. Preoperative Radiotherapy of Advanced Rectal Cancer With Capecitabine and Oxaliplatin With or Without Cetuximab: A Pooled Analysis of Three Prospective Phase I-II Trials

    SciTech Connect

    Weiss, Christian; Arnold, Dirk; Dellas, Kathrin; Liersch, Torsten; Hipp, Matthias; Fietkau, Rainer; Sauer, Rolf; Hinke, Axel; Roedel, Claus

    2010-10-01

    Purpose: A pooled analysis of three prospective trials of preoperative radiochemotherapy (RCT) for rectal cancer by using oxaliplatin and capecitabine with or without cetuximab was performed to evaluate the impact of additional cetuximab on pathologic complete response (pCR) rates and tumor regression (TRG) grades. Methods and Materials: Of 202 patients, 172 patients met the inclusion criteria (primary tumor stage II/III, M0). All patients received concurrent RCT, and 46 patients received additional cetuximab therapy. A correlation of pretreatment clinicopathologic factors and cetuximab treatment with early pCR rates (TRG > 50%) was performed with univariate and multivariate analyses. Toxicity data were recorded for all patients. Results: Of 172 patients, 24 (14%) patients achieved a pCR, and 84 of 172 (71%) patients showed a TRG of >50% in the surgical specimen assessment after preoperative treatment. Age, gender, and T/N stages, as well as localization of the tumor, were not associated with pCR or good TRG. The pCR rate was 16% after preoperative RCT alone and 9% with concurrent cetuximab therapy (p = 0.32). A significantly reduced TRG of >50% was found after RCT with cetuximab compared to RCT alone (p = 0.0035). This was validated by a multivariate analysis with all available clinical factors (p = 0.0037). Acute toxicity and surgical complications were not increased with additional cetuximab. Conclusions: Triple therapy with RCT and cetuximab seems to be feasible, with no unexpected toxicity. Early response assessment (TRG), however, suggests subadditive interaction. A longer follow-up (and finally randomized trials) is needed to draw any firm conclusions with respect to local and distant failure rates.

  12. Toward Restored Bowel Health in Rectal Cancer Survivors.

    PubMed

    Steineck, Gunnar; Schmidt, Heike; Alevronta, Eleftheria; Sjöberg, Fei; Bull, Cecilia Magdalena; Vordermark, Dirk

    2016-07-01

    As technology gets better and better, and as clinical research provides more and more knowledge, we can extend our ambition to cure patients from cancer with restored physical health among the survivors. This increased ambition requires attention to grade 1 toxicity that decreases quality of life. It forces us to document the details of grade 1 toxicity and improve our understanding of the mechanisms. Long-term toxicity scores, or adverse events as documented during clinical trials, may be regarded as symptoms or signs of underlying survivorship diseases. However, we lack a survivorship nosology for rectal cancer survivors. Primarily focusing on radiation-induced side effects, we highlight some important observations concerning late toxicity among rectal cancer survivors. With that and other data, we searched for a preliminary survivorship-disease nosology for rectal cancer survivors. We disentangled the following survivorship diseases among rectal cancer survivors: low anterior resection syndrome, radiation-induced anal sphincter dysfunction, gut wall inflammation and fibrosis, blood discharge, excessive gas discharge, excessive mucus discharge, constipation, bacterial overgrowth, and aberrant anatomical structures. The suggested survivorship nosology may form the basis for new instruments capturing long-term symptoms (patient-reported outcomes) and professional-reported signs. For some of the diseases, we can search for animal models. As an end result, the suggested survivorship nosology may accelerate our understanding on how to prevent, ameliorate, or eliminate manifestations of treatment-induced diseases among rectal cancer survivors.

  13. EURECCA consensus conference highlights about colon & rectal cancer multidisciplinary management: the radiology experts review.

    PubMed

    Tudyka, V; Blomqvist, L; Beets-Tan, R G H; Boelens, P G; Valentini, V; van de Velde, C J; Dieguez, A; Brown, G

    2014-04-01

    Some interesting shifts have taken place in the diagnostic approach for detection of colorectal lesions over the past decade. This article accompanies the recent EURECCA consensus group reccomendations for optimal management of colon and rectal cancers. In summary, imaging has a crucial role to play in the diagnosis, staging assessment and follow up of patients with colon and rectal cancer. Recent advances include the use of CT colonography instead of Barium Enema in the diagnosis of colonoic cancer and as an alternative to colonoscopy. Modern mutlidetector CT scanning techniques have also shown improvements in prognostic stratification of patients with colonic cancer and clinical trials are underway testing the selective use of neoadjuvant therapy for imaging identified high risk colon cancers. In rectal cancer, high resolution MRI with a voxel size less or equal to 3 × 1 × 1 mm3 on T2-weighted images has a proven ability to accurately stage patients with rectal cancer. Moreover, preoperative identification of prognostic features allows stratification of patients into different prognostic groups based on assessment of depth of extramural spread, relationship of the tumour edge to the mesorectal fascia (MRF) and extramural venous invasion (EMVI). These poor prognostic features predict an increased risk of local recurrence and/or metastatic disease and should form the basis for preoperative local staging and multidisciplinary preoperative discussion of patient treatment options.

  14. Low Rectal Cancer Study (MERCURY II)

    ClinicalTrials.gov

    2016-03-11

    Adenocarcinoma; Adenocarcinoma, Mucinous; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Cystic, Mucinous, and Serous; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

  15. Laparoscopic versus open total mesorectal excision for rectal cancer.

    PubMed

    Vennix, Sandra; Pelzers, Loeki; Bouvy, Nicole; Beets, Geerard L; Pierie, Jean-Pierre; Wiggers, Theo; Breukink, Stephanie

    2014-04-15

    effects on five-year disease-free survival (OR 1.02; 95% CI 0.76 to1.38, 4 studies, N = 943). The estimated effects of laparoscopic and open TME on local recurrence and overall survival were similar, although confidence intervals were wide, both with moderate quality evidence (local recurrence: OR 0.89; 95% CI 0.57 to1.39 and overall survival rate: OR 1.15; 95% CI 0.87 to1.52). There was moderate to high quality evidence that the number of resected lymph nodes and surgical margins were similar between the two groups.For the short-term results, length of hospital stay was reduced by two days (95% CI -3.22 to -1.10), moderate quality evidence), and the time to first defecation was shorter in the LTME group (-0.86 days; 95% CI -1.17 to -0.54). There was moderate quality evidence that 30 days morbidity were similar in both groups (OR 0.94; 95% CI 0.8 to 1.1). There were fewer wound infections (OR 0.68; 95% CI 0.50 to 0.93) and fewer bleeding complications (OR 0.30; 95% CI 0.10 to 0.93) in the LTME group.There was no clear evidence of any differences in quality of life after LTME or OTME regarding functional recovery, bladder and sexual function. The costs were higher for LTME with differences up to GBP 2000 for direct costs only. We have found moderate quality evidence that laparoscopic total mesorectal excision (TME) has similar effects to open TME on long term survival outcomes for the treatment of rectal cancer. The quality of the evidence was downgraded due to imprecision and further research could impact on our confidence in this result. There is moderate quality evidence that it leads to better short-term post-surgical outcomes in terms of recovery for non-locally advanced rectal cancer. Currently results are consistent in showing a similar disease-free survival and overall survival, and for recurrences after at least three years and up to 10 years, although due to imprecision we cannot rule out superiority of either approach. We await long-term data from a number of

  16. Sexual Function in Males After Radiotherapy for Rectal Cancer

    SciTech Connect

    Bruheim, Kjersti; Guren, Marianne G.; Dahl, Alv A.; Skovlund, Eva; Balteskard, Lise; Carlsen, Erik; Fossa, Sophie D.; Tveit, Kjell Magne

    2010-03-15

    Purpose: Knowledge of sexual problems after pre- or postoperative radiotherapy (RT) with 50 Gy for rectal cancer is limited. In this study, we aimed to compare self-rated sexual functioning in irradiated (RT+) and nonirradiated (RT-) male patients at least 2 years after surgery for rectal cancer. Methods and Materials: Patients diagnosed with rectal cancer from 1993 to 2003 were identified from the Norwegian Rectal Cancer Registry. Male patients without recurrence at the time of the study. The International Index of Erectile Function, a self-rated instrument, was used to assess sexual functioning, and serum levels of serum testosterone were measured. Results: Questionnaires were returned from 241 patients a median of 4.5 years after surgery. The median age was 67 years at survey. RT+ patients (n = 108) had significantly poorer scores for erectile function, orgasmic function, intercourse satisfaction, and overall satisfaction with sex life compared with RT- patients (n = 133). In multiple age-adjusted analysis, the odds ratio for moderate-severe erectile dysfunction in RT+ patients was 7.3 compared with RT- patients (p <0.001). Furthermore, erectile dysfunction of this degree was associated with low serum testosterone (p = 0.01). Conclusion: RT for rectal cancer is associated with significant long-term effects on sexual function in males.

  17. Elevated Platelet Count as Predictor of Recurrence in Rectal Cancer Patients Undergoing Preoperative Chemoradiotherapy Followed by Surgery

    PubMed Central

    Toiyama, Yuji; Inoue, Yasuhiro; Kawamura, Mikio; Kawamoto, Aya; Okugawa, Yoshinaga; Hiro, Jyunichiro; Saigusa, Susumu; Tanaka, Koji; Mohri, Yasuhiko; Kusunoki, Masato

    2015-01-01

    The impact of systemic inflammatory response (SIR) on prognostic and predictive outcome in rectal cancer after neoadjuvant chemoradiotherapy (CRT) has not been fully investigated. This retrospective study enrolled 89 patients with locally advanced rectal cancer who underwent neoadjuvant CRT and for whom platelet (PLT) counts and SIR status [neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR)] were available. Both clinical values of PLT and SIR status in rectal cancer patients were investigated. Elevated PLT, NLR, PLR, and pathologic TNM stage III [ypN(+)] were associated with significantly poor overall survival (OS). Elevated PLT, NLR, and ypN(+) were shown to independently predict OS. Elevated PLT and ypN(+) significantly predicted poor disease-free survival (DFS). Elevated PLT was identified as the only independent predictor of DFS. PLT counts are a promising pre-CRT biomarker for predicting recurrence and poor prognosis in rectal cancer. PMID:25692418

  18. Lifetime costs of colon and rectal cancer management in Canada.

    PubMed

    Maroun, Jean; Ng, Edward; Berthelot, Jean-Marie; Le Petit, Christel; Dahrouge, Simone; Flanagan, William M; Walker, Hugh; Evans, William K

    2003-01-01

    Colorectal cancer is the second leading cause of cancer-related mortality among Canadians. We derived the direct health care costs associated with the lifetime management of an estimated 16,856 patients with a diagnosis of colon and rectal cancer in Canada in 2000. Information on diagnostic approaches, treatment algorithms, follow-up and care at disease progression was obtained from various databases and was integrated into Statistics Canada's Population Health Model (POHEM) to estimate lifetime costs. The average lifetime cost (in Canadian dollars) of managing patients with colorectal cancer ranged from $20,319 per case for TNM stage I colon cancer to $39,182 per case for stage III rectal cancer. The total lifetime treatment cost for the cohort of patients in 2000 was estimated to be over $333 million for colon and $187 million for rectal cancer. Hospitalization represented 65% and 61% of the lifetime costs of colon and rectal cancer respectively. Disease costing models can be important policy- relevant tools to assist in resource allocation. Our results highlight the importance of performing preoperative tests and staging in an ambulatory care setting, where possible, to achieve optimal cost efficiencies. Similarly, terminal care might be delivered more efficiently in the home environment or in palliative care units.

  19. Results of radical surgery for rectal cancer.

    PubMed

    Heald, R J; Karanjia, N D

    1992-01-01

    This paper examines the hypothesis that a reduction in the distal mural margin during anterior resection for sphincter conservation in rectal cancer excision is safe, provided total mesorectal excision is undertaken with wash-out of the clamped rectum. One hundred ninety-two patients underwent anterior resection and 21 (less than 10%) patients underwent abdomino-perineal excision (APE) by one surgeon (RJH). Anterior resections were classified as "curative" (79%) and "non-curative" (21%); in the "curative" sub-group less than 4% of patients developed local recurrence. The series was retrospectively analyzed for the effect of mural margins on local recurrence with 152 patients undergoing "curative" anterior resections and 40 patients undergoing "non-curative" resections. In the 152 specimens from curative resections, 110 had a resection margin greater than 1 cm and 42 had a resection margin less than 1 cm. Four patients developed local recurrence in the greater than 1 cm margin group (95% confidence interval: 0.8%-7.8%) and no patients developed local recurrence in the less than or equal to 1 cm margin group (95% confidence interval: 0%-5.9%). In each patient with local recurrence a cause for failure was apparent. There was no statistically significant difference in local recurrence rate between the less than or equal to 1 cm margin group and the greater than 1 cm margin group. A reduction in resection margin therefore did not compromise survival after anterior resection. The significance of lateral resection margins is discussed. The role of deep radiotherapy and cytotoxics are considered.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. 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

  1. Definition and delineation of the clinical target volume for rectal cancer

    SciTech Connect

    Roels, Sarah; Duthoy, Wim; Haustermans, Karin . E-mail: Karin.Haustermans@uzleuven.be; Penninckx, Freddy; Vandecaveye, Vincent; Boterberg, Tom; Neve, Wilfried de

    2006-07-15

    Purpose: Optimization of radiation techniques to maximize local tumor control and to minimize small bowel toxicity in locally advanced rectal cancer requires proper definition and delineation guidelines for the clinical target volume (CTV). The purpose of this investigation was to analyze reported data on the predominant locations and frequency of local recurrences and lymph node involvement in rectal cancer, to propose a definition of the CTV for rectal cancer and guidelines for its delineation. Methods and Materials: Seven reports were analyzed to assess the incidence and predominant location of local recurrences in rectal cancer. The distribution of lymphatic spread was analyzed in another 10 reports to record the relative frequency and location of metastatic lymph nodes in rectal cancer, according to the stage and level of the primary tumor. Results: The mesorectal, posterior, and inferior pelvic subsites are most at risk for local recurrences, whereas lymphatic tumor spread occurs mainly in three directions: upward into the inferior mesenteric nodes; lateral into the internal iliac lymph nodes; and, in a few cases, downward into the external iliac and inguinal lymph nodes. The risk for recurrence or lymph node involvement is related to the stage and the level of the primary lesion. Conclusion: Based on a review of articles reporting on the incidence and predominant location of local recurrences and the distribution of lymphatic spread in rectal cancer, we defined guidelines for CTV delineation including the pelvic subsites and lymph node groups at risk for microscopic involvement. We propose to include the primary tumor, the mesorectal subsite, and the posterior pelvic subsite in the CTV in all patients. Moreover, the lateral lymph nodes are at high risk for microscopic involvement and should also be added in the CTV.

  2. Rectal Cancer in Patients Under 50 Years of Age.

    PubMed

    Dinaux, A M; Leijssen, L G J; Bordeianou, L G; Kunitake, H; Berger, D L

    2017-08-25

    General population screening for colorectal cancer starts at 50, and incidence rates of rectal cancer in patients over 50 years old are decreasing. However, incidence of rectal cancer under age 50 is increasing. This paper analyzes short-and long-term outcomes for rectal cancer patients under 50 years of age. Retrospective analyses of consecutive patient cohort, who all received surgical treatment for primary rectal adenocarcinoma at a single institute were used in the study. Outcomes were stratified based on age under or over 50 at the time of surgery. A total of 582 patients was included, of whom 125 were younger than 50. ASA-score was higher for older patients, with no other significant differences in baseline characteristics. AJCC-staging, based on surgical pathology, differed significantly due to higher stage II-rate in the older group and higher stages III- and IV-rates in the younger group. Percentages of high-grade disease, small vessel-, and perineural invasion were higher for younger patients. Stage-for-stage oncologic survival analyses did not demonstrate a significant difference between younger and older patients. Additionally, an age under/over 50 did not have a significant effect in multivariable analyses for disease free-, and disease specific survival. Patients who present with rectal cancer under the age of 50 do not seem to have more aggressive disease, while they present with more advanced disease when compared to patients older than 50. Identifying young people at risk of developing rectal cancer and start screening earlier in a selective group might improve disease stage on presentation.

  3. Prognostic significance of tumor budding in rectal cancer biopsies before neoadjuvant therapy.

    PubMed

    Rogers, Ailín C; Gibbons, David; Hanly, Ann M; Hyland, John M P; O'Connell, P Ronan; Winter, Desmond C; Sheahan, Kieran

    2014-01-01

    Tumor budding is an increasingly important prognostic feature for pathologists to recognize. The aim of this study was to correlate intra-tumoral budding in pre-treatment rectal cancer biopsies with pathological response to neoadjuvant chemoradiotherapy and with long-term outcome. Data from a prospectively maintained database were acquired from patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiotherapy. Pre-treatment rectal biopsies were retrospectively reviewed for evidence of intra-tumoral budding. Multivariate logistic regression was used to identify factors contributing to cancer-specific death, expressed as hazard ratios with 95% confidence intervals. Of the 185 patients with locally advanced rectal cancer, 89 patients met the eligibility criteria, of whom 18 (20%) exhibited budding in a pre-treatment tumor biopsy. Intra-tumoral budding predicted a poor pathological response to neoadjuvant chemoradiotherapy (higher ypT stage, P=0.032; lymph node involvement, P=0.018; lymphovascular invasion, P=0.004; and residual poorly differentiated tumors, P=0.005). No patient with intra-tumoral budding exhibited a tumor regression grade 1 or complete pathological response, providing a 100% specificity and positive predictive value for non-response to neoadjuvant chemoradiotherapy. Intra-tumoral budding was associated with a lower disease-free 5-year survival rate (33 vs 78%, P<0.001), cancer-specific 5-year survival rate (61 vs 87%, P=0.021) and predicted cancer-specific death (hazard ratio 3.51, 95% confidence interval 1.03-11.93, P=0.040). Intra-tumoral budding at diagnosis of rectal cancer identifies those who will poorly respond to neoadjuvant chemoradiotherapy and those with a poor prognosis.

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

    PubMed Central

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

    2017-01-01

    The standard of care in locally advanced rectal cancer is neoadjuvant chemoradiation (nCRT) followed by radical surgery. Response to nCRT varies among patients and pathological complete response is associated with better outcome. However, there is a lack of effective methods to select rectal cancer patients who would or would not have a benefit from nCRT. The utility of clinicopathological and radiological features are limited due to lack of adequate sensitivity and specificity. Molecular biomarkers have the potential to predict response to nCRT at an early time point, but none have currently reached the clinic. Integration of diverse types of biomarkers including clinicopathological and imaging features, identification of mechanistic link to tumor biology, and rigorous validation using samples which represent disease heterogeneity, will allow to develop a sensitive and cost-effective molecular biomarker panel for precision medicine in rectal cancer. Here, we aim to review the recent advance in tissue- and blood-based molecular biomarker research and illustrate their potential in predicting nCRT response in rectal cancer. PMID:28272347

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

    PubMed

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

    2017-03-07

    The standard of care in locally advanced rectal cancer is neoadjuvant chemoradiation (nCRT) followed by radical surgery. Response to nCRT varies among patients and pathological complete response is associated with better outcome. However, there is a lack of effective methods to select rectal cancer patients who would or would not have a benefit from nCRT. The utility of clinicopathological and radiological features are limited due to lack of adequate sensitivity and specificity. Molecular biomarkers have the potential to predict response to nCRT at an early time point, but none have currently reached the clinic. Integration of diverse types of biomarkers including clinicopathological and imaging features, identification of mechanistic link to tumor biology, and rigorous validation using samples which represent disease heterogeneity, will allow to develop a sensitive and cost-effective molecular biomarker panel for precision medicine in rectal cancer. Here, we aim to review the recent advance in tissue- and blood-based molecular biomarker research and illustrate their potential in predicting nCRT response in rectal cancer.

  6. A tertiary care hospital's 10 years' experience with rectal ultrasound in early rectal cancer.

    PubMed

    Akhter, Ahmed; Walker, Andrew; Heise, Charles P; Kennedy, Gregory D; Benson, Mark E; Pfau, Patrick R; Johnson, Eric A; Frick, Terrence J; Gopal, Deepak V

    2017-08-24

    Rectal endoscopic ultrasound (RUS) has become an essential tool in the management of rectal adenocarcinoma because of the ability to accurately stage lesions. The aim of this study was to identify the staging agreement of early RUS-staged rectal adenocarcinoma with surgical resected pathology and ultimately determine how this impacts the management of early rectal cancer (T1-T2). Retrospective chart review was performed from November 2002 to November 2013 to identify procedure indication, RUS staging data, surgical management, and postoperative surgical pathology data. There were a total of 693 RUS examinations available for review and 282 of these were performed for a new diagnosis of rectal adenocarcinoma. There was staging agreement between RUS and surgical pathology in 19 out of 20 (95%) RUS-staged T1 cases. There was staging agreement between RUS and surgical pathology in 3 out of 9 (33%) RUS-staged T2 cases. There was significantly better staging agreement for RUS-staged T1 lesions compared to RUS staged T2 lesions (P = 0.002). Nearly 60% of T1N0 cancers were referred for transanal excisions (TAEs), and 78% of T2N0 cancers underwent low anterior resection. This study identified only a small number of T1-T2 adenocarcinomas. There was good staging agreement between RUS and surgical pathology among RUS-staged T1 lesions whereas poor staging agreement among RUS-staged T2 lesions. Although TAE is largely indicated by the staging of a T1 lesion, this approach may be less appropriate for T2 lesions due to high reported local recurrence.

  7. Is rectal MRI beneficial for determining the location of rectal cancer with respect to the peritoneal reflection?

    PubMed

    Jung, Eun Joo; Ryu, Chun Geun; Kim, Gangmi; Kim, Su Ran; Nam, Sang Eun; Park, Hee Sun; Kim, Young Jun; Hwang, Dae-Yong

    2012-12-01

    An objective method for determining the location of the cancer with respect to peritoneal reflection would be helpful to decide the treatment modality for rectal cancer. This study was designed to evaluate the accuracy and usefulness of rectal MRI to determine spatial relations between the peritoneal reflection and rectal cancer and to compare these with operative findings. Patients that underwent a rectal cancer operation after a rectal MRI check between November 2008 and June 2010 were considered for the study. The patients that received preoperative concurrent chemoradiation or trans-anal local excision were excluded. Fifty-four patients constituted the study cohort. By comparing surgical and radiologic findings, the accuracy for predicting tumour location in relation to the peritoneal reflection by rectal MRI in all patients was 90.7%. In terms of tumour location in relation to peritoneal reflection, the accuracy of rectal MRI was 93.5% in patients with a tumour located above the peritoneal reflection, 90.0% in patients with a tumour located on the peritoneal reflection, and 84.6% in patients with a tumour located below the peritoneal reflection (p=0.061). When the cohort was subdivided by gender, body mass index (BMI), operative findings, or tumour size, no significant difference was observed among subgroups. Rectal MRI could be a useful tool for evaluating the relation between rectal cancer and peritoneal reflection especially when tumour size is less than 8cm. Rectal MRI can provide information regarding the location of rectal cancer in relation to the peritoneal reflection for treatment planning purposes.

  8. Could tumor characteristics identified by colonoscopy predict the locally advanced rectal carcinoma?

    PubMed

    Wang, Hao; Cao, Fu-ao; Gong, Hai-feng; Zheng, Jian-ming; Fu, Chuan-gang

    2010-09-01

    Neoadjuvant chemoradiation is now considered the standard care for locally advanced rectal carcinoma (T3-4 or/and N1-2 lesions), but the accuracy of staging examinations including endorectal ultrasonography (ERUS) and MRI is far from excellent. In addition, the above staging equipment or professionals who perform the examinations may not be available in some hospitals, while preoperative colonoscopy and biopsy are usually obtainable in most hospitals. The objective of the present study was to investigate the clinical and pathological characteristics of locally advanced rectal carcinoma and identify candidates for neoadjuvant chemoradiation. This was a retrospective study. Patients who were treated for rectal cancer at Changhai Hospital from January 1999 to July 2008 were identified from our prospectively collected database. Statistical analysis was performed using SPSS Software System (version 15.0). The Mann-Whitney test, chi-square test and multivariate Logistic regression analysis were performed. A total of 1005 cases were included in this research, of which 761 cases were identified as locally advanced rectal carcinoma depending on postoperative TNM staging. The results of multivariate Logistic regression analysis indicated seven independent risk factors that could be used to predict a locally advanced rectal carcinoma independently: a high grade (including poor differentiation and undifferentiation) (OR: 3.856; 95% CI: 2.064 to 7.204; P = 0.000); large tumor size (OR: 2.455; 95% CI: 1.755 to 3.436; P = 0.000); elevated preoperative serum CEA level (OR: 1.823; 95% CI: 1.309 to 2.537; P = 0.000); non-polypoid tumor type (OR: 1.758; 95% CI: 1.273 to 2.427; P = 0.001); the absence of synchronous polyps (OR: 1.602; 95% CI: 1.103 to 2.327; P = 0.013); the absence of blood in stool (OR: 1.659; 95% CI: 1.049 to 2.624; P = 0.030); and a greater circumferential tumor extent (OR: 1.813; 95% CI: 1.055 to 3.113; P = 0.031). Based on these findings, a Logistic equation was

  9. Reproducibility with repeat CT in radiomics study for rectal cancer

    PubMed Central

    Hu, Panpan; Wang, Jiazhou; Zhong, Haoyu; Zhou, Zhen; Shen, Lijun; Hu, Weigang; Zhang, Zhen

    2016-01-01

    Purpose To evaluate the reproducibility of radiomics features by repeating computed tomographic (CT) scans in rectal cancer. To choose stable radiomics features for rectal cancer. Results Volume normalized features are much more reproducible than unnormalized features. The average value of all slices is the most reproducible feature type in rectal cancer. Different filters have little effect for the reproducibility of radiomics features. For the average type features, 496 out of 775 features showed high reproducibility (ICC ≥ 0.8), 225 out of 775 features showed medium reproducibility (0.8 > ICC ≥ 0.5) and 54 out of 775 features showed low reproducibility (ICC < 0.5). Methods 40 rectal cancer patients with stage II were enrolled in this study, each of whom underwent two CT scans within average 8.7 days. 775 radiomics features were defined in this study. For each features, five different values (value from the largest slice, maximum value, minimum value, average value of all slices and value from superposed intermediate matrix) were extracted. Meanwhile a LOG filter with different parameters was applied to these images to find stable filter value. Concordance correlation coefficients (CCC) and inter-class correlation coefficients (ICC) of two CT scans were calculated to assess the reproducibility, based on original features and volume normalized features. Conclusions Features are recommended to be normalized to volume in radiomics analysis. The average type radiomics features are the most stable features in rectal cancer. Further analysis of these features of rectal cancer can be warranted for treatment monitoring and prognosis prediction. PMID:27669756

  10. High Rate of Positive Circumferential Resection Margins Following Rectal Cancer Surgery: A Call to Action

    PubMed Central

    Rickles, Aaron S.; Dietz, David W.; Chang, George J.; Wexner, Steven D.; Berho, Mariana E.; Remzi, Feza H.; Greene, Frederick L.; Fleshman, James W.; Abbas, Maher A.; Peters, Walter; Noyes, Katia; Monson, John R.T.; Fleming, Fergal J.

    2017-01-01

    Objective To identify predictors of positive circumferential resection margin following rectal cancer resection in the United States. Background Positive circumferential resection margin is associated with a high rate of local recurrence and poor morbidity and mortality for rectal cancer patients. Prior study has shown poor compliance with national rectal cancer guidelines, but whether this finding is reflected in patient outcomes has yet to be shown. Methods Patients who underwent resection for stage I-III rectal cancer were identified from the 2010-2011 National Cancer Database. The primary outcome was a positive circumferential resection margin. The relationship between patient, hospital, tumor, and treatment-related characteristics was analyzed using bivariate and multivariate analysis. Findings A positive circumferential resection margin was noted in 2,859 (17.2%) of the 16,619 patients included. Facility location, clinical T and N stage, histologic type, tumor size, tumor grade, lymphovascular invasion, perineural invasion, type of operation, and operative approach were significant predictors of positive circumferential resection margin on multivariable analysis. Total proctectomy had nearly a 30% increased risk of positive margin compared to partial proctectomy (OR 1.293, 95%CI 1.185-1.411) and a laparoscopic approach had nearly 22% less risk of a positive circumferential resection margin compared to an open approach (OR 0.882, 95%CI 0.790-0.985). Interpretation Despite advances in surgical technique and multimodality therapy, rates of positive circumferential resection margin remain high in the United States. Several tumor and treatment characteristics were identified as independent risk factors, and advances in rectal cancer care are necessary to approach the outcomes seen in other countries. PMID:26473651

  11. Evidence of improving survival of patients with rectal cancer in France: a population based study

    PubMed Central

    Finn-Faivre, C; Maurel, J; Benhamiche, A; Herbert, C; Mitry, E; Launoy, G; Faivre, J

    1999-01-01

    BACKGROUND—Over the past 20 years there have been many changes in the management of rectal cancer. Their impact on the overall population is not well known. 
AIMS—To determine trends in management and prognosis of rectal cancer in two French regions. 
SUBJECTS—1978 patients with a rectal carcinoma diagnosed between 1978 and 1993. 
METHODS—Time trends in treatment, stage at diagnosis, operative mortality, and survival were studied on a four year basis. A non-conditional logistic regression was performed to obtain an odds ratio for each period adjusted for the other variables. To estimate the independent effect of the period a multivariate relative survival analysis was performed. 
RESULTS—Over the 16 year period resection rates increased from 66.0% to 80.1%; the increase was particularly noticeable for sphincter saving procedures (+30.6% per four years, p=0.03). The percentage of patients receiving adjuvant radiotherapy increased from 24.0% to 40.0% (p=0.02). The proportion of patients with Dukes' type A cancer increased from 17.7% to 30.6% with a corresponding decrease in those with more advanced disease. Operative mortality decreased by 31.1% per four years (p=0.03). All these improvements have resulted in a dramatic increase in relative survival (from 35.4% for the 1978-1981 period to 57.0% for the 1985-1989 period). 
CONCLUSIONS—Substantial advances in the management of rectal cancer have been achieved, but there is evidence that further improvements can be made in order to increase survival. 

 Keywords: rectal cancer; treatment; stage at diagnosis; survival; time trends; cancer registries PMID:10026324

  12. Preoperative chemoradiotherapy followed by transanal local excision for T3 distal rectal cancer: A case report

    PubMed Central

    YEO, SEUNG-GU

    2016-01-01

    Local excision (LE) for rectal cancer is currently indicated for selected T1 stage tumors. However, preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer not only improves local disease control, but also leads to a decrease in the stage and size of the primary mural tumor, along with a decrease in the risk of regional lymphadenopathy. The present study reports the outcome of a patient with T3N0M0 rectal cancer who was treated with LE following preoperative CRT. The distal pole of the tumor was located 2 cm from the anal verge. Preoperative pelvic radiotherapy of 50.4 Gy was administered in 28 fractions. Chemotherapy using 5-fluorouracil and leucovorin was administered during the first and last weeks of radiotherapy. The tumor response to CRT, was found to be marked at 7 weeks after CRT completion, and a complete response was presumed clinically. Transanal full-thickness LE was performed, and pathological examination revealed the absence of residual cancer cells. After 30 months of close follow-up, the patient was alive with no evidence of disease, and treatment-associated severe toxicities were not observed. Although a longer follow-up period is required, this case report suggests that LE may also be a feasible alternative treatment for T3 rectal cancer, which exhibits a marked response to preoperative CRT, particularly in elderly and comorbid patients contraindicated for radical surgery, or patients who are reluctant to undergo sphincter-ablation surgery. PMID:27073466

  13. Total mesorectal excision and management of rectal cancer.

    PubMed

    Pinsk, Ilia; Phang, P Terry

    2007-10-01

    Treatment of rectal cancer over the last two decades has evolved with changes in techniques of surgery and radiation based on national and international trials. Preoperative adjuvant radiation is now preferred over postoperative adjuvant radiation, and total mesorectal excision with preservation of pelvic nerves is the gold standard for surgical treatment of rectal cancer. Preservation of the anal sphincter without compromising oncological outcome is an additional benefit for patients with carcinoma in the distal rectum. Further progress in imaging and a multidisciplinary team approach will facilitate individualization of treatment strategy with more focus on quality of life.

  14. Sequential PET/CT with [18F]-FDG Predicts Pathological Tumor Response to Preoperative Short Course Radiotherapy with Delayed Surgery in Patients with Locally Advanced Rectal Cancer Using Logistic Regression Analysis

    PubMed Central

    Pecori, Biagio; Lastoria, Secondo; Caracò, Corradina; Celentani, Marco; Tatangelo, Fabiana; Avallone, Antonio; Rega, Daniela; De Palma, Giampaolo; Mormile, Maria; Budillon, Alfredo; Muto, Paolo; Bianco, Francesco; Aloj, Luigi; Petrillo, Antonella; Delrio, Paolo

    2017-01-01

    Previous studies indicate that FDG PET/CT may predict pathological response in patients undergoing neoadjuvant chemo-radiotherapy for locally advanced rectal cancer (LARC). Aim of the current study is evaluate if pathological response can be similarly predicted in LARC patients after short course radiation therapy alone. Methods: Thirty-three patients with cT2-3, N0-2, M0 rectal adenocarcinoma treated with hypo fractionated short course neoadjuvant RT (5x5 Gy) with delayed surgery (SCRTDS) were prospectively studied. All patients underwent 3 PET/CT studies at baseline, 10 days from RT end (early), and 53 days from RT end (delayed). Maximal standardized uptake value (SUVmax), mean standardized uptake value (SUVmean) and total lesion glycolysis (TLG) of the primary tumor were measured and recorded at each PET/CT study. We use logistic regression analysis to aggregate different measures of metabolic response to predict the pathological response in the course of SCRTDS. Results: We provide straightforward formulas to classify response and estimate the probability of being a major responder (TRG1-2) or a complete responder (TRG1) for each individual. The formulas are based on the level of TLG at the early PET and on the overall proportional reduction of TLG between baseline and delayed PET studies. Conclusions: This study demonstrates that in the course of SCRTDS it is possible to estimate the probabilities of pathological tumor responses on the basis of PET/CT with FDG. Our formulas make it possible to assess the risks associated to LARC borne by a patient in the course of SCRTDS. These risk assessments can be balanced against other health risks associated with further treatments and can therefore be used to make informed therapy adjustments during SCRTDS. PMID:28060889

  15. Patient surveillance after curative-intent surgery for rectal cancer.

    PubMed

    Johnson, Frank E; Longo, Walter E; Ode, Kenichi; Shariff, Umar S; Papettas, Trifonas; McGarry, Alaine E; Gammon, Steven R; Lee, Paul A; Audisio, Riccardo A; Grossmann, Erik M; Virgo, Katherine S

    2005-09-01

    The follow-up of patients with rectal cancer after potentially curative resection has significant financial and clinical implications for patients and society. The ideal regimen for monitoring patients is unknown. We evaluated the self-reported practice patterns of a large, diverse group of experts. There is little information available describing the actual practice of clinicians who perform potentially curative surgery on rectal cancer patients and follow them after recovery. The 1795 members of the American Society of Colon and Rectal Surgeons were asked, via a detailed questionnaire, how often they request 14 discrete follow-up modalities in their patients treated for cure with TNM stage I, II, or III rectal cancer over the first five post-treatment years. 566/1782 (32%) responded and 347 of the respondents (61%) provided evaluable data. Members of the American Society of Colon and Rectal Surgeons typically follow their own patients postoperatively rather than sending them back to their referral source. Office visit and serum CEA level are the most frequently requested items for each of the first five postoperative years. Endoscopy and imaging tests are also used regularly. Considerable variation exists among these highly experienced, highly credentialed experts. The surveillance strategies reported here rely most heavily on relatively simple and inexpensive tests. Endoscopy is employed frequently; imaging tests are employed less often. The observed variation in the intensity of postoperative monitoring is of concern.

  16. [Advanced rectal cancer in an older patient, in whom metastatic liver lesions were effectively controlled with oral UFT+LV and venous CPT-11 administration--case report].

    PubMed

    Shibaki, Taiichiro; Morimoto, Norio

    2006-06-01

    An 81-year-old man was admitted to our department due to acute ileus. He was diagnosed with sigmoid colon cancer with multiple metastatic lesions in the right lobe of the liver. Two weeks after insertion of an ileus tube, he underwent sigmoidectomy and permanent colostomy. The final diagnosis was stage IV sigmoid colon cancer with metastasis to the omentum. One month after the operation, adjuvant chemotherapy with oral administration of tegafur/uracil compound (UFT) and Leucovorin (LV), and drip venous infusion of irinotecan hydrochloride (CPT-11) was initiated (UFT 300 mg/day for 14 days, LV 75 mg/day for 14 days, CPT-11 90 mg/m(2) on the 1 st day, with 1 course consisting of 21 days). The levels of tumor markers, CA19-9 and CEA, and the size of metastases on CT were reduced remarkably after one and 4 courses of this therapy, respectively. Although the administration was temporarily discontinued due to low-grade nausea, we continued the treatment. Adjuvant chemotherapy with an oral administering agent is favorable for older patients with advanced colorectal cancer to reduce side effects and preserve the quality of life.

  17. Intermediate-fraction neoadjuvant radiotherapy for rectal cancer.

    PubMed

    Zhan, Tiancheng; Gu, Jin; Li, Ming; Du, Changzheng

    2013-04-01

    In China, standard neoadjuvant chemoradiation therapy has not been well accepted, not only because of financial constraints but also because of the poorly-tolerated long duration of the regimen. The current study aimed to evaluate the impact of a modified neoadjuvant radiation regimen on the prognosis of rectal cancer patients in China. This was a nonrandomized cohort study evaluating outcomes of patients who chose to undergo preoperative radiotherapy compared with those who chose not to undergo preoperative radiotherapy (controls). The study was carried out in Peking University Cancer Hospital, a tertiary care cancer center in China. Records of patients with locally advanced, mid-to-low rectal cancer who underwent total mesorectal excision at Peking University Cancer Hospital from 2001 through 2005 were analyzed in this study. Patients who chose preoperative radiotherapy received a total dose of 30 Gy delivered in 10 once-daily fractions of 3.0 Gy each, with at least a 14-day delay of surgery after delivery of the last fraction. Tumor downstaging was evaluated. Local recurrence, distant metastases, and disease-free and overall survival were analyzed with the Kaplan-Meier method. A total of 101 patients accepted and 162 patients declined the modified preoperative radiotherapy regimen. Of the 101 patients receiving preoperative radiotherapy, 5 (5%) had a complete response, and 50 (50%) achieved TNM downstaging. The local recurrence rate was 5% with preoperative radiotherapy and 18% in the control groups (p = 0.02). Within the preoperative radiotherapy group, 5-year disease-free survival and overall survival rates were significantly higher in patients with T-, N-, or TNM-downstaging than in patients without downstaging. Evaluation of literature reports indicated that clinical safety and effectiveness of the modified protocol are comparable to results of standard neoadjuvant procedures. The allocation to study groups was not randomized, and patient self-selection may

  18. Metachronous penile metastasis from rectal cancer after total pelvic exenteration.

    PubMed

    Kimura, Yuta; Shida, Dai; Nasu, Keiichi; Matsunaga, Hiroki; Warabi, Masahiro; Inoue, Satoru

    2012-10-14

    Despite its abundant vascularization and extensive circulatory communication with neighboring organs, metastases to the penis are a rare event. A 57-year-old male, who had undergone total pelvic exenteration for rectal cancer sixteen months earlier, demonstrated an abnormal uptake within his penis by positron emission tomography/computed tomography. A single elastic nodule of the middle penis shaft was noted deep within Bucks fascia. No other obvious recurrent site was noted except the penile lesion. Total penectomy was performed as a curative resection based on a diagnosis of isolated penile metastasis from rectal cancer. A histopathological examination revealed an increase of well differentiated adenocarcinoma in the corpus spongiosum consistent with his primary rectal tumor. The immunohistochemistry of the tumor cells demonstrated positive staining for cytokeratin 20 and negative staining for cytokeratin 7, which strongly supported a diagnosis of penile metastasis from the rectum. The patient is alive more than two years without any recurrence.

  19. Impact of Recurrence and Salvage Surgery on Survival After Multidisciplinary Treatment of Rectal Cancer.

    PubMed

    Ikoma, Naruhiko; You, Y Nancy; Bednarski, Brian K; Rodriguez-Bigas, Miguel A; Eng, Cathy; Das, Prajnan; Kopetz, Scott; Messick, Craig; Skibber, John M; Chang, George J

    2017-08-10

    Purpose After preoperative chemoradiotherapy followed by total mesorectal excision for locally advanced rectal cancer, patients who experience local or systemic relapse of disease may be eligible for curative salvage surgery, but the benefit of this surgery has not been fully investigated. The purpose of this study was to characterize recurrence patterns and investigate the impact of salvage surgery on survival in patients with rectal cancer after receiving multidisciplinary treatment. Patients and Methods Patients with locally advanced (cT3-4 or cN+) rectal cancer who were treated with preoperative chemoradiotherapy followed by total mesorectal excision at our institution during 1993 to 2008 were identified. We examined patterns of recurrence location, time to recurrence, treatment factors, and survival. Results A total of 735 patients were included. Tumors were mostly midrectal to lower rectal cancer, with a median distance from the anal verge of 5.0 cm. The most common recurrence site was the lung followed by the liver. Median time to recurrence was shorter in liver-only recurrence (11.2 months) than in lung-only recurrence (18.2 months) or locoregional-only recurrence (24.7 months; P = .001). Salvage surgery was performed in 57% of patients with single-site recurrence and was associated with longer survival after recurrence in patients with lung-only and liver-only recurrence ( P < .001) but not in those with locoregional-only recurrence ( P = .353). Conclusion We found a predilection for lung recurrence in patients with rectal cancer after multidisciplinary treatment. Salvage surgery was associated with prolonged survival in patients with lung-only and liver-only recurrence, but not in those with locoregional recurrence, which demonstrates a need for careful consideration of the indications for resection.

  20. Comparative Analysis of Radiosensitizers for K-RAS Mutant Rectal Cancers

    PubMed Central

    Kim, Stephen Y.; Hong, Theodore S.; Haigis, Kevin M.

    2013-01-01

    Approximately 40% of rectal cancers harbor activating K-RAS mutations, and these mutations are associated with poor clinical response to chemoradiotherapy. We aimed to identify small molecule inhibitors (SMIs) that synergize with ionizing radiation (IR) (“radiosensitizers”) that could be incorporated into current treatment strategies for locally advanced rectal cancers (LARCs) expressing mutant K-RAS. We first optimized a high-throughput assay for measuring individual and combined effects of SMIs and IR that produces similar results to the gold standard colony formation assay. Using this screening platform and K-RAS mutant rectal cancer cell lines, we tested SMIs targeting diverse signaling pathways for radiosensitizing activity and then evaluated our top hits in follow-up experiments. The two most potent radiosensitizers were the Chk1/2 inhibitor AZD7762 and the PI3K/mTOR inhibitor BEZ235. The chemotherapeutic agent 5-fluorouracil (5-FU), which is used to treat LARC, synergized with AZD7762 and enhanced radiosensitization by AZD7762. This study is the first to compare different SMIs in combination with IR for the treatment of K-RAS mutant rectal cancer, and our findings suggest that Chk1/2 inhibitors should be evaluated in new clinical trials for LARC. PMID:24349411

  1. Sphincter-saving surgeries for rectal cancer: A single center study from Kashmir

    PubMed Central

    Mir, Shabeer Ahmed; Chowdri, Nisar A.; Parray, Fazl Q.; Mir, Parvez Ahmed; Bashir, Yasir; Nafae, Muntakhab

    2013-01-01

    Summary and Background Data: The goals in the treatment of rectal cancer are cure, local control, and preservation of sphincter, bladder and sexual function. Surgical resection using sharp mesorectal dissection is important for achieving these goals. Objectives: The current treatment of choice for carcinoma rectum is sphincter saving procedures, which have practically replaced the previously done abdominoperineal resection. We performed a study in our institute to evaluate the surgical outcome and complications of rectal cancer. Materials and Methods: This prospectivestudy included 117 patients, treated for primary rectal cancer by low anterior resection (LAR) from May 2007 to December 2010. All patients underwent standard total mesorectal excision (TME) followed by restoration of continuity. Results: The peri-operative mortality rate was 2.5% (3/117). Post-operative complications occurred in 32% of the patients. After a median follow up of 42 months, local recurrences developed in 6 (5%) patients and distant metastasis in 5 (4.2%). The survival rate was 93%. Conclusion: The concept of total mesorectal excision (TME), advances in stapling technology and neoadjuvant therapy have made it possible to preserve the anal sphincter in most of the patients. Rectal cancer needs to be managed especially in a specialized unit for better results. PMID:24455643

  2. [Liver metastases from colon and rectal cancer in terms of differences in their clinical parameters].

    PubMed

    Liška, V; Emingr, M; Skála, M; Pálek, R; Troup, O; Novák, P; Vyčítal, O; Skalický, T; Třeška, V

    2016-02-01

    From the clinical point of view, rectal cancer and colon cancer are clearly different nosological units in their progress and treatment. The aim of this study was to analyse and clarify the differences between the behaviour of liver metastases from colon and rectal cancer. The study of these factors is important for determining an accurate prognosis and indication of the most effective surgical therapy and oncologic treatment of colon and rectal cancer as a systemic disease. 223 patients with metastatic disease of colorectal carcinoma operated at the Department of Surgery, University Hospital in Pilsen between January 1, 2006 and January 31, 2012 were included in our study. The group of patients comprised 145 men (65%) and 117 women (35%). 275 operations were performed. Resection was done in 177 patients and radiofrequency ablation (RFA) in the total of 98 cases. Our sample was divided into 3 categories according to the location of the primary tumor to C (colon), comprising 58 patients, S (c. sigmoideum) in 61 patients, and R (rectum), comprising 101 patients. Significance analysis of the studied factors (age, gender, staging [TNM classification], grading, presence of mucinous carcinoma, type of operation) was performed using ANOVA test. Overall survival (OS), disease-free interval (DFI) or no evidence of disease (NED) were estimated using Kaplan-Meier curves, which were compared with the log-rank and Wilcoxon tests. As regards the comparison of primary origin of colorectal metastases in liver regardless of their treatment (resection and RFA), our study indicated that rectal liver metastases showed a significantly earlier recurrence than colon liver metastases (shorter NED/DFI). Among other factors, a locally advanced finding, further R2 resection of liver metastases and positivity of lymph node metastases were statistically significant for the prognosis of an early recurrence of the primary colon and sigmoid tumor. Furthermore, we proved that in patients with

  3. 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

  4. [Preoperative intra-arterial chemotherapy for progressive lower rectal cancer].

    PubMed

    Tang, Yun-qiang; Tan, Zhi-ming; Wang, Jia-kang; Tang, Ri-jie; Wang, Jun; Zhao, Hong-yu; Mai, Cong; Zhang, Xiang-liang; Cui, Shu-zhong

    2008-07-01

    To evaluate the therapeutic effect of preoperative regional intra-arterial chemotherapy (PRAC) on progressive lower rectal cancer. Forty-five patients with progressive lower rectal cancer were divided into groups A (23 cases) and B (22 cases) for treatment with PRAC 1 to 2 weeks prior to surgical tumor resection or with surgical resection only, respectively. PRAC caused obvious tissue degeneration and necrosis of rectal cancer with a total effective rate of 95.65%. The rates of radical resection in groups A and B were 91.3% and 72.27%, respectively. The 1-year postoperative survival rates of the two groups were 95.65% and 86.36%, with 3-year survival of 89.96% and 68.18%, and 3-year postoperative recurrence rates of 8.69% and 27.27%, respectively. The anal preservation rates of the two groups were 78.26% and 59.09%. PRAC can increase radical resection rates, promote the postoperative survival and anal preservation rate, and lower the recurrence rate in patients with lower rectal cancer.

  5. Multidisciplinary management of resectable rectal cancer. New developments and controversies.

    PubMed

    Minsky, Bruce D; Guillem, Jose G

    2008-11-15

    Until 2004, initial surgery and, in cases of pT3 and/or node-positive disease, postoperative chemoradiotherapy (radiation plus concurrent chemotherapy) was the conventional approach for patients with clinical T3 and/or node-positive rectal cancer. The German CAO/ARO/AIO 94 trial confirmed that, compared with preoperative chemoradiotherapy, postoperative chemoradiotherapy is associated with significantly higher local failure and toxicity rates as well as a decrease in the incidence of sphincter preservation. These data resulted in a change from postoperative to preoperative chemoradiotherapy. This shift to preoperative therapy has prompted a series of new questions regarding the multidisciplinary management of rectal cancer, including: What is the ideal neoadjuvant approach (short-course vs. combined-modality therapy)? Is postoperative adjuvant chemotherapy necessary for all patients following preoperative chemoradiotherapy? Do patients with node-negative rectal cancer require pelvic radiation? What is the ideal combined-modality regimen? Does an increase in response rate translate into improved local control and survival? And lastly, what is the benefit of novel radiation sensitization and delivery techniques? This review will address these and other questions surrounding the multidisciplinary management of rectal cancer.

  6. Effect of misclassified underlying cause of death on survival estimates of colon and rectal cancer.

    PubMed

    Yin, Daixin; Morris, Cyllene R; Bates, Janet H; German, Robert R

    2011-07-20

    Inaccurate coding of patients' Underlying Cause of Death (UCOD) has constrained cause-specific survival estimates for colon and rectal cancers. Using California data from the Accuracy of Cancer Mortality study, we compared the cancer site data from the California Cancer Registry (CCR) with UCODs reported on death certificates and reclassified the UCODs based on cancer registry data when they disagreed. We then calculated 1-, 3-, 5-, and 10-year cause-specific survival for colon and rectal cancers separately, before and after the reclassification. Records from 26 312 colon and 10 687 rectal cancer patients were examined. UCOD records disagreed with CCR records for 700 (6%) of 11 404 colon cancer deaths and with 1958 (39%) of 5011 rectal cancer deaths, and 82% of the misclassified rectal cancer deaths were coded as colon cancer deaths in the UCOD. Reclassification decreased cause-specific survival for both colon and rectal cancers, but the impact was more pronounced for rectal cancer (eg, 5-year cause-specific survival of colon cancer decreased by 2.8% and of rectal cancer decreased by 20.0% relative to previous estimates; absolute rates changed from 65.4% to 63.6%, and 81.2% to 64.9%, respectively, after reclassification). Interchangeable use of the terms colon cancer and colorectal cancer is likely to be one of the reasons for UCOD misclassification. Educational measures could improve the accuracy of UCOD for colon and rectal cancer deaths.

  7. How to identify rectal sub-regions likely involved in rectal bleeding in prostate cancer radiotherapy

    NASA Astrophysics Data System (ADS)

    Dréan, G.; Acosta, O.; Ospina, J. D.; Voisin, C.; Rigaud, B.; Simon, A.; Haigron, P.; de Crevoisier, R.

    2013-11-01

    Nowadays, the de nition of patient-speci c constraints in prostate cancer radiotherapy planning are solely based on dose-volume histogram (DVH) parameters. Nevertheless those DVH models lack of spatial accuracy since they do not use the complete 3D information of the dose distribution. The goal of the study was to propose an automatic work ow to de ne patient-speci c rectal sub-regions (RSR) involved in rectal bleeding (RB) in case of prostate cancer radiotherapy. A multi-atlas database spanning the large rectal shape variability was built from a population of 116 individuals. Non-rigid registration followed by voxel-wise statistical analysis on those templates allowed nding RSR likely correlated with RB (from a learning cohort of 63 patients). To de ne patient-speci c RSR, weighted atlas-based segmentation with a vote was then applied to 30 test patients. Results show the potentiality of the method to be used for patient-speci c planning of intensity modulated radiotherapy (IMRT).

  8. Nomogram to predict rectal toxicity following prostate cancer radiotherapy

    PubMed Central

    Delobel, Jean-Bernard; Ospina, Juan David; Beckendorf, Véronique; Chira, Ciprian; Zhu, Jian; Bossi, Alberto; Messai, Taha; Acosta, Oscar; Castelli, Joël; de Crevoisier, Renaud

    2017-01-01

    Background To identify predictors of acute and late rectal toxicity following prostate cancer radiotherapy (RT), while integrating the potential impact of RT technique, dose escalation, and moderate hypofractionation, thus enabling us to generate a nomogram for individual prediction. Methods In total, 972 patients underwent RT for localized prostate cancer, to a total dose of 70 Gy or 80 Gy, using two different fractionations (2 Gy or 2.5 Gy/day), by means of several RT techniques (3D conformal RT [3DCRT], intensity-modulated RT [IMRT], or image-guided RT [IGRT]). Multivariate analyses were performed to identify predictors of acute and late rectal toxicity. A nomogram was generated based on the logistic regression model used to predict the 3-year rectal toxicity risk, with its accuracy assessed by dividing the cohort into training and validation subgroups. Results Mean follow-up for the entire cohort was 62 months, ranging from 6 to 235. The rate of acute Grade ≥2 rectal toxicity was 22.2%, decreasing when combining IMRT and IGRT, compared to 3DCRT (RR = 0.4, 95%CI: 0.3–0.6, p<0.01). The 5-year Grade ≥2 risks for rectal bleeding, urgency/tenesmus, diarrhea, and fecal incontinence were 9.9%, 4.5%, 2.8%, and 0.4%, respectively. The 3-year Grade ≥2 risk for overall rectal toxicity increased with total dose (p<0.01, RR = 1.1, 95%CI: 1.0–1.1) and dose per fraction (2Gy vs. 2.5Gy) (p = 0.03, RR = 3.3, 95%CI: 1.1–10.0), and decreased when combining IMRT and IGRT (RR = 0.50, 95% CI: 0.3–0.8, p<0.01). Based on these three parameters, a nomogram was generated. Conclusions Dose escalation and moderate hypofractionation increase late rectal toxicity. IMRT combined with IGRT markedly decreases acute and late rectal toxicity. Performing combined IMRT and IGRT can thus be envisaged for dose escalation and moderate hypofractionation. Our nomogram predicts the 3-year rectal toxicity risk by integrating total dose, fraction dose, and RT technique. PMID:28640871

  9. Standardized Index of Shape (DCE-MRI) and Standardized Uptake Value (PET/CT): Two quantitative approaches to discriminate chemo-radiotherapy locally advanced rectal cancer responders under a functional profile.

    PubMed

    Petrillo, Antonella; Fusco, Roberta; Petrillo, Mario; Granata, Vincenza; Delrio, Paolo; Bianco, Francesco; Pecori, Biagio; Botti, Gerardo; Tatangelo, Fabiana; Caracò, Corradina; Aloj, Luigi; Avallone, Antonio; Lastoria, Secondo

    2017-01-31

    To investigate dynamic contrast enhanced-MRI (DCE-MRI) in the preoperative chemo-radiotherapy (CRT) assessment for locally advanced rectal cancer (LARC) compared to18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). 75 consecutive patients with LARC were enrolled in a prospective study. DCE-MRI analysis was performed measuring SIS: linear combination of percentage change (Δ) of maximum signal difference (MSD) and wash-out slope (WOS). 18F-FDG PET/CT analysis was performed using SUV maximum (SUVmax). Tumor regression grade (TRG) were estimated after surgery. Non-parametric tests, receiver operating characteristic were evaluated. 55 patients (TRG1-2) were classified as responders while 20 subjects as non responders. ΔSIS reached sensitivity of 93%, specificity of 80% and accuracy of 89% (cut-off 6%) to differentiate responders by non responders, sensitivity of 93%, specificity of 69% and accuracy of 79% (cut-off 30%) to identify pathological complete response (pCR). Therapy assessment via ΔSUVmax reached sensitivity of 67%, specificity of 75% and accuracy of 70% (cut-off 60%) to differentiate responders by non responders and sensitivity of 80%, specificity of 31% and accuracy of 51% (cut-off 44%) to identify pCR. CRT response assessment by DCE-MRI analysis shows a higher predictive ability than 18F-FDG PET/CT in LARC patients allowing to better discriminate significant and pCR.

  10. SB-715992 in Treating Patients With Advanced or Metastatic Colorectal Cancer

    ClinicalTrials.gov

    2015-02-13

    Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage IIIA Colon Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

  11. Robotic Surgery for Colon and Rectal Cancer.

    PubMed

    Park, Eun Jung; Baik, Seung Hyuk

    2016-01-01

    Robotic surgery, used generally for colorectal cancer, has the advantages of a three-dimensional surgical view, steadiness, and seven degrees of robotic arms. However, there are disadvantages, such as a decreased sense of touch, extra time needed to dock the robotic cart, and high cost. Robotic surgery is performed using various techniques, with or without laparoscopic surgery. Because the results of this approach are reported to be similar to or less favorable than those of laparoscopic surgery, the learning curve for robotic colorectal surgery remains controversial. However, according to short- and long-term oncologic outcomes, robotic colorectal surgery is feasible and safe compared with conventional surgery. Advanced technologies in robotic surgery have resulted in favorable intraoperative and perioperative clinical outcomes as well as functional outcomes. As the technical advances in robotic surgery improve surgical performance as well as outcomes, it increasingly is being regarded as a treatment option for colorectal surgery. However, a multicenter, randomized clinical trial is needed to validate this approach.

  12. Impact of a multidisciplinary team training programme on rectal cancer outcomes in Spain.

    PubMed

    Ortiz, H; Wibe, A; Ciga, M A; Lujan, J; Codina, A; Biondo, S

    2013-05-01

    The Spanish Rectal Cancer Project was established in 2006, inspired by the Norwegian Rectal Cancer Project. It consisted of an educational project aiming to introduce mesorectal excision surgery to surgeons, pathologists and radiologists. Its effect on local recurrence (LR) was compared with the Norwegian Project. An observational cohort study was carried out including all patients (4700) with rectal cancer from a population of 19 329 992 inhabitants operated on in 51 Spanish hospitals between March 2006 and June 2010. Curative resection was defined as a resection with an uninvolved circumferential margin in patients without distant metastases and without intra-operative rectal perforation. The effectiveness of the programme was measured by a central registry with feedback to participating institutions of their own results compared with the national average. The main outcome measures were LR and adverse effects in curative resections. Of the 4700 patients, 3213 had a resection considered to be curative. LR rates were 4.7% (95% CI 0.03-0.59), metastasis rate was 16% (95% CI 0.14-0.17) and overall survival was 87.8% (95% CI 0.86-0.89). Multivariate analysis showed that advanced TNM stage and decreasing distance of the tumour from the anal verge had a negative influence on LR. This study shows that the results obtained in Norway have been reproduced in a larger population in Spain applying a similar methodology. Colorectal Disease © 2013 The Association of Coloproctology of Great Britain and Ireland.

  13. Retrospective review of rectal cancer surgery in northern Alberta

    PubMed Central

    Pelletier, Jean-Sébastien; DeGara, Christopher; Porter, Geoff; Ghosh, Sunita; Schiller, Dan

    2013-01-01

    Introduction Previous studies, including research published more than 10 years ago in Northern Alberta, have demonstrated improved outcomes with increased surgical volume and subspecialisation in the treatment of rectal cancer. We sought to examine contemporary rectal cancer care in the same region to determine whether practice patterns have changed and whether outcomes have improved. Methods We reviewed the charts of all patients with rectal adenocarcinoma diagnosed between 1998 and 2003 who had a potentially curative resection. The main outcomes examined were 5-year local recurrence (LR) and disease-specific survival (DSS). Surgeons were classified into 3 groups according to training and volume, and we compared outcome measures among them. We also compared our results to those of the previous study from our region. Results We included 433 cases in the study. Subspecialty-trained colorectal surgeons performed 35% of all surgeries in our study compared to 16% in the previous study. The overall 5-year LR rate and DSS in our study were improved compared to the previous study. On multivariate analysis, the only factor associated with increased 5-year LR was presence of obstruction, and the factors associated with decreased 5-year DSS were high-volume noncolorectal surgeons, presence of obstruction and increased stage. Conclusion Over the past 10 years, the long-term outcomes of treatment for rectal cancer have improved. We found that surgical subspecialization was associated with improved DSS but not LR. Increased surgical volume was not associated with LR or DSS. PMID:23883504

  14. Retrospective review of rectal cancer surgery in northern Alberta.

    PubMed

    Pelletier, Jean-Sébastien; Degara, Christopher; Porter, Geoff; Ghosh, Sunita; Schiller, Dan

    2013-08-01

    Previous studies, including research published more than 10 years ago in Northern Alberta, have demonstrated improved outcomes with increased surgical volume and subspecialisation in the treatment of rectal cancer. We sought to examine contemporary rectal cancer care in the same region to determine whether practice patterns have changed and whether outcomes have improved. We reviewed the charts of all patients with rectal adenocarcinoma diagnosed between 1998 and 2003 who had a potentially curative resection. The main outcomes examined were 5-year local recurrence (LR) and disease-specific survival (DSS). Surgeons were classified into 3 groups according to training and volume, and we compared outcome measures among them. We also compared our results to those of the previous study from our region. We included 433 cases in the study. Subspecialty-trained colorectal surgeons performed 35% of all surgeries in our study compared to 16% in the previous study. The overall 5-year LR rate and DSS in our study were improved compared to the previous study. On multivariate analysis, the only factor associated with increased 5-year LR was presence of obstruction, and the factors associated with decreased 5-year DSS were high-volume noncolorectal surgeons, presence of obstruction and increased stage. Over the past 10 years, the long-term outcomes of treatment for rectal cancer have improved. We found that surgical subspecialization was associated with improved DSS but not LR. Increased surgical volume was not associated with LR or DSS.

  15. NPTX2 is associated with neoadjuvant therapy response in rectal cancer.

    PubMed

    Karagkounis, Georgios; Thai, Leo; DeVecchio, Jennifer; Gantt, Gerald A; Duraes, Leonardo; Pai, Rish K; Kalady, Matthew F

    2016-05-01

    Neoadjuvant chemoradiation (CRT) is recommended for locally advanced rectal cancer. Tumor response varies from pathologic complete response (pCR) to no tumor regression. The mechanisms behind CRT resistance remain undefined. In our previously generated complementary DNA microarrays of pretreatment biopsies from rectal cancer patients, neuronal pentraxin 2 (NPTX2) expression discriminated patients with pCR from those with residual tumor. As tumor response is prognostic for survival, we sought to evaluate the clinical relevance of NPTX2 in rectal cancer. Real-time quantitative polymerase chain reaction was used to evaluate NPTX2 messenger RNA expression in individual rectal cancers before CRT. Tumors with NPTX2 expression <50% of normal rectum were defined as NPTX2-low and those with >50% were defined as NPTX2-high. NPTX2 levels were compared to response to therapy and oncologic outcomes using Mann-Whitney, Kruskal-Wallis, chi-square, and Mantel-Cox (log-rank) tests, as appropriate. Rectal cancers from 40 patients were included. The mean patient age was 56.8 years, and 30% were female. pCR was achieved in eight of 40 patients (20%). In these patients, messenger RNA NPTX2 levels were significantly decreased compared to those with residual cancer (fold change 30.4, P = 0.017). Patients with NPTX2-low tumors (n = 13) achieved improved response to treatment (P = 0.012 versus NPXT2-high tumors), with 38.5% and 46.1% of patients achieving complete or moderate response, respectively. Of patients with NPTX2-high tumors (n = 27), 11.1% and 18.5% achieved complete or moderate response, respectively. No recurrence or death was recorded in patients with NPTX2-low tumors, reflecting more favorable disease-free survival (P = 0.045). Decreased NPTX2 expression in rectal adenocarcinomas is associated with improved response to CRT and improved prognosis. Further studies to validate these results and elucidate the biological role of NPTX2 in rectal cancer are needed. Copyright © 2016

  16. Factors Associated With Receipt of Radiation Therapy for Rectal Cancer.

    PubMed

    McClure, Laura A; Sussman, Daniel A; Hernandez, Monique N; Tannenbaum, Stacey L; Yechieli, Raphael L; Bonner, Judith M; Zheng, D Diane; Lee, David J

    2015-12-22

    Appropriate treatment for cancer is vital to increasing the likelihood of survival; however, for rectal cancer, there are demonstrated disparities in receipt of treatment by race/ethnicity and socioeconomic status. We evaluated factors associated with receipt of appropriate radiation therapy for rectal cancer using data from the Florida Cancer Data System that had been previously enriched with detailed treatment information collected from a Centers for Disease Control and Prevention Comparative Effectiveness Research study. This treatment information is not routinely available in cancer registry data and represents a unique data resource. Using multivariable regression, we evaluated factors associated with receiving radiation therapy among rectal cancer cases stage II/III. Our sample (n=403) included cases diagnosed in Florida in 2011 who were 18 years and older. Cases clinically staged as 0/I/IV were excluded. Older age (odds ratio=0.96; 95% confidence interval, 0.94-0.97), the presence of one or more comorbidities (0.61; 0.39-0.96), and receipt of surgical intervention (0.44; 0.22-0.90) were associated with lack of radiation. In this cohort of patients, sociodemographic factors such as race/ethnicity, insurance status, and socioeconomic status, did not influence the receipt of radiation. Further research is needed, however, to understand why aging, greater comorbidity, and having surgery present a barrier to radiation therapy, particularly given that it is a well-tolerated treatment in most patients.

  17. Surgeon-related factors and outcome in rectal cancer.

    PubMed Central

    Porter, G A; Soskolne, C L; Yakimets, W W; Newman, S C

    1998-01-01

    OBJECTIVE: To determine whether surgical subspecialty training in colorectal surgery or frequency of rectal cancer resection by the surgeon are independent prognostic factors for local recurrence (LR) and survival. SUMMARY BACKGROUND DATA: Variation in patient outcome in rectal cancer has been shown among centers and among individual surgeons. However, the prognostic importance of surgeon-related factors is largely unknown. METHODS: All patients undergoing potentially curative low anterior resection or abdominoperineal resection for primary adenocarcinoma of the rectum between 1983 and 1990 at the five Edmonton general hospitals were reviewed in a historic-prospective study design. Preoperative, intraoperative, pathologic, adjuvant therapy, and outcome variables were obtained. Outcomes of interest included LR and disease-specific survival (DSS). To determine survival rates and to control both confounding and interaction, multivariate analysis was performed using Cox proportional hazards regression. RESULTS: The study included 683 patients involving 52 surgeons, with > 5-year follow-up obtained on 663 (97%) patients. There were five colorectal-trained surgeons who performed 109 (16%) of the operations. Independent of surgeon training, 323 operations (47%) were done by surgeons performing < 21 rectal cancer resections over the study period. Multivariate analysis showed that the risk of LR was increased in patients of both noncolorectal trained surgeons (hazard ratio (HR) = 2.5, p = 0.001) and those of surgeons performing < 21 resections (HR = 1.8, p < 0.001). Stage (p < 0.001), use of adjuvant therapy (p = 0.002), rectal perforation or tumor spill (p < 0.001), and vascular/neural invasion (p = 0.002) also were significant prognostic factors for LR. Similarly, decreased disease-specific survival was found to be independently associated with noncolorectal-trained surgeons (HR = 1.5, p = 0.03) and surgeons performing < 21 resections (HR = 1.4, p = 0.005). Stage (p < 0

  18. ACR Appropriateness Criteria®  Resectable Rectal Cancer

    PubMed Central

    2012-01-01

    The management of resectable rectal cancer continues to be guided by clinical trials and advances in technique. Although surgical advances including total mesorectal excision continue to decrease rates of local recurrence, the management of locally advanced disease (T3-T4 or N+) benefits from a multimodality approach including neoadjuvant concomitant chemotherapy and radiation. Circumferential resection margin, which can be determined preoperatively via MRI, is prognostic. Toxicity associated with radiation therapy is decreased by placing the patient in the prone position on a belly board, however for patients who cannot tolerate prone positioning, IMRT decreases the volume of normal tissue irradiated. The use of IMRT requires knowledge of the patterns of spreads and anatomy. Clinical trials demonstrate high variability in target delineation without specific guidance demonstrating the need for peer review and the use of a consensus atlas. Concomitant with radiation, fluorouracil based chemotherapy remains the standard, and although toxicity is decreased with continuous infusion fluorouracil, oral capecitabine is non-inferior to the continuous infusion regimen. Additional chemotherapeutic agents, including oxaliplatin, continue to be investigated, however currently should only be utilized on clinical trials as increased toxicity and no definitive benefit has been demonstrated in clinical trials. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every two years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment

  19. Surgical and oncology trials for rectal cancer: who will participate?

    PubMed

    Harrison, James D; Solomon, Michael J; Young, Jane M; Meagher, Alan; Hruby, George; Salkeld, Glenn; Clarke, Stephen

    2007-07-01

    The assessment of patients' and clinicians' willingness to participate in clinical trials is advisable as part of a feasibility exercise prior to the commencement of randomized controlled trials (RCTs) to ensure adequate support in terms of likely accrual to achieve the required sample size in a timely fashion. Furthermore, understanding why patients are unwilling to enter RCTs is imperative before the current trend of low participation can be reversed. Patients, colorectal surgeons, and medical and radiation oncologists, were presented with 5 different, detailed treatments for locally advanced rectal cancer. They were asked whether they would be willing to enter an RCT comparing each treatment choice. Patients who would not participate were asked to indicate their reason for refusal. Patients' willingness to participate in each trial was consistently low (19% to 32%). Similar low levels of participation were indicated by each clinical subspecialty (15% to 38%). Of the scenarios, patients and clinicians were most willing to enter a trial investigating surgery plus preoperative radiotherapy. A dislike of randomization, a desire to be involved in decision-making, and quality of life considerations were the most commonly stated reasons for refusal. This study highlights the difficulties in performing RCTs in surgery and oncology. However, results suggest that improvements in communication regarding randomization and clinical trial processes and the actual, rather than perceived, side effects of treatments are strategies that may enhance patient participation.

  20. Biomarkers for Response to Neoadjuvant Chemoradiation for Rectal Cancer

    SciTech Connect

    Kuremsky, Jeffrey G.; Tepper, Joel E.; McLeod, Howard L. Phar

    2009-07-01

    Locally advanced rectal cancer (LARC) is currently treated with neoadjuvant chemoradiation. Although approximately 45% of patients respond to neoadjuvant therapy with T-level downstaging, there is no effective method of predicting which patients will respond. Molecular biomarkers have been investigated for their ability to predict outcome in LARC treated with neoadjuvant chemotherapy and radiation. A literature search using PubMed resulted in the initial assessment of 1,204 articles. Articles addressing the ability of a biomarker to predict outcome for LARC treated with neoadjuvant chemotherapy and radiation were included. Six biomarkers met the criteria for review: p53, epidermal growth factor receptor (EGFR), thymidylate synthase, Ki-67, p21, and bcl-2/bax. On the basis of composite data, p53 is unlikely to have utility as a predictor of response. Epidermal growth factor receptor has shown promise as a predictor when quantitatively evaluated in pretreatment biopsies or when EGFR polymorphisms are evaluated in germline DNA. Thymidylate synthase, when evaluated for polymorphisms in germline DNA, is promising as a predictive biomarker. Ki-67 and bcl-2 are not useful in predicting outcome. p21 needs to be further evaluated to determine its usefulness in predicting outcome. Bax requires more investigation to determine its usefulness. Epidermal growth factor receptor, thymidylate synthase, and p21 should be evaluated in larger prospective clinical trials for their ability to guide preoperative therapy choices in LARC.

  1. Nanocytology of rectal colonocytes to assess risk of colon cancer based on field cancerization

    PubMed Central

    Damania, Dhwanil; Roy, Hemant K.; Subramanian, Hariharan; Weinberg, David S.; Rex, Douglas K.; Goldberg, Michael J.; Muldoon, Joseph; Cherkezyan, Lusik; Zhu, Yuanjia; Bianchi, Laura K.; Shah, Dhiren; Pradhan, Prabhakar; Borkar, Monica; Lynch, Henry; Backman, Vadim

    2013-01-01

    Developing a minimally invasive and cost effective pre-screening strategy for colon cancer is critical, because of the impossibility of performing colonoscopy on the entire at-risk population. The concept of field carcinogenesis, in which normal-appearing tissue away from a tumor has molecular and, consequently, nano-architectural abnormalities, offers one attractive approach to identify high-risk patients. In this study, we investigated whether the novel imaging technique partial-wave spectroscopic (PWS) microscopy could risk-stratify patients harboring precancerous lesions of the colon, using an optically measured biomarker (Ld) obtained from microscopically normal but nanoscopically altered cells. Rectal epithelial cells were examined from 146 patients, including 72 control patients, 14 patients with diminutive adenomas, 20 patients with non-advanced-non-diminutive adenomas, 15 patients with advanced adenomas/high-grade dysplasia, 12 patients with genetic mutation leading to Lynch syndrome, and 13 cancer patients. We found that the Ld obtained from rectal colonocytes was well-correlated with colon tumorigenicity in our patient cohort and in an independent validation set of 39 additional patients. Therefore, our findings suggest that PWS-measured Ld is an accurate marker of field carcinogenesis. This approach provides a potential pre-screening strategy for risk stratification before colonoscopy. PMID:22491589

  2. [Radiotherapy in pelvic recurrences of rectal cancer].

    PubMed

    Morganti, A G; Santoni, R; Osti, M F

    2001-01-01

    Patients with locally recurrent rectal carcinoma have an unfavourable prognosis for the high incidence of distant metastases, the infrequent feasibility of radical surgical resection, and, in these last cases, the high incidence of re-recurrences. Based on the low resectability rate of pelvic recurrences, the clear impact of tumor diameter on resectability and outcome, and the documented possibility to achieve a significant tumor downstaging and downsizing with the use of concurrent chemoradiation, it is evident that the most promising treatment several authors have considered concurrent chemoradiation followed, if feasible, by radical resection. Furthermore, based on the high local and distant failure rate after surgery, the utilization of intraoperative radiation therapy (IORT) and adjuvant chemotherapy seems justified. Some published comparisons between patients treated with and without IORT seems to suggest the possible improvement in both local control and survival in these patients. Particularly interesting issues in this field are: 1) the definition of the most effective treatment modality (both in terms of radiation dose, fractionation and techniques, and drugs to be used concurrently to radiotherapy); 2) the analysis of the prognostic impact of several factors, with the aim of designing and validating staging systems of local rectal recurrences; 3) the possibility to treat with relatively high doses also patients previously irradiated on the pelvis.

  3. Systematic review of FDG-PET prediction of complete pathological response and survival in rectal cancer.

    PubMed

    Memon, Sameer; Lynch, A Craig; Akhurst, Timothy; Ngan, Samuel Y; Warrier, Satish K; Michael, Michael; Heriot, Alexander G

    2014-10-01

    Advances in the management of rectal cancer have resulted in an increased application of multimodal therapy with the aim of tailoring therapy to individual patients. Complete pathological response (pCR) is associated with improved survival and may be potentially managed without radical surgical resection. Over the last decade, there has been increasing interest in the ability of functional imaging to predict complete response to treatment. The aim of this review was to assess the role of (18)F-flurordeoxyglucose positron emission tomography (FDG-PET) in prediction of pCR and prognosis in resectable locally advanced rectal cancer. A search of the MEDLINE and Embase databases was conducted, and a systematic review of the literature investigating positron emission tomography (PET) in the prediction of pCR and survival in rectal cancer was performed. Seventeen series assessing PET prediction of pCR were included in the review. Seven series assessed postchemoradiation SUVmax, which was significantly different between response groups in all six studies that assessed this. Nine series assessed the response index (RI) for SUVmax, which was significantly different between response groups in seven series. Thirteen studies investigated PET response for prediction of survival. Metabolic complete response assessed by SUV2max or visual response and RISUVmax showed strong associations with disease-free survival (DFS) and overall survival (OS). SUV2max and RISUVmax appear to be useful FDG-PET markers for prediction of pCR and these parameters also show strong associations with DFS and OS. FDG-PET may have a role in outcome prediction in patients with advanced rectal cancer.

  4. CoReCG: a comprehensive database of genes associated with colon-rectal cancer

    PubMed Central

    Agarwal, Rahul; Kumar, Binayak; Jayadev, Msk; Raghav, Dhwani; Singh, Ashutosh

    2016-01-01

    Cancer of large intestine is commonly referred as colorectal cancer, which is also the third most frequently prevailing neoplasm across the globe. Though, much of work is being carried out to understand the mechanism of carcinogenesis and advancement of this disease but, fewer studies has been performed to collate the scattered information of alterations in tumorigenic cells like genes, mutations, expression changes, epigenetic alteration or post translation modification, genetic heterogeneity. Earlier findings were mostly focused on understanding etiology of colorectal carcinogenesis but less emphasis were given for the comprehensive review of the existing findings of individual studies which can provide better diagnostics based on the suggested markers in discrete studies. Colon Rectal Cancer Gene Database (CoReCG), contains 2056 colon-rectal cancer genes information involved in distinct colorectal cancer stages sourced from published literature with an effective knowledge based information retrieval system. Additionally, interactive web interface enriched with various browsing sections, augmented with advance search facility for querying the database is provided for user friendly browsing, online tools for sequence similarity searches and knowledge based schema ensures a researcher friendly information retrieval mechanism. Colorectal cancer gene database (CoReCG) is expected to be a single point source for identification of colorectal cancer-related genes, thereby helping with the improvement of classification, diagnosis and treatment of human cancers. Database URL: lms.snu.edu.in/corecg PMID:27114494

  5. Do Older Americans Undergo Stoma Reversal Following Low Anterior Resection for Rectal Cancer?

    PubMed Central

    Dodgion, Christopher M.; Neville, Bridget A.; Lipsitz, Stuart R.; Hu, Yue-Yung; Schrag, Deborah; Breen, Elizabeth; Greenberg, Caprice C.

    2013-01-01

    Objective For low-lying rectal cancers, proximal diversion can reduce anastomotic leak after sphincter preserving surgery; however, evidence suggests that such temporary diversions are often not reversed. We aimed to evaluate non-reversal and delayed stoma reversal in elderly patients undergoing low anterior resection (LAR). Design SEER-Medicare linked analysis from 1991-2007. Settings and Participants 1,179 primary stage I-III rectal cancer patients over age 66 who underwent LAR with synchronous diverting stoma. Main Outcome Measures 1) Stoma creation and reversal rates. 2) Time to reversal. 3) Characteristics associated with reversal and shorter time to reversal. Results Within 18 months of LAR, 51% (603/1179) of patients underwent stoma reversal. Stoma reversal was associated with age < 80 years (p<0.0001), male gender (p=0.018), less comorbidities (p=0.017), higher income [quartile 4 vs. 1, (p=0.002)], early tumor stage [1 vs. 3; (p<0.001)], neoadjuvant radiation (p<0.0001), rectal tumor location [vs. rectosigmoid, (p=0.001)], more recent diagnosis (p=0.021), and shorter length of stay on LAR admission (p=0.021). Median time to reversal was 126 days (IQR: 79-249). Longer time to reversal was associated with older age (p=0.031), presence of comorbidities (p=0.014), more advanced tumor stage (p=0.007), positive lymph nodes (p=0.009), receipt of adjuvant radiation therapy (p=0.008), more recent diagnosis (p=0.004) and longer LOS on LAR admission (p <0.0001). Conclusions Half of elderly rectal cancer patients who undergo LAR with temporary stoma have not undergone stoma reversal by 18 months. Identifiable risk factors predict both non-reversal and longer time to reversal. These results help inform pre-operative discussions and promote realistic expectations for elderly rectal cancer patients. PMID:23298948

  6. 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.

  7. Metachronous adenoma on ileorectal anastomosis suture line and submucosal deep invasive cancer suspected of rapid growth in rectal remnant following long-term interval after curative surgery for advanced colon cancer.

    PubMed

    Uraoka, Toshio; Horii, Joichiro; Goto, Osamu; Shimoda, Masayuki; Yahagi, Naohisa

    2013-05-01

    There is general agreement as to the value of postoperative surveillance and the effectiveness of colonoscopy in the early detection of metachronous colorectal lesions. In the present case, a 56-year-old woman with no family history of colon cancer underwent surveillance colonoscopy in which a metachronous flat adenoma was detected following an interval of 23 years after a colectomy and 20 years subsequent to treatment for uterine cancer. A second metachronous flat lesion histopathologically determined to be a submucosal (sm) deep invasive cancer with lymphovascular involvement was detected 12 months later. This second metachronous lesion was suspected of having developed rapidly in the rectal remnant accounting for its sm deep invasion. The findings of this case suggest colonoscopy surveillance guidelines proposed for individuals at high risk should be evaluated based on cancer history and an analysis of possible mismatch repair gene mutations. In addition, the first metachronous lesion was located directly on the suture line of the anastomosis. Endoscopic submucosal dissection (ESD) was indicated despite severe fibrosis into the sm layer. This case also demonstrates the successful use of improved ESD instruments, sm injection agents and technique refinements in the treatment of a technically difficult lesion with a high risk of complications.

  8. TEM and conventional rectal surgery for T1 rectal cancer: a meta-analysis.

    PubMed

    Wu, Yong; Wu, Yong-You; Li, Shan; Zhu, Bao-Song; Zhao, Kui; Yang, Xiao-Dong; Xing, Chun Gen

    2011-01-01

    To compare transanal endoscopic microsurgery (TEM) with conventional radical surgery (CRS) for T1 rectal cancer focusing on safety, feasibility and efficacy of both procedures. An online search of Ovid, Medline, Embase, Pubmed and Cochrane Controlled Trials Register was undertaken to identify studies comparing TEM with CRS published in English between 1984 and March 2010. Only studies comparing TEM with CRS for T1 rectal cancer treatment and with a minimum of 20 cases were included. The parameters compared were postoperative complications, hospital mortality, recurrence rate and 5-year survival. Five studies met screening criteria and 397 patients were enrolled in the meta-analysis; 216 were treated with TEM and the rest received CRS. Complications were observed in 16/196 in the TEM group and 77/163 in the CRS group. The difference was significant (p=0.01). The rate of mortality was 3.68% in CRS group, and 0 in TEM group (p=0.01). The 5-year survival was similar (p=0.84), the TEM group was 80.1% and the CRS group was 81.0%. However, there was more recurrence in the TEM group compared to CRS group (p=0.0004). TEM group was 12.0%, while CRS group was 0.5%. Compared with CRS, TEM had significant shorter hospital stay and fewer postoperative complications. TEM is a safe, feasible and effective option for T1 rectal cancer. Though TEM had a slightly higher rate of recurrence than CRS, no significant difference on 5-year survival was observed.

  9. Could preoperative short-course radiotherapy be the treatment of choice for localized advanced rectal carcinoma?

    PubMed Central

    Ciria, Juan Pablo; Eguiguren, Mikel; Cafiero, Sergio; Uranga, Intza; Diaz de Cerio, Ivan; Querejeta, Arrate; Urraca, Jose Maria; Minguez, Julian; Guimon, Elena; Puertolas, Jose Ramón

    2014-01-01

    Short-course preoperative radiotherapy (RT) is widely used in northern Europe for locally advanced resectable rectal cancer, but its role in the era of advanced imaging techniques is uncertain. Here, we reviewed articles and abstracts on SCRT published from 1974 through 2013 with the goal of identifying patients who might be best suited for short-course RT. We included relevant articles comparing surgery with or without preoperative radiation published before and after the advent of total mesorectal excision. We also analyzed two randomized trials directly comparing short-course RT with conventionally fractionated chemoradiation (the Polish Colorectal Study Group and the Trans-Tasman Radiation Oncology Group) that compared short-course RT with conventional chemoradiotherapy. We conclude from our review that short-course RT can be generally applied for operable rectal cancer and produces high rates of pelvic control with acceptable toxicity; it reduces local recurrence rates but does not increase overall survival. SCRT seems to be best used for tumors considered “low risk,” i.e., those that are >5 cm from the anal margin, without circumferential margin involvement, and involvement of fewer than 4 lymph nodes. Whether sequential chemotherapy can further improve outcomes remains to be seen, as does the best time for surgery (immediately or 6–8 weeks after RT). We further recommend that selection of patients for short-course RT should be based on findings from magnetic resonance imaging or transrectal ultrasonography. PMID:25535578

  10. Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the German CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trial.

    PubMed

    Rödel, Claus; Graeven, Ullrich; Fietkau, Rainer; Hohenberger, Werner; Hothorn, Torsten; Arnold, Dirk; Hofheinz, Ralf-Dieter; Ghadimi, Michael; Wolff, Hendrik A; Lang-Welzenbach, Marga; Raab, Hans-Rudolf; Wittekind, Christian; Ströbel, Philipp; Staib, Ludger; Wilhelm, Martin; Grabenbauer, Gerhard G; Hoffmanns, Hans; Lindemann, Fritz; Schlenska-Lange, Anke; Folprecht, Gunnar; Sauer, Rolf; Liersch, Torsten

    2015-08-01

    Preoperative chemoradiotherapy with infusional fluorouracil, total mesorectal excision surgery, and postoperative chemotherapy with fluorouracil was established by the German CAO/ARO/AIO-94 trial as a standard combined modality treatment for locally advanced rectal cancer. Here we compare the previously established regimen with an investigational regimen in which oxaliplatin was added to both preoperative chemoradiotherapy and postoperative chemotherapy. In this multicentre, open-label, randomised, phase 3 study we randomly assigned patients with rectal adenocarcinoma, clinically staged as cT3-4 or any node-positive disease, to two groups: a control group receiving standard fluorouracil-based combined modality treatment, consisting of preoperative radiotherapy of 50·4 Gy in 28 fractions plus infusional fluorouracil (1000 mg/m(2) on days 1-5 and 29-33), followed by surgery and four cycles of bolus fluorouracil (500 mg/m(2) on days 1-5 and 29); or to an investigational group receiving preoperative radiotherapy of 50·4 Gy in 28 fractions plus infusional fluorouracil (250 mg/m(2) on days 1-14 and 22-35) and oxaliplatin (50 mg/m(2) on days 1, 8, 22, and 29), followed by surgery and eight cycles of oxaliplatin (100 mg/m(2) on days 1 and 15), leucovorin (400 mg/m(2) on days 1 and 15), and infusional fluorouracil (2400 mg/m(2) on days 1-2 and 15-16). Randomisation was done with computer-generated block-randomisation codes stratified by centre, clinical T category (cT1-3 vs cT4), and clinical N category (cN0 vs cN1-2) without masking. The primary endpoint was disease-free survival, defined as the time between randomisation and non-radical surgery of the primary tumour (R2 resection), locoregional recurrence after R0/1 resection, metastatic disease or progression, or death from any cause, whichever occurred first. Survival and cumulative incidence of recurrence analyses followed the intention-to-treat principle; toxicity analyses included all patients treated. Enrolment of

  11. Irinotecan-Eluting Beads in Treating Patients With Refractory Metastatic Colon or Rectal Cancer That Has Spread to the Liver

    ClinicalTrials.gov

    2017-04-12

    Liver Metastases; Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

  12. Experts reviews of the multidisciplinary consensus conference colon and rectal cancer 2012: science, opinions and experiences from the experts of surgery.

    PubMed

    van de Velde, C J H; Boelens, P G; Tanis, P J; Espin, E; Mroczkowski, P; Naredi, P; Pahlman, L; Ortiz, H; Rutten, H J; Breugom, A J; Smith, J J; Wibe, A; Wiggers, T; Valentini, V

    2014-04-01

    The first multidisciplinary consensus conference on colon and rectal cancer was held in December 2012, achieving a majority of consensus for diagnostic and treatment decisions using the Delphi Method. This article will give a critical appraisal of the topics discussed during the meeting and in the consensus document by well-known leaders in surgery that were involved in this multidisciplinary consensus process. Scientific evidence, experience and opinions are collected to support multidisciplinary teams (MDT) with arguments for medical decision-making in diagnosis, staging and treatment strategies for patients with colon or rectal cancer. Surgery is the cornerstone of curative treatment for colon and rectal cancer. Standardizing treatment is an effective instrument to improve outcome of multidisciplinary cancer care for patients with colon and rectal cancer. In this article, a review of the following focuses; Perioperative care, age and colorectal surgery, obstructive colorectal cancer, stenting, surgical anatomical considerations, total mesorectal excision (TME) surgery and training, surgical considerations for locally advanced rectal cancer (LARC) and local recurrent rectal cancer (LRRC), surgery in stage IV colorectal cancer, definitions of quality of surgery, transanal endoscopic microsurgery (TEM), laparoscopic colon and rectal surgery, preoperative radiotherapy and chemoradiotherapy, and how about functional outcome after surgery?

  13. Bladder filling variation during conformal radiotherapy for rectal cancer

    NASA Astrophysics Data System (ADS)

    Sithamparam, S.; Ahmad, R.; Sabarudin, A.; Othman, Z.; Ismail, M.

    2017-05-01

    Conformal radiotherapy for rectal cancer is associated with small bowel toxicity mainly diarrhea. Treating patients with a full bladder is one of the practical solutions to reduce small bowel toxicity. Previous studies on prostate and cervix cancer patients revealed that maintaining consistent bladder volume throughout radiotherapy treatment is challenging. The aim of this study was to measure bladder volume variation throughout radiotherapy treatment. This study also measured the association between bladder volume changes and diarrhea. Twenty two rectal cancer patients were recruited prospectively. Patients were planned for treatment with full bladder following departmental bladder filling protocol and the planning bladder volume was measured during CT-simulation. During radiotherapy, the bladder volume was measured weekly using cone-beam computed tomography (CBCT) and compared to planning bladder volume. Incidence and severity of diarrhea were recorded during the weekly patient review. There was a negative time trend for bladder volume throughout five weeks treatment. The mean bladder volume decreased 18 % from 123 mL (SD 54 mL) during CT-simulation to 101 mL (SD 71 mL) on the 5th week of radiotherapy, but the decrease is not statistically significant. However, there was a large variation of bladder volume within each patient during treatment. This study showed an association between changes of bladder volume and diarrhea (P = 0.045). In conclusion bladder volume reduced throughout radiotherapy treatment for conformal radiotherapy for rectal cancer and there was a large variation of bladder volume within patients.

  14. Differences in gene expression profiles and carcinogenesis pathways between colon and rectal cancer.

    PubMed

    Li, Jing Nan; Zhao, Li; Wu, Jun; Wu, Bin; Yang, Hong; Zhang, Heng Hui; Qian, Jia Ming

    2012-01-01

    Colon cancer is more common in the USA and Europe than that in China, for reasons that are unclear. The aim of this study was to investigate the differences in gene expression profiles and carcinogenesis pathways between colon and rectal cancer. Expression profiling of primary tumor tissues from 12 colon and 12 rectal cancers was performed using oligonucleotide microarray analysis. All samples were strictly matched by clinical features. Bioinformatic analyses such as the Kyoto Encyclopedia of Genes and Genomes were used to identify genes and pathways specifically associated with colon or rectal cancers. A total of 824 genes were differentially expressed in colon and rectal cancers. All differential gene interactions in the Signal-Net were analyzed. More genes were differentially expressed and included in the Signal-Net for rectal than colon cancer. Of the genes differentially expressed between colon and rectal cancer, S100P, the Reg family, ACTN1, CAMK2G and ACAT1 were the most significantly altered. Genes involved in the cell cycle pathway were present in rectal and colon cancers, but were more important in rectal cancer. The p53 and metabolic signaling pathways were significantly different in colon and rectal cancers. Gene expression profiles differed between colon and rectal cancer, with metabolic pathways being more important in rectal cancer. The oncogenesis of rectal cancer may be more complex than that of colon cancer. Some genes could be new biomarkers for distinguishing between these two cancers. © 2011 The Authors. Journal of Digestive Diseases © 2011 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd.

  15. Second primary cancers after anogenital, skin, oral, esophageal and rectal cancers: etiological links?

    PubMed

    Hemminki, K; Jiang, Y; Dong, C

    2001-07-15

    The Swedish Family-Cancer Database was used to analyze second cancers after oral, esophageal, rectal, cervical, genital and skin (squamous cell carcinoma) cancers. A strong and consistent association of second cancers was observed at all these sites, in men and women. As a novel finding, an association of rectal cancer with the human papillomavirus (HVP)-related cancers was shown. New evidence on an excess of skin cancer with the HPV-related cancers was also provided. As an epidemiological study, the associations were strong and often supported by a number of comparisons. These could not be explained by bias or long-term treatment related effects. However, whether the findings on rectal and skin cancer are due to HPV or other infections, transient or inherited depressed immune function or other constitutional factors remains to be established. Copyright 2001 Wiley-Liss, Inc.

  16. Prognostic Value of MicroRNAs in Preoperative Treated Rectal Cancer

    PubMed Central

    Azizian, Azadeh; Epping, Ingo; Kramer, Frank; Jo, Peter; Bernhardt, Markus; Kitz, Julia; Salinas, Gabriela; Wolff, Hendrik A.; Grade, Marian; Beißbarth, Tim; Ghadimi, B. Michael; Gaedcke, Jochen

    2016-01-01

    Background: Patients with locally advanced rectal cancer are treated with preoperative chemoradiotherapy followed by surgical resection. Despite similar clinical parameters (uT2-3, uN+) and standard therapy, patients’ prognoses differ widely. A possible prediction of prognosis through microRNAs as biomarkers out of treatment-naïve biopsies would allow individualized therapy options. Methods: Microarray analysis of 45 microdissected preoperative biopsies from patients with rectal cancer was performed to identify potential microRNAs to predict overall survival, disease-free survival, cancer-specific survival, distant-metastasis-free survival, tumor regression grade, or nodal stage. Quantitative real-time polymerase chain reaction (qPCR) was performed on an independent set of 147 rectal cancer patients to validate relevant miRNAs. Results: In the microarray screen, 14 microRNAs were significantly correlated to overall survival. Five microRNAs were included from previous work. Finally, 19 miRNAs were evaluated by qPCR. miR-515-5p, miR-573, miR-579 and miR-802 demonstrated significant correlation with overall survival and cancer-specific survival (p < 0.05). miR-573 was also significantly correlated with the tumor regression grade after preoperative chemoradiotherapy. miR-133b showed a significant correlation with distant-metastasis-free survival. miR-146b expression levels showed a significant correlation with nodal stage. Conclusion: Specific microRNAs can be used as biomarkers to predict prognosis of patients with rectal cancer and possibly stratify patients’ therapy if validated in a prospective study. PMID:27092493

  17. Duration of symptoms, stage at diagnosis and relative survival in colon and rectal cancer.

    PubMed

    Jullumstrø, Eivind; Lydersen, Stian; Møller, Bjørn; Dahl, Olav; Edna, Tom-H

    2009-09-01

    In colorectal cancer, the relation between duration of symptoms and stage at presentation and prognosis is not yet settled. All 1263 patients treated for colorectal cancer at Levanger Hospital, 1980-2004, and 2892 patients treated in Norway during 2004 were included. The association between symptom duration as an explanatory variable and tumour stage as a dependent variable was analysed using a proportional odds logistic regression model. Known duration of symptoms was divided into four categories: <1 week, 1-8 weeks, 2-6 months and >6 months. There was an inverse relationship between symptom duration and colon cancer TNM-stage, OR=0.73 (95% CI 0.63-0.84), p<0.001 (Levanger Hospital) and 0.84 (0.75-0.95), p=0.004 (Norway 2004), where the OR is per category of symptom duration. Duration of symptoms were also inversely associated with T-stage, N-stage and M-stage in colon cancer. These relationships were not found for rectal cancer. In colon cancer the relative five-year survival for the four intervals of symptom duration was 44%, 39%, 54% and 66%, p<0.001, in Levanger, 1980-2004, and four-year survival was 46%, 62%, 75% and 74%, p<0.001, in Norway 2004, respectively. For rectal cancer survival was not dependent on symptom duration. In a multivariate analysis of relative survival of patients with colon cancer, duration of symptoms was associated with survival independent of tumour differentiation and TNM-stage. Increasing duration of symptoms was positively associated with less advanced disease and better survival in colon cancer, but not in rectal cancer.

  18. SEOM Clinical Guideline of localized rectal cancer (2016).

    PubMed

    González-Flores, E; Losa, F; Pericay, C; Polo, E; Roselló, S; Safont, M J; Vera, R; Aparicio, J; Cano, M T; Fernández-Martos, C

    2016-12-01

    Localized rectal adenocarcinoma is a heterogeneous disease and current treatment recommendations are based on a preoperative multidisciplinary evaluation. High-resolution magnetic resonance imaging and endoscopic ultrasound are complementary to do a locoregional accurate staging. Surgery remains the mainstay of treatment and preoperative therapies with chemoradiation (CRT) or short-course radiation (SCRT) must be considered in more locally advanced cases. Novel strategies with induction chemotherapy alone or preceding or after CRT (SCRT) and surgery are in development.

  19. Critical appraisal of laparoscopic vs open rectal cancer surgery

    PubMed Central

    Tan, Winson Jianhong; Chew, Min Hoe; Dharmawan, Angela Renayanti; Singh, Manraj; Acharyya, Sanchalika; Loi, Carol Tien Tau; Tang, Choong Leong

    2016-01-01

    AIM: To evaluate the long-term clinical and oncological outcomes of laparoscopic rectal resection (LRR) and the impact of conversion in patients with rectal cancer. METHODS: An analysis was performed on a prospective database of 633 consecutive patients with rectal cancer who underwent surgical resection. Patients were compared in three groups: Open surgery (OP), laparoscopic surgery, and converted laparoscopic surgery. Short-term outcomes, long-term outcomes, and survival analysis were compared. RESULTS: Among 633 patients studied, 200 patients had successful laparoscopic resections with a conversion rate of 11.1% (25 out of 225). Factors predictive of survival on univariate analysis include the laparoscopic approach (P = 0.016), together with factors such as age, ASA status, stage of disease, tumor grade, presence of perineural invasion and vascular emboli, circumferential resection margin < 2 mm, and postoperative adjuvant chemotherapy. The survival benefit of laparoscopic surgery was no longer significant on multivariate analysis (P = 0.148). Neither 5-year overall survival (70.5% vs 61.8%, P = 0.217) nor 5-year cancer free survival (64.3% vs 66.6%, P = 0.854) were significantly different between the laparoscopic group and the converted group. CONCLUSION: LRR has equivalent long-term oncologic outcomes when compared to OP. Laparoscopic conversion does not confer a worse prognosis. PMID:27358678

  20. [Causes of local recurrence after curative surgery for rectal cancer].

    PubMed

    Hôhn, József; Varga, László; Baradnay, Gellért; Simonka, Zsolt; Géczi, Tibor; Nagy, Ferenc; Molnár, Tamás; Maráz, Anikó; Kahán, Zsuzsa; Balogh, Adám

    2003-01-01

    The rate of local recurrence (LR) has been 20-40% after resective surgery for rectal cancer by the traditional - Miles or Dixon - operative technics. The authors performed curative resection in 358 patients with rectal cancer in a 10 year period (01.01.1990 - 31.12.2000) in the Surgical Department of Szeged University. Since 01.01.1996 the authors changed this type of surgery for the Heald technics (total mesorectal excision - TME - with sharp dissection, using the UltraCision device) for the surgical treatment of middle or lower third rectal cancer. To compare the results of the two procedures, the authors analysed their material in two periods: Period I: 01.01.1991 - 31.12.1992: 62 patients operated on with the traditional operative technics; LR 15% within 2 years after surgery. Period II: 01.01.1997 - 31.12.1998: 78 patients operated on with the Heald technics (TME with sharp dissection); LR 6.4% within 2 years after surgery. Based on their results, the authors found that the modern operative technics by Heald, used in the second period of the study, was a relevant factor decreasing LR from 15% to 6.4%, while the gender, age of the patients, ratio of the abdominoperineal extirpation versus anterior resection (APRE/AR) and the free margin of more than 3 cm proved to be irrelevant.

  1. Use of brachytherapy in management of locally recurrent rectal cancer.

    PubMed

    Goes, R N; Beart, R W; Simons, A J; Gunderson, L L; Grado, G; Streeter, O

    1997-10-01

    Locally recurrent rectal cancer is associated with poor quality of life and has justified aggressive surgical and adjuvant approaches to control the disease. This study was designed to evaluate if the use of brachytherapy in association with wide surgical excision (debulking operation) can offer reasonable palliation for patients with locally recurrent rectal cancer. Patients with biopsy-proven locally recurrent rectal cancer who were not candidates for intraoperative radiation therapy and who were previously considered as having unresectable tumors were included in the study and were followed-up from May 1981 to November 1990. All of them had undergone laparotomy and had either radical or debulking surgical resection performed. At the same time, brachytherapy was used with temporary or permanent implant of seeds of iridium-192 or iodine-125. Thirty patients were included. Patients ranged in age from 28 to 74 years, and 16 patients were female. No mortality was observed, and morbidity was low (small-bowel obstruction (1 patient), intestinal fistula (1 patient), and urinary fistula (1 patient). Histologic examination of the specimen showed gross residual disease in 67 percent of patients and microscopic disease in 25 percent of patients. Long-term follow-up was possible in 28 patients. Mean follow-up and local control were, respectively, 26.5 months and 37.5 percent for gross residual disease and 34 months and 66 percent for microscopic residual disease. Eighteen patients (64 percent) had locally recurrent rectal cancer under control at the time of the last follow-up, with seven patients (25 percent) having no evidence of local or distant recurrence. This is the first report of brachytherapy for locally recurrent rectal cancer. This appears to offer a therapeutic alternative to patients who are not candidates for intraoperative radiation therapy. Surgical morbidity and mortality are acceptable. Local control in 18 patients (64 percent) is comparable with

  2. Focal adhesion kinase: predictor of tumour response and risk factor for recurrence after neoadjuvant chemoradiation in rectal cancer.

    PubMed

    Gómez Del Pulgar, Teresa; Cebrián, Arancha; Fernández-Aceñero, Maria Jesús; Borrero-Palacios, Aurea; Del Puerto-Nevado, Laura; Martínez-Useros, Javier; Marín-Arango, Juan Pablo; Caramés, Cristina; Vega-Bravo, Ricardo; Rodríguez-Remírez, María; Cruz-Ramos, Marlid; Manzarbeitia, Félix; García-Foncillas, Jesús

    2016-09-01

    Rectal cancer represents about 30% of colorectal cancers, being around 50% locally advanced at presentation. Chemoradiation (CRT) followed by total mesorectal excision is the standard of care for these locally advanced stages. However, it is not free of adverse effects and toxicity and the complete pathologic response rate is between 10% and 30%. This makes it extremely important to define factors that can predict response to this therapy. Focal adhesion kinase (FAK) expression has been correlated with worse prognosis in several tumours and its possible involvement in cancer radio- and chemosensitivity has been suggested; however, its role in rectal cancer has not been analysed yet. To analyse the association of FAK expression with tumour response to CRT in locally advanced rectal cancer. This study includes 73 patients with locally advanced rectal cancer receiving standard neoadjuvant CRT followed by total mesorectal excision. Focal adhesion kinase protein levels were immunohistochemically analysed in the pre-treatment biopsies of these patients and correlated with tumour response to CRT and patients survival. Low FAK expression was significantly correlated with local and distant recurrence (P = 0.013). Low FAK expression was found to be a predictive marker of tumour response to neoadjuvant therapy (P = 0.007) and patients whose tumours did not express FAK showed a strong association with lower disease-free survival (P = 0.01). Focal adhesion kinase expression predicts neoadjuvant CRT response in rectal cancer patients and it is a clinically relevant risk factor for local and distant recurrence. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  3. Laparoscopic and Robotic Total Mesorectal Excision in the Treatment of Rectal Cancer. Brief Review and Personal Remarks

    PubMed Central

    Bianchi, Paolo Pietro; Petz, Wanda; Luca, Fabrizio; Biffi, Roberto; Spinoglio, Giuseppe; Montorsi, Marco

    2014-01-01

    The current standard treatment for rectal cancer is based on a multimodality approach with preoperative radiochemotherapy in advanced cases and complete surgical removal through total mesorectal excision (TME). The most frequent surgical approach is traditional open surgery, as laparoscopic TME requires high technical skill, a long learning curve, and is not widespread, still being confined to centers with great experience in minimally invasive techniques. Nevertheless, in several studies, the laparoscopic approach, when compared to open surgery, has shown some better short-term clinical outcomes and at least comparable oncologic results. Robotic surgery for the treatment of rectal cancer is an emerging technique, which could overcome some of the technical difficulties posed by standard laparoscopy, but evidence from the literature regarding its oncologic safety and clinical outcomes is still lacking. This brief review analyses the current status of minimally invasive surgery for rectal cancer therapy, focusing on oncologic safety and the new robotic approach. PMID:24834429

  4. Nanocytology of rectal colonocytes to assess risk of colon cancer based on field cancerization.

    PubMed

    Damania, Dhwanil; Roy, Hemant K; Subramanian, Hariharan; Weinberg, David S; Rex, Douglas K; Goldberg, Michael J; Muldoon, Joseph; Cherkezyan, Lusik; Zhu, Yuanjia; Bianchi, Laura K; Shah, Dhiren; Pradhan, Prabhakar; Borkar, Monica; Lynch, Henry; Backman, Vadim

    2012-06-01

    Developing a minimally invasive and cost-effective prescreening strategy for colon cancer is critical because of the impossibility of conducting colonoscopy on the entire at-risk population. The concept of field carcinogenesis, in which normal-appearing tissue away from a tumor has molecular and, consequently, nano-architectural abnormalities, offers one attractive approach to identify high-risk patients. In this study, we investigated whether the novel imaging technique partial wave spectroscopic (PWS) microscopy could risk-stratify patients harboring precancerous lesions of the colon, using an optically measured biomarker (L(d)) obtained from microscopically normal but nanoscopically altered cells. Rectal epithelial cells were examined from 146 patients, including 72 control patients, 14 patients with diminutive adenomas, 20 patients with nondiminutive/nonadvanced adenomas, 15 patients with advanced adenomas/high-grade dysplasia, 12 patients with genetic mutation leading to Lynch syndrome, and 13 patients with cancer. We found that the L(d) obtained from rectal colonocytes was well correlated with colon tumorigenicity in our patient cohort and in an independent validation set of 39 additional patients. Therefore, our findings suggest that PWS-measured L(d) is an accurate marker of field carcinogenesis. This approach provides a potential prescreening strategy for risk stratification before colonoscopy.

  5. Infusional 5-Fluorouracil and ZD1839 (Gefitinib-Iressa) in Combination With Preoperative Radiotherapy in Patients With Locally Advanced Rectal Cancer: A Phase I and II Trial (1839IL/0092)

    SciTech Connect

    Valentini, Vincenzo; De Paoli, Antonino; Gambacorta, Maria Antonietta Mantini, Giovanna; Ratto, Carlo; Vecchio, Fabio Maria; Barbaro, Brunella; Innocente, Roberto; Rossi, Carlo; Boz, Giovanni; Barba, Maria Cristina; Frattegiani, Alessandro; Lupattelli, Marco; Doglietto, Giovan Battista

    2008-11-01

    Purpose: To report the final data of a Phase I and II study (1839IL/0092) on the combination of an anti-epidermal growth factor receptor drug (gefitinib), infusional 5-fluorouracil, and preoperative radiotherapy in locally advanced, resectable rectal cancer. Methods and Materials: Patients received 45 Gy in the posterior pelvis plus a boost of 5.4 Gy on the tumor and corresponding mesorectum. Infusional 5-fluorouracil (5-FU) and gefitinib (250 and 500 mg/day) were delivered during all radiotherapy course. An IORT boost of 10 Gy was allowed. The main endpoints of the study were to establish dose-limiting toxicity (DLT) and to evaluate the rate of pathologic response according to the tumor regression grade (TRG) Mandard score. Results: A total of 41 patients were enrolled. The DLT was not reached in the 6 patients enrolled in the dose-escalation part of the study. Of the 33 patients in the Phase II, TRG 1 was recorded in 10 patients (30.3%) and TRG 2 in 7 patients (21.2 %); overall 17 of 33 patients (51.5%) had a favorable endpoint. Overall, Grade 3+ toxicity was recorded in 16 patients (41%); these included Grade 3+ gastrointestinal toxicity in 8 patients (20.5%), Grade 3+ skin toxicity in 6 (15.3%), and Grade 3+ genitourinary toxicity in 4 (10.2%). A dose reduction of gefitinib was necessary in 24 patients (61.5%). Conclusions: Gefitinib can be associated with 5-FU-based preoperative chemoradiation at the dose of 500 mg without any life-threatening toxicity and with a high pCR (30.3%). The relevant rate of Grade 3 gastrointestinal toxicity suggests that 250 mg would be more tolerable dose in a neaoadjuvant approach with radiotherapy and infusional 5-FU.

  6. Standardized Index of Shape (DCE-MRI) and Standardized Uptake Value (PET/CT): Two quantitative approaches to discriminate chemo-radiotherapy locally advanced rectal cancer responders under a functional profile

    PubMed Central

    Petrillo, Antonella; Fusco, Roberta; Petrillo, Mario; Granata, Vincenza; Delrio, Paolo; Bianco, Francesco; Pecori, Biagio; Botti, Gerardo; Tatangelo, Fabiana; Caracò, Corradina; Aloj, Luigi; Avallone, Antonio; Lastoria, Secondo

    2017-01-01

    Purpose To investigate dynamic contrast enhanced-MRI (DCE-MRI) in the preoperative chemo-radiotherapy (CRT) assessment for locally advanced rectal cancer (LARC) compared to18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). Methods 75 consecutive patients with LARC were enrolled in a prospective study. DCE-MRI analysis was performed measuring SIS: linear combination of percentage change (Δ) of maximum signal difference (MSD) and wash-out slope (WOS). 18F-FDG PET/CT analysis was performed using SUV maximum (SUVmax). Tumor regression grade (TRG) were estimated after surgery. Non-parametric tests, receiver operating characteristic were evaluated. Results 55 patients (TRG1-2) were classified as responders while 20 subjects as non responders. ΔSIS reached sensitivity of 93%, specificity of 80% and accuracy of 89% (cut-off 6%) to differentiate responders by non responders, sensitivity of 93%, specificity of 69% and accuracy of 79% (cut-off 30%) to identify pathological complete response (pCR). Therapy assessment via ΔSUVmax reached sensitivity of 67%, specificity of 75% and accuracy of 70% (cut-off 60%) to differentiate responders by non responders and sensitivity of 80%, specificity of 31% and accuracy of 51% (cut-off 44%) to identify pCR. Conclusions CRT response assessment by DCE-MRI analysis shows a higher predictive ability than 18F-FDG PET/CT in LARC patients allowing to better discriminate significant and pCR. PMID:28042958

  7. The Role of Dual-Time Combined 18-Fluorideoxyglucose Positron Emission Tomography and Computed Tomography in the Staging and Restaging Workup of Locally Advanced Rectal Cancer, Treated With Preoperative Chemoradiation Therapy and Radical Surgery

    SciTech Connect

    Capirci, Carlo Rubello, Domenico; Pasini, Felice; Galeotti, Fabrizio; Bianchini, Enzo; Del Favero, Giuseppe; Panzavolta, Riccardo; Crepaldi, Giorgio; Rampin, Lucia; Facci, Enzo; Gava, Marcello; Banti, Elena; Marano, Gianfranco

    2009-08-01

    Purpose: In patients with locally advanced rectal cancer (LARC) staging and, after preoperative chemo-radiation therapy (CRT), restaging workup could be useful to tailor therapeutic approaches. Fluorine-18-fluorodeoxyglucose positron emission tomography ([{sup 18}F]FDG-PET) is a promising tool for monitoring the effect of antitumor therapy. This study was aimed to evaluate the possible role of dual time sequential FDG-PET scans in the staging and restaging workup of LARC. Methods and Materials: Eighty-seven consecutive patients with LARC were enrolled. CRT consisted of external-beam intensified radiotherapy (concurrent boost), with concomitant chemotherapy PVI 5-FU (300mg/m{sup 2}/day) followed 8-10 weeks later by surgery. All patients underwent [{sup 18}F]FDG-PET/CT before and 5-6 weeks later after the completion of CRT. Measurements of FDG uptake (SUV{sub max}), and percentage of SUV{sub max} difference (Response Index = RI) between pre- and post-CRT [{sup 18}F]FDG-PET scans were evaluated. Results: Six of 87 patients were excluded due to protocol deviation. Following CRT, 40/81 patients (49%) were classified as responders according to Mandard's criteria (TRG1-2). The mean pre-CRT SUV{sub max} was significantly higher than post-CRT (15.8, vs 5.9; p < 0.001). The mean RI was significantly higher in responders than in nonresponder patients (71.3% vs 38%; p = 0.0038). Using a RI cut-off of 65% for defining response to therapy, the following parameters have been obtained: 84.5% sensitivity, 80% specificity, 81.4% positive predictive value, 84.2% negative predictive value, and 81% overall accuracy. Conclusion: These results suggest the potential role of [{sup 18}F]FDG-PET in the restaging workup after preoperative CRT in LARC. RI seems the best predictor to identify CRT response.

  8. Critical role of bevacizumab scheduling in combination with pre-surgical chemo-radiotherapy in MRI-defined high-risk locally advanced rectal cancer: results of the branch trial

    PubMed Central

    Avallone, Antonio; Pecori, Biagio; Bianco, Franco; Aloj, Luigi; Tatangelo, Fabiana; Romano, Carmela; Granata, Vincenza; Marone, Pietro; Leone, Alessandra; Botti, Gerardo; Petrillo, Antonella; Caracò, Corradina; Iaffaioli, Vincenzo R.; Muto, Paolo; Romano, Giovanni; Comella, Pasquale; Budillon, Alfredo; Delrio, Paolo

    2015-01-01

    Background We have previously shown that an intensified preoperative regimen including oxaliplatin plus raltitrexed and 5-fluorouracil/folinic acid (OXATOM/FUFA) during preoperative pelvic radiotherapy produced promising results in locally advanced rectal cancer (LARC). Preclinical evidence suggests that the scheduling of bevacizumab may be crucial to optimize its combination with chemo-radiotherapy. Patients and methods This non-randomized, non-comparative, phase II study was conducted in MRI-defined high-risk LARC. Patients received three biweekly cycles of OXATOM/FUFA during RT. Bevacizumab was given 2 weeks before the start of chemo-radiotherapy, and on the same day of chemotherapy for 3 cycles (concomitant-schedule A) or 4 days prior to the first and second cycle of chemotherapy (sequential-schedule B). Primary end point was pathological complete tumor regression (TRG1) rate. Results The accrual for the concomitant-schedule was early terminated because the number of TRG1 (2 out of 16 patients) was statistically inconsistent with the hypothesis of activity (30%) to be tested. Conversely, the endpoint was reached with the sequential-schedule and the final TRG1 rate among 46 enrolled patients was 50% (95% CI 35%–65%). Neutropenia was the most common grade ≥3 toxicity with both schedules, but it was less pronounced with the sequential than concomitant-schedule (30% vs. 44%). Postoperative complications occurred in 8/15 (53%) and 13/46 (28%) patients in schedule A and B, respectively. At 5 year follow-up the probability of PFS and OS was 80% (95%CI, 66%–89%) and 85% (95%CI, 69%–93%), respectively, for the sequential-schedule. Conclusions These results highlights the relevance of bevacizumab scheduling to optimize its combination with preoperative chemo-radiotherapy in the management of LARC. PMID:26320185

  9. Comparison of laparoscopic vs. open surgery for rectal cancer

    PubMed Central

    Ding, Zihai; Wang, Zheng; Huang, Shijie; Zhong, Shizhen; Lin, Jianhua

    2017-01-01

    This study was conducted to evaluate the safety of laparoscopic radical resection for rectal cancer. A total of 64 cases of rectal cancer patients undergoing radical surgery between January, 1998 and March, 2010 were collected. The patients were divided into the laparoscopic rectal surgery group (LS group, n=31) and the open surgery group (OS group, n=33). Operation time, postoperative recovery, complications and tumor-free survival rate were compared between the two groups. The inclusion criteria were as follows: Standard Karnofsky score >70 prior to surgery, definitive pathological diagnosis and complete clinical data. The exclusion criteria were concomitant tumors affecting survival. With the Dixon operation, the LS group had a longer operation time compared with the OS group (271.2±56.2 vs. 216.0±62.7 min, respectively; P=0.036), and an earlier time of oral intake (3.0±0.9 vs. 4.7±1.0 days, respectively; P=0.000). There were no significant differences between the LS and OS groups in terms of intraoperative blood loss, number of lymph nodes retrieved, duration of postoperative hyperthermia and hospitalization time (P>0.05). With the Miles operation, there were no obvious differences between the LS and OS groups regarding operation time, intraoperative blood loss, number of lymph nodes retrieved, time of oral intake, duration of postoperative hyperthermia and hospitalization time (P>0.05). Furthermore, there were no significant differences between the LS and OS groups with the Dixon or Miles operation in terms of 3-year tumor-free survival rate (P>0.05). Thus, laparoscopic surgery appears to be a safe and feasible option for the treatment of rectal cancer. PMID:28357087

  10. Colon and Rectal Cancer Survival by Tumor Location and Microsatellite Instability: The Colon Cancer Family Registry

    PubMed Central

    Phipps, Amanda I.; Lindor, Noralane M.; Jenkins, Mark A.; Baron, John A.; Win, Aung Ko; Gallinger, Steven; Gryfe, Robert; Newcomb, Polly A.

    2013-01-01

    Background Cancers in the proximal colon, distal colon, and rectum are frequently studied together; however, there are biological differences in cancers across these sites, particularly in the prevalence of microsatellite instability. Objective We assessed differences in survival by colon or rectal cancer site, considering the contribution of microsatellite instability to such differences. Design This is a population-based prospective cohort study for cancer survival. Settings This study was conducted within the Colon Cancer Family Registry, an international consortium. Participants were identified from population-based cancer registries in the United States, Canada, and Australia. Patients Information on tumor site, microsatellite instability, and survival after diagnosis was available for 3284 men and women diagnosed with incident invasive colon or rectal cancer between 1997–2002, with ages at diagnosis ranging from 18–74. Main Outcome Measures Cox regression was used to calculate hazard ratios for the association between all-cause mortality and tumor location, overall and by microsatellite instability status. Results Distal colon (hazard ratio=0.59, 95% confidence interval: 0.49–0.71) and rectal cancers (hazard ratio=0.68, 95% confidence interval: 0.57–0.81) were associated with lower mortality than proximal colon cancer overall. Compared specifically to cases with proximal colon cancer exhibiting no/low microsatellite instability, cases with distal colon and rectal cancers experienced lower mortality, regardless of microsatellite instability status; cases with proximal colon cancer exhibiting high microsatellite instability had the lowest mortality. Limitations Study limitations include the absence of stage at diagnosis and cause of death information for all but a subset of study participants. Some case groups defined jointly by tumor site and microsatellite instability status are subject to small numbers. Conclusion Proximal colon cancer survival

  11. Colon and rectal cancer survival by tumor location and microsatellite instability: the Colon Cancer Family Registry.

    PubMed

    Phipps, Amanda I; Lindor, Noralane M; Jenkins, Mark A; Baron, John A; Win, Aung Ko; Gallinger, Steven; Gryfe, Robert; Newcomb, Polly A

    2013-08-01

    Cancers in the proximal colon, distal colon, and rectum are frequently studied together; however, there are biological differences in cancers across these sites, particularly in the prevalence of microsatellite instability. We assessed the differences in survival by colon or rectal cancer site, considering the contribution of microsatellite instability to such differences. This is a population-based prospective cohort study for cancer survival. This study was conducted within the Colon Cancer Family Registry, an international consortium. Participants were identified from population-based cancer registries in the United States, Canada, and Australia. Information on tumor site, microsatellite instability, and survival after diagnosis was available for 3284 men and women diagnosed with incident invasive colon or rectal cancer between 1997 and 2002, with ages at diagnosis ranging from 18 to 74. Cox regression was used to calculate hazard ratios for the association between all-cause mortality and tumor location, overall and by microsatellite instability status. Distal colon (HR, 0.59; 95% CI, 0.49-0.71) and rectal cancers (HR, 0.68; 95% CI, 0.57-0.81) were associated with lower mortality than proximal colon cancer overall. Compared specifically with patients with proximal colon cancer exhibiting no/low microsatellite instability, patients with distal colon and rectal cancers experienced lower mortality, regardless of microsatellite instability status; patients with proximal colon cancer exhibiting high microsatellite instability had the lowest mortality. Study limitations include the absence of stage at diagnosis and cause-of-death information for all but a subset of study participants. Some patient groups defined jointly by tumor site and microsatellite instability status are subject to small numbers. Proximal colon cancer survival differs from survival for distal colon and rectal cancer in a manner apparently dependent on microsatellite instability status. These

  12. Learning curve for robotic-assisted laparoscopic rectal cancer surgery.

    PubMed

    Jiménez-Rodríguez, Rosa M; Díaz-Pavón, José Manuel; de la Portilla de Juan, Fernando; Prendes-Sillero, Emilio; Dussort, Hisnard Cadet; Padillo, Javier

    2013-06-01

    One of the main uses of robotic assisted abdominal surgery is the mesorectal excision in patients with rectal cancer. The aim of the present study is to analyse the learning curve for robotic assisted laparoscopic resection of rectal cancer. We included in our study 43 consecutive rectal cancer resections (16 females and 27 males) performed from January 2008 through December 2010. Mean age of patients was 66 ± 9.0 years. Surgical procedures included both abdomino-perineal and anterior resections. We analysed the following parameters: demographic data of the patients included in the study, intra- and postoperative data, time taking to set up the robot for operations (set-up or docking time), operative time, intra- and postoperative complications, conversion rates and pathological specimen features. The learning curve was analysed using cumulative sum (CUSUM) methodology. The procedures understudied included seven abdomino-perineal resections and 36 anterior resections. In our series of patients, mean robotic set-up time was 62.9 ± 24.6 min, and the mean operative time was 197.4 ± 44.3 min. Once we applied CUSUM methodology, we obtained two graphs for CUSUM values (operating time and success), both of them showing three well-differentiated phases: phase 1 (the initial 9-11 cases), phase 2 (the middle 12 cases) and phase 3 (the remaining 20-22 cases). Phase 1 represents initial learning; phase 2 plateau represents increased competence in the use of the robotic system, and finally, phase 3 represents the period of highest skill or mastery with a reduction in docking time (p = 0.000), but a slight increase in operative time (p = 0.007). The CUSUM curve shows three phases in the learning and use of robotic assisted rectal cancer surgery which correspond to the phases of initial learning of the technique, consolidation and higher expertise or mastery. The data obtained suggest that the estimated learning curve for robotic assisted rectal cancer

  13. Clinical application of multimodality imaging in radiotherapy treatment planning for rectal cancer.

    PubMed

    Wang, Yan Yang; Zhe, Hong

    2013-12-11

    Radiotherapy plays an important role in the treatment of rectal cancer. Three-dimensional conformal radiotherapy and intensity-modulated radiotherapy are mainstay techniques of radiotherapy for rectal cancer. However, the success of these techniques is heavily reliant on accurate target delineation and treatment planning. Computed tomography simulation is a cornerstone of rectal cancer radiotherapy, but there are limitations, such as poor soft-tissue contrast between pelvic structures and partial volume effects. Magnetic resonance imaging and positron emission tomography (PET) can overcome these limitations and provide additional information for rectal cancer treatment planning. PET can also reduce the interobserver variation in the definition of rectal tumor volume. However, there is a long way to go before these image modalities are routinely used in the clinical setting. This review summarizes the most promising studies on clinical applications of multimodality imaging in target delineation and treatment planning for rectal cancer radiotherapy.

  14. Long-term results of local excision for rectal cancer.

    PubMed

    Paty, Philip B; Nash, Garrett M; Baron, Paul; Zakowski, Maureen; Minsky, Bruce D; Blumberg, David; Nathanson, Daniel R; Guillem, Jose G; Enker, Warren E; Cohen, Alfred M; Wong, W Douglas

    2002-10-01

    To review the authors' experience with local excision of early rectal cancers to assess the effectiveness of initial treatment and of salvage surgery. Local excision for rectal cancer is appealing for its low morbidity and excellent functional results. However, its use is limited by inability to assess regional lymph nodes and uncertainty of oncologic outcome. Patients with T1 and T2 adenocarcinomas of the rectum treated by local excision as definitive surgery between 1969 to 1996 at the authors' institution were reviewed. Pathology slides were reviewed. Among 125 assessable patients, 74 were T1 and 51 were T2. Thirty-one patients (25%) were selected to receive adjuvant radiation therapy. Fifteen of these 31 patients received adjuvant radiation in combination with 5-fluorouracil chemotherapy. Median follow-up was 6.7 years. One hundred fifteen patients (92%) were followed until death or for greater than 5 years, and 69 patients (55%) were followed until death or for greater than 10 years. Recurrence was recorded as local, distant, and overall. Survival was disease-specific. Ten-year local recurrence and survival rates were 17% and 74% for T1 rectal cancers and 26% and 72% for T2 cancers. Median time to relapse was 1.4 years (range 0.4-7.0) for local recurrence and 2.5 years (0.8-7.5) for distant recurrence. In patients receiving radiotherapy, local recurrence was delayed (median 2.1 years vs. 1.1 years), but overall rates of local and overall recurrence and survival rates were similar to patients not receiving radiotherapy. Among 26 cancer deaths, 8 (28%) occurred more than 5 years after local excision. On multivariate analysis, no clinical or pathologic features were predictive of local recurrence. Intratumoral vascular invasion was the only significant predictor of survival. Among 34 patients who developed tumor recurrence, the pattern of first clinical recurrence was predominantly local: 50% local only, 18% local and distant, and 32% distant only. Among the 17

  15. Impact of Diabetes on Oncologic Outcome of Colorectal Cancer Patients: Colon vs. Rectal Cancer

    PubMed Central

    Park, Min Geun; Lee, Ji-Won; Chu, Sang Hui; Park, Ji-Hye; Lee, Mi Kyung; Sato, Kaori; Ligibel, Jennifer A.; Meyerhardt, Jeffrey A.; Kim, Nam Kyu

    2013-01-01

    Background To evaluate the impact of diabetes on outcomes in colorectal cancer patients and to examine whether this association varies by the location of tumor (colon vs. rectum). Patients and methods This study includes 4,131 stage I-III colorectal cancer patients, treated between 1995 and 2007 (12.5% diabetic, 53% colon, 47% rectal) in South Korea. Cox proportional hazards modeling was used to determine the prognostic influence of DM on survival endpoints. Results Colorectal cancer patients with DM had significantly worse disease-free survival (DFS) [hazard ratio (HR) 1.17, 95% confidence interval (CI): 1.00–1.37] compared with patients without DM. When considering colon and rectal cancer independently, DM was significantly associated with worse overall survival (OS) (HR: 1.46, 95% CI: 1.11–1.92), DFS (HR: 1.45, 95% CI: 1.15–1.84) and recurrence-free survival (RFS) (HR: 1.32, 95% CI: 0.98–1.76) in colon cancer patients. No association for OS, DFS or RFS was observed in rectal cancer patients. There was significant interaction of location of tumor (colon vs. rectal cancer) with DM on OS (P = 0.009) and DFS (P = 0.007). Conclusions This study suggests that DM negatively impacts survival outcomes of patients with colon cancer but not rectal cancer. PMID:23405123

  16. Association of statin use with a pathologic complete response to neoadjuvant chemoradiation for rectal cancer

    SciTech Connect

    Katz, Matthew S.; Minsky, Bruce D. . E-mail: minskyb@mskcc.org; Saltz, Leonard B.; Riedel, Elyn; Chessin, David B.; Guillem, Jose G.

    2005-08-01

    Purpose: To assess whether 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, might enhance the efficacy of neoadjuvant chemoradiation in rectal cancer. Methods and Materials: Between 1996 and 2001, 358 patients with clinically resectable, nonmetastatic rectal cancer underwent surgery at Memorial Sloan-Kettering Cancer Center after neoadjuvant chemoradiation for either locally advanced tumors or low-lying tumors that would require abdominoperineal resection. We excluded 9 patients for radiation therapy dose <45 Gy or if statin use was unknown, leaving 349 evaluable patients. Median radiation therapy dose was 50.4 Gy (range, 45-55.8 Gy), and 308 patients (88%) received 5-flurouracil-based chemotherapy. Medication use, comorbid illnesses, clinical stage as assessed by digital rectal examination and ultrasound, and type of chemotherapy were analyzed for associations with pathologic complete response (pCR), defined as no microscopic evidence of tumor. Fisher's exact test was used for categoric variables, Mantel-Haenszel test for ordered categoric variables, and logistic regression for multivariate analysis. Results: Thirty-three patients (9%) used a statin, with no differences in clinical stage according to digital rectal examination or ultrasound compared with the other 324 patients. At the time of surgery, 23 nonstatin patients (7%) were found to have metastatic disease, compared with 0% for statin patients. The unadjusted pCR rates with and without statin use were 30% and 17%, respectively (p = 0.10). Variables significant univariately at the p = 0.15 level were entered into a multivariate model, as were nonsteroidal anti-inflammatory drugs (NSAIDs), which were strongly associated with statin use. The odds ratio for statin use on pCR was 4.2 (95% confidence interval, 1.7-12.1; p = 0.003) after adjusting for NSAID use, clinical stage, and type of chemotherapy. Conclusion: In multivariate analysis, statin use is associated with an improved p

  17. Sexual and urinary dysfunction after proctectomy for rectal cancer.

    PubMed

    Eveno, C; Lamblin, A; Mariette, C; Pocard, M

    2010-02-01

    Sexual and urinary dysfunction occur frequently after rectal surgery. Total mesorectal excision (TME) is currently the optimal technique for resection of rectal cancer, providing superior carcinological and functional outcomes. Age, pre-operative radiation therapy, abdominoperineal resection, and surgery which fails to respect the "sacred planes" of TME are the four major risk factors for post-operative sexual and urinary sequelae. In the era of TME, postoperative sexual dysfunction ranges from 10-35%, depending on the scores used to assess it, while urinary sequelae have decreased to less than 5%. The place of laparoscopic surgery remains to be defined, particularly with respect to these complications. It is essential to inform the patient pre-operatively about the possibility of such disorders not only for patient informed consent but also to help with correct post-operative management of the problem. Management is multifaceted, and includes psychological, pharmacological, and sometimes surgical therapy. (c) 2010 Elsevier Masson SAS. All rights reserved.

  18. The learning curve of laparoscopic treatment of rectal cancer does not increase morbidity.

    PubMed

    Luján, Juan; Gonzalez, Antonio; Abrisqueta, Jesús; Hernandez, Quiteria; Valero, Graciela; Abellán, Israel; Frutos, María Dolores; Parrilla, Pascual

    2014-01-01

    The treatment of rectal cancer via laparoscopy is controversial due to its technical complexity. Several randomized prospective studies have demonstrated clear advantages for the patient with similar oncological results to those of open surgery, although during the learning of this surgical technique there may be an increase in complications and a worse prognosis. Our aim is to analyze how the learning curve for rectal cancer via laparoscopy influences intra- and postoperative results and oncological markers. A retrospective review was conducted of the first 120 patients undergoing laparoscopic surgery for rectal neoplasia. The operations were performed by the same surgical team with a wide experience in the treatment of open colorectal cancer and qualified to perform advanced laparoscopic surgery. We analyzed sex, ASA, tumour location, neoadjuvant treatment, surgical technique, operating time, conversion, postoperative complications, length of hospital stay, number of lymph nodes, stage and involvement of margins. Significant differences were observed with regard to surgical time (224 min in the first group, 204 min in the second group), with a higher rate of conversion in the first group (22.5%) than in the second (11.3%). No significant differences were noted for rate of conservative sphincter surgery, length of hospital stay, post-surgical complications, number of affected/isolated lymph nodes or affected circumferential and distal margins. It is possible to learn this complex surgical technique without compromising the patient's safety and oncological outcome. Copyright © 2013 AEC. Published by Elsevier Espana. All rights reserved.

  19. Neoadjuvant Long-Course Chemoradiotherapy for Rectal Cancer: Does Time to Surgery Matter?

    PubMed Central

    Panagiotopoulou, Ioanna G.; Parashar, Deepak; Qasem, Eyas; Mezher-Sikafi, Rasha; Parmar, Jitesh; Wells, Alan D.; Bajwa, Farrukh M.; Menon, Madhav; Jephcott, Catherine R.

    2015-01-01

    The objective of this paper was to evaluate whether delaying surgery following long-course chemoradiotherapy for rectal cancer correlates with pathologic complete response. Pre-operative chemoradiotherapy (CRT) is standard practice in the UK for the management of locally advanced rectal cancer. Optimal timing of surgery following CRT is still not clearly defined. All patients with a diagnosis of rectal cancer who had undergone long-course CRT prior to surgery between January 2008 and December 2011 were included. Statistical analysis was performed using Stata 11. Fifty-nine patients received long-course CRT prior to surgery in the selected period. Twenty-seven percent (16/59) of patients showed a complete histopathologic response and 59.3% (35/59) of patients had tumor down-staging from radiologically-assessed node positive to histologically-proven node negative disease. There was no statistically significant delay to surgery after completion of CRT in the 16 patients with complete response (CR) compared with the rest of the group [IR: incomplete response; CR group median: 74.5 days (IQR: 70–87.5) and IR group median: 72 days (IQR: 57–83), P = 0.470]. Although no statistically significant predictors of either complete response or tumor nodal status down-staging were identified in logistic regression analyses, a trend toward complete response was seen with longer delay to surgery following completion of long-course CRT. PMID:26414816

  20. Neoadjuvant Long-Course Chemoradiotherapy for Rectal Cancer: Does Time to Surgery Matter?

    PubMed

    Panagiotopoulou, Ioanna G; Parashar, Deepak; Qasem, Eyas; Mezher-Sikafi, Rasha; Parmar, Jitesh; Wells, Alan D; Bajwa, Farrukh M; Menon, Madhav; Jephcott, Catherine R

    2015-06-01

    The objective of this paper was to evaluate whether delaying surgery following long-course chemoradiotherapy for rectal cancer correlates with pathologic complete response. Pre-operative chemoradiotherapy (CRT) is standard practice in the UK for the management of locally advanced rectal cancer. Optimal timing of surgery following CRT is still not clearly defined. All patients with a diagnosis of rectal cancer who had undergone long-course CRT prior to surgery between January 2008 and December 2011 were included. Statistical analysis was performed using Stata 11. Fifty-nine patients received long-course CRT prior to surgery in the selected period. Twenty-seven percent (16/59) of patients showed a complete histopathologic response and 59.3% (35/59) of patients had tumor down-staging from radiologically-assessed node positive to histologically-proven node negative disease. There was no statistically significant delay to surgery after completion of CRT in the 16 patients with complete response (CR) compared with the rest of the group [IR: incomplete response; CR group median: 74.5 days (IQR: 70-87.5) and IR group median: 72 days (IQR: 57-83), P = 0.470]. Although no statistically significant predictors of either complete response or tumor nodal status down-staging were identified in logistic regression analyses, a trend toward complete response was seen with longer delay to surgery following completion of long-course CRT.

  1. Clinical predictive circulating peptides in rectal cancer patients treated with neoadjuvant chemoradiotherapy.

    PubMed

    Crotti, Sara; Enzo, Maria Vittoria; Bedin, Chiara; Pucciarelli, Salvatore; Maretto, Isacco; Del Bianco, Paola; Traldi, Pietro; Tasciotti, Ennio; Ferrari, Mauro; Rizzolio, Flavio; Toffoli, Giuseppe; Giordano, Antonio; Nitti, Donato; Agostini, Marco

    2015-08-01

    Preoperative chemoradiotherapy is worldwide accepted as a standard treatment for locally advanced rectal cancer. Current standard of treatment includes administration of ionizing radiation for 45-50.4 Gy in 25-28 fractions associated with 5-fluorouracil administration during radiation therapy. Unfortunately, 40% of patients have a poor or absent response and novel predictive biomarkers are demanding. For the first time, we apply a novel peptidomic methodology and analysis in rectal cancer patients treated with preoperative chemoradiotherapy. Circulating peptides (Molecular Weight <3 kDa) have been harvested from patients' plasma (n = 33) using nanoporous silica chip and analyzed by Matrix-Assisted Laser Desorption/Ionization-Time of Flight mass spectrometer. Peptides fingerprint has been compared between responders and non-responders. Random Forest classification selected three peptides at m/z 1082.552, 1098.537, and 1104.538 that were able to correctly discriminate between responders (n = 16) and non-responders (n = 17) before therapy (T0) providing an overall accuracy of 86% and an area under the receiver operating characteristic (ROC) curve of 0.92. In conclusion, the nanoporous silica chip coupled to mass spectrometry method was found to be a realistic method for plasma-based peptide analysis and we provide the first list of predictive circulating biomarker peptides in rectal cancer patients underwent preoperative chemoradiotherapy.

  2. ¹H NMR-based metabolic profiling of human rectal cancer tissue

    PubMed Central

    2013-01-01

    Background Rectal cancer is one of the most prevalent tumor types. Understanding the metabolic profile of rectal cancer is important for developing therapeutic approaches and molecular diagnosis. Methods Here, we report a metabonomics profiling of tissue samples on a large cohort of human rectal cancer subjects (n = 127) and normal controls (n = 43) using 1H nuclear magnetic resonance (1H NMR) based metabonomics assay, which is a highly sensitive and non-destructive method for the biomarker identification in biological systems. Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and orthogonal projection to latent structure with discriminant analysis (OPLS-DA) were applied to analyze the 1H-NMR profiling data to identify the distinguishing metabolites of rectal cancer. Results Excellent separation was obtained and distinguishing metabolites were observed among the different stages of rectal cancer tissues (stage I = 35; stage II = 37; stage III = 37 and stage IV = 18) and normal controls. A total of 38 differential metabolites were identified, 16 of which were closely correlated with the stage of rectal cancer. The up-regulation of 10 metabolites, including lactate, threonine, acetate, glutathione, uracil, succinate, serine, formate, lysine and tyrosine, were detected in the cancer tissues. On the other hand, 6 metabolites, including myo-inositol, taurine, phosphocreatine, creatine, betaine and dimethylglycine were decreased in cancer tissues. These modified metabolites revealed disturbance of energy, amino acids, ketone body and choline metabolism, which may be correlated with the progression of human rectal cancer. Conclusion Our findings firstly identify the distinguishing metabolites in different stages of rectal cancer tissues, indicating possibility of the attribution of metabolites disturbance to the progression of rectal cancer. The altered metabolites may be as potential biomarkers, which would

  3. Watch and wait approach to rectal cancer: A review.

    PubMed

    Pozo, Marcos E; Fang, Sandy H

    2015-11-27

    In 2014, there were an estimated 136800 new cases of colorectal cancer, making it the most common gastrointestinal malignancy. It is the second leading cause of cancer death in both men and women in the United States and over one-third of newly diagnosed patients have stage III (node-positive) disease. For stage II and III colorectal cancer patients, the mainstay of curative therapy is neoadjuvant therapy, followed by radical surgical resection of the rectum. However, the consequences of a proctectomy, either by low anterior resection or abdominoperineal resection, can lead to very extensive comorbidities, such as the need for a permanent colostomy, fecal incontinence, sexual and urinary dysfunction, and even mortality. Recently, trends of complete regression of the rectal cancer after neoadjuvant chemoradiation therapy have been confirmed by clinical and radiographic evaluation-this is known as complete clinical response (cCR). The "watch and wait" approach was first proposed by Dr. Angelita Habr-Gama in Brazil in 2009. Those patients with cCR are followed with close surveillance physical examinations, endoscopy, and imaging. Here, we review management of rectal cancer, the development of the "watch and wait" approach and its outcomes.

  4. Protocol for a multicentre randomised feasibility trial evaluating early Surgery Alone In LOw Rectal cancer (SAILOR)

    PubMed Central

    Thorne, Kymberley; Hutchings, Hayley; Islam, Saiful; Holland, Gail; Hatcher, Olivia; Gwynne, Sarah; Jenkins, Ian; Coyne, Peter; Duff, Michael; Feldman, Melanie; Winter, Des C; Gollins, Simon; Quirke, Phil; West, Nick; Brown, Gina; Fitzsimmons, Deborah; Brown, Alan; Beynon, John

    2016-01-01

    Introduction There are 11 500 rectal cancers diagnosed annually in the UK. Although surgery remains the primary treatment, there is evidence that preoperative radiotherapy (RT) improves local recurrence rates. High-quality surgery in rectal cancer is equally important in minimising local recurrence. Advances in MRI-guided prediction of resection margin status and improvements in abdominoperineal excision of the rectum (APER) technique supports a reassessment of the contribution of preoperative RT. A more selective approach to RT may be appropriate given the associated toxicity. Methods and analysis This trial will explore the feasibility of a definitive trial evaluating the omission of RT in resectable low rectal cancer requiring APER. It will test the feasibility of randomising patients to (1) standard care (neoadjuvant long course RT±chemotherapy and APER, or (2) APER surgery alone for cT2/T3ab N0/1 low rectal cancer with clear predicted resection margins on MRI. RT schedule will be 45 Gy over 5 weeks as current standard, with restaging and surgery after 8–12 weeks. Recruitment will be for 24 months with a minimum 12-month follow-up. Objectives Objectives include testing the ability to recruit, consent and retain patients, to quantify the number of patients eligible for a definitive trial and to test feasibility of outcomes measures. These include locoregional recurrence rates, distance to circumferential resection margin, toxicity and surgical complications including perineal wound healing, quality of life and economic analysis. The quality of MRI staging, RT delivery and surgical specimen quality will be closely monitored. Ethics and dissemination The trial is approved by the Regional Ethics Committee and Health Research Authority (HRA) or equivalent. Written informed consent will be obtained. Serious adverse events will be reported to Swansea Trials Unit (STU), the ethics committee and trial sites. Trial results will be submitted for peer review

  5. Rate of pulmonary metastasis varies with location of rectal cancer in the patients undergoing curative resection.

    PubMed

    Lee, Jong Lyul; Yu, Chang Sik; Kim, Tae Won; Kim, Jong Hoon; Kim, Jin Cheon

    2015-03-01

    Precise understanding of recurrence patterns permits efficient surveillance and effective treatment strategies. The aim of this study was to evaluate recurrence patterns after treatment of rectal cancers, specifically with respect to tumor location and chemoradiotherapy (CRT). A single-institution, retrospective cohort of 2,086 consecutive rectal cancer patients, was enrolled between January 2000 and December 2007. All the patients underwent curative operations (R0). Tumor location was classified into lower (≤5 cm), middle (>5 to ≤8 cm), and upper (>8 cm) groups based on the distance of the inferior tumor border from the anal verge; the patients were also characterized according to whether they received preoperative/postoperative CRT. The lung was the most common recurrence site in the lower group (lower vs. middle/upper; 14.6 vs. 8.9%/8.0%, P = 0.001/0.001). Recurrence patterns were not associated with receipt of preoperative/postoperative CRT. Additionally, RT and CRT did not reduce the rate of pulmonary recurrence (no-RT/preoperative CRT/postoperative CRT, 37.5/37.9/42.6%; P = 0.13). In a multivariate analysis, preoperative level of serum carcinoembryonic antigen, abdominoperineal resection, advanced T category, N category, and circumferential resection margin were identified as independent risk factors for pulmonary recurrence in all groups. Otherwise, low rectal cancer was associated with unresectable pulmonary recurrence (RR = 2.19; 95% CI 1.012-3.072; P = 0.04). Neither RT nor CRT affects the pattern and rate of recurrence. Tumor location specifically affects recurrence in rectal cancer patients, such that the lower group is a risk factor for unresectable pulmonary recurrences.

  6. Changes of Microrna Levels in Plasma of Patients with Rectal Cancer during Chemoradiotherapy

    PubMed Central

    Jo, Peter; Azizian, Azadeh; Salendo, Junius; Kramer, Frank; Bernhardt, Markus; Wolff, Hendrik A.; Gruber, Jens; Grade, Marian; Beißbarth, Tim; Ghadimi, B. Michael; Gaedcke, Jochen

    2017-01-01

    Since the response to chemoradiotherapy in patients with locally advanced rectal cancer is heterogeneous, valid biomarkers are needed to monitor tumor response. Circulating microRNAs are promising candidates, however analyses of circulating microRNAs in rectal cancer are still rare. 111 patients with rectal cancer and 46 age-matched normal controls were enrolled. The expression levels of 30 microRNAs were analyzed in 17 pre-treatment patients’ plasma samples. Differentially regulated microRNAs were validated in 94 independent patients. For 52 of the 94 patients a paired comparison between pre-treatment and post-treatment samples was performed. miR-17, miR-18b, miR-20a, miR-31, and miR-193a_3p, were significantly downregulated in pre-treatment plasma samples of patients with rectal cancer (p < 0.05). miR-29c, miR-30c, and miR-195 showed a trend of differential regulation. After validation, miR-31 and miR-30c were significantly deregulated by a decrease of expression. In 52 patients expression analyses of the 8 microRNAs in matched pre-treatment and post-treatment samples showed a significant decrease for all microRNAs (p < 0.05) after treatment. Expression levels of miR-31 and miR-30c could serve as valid biomarkers if validated in a prospective study. Plasma microRNA expression levels do not necessarily represent miRNA expression levels in tumor tissue. Also, expression levels of microRNAs change during multimodal therapy. PMID:28554991

  7. VNN1 overexpression is associated with poor response to preoperative chemoradiotherapy and adverse prognosis in patients with rectal cancers

    PubMed Central

    Chai, Chi-Yung; Zhang, Yimin; Song, Junlong; Lin, Shih-Chun; Sun, Shengrong; Chang, I-Wei

    2016-01-01

    Background: Colorectal cancer is prevalent worldwide and it is also the fourth most common cause of cancer mortality. For rectal cancer, neoadjuvant concurrent chemoradiotherapy (CCRT) followed by radical proctectomy is gold standard treatment for patients with stage II/III rectal cancer. By data mining a public dataset of rectal cancer transcriptome (GSE35452) from Gene Expression Omnibus, National Center of Biotechnology Information (GEO, NCBI), we identified that VNN1 was the most significantly upregulated gene among those related to nitrogen compound metabolic process (GO:0006807). Therefore, we analyzed the clinicopathological correlation and prognostic impact of VNN1 protein (pantetheinase), which encoded by VNN1 gene. Methods: VNN1 immunostaining was performed in 172 rectal adenocarcinomas treated with preoperative CCRT followed by surgery, which were bisected into high- and low-expression subgroups. Furthermore, statistical analyses were performed to correlate the relationship between VNN1 immunoreactivity and clinicopathological features, as well as three survival indices: disease-specific survival (DSS), local recurrence-free survival (LRFS) and metastasis-free survival (MeFS). Results: High VNN1 immunoexpression was significantly associated with advanced pre-treatment and post-treatment disease and poor response to CCRT (all P ≤ .026). In addition, VNN1 overexpression was linked to adverse DSS, LRFS and MeFS in univariate analysis and served as an independent prognosticator indicating worse DSS and LRFS in multivariate analysis (all P ≤ .019). Conclusion: VNN1 may play a crucial role in rectal cancer progression and responsiveness to CCRT, and serve as a novel prognostic biomarker. Additional studies to clarify the molecular pathway are essential for developing potential VNN1-targeted therapies for rectal cancer. PMID:27830030

  8. The use of capecitabine in the combined-modality therapy for rectal cancer.

    PubMed

    Liauw, Stanley L; Minsky, Bruce D

    2008-03-01

    Locally advanced rectal adenocarcinoma is treated by combined-modality therapy, which consists of surgery, chemotherapy, and radiation therapy. A series of randomized trials established a preferred treatment sequence of preoperative radiation therapy and 5-fluorouracil(5-FU)-based chemotherapy, total mesorectal excision, and adjuvant 5-FU-based chemotherapy for patients with stage II/III disease. Capecitabine is an oral prodrug of 5-FU that has potential advantages compared with intravenous 5-FU, including ease of administration and potentially increased therapeutic effect. Capecitabine is converted by a 3-step enzymatic process; the last step involves the enzyme thymidine phosphorylase, which is overexpressed in tumor tissues and is stimulated by concurrent radiation therapy. Over the past 5 years, several phase I/II trials of capecitabine-based therapy were reported. This review discusses the evolution of combined-modality therapy for rectal cancer with specific attention given to the use of capecitabine in conjunction with radiation therapy.

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

    PubMed Central

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

    2015-01-01

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

  10. Clinical impact of HLA class I expression in rectal cancer

    PubMed Central

    Speetjens, Frank M.; de Bruin, Elza C.; Morreau, Hans; Zeestraten, Eliane C. M.; Putter, Hein; van Krieken, J. Han; van Buren, Maaike M.; van Velzen, Monique; Dekker-Ensink, N. Geeske; van de Velde, Cornelis J. H.

    2007-01-01

    Purpose To determine the clinical impact of human leukocyte antigen (HLA) class I expression in irradiated and non-irradiated rectal carcinomas. Experimental design Tumor samples in tissue micro array format were collected from 1,135 patients. HLA class I expression was assessed after immunohistochemical staining with two antibodies (HCA2 and HC10). Results Tumors were split into two groups: (1) tumors with >50% of tumor cells expressing HLA class I (high) and (2) tumors with ≤50% of tumor cells expressing HLA class I (low). No difference in distribution or prognosis of HLA class I expression was found between irradiated and non-irradiated patients. Patients with low expression of HLA class I (15% of all patients) showed an independent significantly worse prognosis with regard to overall survival and disease-free survival. HLA class I expression had no effect on cancer-specific survival or recurrence-free survival. Conclusions Down-regulation of HLA class I in rectal cancer is associated with poor prognosis. In contrast to our results, previous reports on HLA class I expression in colorectal cancer described a large population of patients with HLA class I negative tumors, having a good prognosis. This difference might be explained by the fact that a large proportion of HLA negative colon tumors are microsatellite instable (MSI). MSI tumors are associated with a better prognosis than microsatellite stable (MSS). As rectal tumors are mainly MSS, our results suggest that it is both, oncogenic pathway and HLA class I expression, that dictates patient’s prognosis in colorectal cancer. Therefore, to prevent confounding in future prognostic analysis on the impact of HLA expression in colorectal tumors, separate analysis of MSI and MSS tumors should be performed. PMID:17874100

  11. Surgery for Locally Recurrent Rectal Cancer: Tips, Tricks, and Pitfalls

    PubMed Central

    Warrier, Satish K.; Heriot, Alexander G.; Lynch, Andrew Craig

    2016-01-01

    Rectal cancer can recur locally in up to 10% of the patients who undergo definitive resection for their primary cancer. Surgical salvage is considered appropriate in the curative setting as well as select cases with palliative intent. Disease-free survival following salvage resection is dependent upon achieving an R0 resection margin. A clear understanding of applied surgical anatomy, appropriate preoperative planning, and a multidisciplinary approach to aggressive soft tissue, bony, and vascular resection with appropriate reconstruction is necessary. Technical tips, tricks, and pitfalls that may assist in managing these cancers are discussed and the roles of additional boost radiation and intraoperative radiation therapy in the management of such cancers are also discussed. PMID:27247536

  12. Surgery for Locally Recurrent Rectal Cancer: Tips, Tricks, and Pitfalls.

    PubMed

    Warrier, Satish K; Heriot, Alexander G; Lynch, Andrew Craig

    2016-06-01

    Rectal cancer can recur locally in up to 10% of the patients who undergo definitive resection for their primary cancer. Surgical salvage is considered appropriate in the curative setting as well as select cases with palliative intent. Disease-free survival following salvage resection is dependent upon achieving an R0 resection margin. A clear understanding of applied surgical anatomy, appropriate preoperative planning, and a multidisciplinary approach to aggressive soft tissue, bony, and vascular resection with appropriate reconstruction is necessary. Technical tips, tricks, and pitfalls that may assist in managing these cancers are discussed and the roles of additional boost radiation and intraoperative radiation therapy in the management of such cancers are also discussed.

  13. Assessment of T staging and mesorectal fascia status using high-resolution MRI in rectal cancer with rectal distention

    PubMed Central

    Rao, Sheng-Xiang; Zeng, Meng-Su; Xu, Jian-Ming; Qin, Xin-Yu; Chen, Cai-Zhong; Li, Ren-Chen; Hou, Ying-Yong

    2007-01-01

    AIM: To determine the accuracy of high-resolution magnetic resonance imaging (MRI) using phased-array coil for preoperative assessment of T staging and mesorectal fascia infiltration in rectal cancer with rectal distention. METHODS: In a prospective study of 67 patients with primary rectal cancer, high-resolution magnetic resonance imaging (in-plane resolution, 0.66 × 0.56) with phased-array coil were performed for T-staging and measurement of distance between the tumor and the mesorectal fascia. The assessment of MRI was compared with postoperative histopathologic findings. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were evaluated. RESULTS: The overall magnetic resonance accuracy was 85.1% for T staging and 88% for predicting mesorectal fascia involvement. Magnetic resonance sensitivity, specificity, accuracy, positive predictive value, and negative predictive value was 70%, 97.9%, 89.6%, 93.3% and 88.5% for ≤ T2 tumors, 90.5%, 76%, 85.1%, 86.4% and 82.6% for T3 tumors, 100%, 95.2%, 95.5%, 62.5% and 100% for T4 tumors, and 80%, 90.4%, 88%, 70.6% and 94% for predicting mesorectal fascia involvement, respectively. CONCLUSION: High-resolution MRI enables accurate preoperative assessment for T staging and mesorectal fascia infiltration in rectal cancer with rectal distention. PMID:17696238

  14. Formulation and delivery of anti-HIV rectal microbicides: advances and challenges.

    PubMed

    Nunes, Rute; Sarmento, Bruno; das Neves, José

    2014-11-28

    Men and women engaged in unprotected receptive anal intercourse (RAI) are at higher risk of acquiring HIV from infected partners. The implementation of preventive strategies is urgent and rectal microbicides may be a useful tool in reducing the sexual transmission of HIV. However, pre-clinical and first clinical trials have been able to identify limitations of candidate products, mostly related with safety issues, which can in turn enhance viral infection. Indeed, the development of suitable formulations for the rectal delivery of promising antiretroviral drugs is not an easy task, and has been mostly based on products specifically intended for vaginal delivery, but these have been shown to provide sub-optimal outcomes when administered rectally. Research and development in the rectal microbicide field are now charting their own path and important information is now available. In particular, specific formulation requirements of rectal microbicide products that need to be met have just recently been acknowledged despite additional work being still required. Desirable rectal microbicide product features regarding characteristics such as pH, osmolality, excipients, dosage forms, volume to be administered and the need for applicator use have been studied and defined in recent years, and specific guidance is now possible. This review provides a synopsis of the field of rectal microbicides, namely past and ongoing clinical studies, and details on formulation and drug delivery issues regarding the specific development of rectal microbicide products. Also, future work, as required for the advancement of the field, is discussed.

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

    SciTech Connect

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

    2012-12-01

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

  16. Water-jet dissection in rectal cancer surgery: surgical and oncological outcomes.

    PubMed

    Touloumtzidis, Aristotelis; Kühn, Petra; Goretzki, Peter E; Lammers, Bernhard J

    2010-10-01

    These days the treatment of rectal cancer remains an encounter for various medical disciplines. A key position in the whole concept of therapy is still taken by surgery itself. To facilitate the advantages of the total mesorectal excision (TME) we used the water-jet dissector (WJD) in our surgical routine. Our object was to analyze perioperative data as well as oncological long-term results following WJD-assisted rectal resection. A total of 226 patients underwent surgery for rectal cancer in our center between October 2001 and June 2009. A retrospective review was performed of all WJD-assisted rectal resections during this time. One hundred and five patients with adenocarcinoma of the lower and middle rectum were operated on by 7 surgeons according to the concept of TME. Seventy-six patients underwent a low anterior resection, 29 patients an abdominoperineal resection. Twenty-eight patients received preoperative radiochemotherapy. The median follow-up period amounted to 35 (2-96) months. Survival rates were calculated using the Kaplan-Meier method. Anastomotic leakage occurred in 5.7%, wound healing disturbance (including perineal wound infections) in 29.5%, intra-abdominal infections in 7.6% and urinary tract infections in 7.6%. Postoperative bladder dysfunction (requiring catheterization) occurred in 1.9%. Postoperative 30-day mortality was 0%, 60-day mortality 1%. The rate of local recurrence (including three patients who refused postoperative radiochemotherapy) was 8.5%. Cancer-specific survival at 5 years was 74% and differed significantly by stage. The particular advance of the WJD is the facile development of the embryological plane between the mesorectal fascia and the surrounding pelvic nerves. Without harming one of them, maximum radicality and excellent autonomic nerve preservation can be achieved. The WJD is a technique with acceptable postoperative morbidity and low mortality. Local control and survival are comparable to other surgical centers in

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

    PubMed Central

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

    2016-01-01

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

  18. Robotic-Laparoscopic Rectal Cancer Excision Versus Traditional Laparoscopy

    PubMed Central

    Tam, Michael S.; Abbass, Mohammad

    2014-01-01

    Background and Objectives: Robotic surgery has been advocated for the radical excision of rectal cancer. Most data supporting its use have been reported from European and Asian centers, with a paucity of data from the United States documenting clear advantages of the robotic technique. This study compares the short-term outcome of robotic versus laparoscopic surgery. Methods: Consecutive patients who underwent laparoscopic (group 1) or robotic (group 2) rectal cancer excision at a single institution over a 2-year period were retrospectively reviewed. The main outcome measures were operative time, blood loss, conversion rates, number of lymph nodes, margin positivity, length of hospital stay, complications, and readmission rates. Results: Forty-two patients were analyzed. The median operative time was shorter in group 1 than that in group 2 (240 minutes vs 260 minutes, P = .04). No difference was noted in blood loss, transfusion rates, intraoperative complications, or conversion rates. There was no difference in circumferential or distal margin positivity. The median length of stay was shorter in group 1 (5 days vs 6 days, P = .05). The 90-day complication rate was similar in both groups (33% vs 43%, P = .75), but there was a trend toward more anastomotic leaks in group 1 (14% vs 0%, P = .23). Similarly, a non–statistically significant trend toward a higher readmission rate was noted in group 1 (24% vs 5%, P = .18). Conclusion: Robotic rectal cancer excision yielded a longer operative time and hospital length of stay, although immediate oncologic results were comparable. The need for randomized data is critical to determine whether the added resource utilization in robotic surgery is justifiable. PMID:25392653

  19. Patient factors may predict anastomotic complications after rectal cancer surgery

    PubMed Central

    Hayden, Dana M.; Mora Pinzon, Maria C.; Francescatti, Amanda B.; Saclarides, Theodore J.

    2014-01-01

    Purpose Anastomotic complications following rectal cancer surgery occur with varying frequency. Preoperative radiation, BMI, and low anastomoses have been implicated as predictors in previous studies, but their definitive role is still under review. The objective of our study was to identify patient and operative factors that may be predictive of anastomotic complications. Methods A retrospective review was performed on patients who had sphincter-preservation surgery performed for rectal cancer at a tertiary medical center between 2005 and 2011. Results 123 patients were included in this study, mean age was 59 (26–86), 58% were male. There were 33 complications in 32 patients (27%). Stenosis was the most frequent complication (24 of 33). 11 patients required mechanical dilatation, and 4 had operative revision of the anastomosis. Leak or pelvic abscess were present in 9 patients (7.3%); 4 were explored, 2 were drained and 3 were managed conservatively. 4 patients had permanent colostomy created due to anastomotic complications. Laparoscopy approach, BMI, age, smoking and tumor distance from anal verge were not significantly associated with anastomotic complications. After a multivariate analysis chemoradiation was significantly associated with overall anastomotic complications (Wall = 0.35, p = 0.05), and hemoglobin levels were associated with anastomotic leak (Wald = 4.09, p = 0.04). Conclusion Our study identifies preoperative anemia as possible risk factor for anastomotic leak and neoadjuvant chemoradiation may lead to increased risk of complications overall. Further prospective studies will help to elucidate these findings as well as identify amenable factors that may decrease risk of anastomotic complications after rectal cancer surgery. PMID:25685338

  20. Oncological results according to type of resection for rectal cancer.

    PubMed

    Ciga Lozano, Miguel Ángel; Codina Cazador, Antonio; Ortiz Hurtado, Héctor

    2015-04-01

    This multicentre observational study aimed to compare outcomes of anterior resection (AR) and abdominal perineal resection (APR) in patients treated for rectal cancer. Between March 2006 and March 2009 a cohort of 1,598 patients diagnosed with low and mid rectal cancer were operated on in the first 38 hospitals included in the Spanish Rectal Cancer Project. In 1,343 patients the procedure was considered curative. Clinical and outcome results were analysed in relation to the type of surgery performed. All patients were included in the analysis of clinical results. The analysis of outcomes was performed only on patients treated by a curative procedure. Of the 1,598 patients, 1,139 (71.3%) underwent an AR and 459 (28.7%) an APR. In 1,343 patients the procedure was performed with curative intent; from these 973 (72.4%) had an AR and 370 (27.6%) an APR. There were no differences between AR and APR in mortality (29 vs. 18 patients; P=.141). After a median follow up of 60.0 [49.0-60.0] months there were no differences in local recurrence (HR 1.68 [0.87-3.23]; P=.12), metastases (HR 1.31 [0.98-1.76]; P=.064). However, overall survival was worse after APR (HR 1.37 [1.00-1.86]; P=.048). This study did not identify abdominoperineal excision as a determinant of local recurrence or metastases. However, patients treated by this operation have a decreased overall survival. Copyright © 2014 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. Necrotizing Fasciitis of the Thigh Secondary to Radiation Colitis in a Rectal Cancer Patient

    PubMed Central

    Park, So Hyun; Choi, Jung Ran; Song, Ji Young; Kang, Kyu Keun; Yoo, Woong Sun; Han, Sung Wan

    2012-01-01

    Necrotizing fasciitis usually occurs after dermal injury or through hematogenous spread. To date, few cases have been reported as necrotizing fasciitis of the thigh secondary to rectal perforation in rectal cancer patients. A 66-year-old male complained of pelvic and thigh pain and subsequently developed necrotizing fasciitis in his right thigh. Four years earlier, he had undergone a low anterior resection and radiotherapy due to of rectal cancer. An ulcerative lesion had been observed around the anastomosis site during the colonoscopy that had been performed two months earlier. Pelvic computed tomography and sigmoidoscopy showed rectal perforation and presacral abscess extending to buttock and the right posterior thigh fascia. Thus, the necrotizing fasciitis was believed to have occurred because of ulcer perforation, one of the complications of chronic radiation colitis, at the anastomosis site. When a rectal-cancer patient complains of pelvic and thigh pain, the possibility of a rectal perforation should be considered. PMID:23346513

  2. Oxaliplatin-based combined-modality therapy for rectal cancer.

    PubMed

    Minsky, Bruce D

    2003-08-01

    There are two conventional treatments for clinically resectable rectal cancer. The first is surgery, and, if the tumor is T3 and/or N1-2, this is followed by postoperative combined-modality therapy. The second, for patients with ultrasound T3 or clinical T4 disease, is preoperative combined-modality therapy followed by surgery and postoperative chemotherapy. In this review, the results of these approaches as well as novel combined-modality approaches using oxaliplatin-based regimens will be presented.

  3. 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.

  4. [(18)F]Fluoromisonidazole PET in rectal cancer.

    PubMed

    Puri, Tanuj; Greenhalgh, Tessa A; Wilson, James M; Franklin, Jamie; Wang, Lia Mun; Strauss, Victoria; Cunningham, Chris; Partridge, Mike; Maughan, Tim

    2017-09-20

    There is an increasing interest in developing predictive biomarkers of tissue hypoxia using functional imaging for personalised radiotherapy in patients with rectal cancer that are considered for neoadjuvant chemoradiotherapy (CRT). The study explores [(18)F]fluoromisonidazole ([(18)F]FMISO) positron emission tomography (PET) scans for predicting clinical response in rectal cancer patients receiving neoadjuvant CRT. Patients with biopsy-proven rectal adenocarcinoma were imaged at 0-45 min, 2 and 4 h, at baseline and after 8-10 fractions of CRT (week 2). The first 6 patients did not receive an enema (the non-enema group) and the last 4 patients received an enema before PET-CT scan (the enema group). [(18)F]FMISO production failed on 2 occasions. Static PET images at 4 h were analysed using tumour-to-muscle (T:M) SUVmax and tumour-to-blood (T:B) SUVmax. The 0-45 min dynamic PET scans were analysed using Casciari model to report hypoxia and perfusion. Akaike information criteria (AIC) were used to compare data fittings for different pharmacokinetic models. Pathological tumour regression grade was scored using American Joint Committee on Cancer (AJCC) 7.0. Shapiro-Wilk test was used to evaluate the normality of the data. Five out of eleven (5/11) patients were classed as good responders (AJCC 0/1 or good clinical response) and 6/11 as poor responders (AJCC 2/3 or poor clinical response). The median T:M SUVmax was 2.14 (IQR 0.58) at baseline and 1.30 (IQR 0.19) at week 2, and the corresponding median tumour hypoxia volume was 1.08 (IQR 1.31) cm(3) and 0 (IQR 0.15) cm(3), respectively. The median T:B SUVmax was 2.46 (IQR 1.50) at baseline and 1.61 (IQR 0.14) at week 2, and the corresponding median tumour hypoxia volume was 5.68 (IQR 5.86) cm(3) and 0.76 (IQR 0.78) cm(3), respectively. For 0-45 min tumour modelling, the median hypoxia was 0.92 (IQR 0.41) min(-1) at baseline and 0.70 (IQR 0.10) min(-1) at week 2. The median perfusion was 4.10 (IQR 1.71) ml g(-1)

  5. [Secondary retroperitoneal fibrosis in a 39-year-old man after rectal cancer].

    PubMed

    Jarosch, A; Tiller, M; Rohrbach, H; Leimbach, T; Schepp, W

    2016-05-01

    A 39-year-old man had been treated for rectal cancer 6 years ago by lower anterior resection of the rectum and perioperative radiochemotherapy. Since then follow-up had been unremarkable but now the patient presented with unspecific lower abdominal pain. The cause of the pain was identified as paraneoplastic retroperitoneal fibrosis secondary to metachronous pulmonary metastases of the rectal cancer.

  6. Differences of protein expression profiles, KRAS and BRAF mutation, and prognosis in right-sided colon, left-sided colon and rectal cancer.

    PubMed

    Gao, Xian Hua; Yu, Guan Yu; Gong, Hai Feng; Liu, Lian Jie; Xu, Yi; Hao, Li Qiang; Liu, Peng; Liu, Zhi Hong; Bai, Chen Guang; Zhang, Wei

    2017-08-11

    To compare protein expression levels, gene mutation and survival among Right-Sided Colon Cancer (RSCC), Left-Sided Colon Cancer (LSCC) and rectal cancer patients, 57 cases of RSCC, 87 LSCC and 145 rectal cancer patients were included retrospectively. Our results demonstrated significant differences existed among RSCC, LSCC and rectal cancer regarding tumor diameter, differentiation, invasion depth and TNM stage. No significant difference was identified in expression levels of MLH1, MSH2, MSH6, PMS2, β-Tubulin III, P53, Ki67 and TOPIIα, and gene mutation of KRAS and BRAF among three groups. Progression Free Survival (PFS) of RSCC was significantly lower than that of LRCC and rectal cancer. In univariate analyses, RSCC, preoperative chemoradiotherapy, poor differentiation, advanced TNM stage, elevated serum CEA and CA19-9 level, tumor deposit, perineural and vascular invasion were found to be predictive factors of shorter PFS. In multivariate analyses, only differentiation and TNM stages were found to be independent predictors of PFS. In conclusion, compared with LSCC and rectal cancer, RSCC has larger tumor size, poor differentiation, advanced TNM stage and shorter survival. The shorter survival in RSCC might be attributed to the advanced tumor stage caused by its inherent position feature of proximal colon rather than genetic difference.

  7. Interleukin genes and associations with colon and rectal cancer risk and overall survival

    PubMed Central

    Bondurant, Kristina L.; Lundgreen, Abbie; Herrick, Jennifer S.; Kadlubar, Susan; Wolff, Roger K.; Slattery, Martha L.

    2012-01-01

    Interleukins are a group of cytokines that contribute to growth and differentiation, cell migration, and inflammatory and anti-inflammatory responses by the immune system. In this study we examined genetic variation in genes from various anti-inflammatory and pro-inflammatory interleukins to determine association with colon and rectal cancer risk and overall survival. Data from two population-based incident studies of colon cancer (1555 cases and 1956 controls) and rectal cancer (754 cases and 954 controls) were utilized. After controlling for multiple comparisons, single nucleotide polymorphisms (SNPs) from four genes, IL3, IL6R, IL8, IL15, were associated with increased colon cancer risk and CXCR1, and CXCR2 were significantly associated with increased rectal cancer risk. Only SNPs from genes within the IL-8 pathway (IL8, CXCR1, and CXCR2) showed a significant association with both colon and rectal cancer risk. Several SNPs interacted significantly with IL8 and IFNG SNPs and with aspirin/NSAID, cigarette smoking, estrogen use and BMI. For both colon and rectal cancer, increasing numbers of risk alleles were associated with increased hazard of death from cancer; the estimated hazard of death for colon cancer for the highest category of risk alleles was 1.74 (95% CI 1.18–2.56) and 1.96 (95% CI 1.28–2.99) for rectal cancer. These data suggest interleukin genes play a role in risk and overall survival for colon and rectal cancer. PMID:22674296

  8. Rectal metastasis from Breast cancer: A rare entity

    PubMed Central

    Ng, Cho Ee; Wright, Lucie; Pieri, Andrew; Belhasan, Anas; Fasih, Tarannum

    2015-01-01

    Introduction Breast cancer metastases occurs in around 50% of all presentation. It is the second most common type of cancer to metastasise to the GI tract but this only occurs in less than 1% of cases. Presentation of case We report a case that underwent treatment for invasive lobular cancer (ILC) of the breast and 5 years later was found to have rectal and peritoneal metastasis. She is currently receiving palliative management including chemotherapy in the form of weekly Paclitaxel (Taxol®) and stenting to relieve obstruction. Conclusion There should be high clinical suspicion of bowel metastasis in patients presenting with positive faecal occult blood with or without bowel symptoms even if the incidence is less <1% of metastases, particularly in cases where the initial breast tumour was large, with positive axillary nodes. PMID:26188979

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

    PubMed

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

    2016-09-01

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

  10. Local excision for early rectal cancer: transanal endoscopic microsurgery and beyond

    PubMed Central

    Althumairi, Azah A.

    2015-01-01

    The goal of treatment for early stage rectal cancer is to optimize oncologic control while minimizing the long-term impact of treatment on quality of life. The standard of care treatment for most stage I and II rectal cancers is radical surgery alone, specifically total mesorectal excision (TME). For early rectal cancers, this procedure is usually curative but can have a substantial impact on quality of life, including the possibility of permanent colostomy and the potential for short and long-term bowel, bladder, and sexual dysfunction. Given the morbidity associated with radical surgery, alternative approaches to management of early rectal cancer have been explored, including local excision (LE) via transanal excision (TAE) or transanal endoscopic microsurgery (TEM) and transanal minimally invasive surgery (TAMIS). Compared to the gold standard of radical surgery, local procedures for strictly selected early rectal cancers should lead to identical oncological results and even better outcomes regarding morbidity, mortality, and quality of life. PMID:26029457

  11. Re-Staging Following Long-Course Chemoradiotherapy For Rectal Cancer: Does It Influence Management?

    PubMed

    McBrearty, A; McCallion, K; Moorehead, R J; McAllister, I; Mulholland, K; Gilliland, R; Campbell, W J

    2016-09-01

    In patients with locally advanced or low rectal cancers, long-course chemoradiotherapy (LCCRT) is recommended prior to surgical management.(1) The need for restaging afterwards has been questioned as it may be difficult to interpret imaging due to local tissue effects of chemoradiotherapy. The purpose of this study was to determine if restaging affected the management of patients receiving long-course chemoradiotherapy for rectal cancer. A retrospective review of patients with rectal cancer discussed at the South Eastern Health and Social Care Trust Lower Gastrointestinal Multi-Disciplinary Team Meeting (LGIMDT) in 2013 who had received long-course chemoradiotherapy was performed. Patients were identified from the Trust Audit Department, LGIMDT notes and patient records. Imaging results and outcomes from meetings were obtained through the Northern Ireland Picture Archiving and Communications System(®) (NIPACS) and Electronic Care Record(®) (ECR). Data including patient demographics, initial radiological staging and LGIMDT discussion, restaging modality and result, outcome from post-treatment LGIMDT discussion and recorded changes in management plans were documented using a proforma. Seventy-one patients with rectal cancer were identified as having LCCRT in 2013 (M:F 36:35; age range 31 - 85 years). Fifty-nine patients were restaged following long-course treatment with computed tomography (CT) and magnetic resonance imaging (MRI). Twelve patients did not undergo restaging. Data was not available for 6 patients, one patient underwent emergency surgery, two patients were not fit for treatment, one failed to attend for restaging and two patients died prior to completion of treatment. Of the 59 patients restaged, 19 patients (32%) had their management plan altered from that which had been proposed at the initial LGIMDT discussion. The most common change in plan was not to operate. Ten patients had a complete clinical and radiological response to treatment and have

  12. Phase II, randomized study of concomitant chemoradiotherapy followed by surgery and adjuvant capecitabine plus oxaliplatin (CAPOX) compared with induction CAPOX followed by concomitant chemoradiotherapy and surgery in magnetic resonance imaging-defined, locally advanced rectal cancer: Grupo cancer de recto 3 study.

    PubMed

    Fernández-Martos, Carlos; Pericay, Carles; Aparicio, Jorge; Salud, Antonieta; Safont, Mariajose; Massuti, Bertomeu; Vera, Ruth; Escudero, Pilar; Maurel, Joan; Marcuello, Eugenio; Mengual, Jose Luis; Saigi, Eugenio; Estevan, Rafael; Mira, Moises; Polo, Sonia; Hernandez, Ana; Gallen, Manuel; Arias, Fernando; Serra, Javier; Alonso, Vicente

    2010-02-10

    PURPOSE The optimal therapeutic sequence of the adjuvant chemotherapy component of preoperative chemoradiotherapy (CRT) for patients with locally advanced rectal cancer is controversial. Induction chemotherapy before preoperative CRT may be associated with better efficacy and compliance. PATIENTS AND METHODS A total of 108 patients with locally advanced rectal cancer were randomly assigned to arm A-preoperative CRT with capecitabine, oxaliplatin, and concurrent radiation followed by surgery and four cycles of postoperative adjuvant capecitabine and oxaliplatin (CAPOX)-or arm B-induction CAPOX followed by CRT and surgery. The primary end point was pathologic complete response rate (pCR). Results On an intention-to-treat basis, the pCR for arms A and B were 13.5% (95% CI, 5.6% to 25.8%) and 14.3% (95% CI, 6.4% to 26.2%), respectively. There were no statistically significant differences in other end points, including downstaging, tumor regression, and R0 resection. Overall, chemotherapy treatment exposure was higher in arm B than in arm A for both oxaliplatin (P < .0001) and capecitabine (P < .0001). During CRT, grades 3 to 4 adverse events were similar in both arms but were significantly higher in arm A during postoperative adjuvant CT than with induction CT in arm B. There were three deaths in each arm during the treatment period. CONCLUSION Compared with postoperative adjuvant CAPOX, induction CAPOX before CRT had similar pCR and complete resection rates. It did achieve more favorable compliance and toxicity profiles. On the basis of these findings, a phase III study to definitively test the induction strategy is warranted.

  13. Defining the distal margin of rectal cancer for surgical planning

    PubMed Central

    Kato, Takashi; Tanaka, Jun-Ichi

    2017-01-01

    Accurate measurement of the distal rectal tumor margin is essential in selecting the appropriate surgical procedure. However, there is no standard measurement method. The National Cancer Institute consensus group recommends use of the anal verge (AV) as a landmark, and the European Society of Gastrointestinal and Abdominal Radiology recommends use of the anorectal ring (ARR). In addition, whether measurements should be made on double contrast barium enema (BE) radiographs or magnetic resonance (MR) images remains controversial. We measured the distal tumor margin on both BE and MR images obtained preoperatively from 52 patients who underwent sphincter-saving resection for rectal cancer. The distances from the distal end of the tumor to the AV and the ARR were measured on both types of images, and the variability was investigated by Bland-Altman analysis. The mean distance from the tumor to the AV was 8.9 cm on the BE radiographs and 7.7 cm on the MR images (P=0.013). The mean distances to the ARR were 6.8 and 5.6 cm, respectively (P=0.070). Significant proportional bias was shown as the measured distances increased, the difference between the BE- and magnetic resonance imaging (MRI)-based measurements increased. Use of one or the other landmark did not affect selection of the appropriate surgical procedure. We conclude that an approximate 1-cm underestimation should be taken into account when MRI-based measurement of the distal rectal tumor margin is used to choose between sphincter-saving resection and abdominoperineal resection. PMID:28280625

  14. Restaging after neoadjuvant chemoradiation in rectal cancers: is histology the key in patient selection?

    PubMed Central

    Singhal, Nitin; Vallam, Karthik; Engineer, Reena; Ostwal, Vikas; Arya, Supreeta

    2016-01-01

    Background Neoadjuvant chemoradiation is the standard of care for locally advanced rectal cancer. However, there is no clarity regarding the necessity for restaging scans to rule out systemic progression of disease post chemoradiation with existing literature being divided on the need for the same. Methods Data from a prospectively maintained database was retrospectively analysed. All locally advanced rectal cancers (node positive/T4/T3 with threatened or involved CRM) were included. Biopsy proof of adenocarcinoma and CT scan of abdomen and chest were mandatory. Grade of tumor and response to CTRT on restaging magnetic resonance imaging (MRI) were documented. Results Out of 119 patients subjected to CTRT, 72 underwent definitive total mesorectal excision while 13 patients progressed locoregionally on restaging MR pelvis and 15 other patients progressed systemically while the rest defaulted. Patients with poorly differentiated (PD) cancers were compared to those with well/moderately differentiated (WMD) tumors. PD tumors had a significantly higher rate of local progression (32.1% vs. 5.6% %, P=0.0011) and systemic progression (35.7% vs. 6.9%, P=0.0008) as compared to WMD tumors. Only one-third (9/28) of PD patients underwent TME while the rest progressed. Conclusions Selecting poorly differentiated tumors alone for restaging CECT abdomen and thorax will be a cost effective strategy as the rate of progression is very high. Also patients with PD tumors need to be consulted about the high probability of progression of disease. PMID:27284467

  15. Pilot Study of a Clinical Pathway Implementation in Rectal Cancer

    PubMed Central

    Uña, Esther; López-Lara, Francisco

    2010-01-01

    Background: Rectal cancer is a highly prevalent disease which needs a multidisciplinary approach to be treated. The absence of specific protocols implies a significant and unjustifiable variability among the different professionals involved in this disease. The purpose is to develop a clinical pathway based on the analysis process and aims to reduce this variability and to reduce unnecessary costs. Methods: We created a multidisciplinary team with contributors from every clinical area involved in the diagnosis and treatment in this disease. We held periodic meetings to agree on a protocol based on the best available clinical practice guidelines. Once we had agreed on the protocol, we implemented its use as a standard in our institution. Every patient older than 18 years who was diagnosed with rectal cancer was considered a candidate to be treated via the pathway. Results: We evaluated 48 patients during the course of this study. Every parameter measured was improved after the implementation of the pathway, except the proportion of patients with 12 nodes or more analysed. The perception that our patients had about this project was very good. Conclusions: Clinical pathways are needed to improve the quality of health care. This kind of project helps reduce hospital costs and optimizes the use of limited resources. On the other hand, unexplained variability is also reduced, with consequent benefits for the patients. PMID:21151842

  16. Presacral venous bleeding during mobilization in rectal cancer

    PubMed Central

    Casal Núñez, Jose Enrique; Vigorita, Vincenzo; Ruano Poblador, Alejandro; Gay Fernández, Ana María; Toscano Novella, Maria Ángeles; Cáceres Alvarado, Nieves; Pérez Dominguez, Lucinda

    2017-01-01

    AIM To analyze the anatomy of sacral venous plexus flow, the causes of injuries and the methods for controlling presacral hemorrhage during surgery for rectal cancer. METHODS A review of the databases MEDLINE® and Embase™ was conducted, and relevant scientific articles published between January 1960 and June 2016 were examined. The anatomy of the sacrum and its venous plexus, as well as the factors that influence bleeding, the causes of this complication, and its surgical management were defined. RESULTS This is a review of 58 published articles on presacral venous plexus injury during the mobilization of the rectum and on techniques used to treat presacral venous bleeding. Due to the lack of cases published in the literature, there is no consensus on which is the best technique to use if there is presacral bleeding during mobilization in surgery for rectal cancer. This review may provide a tool to help surgeons make decisions regarding how to resolve this serious complication. CONCLUSION A series of alternative treatments are described; however, a conventional systematic review in which optimal treatment is identified could not be performed because few cases were analyzed in most publications. PMID:28321171

  17. Selective approach for upper rectal cancer treatment: total mesorectal excision and preoperative chemoradiation are seldom necessary.

    PubMed

    Marinello, Franco G; Frasson, Matteo; Baguena, Gloria; Flor-Lorente, Blas; Cervantes, Andres; Roselló, Susana; Espí, Alejandro; García-Granero, Eduardo

    2015-06-01

    The implementation of preoperative chemoradiation combined with total mesorectal excision has reduced local recurrence rates in rectal cancer. However, the use of both types of treatment in upper rectal cancer is controversial. The purpose of this work was to assess oncological results after radical resection of upper rectal cancers compared with sigmoid, middle, and lower rectal cancers and to determine risk factors for local recurrence in upper rectal cancer. This was a retrospective analysis of prospectively collected data. This study was conducted in a tertiary care referral hospital in Valencia, Spain. Analysis included 1145 patients who underwent colorectal resection with primary curative intent for primary sigmoid (n = 450), rectosigmoid (n = 70), upper rectal (n = 178), middle rectal (n = 186), or lower rectal (n = 261) cancer. Oncological results, including local recurrence, disease-free survival, and cancer-specific survival, were compared between the different tumor locations. Univariate and multivariate analyses were performed to identify risk factors for local recurrence in upper rectal cancer. A total of 147 patients (82.6%) with upper rectal tumors underwent partial mesorectal excision, and only 10 patients (5.6%) of that group received preoperative chemoradiation. The 5-year actuarial local recurrence, disease-free survival, and cancer-specific survival rates for upper rectal tumors were 4.9%, 82.0%, and 91.6%. Local recurrence rates showed no differences when compared among all of the locations (p = 0.20), whereas disease-free survival and cancer-specific survival were shorter for lower rectal tumors (p = 0.006; p = 0.003). The only independent risk factor for local recurrence in upper rectal cancer was an involved circumferential resection margin at pathologic analysis (HR, 14.23 (95% CI, 2.75-73.71); p = 0.002). This was a single-institution, retrospective study. Most upper rectal tumors can be treated with partial mesorectal excision without the

  18. Proteogenomic characterization of human colon and rectal cancer

    SciTech Connect

    Zhang, Bing; Wang, Jing; Wang, Xiaojing; Zhu, Jing; Liu, Qi; Shi, Zhiao; Chambers, Matthew C.; Zimmerman, Lisa J.; Shaddox, Kent F.; Kim, Sangtae; Davies, Sherri; Wang, Sean; Wang, Pei; Kinsinger, Christopher; Rivers, Robert; Rodriguez, Henry; Townsend, Reid; Ellis, Matthew; Carr, Steven A.; Tabb, David L.; Coffey, Robert J.; Slebos, Robbert; Liebler, Daniel

    2014-09-18

    We analyzed proteomes of colon and rectal tumors previously characterized by the Cancer Genome Atlas (TCGA) and performed integrated proteogenomic analyses. Protein sequence variants encoded by somatic genomic variations displayed reduced expression compared to protein variants encoded by germline variations. mRNA transcript abundance did not reliably predict protein expression differences between tumors. Proteomics identified five protein expression subtypes, two of which were associated with the TCGA "MSI/CIMP" transcriptional subtype, but had distinct mutation and methylation patterns and associated with different clinical outcomes. Although CNAs showed strong cis- and trans-effects on mRNA expression, relatively few of these extend to the protein level. Thus, proteomics data enabled prioritization of candidate driver genes. Our analyses identified HNF4A, a novel candidate driver gene in tumors with chromosome 20q amplifications. Integrated proteogenomic analysis provides functional context to interpret genomic abnormalities and affords novel insights into cancer biology.

  19. Long-Term Results of Local Excision for Rectal Cancer

    PubMed Central

    Paty, Philip B.; Nash, Garrett M.; Baron, Paul; Zakowski, Maureen; Minsky, Bruce D.; Blumberg, David; Nathanson, Daniel R.; Guillem, Jose G.; Enker, Warren E.; Cohen, Alfred M.; Wong, W. Douglas

    2002-01-01

    Objective To review the authors’ experience with local excision of early rectal cancers to assess the effectiveness of initial treatment and of salvage surgery. Summary Background Data Local excision for rectal cancer is appealing for its low morbidity and excellent functional results. However, its use is limited by inability to assess regional lymph nodes and uncertainty of oncologic outcome. Methods Patients with T1 and T2 adenocarcinomas of the rectum treated by local excision as definitive surgery between 1969 to 1996 at the authors’ institution were reviewed. Pathology slides were reviewed. Among 125 assessable patients, 74 were T1 and 51 were T2. Thirty-one patients (25%) were selected to receive adjuvant radiation therapy. Fifteen of these 31 patients received adjuvant radiation in combination with 5-fluorouracil chemotherapy. Median follow-up was 6.7 years. One hundred fifteen patients (92%) were followed until death or for greater than 5 years, and 69 patients (55%) were followed until death or for greater than 10 years. Recurrence was recorded as local, distant, and overall. Survival was disease-specific. Results Ten-year local recurrence and survival rates were 17% and 74% for T1 rectal cancers and 26% and 72% for T2 cancers. Median time to relapse was 1.4 years (range 0.4–7.0) for local recurrence and 2.5 years (0.8–7.5) for distant recurrence. In patients receiving radiotherapy, local recurrence was delayed (median 2.1 years vs. 1.1 years), but overall rates of local and overall recurrence and survival rates were similar to patients not receiving radiotherapy. Among 26 cancer deaths, 8 (28%) occurred more than 5 years after local excision. On multivariate analysis, no clinical or pathologic features were predictive of local recurrence. Intratumoral vascular invasion was the only significant predictor of survival. Among 34 patients who developed tumor recurrence, the pattern of first clinical recurrence was predominantly local: 50% local only

  20. Management of Rectal Cancer: Short- vs. Long-Course Preoperative Radiation

    SciTech Connect

    Mohiuddin, Mohammed Marks, John; Marks, Gerald

    2008-11-01

    There is considerable debate on the optimum approach to neoadjuvant therapy in rectal cancer. This review of major published studies of short-course preoperative radiation and the more conventional approach of long-course neoadjuvant chemoradiation was undertaken in an effort to understand the potential advantages and disadvantages of each of these approaches. Studies were evaluated with regard to patient selection, clinical outcomes, and toxicities. Short-course preoperative radiation has shown a clear advantage over surgery alone in reducing local recurrence rates and improving survival of patients with rectal cancer. However, studies using short-course preoperative treatment have included a significant number of early (30%; Stage I/II) and more proximal cancers yet appear to have higher positive margin rates, higher abdominoperineal resection rates, and lower aggregate survival than patients treated with long-course neoadjuvant chemoradiation. Although long-course preoperative chemoradiation is associated with higher rates of reversible acute toxicity, there appears to be more significant and a higher rate of late gastrointestinal toxicity observed in short-course preoperative radiation studies. Patient convenience and lower cost of treatment, however, can be a significant advantage in using a short-course treatment schedule. Selective utilization of either of these approaches should be based on extent of disease and goals of treatment. Patients with distal cancers or more advanced disease (T3/T4) appear to have better outcomes with neoadjuvant chemoradiation, especially where downstaging of disease is critical for more complete surgical resection and sphincter preservation.

  1. An integrative approach for the identification of prognostic and predictive biomarkers in rectal cancer

    PubMed Central

    Agostini, Marco; Janssen, Klaus-Peter; Kim, ll-Jin; D'Angelo, Edoardo; Pizzini, Silvia; Zangrando, Andrea; Zanon, Carlo; Pastrello, Chiara; Maretto, Isacco; Digito, Maura; Bedin, Chiara; Jurisica, Igor; Rizzolio, Flavio; Giordano, Antonio; Bortoluzzi, Stefania

    2015-01-01

    Introduction Colorectal cancer is the third most common cancer in the world, a small fraction of which is represented by locally advanced rectal cancer (LARC). If not medically contraindicated, preoperative chemoradiotherapy, represent the standard of care for LARC patients. Unfortunately, patients shows a wide range of response rates in which approximately 20% has a complete pathological response, whereas in 20 to 40% the response is poor or absent. Results The following specific gene signature, able to discriminate responders' patients from non-responders, were founded: AKR1C3, CXCL11, CXCL10, IDO1, CXCL9, MMP12 and HLA-DRA. These genes are mainly involved in immune system pathways and interact with drugs traditionally used in the adjuvant treatment of rectal cancer. Discussion The present study suggests that new ideas for therapy could be found not only limited to studying genes differentially expressed between the two groups of patients but deepening the mechanisms, associated to response, in which they are involved. Methods Gene expression studies performed by: Agostini et al., Rimkus et al. and Kim et al. have been merged through a meta-analysis of the raw data. Gene expression data-sets have been processed using A-MADMAN. Common differentially expressed gene (DEG) were identified through SAM analysis. To further characterize the identified DEG we deeply investigated its biological role using an integrative computational biology approach. PMID:26359356

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

    SciTech Connect

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

    2015-09-01

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

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

    SciTech Connect

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

    2012-03-15

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

  4. Rectal cancer and Fournier’s gangrene - current knowledge and therapeutic options

    PubMed Central

    Bruketa, Tomislav; Majerovic, Matea; Augustin, Goran

    2015-01-01

    Fournier’s gangrene (FG) is a rapid progressive bacterial infection that involves the subcutaneous fascia and part of the deep fascia but spares the muscle in the scrotal, perianal and perineal region. The incidence has increased dramatically, while the reported incidence of rectal cancer-induced FG is unknown but is extremely low. Pathophysiology and clinical presentation of rectal cancer-induced FG per se does not differ from the other causes. Only rectal cancer-specific symptoms before presentation can lead to the diagnosis. The diagnosis of rectal cancer-induced FG should be excluded in every patient with blood on digital rectal examination, when urogenital and dermatological causes are excluded and when fever or sepsis of unknown origin is present with perianal symptomatology. Therapeutic options are more complex than for other forms of FG. First, the causative rectal tumor should be removed. The survival of patients with rectal cancer resection is reported as 100%, while with colostomy it is 80%. The preferred method of rectal resection has not been defined. Second, oncological treatment should be administered but the timing should be adjusted to the resolution of the FG and sometimes for the healing of plastic reconstructive procedures that are commonly needed for the reconstruction of large perineal, scrotal and lower abdominal wall defects. PMID:26290629

  5. Multivariate Analysis of Risk Factors Associated With the Nonreversal Ileostomy Following Sphincter-Preserving Surgery for Rectal Cancer

    PubMed Central

    Kim, Young Ah; Lee, Gil Jae; Park, Sung Won; Lee, Won-Suk

    2015-01-01

    Purpose A loop ileostomy is used to protect an anastomosis after anal sphincter-preserving surgery, especially in patients with low rectal cancer, but little information is available concerning risk factors associated with a nonreversal ileostomy. The purpose of this study was to identify risk factors of ileostomy nonreversibility after a sphincter-saving resection for rectal cancer. Methods Six hundred seventy-nine (679) patients with rectal cancer who underwent sphincter-preserving surgery between January 2004 and December 2011 were evaluated retrospectively. Of the 679, 135 (19.9%) underwent a defunctioning loop ileostomy of temporary intent, and these patients were divided into two groups, that is, a reversal group (RG, 112 patients) and a nonreversal group (NRG, 23 patients) according to the reversibility of the ileostomy. Results In 23 of the 135 rectal cancer patients (17.0%) that underwent a diverting ileostomy, stoma reversal was not possible for the following reasons; stage IV rectal cancer (11, 47.8%), poor tone of the anal sphincter (4, 17.4%), local recurrence (2, 8.7%), anastomotic leakage (1, 4.3%), radiation proctitis (1, 4.3%), and patient refusal (4, 17.4%). The independent risk factors of the nonreversal group were anastomotic leakage or fistula, stage IV cancer, local recurrence, and comorbidity. Conclusion Postoperative complications such as anastomotic leakage or fistula, advanced primary disease (stage IV), local recurrence and comorbidity were identified as risk factors of a nonreversal ileostomy. These factors should be considered when drafting prudential guidelines for ileostomy closure. PMID:26161377

  6. Pertuzumab and Cetuximab in Treating Patients With Previously Treated Locally Advanced or Metastatic Colorectal Cancer

    ClinicalTrials.gov

    2015-03-11

    Adenocarcinoma of the Colon; Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage III Colon Cancer; Stage III Rectal Cancer; Stage IV Colon Cancer; Stage IV Rectal Cancer

  7. SU5416 and Irinotecan in Treating Patients With Advanced Colorectal Cancer

    ClinicalTrials.gov

    2013-01-22

    Adenocarcinoma of the Colon; Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage III Colon Cancer; Stage III Rectal Cancer; Stage IV Colon Cancer; Stage IV Rectal Cancer

  8. Combination Chemotherapy and Bevacizumab in Treating Patients With Locally Advanced, Metastatic, or Recurrent Colorectal Cancer

    ClinicalTrials.gov

    2013-01-24

    Adenocarcinoma of the Colon; Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage III Colon Cancer; Stage III Rectal Cancer; Stage IV Colon Cancer; Stage IV Rectal Cancer

  9. Update and Debate Issues in Surgical Treatment of Middle and Low Rectal Cancer

    PubMed Central

    Kim, Min Sung; AL-Asari, Sami F.

    2012-01-01

    Based on a review of the literature, this paper provides an update on surgical treatment of middle and low rectal cancer and discusses issues of debate surrounding that treatment. The main goal of the surgical treatment of rectal cancer is radical resection of the tumor and surrounding lymphatic tissue. Local excision of early rectal cancer can be another treatment option, in which the patient can avoid possible complications related to radical surgery. Neoadjuvant chemoradiation therapy (CRT) has been recommended for patients with cT3-4N0 or any T N+ rectal cancer because CRT shows better local control and less toxicity than adjuvant CRT. However, recent clinical trials showed promising results for local excision after neoadjuvant CRT in selected patients with low rectal cancer. In addition, the "wait and see" concept is another modality that has been reported for the management of tumors that show complete clinical remission after neoadjuvant CRT. Although radical surgery for middle and low rectal cancer is the cornerstone therapy, an ultralow anterior resection with or without intersphincteric resection (ISR) has become an alternative standard surgical method for selected patients. Many studies have reported on the oncological safety of the ISR, but few of them have addressed the issue the functional outcome. Furthermore, an abdominoperineal resection (APR) has problems with high rates of tumor perforations and positive circumferential resection margins, and those factors have contributed to its having a high rate of local recurrence and a poor survival rate for rectal cancer compared with sphincter-saving procedures. Recently, great efforts have been made to reduce these problems, and the total levator excision or the extended APR concept has emerged. Surgical management for low rectal cancer should aim to radically excise the tumor and to preserve as much of the sphincter function as possible by using multidisciplinary approaches. However, further prospective

  10. Have the changes in treatment of rectal cancer made a significant difference to our patients?

    PubMed

    Benson, Al B; Guillem, José G; Minsky, Bruce D

    2011-12-01

    The treatment for patients with locally advanced, resectable rectal cancer has evolved over the years. Various combinations and sequences of chemotherapy, radiation therapy, and total mesorectal excision (TME)-based surgery are the mainstay of current therapy. Preoperative combined chemoradiation, followed by surgery, is now the preferred treatment strategy, with the majority of patients receiving either infusion fluorouracil (5-FU) or capecitabine (Xeloda) with radiation. Clinical trials with oxaliplatin (Eloxatin)-based neoadjuvant chemoradiation have not shown improvement in the pathologic complete response rate (pCR) compared with 5-FU; however, final data addressing local recurrence rates and disease-free survival are pending.The use of adjuvant chemotherapy following preoperative chemoradiation and surgery has not been optimally defined. Some studies have shown that patients who obtained significant pathologic downstaging after chemoradiation and surgery have improved survival with the use of adjuvant chemotherapy. Since FOLFOX (folinic acid, 5-FU, and oxaliplatin) is the preferred adjuvant chemotherapy regimen for stage III colon cancer based on randomized clinical trial results, FOLFOX is also recommended for rectal cancer patients as an adjuvant therapy approach.

  11. A systematic approach to the interpretation of preoperative staging MRI for rectal cancer.

    PubMed

    Taylor, Fiona G M; Swift, Robert I; Blomqvist, Lennart; Brown, Gina

    2008-12-01

    The purpose of this article is to provide an aid to the systematic evaluation of MRI in staging rectal cancer. MRI has been shown to be an effective tool for the accurate preoperative staging of rectal cancer. In the Magnetic Resonance Imaging and Rectal Cancer European Equivalence Study (MERCURY), imaging workshops were held for participating radiologists to ensure standardization of scan acquisition techniques and interpretation of the images. In this article, we report how the information was obtained and give examples of the images and how they are interpreted, with the aim of providing a systematic approach to the reporting process.

  12. A Complete Response Case in a Patient with Multiple Lung Metastases of Rectal Cancer Treated with Bevacizumab plus XELIRI Therapy

    PubMed Central

    Hashida, Hiroki; Satake, Hironaga; Kaihara, Satoshi

    2017-01-01

    It has been reported that many patients with lung metastasis of colorectal cancer (CRC) underwent chemotherapy with fluorouracil, folinic acid, oxaliplatin, irinotecan, or capecitabine. There is a small number of reports about the capecitabine and irinotecan (XELIRI) plus bevacizumab (BV) therapy for patients with metastatic CRC in Japan. We report a case of successful BV+XELIRI therapy for rectal cancer with multiple lung metastases as first-line chemotherapy. A 53-year-old female presented with advanced rectal cancer and metastatic lung tumors. Following surgery, the patient was treated with XELIRI+BV. After 6 courses, a computed tomography scan showed complete response of the lung metastases. No recurrence has occurred for 3 years after chemotherapy was stopped. PMID:28203168

  13. Irinotecan Compared With Combination Chemotherapy in Treating Patients With Advanced Colorectal Cancer

    ClinicalTrials.gov

    2013-05-01

    Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage IIIA Colon Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

  14. Proteogenomic characterization of human colon and rectal cancer.

    PubMed

    Zhang, Bing; Wang, Jing; Wang, Xiaojing; Zhu, Jing; Liu, Qi; Shi, Zhiao; Chambers, Matthew C; Zimmerman, Lisa J; Shaddox, Kent F; Kim, Sangtae; Davies, Sherri R; Wang, Sean; Wang, Pei; Kinsinger, Christopher R; Rivers, Robert C; Rodriguez, Henry; Townsend, R Reid; Ellis, Matthew J C; Carr, Steven A; Tabb, David L; Coffey, Robert J; Slebos, Robbert J C; Liebler, Daniel C

    2014-09-18

    Extensive genomic characterization of human cancers presents the problem of inference from genomic abnormalities to cancer phenotypes. To address this problem, we analysed proteomes of colon and rectal tumours characterized previously by The Cancer Genome Atlas (TCGA) and perform integrated proteogenomic analyses. Somatic variants displayed reduced protein abundance compared to germline variants. Messenger RNA transcript abundance did not reliably predict protein abundance differences between tumours. Proteomics identified five proteomic subtypes in the TCGA cohort, two of which overlapped with the TCGA 'microsatellite instability/CpG island methylation phenotype' transcriptomic subtype, but had distinct mutation, methylation and protein expression patterns associated with different clinical outcomes. Although copy number alterations showed strong cis- and trans-effects on mRNA abundance, relatively few of these extend to the protein level. Thus, proteomics data enabled prioritization of candidate driver genes. The chromosome 20q amplicon was associated with the largest global changes at both mRNA and protein levels; proteomics data highlighted potential 20q candidates, including HNF4A (hepatocyte nuclear factor 4, alpha), TOMM34 (translocase of outer mitochondrial membrane 34) and SRC (SRC proto-oncogene, non-receptor tyrosine kinase). Integrated proteogenomic analysis provides functional context to interpret genomic abnormalities and affords a new paradigm for understanding cancer biology.

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

    PubMed

    Minsky, Bruce D

    2010-10-01

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

  16. [Experience with radiofrequency ablation in the treatment of unresectable pelvic recurrence of rectal cancer].

    PubMed

    Mátrai, Zoltán; Fehér, István; Péley, Gábor; Rényi Vámos, Ferenc; Farkas, Emil; Sulyok, Zoltán; Kovács, Tibor; Köves, István

    2005-02-01

    More than half of colorectal cancers are located in the rectum, and the number of such cancers is increasing. In Hungary colorectal cancers are diagnosed predominantly in advanced stages. In the last five years 736 patients with colorectal cancer were operated on at our Department, with the following stage distribution: Dukes A 10%, BI 10%, B2 31%, C 36% and D 13%. The local recurrence rate is decreasing since the introduction of total mesorectal excision and preoperative radiation. Effective treatment options are however poor for unresectable pelvic recurrences. Chemo- and radiotherapy have severe limitations in this advanced stage cancer. In recent years there are a few publications on the minimal-invasive radiofrequency tumour ablation (RFTA) technique, which is an effective treatment for primary and metastatic liver carcinomas and is a new palliative for the local treatment of pelvic recurrence. The aim of this study was to assess the response to treatment using ultrasound-guided radiofrequency ablation in two patients with unresectable pelvic recurrent rectal cancer.

  17. An 80-gene set to predict response to preoperative chemoradiotherapy for rectal cancer by principle component analysis.

    PubMed

    Empuku, Shinichiro; Nakajima, Kentaro; Akagi, Tomonori; Kaneko, Kunihiko; Hijiya, Naoki; Etoh, Tsuyoshi; Shiraishi, Norio; Moriyama, Masatsugu; Inomata, Masafumi

    2016-05-01

    Preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer not only improves the postoperative local control rate, but also induces downstaging. However, it has not been established how to individually select patients who receive effective preoperative CRT. The aim of this study was to identify a predictor of response to preoperative CRT for locally advanced rectal cancer. This study is additional to our multicenter phase II study evaluating the safety and efficacy of preoperative CRT using oral fluorouracil (UMIN ID: 03396). From April, 2009 to August, 2011, 26 biopsy specimens obtained prior to CRT were analyzed by cyclopedic microarray analysis. Response to CRT was evaluated according to a histological grading system using surgically resected specimens. To decide on the number of genes for dividing into responder and non-responder groups, we statistically analyzed the data using a dimension reduction method, a principle component analysis. Of the 26 cases, 11 were responders and 15 non-responders. No significant difference was found in clinical background data between the two groups. We determined that the optimal number of genes for the prediction of response was 80 of 40,000 and the functions of these genes were analyzed. When comparing non-responders with responders, genes expressed at a high level functioned in alternative splicing, whereas those expressed at a low level functioned in the septin complex. Thus, an 80-gene expression set that predicts response to preoperative CRT for locally advanced rectal cancer was identified using a novel statistical method.

  18. Rectal cancer staging: Multidetector-row computed tomography diagnostic accuracy in assessment of mesorectal fascia invasion.

    PubMed

    Ippolito, Davide; Drago, Silvia Girolama; Franzesi, Cammillo Talei; Fior, Davide; Sironi, Sandro

    2016-05-28

    reference magnetic resonance images. The difference in accuracy was statistically significant (P = 0.02). New generation CT scanner, using high resolution MPR images, represents a reliable diagnostic tool in assessment of loco-regional and whole body staging of advanced rectal cancer, especially in patients with MRI contraindications.

  19. A novel approach to inoperable or recurrent rectal cancer by chemoembolization. A new arrow in our quiver?

    PubMed Central

    Bini, Roberto; Comelli, Simone; Leli, Renzo; Vaudano, Giacomo Paolo; Savio, Daniele; Viora, Tiziana; Addeo, Alfredo

    2016-01-01

    Purpose Assess the feasibility, safety and efficacy of TACE with irinotecan loaded micro particles (debiri) for the treatment of locally advanced rectal cancer patients. Results We assessed the Edmonton Symptom Assessment System (ESAS). The tool is designed to assess nine common symptoms in cancer patients: pain, tiredness, nausea, depression, anxiety, drowsiness, appetite, wellbeing and shortness of breath. The ESAS score was 7 in 10/12 (83%) patients before treatment and 6 in 2/12 (16.5%) patients. After treatment in 6/12 (50%) patients the score dropped to 3; 3/12 (33%) reported 4, 1/12 (8%) reported 2. All patients experienced local control disease with a degree of citoreduction; in 4 cases (33%) we observed outstanding responses with a dramatic reduction in the tumors size which led us to surgical radical resections. Materials and methods We run a prospective mono-institutional study where we recruited, 12 non- consecutive patients with histology confirmation of rectal cancer, inoperable and not treatable due to severe comorbidities, or pelvic recurrence/progression after curative treatment, chemotherapy, radiotherapy and/or surgery. Their performance status (PS) ECOG was 2-3. Twelve patients (10 male and 2 female) with a median age 71 (range 56-89) were recruited in the study. Conclusions The study has met the primary endpoint and showed encouraging activity. Debiri could be a possible option for locally advanced/inoperable or recurred rectal cancer patients. Further trials are warranted to validate this methodic in early stages. PMID:27303924

  20. p53 protein overexpression and response to induction chemoradiation therapy in patients with locally advanced rectal adenocarcinoma.

    PubMed

    Luna-Perez, P; Arriola, E L; Cuadra, Y; Alvarado, I; Quintero, A

    1998-01-01

    The association between mutations in the p53 gene and prognosis in colorectal cancer remains controversial. This report evaluates the role of p53 protein to predict the response of neoadjuvant chemoradiation therapy in patients with primary locally advanced rectal adenocarcinoma. Between January 1993 and December 1994, 26 patients were seen with locally advanced primary rectal adenocarcinoma, located between 0 and 10 cm from the anal verge, demonstrated clinically and by CT scan. Each received 45 Gy of preoperative radiation therapy (RT) concomitantly with bolus infusion of 5-fluorouracil (5-Fu) (450/mg/m2 on days 1 to 5 and 28 to 33 of RT). Surgery was performed between 4 and 8 weeks later. All the primary tumors were mapped and sliced. The response rate was divided according to the percentage of malignant cells in the rectal wall and perirectal fat. Lymph nodes were studied with the manual or modified clearing technique. p53 mutant status was assessed immunohistochemically from sections of the formalin-fixed, paraffin-embedded pretreatment biopsy and the resected specimen. There were 14 females and 12 males, with a mean age of 54 years. All received the scheduled treatment. An abdominoperineal resection (n = 10), low anterior resection (n = 10), and pelvic exenteration (n = 6) were performed. The stages of tumors were as follows: no residual tumor (n = 4); T2 (n = 6); T3-4 (N = 9); and T3-4, N1,2 (n = 7). Fourteen specimens (54%) had mutated p53, and 10 (71%) had >50% of residual tumor, whereas only two (17%) of the specimens with normal p53 had >50% of residual tumor (P = .018). Eight of the 10 low anterior resections were performed in patients whose specimens expressed normal p53. Our results suggest that the determination of p53 is a factor in predicting tumor response in patients who undergo preoperative chemoradiation therapy for rectal adenocarcinoma.

  1. Multicenter study of outcome in relation to the type of resection in rectal cancer.

    PubMed

    Ortiz, Hector; Wibe, Arne; Ciga, Miguel Angel; Kreisler, Esther; Garcia-Granero, Eduardo; Roig, Jose Vicente; Biondo, Sebastiano

    2014-07-01

    A surgical teaching and auditing program has been implemented to improve the results of treatment for patients with rectal cancer. The aim of this study was to assess the treatment and outcome in patients resected for rectal cancer, focusing on differences relating to the type of resection. This was an observational study. The study took place throughout the network of hospitals that compose the National Health Service in Spain. This study included a consecutive cohort of 3355 patients from the Spanish Rectal Cancer Project. The data of patients who were operated on electively, with curative intent, by anterior resection (n = 2333 [69.5%]), abdominoperineal excision (n = 774 [23.1%]), and Hartmann procedure (n = 248 [7.4%]) between March 2006 and May 2010 were analyzed. Clinical, pathologic, and outcome results were analyzed in relation to the type of surgery performed. After a median follow-up time of 37 months (interquartile range, 30-48 months), bowel perforations were found to be more common in the Hartmann procedure (12.6%) and abdominoperineal groups (10.1%) than in the anterior resection group (2.3%; p < 0.001). Involvement of the circumferential resection margin was also more common in the Hartmann (16.6%) and abdominoperineal groups (14.3%) than in the anterior resection group (6.6%; p < 0.001). Multivariate analysis showed a negative influence on local recurrence, metastasis, survival for advanced stage, intraoperative perforation, invaded circumferential margin, and Hartmann procedure. However, abdominoperineal excision did not significantly influence local recurrence (HR, 0.945; 95% CI, 0.571-1.563; p = 0.825). The main weakness of this study was the voluntary nature of registration in the Spanish Rectal Cancer Project. Although bowel perforation and involvement of the circumferential resection margin were more common after abdominoperineal excision than after anterior resection, this study did not identify abdominoperineal excision as a determinant of

  2. Study protocol: multi-parametric magnetic resonance imaging for therapeutic response prediction in rectal cancer.

    PubMed

    Pham, Trang Thanh; Liney, Gary; Wong, Karen; Rai, Robba; Lee, Mark; Moses, Daniel; Henderson, Christopher; Lin, Michael; Shin, Joo-Shik; Barton, Michael Bernard

    2017-07-04

    Response to neoadjuvant chemoradiotherapy (CRT) of rectal cancer is variable. Accurate imaging for prediction and early assessment of response would enable appropriate stratification of management to reduce treatment morbidity and improve therapeutic outcomes. Use of either diffusion weighted imaging (DWI) or dynamic contrast enhanced (DCE) imaging alone currently lacks sufficient sensitivity and specificity for clinical use to guide individualized treatment in rectal cancer. Multi-parametric MRI and analysis combining DWI and DCE may have potential to improve the accuracy of therapeutic response prediction and assessment. This protocol describes a prospective non-interventional single-arm clinical study. Patients with locally advanced rectal cancer undergoing preoperative CRT will prospectively undergo multi-parametric MRI pre-CRT, week 3 CRT, and post-CRT. The protocol consists of DWI using a read-out segmented sequence (RESOLVE), and DCE with pre-contrast T1-weighted (VIBE) scans for T1 calculation, followed by 60 phases at high temporal resolution (TWIST) after gadoversetamide injection. A 3-dimensional voxel-by-voxel technique will be used to produce colour-coded ADC and K(trans) histograms, and data evaluated in combination using scatter plots. MRI parameters will be correlated with surgical histopathology. Histopathology analysis will be standardized, with chemoradiotherapy response defined according to AJCC 7th Edition Tumour Regression Grade (TRG) criteria. Good response will be defined as TRG 0-1, and poor response will be defined as TRG 2-3. The combination of DWI and DCE can provide information on physiological tumour factors such as cellularity and perfusion that may affect radiotherapy response. If validated, multi-parametric MRI combining DWI and DCE can be used to stratify management in rectal cancer patients. Accurate imaging prediction of patients with a complete response to CRT would enable a 'watch and wait' approach, avoiding surgical morbidity

  3. Predictive utility of cyclo-oxygenase-2 expression by colon and rectal cancer.

    PubMed

    Lobo Prabhu, Kristel C; Vu, Lan; Chan, Simon K; Phang, Terry; Gown, Allen; Jones, Steven J; Wiseman, Sam M

    2014-05-01

    Cyclo-oxygenase-2 (COX-2), an inducible enzyme expressed in areas of inflammation, is a target of interest for colorectal cancer therapy. Currently, the predictive significance of COX-2 in colorectal cancer remains unclear. Tissue microarrays were constructed using 118 colon cancer and 85 rectal cancer specimens; 44 synchronous metastatic colon cancer and 22 rectal cancer lymph nodes were also evaluated. COX-2 expression was assessed by immunohistochemistry. Univariate analysis was used to determine the predictive significance of clinicopathologic variables. Overall survival, disease-specific survival, and disease-free survival were the main outcomes examined. COX-2 was found to be expressed in 93% of colon cancers and 87% of rectal cancers. Decreased COX-2 expression was related to decreased disease-specific survival (P = .016) and decreased disease-free survival (P = .019) in the rectal cancer cohort but not in the colon cancer cohort. COX-2 expression has predictive utility for management of rectal but not colon cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. [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.

  5. Additional chemotherapy and salvage surgery for poor response to chemoradiotherapy in rectal cancers.

    PubMed

    Engineer, Reena; Ostwal, Vikas; Arya, Supreeta; Gupta, Priyamvada; Chopra, Supriya; Patil, Prachi; Jatal, Sudhir; Saklani, Avanish

    2017-08-01

    A proportion of locally advanced rectal cancer patients who receive neoadjuvant chemoradiotherapy (NACRT) are still unresectable. This study was undertaken to assess the outcomes of giving additional chemotherapy to rectal cancer patients with unresectable disease after NACRT. Patients with poor response to NACRT where mesorectal fascia was still involved on MRI and R0 resection was doubtful, received additional four cycles of chemotherapy with either CAPOX or FOLFIRINOX regimen, and the response was reevaluated with MRI and reassessed for surgical resection. Between June 2012 and December 2014, 50 patients received additional chemotherapy with CAPOX regime (19%, 38%) or FOLFIRINOX (31%, 62%) after CRT. Median number of chemotherapy cycles received was four (range 2-8 cycles). Overall 34 (68%) patients underwent exploration and 31 (62%) underwent R0 resection. The median time to surgery following chemoradiation was 5 months (range 3-18 months). Complete pathological response was seen in seven (22%) patients. Patients with poor response to NACRT may be further downstaged using additional chemotherapy so as to achieve R0 resection in 62% of cases. © 2017 John Wiley & Sons Australia, Ltd.

  6. Matched case-control analysis comparing oncologic outcomes between preoperative and postoperative chemoradiotherapy for rectal cancer

    PubMed Central

    Lee, Byoung Chul; Park, In Ja; Kim, Chan Wook; Lim, Seok-Byung; Yu, Chang Sik

    2017-01-01

    Purpose To investigate patterns of recurrence and oncologic outcomes after recurrence between preoperative and postoperative chemoradiotherapy (CRT). Methods Records of patients with stage II or III locally advanced rectal cancer seen between January 2000 and December 2010 were analyzed. The outcomes for patients undergoing preoperative CRT followed by radical resection (n = 466) were compared with outcomes of patients matched for sex, age, and stage who had surgery and then postoperative CRT (n = 466). Recurrence rates and sites, treatment of recurrence, and oncologic outcomes after recurrence were investigated. The rate of sphincter preservation and permanent stoma formation were also evaluated. Results Recurrence occurred in 124 and 140 patients in the pre- and postoperative CRT groups, respectively. The local and systemic recurrence rates were 3.6% and 20.8%, respectively, in the preoperative CRT group and 3.0% and 25.3%, respectively, in the postoperative CRT group (P = 0.245). Time to recurrence was longer in the postoperative CRT group (19 months vs. 24.2 months, P = 0.029). The overall rates of sphincter preservation (sphincter preservation operation and postoperative permanent stoma formation) did not significantly different between the two groups (P = 0.381). The 5-year overall survival rate after recurrence did not differ between the two groups (25.6% vs. 18.6%, P = 0.051). Conclusion Preoperative and postoperative CRT are both safe and suitable treatment methods for rectal cancer, so the choice can be tailored to the patient's situation. PMID:28382292

  7. Does gadolinium-based contrast material improve diagnostic accuracy of local invasion in rectal cancer MRI? A multireader study.

    PubMed

    Gollub, Marc J; Lakhman, Yulia; McGinty, Katrina; Weiser, Martin R; Sohn, Michael; Zheng, Junting; Shia, Jinru

    2015-02-01

    OBJECTIVE. The purpose of this study was to compare reader accuracy and agreement on rectal MRI with and without gadolinium administration in the detection of T4 rectal cancer. MATERIALS AND METHODS. In this study, two radiologists and one fellow independently interpreted all posttreatment MRI studies for patients with locally advanced or recurrent rectal cancer using unenhanced images alone or combined with contrast-enhanced images, with a minimum interval of 4 weeks. Readers evaluated involvement of surrounding structures on a 5-point scale and were blinded to pathology and disease stage. Sensitivity, specificity, negative predictive value, positive predictive value, and AUC were calculated and kappa statistics were used to describe interreader agreement. RESULTS. Seventy-two patients (38 men and 34 women) with a mean age of 61 years (range, 32-86 years) were evaluated. Fifteen patients had 32 organs invaded. Global AUCs without and with gadolinium administration were 0.79 and 0.77, 0.91 and 0.86, and 0.83 and 0.78 for readers 1, 2, and 3, respectively. AUCs before and after gadolinium administration were similar. Kappa values before and after gadolinium administration for pairs of readers ranged from 0.5 to 0.7. CONCLUSION. On the basis of pathology as a reference standard, the use of gadolinium during rectal MRI did not significantly improve radiologists' agreement or ability to detect T4 disease.

  8. High risk of rectal cancer and of metachronous colorectal cancer in probands of families fulfilling the Amsterdam criteria.

    PubMed

    Cirillo, Laura; Urso, Emanuele Dl; Parrinello, Giovanni; Pucciarelli, Salvatore; Moneghini, Dario; Agostini, Marco; Nitti, Donato; Nascimbeni, Riccardo

    2013-05-01

    To investigate the risk of metachronous colorectal cancer (CRC), its impact on survival, and the risk of rectal cancer in a cohort of probands meeting the Amsterdam criteria. Several determinants of decision-making for the management of CRC in patients with a putative diagnosis of Lynch syndrome are scarcely defined, and many of them undergo segmental bowel resection instead of the advised total colectomy. A retrospective cohort study was conducted on 65 probands of the Amsterdam-positive families who had surgery for primary CRC and at least 5-year surveillance thereafter. The rates of metachronous CRC and of rectal cancer were evaluated, together with their association with preoperatively available clinical predictors. Differences in overall survival between patients with and without metachronous CRC were evaluated using a time-dependent Cox model. Seventeen patients (26.2%) had metachronous CRC. No clinical feature was associated with an increased risk of its development. The risk of death in patients with metachronous CRC was 6-fold increased. Neither a 2-year interval endoscopic surveillance after surgery, nor total colectomy was associated with a significant reduction in metachronous CRC. Eighteen patients (23.7%) had rectal cancer at first presentation, 5 patients of the remainder (10.6%) developed rectal cancer after primary colon resection. Two patients undergoing total colectomy developed a metachronous rectal cancer (18.2%). A first-degree family history of rectal cancer was associated with an increased risk of rectal cancer. Probands of families fulfilling the Amsterdam criteria carry a high risk of rectal cancer and of metachronous CRC. Total proctocolectomy, or total colectomy and a 1-year interval of proctoscopic surveillance should be advised when a high risk of rectal cancer can be predicted.

  9. Systematic review: anal and rectal changes after radiotherapy for prostate cancer.

    PubMed

    Krol, Robin; Smeenk, Robert Jan; van Lin, Emile N J T; Yeoh, Eric E K; Hopman, Wim P M

    2014-03-01

    Pelvic radiotherapy may lead to changes of anorectal function resulting in incontinence-related complaints. The aim of this study was to systematically review objective findings of late anorectal physiology and mucosal appearance after irradiation for prostate cancer. MEDLINE, EMBASE, and the Cochrane library were searched. Original articles in which anal function, rectal function, or rectal mucosa were examined ≥3 months after EBRT for prostate cancer were included. Twenty-one studies were included with low to moderate quality. Anal resting pressures significantly decreased in 6 of the 9 studies including 277 patients. Changes of squeeze pressure and rectoanal inhibitory reflex were less uniform. Rectal distensibility was significantly impaired after EBRT in 7 of 9 studies (277 patients). In 4 of 9 studies on anal and in 5 of 9 on rectal function, disturbances were associated with urgency, frequent bowel movements or fecal incontinence. Mucosal changes as assessed by the Vienna Rectoscopy Score revealed telangiectasias in 73 %, congestion in 33 %, and ulceration in 4 % of patients in 8 studies including 346 patients, but no strictures or necrosis. Three studies reported mucosal improvement during follow-up. Telangiectasias, particularly multiple, were associated with rectal bleeding. Not all bowel complaints (30 %) were related to radiotherapy. Low to moderate quality evidence indicates that EBRT reduces anal resting pressure, decreases rectal distensibility, and frequently induces telangiectasias of rectal mucosa. Objective changes may be associated with fecal incontinence, urgency, frequent bowel movements, and rectal bleeding, but these symptoms are not always related to radiation damage.

  10. Interleukin genes and associations with colon and rectal cancer risk and overall survival.

    PubMed

    Bondurant, Kristina L; Lundgreen, Abbie; Herrick, Jennifer S; Kadlubar, Susan; Wolff, Roger K; Slattery, Martha L

    2013-02-15

    Interleukins are a group of cytokines that contribute to growth and differentiation, cell migration, and inflammatory and anti-inflammatory responses by the immune system. In our study, we examined genetic variation in genes from various anti-inflammatory and proinflammatory interleukins to determine association with colon and rectal cancer risk and overall survival. Data from two population-based incident studies of colon cancer (1,555 cases and 1,956 controls) and rectal cancer (754 cases and 954 controls) were used. After controlling for multiple comparisons, single nucleotide polymorphisms (SNPs) from four genes, IL3, IL6R, IL8, IL15, were associated with increased colon cancer risk, and CXCR1 and CXCR2 were significantly associated with increased rectal cancer risk. Only SNPs from genes within the IL-8 pathway (IL8, CXCR1 and CXCR2) showed a significant association with both colon and rectal cancer risk. Several SNPs interacted significantly with IL8 and IFNG SNPs and with aspirin/non-steroidal anti-inflammatory drug (NSAID), cigarette smoking, estrogen use and BMI. For both colon and rectal cancer, increasing numbers of risk alleles were associated with increased hazard of death from cancer; the estimated hazard of death for colon cancer for the highest category of risk alleles was 1.74 (95% confidence interval [CI] 1.18-2.56) and 1.96 (95% CI 1.28-2.99) for rectal cancer. These data suggest that interleukin genes play a role in risk and overall survival for colon and rectal cancer. Copyright © 2012 UICC.

  11. Mismatch Repair Gene Expression as a Predictor of Tumor Responses in Patients With Rectal Cancer Treated With Preoperative Chemoradiation

    PubMed Central

    Huh, Jung Wook; Kim, Hee Cheol; Kim, Seok Hyung; Park, Yoon Ah; Cho, Yong Beom; Yun, Seong Hyeon; Lee, Woo Yong; Park, Hee Chul; Choi, Doo Ho; Park, Joon Oh; Park, Young Suk; Chun, Ho-Kyung

    2016-01-01

    Abstract This study evaluated the predictive and prognostic value of expression of mismatch repair (MMR) protein, including MLH1, MSH2, and MSH6 in rectal cancer patients with preoperative chemoradiotherapy. MMR protein expression was measured by immunohistochemistry in both pretreatment biopsies (pre-) and pathologic specimens (post-) from 209 patients with locally advanced rectal cancer who underwent preoperative chemoradiotherapy and radical surgery. The patients were followed for a median period of 44 months. A pathologic complete response (pCR) was observed in 30 patients (14.4%). The expression levels of MLH1, MSH2, and MSH6 were not significantly different between the pCR and non-pCR groups. A multivariate analysis revealed that tumor differentiation, postoperative chemotherapy, and pre-MSH6 expression were independent predictors of overall survival; ypN category and perineural invasion were independent predictors of disease-free survival. The pre-MSH6 expression was significantly associated with tumor budding and expression of all MMR proteins. On multivariate analysis, ypN category and post-MSH6 expression were independent predictors for local recurrence. In our study, we observed the independent prognostic value of MSH6 expression in pretreatment tissue on overall survival and MSH6 expression after chemoradiation on local recurrence. Constitutive MSH6 expression before and after preoperative therapy may be a useful tool for prediction of oncologic outcome in locally advanced rectal cancer. PMID:26817916

  12. A case of metastatic carcinoma of anal fistula caused by implantation from rectal cancer.

    PubMed

    Takahashi, Rina; Ichikawa, Ryosuke; Ito, Singo; Mizukoshi, Kosuke; Ishiyama, Shun; Sgimoto, Kiichi; Kojima, Yutaka; Goto, Michitoshi; Tomiki, Yuichi; Yao, Takashi; Sakamoto, Kazuhiro

    2015-12-01

    This case involved an 80-year-old man who was seen for melena. Further testing revealed a tubular adenocarcinoma 50 mm in size in the rectum. In addition, an anal fistula was noted behind the anus along with induration. A biopsy of tissue from the external (secondary) opening of the fistula also revealed adenocarcinoma. Nodules suspected of being metastases were noted in both lung fields. The patient was diagnosed with rectal cancer, a cancer arising from an anal fistula, and a metastatic pulmonary tumor, and neoadjuvant chemotherapy was begun. A laparoscopic abdominoperineal resection was performed 34 days after 6 cycles of mFOLFOX-6 therapy. Based on pathology, the rectal cancer was diagnosed as moderately differentiated adenocarcinoma, and this adenocarcinoma had lymph node metastasis (yp T3N2aM1b). There was no communication between the rectal lesion and the anal fistula, and a moderately differentiated tubular adenocarcinoma resembling the rectal lesion was noted in the anal fistula. Immunohistochemical staining indicated that both the rectal lesion and anal fistula were cytokeratin 7 (CK7) (-) and cytokeratin 20 (CK20) (+), and the patient's condition was diagnosed as implantation of rectal cancer in an anal fistula.In instances where an anal fistula develops in colon cancer, cancer implantation in that fistula must also be taken into account, and further testing should be performed prior to surgery.

  13. Clinical value of MRI-detected extramural venous invasion in rectal cancer.

    PubMed

    Tripathi, Pratik; Rao, Sheng Xiang; Zeng, Meng Su

    2017-01-01

    Extramural venous invasion (EMVI) is associated with a poor prognosis and a poor overall survival rate in rectal cancer. It can independently predict local and distant tumor recurrences. Preoperative EMVI detection in rectal cancer is useful for determining the treatment strategy. EMVI status is beneficial for the post-treatment evaluation and analysis of rectal cancer. Magnetic resonance imaging (MRI) is a non-invasive diagnostic modality with no radiation effects. High-resolution MRI can detect EMVI with high accuracy. In addition, MRI results are equal to or even better than pathological results in the detection of medium to large EMVI in rectal cancer. MRI-detected EMVI (mrEMVI) can be used as a potential biomarker that facilitates treatment methods. This review highlights the importance of MRI before and after rectal cancer treatment. In addition, we analyze the prognostic correlation between mrEMVI and circulating tumor cells (CTC) in rectal cancer. This article may help shed light on the significance of mrEMVI.

  14. An Internet-Based Collaborative Cancer Conference for Rectal Cancer Influenced Surgeon Treatment Recommendations.

    PubMed

    Francescutti, Valerie; Amin, Nalin; Cadeddu, Margherita; Eskicioglu, Cagla; Forbes, Shawn; Kelly, Stephen; Yang, Ilun; Tsai, Scott; Coates, Angela; Grubac, Vanja; Simunovic, Marko

    2015-07-01

    In many jurisdictions geographic and resource constraints are barriers to multidisciplinary cancer conference review of all patients undergoing cancer surgery. We piloted an internet-based collaborative cancer conference (I-CCC) for rectal cancer to overcome these barriers in the LHIN4 region of Ontario (population 1.4 million). Surgeons practicing at one of 10 LHIN4 hospitals were invited to participate in I-CCC reviews. A secure internet audio and visual link facilitated review of cross-sectional images and case details. Before review, referring surgeons detailed initial treatment plans. Main treatment options included preoperative radiation, straight to surgery, and plan uncertain. Changes were noted following I-CCC review from initial to final treatment plan. Major changes included: redirect patient to preoperative radiation from straight to surgery or plan uncertain; and redirect patient to straight to surgery from preoperative radiation or plan uncertain. Minor changes included: change type of neoadjuvant therapy; request additional tests (e.g., pelvic MRI); or formal MCC review. From November 2010 to May 2012, 20 surgeons (7 academic and 13 community) submitted 57 rectal cancer cases for I-CCC review. After I-CCC review, 30 of 57 (53 %) cases had treatment plan changes: 17 major and 13 minor. No patient or tumour factors predicted for treatment plan change. An I-CCC for rectal cancer in a large geographic region was feasible and influenced surgeon treatment recommendations in 53 % of cases. Because no factor predicted for treatment plan change, it is likely prudent that all rectal cancer patients undergo some form of collaborative review.

  15. Differences in carcinoembryonic antigen levels between colon and rectal cancer.

    PubMed

    Ding, Yunlong; Xuan, Weibo; Chen, Chunlin; Chen, Zhe; Yang, Ziyi; Zuo, Yunfei; Ren, Shuangyi

    2014-07-01

    The aim of the present study was to investigate the levels of the serum tumor biomarker carcinoembryonic antigen (CEA) in patients with carcinoma of the colon and rectum in different clinical stages. Colorectal cancer (CRC) is one of the most commonly diagnosed types of cancer worldwide and previous studies have reported rapidly updated therapeutic regimes. While the majority of studies focus on CRC as a single entity, certain studies distinguish colon cancer (CC) from rectal cancer (RC), as there is a hypothesis stating that CC and RC are two naturally different entities. CEA is reported to be an important tumor-associated antigen overexpressed in CRC, which is routinely detected as a significant indicator of CRC. Our study aimed to identify potential differences in the expression of CEA between CC and RC, which may, to some degree, reflect the natural differences between the two. We investigated 240 CRC cases between July, 2010 and December, 2012 from The First and Second Affiliated Hospitals of Dalian Medical University, including 117 CC and 123 RC patients with tumors classified by Duke's staging as A-D. The serum CEA level was measured preoperatively by radioimmunoassays as a routinely used auxiliary indicator. The expression of CEA differed between CC and RC, with the former exhibiting variation among the four stages, whereas no variation was observed in RC. In addition, there were differences between CC and RC regarding the CEA level in stage C and D. Furthermore, the CEA level in stage C of CC was significantly lower compared to that in any other stage. In conclusion, the intrinsic distribution of the CEA level between CC and RC suggests that CC and RC may be two naturally different entities; the significantly low CEA level in stage C of CC indicates that stage C may be crucial in the evolution of CC.

  16. Is Preoperative Chemoradiotherapy Beneficial for Sphincter Preservation in Low-Lying Rectal Cancer Patients?

    PubMed Central

    Park, In Ja; Yu, Chang Sik; Lim, Seok-Byung; Lee, Jong Lyul; Kim, Chan Wook; Yoon, Yong Sik; Park, Seong Ho; Kim, Jin Cheon

    2016-01-01

    Abstract The present study explored the benefit of preoperative chemoradiotherapy (PCRT) for sphincter preservation in locally advanced low-lying rectal cancer patients who underwent stapled anastomosis, especially in those with deep and narrow pelvises determined by magnetic resonance imaging. Patients with locally advanced low-lying rectal cancer (≤5 cm from the anal verge) who underwent stapled anastomosis were included. Patients were categorized into two groups (PCRT+ vs. PCRT–) according to PCRT application. Patients in the PCRT+ group were matched to those in the PCRT– group according to potential confounding factors (age, gender, clinical stage, and body mass index) for sphincter preservation. Sphincter preservation, permanent stoma, and anastomosis-related complications were compared between the groups. Pelvic magnetic resonance imaging was used to measure 12 dimensions representing pelvic cavity depth and width with which deep and narrow pelvis was defined. The impact of PCRT on sphincter preservation and permanent stoma in pelvic dimensions defined as deep and narrow pelvis was evaluated, and factors associated with sphincter preservation and permanent stoma were analyzed. One hundred sixty-six patients were one-to-one matched between the PCRT+ and PCRT− groups. Overall, sphincter-saving surgery was performed in 66.3% and the rates were not different between the 2 groups. Anastomotic complications and permanent stoma occurred nonsignificantly more frequently in the PCRT+ group. PCRT was not associated with higher rate of sphincter preservation in al