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Sample records for advanced rectal cancers

  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. [Multidisciplinary treatment of locally advanced rectal cancer].

    PubMed

    Faes, Seraina; Gié, Olivier; Demartines, Nicolas; Hahnloser, Dieter

    2016-06-15

    Treatment of patients with locally advanced rectal cancer remains challenging. Preoperative imaging with pelvic MRI allows to identify patients for multimodal treatment including induction chemothe- rapy or neoadjuvant radio-chemotherapy and an extended surgical resection. With multidisciplinary approach and an experienced team, excellent oncologic results may be achieved, as well as a good function and quality of life, even with preservation of the anus in the majority of patients. PMID:27487624

  3. 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.

  4. 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

  5. Immunoscore in Rectal Cancer

    ClinicalTrials.gov

    2016-03-28

    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

  6. Neoadjuvant treatment for locally advanced rectal cancer: a systematic review.

    PubMed

    Uehara, Keisuke; Nagino, Masato

    2016-02-01

    We reviewed the history and the current status of neoadjuvant treatment for locally advanced rectal cancer (LARC) in Western countries and Japan. The introduction of total mesorectal excision (TME) and preoperative radiotherapy (RT) were treatment revolutions that resulted in improved local control after curative resection for rectal cancer. However, local relapses still occur, even in the era of TME, and remain a cause of recurrence worldwide. The high rate of distant metastasis after curative resection remains a problem. Furthermore, the introduction of newly developed cytotoxic agents into the LARC treatment strategy continues to be an ongoing challenge. Shifting part of an adjuvant chemotherapy (CTx) regimen to the preoperative period is a promising strategy. Currently, various novel methods, such as induction CTx, consolidation CTx, concomitant administration with RT, and neoadjuvant CTx without RT, have been attempted worldwide. Although some strategies have shown favorable short-term outcomes, the long-term efficacy of the treatments needs be evaluated. At the same time, we must investigate clinical and/or molecular biomarkers to predict the therapeutic effects of each treatment, which is the fastest route to providing ideal personalized therapy for patients with LARC.

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

    ClinicalTrials.gov

    2015-09-03

    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

  8. 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. PMID:26645661

  9. Radiofrequency thermal treatment with chemoradiotherapy for advanced rectal cancer

    PubMed Central

    SHOJI, HISANORI; MOTEGI, MASAHIKO; OSAWA, KIYOTAKA; OKONOGI, NORIYUKI; OKAZAKI, ATSUSHI; ANDOU, YOSHITAKA; ASAO, TAKAYUKI; KUWANO, HIROYUKI; TAKAHASHI, TAKEO; OGOSHI, KYOJI

    2016-01-01

    We previously reported that patients with a clinical complete response (CR) following radiofrequency thermal treatment exhibit significantly increased body temperature compared with other groups, whereas patients with a clinical partial response or stable disease depended on the absence or presence of output limiting symptoms. The aim of this study was to evaluate the correlation among treatment response, Hidaka radiofrequency (RF) output classification (HROC: termed by us) and changes in body temperature. From December 2011 to January 2014, 51 consecutive rectal cancer cases were included in this study. All patients underwent 5 RF thermal treatments with concurrent chemoradiation. Patients were classified into three groups based on HROC: with ≤9, 10–16, and ≥17 points, calculated as the sum total points of five treatments. Thirty-three patients received surgery 8 weeks after treatment, and among them, 32 resected specimens were evaluated for histological response. Eighteen patients did not undergo surgery, five because of progressive disease (PD) and 13 refused because of permanent colostomy. We demonstrated that good local control (ypCR + CR + CRPD) was observed in 32.7% of cases in this study. Pathological complete response (ypCR) was observed in 15.7% of the total 51 patients and in 24.2% of the 33 patients who underwent surgery. All ypCR cases had ≥10 points in the HROC, but there were no patients with ypCR among those with ≤9 points in the HROC. Standardization of RF thermal treatment was performed safely, and two types of patients were identified: those without or with increased temperatures, who consequently showed no or some benefit, respectively, for similar RF output thermal treatment. We propose that the HROC is beneficial for evaluating the efficacy of RF thermal treatment with chemoradiation for rectal cancer, and the thermoregulation control mechanism in individual patients may be pivotal in predicting the response to RF thermal treatment

  10. Review of systemic therapies for locally advanced and metastatic rectal cancer

    PubMed Central

    Osipov, Arsen; Tan, Carlyn; Tuli, Richard; Hendifar, Andrew

    2015-01-01

    Rectal cancer, along with colon cancer, is the second leading cause of cancer-related deaths in the U.S. Up to a quarter of patients have metastatic disease at diagnosis and 40% will develop metastatic disease. The past 10 years have been extremely exciting in the treatment of both locally advanced and metastatic rectal cancer (mRC). With the advent of neoadjuvant chemoradiation, increased numbers of patients with locally advanced rectal cancer (LARC) are surviving longer and some are seeing their tumors shrink to sizes that allow for resection. The advent of biologics and monoclonal antibodies has propelled the treatment of mRC further than many could have hoped. Combined with regimens such as FOLFOX or FOLFIRI, median survival rates have been increased to an average of 23 months. However, the combinations of chemotherapy regimens seem endless for rectal cancer. We will review the major chemotherapies available for locally advanced and mRC as well as regimens currently under investigation such as FOLFOXIRI. We will also review vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) inhibitors as single agents and in combination with traditional chemotherapy regimens. PMID:25830038

  11. [A Case of Locally Advanced Rectal Cancer with a Pathological Complete Response to Preoperative Chemoradiotherapy].

    PubMed

    Akahoshi, Shin-ichi; Iizaka, Masayoshi; Murakami, Seiichi; Nimura, Satoshi; Takeguchi, Touichirou

    2015-11-01

    A 61-year-old woman presented with the chief complaint of melena. She was diagnosed with rectal cancer via colonoscopy. Computed tomography (CT) revealed a rectal cancer with wall thickening, accompanied by several regional lymph node metastases with no distant metastasis. The tumor stage was cT3, cN2a, cM0 according to the TNM Classification of Malignant Tumors (7th Edition, UICC). Preoperative chemoradiotherapy (CRT) (UFT 400 mg/day tegafur-uracil and 75 mg/day Leucovorin; 1.8 Gy in 25 fractions, total 45 Gy) was administered. Eight weeks after CRT, laparoscopy-assisted low anterior resection was performed. A pathological examination revealed that both the primary site and regional lymph nodes had no residual cancer cells, and a diagnosis of pathological complete response was made. The patient has been disease-free for 4 years since the operation. We report a case of rectal cancer that was successfully treated via preoperative CRT. This case may aid the development of a standard therapy for advanced rectal cancer.

  12. [Two cases of advanced rectal cancer resected successfully after neoadjuvant chemotherapy with FOLFOX regimen].

    PubMed

    Shimizu, Hiroki; Taniguchi, Fumihiro; Sonoda, Hiromichi; Itokawa, Yoshiki; Ikeda, Jun; Yamashita, Tetsuro; Koide, Kazuma; Ueshima, Yasuo; Takashina, Kenichiro; Lee, Chol-Jou; Shioaki, Yasuhiro

    2009-11-01

    We describe here two cases of locally advanced rectal cancer treated with neoadjuvant chemotherapy prior to surgery. The first patient was a 54-year-old man whose chief complaint was bloody stool. A detailed examination revealed a rectal cancer with direct invasion of the primary rectal carcinoma into the prostate. Four courses of FOLFOX4 were administered as neoadjuvant chemotherapy. Because the invasion to the prostate was difficult to determine by subsequent CT evaluation, we performed a radical resection. The pathological examination revealed that all surgical margins were negative for malignancy and no metastasis to lymph nodes was found, therefore a surgical evaluation of curability was classified as A. The second patient was a 49-year-old woman whose chief complaint was irregular menstruation. A detailed examination revealed a rectal cancer with metastasis to an ovary and paraaortic lymph node. One course of FOLFOX4 and six courses of mFOLFOX6 (combined with bevacizumab in the first five courses) were administered as neoadjuvant chemotherapy. Subsequent examinations revealed significantly reduced primary tumor and the size of metastatic lesion. Given that metastasis to the paraaortic lymph node was difficult to determine, we performed a radical resection. The pathological examination revealed that all surgical margins were negative for malignancy, and the postoperative FDG-PET evaluation did not find FDG accumulation to paraaortic lymph node. We determined that there was no residual cancer and evaluated the surgery as curability B. We conclude that neoadjuvant chemotherapy against locally advanced rectal cancer may improve the curability of the surgery and save the surrounding organs.

  13. [Two Cases of Curative Resection of Locally Advanced Rectal Cancer after Preoperative Chemotherapy].

    PubMed

    Mitsuhashi, Noboru; Shimizu, Yoshiaki; Kuboki, Satoshi; Yoshitomi, Hideyuki; Kato, Atsushi; Ohtsuka, Masayuki; Shimizu, Hiroaki; Miyazaki, Masaru

    2015-11-01

    Reports of conversion in cases of locally advanced colorectal cancer have been increasing. Here, we present 2 cases in which curative resection of locally advanced rectal cancer accompanied by intestinal obstruction was achieved after establishing a stoma and administering chemotherapy. The first case was of a 46-year-old male patient diagnosed with upper rectal cancer and intestinal obstruction. Because of a high level of retroperitoneal invasion, after establishing a sigmoid colostomy, 13 courses of mFOLFOX6 plus Pmab were administered. Around 6 months after the initial surgery, low anterior resection for rectal cancer and surgery to close the stoma were performed. Fourteen days after curative resection, the patient was discharged from the hospital. The second case was of a 66-year-old male patient with a circumferential tumor extending from Rs to R, accompanied by right ureter infiltration and sub-intestinal obstruction. After establishing a sigmoid colostomy, 11 courses of mFOLFOX6 plus Pmab were administered. Five months after the initial surgery, anterior resection of the rectum and surgery to close the stoma were performed. Twenty days after curative resection, the patient was released from the hospital. No recurrences have been detected in either case.

  14. [Two Cases of Curative Resection of Locally Advanced Rectal Cancer after Preoperative Chemotherapy].

    PubMed

    Mitsuhashi, Noboru; Shimizu, Yoshiaki; Kuboki, Satoshi; Yoshitomi, Hideyuki; Kato, Atsushi; Ohtsuka, Masayuki; Shimizu, Hiroaki; Miyazaki, Masaru

    2015-11-01

    Reports of conversion in cases of locally advanced colorectal cancer have been increasing. Here, we present 2 cases in which curative resection of locally advanced rectal cancer accompanied by intestinal obstruction was achieved after establishing a stoma and administering chemotherapy. The first case was of a 46-year-old male patient diagnosed with upper rectal cancer and intestinal obstruction. Because of a high level of retroperitoneal invasion, after establishing a sigmoid colostomy, 13 courses of mFOLFOX6 plus Pmab were administered. Around 6 months after the initial surgery, low anterior resection for rectal cancer and surgery to close the stoma were performed. Fourteen days after curative resection, the patient was discharged from the hospital. The second case was of a 66-year-old male patient with a circumferential tumor extending from Rs to R, accompanied by right ureter infiltration and sub-intestinal obstruction. After establishing a sigmoid colostomy, 11 courses of mFOLFOX6 plus Pmab were administered. Five months after the initial surgery, anterior resection of the rectum and surgery to close the stoma were performed. Twenty days after curative resection, the patient was released from the hospital. No recurrences have been detected in either case. PMID:26805302

  15. 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

    2016-06-10

    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

  16. Prediction of response to preoperative chemoradiotherapy and establishment of individualized therapy in advanced rectal cancer.

    PubMed

    Nakao, Toshihiro; Iwata, Takashi; Hotchi, Masanori; Yoshikawa, Kozo; Higashijima, Jun; Nishi, Masaaki; Takasu, Chie; Eto, Shohei; Teraoku, Hiroki; Shimada, Mitsuo

    2015-10-01

    Preoperative chemoradiotherapy (CRT) has become the standard treatment for patients with locally advanced rectal cancer. However, no specific biomarker has been identified to predict a response to preoperative CRT. The aim of the present study was to assess the gene expression patterns of patients with advanced rectal cancer to predict their responses to preoperative CRT. Fifty-nine rectal cancer patients were subjected to preoperative CRT. Patients were randomly assigned to receive CRT with tegafur/gimeracil/oteracil (S-1 group, n=30) or tegafur-uracil (UFT group, n=29). Gene expression changes were studied with cDNA and miRNA microarray. The association between gene expression and response to CRT was evaluated. cDNA microarray showed that 184 genes were significantly differentially expressed between the responders and the non‑responders in the S-1 group. Comparatively, 193 genes were significantly differentially expressed in the responders in the UFT group. TBX18 upregulation was common to both groups whereas BTNL8, LOC375010, ADH1B, HRASLS2, LOC284232, GCNT3 and ALDH1A2 were significantly differentially lower in both groups when compared with the non-responders. Using miRNA microarray, we found that 7 and 16 genes were significantly differentially expressed between the responders and non-responders in the S-1 and UFT groups, respectively. miR-223 was significantly higher in the responders in the S-1 group and tended to be higher in the responders in the UFT group. The present study identified several genes likely to be useful for establishing individualized therapies for patients with rectal cancer.

  17. 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

  18. Laparoscopic ovarian transposition prior to pelvic irradiation in a young female patient with advanced rectal cancer.

    PubMed

    Kihara, Kyoichi; Yamamoto, Seiichiro; Ohshiro, Taihei; Fujita, Shin

    2015-12-01

    In the report, we describe the first case of laparoscopic ovarian transposition prior to pelvic radio-chemo therapy in a young female patient with advanced rectal cancer in Japan. A 14-year-old female visited a hospital because of consistent diarrhea and melena. Colonoscopy examination showed a bulky tumor of the rectum, which was diagnosed as moderately to poorly differentiated adenocarcinoma. The diagnosis was cT3N2aM1a (due to lymph node in pelvic side wall), cStage IVA. In an attempt to improve local control and sphincter preservation, neoadjuvant concurrent radio-chemo therapy was planned. Considering that pelvic irradiation particularly in young female might cause ovarian failure, laparoscopic ovarian transposition was carried out prior to pelvic irradiation. Sequentially the patient underwent low anterior resection of the rectum and lymphadenectomy including pelvic side wall. The menstruation was maintained with delay for 6 months after adjuvant chemotherapy. There is no evidence of cancer recurrence at 3 years after the surgery.In premenopausal patients with rectal cancer undergoing pelvic irradiation, laparoscopic ovarian transposition is one of the choices to prevent ovarian failure. PMID:26943437

  19. 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

  20. 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

  1. [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. PMID:27210100

  2. [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.

  3. Predictive and prognostic biomarkers for neoadjuvant chemoradiotherapy in locally advanced rectal cancer.

    PubMed

    Lim, S H; Chua, W; Henderson, C; Ng, W; Shin, J-S; Chantrill, L; Asghari, R; Lee, C S; Spring, K J; de Souza, P

    2015-10-01

    Locally advanced rectal cancer is regularly treated with trimodality therapy consisting of neoadjuvant chemoradiation, surgery and adjuvant chemotherapy. There is a need for biomarkers to assess treatment response, and aid in stratification of patient risk to adapt and personalise components of the therapy. Currently, pathological stage and tumour regression grade are used to assess response. Experimental markers include proteins involved in cell proliferation, apoptosis, angiogenesis, the epithelial to mesenchymal transition and microsatellite instability. As yet, no single marker is sufficiently robust to have clinical utility. Microarrays that screen a tumour for multiple promising candidate markers, gene expression and microRNA profiling will likely have higher yield and it is expected that a combination or panel of markers would prove most useful. Moving forward, utilising serial samples of circulating tumour cells or circulating nucleic acids can potentially allow us to demonstrate tumour heterogeneity, document mutational changes and subsequently measure treatment response. PMID:26032919

  4. 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

  5. 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.

  6. 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

  7. General Information about Rectal Cancer

    MedlinePlus

    ... Research Rectal Cancer Treatment (PDQ®)–Patient Version General Information About Rectal Cancer Go to Health Professional Version ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  8. 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.

  9. 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. PMID:23584263

  10. Pathologic response to neoadjuvant treatment in locally advanced rectal cancer and impact on outcome

    PubMed Central

    Davis, Sidney; Mohebbi, Mohammadreza; Sugamaran, Bhuvana; Porter, Ian W.; Bell, Stephen; Warrier, Satish K.; Wale, Roger

    2016-01-01

    Background Downstaging and pathologic complete response (pCR) after chemoradiotherapy (CRT) may improve progression-free survival and overall survival (OS) after curative therapy of locally advanced adenocarcinoma of rectum. The purpose of this study is to evaluate the pathologic response subsequent to neoadjuvant chemoradiation in locally advanced rectal adenocarcinoma and any impact of response on oncological outcome [disease-free survival (DFS), OS]. Methods A total of 127 patients with histologically-proven rectal adenocarcinoma, locally advanced, were treated with preoperative radiotherapy and concurrent 5-fluorouracil (5 FU), and followed by curative surgery. Pathologic response to neoadjuvant treatment was evaluated by comparing pathologic TN (tumour and nodal) staging (yp) with pre-treatment clinical staging. DFS and OS were compared in patients with: pCR, partial pathologic response and no response to neoadjuvant therapy. Results 14.96% (19 patients) had a pCR, 58.27% [74] showed downstaging and 26.77% [34] had no change in staging. At follow-up (range, 4–9 years, median 6 years 2 months or 74 months), 17.32% [22] showed recurrence: 15.74% [20] distant metastasis, 1.57% [2] pelvic failure. 10.5% [2] of the patients with pCR showed distant metastasis, none showed local recurrence. In the downstaged group, nine developed distant failure and two had local recurrence (14.86%). Distant failure was seen in 26.47% [9] of those with no response to neoadjuvant treatment. DFS and OS rates for all groups were 82.67% and 88.97% respectively. Patients with pCR showed 89.47% DFS and 94.7% OS. In partial responders, DFS was 85.1% and OS was 90.5%. In non-responders, DFS and OS were 73.5% and 82.3% respectively. Patients with pCR had a significantly greater probability of DFS and OS than non-responders. Rectal cancer-related death was 11.02% [14]: one patient (5.26%) with pCR, 9.47% [7] in the downstaged group and 17.64% [6] of non-responders. Conclusions The majority

  11. 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.

  12. 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.

  13. 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

  14. Radiation Dose-Response Model for Locally Advanced Rectal Cancer After Preoperative Chemoradiation Therapy

    SciTech Connect

    Appelt, Ane L.; Ploen, John; Vogelius, Ivan R.; Bentzen, Soren M.; Jakobsen, Anders

    2013-01-01

    Purpose: Preoperative chemoradiation therapy (CRT) is part of the standard treatment of locally advanced rectal cancers. Tumor regression at the time of operation is desirable, but not much is known about the relationship between radiation dose and tumor regression. In the present study we estimated radiation dose-response curves for various grades of tumor regression after preoperative CRT. Methods and Materials: A total of 222 patients, treated with consistent chemotherapy and radiation therapy techniques, were considered for the analysis. Radiation therapy consisted of a combination of external-beam radiation therapy and brachytherapy. Response at the time of operation was evaluated from the histopathologic specimen and graded on a 5-point scale (TRG1-5). The probability of achieving complete, major, and partial response was analyzed by ordinal logistic regression, and the effect of including clinical parameters in the model was examined. The radiation dose-response relationship for a specific grade of histopathologic tumor regression was parameterized in terms of the dose required for 50% response, D{sub 50,i}, and the normalized dose-response gradient, {gamma}{sub 50,i}. Results: A highly significant dose-response relationship was found (P=.002). For complete response (TRG1), the dose-response parameters were D{sub 50,TRG1} = 92.0 Gy (95% confidence interval [CI] 79.3-144.9 Gy), {gamma}{sub 50,TRG1} = 0.982 (CI 0.533-1.429), and for major response (TRG1-2) D{sub 50,TRG1} and {sub 2} = 72.1 Gy (CI 65.3-94.0 Gy), {gamma}{sub 50,TRG1} and {sub 2} = 0.770 (CI 0.338-1.201). Tumor size and N category both had a significant effect on the dose-response relationships. Conclusions: This study demonstrated a significant dose-response relationship for tumor regression after preoperative CRT for locally advanced rectal cancer for tumor dose levels in the range of 50.4-70 Gy, which is higher than the dose range usually considered.

  15. 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.

  16. Long-term Oncologic Outcome Following Preoperative Combined Modality Therapy and Total Mesorectal Excision of Locally Advanced Rectal Cancer

    PubMed Central

    Guillem, Jose G.; Chessin, David B.; Cohen, Alfred M.; Shia, Jinru; Mazumdar, Madhu; Enker, Warren; Paty, Philip B.; Weiser, Martin R.; Klimstra, David; Saltz, Leonard; Minsky, Bruce D.; Wong, W Douglas

    2005-01-01

    Objective: Our aims were to (1) determine the long-term oncologic outcome for patients with rectal cancer treated with preoperative combined modality therapy (CMT) followed by total mesorectal excision (TME), (2) identify factors predictive of oncologic outcome, and (3) determine the oncologic significance of the extent of pathologic tumor response. Summary Background Data: Locally advanced (T3–4 and/or N1) rectal adenocarcinoma is commonly treated with preoperative CMT and TME. However, the long-term oncologic results of this approach and factors predictive of a durable outcome remain largely unknown. Methods: Two hundred ninety-seven consecutive patients with locally advanced rectal adenocarcinoma at a median distance of 6cm from the anal verge (range 0–15 cm) were treated with preoperative CMT (radiation: 5040 centi-Gray (cGy) and 5-fluorouracil (5-FU)-based chemotherapy) followed by TME from 1988 to 2002. A prospectively collected database was queried for long-term oncologic outcome and predictive clinicopathologic factors. Results: With a median follow-up of 44 months, the estimated 10-year overall survival (OS) was 58% and 10 year recurrence-free survival (RFS) was 62%. On multivariate analysis, pathologic response >95%, lymphovascular invasion and/or perineural invasion (PNI), and positive lymph nodes were significantly associated with OS and RFS. Patients with a >95% pathologic response had a significantly improved OS (P = 0.003) and RFS (P = 0.002). Conclusions: Treatment of locally advanced rectal cancer with preoperative CMT followed by TME can provide for a durable 10-year OS of 58% and RFS of 62%. Patients who achieve a >95% response to preoperative CMT have an improved long-term oncologic outcome, a novel finding that deserves further study. PMID:15849519

  17. 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.

  18. 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.

  19. Optimal time interval between capecitabine intake and radiotherapy in preoperative chemoradiation for locally advanced rectal cancer

    SciTech Connect

    Yu, Chang Sik; Kim, Tae Won; Kim, Jong Hoon . E-mail: jhkim2@amc.seoul.kr; Choi, Won Sik; Kim, Hee Cheol; Chang, Heung Moon; Ryu, Min Hee; Jang, Se Jin; Ahn, Seung Do; Lee, Sang-wook; Shin, Seong Soo; Choi, Eun Kyung; Kim, Jin Cheon

    2007-03-15

    Purpose: Capecitabine and its metabolites reach peak plasma concentrations 1 to 2 hours after a single oral administration, and concentrations rapidly decrease thereafter. We performed a retrospective analysis to find the optimal time interval between capecitabine administration and radiotherapy for rectal cancer. Methods and Materials: The time interval between capecitabine intake and radiotherapy was measured in patients who were treated with preoperative radiotherapy and concurrent capecitabine for rectal cancer. Patients were classified into the following groups. Group A1 included patients who took capecitabine 1 hour before radiotherapy, and Group B1 included all other patients. Group B1 was then subdivided into Group A2 (patients who took capecitabine 2 hours before radiotherapy) and Group B2. Group B2 was further divided into Group A3 and Group B3 with the same method. Total mesorectal excision was performed 6 weeks after completion of chemoradiation and the pathologic response was evaluated. Results: A total of 200 patients were enrolled in this study. Pathologic examination showed that Group A1 had higher rates of complete regression of primary tumors in the rectum (23.5% vs. 9.6%, p = 0.01), good response (44.7% vs. 25.2%, p = 0.006), and lower T stages (p = 0.021) compared with Group B1; however, Groups A2 and A3 did not show any improvement compared with Groups B2 and B3. Multivariate analysis showed that increases in primary tumors in the rectum and good response were only significant when capecitabine was administered 1 hour before radiotherapy. Conclusion: In preoperative chemoradiotherapy for rectal cancer, the pathologic response could be improved by administering capecitabine 1 hour before radiotherapy.

  20. Rectal cancer: Neoadjuvant chemoradiotherapy.

    PubMed

    Rödel, Claus; Hofheinz, Ralf; Fokas, Emmanouil

    2016-08-01

    The monolithic approach to apply the same schedule of preoperative 5-fluorouracil (5-FU)- or capecitabine-based chemoradiotherapy (CRT) to all patients with clinically staged TNM stage II/III rectal cancer need to be questioned. Five randomized trials have been completed to determine if the addition of oxaliplatin to preoperative 5-FU/capecitabine-based CRT offers an advantage compared with single-agent CRT. In contrast to the German CAO/ARO/AIO-04 trial, results from the ACCORD 12, STAR-01, PETACC-6 and NSAPB R-04 trials failed to demonstrate a significant improvement of early or late efficacy endpoints with the addition of oxaliplatin. Most of the phase II trials incorporating cetuximab into CRT reported disappointingly low rates of pCR; the combination of CRT with VEGF inhibition showed encouraging pCR rates but at the cost of increased surgical complications. Novel clinical trials currently address (1) the role of induction and consolidation chemotherapy before or after CRT, (2) minimal or omitted surgery following complete response to CRT, or (3) the omission of radiotherapy for selected patients with response to neoadjuvant chemotherapy. The notion of different multimodal treatment concepts according to tumor stage, location, mesorectal fascia margin status, molecular profiles, tumor response, and patients' preferences becomes increasingly popular and will render the multimodal treatment approach of rectal cancer more risk-adapted. PMID:27644910

  1. 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.

  2. Neoadjuvant capecitabine, bevacizumab and radiotherapy for locally advanced rectal cancer: results of a single-institute Phase I study.

    PubMed

    Miki, Yoshitaka; Maeda, Kiyoshi; Hosono, Masako; Nagahara, Hisashi; Hirakawa, Kosei; Shimatani, Yasuhiko; Tsutsumi, Shinichi; Miki, Yukio

    2014-11-01

    The aim of this Phase I clinical trial was to assess the feasibility and safety of capecitabine-based preoperative chemoradiotherapy (CRT) combined with bevacizumab and to determine the optimal capecitabine dose for Japanese patients with locally advanced rectal cancer. Patients with cT3/T4 rectal cancer were eligible. Bevacizumab was administered at 5 mg/kg intravenously on Days 1, 15 and 29. Capecitabine was administered on weekdays concurrently with pelvic radiotherapy at a daily dose of 1.8 Gy, totally to 50.4 Gy. Capecitabine was initiated at 825 mg/m(2) twice daily at Dose Level 1, with a planned escalation to 900 mg/m(2) twice daily at Dose Level 2. Within 6.1-10.3 (median, 9.4) weeks after the completion of the CRT, surgery was performed. Three patients were enrolled at each dose level. Regarding the CRT-related acute toxicities, all of the adverse events were limited to Grade 1. There was no Grade 2 or greater toxicity. No patient needed attenuation or interruption of bevacizumab, capecitabine or radiation. All of the patients received the scheduled dose of CRT. All of the patients underwent R0 resection. Two (33.3%) of the six patients had a pathological complete response, and five (83.3%) patients experienced downstaging. In total, three patients (50%) developed postoperative complications. One patient developed an intrapelvic abscess and healed with incisional drainage. The other two patients healed following conservative treatment. This regimen was safely performed as preoperative CRT for Japanese patients with locally advanced rectal cancer. The recommended capecitabine dose is 900 mg/m(2) twice daily.

  3. PET/CT with Fluorodeoxyglucose During Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer

    PubMed Central

    Travaini, Laura L; Zampino, Maria G; Colandrea, Marzia; Ferrari, Mahila E; Gilardi, Laura; Leonardi, Maria C; Santoro, Luigi; Orecchia, Roberto; Grana, Chiara M

    2016-01-01

    Objective The aim of the present study is to evaluate the accuracy of Positron Emission Tomography/Computed Tomography (PET/CT) with Fluorodeoxyglucose ([18F]FDG) to predict treatment response in patients with locally advanced rectal cancer (LARC) during neoadjuvant chemoradiotherapy. Patients and methods Forty-one LARC patients performed [18F]FDG-PET/CT at baseline (PET0). All patients received continuous capecitabine concomitant to radiotherapy on the pelvis, followed by intermittent capecitabine until two weeks before curative surgery. [18F]FDG-PET/CT was also carried out at 40 Gy-time (PET1) and at the end of neoadjuvant therapy (PET2). PET imaging was analysed semi-quantitatively through the measurement of maximal standardised uptake value (SUVmax) and the tumour volume (TV). Histology was expressed through pTNM and Dworak tumor regression grading. Patients were categorised into responder (downstaging or downsizing) and non-responder (stable or progressive disease by comparison pretreatment parameters with clinical/pathological characteristics posttreatment/after surgery). Logistic regression was used to evaluate SUVmax and TV absolute and percent reduction as predictors of response rate using gender, age, and CEA as covariates. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Survivals were compared by the Log-Rank test. Results Twenty-three responders (9 ypCR, 14 with downstaged disease) and 18 non-responders showed differences in terms of both early and posttreatment SUVmax percent reduction (median comparison: responder = 63.2%, non-responder = 44.2%, p = 0.04 and responder = 76.9%, non-responder = 61.6%, p = 0.06 respectively). The best predictive cut-offs of treatment response for early and posttreatment SUVmax percent reduction were ≥57% and ≥66% from baseline (p = 0.02 and p = 0.01 respectively). Conclusions [18F]FDG-PET/CT is a reliable technique for evaluating therapy response during neoadjuvant

  4. 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

  5. [A case of huge advanced rectal cancer invaded into the surrounding organs resected successfully after preoperative chemotherapy with mFOLFOX6].

    PubMed

    Sakakura, Chouhei; Nishio, Minoru; Miyashita, Atsushi; Nagata, Hiroyuki; Hamada, Takuo; Nakanishi, Masayoshi; Ikoma, Hisashi; Kubota, Ken; Ichikawa, Daisuke; Kikuchi, Syoujirou; Fujiwara, Hitoshi; Okamoto, Kazuma; Ochiai, Toshiya; Kokuba, Yukihito; Taniguchi, Hiroki; Sonoyama, Teruhisa; Otsuji, Eigo

    2008-11-01

    In the recent improvement in chemotherapy for advanced rectal cancer, a treatment for rectal cancer involving the surrounding organs has been well thought out. In this report, we described a case of advanced rectal cancer invaded into the surrounding organs was resected successfully after preoperative chemotherapy with mFOLFOX6. The case was a 74-year-old man with advanced rectal cancer (type 3). A close examination of the patient revealed a bowel movement disturbance. Bowel obstruction was treated with transverse colostomy. Then chemotherapy (mFOLFOX6) was performed six times. It was judged at first to be a huge tumor of 15 cm in diameter, which was unresectable due to invasion into the urinary bladder and sacrum. However, after mFOLFOX6 was enforced, the tumor was shrunk to about 5 cm in diameter (effect judgment PR). Then the tumor was successfully resected. A pathologic histology inspection of the tumor, judged to be Grade 2 prior to resection, revealed a differentiation type glandular carcinoma and a highly lymphocytic infiltration. These results suggested that an appropriate preoperative chemotherapy was useful for huge rectal cancers involving the surrounding organs such as urinary bladder and sacrum.

  6. Drugs Approved for Colon and Rectal Cancer

    MedlinePlus

    ... Professionals Questions to Ask about Your Treatment Research Drugs Approved for Colon and Rectal Cancer This page ... and rectal cancer that are not listed here. Drugs Approved for Colon Cancer Avastin (Bevacizumab) Bevacizumab Camptosar ( ...

  7. Preoperative chemoradiotherapy with 5-fluorouracil and oxaliplatin for locally advanced rectal cancer: long-term results of a phase II trial.

    PubMed

    Liu, Luying; Cao, Caineng; Zhu, Yuan; Li, Dechuan; Feng, Haiyang; Luo, Jialin; Tang, Zhongzhu; Liu, Peng; Lu, Ke; Ju, Haixing; Zhang, Na

    2015-03-01

    The aim of this study was to report long-term results of patients with locally advanced rectal cancer treated by neoadjuvant chemoradiotherapy with fluorouracil, leucovorin, and oxaliplatin. From February 2002 to November 2006, a total of 58 patients with locally advanced rectal cancer were recruited. Secondary endpoints included the cumulative incidence of local and distant recurrences, disease-free survival, and overall survival. The median follow-up time was 138 months (109-151 months). The cumulative incidence of local recurrence at 10 years was 12.1%. The cumulative incidence of distant recurrence at 10 years was 53.4%. The overall survival in the intention-to-treat population was 39.5% at 10 years. Disease-free survival in the intention-to-treat population was 41.8% at 10 years. Univariate analysis revealed that pathologic complete response was associated with local recurrence, distant recurrence, disease-free survival, and overall survival (p < .05). Distant recurrence remains the predominant pattern of failure for patients with locally advanced rectal cancer after preoperative chemoradiotherapy and total mesorectal excision. Pathologic complete response is an independent prognostic factor for locally advanced rectal cancer after preoperative chemoradiotherapy.

  8. 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

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

    PubMed Central

    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

    2015-01-01

    Abstract 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. PMID:26632714

  10. 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.

  11. Prognostic role of the LCS6 KRAS variant in locally advanced rectal cancer: results of the EXPERT-C trial

    PubMed Central

    Sclafani, F.; Chau, I.; Cunningham, D.; Peckitt, C.; Lampis, A.; Hahne, J.C.; Braconi, C.; Tabernero, J.; Glimelius, B.; Cervantes, A.; Begum, R.; Gonzalez De Castro, D.; Hulkki Wilson, S.; Eltahir, Z.; Wotherspoon, A.; Tait, D.; Brown, G.; Oates, J.; Valeri, N.

    2015-01-01

    Background Lethal-7 (let-7) is a tumour suppressor miRNA which acts by down-regulating several oncogenes including KRAS. A single-nucleotide polymorphism (rs61764370, T > G base substitution) in the let-7 complementary site 6 (LCS-6) of KRAS mRNA has been shown to predict prognosis in early-stage colorectal cancer (CRC) and benefit from anti-epidermal growth factor receptor monoclonal antibodies in metastatic CRC. Patients and methods We analysed rs61764370 in EXPERT-C, a randomised phase II trial of neoadjuvant CAPOX followed by chemoradiotherapy, surgery and adjuvant CAPOX plus or minus cetuximab in locally advanced rectal cancer. DNA was isolated from formalin-fixed paraffin-embedded tumour tissue and genotyped using a PCR-based commercially available assay. Kaplan–Meier method and Cox regression analysis were used to calculate survival estimates and compare treatment arms. Results A total of 155/164 (94.5%) patients were successfully analysed, of whom 123 (79.4%) and 32 (20.6%) had the LCS-6 TT and LCS-6 TG genotype, respectively. Carriers of the G allele were found to have a statistically significantly higher rate of complete response (CR) after neoadjuvant therapy (28.1% versus 10.6%; P = 0.020) and a trend for better 5-year progression-free survival (PFS) [77.4% versus 64.5%: hazard ratio (HR) 0.56; P = 0.152] and overall survival (OS) rates (80.3% versus 71.9%: HR 0.59; P = 0.234). Both CR and survival outcomes were independent of the use of cetuximab. The negative prognostic effect associated with KRAS mutation appeared to be stronger in patients with the LCS-6 TT genotype (HR PFS 1.70, P = 0.078; HR OS 1.79, P = 0.082) compared with those with the LCS-6 TG genotype (HR PFS 1.33, P = 0.713; HR OS 1.01, P = 0.995). Conclusion This analysis suggests that rs61764370 may be a biomarker of response to neoadjuvant treatment and an indicator of favourable outcome in locally advanced rectal cancer possibly by mitigating the poor prognosis of KRAS mutation. In

  12. 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

  13. 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.

  14. MicroRNA in rectal cancer

    PubMed Central

    Azizian, Azadeh; Gruber, Jens; Ghadimi, B Michael; Gaedcke, Jochen

    2016-01-01

    In rectal cancer, one of the most common cancers worldwide, the proper staging of the disease determines the subsequent therapy. For those with locally advanced rectal cancer, a neoadjuvant chemoradiotherapy (CRT) is recommended before any surgery. However, response to CRT ranges from complete response (responders) to complete resistance (non-responders). To date we are not able to separate in advance the first group from the second, due to the absence of a valid biomarker. Therefore all patients receive the same therapy regardless of whether they reap benefits. On the other hand almost all patients receive a surgical resection after the CRT, although a watch-and-wait procedure or an endoscopic resection might be sufficient for those who responded well to the CRT. Being highly conserved regulators of gene expression, microRNAs (miRNAs) seem to be promising candidates for biomarkers. Many studies have been analyzing the miRNAs expressed in rectal cancer tissue to determine a specific miRNA profile for the ailment. Unfortunately, there is only a small overlap of identified miRNAs between different studies, posing the question as to whether different methods or differences in tissue storage may contribute to that fact or if the results simply are not reproducible, due to unknown factors with undetected influences on miRNA expression. Other studies sought to find miRNAs which correlate to clinical parameters (tumor grade, nodal stage, metastasis, survival) and therapy response. Although several miRNAs seem to have an impact on the response to CRT or might predict nodal stage, there is still only little overlap between different studies. We here aimed to summarize the current literature on rectal cancer and miRNA expression with respect to the different relevant clinical parameters. PMID:27190581

  15. 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

    2016-01-01

    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

  16. Dosimetric comparisons of VMAT, IMRT and 3DCRT for locally advanced rectal cancer with simultaneous integrated boost

    PubMed Central

    Cai, Gang; Wang, Jiazhou; Xie, Jiang; Peng, Jiayuan; Zhang, Zhen

    2016-01-01

    The simultaneous integrated boost radiotherapy for preoperative locally advanced rectal cancer (LARC) can improve the local control and overall survival rates. 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 (3DCRT) for the LARC. 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. VMAT plans were designed using SmartArc planning module. Both IMRT and SmartArc had similar optimization objectives. The prescription was 50 Gy to the planning clinical target volume (PTV-C) and 56 Gy to the planning gross target volume (PTV-G). The target coverage and organs at risk (OARs) were compared for all the techniques. The paired, two-tailed Wilcoxon signed-rank test was applied for statistical analysis. Results of this study indicate that IMRT and SmartArc were all significantly superior to 3DCRT in most of the relevant values evaluated of target response, OARs and normal tissue sparing. They provided comparable dosimetric parameters for target volume. But IMRT shows better sparing for OARs and normal tissue. PMID:26621840

  17. Dosimetric comparisons of VMAT, IMRT and 3DCRT for locally advanced rectal cancer with simultaneous integrated boost.

    PubMed

    Zhao, Jun; Hu, Weigang; Cai, Gang; Wang, Jiazhou; Xie, Jiang; Peng, Jiayuan; Zhang, Zhen

    2016-02-01

    The simultaneous integrated boost radiotherapy for preoperative locally advanced rectal cancer (LARC) can improve the local control and overall survival rates. 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 (3DCRT) for the LARC. 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. VMAT plans were designed using SmartArc planning module. Both IMRT and SmartArc had similar optimization objectives. The prescription was 50 Gy to the planning clinical target volume (PTV-C) and 56 Gy to the planning gross target volume (PTV-G). The target coverage and organs at risk (OARs) were compared for all the techniques. The paired, two-tailed Wilcoxon signed-rank test was applied for statistical analysis. Results of this study indicate that IMRT and SmartArc were all significantly superior to 3DCRT in most of the relevant values evaluated of target response, OARs and normal tissue sparing. They provided comparable dosimetric parameters for target volume. But IMRT shows better sparing for OARs and normal tissue.

  18. 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

  19. 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.

  20. Long-term oncologic outcomes of neoadjuvant concurrent chemoradiotherapy with capecitabine and radical surgery in locally advanced rectal cancer: 10-year experiences at a single institution

    PubMed Central

    Lee, Kyung Ha; Kim, Jin Soo

    2016-01-01

    Purpose Oral capecitabine has demonstrated to be safe and efficient as neoadjuvant concurrent chemoradiotherapy (NCRT) for locally advanced rectal cancers. The aim of this study was to evaluate the long-term oncologic outcomes of NCRT with capecitabine and radical surgery. Methods From January 2000 to June 2010, 238 patients were treated at our center for locally advanced rectal cancers using conventional NCRT with capecitabine and radical surgery. Univariate and multivariate analyses were used to evaluate the factors associated with oncologic outcomes with log rank and Cox regression tests. Results The incidence of grade >3 capecitabine-related toxicity was found to be 4.6%. A pathologic complete response was observed in 14.7% of patients. The 5-year overall and 5-year disease-free survival rate, local and systemic recurrence rate were 82.8%, 75.1%, 4.8%, and 20.3%. Abdominoperineal resection and node-positive disease were independent prognostic factors of 5-year overall survival, 5-year disease-free survival, and systemic recurrence. Conclusion NCRT with capecitabine and radical surgery showed favorable long-term oncologic outcomes with benefits of acceptable toxicity and convenience. We suggest that capecitabine can be one of the favorable therapeutic options for NCRT in rectal cancer. PMID:27757395

  1. 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.

  2. Chemoradiotherapy response in recurrent rectal cancer

    PubMed Central

    Yu, Stanley K T; Bhangu, Aneel; Tait, Diana M; Tekkis, Paris; Wotherspoon, Andrew; Brown, Gina

    2014-01-01

    The efficacy of response to preoperative chemoradiotherapy (CRT) in recurrent versus primary rectal cancer has not been investigated. We compared radiological downsizing between primary and recurrent rectal cancers following CRT and determined the optimal size reduction threshold for response validated by survival outcomes. The proportional change in tumor length for primary and recurrent rectal cancers following CRT was compared using the independent sample t-test. Overall survival (OS) was calculated using the Kaplan–Meier product limit method and differences between survival for tumor size reduction thresholds of 30% (response evaluation criteria in solid tumors [RECIST]), 40%, and 50% after CRT in primary and recurrent rectal cancer groups. A total of 385 patients undergoing CRT were analyzed, 99 with recurrent rectal cancer and 286 with primary rectal cancer. The mean proportional reduction in maximum craniocaudal length was significantly higher for primary rectal tumors (33%) compared with recurrent rectal cancer (11%) (P < 0.01). There was no difference in OS for either primary or recurrent rectal cancer when ≤30% or ≤40% definitions were used. However, for both primary and recurrent tumors, significant differences in median 3-year OS were observed when a RECIST cut-off of 50% was used. OS was 99% versus 77% in primary and 100% versus 42% in recurrent rectal cancer (P = 0.002 and P = 0.03, respectively). Only patients that demonstrated >50% size reduction showed a survival benefit. Recurrent rectal cancer appears radioresistant compared with primary tumors for tumor size after CRT. Further investigation into improving/intensifying chemotherapy and radiotherapy for locally recurrent rectal cancer is justified. PMID:24403010

  3. Effect of adding mFOLFOX6 after neoadjuvant chemoradiation in locally advanced rectal cancer: a multicentre, phase 2 trial

    PubMed Central

    Garcia-Aguilar, Julio; Chow, Oliver S; Smith, David D; Marcet, Jorge E; Cataldo, Peter A; Varma, Madhulika G; Kumar, Anjali S; Oommen, Samuel; Coutsoftides, Theodore; Hunt, Steven R; Stamos, Michael J; Ternent, Charles A; Herzig, Daniel O; Fichera, Alessandro; Polite, Blase N; Dietz, David W; Patil, Sujata; Avila, Karin

    2015-01-01

    Summary Background Patients with locally advanced rectal cancer who achieve a pathological complete response to neoadjuvant chemoradiation have an improved prognosis. The need for surgery in these patients has been questioned, but the proportion of patients achieving a pathological complete response is small. We aimed to assess whether adding cycles of mFOLFOX6 between chemoradiation and surgery increased the proportion of patients achieving a pathological complete response. Methods We did a phase 2, non-randomised trial consisting of four sequential study groups of patients with stage II–III locally advanced rectal cancer at 17 institutions in the USA and Canada. All patients received chemoradiation (fluorouracil 225 mg/m2 per day by continuous infusion throughout radiotherapy, and 45.0 Gy in 25 fractions, 5 days per week for 5 weeks, followed by a minimum boost of 5.4 Gy). Patients in group 1 had total mesorectal excision 6–8 weeks after chemoradiation. Patients in groups 2–4 received two, four, or six cycles of mFOLFOX6, respectively, between chemoradiation and total mesorectal excision. Each cycle of mFOLFOX6 consisted of racemic leucovorin 200 mg/m2 or 400 mg/m2, according to the discretion of the treating investigator, oxaliplatin 85 mg/m2 in a 2-h infusion, bolus fluorouracil 400 mg/m2 on day 1, and a 46-h infusion of fluorouracil 2400 mg/m2. The primary endpoint was the proportion of patients who achieved a pathological complete response, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00335816. Findings Between March 24, 2004, and Nov 16, 2012, 292 patients were registered, 259 of whom (60 in group 1, 67 in group 2, 67 in group 3, and 65 in group 4) met criteria for analysis. 11 (18%, 95% CI 10–30) of 60 patients in group 1, 17 (25%, 16–37) of 67 in group 2, 20 (30%, 19–42) of 67 in group 3, and 25 (38%, 27–51) of 65 in group 4 achieved a pathological complete response (p=0.0036). Study group was

  4. 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.

  5. Long-term results of intraoperative presacral electron boost radiotherapy (IOERT) in combination with total mesorectal excision (TME) and chemoradiation in patients with locally advanced rectal cancer

    SciTech Connect

    Krempien, Robert . E-mail: robert_krempien@med.uni-heidelberg.de; Roeder, Falk; Oertel, Susanne; Roebel, Marianne; Weitz, Juergen; Hensley, Frank W.; Timke, Carmen; Funk, Angela; Bischof, Marc; Zabel-Du Bois, Angelika; Niethammer, Andreas G.; Eble, Michael J.; Buchler, Markus W.; Treiber, Martina; Debus, Juergen

    2006-11-15

    Background: We analyzed the long-term results of patients with locally advanced rectal cancer using a multimodal approach consisting of total mesorectal excision (TME), intraoperative electron-beam radiation therapy (IOERT), and pre- or postoperative chemoradiation (CRT). Patients and Methods: Between 1991 and 2003, 210 patients with locally advanced rectal cancer (65 International Union Against Cancer [UICC] Stage II, 116 UICC Stage III, and 29 UICC Stage IV cancers) were treated with TME, IOERT, and preoperative or postoperative CHT. A total of 122 patients were treated postoperatively; 88 patients preoperatively. Preoperative or postoperative fluoropyrimidine-based CRT was applied in 93% of these patients. Results: Median age was 61 years (range, 26-81). Median follow-up was 61 months. The 5-year actuarial overall survival (OS), disease-free survival (DFS), local control rate (LC), and distant relapse free survival (DRS) of all patients was 69%, 66%, 93%, and 67%, respectively. Multivariate analysis revealed that UICC stage and resection status were the most important independent prognostic factors for OS, DFS, and DRS. The resection status was the only significant factor for local control. T-stage, tumor localization, type of resection, and type of chemotherapy had no significant impact on OS, DFS, DRS, and LC. Acute and late complications {>=}Grade 3 were seen in 17% and 13% of patients, respectively. Conclusion: Multimodality treatment with TME and IOERT boost in combination with moderate dose pre- or postoperative CRT is feasible and results in excellent long-term local control rates in patients with intermediate to high-risk locally advanced rectal cancer.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. Extended Intervals after Neoadjuvant Therapy in Locally Advanced Rectal Cancer: The Key to Improved Tumor Response and Potential Organ Preservation

    PubMed Central

    Probst, Christian P; Becerra, Adan Z; Aquina, Christopher T; Tejani, Mohamedtaki A; Wexner, Steven D; Garcia-Aguilar, Julio; Remzi, Feza H; Dietz, David W; Monson, John RT; Fleming, Fergal J

    2016-01-01

    Background Many rectal cancer patients experience tumor downstaging and some are found to achieve a pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT). Previous data suggest that there is an association between the time interval from nCRT completion to surgery and tumor response rates, including pCR. However, these studies have been primarily from single institutions with small sample sizes. The aim of this study was to examine the relationship between a longer interval after nCRT and pCR in a nationally representative cohort of rectal cancer patients. Study Design Clinical stage II–III rectal cancer patients undergoing nCRT with a documented surgical resection were selected from the 2006 – 2011 National Cancer Data Base. Multivariable logistic regression analysis was used to assess the association between nCRT-surgery interval time (<6 weeks, 6–8 weeks, >8 weeks) and the odds of pCR. The relationship between nCRT-surgery interval, surgical morbidity, and tumor downstaging was also examined. Results Overall, 17,255 patients met the inclusion criteria. A nCRT-surgery interval time >8 weeks was associated with higher odds of pCR (OR=1.12, 95%CI=1.01–1.25) and tumor downstaging (OR=1.11, 95%CI =1.02–1.25). The longer time delay was also associated with lower odds of 30-day readmission (OR=0.82, 95%CI: 0.70–0.92). Conclusions A nCRT-surgery interval time >8 weeks results in increased odds of pCR with no evidence of associated increased surgical complications compared to 6–8 weeks. This data supports the implementation of a lengthened interval after nCRT to optimize the chances of pCR and perhaps add to the possibility of ultimate organ preservation (non-operative management). PMID:26206642

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

    ClinicalTrials.gov

    2015-10-24

    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

  12. 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.

  13. 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

  14. 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.

  15. [A Case of an Unresectable Locally Advanced Rectal Cancer with Surrounding Organ Invasion Successfully Resected after Chemotherapy with mFOLFOX6 plus Cetuximab].

    PubMed

    Takagi, Hironori; Ariake, Kyohei; Takemura, Shinichi; Doi, Takashi

    2016-03-01

    A 63-year-old man visited our hospital with pain on micturition and was found to have a large rectal tumor with urinary bladder invasion on enhanced abdominal computed tomography (CT). The tumor appeared to be unresectable at presentation; thus, sigmoid colostomy was performed and chemotherapy was initiated. The tumor was found to be EGFR-positive and contained a wild-type KRAS. The mFOLFOX6 plus cetuximab (c-mab) regimen was initiated. The follow-up CT scan showed good tumor shrinkage after 4 courses of chemotherapy; 4 additional courses were administered. The tumor eventually regressed by more than 60% and was judged to be resectable. High anterior resection of the rectum with partial resection of the bladder was performed. Abdominal wall metastasis was detected 8 months after surgery, and additional resection was performed. The patient remained well with no other recurrence 8 months after the high anterior resection. Although chemoradiotherapy is the standard preoperative treatment of locally advanced rectal cancer, systemic therapy is effective in certain cases such as substantial tumor invasion of adjacent organs or metastasis. Here, we present a case of rectal cancer that became curatively resectable after preoperative chemotherapy with mFOLFOX6 plus c-mab.

  16. 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.

  17. 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.

  18. Oncologic Impact of Fewer Than 12 Lymph Nodes in Patients Who Underwent Neoadjuvant Chemoradiation Followed by Total Mesorectal Excision for Locally Advanced Rectal Cancer

    PubMed Central

    Kim, Woo Ram; Han, Yoon Dae; Cho, Min Soo; Hur, Hyuk; Min, Byung Soh; Lee, Kang Young; Kim, Nam Kyu

    2015-01-01

    Abstract A minimum of 12 harvested lymph nodes (hLNs) are recommended in colorectal cancer. However, a paucity of hLNs is frequently presented after preoperative chemoradiation (pCRT) in rectal cancer and the significance of this is still uncertain. The aim of this study is to analyze the impact of hLNs on long-term oncologic outcomes. A total of 302 patients with locally advanced rectal cancer who underwent pCRT and curative resection between 1989 and 2009 were reviewed. Patients were categorized into 2 groups according to the number of hLNs: <12 versus ≥12 LN. The 2 groups were compared with respect to 5-year disease-free and overall survival. The optimal number or ratio of hLNs was investigated in subgroup analysis according to LN status. The median follow-up was 57 months. Patient characteristics other than age did not differ between the 2 groups. The group with <12 LNs had more favorable ypTNM and ypN stage than those with ≥12 LNs. However, the long-term oncologic outcomes were not significantly different between the 2 groups. In subgroup analysis of ypN(−), the group with <5 hLNs had the most favorable oncologic outcomes. In ypN(+) cases, a higher LN ratio tended to be associated with poorer 5-year overall survival. The paucity of hLNs in locally advanced rectal cancer after chemoradiation did not imply poor oncologic outcomes in this study. In addition, <5 hLNs in ypN(−) patients could reflect a good tumor response rather than suboptimal radicality. PMID:26181550

  19. Nonoperative management of rectal cancer.

    PubMed

    Torok, Jordan A; Palta, Manisha; Willett, Christopher G; Czito, Brian G

    2016-01-01

    Surgery has long been the primary curative modality for localized rectal cancer. Neoadjuvant chemoradiation has significantly improved local control rates and, in a significant minority, eradicated all disease. Patients who achieve a pathologic complete response to neoadjuvant therapy have an excellent prognosis, although the combination treatment is associated with long-term morbidity. Because of this, a nonoperative management (NOM) strategy has been pursued to preserve sphincter function in select patients. Clinical and radiographic findings are used to identify patients achieving a clinical complete response to chemoradiation, and they are then followed with intensive surveillance. Incomplete, nonresponding and those demonstrating local progression are referred for salvage with standard surgery. Habr-Gama and colleagues have published extensively on this treatment strategy and have laid the groundwork for this approach. This watch-and-wait strategy has evolved over time, and several groups have now reported their results, including recent prospective experiences. Although initial results appear promising, several significant challenges remain for NOM of rectal cancer. Further study is warranted before routine implementation in the clinic.

  20. 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.

  1. 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.

  2. Combined therapy: surgery and intraoperative HDR brachytherapy for locally advanced and recurrent rectal cancer. Practical experience of Brachytherapy Department in Warsaw

    PubMed Central

    Radziszewski, Jakub; Lyczek, Jaroslaw; Kawczynska, Maria; Kulik, Anna

    2009-01-01

    Purpose Patients with locally advanced and recurrent rectal cancer have a dismal prognosis. The aim of proposed combined therapy – surgery and intraoperative brachytherapy, is to improve results of already applied methods and to define optimal group of patients for this treatment. We introduce practical experience of Brachytherapy Department in Cancer Centre – Institute in Warsaw. Material and methods Patients with primary T4NxM0 rectal cancer and isolated local pelvic recurrence were qualified for therapy. Between January 2005 and September 2008, 13 patients were included: 4 with primary cancer and 9 with recurrence, median age of 56. After surgical resection intraoperative radiotherapy was delivered with boost of high dose rate brachytherapy of 20Gy dose to the tumor bed. Results Primary point of the study is to evaluate impact of applied therapy on local control (LC), overall survival (OS) and disease free survival (DFS). Median follow-up is 16 months. Four of the patients died and 3 survivors are disease-free. There was no case of perioperative mortality. Conclusions A multimodality approach, using surgical resection with intra operative brachytherapy improves local control as well as patients survival in comparison with historical treatment group. Combined therapy is related to high morbidity, but low mortality. The preliminary observations seem to correspond with other authors data.

  3. 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

  4. 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

  5. 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

  6. [The treatment of locally recurrent rectal cancer].

    PubMed

    Alberda, Wijnand J; Verhoef, Cornelis; Nuyttens, Joost J; Rothbarth, Joost; Burger, Jacobus W A

    2015-01-01

    Its incidence has decreased in recent decades due to advances in the treatment of patients with primary rectal cancer, but LRRC still occurs in 6-10% of these patients. LRRC is often accompanied by severe, progressive pain and has a major impact on quality of life. Curative treatment is possible based on surgical resection combined with chemoradiotherapy. Radical resection is the most important prognostic factor in curative treatment. Neo-adjuvant systemic therapy may further improve outcomes in LRRC patients. Many patients are not eligible for surgical treatment due to the presence of metastases or irresectability of the local recurrence. These patients should receive optimal palliative care for the disabling pain. Radiotherapy is effective against local pain in around 75% of patients but the duration of palliation is limited.

  7. Long-Term Survival and Local Relapse Following Surgery Without Radiotherapy for Locally Advanced Upper Rectal Cancer: An International Multi-Institutional Study.

    PubMed

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

    2016-05-01

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

  8. Long-Term Survival and Local Relapse Following Surgery Without Radiotherapy for Locally Advanced Upper Rectal Cancer: An International Multi-Institutional Study.

    PubMed

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

    2016-05-01

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

  9. Phase I Trial of Neoadjuvant Preoperative Chemotherapy With S-1 and Irinotecan Plus Radiation in Patients With Locally Advanced Rectal Cancer

    SciTech Connect

    Sato, Takeo; Kokuba, Yukihito; Koizumi, Wasaburo; Hayakawa, Kazushige; Okayasu, Isao; Watanabe, Masahiko

    2007-12-01

    Purpose: To determine the maximum tolerated dose (MTD) and recommended dose (RD) of irinotecan combined with preoperative chemoradiotherapy with S-1 in patients with locally advanced rectal cancer. Patients and Methods: We gave preoperative radiotherapy (total dose, 45 Gy) to 23 patients with locally advanced (T3/T4) rectal cancer. Concurrently, S-1 was given orally at a fixed dose of 80 mg/m{sup 2}/day on Days 1-5, 8-12, 22-26, and 29-33, and irinotecan was given as a 90-min continuous i.v. infusion on Days 1, 8, 22, and 29. The dose of irinotecan was initially 40 mg/m{sup 2}/day and gradually increased to determine the MTD and RD of this regimen. Results: Among the 4 patients who received 90 mg/m{sup 2} irinotecan, 2 had Grade 4 neutropenia and 1 had Grade 3 diarrhea. Because dose-limiting toxicity (DLT) occurred in 3 of the 4 patients, 90 mg/m{sup 2} irinotecan was designated as the MTD. Consequently, 80 mg/m{sup 2} irinotecan was given to 7 additional patients, with no DLT, and this was considered the RD. Of the patients who received irinotecan at the RD or lower doses, 6 (31.6%) had a complete pathologic response (Grade 3) and 9 (47.4%) underwent sphincter-preserving surgery. Conclusions: With our new regimen, the MTD of irinotecan was 90 mg/m{sup 2}, and the RD of irinotecan for Phase II studies was 80 mg/m{sup 2}. Although our results are preliminary, this new neoadjuvant chemoradiotherapy was considered safe and active, meriting further investigation in Phase II studies.

  10. Cetuximab in Combination With Capecitabine, Irinotecan, and Radiotherapy for Patients With Locally Advanced Rectal Cancer: Results of a Phase II MARGIT Trial

    SciTech Connect

    Horisberger, Karoline; Treschl, Anne; Mai, Sabine; Barreto-Miranda, Manuel; Kienle, Peter; Stroebel, Philipp; Erben, Philipp; Woernle, Christoph; Dinter, Dietmar; Kaehler, Georg; Hochhaus, Andreas; Post, Stefan; Willeke, Frank; Wenz, Frederik

    2009-08-01

    Purpose: To evaluate the safety and efficacy of preoperative radiotherapy (RT) in combination with cetuximab, capecitabine, and irinotecan in patients with locally advanced rectal cancer. Methods and Materials: Patients with rectal cancer (clinical stage T3/4 or N+) were scheduled to receive cetuximab (400 mg/m{sup 2} Day 1, 250 mg/m{sup 2} Days 8, 15, 22, 29) in combination with weekly irinotecan 40 mg/m{sup 2} and capecitabine 500 mg/m{sup 2} twice daily (Days 1-38). RT was given to a dose of 50.4 Gy (45 + 5.4 Gy). Primary endpoint was toxicity, and antitumor activity as assessed by the pathologic complete remission (pCR) rate was a secondary endpoint. Results: Fifty patients were enrolled; 88% showed T3 or T4 and 76% nodal-positive tumors with a median distance from the anal verge of 7.5 cm. The actual dose intensity was as follows (median/mean, %): cetuximab 100/92, irinotecan 100/91, capecitabine 100/89). Main adverse events Grades 2/3/4 were (National Cancer Institute common toxicity criteria version 3.0, %): leukocytopenia 6/2/2, nausea/vomiting 4/2/0, diarrhea 34/30/0, proctitis 26/2/0, elevation of liver transaminases 8/10/0, and acnelike skin rash 46/6/0. All patients underwent surgery, and no postoperative deaths occurred. Eighty-four percent underwent low-anterior resection, and 68% of the specimen exhibited moderate or good tumor regression, but only 4 patients had a pCR. Conclusion: Preoperative chemoradiation with cetuximab-CapIri-RT has manageable toxicity, with diarrhea being the most commonly observed adverse event. Nevertheless, the efficacy of this regimen with a pCR rate of only 8% was significantly lower than that observed in a previous Phase I trial.

  11. 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.

  12. Predictive role of microRNA-related genetic polymorphisms in the pathological complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer patients

    PubMed Central

    Dreussi, Eva; Pucciarelli, Salvatore; De Paoli, Antonino; Polesel, Jerry; Canzonieri, Vincenzo; Agostini, Marco; Friso, Maria Luisa; Belluco, Claudio; Buonadonna, Angela; Lonardi, Sara; Zanusso, Chiara; De Mattia, Elena; Toffoli, Giuseppe; Cecchin, Erika

    2016-01-01

    In rectal cancer, a pathologic complete response (pCR) to pre-operative treatment is a favourable prognostic marker, but is reported in a minority of the patients. We aimed at identifying microRNA-related host genetic polymorphisms predictive of pCR. A panel of 114 microRNA-related tagging polymorphisms was selected and analyzed on 265 locally advanced rectal cancer patients treated with neoadjuvant chemo-radiotherapy. Patients were stratified in two subgroups according to the radiotherapy dose (50.4Gy for 202 patients, 55.0Gy for 78 patients). Interactions among genetic and clinical-pathological variants were investigated by recursive partitioning analysis. Only polymorphisms with a consistent significant effect in the two subgroups of patients were selected as predictive markers of pCR. The results were validated by bootstrap analysis. SMAD3-rs744910, SMAD3-rs745103, and TRBP-rs6088619 were associated to an increased chance of pCR (p=0.0153, p=0.0471, p=0.0125). DROSHA-rs10719 and SMAD3-rs17228212 had an opposite detrimental effect on pathological tumour response (p=0.0274, p=0.0049). Recursive partitioning analysis highlighted that a longer interval time between the end of radiotherapy and surgery increases the chance of pCR in patients with a specific combination of SMAD3-rs744910 and TRBP-rs6088619 genotypes. This study demonstrated that microRNA-related host genetic polymorphisms can predict pCR to neo-adjuvant chemo-radiotherapy, and could be used to personalize the interval time between the end of radiotherapy and surgery. PMID:26934318

  13. A Phase II Trial of Neoadjuvant Preoperative Chemoradiotherapy With S-1 Plus Irinotecan and Radiation in Patients With Locally Advanced Rectal Cancer: Clinical Feasibility and Response Rate

    SciTech Connect

    Sato, Takeo; Ozawa, Heita; Hatate, Kazuhiko; Onosato, Wataru; Naito, Masanori; Nakamura, Takatoshi; Ihara, Atsushi; Koizumi, Wasaburo; Hayakawa, Kazushige; Okayasu, Isao; Yamashita, Keishi; Watanabe, Masahiko

    2011-03-01

    Purpose: We aimed to validate our hypothesis that a preoperative chemoradiotherapy regimen with S-1 plus irinotecan is feasible, safe, and active for the management of locally advanced rectal cancer in a single-arm Phase II setting. Methods and Materials: Eligible patients had previously untreated, locally advanced rectal adenocarcinoma. Radiotherapy was administered in fractions of 1.8Gy/d for 25 days. S-1 was administered orally in a fixed daily dose of 80mg/m{sup 2} on Days 1 to 5, 8 to 12, 22 to 26, and 29 to 33. Irinotecan (80mg/m{sup 2}) was infused on Days 1, 8, 22, and 29. Four or more weeks after the completion of the treatment, total mesorectal excision with lateral lymph node dissection was performed. The primary endpoint was the rate of completing treatment in terms of feasibility. The secondary endpoints were the response rate and safety. Results: We enrolled 43 men and 24 women in the study. The number of patients who completed treatment was 58 (86.6%). Overall, 46 patients (68.7%) responded to treatment and 24 (34.7%) had a complete histopathologic response. Three patients had Grade 3 leukopenia, and another three patients had Grade 3 neutropenia. Diarrhea was the most common type of nonhematologic toxicity: 3 patients had Grade 3 diarrhea. Conclusions: A preoperative regimen of S-1, irinotecan, and radiotherapy to the rectum was feasible, and it appeared safe and effective in this nonrandomized Phase II setting. It exhibited a low incidence of adverse events, a high rate of completion of treatment, and an extremely high rate of pathologic complete response.

  14. 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

  15. 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.

  16. 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

  17. Can an IL13 -1112 C/T (rs1800925) polymorphism predict responsiveness to neoadjuvant chemoradiotherapy and survival of Chinese Han patients with locally advanced rectal cancer?

    PubMed Central

    Chang, Hui; Xi, Shaoyan; Xiao, Weiwei; Zeng, Zhifan; Zhang, Huizhong; Xu, Ruihua; Gao, Yuanhong

    2016-01-01

    We sought to determine whether a polymorphism in the Interleukin 13 gene (IL13), 1112 C/T (rs1800925) predicts responsiveness to neoadjuvant chemoradiotherapy (neoCRT) and prognosis in Chinese Han patients with locally advanced rectal cancer (LARC). Pre-treatment biopsies of primary rectal lesion and surgical specimens were collected from 58 patients with LARC, who were treated with neoCRT and surgery. Tumor DNA was extracted from these biopsies and sequenced to analyze the rs1800925 polymorphism. The tumor response to neoCRT was categorized using a tumor regression grade (TRG, 0-2 were poor responders; 3-4 were good responders). Analyses of progression free survival (PFS) and overall survival (OS) were carried out using the Kaplan-Meier method. Of the forty-six patients for whom tumor DNA was successfully sequenced, 23 were good responders to neoCRT (11 patients with a pathological complete response, i.e. pCR) and the other 23 were poor responders. Good and poor responders were equally likely to have a C/C genotype at rs1800925 (73.9%) as a T/T or C/T genotype (26.1%). There were no differences between the C/C and T/T+C/T genotypes with respect to the ypT0-2 ratio (38.2% vs. 41.7%, P = 1.0), ypN0 nodal status (67.6% vs. 50.0%, P= 0.314), 6-year PFS (67.6% vs. 50%, P=0.274), or 6-year OS (76.5% vs. 66.7%, P=0.441). Thus, the IL13-1112 C/T (rs1800925) polymorphism does not predict responsiveness to neoCRT or prognosis of Chinese Han patients with LARC. PMID:27167201

  18. 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.

  19. Prognostic Impact of mRNA Expression Levels of HER1–4 (ERBB1–4) in Patients with Locally Advanced Rectal Cancer

    PubMed Central

    Kripp, Melanie; Merx, Kirsten; Wirtz, Ralph Markus; Gaiser, Timo; Eidt, Sebastian; Schwaab, Juliana; Post, Stefan; Wenz, Frederik; Hochhaus, Andreas

    2016-01-01

    Background. No predictive or prognostic biomarker is available for patients with locally advanced rectal cancer (LARC) undergoing perioperative chemoradiotherapy (CRT). Members of the human epidermal growth factor receptor (HER) family of receptor tyrosine kinases EGFR (HER1, ERBB1), HER2 (ERBB2), HER3 (ERBB3), and HER4 (ERBB4) are therapeutic targets in several cancers. The analysis was performed to assess expression levels and study the potential prognostic impact for disease-free and overall survival in patients with LARC. Patients and Methods. ERBB1–4 mRNA expression and tumor proliferation using Ki-67 (MKI67) mRNA were evaluated using RT-quantitative PCR in paraffin-embedded tumor samples from 86 patients (median age: 63) treated with capecitabine or 5-fluorouracil-based CRT within a phase 3 clinical trial. Results. A positive correlation of HER4 and HER2, HER3 and HER2, and HER4 and HER3 with each other was observed. Patients with high mRNA expression of ERBB1 (EGFR, HER1) had significantly increased risk for recurrence and death. Patients with high mRNA expression of MKI67 had reduced risk for relapse. Conclusion. This analysis suggests a prognostic impact of both ERBB1 and MKi67 mRNA expression in LARC patients treated with capecitabine or fluorouracil-based chemoradiotherapy.

  20. Prognostic Impact of mRNA Expression Levels of HER1-4 (ERBB1-4) in Patients with Locally Advanced Rectal Cancer.

    PubMed

    Kripp, Melanie; Merx, Kirsten; Wirtz, Ralph Markus; Gaiser, Timo; Eidt, Sebastian; Schwaab, Juliana; Post, Stefan; Wenz, Frederik; Hochhaus, Andreas; Hofheinz, Ralf-Dieter; Erben, Philipp

    2016-01-01

    Background. No predictive or prognostic biomarker is available for patients with locally advanced rectal cancer (LARC) undergoing perioperative chemoradiotherapy (CRT). Members of the human epidermal growth factor receptor (HER) family of receptor tyrosine kinases EGFR (HER1, ERBB1), HER2 (ERBB2), HER3 (ERBB3), and HER4 (ERBB4) are therapeutic targets in several cancers. The analysis was performed to assess expression levels and study the potential prognostic impact for disease-free and overall survival in patients with LARC. Patients and Methods. ERBB1-4 mRNA expression and tumor proliferation using Ki-67 (MKI67) mRNA were evaluated using RT-quantitative PCR in paraffin-embedded tumor samples from 86 patients (median age: 63) treated with capecitabine or 5-fluorouracil-based CRT within a phase 3 clinical trial. Results. A positive correlation of HER4 and HER2, HER3 and HER2, and HER4 and HER3 with each other was observed. Patients with high mRNA expression of ERBB1 (EGFR, HER1) had significantly increased risk for recurrence and death. Patients with high mRNA expression of MKI67 had reduced risk for relapse. Conclusion. This analysis suggests a prognostic impact of both ERBB1 and MKi67 mRNA expression in LARC patients treated with capecitabine or fluorouracil-based chemoradiotherapy. PMID:27610130

  1. Prognostic Impact of mRNA Expression Levels of HER1–4 (ERBB1–4) in Patients with Locally Advanced Rectal Cancer

    PubMed Central

    Kripp, Melanie; Merx, Kirsten; Wirtz, Ralph Markus; Gaiser, Timo; Eidt, Sebastian; Schwaab, Juliana; Post, Stefan; Wenz, Frederik; Hochhaus, Andreas

    2016-01-01

    Background. No predictive or prognostic biomarker is available for patients with locally advanced rectal cancer (LARC) undergoing perioperative chemoradiotherapy (CRT). Members of the human epidermal growth factor receptor (HER) family of receptor tyrosine kinases EGFR (HER1, ERBB1), HER2 (ERBB2), HER3 (ERBB3), and HER4 (ERBB4) are therapeutic targets in several cancers. The analysis was performed to assess expression levels and study the potential prognostic impact for disease-free and overall survival in patients with LARC. Patients and Methods. ERBB1–4 mRNA expression and tumor proliferation using Ki-67 (MKI67) mRNA were evaluated using RT-quantitative PCR in paraffin-embedded tumor samples from 86 patients (median age: 63) treated with capecitabine or 5-fluorouracil-based CRT within a phase 3 clinical trial. Results. A positive correlation of HER4 and HER2, HER3 and HER2, and HER4 and HER3 with each other was observed. Patients with high mRNA expression of ERBB1 (EGFR, HER1) had significantly increased risk for recurrence and death. Patients with high mRNA expression of MKI67 had reduced risk for relapse. Conclusion. This analysis suggests a prognostic impact of both ERBB1 and MKi67 mRNA expression in LARC patients treated with capecitabine or fluorouracil-based chemoradiotherapy. PMID:27610130

  2. [Palliative Care for Rectal Cancer Complicated with Gastric Cancer].

    PubMed

    Furukawa, Takeshi; Takahashi, Hitoshi; Tanaka, Kei; Muto, Takaaki

    2015-11-01

    Medical advancements have led to an increase in the number of elderly people. However, standard treatments may sometimes be difficult to use in elderly people. Here, we report the case of an elderly patient with rectal and gastric cancer who refused radical surgery. The patient was an 83-year-old man who had type-2 diabetes, hypertension, hyperuricemia, mitral valve regurgitation, and mild dementia. Furthermore, he was blind in both eyes owing to glaucoma. He first visited our hospital in 2005. In 2010, he was diagnosed with anemia, but he refused a thorough examination; however, he did consent to take iron supplements. In July 2011, he consulted our hospital for symptoms of frequent diarrhea, and agreed to an examination. After colonoscopy, he was diagnosed with rectal cancer that was becoming obstructive. There were no metastases to other organs, but he was also diagnosed with gastric cancer. As he and his family refused radical surgery, a stoma was constructed. After the operation, he received palliative care but died in September 2013. PMID:26805335

  3. 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.

  4. 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.

  5. 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.

  6. Importance of surgical margins in rectal cancer.

    PubMed

    Mukkai Krishnamurty, Devi; Wise, Paul E

    2016-03-01

    Distal resection margin (DRM) and circumferential resection margin (CRM) are two important considerations in rectal cancer management. Although guidelines recommend a 2 cm DRM, studies have shown that a shorter DRM is adequate, especially in patients receiving neoadjuvant chemoradiation. Standardization of total mesorectal excision has greatly improved quality of CRM. Although more patients are undergoing sphincter-saving procedures, abdominoperineal resection is indicated for very distal tumors, and pelvic exenteration is often necessary for tumors involving pelvic organs. PMID:27094456

  7. 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.

  8. The influence of hormone therapies on colon and rectal cancer.

    PubMed

    Mørch, Lina Steinrud; Lidegaard, Øjvind; Keiding, Niels; Løkkegaard, Ellen; Kjær, Susanne Krüger

    2016-05-01

    Exogenous sex hormones seem to play a role in colorectal carcinogenesis. Little is known about the influence of different types or durations of postmenopausal hormone therapy (HT) on colorectal cancer risk. A nationwide cohort of women 50-79 years old without previous cancer (n = 1,006,219) were followed 1995-2009. Information on HT exposures was from the National Prescription Register and updated daily, while information on colon (n = 8377) and rectal cancers (n = 4742) were from the National Cancer Registry. Potential confounders were obtained from other national registers. Poisson regression analyses with 5-year age bands included hormone exposures as time-dependent covariates. Use of estrogen-only therapy and combined therapy were associated with decreased risks of colon cancer (adjusted incidence rate ratio 0.77, 95 % confidence interval 0.68-0.86 and 0.88, 0.80-0.96) and rectal cancer (0.83, 0.72-0.96 and 0.89, 0.80-1.00), compared to never users. Transdermal estrogen-only therapy implied more protection than oral administration, while no significant influence was found of regimen, progestin type, nor of tibolone. The benefit of HT was stronger for long-term hormone users; and hormone users were at lower risk of advanced stage of colorectal cancer, which seems supportive for a causal association between hormone therapy and colorectal cancer. PMID:26758900

  9. 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

  10. 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.

  11. Techniques and technology evolution of rectal cancer surgery: a history of more than a hundred years.

    PubMed

    Lirici, Marco Maria; Hüscher, Cristiano G S

    2016-10-01

    History of rectal cancer surgery has shown a continuous evolution of techniques and technologies over the years, with the aim of improving both oncological outcomes and patient's quality of life. Progress in rectal cancer surgery depended on a better comprehension of the disease and its behavior, and also, it was strictly linked to advances in technologies and amazing surgical intuitions by some surgeons who pioneered in rectal surgery, and this marked a breakthrough in the surgical treatment of rectal cancer. Rectal surgery with radical intent was first performed by Miles in 1907 and the procedure he developed, abdomino-perineal resection, became a gold standard for many years. In the following years and over the last century other procedures were introduced which became new gold standards: Hartmann's procedure, anterior rectal resection, total mesorectal excision (TME); the last one, developed by Heald in 1982, is the present gold standard treatment of rectal cancer. At the same time, new technologies were developed and introduced into the clinical practice, which enhanced results of surgery and even made possible performing new operations: leg-rests, stapling devices, instruments, appliances and platforms for laparoscopic surgery and transanal rectal surgery. In more recent years the transanal approach to TME has been introduced, which might improve oncologic results of surgery of the rectum. Ongoing randomized studies, future systematic reviews and metanalyses will show whether the transanal approach to TME will become a new gold standard.

  12. Local staging of rectal cancer: the current role of MRI

    PubMed Central

    Rogalla, Patrik; Taupitz, Matthias

    2006-01-01

    With the advent of powerful gradient coil systems and high-resolution surface coils, magnetic resonance imaging (MRI) has recently extended its role in the staging of rectal cancer. MRI is superior to endorectal ultrasound, the most widely used staging modality in patients with rectal tumors, in that it visualizes not only the intestinal wall but also the surrounding pelvic anatomy. The crucial advantage of MRI is not that it enables exact T-staging but precise evaluation of the topographic relationship of a tumor to the mesorectal fascia. This fascia is the most important anatomic landmark for the feasibility of total mesorectal excision, which has evolved into the standard operative procedure for the resection of cancer located in the middle or lower third of the rectum. MRI is currently the only imaging modality that is highly accurate in predicting whether or not it is likely that a tumor-free margin can be achieved and thus provides important information for planning of an effective therapeutic strategy, especially in patients with advanced rectal cancer. PMID:17008990

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

    PubMed

    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/mm(2)), 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

  15. 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

  16. [Rectal cancer in a pregnant woman, a case report].

    PubMed

    Højgaard, Helle Manfeld; Rahr, Hans

    2012-06-25

    A case of disseminated rectal cancer in a 32-year-old pregnant woman is described. Pain was her main complaint, but this had been ascribed to haemorrhoids and treated with topical agents. She was diagnosed with rectal cancer late in the third trimester when her midwife referred her for surgical assessment. Following caesarian section, diagnostic workup showed multiple liver metastases. Rectal cancer in pregnancy is rare, while haemorrhoids are common. We recommend keeping the differential diagnoses in mind and performing a digital rectal examination if pregnant women have anal symptoms.

  17. Disseminated lung cancer presenting as a rectal mass.

    PubMed

    Noergaard, Mia M; Stamp, Inger M H; Bodtger, Uffe

    2016-01-01

    Primary lung cancer is the leading cause of cancer-related deaths globally, and approximately 50% had metastatic disease at the time of diagnosis. A rectal mass and unintended weight loss are common manifestations of rectal cancer. Our case presented with a rectal mass, but workup revealed a metastatic lesion from lung cancer. Lung cancer metastases to the lower gastrointestinal tract imply reduced survival compared with the already poor mean survival of stage IV lung cancer. Despite relevant therapy, the patient died 5 months after referral. PMID:27683028

  18. MR imaging for rectal cancer: the role in staging the primary and response to neoadjuvant therapy.

    PubMed

    Battersby, Nick J; Moran, Brendan; Yu, Stanley; Tekkis, Paris; Brown, Gina

    2014-08-01

    Pre-operative staging is an essential aspect of modern rectal cancer management and radiological assessment is central to this process. An ideal radiological assessment should provide sufficient information to reliably guide pre-operative decision-making. Technical advances allow high-resolution imaging to not only provide prognostic information but to define the anatomy, helping the surgeon to anticipate potential pitfalls during the operation. The main imaging modality for local staging of rectal cancer is Magnetic Resonance Imaging (MRI), as it defines the tumour and relevant anatomy providing the most detail on the important prognostic factors that influence treatment choice. In addition, there is an emerging role for MRI in the assessment of the response to neoadjuvant therapy. This article is an evidence-based review of rectal cancer staging focusing on post-treatment assessment of response using MRI. The discussion extends into the implications for reliably assessing response and how this may influence future rectal cancer management. PMID:24954622

  19. 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.

  20. Sequence variation in mature microRNA-608 and benefit from neo-adjuvant treatment in locally advanced rectal cancer patients.

    PubMed

    Sclafani, Francesco; Chau, Ian; Cunningham, David; Lampis, Andrea; Hahne, Jens Claus; Ghidini, Michele; Lote, Hazel; Zito, Domenico; Tabernero, Josep; Glimelius, Bengt; Cervantes, Andres; Begum, Ruwaida; De Castro, David Gonzalez; Wilson, Sanna Hulkki; Peckitt, Clare; Eltahir, Zakaria; Wotherspoon, Andrew; Tait, Diana; Brown, Gina; Oates, Jacqueline; Braconi, Chiara; Valeri, Nicola

    2016-09-01

    Single nucleotide polymorphisms (SNPs) in microRNA genes have been associated with colorectal cancer (CRC) risk, survival and response to treatment. Conflicting results are available on the association between rs4919510, a SNP in mature miR-608 and clinical outcome in CRC. Here, we analyzed the association between rs4919510 and benefit from perioperative treatment in a randomised phase II trial of neoadjuvant Capecitabine and Oxaliplatin (CAPOX) followed by chemo-radiotherapy, surgery and adjuvant CAPOX ± Cetuximab in high-risk locally advanced rectal cancer (LARC). A total of 155/164 (94.5%) patients were assessable. 95 (61.3%) were homozygous for CC, 55 (35.5%) heterozygous (CG) and 5 (3.2%) homozygous for GG. Median follow-up was 64.9 months. In the CAPOX arm the 5-year progression-free survival (PFS) and overall survival (OS) rates were 54.6% and 60.7% for CC and 82.0% and 82.1% for CG/GG, respectively (HR PFS 0.13, 95% CI: 0.12-0.83, P = 0.02; HR OS 0.38, 95% CI: 0.14-1.01, P = 0.05). In the CAPOX-C arm PFS and OS were 73.2 and 82.2%, respectively for CC carriers and 64.6 and 73.1% for CG/GG carriers (HR PFS 1.38, 95% CI: 0.61-3.13, P = 0.44; HR OS 1.34, 95% CI: 0.52-3.48, P = 0.55). An interaction was found between study treatment and rs4919510 genotype for both PFS (P = 0.02) and OS (P = 0.07). This is the first study investigating rs4919510 in LARC. The CC genotype appeared to be associated with worse prognosis compared to the CG/GG genotype in patients treated with chemotherapy and chemo-radiotherapy alone. Addition of Cetuximab to chemotherapy and chemo-radiotherapy in CC carriers appeared to improve clinical outcome. PMID:27381831

  1. Sequence variation in mature microRNA-608 and benefit from neo-adjuvant treatment in locally advanced rectal cancer patients

    PubMed Central

    Sclafani, Francesco; Chau, Ian; Cunningham, David; Lampis, Andrea; Hahne, Jens Claus; Ghidini, Michele; Lote, Hazel; Zito, Domenico; Tabernero, Josep; Glimelius, Bengt; Cervantes, Andres; Begum, Ruwaida; De Castro, David Gonzalez; Wilson, Sanna Hulkki; Peckitt, Clare; Eltahir, Zakaria; Wotherspoon, Andrew; Tait, Diana; Brown, Gina; Oates, Jacqueline; Braconi, Chiara; Valeri, Nicola

    2016-01-01

    Single nucleotide polymorphisms (SNPs) in microRNA genes have been associated with colorectal cancer (CRC) risk, survival and response to treatment. Conflicting results are available on the association between rs4919510, a SNP in mature miR-608 and clinical outcome in CRC. Here, we analyzed the association between rs4919510 and benefit from perioperative treatment in a randomised phase II trial of neoadjuvant Capecitabine and Oxaliplatin (CAPOX) followed by chemo-radiotherapy, surgery and adjuvant CAPOX ± Cetuximab in high-risk locally advanced rectal cancer (LARC). A total of 155/164 (94.5%) patients were assessable. 95 (61.3%) were homozygous for CC, 55 (35.5%) heterozygous (CG) and 5 (3.2%) homozygous for GG. Median follow-up was 64.9 months. In the CAPOX arm the 5-year progression-free survival (PFS) and overall survival (OS) rates were 54.6% and 60.7% for CC and 82.0% and 82.1% for CG/GG, respectively (HR PFS 0.13, 95% CI: 0.12–0.83, P = 0.02; HR OS 0.38, 95% CI: 0.14–1.01, P = 0.05). In the CAPOX-C arm PFS and OS were 73.2 and 82.2%, respectively for CC carriers and 64.6 and 73.1% for CG/GG carriers (HR PFS 1.38, 95% CI: 0.61–3.13, P = 0.44; HR OS 1.34, 95% CI: 0.52–3.48, P = 0.55). An interaction was found between study treatment and rs4919510 genotype for both PFS (P = 0.02) and OS (P = 0.07). This is the first study investigating rs4919510 in LARC. The CC genotype appeared to be associated with worse prognosis compared to the CG/GG genotype in patients treated with chemotherapy and chemo-radiotherapy alone. Addition of Cetuximab to chemotherapy and chemo-radiotherapy in CC carriers appeared to improve clinical outcome. PMID:27381831

  2. Adjuvant Chemotherapy in Rectal Cancer after Chemoradiotherapy.

    PubMed

    Boustani, J; Caubet, M; Bosset, J-F

    2016-02-01

    The aim of this overview was to investigate whether adjuvant chemotherapy has a favourable effect on the outcome of patients with rectal cancer who had preoperative (chemo)radiotherapy. A review of randomised clinical trials that allocated patients between fluorouracil-based and observation or between fluorouracil-based and oxaliplatin-based adjuvant chemotherapy after preoperative (chemo)radiotherapy was carried out, including their corresponding meta-analyses. None of the five randomised trials has shown a significant benefit of fluorouracil-based adjuvant chemotherapy for overall survival or disease-free survival. Also, the three corresponding meta-analyses failed to show a benefit of adjuvant treatment. Of three randomised trials - two phase III and one phase II with a 3-year disease-free survival end point - two showed a small benefit of adding oxaliplatin to fluorouracil, one failed. The corresponding meta-analyses showed that the pooled difference was not significant. In conclusion, the use of postoperative 5-fluorouracil-based chemotherapy with or without oxaliplatin in patients with rectal cancer after preoperative (chemo)radiotherapy is not scientifically proven.

  3. Combined modality preoperative therapy for unresectable rectal cancer.

    PubMed

    Percarpio, B; Bitterman, J; Sabbath, K; Alfano, F; Ruszkowski, R; Bowen, J

    1992-01-01

    Locally advanced rectal cancer has been a surgical challenge because of fixation of the primary tumor to the boney pelvis or to other pelvic soft tissues. During a 12-month period seven patients with locally advanced adenocarcinoma of the rectum were treated preoperatively with simultaneous pelvic irradiation (4500-5040 cGy) and infusion chemotherapy (5-fluorouracil 1000 mg per m2 per day over 96 hours and mitomycin 10 mg per m2. Tolerance was reasonable and all patients underwent successful resection of the primary lesion. Two patients had a complete response to preoperative combined modality therapy with no cancer found in the surgical specimen. With a short follow-up period, all patients have experienced satisfactory healing and none have suffered local or distant recurrence. The results of this limited series are encouraging for future clinical trials.

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. Generic Planning Target Margin for Rectal Cancer Treatment Setup Variation

    SciTech Connect

    Robertson, John M. Campbell, Jonathon P.; Yan Di

    2009-08-01

    Purpose: To calculate the generic planning target margin (GPTM) for patients receiving radiation therapy (RT) for rectal cancer placed in a prone position with a customized cradle for small-bowel exclusion. Methods and Materials: A total of 25 consecutive rectal cancer patients were treated for 25 or 28 fractions in a prone position using a cradle to maximize small bowel exclusion. Treatment planning computed tomography (CT) scans were used to create orthogonally digitally reconstructed radiographs (DRRs) for portal image registration, which were compared with daily portal images from an electronic portal-imaging device (EPID). Translation values needed to align the DRRs and EPIDs were recorded for the superior to inferior (SI), right to left (RL), and anterior to posterior (AP) directions, and used to calculate the GPTM using the four-parameter model. Age, weight, and body mass index were tested compared with the setup variation using a Pearson correlation and a t test for significance. Gender versus setup variation was compared with a t test. Results: A total of 1,723 EPID images were reviewed. The GPTM was 10 mm superior, 8 mm inferior, 7 mm RL and 10 mm AP. Age and gender were unrelated to setup variation. Weight was significantly associated with systematic AP variation (p < 0.05). BMI was significantly associated with systematic SI (p < 0.05) and AP (p < 0.01) variation and random RL variation (p < 0.05). Conclusions: The GPTM for rectal cancer is asymmetric with a maximum of 10 mm in the superior, anterior and posterior dimensions. Body mass index may effect setup variation. Research using advanced treatment planning should include these margins in the planning target volume definition.

  10. 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.

  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. Laparoscopic anterior pelvic exenteration for locoregionally advanced rectal cancer directly invading the urinary bladder: A case report of low anterior resection with en bloc cystectomy for sphincter preservation

    PubMed Central

    Nakashima, Shinya; Hamada, Takeomi; Nishida, Takahiro; Maehara, Naoki; Ikeda, Takuto; Tsukino, Hiromasa; Mukai, Shoichiro; Kamoto, Toshiyuki; Kondo, Kazuhiro

    2015-01-01

    Abstract Laparoscopic multi‐visceral resection in patients with T4 colorectal cancer remains controversial. A 73‐year‐old man was admitted to the hospital for rectosigmoid cancer directly invading the urinary bladder trigone without distant metastasis. We successfully performed complete resection by laparoscopic anterior pelvic exenteration while preserving the anus. After laparoscopic mobilization of the rectum, urinary bladder, and prostate, the urethra and urethral catheter were dissected to reveal the lower rectum. By pulling the urethral catheter toward the head, the prostate was excised retrogradely from the lower rectum anterior wall. The lower rectum was resected and anastomosed by the double stapling technique with a safe distal margin from the tumor. Pathological findings of the resected specimen indicated no residual tumor in the surgical margin. There was no evidence of recurrence 34 months after surgery. En bloc, R0, laparoscopic anterior pelvic exenteration for T4 rectal cancer is feasible. However, further studies with long‐term follow‐up are required to resolve oncological outcomes. PMID:26303734

  13. Laparoscopic anterior pelvic exenteration for locoregionally advanced rectal cancer directly invading the urinary bladder: A case report of low anterior resection with en bloc cystectomy for sphincter preservation.

    PubMed

    Ishizaki, Hidenobu; Nakashima, Shinya; Hamada, Takeomi; Nishida, Takahiro; Maehara, Naoki; Ikeda, Takuto; Tsukino, Hiromasa; Mukai, Shoichiro; Kamoto, Toshiyuki; Kondo, Kazuhiro

    2015-08-01

    Laparoscopic multi-visceral resection in patients with T4 colorectal cancer remains controversial. A 73-year-old man was admitted to the hospital for rectosigmoid cancer directly invading the urinary bladder trigone without distant metastasis. We successfully performed complete resection by laparoscopic anterior pelvic exenteration while preserving the anus. After laparoscopic mobilization of the rectum, urinary bladder, and prostate, the urethra and urethral catheter were dissected to reveal the lower rectum. By pulling the urethral catheter toward the head, the prostate was excised retrogradely from the lower rectum anterior wall. The lower rectum was resected and anastomosed by the double stapling technique with a safe distal margin from the tumor. Pathological findings of the resected specimen indicated no residual tumor in the surgical margin. There was no evidence of recurrence 34 months after surgery. En bloc, R0, laparoscopic anterior pelvic exenteration for T4 rectal cancer is feasible. However, further studies with long-term follow-up are required to resolve oncological outcomes.

  14. High Rate of Sexual Dysfunction Following Surgery for Rectal Cancer

    PubMed Central

    Ertekin, Caglar; Tinay, Ilker; Yegen, Cumhur

    2014-01-01

    Purpose Although rectal cancer is a very common malignancy and has an improved cure rate in response to oncological treatment, research on rectal-cancer survivors' sexual function remains limited. Sexual dysfunction (SD) after rectal cancer treatment was measured, and possible predisposing factors that may have an impact on the development of this disorder were identified. Methods Patients undergoing curative rectal cancer surgery from January 2012 to September 2013 were surveyed using questionnaires. The female sexual function index or the International Index of Erectile Function was recorded. A multiple logistic regression was used to test associations of clinical factors with outcomes. Results Fifty-six men (56%) and 28 women (44%) who completed the questionnaire were included in the study. A total of 76 patients of the 86 patients (90.5%) with the diagnosis of rectal cancer who were included in this study reported different levels of SD after radical surgery. A total of 64 patients (76%) from the whole cohort reported moderate to severe SD after treatment of rectal cancer. Gender (P = 0.011) was independently associated with SD. Female patients reported significantly higher rates of moderate to severe SD than male patients. Patients were rarely treated for dysfunction. Conclusion Sexual problems after surgery for rectal cancer are common, but patients are rarely treated for SD. Female patients reported higher rates of SD than males. These results point out the importance of sexual (dys)function in survivors of rectal cancer. More attention should be drawn to this topic for clinical and research purposes. PMID:25360427

  15. Laparoscopic resection of rectal cancer in the elderly

    PubMed Central

    Peters, Walter R.

    2016-01-01

    Recent published trials have failed to demonstrate that laparoscopic resection is not inferior to open resection of rectal cancer in terms of pathologic outcomes. However, there have been numerous studies showing the benefit of laparoscopic resection in terms of short-term complications and quality of life. Fewer complications and shorter hospital stays improve the chance of maintaining functional status, which is very important for the elderly population. Thus, laparoscopic resection of rectal cancer remains a viable option for the elderly.

  16. Neoadjuvant Therapy in Rectal Cancer - Biobanking of Preoperative Tumor Biopsies

    PubMed Central

    Jo, Peter; Nietert, Manuel; Gusky, Linda; Kitz, Julia; Conradi, Lena C.; Müller-Dornieden, Annegret; Schüler, Philipp; Wolff, Hendrik A.; Rüschoff, Josef; Ströbel, Philipp; Grade, Marian; Liersch, Torsten; Beißbarth, Tim; Ghadimi, Michael B.; Sax, Ulrich; Gaedcke, Jochen

    2016-01-01

    Translational research relies on high-quality biospecimens. In patients with rectal cancer treated preoperatively with radiochemotherapy tissue based analyses are challenging. To assess quality challenges we analyzed tissue samples taken over the last years in a multicenter setting. We retrospectively evaluated overall 197 patients of the CAO/ARO/AIO-94- and 04-trial with locally advanced rectal cancer that were biopsied preoperatively at the University Medical Center Goettingen as well as in 10 cooperating hospitals in Germany. The cellular content of tumor, mucosa, stroma, necrosis and the amount of isolated DNA and RNA as well as the RNA integrity number (RIN) as quality parameters were evaluated. A high RNA yield (p = 2.75e–07) and the content of tumor (p = 0.004) is significantly associated to high RIN-values, whereas a high content of mucosa (p = 0.07) shows a trend and a high amount of necrosis (p = 0.01) is significantly associated with RNA of poor quality. Correlating biopsies from Goettingen and the cooperating centers showed comparable tumor content results. By taking small sized biopsies we could assess a clear correlation between a good RNA quality and a high amount of RNA and tumor cells. These results also indicate that specimens collected at different centers are of comparable quality. PMID:27752113

  17. 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.

  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. Heterogeneity of KRAS Mutation Status in Rectal Cancer

    PubMed Central

    Jo, Peter; König, Alexander; Schirmer, Markus; Kitz, Julia; Conradi, Lena-Christin; Azizian, Azadeh; Bernhardt, Markus; Wolff, Hendrik A.; Grade, Marian; Ghadimi, Michael; Ströbel, Philipp; Schildhaus, Hans-Ulrich; Gaedcke, Jochen

    2016-01-01

    Introduction Anti-EGFR targeted therapy is of increasing importance in advanced colorectal cancer and prior KRAS mutation testing is mandatory for therapy. However, at which occasions this should be performed is still under debate. We aimed to assess in patients with locally advanced rectal cancer whether there is intra-specimen KRAS heterogeneity prior to and upon preoperative chemoradiotherapy (CRT), and if there are any changes in KRAS mutation status due to this intervention. Materials and Methods KRAS mutation status analyses were performed in 199 tumor samples from 47 patients with rectal cancer. To evaluate the heterogeneity between different tumor areas within the same tumor prior to preoperative CRT, 114 biopsies from 34 patients (mean 3 biopsies per patient) were analyzed (pre-therapeutic intratumoral heterogeneity). For the assessment of heterogeneity after CRT residual tumor tissue (85 samples) from 12 patients (mean 4.2 tissue samples per patient) were analyzed (post-therapeutic intratumoral heterogeneity) and assessment of heterogeneity before and after CRT was evaluated in corresponding patient samples (interventional heterogeneity). Primer extension method (SNaPshot™) was used for initial KRAS mutation status testing for Codon 12, 13, 61, and 146. Discordant results by this method were reevaluated by using the FDA-approved KRAS Pyro Kit 24, V1 and the RAS Extension Pyro Kit 24, V1 Kit (therascreen® KRAS test). Results For 20 (43%) out of the 47 patients, a KRAS mutation was detected. With 12 out of 20, the majority of these mutations affected codon 35. We did not obtained evidence that CRT results in changes of the KRAS mutation pattern. In addition, no intratumoral heterogeneity in the KRAS mutational status could be proven. This was true for both the biopsies prior to CRT and the resection specimens thereafter. The discrepancy observed in some samples when using the SNaPshot™ assay was due to insufficient sensitivity of this technique upon

  20. 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

  1. 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.

  2. 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

  3. Patterns of Failure and Local Control After Intraoperative Electron Boost Radiotherapy to the Presacral Space in Combination with Total Mesorectal Excision in Patients with Locally Advanced Rectal Cancer

    SciTech Connect

    Roeder, Falk; Treiber, Martina; Oertel, Susanne; Dinkel, Julien; Timke, Carmen; Funk, Angela; Garcia-Huttenlocher, Helena; Bischof, Marc; Weitz, Juergen; Harms, Wolfgang; Hensley, Frank W.; Buchler, Markus W.; Debus, Juergen; Krempien, Robert . E-mail: robert_krempien@med.uni-heidelberg.de

    2007-04-01

    Purpose: To evaluate local control and patterns of failure in patients treated with intraoperative electron beam radiotherapy (IOERT) after total mesorectal excision (TME), to appraise the effectiveness of intraoperative target definition. Methods and Materials: We analyzed the outcome of 243 patients with rectal cancer treated with IOERT (median dose, 10 Gy) after TME. Eighty-eight patients received neoadjuvant and 122 patients adjuvant external beam radiotherapy (EBRT) (median dose, 41.4 Gy), and in 88% simultaneous chemotherapy was applied. Median follow-up was 59 months. Results: Local failure was observed in 17 patients (7%), resulting in a 5-year local control rate of 92%. Only complete resection and absence of nodal involvement correlated positively with local control. Considering IOERT fields, seven infield recurrences were seen in the presacral space, resulting in a 5-year local control rate of 97%. The remaining local relapses were located as follows: retrovesical/retroprostatic (5), anastomotic site (2), promontorium (1), ileocecal (1), and perineal (1). Conclusion: Intraoperative electron beam radiotherapy as part of a multimodal treatment approach including TME is a highly effective regimen to prevent local failure. The presacral space remains the site of highest risk for local failure, but IOERT can decrease the percentage of relapses in this area.

  4. MRI staging of low rectal cancer.

    PubMed

    Shihab, Oliver C; Moran, Brendan J; Heald, Richard J; Quirke, Philip; Brown, Gina

    2009-03-01

    Low rectal tumours, especially those treated by abdominoperineal excision (APE), have a high rate of margin involvement when compared with tumours elsewhere in the rectum. Correct surgical management to minimise this rate of margin involvement is reliant on highly accurate imaging, which can be used to plan the planes of excision. In this article we describe the techniques for accurate magnetic resonance imaging (MRI) assessment and a novel staging system for low rectal tumours. Using this staging system it is possible for the radiologist to demonstrate accurately tumour-free planes for surgical excision of low rectal tumours. PMID:18810451

  5. 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

  6. Short-term Outcomes of an Extralevator Abdominoperineal Resection in the Prone Position Compared With a Conventional Abdominoperineal Resection for Advanced Low Rectal Cancer: The Early Experience at a Single Institution

    PubMed Central

    Park, Seungwan; Hur, Hyuk; Min, Byung Soh

    2016-01-01

    Purpose This study compared the perioperative and pathologic outcomes between an extralevator abdominoperineal resection (APR) in the prone position and a conventional APR. Methods Between September 2011 and March 2014, an extralevator APR in the prone position was performed on 13 patients with rectal cancer and a conventional APR on 26 such patients. Patients' demographics and perioperative and pathologic outcomes were obtained from the colorectal cancer database and electronic medical charts. Results Age and preoperative carcinoembryonic antigen (CEA) level were significantly different between the conventional and the extralevator APR in the prone position (median age, 65 years vs. 55 years [P = 0.001]; median preoperative CEA level, 4.94 ng/mL vs. 1.81 ng/mL [P = 0.011]). For perioperative outcomes, 1 (3.8%) intraoperative bowel perforation occurred in the conventional APR group and 2 (15.3%) in the extralevator APR group. In the conventional and extralevator APR groups, 12 (46.2%) and 6 patients (46.2%) had postoperative complications, and 8 (66.7%) and 2 patients (33.4%) had major complications (Clavien-Dindo III/IV), respectively. The circumferential resection margin involvement rate was higher in the extralevator APR group compared with the conventional APR group (3 of 13 [23.1%] vs. 3 of 26 [11.5%]). Conclusion The extralevator APR in the prone position for patients with advanced low rectal cancer has no advantages in perioperative and pathologic outcomes over a conventional APR for such patients. However, through early experience with a new surgical technique, we identified various reasons for the lack of favorable outcomes and expect sufficient experience to produce better peri- or postoperative outcomes. PMID:26962531

  7. Rectal Cancer Magnetic Resonance Imaging: Imaging Beyond Morphology.

    PubMed

    Prezzi, D; Goh, V

    2016-02-01

    Magnetic resonance imaging (MRI) has in recent years progressively established itself as one of the most valuable modalities for the diagnosis, staging and response assessment of rectal cancer and its use has largely focused on accurate morphological assessment. The potential of MRI, however, extends beyond detailed anatomical depiction: aspects of tissue physiology, such as perfusion, oxygenation and water molecule diffusivity, can be assessed indirectly. Functional MRI is rapidly evolving as a promising non-invasive assessment tool for tumour phenotyping and assessment of response to new therapeutic agents. In spite of promising experimental data, the evidence base for the application of functional MRI techniques in rectal cancer remains modest, reflecting the relatively poor agreement on technical protocols, image processing techniques and quantitative methodology to date, hampering routine integration into clinical management. This overview outlines the established strengths and the critical limitations of anatomical MRI in rectal cancer; it then introduces some of the functional MRI techniques and quantitative analysis methods that are currently available, describing their applicability in rectal cancer and reviewing the relevant literature; finally, it introduces the concept of a multi-parametric quantitative approach to rectal cancer.

  8. Rectal Cancer Magnetic Resonance Imaging: Imaging Beyond Morphology.

    PubMed

    Prezzi, D; Goh, V

    2016-02-01

    Magnetic resonance imaging (MRI) has in recent years progressively established itself as one of the most valuable modalities for the diagnosis, staging and response assessment of rectal cancer and its use has largely focused on accurate morphological assessment. The potential of MRI, however, extends beyond detailed anatomical depiction: aspects of tissue physiology, such as perfusion, oxygenation and water molecule diffusivity, can be assessed indirectly. Functional MRI is rapidly evolving as a promising non-invasive assessment tool for tumour phenotyping and assessment of response to new therapeutic agents. In spite of promising experimental data, the evidence base for the application of functional MRI techniques in rectal cancer remains modest, reflecting the relatively poor agreement on technical protocols, image processing techniques and quantitative methodology to date, hampering routine integration into clinical management. This overview outlines the established strengths and the critical limitations of anatomical MRI in rectal cancer; it then introduces some of the functional MRI techniques and quantitative analysis methods that are currently available, describing their applicability in rectal cancer and reviewing the relevant literature; finally, it introduces the concept of a multi-parametric quantitative approach to rectal cancer. PMID:26586163

  9. 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.

  10. 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.

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

    PubMed Central

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

    2012-01-01

    Background 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 and methods 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. Results 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. Conclusions 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. PMID:23411588

  12. Robotic Surgery for Rectal Cancer: An Update in 2015

    PubMed Central

    Kwak, Jung Myun; Kim, Seon Hahn

    2016-01-01

    During the last decade, robotic surgery for rectal cancer has rapidly gained acceptance among colorectal surgeons worldwide, with well-established safety and feasibility. The lower conversion rate and better surgical specimen quality of robotic compared with laparoscopic surgery potentially improves survival. Earlier recovery of voiding and sexual function after robotic total mesorectal excision is another favorable outcome. Long-term survival data are sparse with no evidence that robotic surgery offers major benefits in oncological outcomes. Although initial reports are promising, more rigorous scientific evaluation in multicenter, randomized clinical trials should be performed to definitely determine the advantages of robotic rectal cancer surgery. PMID:26875201

  13. Expression of Human Epidermal Growth Factor Receptor-2 in Resected Rectal Cancer

    PubMed Central

    Meng, Xiangjiao; Huang, Zhaoqin; Di, Jian; Mu, Dianbin; Wang, Yawei; Zhao, Xianguang; Zhao, Hanxi; Zhu, Wanqi; Li, Xiaolin; Kong, Lingling; Xing, Ligang

    2015-01-01

    Abstract The addition of trastuzumab to chemotherapy was demonstrated to be beneficial for advanced human epidermal growth factor receptor-2 (HER-2) positive gastric cancer. However, the HER-2 status of rectal cancer remains uncertain. This study aimed to determine the HER-2 expression in a large multicenter cohort of rectal cancer patients. The clinical and pathological features of 717 patients were retrospectively reviewed. All the patients were diagnosed with primary rectal adenocarcinoma without distant metastasis and took surgery directly without any preoperative anticancer treatment. HER-2 status was assessed on resected samples. A total of 99 cases with IHC3+ and 16 cases with IHC 2+ plus gene amplification were determined as HER-2 positive. 22.6% of HER-2 positive patients had local recurrence, whereas 16.9% of HER-2 negative patients did (P = 0.146). HER-2 positive tumors were more likely to have distant metastasis (P = 0.007). Univariate analysis revealed that pathological tumor stage, pathological node stage, positive margin, and lymphovascular invasion were significantly correlated with 5-year disease-free survival (DFS) and 5-year overall survival (OS). The patients with >10 dissected lymph nodes showed significantly longer OS (P = 0.045) but not DFS (P = 0.054). HER-2 negative patients had significantly better 5-year DFS (P < 0.001) and 5-year OS (P = 0.013) than those of the HER-2 positive patients. In the subgroup analysis for the early rectal cancer and locally advanced rectal cancer, HER-2 was also a poor predictor for survival. Multivariate analysis revealed that HER-2 was an independent prognostic factor for 5-year DFS (hazard ratio [HR] = 1.919, 95% confidence interval [CI] 1.415–2.605, P < 0.001) and for 5-year OS (HR = 1.549, 95% CI 1.097–2.186, P = 0.013). When the treatment was included in the analysis for locally advanced patients, HER-2 was a prognostic factor for 5-year DFS (P = 0.001) but not for

  14. [Novel techniques in the treatment of rectal cancer].

    PubMed

    Rautio, Tero; Kairaluoma, Matti; Sand, Juhani

    2016-01-01

    Rectal cancer is the eighth and tenth most common kind of cancer in men and women, respectively, with an increasing frequency of occurrence. Together with cancer of the large intestine it forms the third most common cancer entity. Surgical therapy is the most important form of treatment of rectal cancer; in combination with adjuvant therapy it will cure a significant proportion of the patients and provide relief for tumor-induced hemorrhagic and obstructive symptoms. The operation has usually been conducted as an open surgery with the use of simple instruments. In recent times, the operative techniques have become more versatile, and mini-invasive techniques have resulted in quicker recovery of the patients from the operation. PMID:27483632

  15. 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).

  16. Methylene blue injection into the rectal artery as a simple method to improve lymph node harvest in rectal cancer.

    PubMed

    Märkl, Bruno; Kerwel, Therese G; Wagner, Theodor; Anthuber, Matthias; Arnholdt, Hans M

    2007-07-01

    Adequate lymph node assessment in colorectal cancer is crucial for prognosis estimation and further therapy stratification. However, there is still an ongoing debate on required minimum lymph node numbers and the necessity of advanced techniques such as immunohistochemistry or PCR. It has been proven in several studies that lymph node harvest is often inadequate under routine analysis. Lymph nodes smaller than 5 mm are especially concerning as they can carry the majority of metastases. These small, but affected lymph nodes may escape detection in routine analysis. Therefore, fat-clearing protocols and sentinel techniques have been developed to improve accuracy of lymph node staging. We describe a novel and simple method of ex vivo methylene blue injection into the superior rectal artery of rectal cancer specimens, which highlights lymph nodes and makes them easy to detect during manual dissection. Initially, this method was developed for proving accuracy of total mesorectal excision. We performed a retrospective study comparing lymph node recovery of 12 methylene blue stained and an equal number of unstained cases. Lymph node recovery differed significantly with average lymph node numbers of 27+/-7 and 14+/-4 (P<0.001) for the methylene blue and the unstained group, respectively. The largest difference was found in size groups between 1 and 4 mm causing a shift in size distribution toward smaller nodes. Metastases were confirmed in 21 and 19 lymph nodes occurring in five and four cases, respectively. Hence, we conclude that methylene blue injection technique improves accuracy of lymph node staging by heightening the lymph node harvest in rectal resections. In our experience, it is a very simple time and cost effective method that can be easily established under routine circumstances.

  17. 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

  18. The Prognostic Value of Circumferential Resection Margin Involvement in Patients with Extraperitoneal Rectal Cancer.

    PubMed

    Shin, Dong Woo; Shin, Jin Yong; Oh, Sung Jin; Park, Jong Kwon; Yu, Hyeon; Ahn, Min Sung; Bae, Ki Beom; Hong, Kwan Hee; Ji, Yong Il

    2016-04-01

    The prognostic influence of circumferential resection margin (CRM) status in extraperitoneal rectal cancer probably differs from that of intraperitoneal rectal cancer because of its different anatomical and biological behaviors. However, previous reports have not provided the data focused on extraperitoneal rectal cancer. Therefore, the aim of this study was to examine the prognostic significance of the CRM status in patients with extraperitoneal rectal cancer. From January 2005 to December 2008, 248 patients were treated for extraperitoneal rectal cancer and enrolled in a prospectively collected database. Extraperitoneal rectal cancer was defined based on tumors located below the anterior peritoneal reflection, as determined intraoperatively by a surgeon. Cox model was used for multivariate analysis to examine risk factors of recurrence and mortality in the 248 patients, and multivariate logistic regression analysis was performed to identify predictors of recurrence and mortality in 135 patients with T3 rectal cancer. CRM involvement for extraperitoneal rectal cancer was present in 29 (11.7%) of the 248 patients, and was the identified predictor of local recurrence, overall recurrence, and death by multivariate Cox analysis. In the 135 patients with T3 cancer, CRM involvement was found to be associated with higher probability of local recurrence and mortality. In extraperitoneal rectal cancer, CRM involvement is an independent risk factor of recurrence and survival. Based on the results of the present study, it seems that CRM involvement in extraperitoneal rectal cancer is considered an indicator for (neo)adjuvant therapy rather than conventional TN status.

  19. 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.

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

    ClinicalTrials.gov

    2016-01-22

    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

  1. 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

  2. The Expression Level and Prognostic Value of Y-Box Binding Protein-1 in Rectal Cancer

    PubMed Central

    Zhang, Yu; Zhao, Ping-Wu; Feng, Gang; Xie, Gang; Wang, An-Qun; Yang, Yong-Hong; Wang, Dong; Du, Xiao-Bo

    2015-01-01

    The aims of this study were to simultaneously evaluate the expression of Y-box binding protein-1 (YB-1) in non-neoplastic rectal tissue and rectal cancer tissue, and to collect clinical follow-up data for individual patients. Additionally, we aimed to investigate the developmental functions and prognostic value of YB-1 in rectal cancer. We performed immunohistochemical studies to examine YB-1 expression in tissue samples from 80 patients with rectal cancer, 30 patients with rectal tubular adenoma, and 30 patients with rectitis. The mean YB-1 histological scores for rectal cancer, rectal tubular adenoma, and rectitis tissue specimens were 205.5, 164.3, and 137.7, respectively. Shorter disease-free and overall survival times were found in patients with rectal cancer who had higher YB-1 expression than in those with lower expression (38.2 months vs. 52.4 months, P = 0.013; and 44.4 months vs. 57.3 months, P = 0.008, respectively). Our results indicate that YB-1 expression is higher in rectal cancer tissue than in rectal tubular adenoma and rectitis tissue and that it may be an independent prognostic factor for rectal cancer. PMID:25790262

  3. 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?

  4. Ostomies in rectal cancer patients: what is their psychosocial impact?

    PubMed

    Kenderian, S; Stephens, E K; Jatoi, A

    2014-05-01

    The resection of a low-lying rectal cancer can lead to the creation of an ostomy to discharge fecal material. In view of this reconfiguration of anatomy and life-changing modification of daily bodily functions, it is not surprising that a rapidly growing literature has examined ostomy patients' psychosocial challenges. The current study was designed (1) to systematically review the published literature on these psychosocial challenges and (2) to explore, in a single-institution setting, whether medical oncologists appear to acknowledge the existence of an ostomy during their post-operative evaluations of rectal cancer patients. This systematic review identified that social isolation, sleep deprivation; financial concerns; sexual inhibition; and other such issues are common among patients. Surprisingly, however, in our review of 66 consecutive rectal cancer patients, in 17%, the ostomy was not mentioned at all in the medical record during the first medical oncology visit; and, in one patient, it was never mentioned at all during months of adjuvant chemotherapy. Even in the setting of ostomy complications, the ostomy was not always mentioned. This study underscores the major psychosocial issues cancer patients confront after an ostomy and suggests that healthcare providers of all disciplines should work to remain sensitive to such issues.

  5. 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

  6. 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

  7. [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.

  8. HOSPITAL VARIATION IN SPHINCTER PRESERVATION FOR ELDERLY RECTAL CANCER PATIENTS

    PubMed Central

    Dodgion, Christopher M.; Neville, Bridget A; Lipsitz, Stuart R.; Schrag, Deborah; Breen, Elizabeth; Zinner, Michael J.; Greenberg, Caprice C.

    2014-01-01

    Purpose To evaluate hospital variation in the use of low anterior resection (LAR), local excision (LE) and abdominoperineal resection (APR) in the treatment of rectal cancer in elderly patients. Methods Using SEER-Medicare linked data, we identified 4,959 stage I–III rectal cancer patients over age 65 diagnosed from 2000–2005 who underwent operative intervention at one of 370 hospitals. We evaluated the distribution of hospital-specific procedure rates and used generalized mixed models with random hospital effects to examine the influence of patient characteristics and hospital on operation type, using APR as a reference. Results The median hospital performed APR on 33% of elderly rectal cancer patients. Hospital was a stronger predictor of LAR receipt than any patient characteristic, explaining 32% of procedure choice, but not a strong predictor of LE, explaining only 3.8%. Receipt of LE was primarily related to tumor size and tumor stage, which, combined, explained 31% of procedure variation. Conclusions Receipt of local excision is primarily determined by patient characteristics. In contrast, the hospital where surgery is performed significantly influences whether a patient undergoes an LAR or APR. Understanding the factors that cause this institutional variation is crucial to ensuring equitable availability of sphincter preservation. PMID:24750983

  9. Endocavitary irradiation for rectal cancer and villous adenomas

    SciTech Connect

    Kovalic, J.J.

    1988-02-01

    Endocavitary irradiation has been used for rectal adenocarcinoma and villous adenoma at St. Joseph's Hospital, Milwaukee, Wisconsin since 1978. The 52 patients treated since that time include 32 patients with adenocarcinoma, 19 patients with villous adenoma, and 1 patient with an adenomatous polyp and associated atypia. The average age of these patients (70.5 years) was a full decade older than the average age of all rectal cancer patients. The treatment was administered by a superficial contact machine with most patients receiving 80 Gy over four treatments in a period of 1.5 months. The overall local recurrence rate was 24% in the cancer group and 32% in the villous adenoma group. The 1-, 2-, and 3-year determinate disease-free survival rates were 90.4%, 78.6%, 74.2% and 80.4%; 60.3%, 45.2% for invasive adenocarcinoma and villous adenoma patients, respectively. There was no mortality and very little morbidity associated with the treatment. It is concluded that endocavitary irradiation is an effective alternative to surgery for the treatment of rectal cancer in selected cases. However, villous adenomas do not respond as well. Better results may be obtained for this group of patients by higher doses than were used in this study.

  10. 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.

  11. [Indications for radiotherapy of rectal cancer].

    PubMed

    Winkler, R; Franke, H D; Dörner, A

    1990-01-01

    Surgery and radiotherapy complete each other in local control of suffering from rectal carcinoma. A radiotherapeutic effect on tumor is secured often. The adjuvant radiotherapy is the most interesting indication, though the most controversial as present too. Analysing all data and with experiences of an own irradiation study we have not any doubt that the indication is qualified for a combined therapy, if the therapeutic aim with priority is to prevent a local relapse as the most frequent and complained of form of therapeutic failure. In this problem, radical irradiation forms, as pre- and accumulating irradiation (sandwich-technique) and after-irradiation, render superior to an exclusive pre irradiation. In result of this study we practise a preirradiation of 25 Gy with immediately following operation and an accumulating irradiation to 50 Gy in proved high-risk-stage (T greater than or equal to 3 NoMo,Tx N1-3 Mo). If there is a primary local incurability by tumor invasion into the neighbourhood a pre-irradiation is done with 50 Gy and following explorative laparatomy within 4-6 weeks. Nearly 60% of these tumors become operable after that. Likewise we practise in unirradiated patients with locoregional tumor recurrence. Also here the extirpation quota of patients with general or systemic incurability, that a stoma construction is required in, we carry out a transanal tumor reduction and irradiate with 50 Gy after that. Especially this therapeutic principle has proved its worth in patients that are past eighty. Here with acceptable living quality and avoiding a stoma construction a survival can be reached that corresponds to the statistical survival of this stage of life. PMID:2101452

  12. 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

  13. GTI-2040, Oxaliplatin, and Capecitabine in Treating Patients With Locally Advanced or Metastatic Colorectal Cancer or Other Solid Tumors

    ClinicalTrials.gov

    2013-03-26

    Recurrent Colon Cancer; Recurrent 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; Unspecified Adult Solid Tumor, Protocol Specific

  14. 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.

  15. Long-Term Prognostic Significance of Extent of Rectal Cancer Response to Preoperative Radiation and Chemotherapy

    PubMed Central

    Ruo, Leyo; Tickoo, Satish; Klimstra, David S.; Minsky, Bruce D.; Saltz, Leonard; Mazumdar, Madhu; Paty, Philip B.; Wong, W. Douglas; Larson, Steven M.; Cohen, Alfred M.; Guillem, Jose G.

    2002-01-01

    Objective To determine whether selected clinicopathologic factors, including the extent of pathologic response to preoperative radiation and chemotherapy (RT ± chemo), have an impact on long-term recurrence-free survival (RFS) in patients with locally advanced primary rectal cancer after optimal multimodality therapy. Summary Background Data Although complete pathologic response to preoperative RT ± chemo has been detected in up to 30% of rectal cancers, its significance on long-term outcome has not been widely reported. Previous retrospective studies evaluating clinical outcome in patients with complete or near-complete pathologic response documented good prognosis in this population but were limited by median follow-up in the range of 2 to 3 years. Methods Sixty-nine patients with locally advanced (T3–4 and/or N1) primary rectal cancer were prospectively identified. All were treated at one institution with preoperative RT to the pelvis (at least 4,500 cGy). Forty patients received concurrent preoperative 5-fluorouracil-based chemotherapy and 27 received both pre- and postoperative chemotherapy. Patients underwent resection 4 to 7 weeks after completion of RT. TNM stage, angiolymphatic or perineural invasion, and extent of response to preoperative RT ± chemo were determined by pathologic evaluation. Adverse pathologic features were defined as the presence of angiolymphatic and/or perineural invasion. RFS at 5 years was determined by the Kaplan-Meier method. Results With a median follow-up of 69 months, 5-year RFS was 79%. RFS was significantly worse for patients with aggressive pathologic features and positive nodal status identified in the postirradiated surgical specimen. Risk ratios for RFS were 3.68 for the presence of aggressive pathologic features and 4.64 for node-positive rectal cancers. In patients with greater than 95% rectal cancer response to preoperative RT ± chemo, only one patient has died as a consequence of cancer, another has died of an

  16. 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.

  17. 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

  18. Rectal wall sparing by dosimetric effect of rectal balloon used during intensity-modulated radiation therapy (IMRT) for prostate cancer.

    PubMed

    Teh, Bin S; Dong, Lei; McGary, John E; Mai, Wei-Yuan; Grant, Walter; Butler, E Brian

    2005-01-01

    The use of an air-filled rectal balloon has been shown to decrease prostate motion during prostate radiotherapy. However, the perturbation of radiation dose near the air-tissue interfaces has raised clinical concerns of underdosing the prostate gland. The aim of this study was to investigate the dosimetric effects of an air-filled rectal balloon on the rectal wall/mucosa and prostate gland. Clinical rectal toxicity and dose-volume histogram (DVH) were also assessed to evaluate for any correlation. A film phantom was constructed to simulate the 4-cm diameter air cavity created by a rectal balloon. Kodak XV2 films were utilized to measure and compare dose distribution with and without air cavity. To study the effect in a typical clinical situation, the phantom was computed tomography (CT) scanned on a Siemens DR CT scanner for intensity-modulated radiation therapy (IMRT) treatment planning. A target object was drawn on the phantom CT images to simulate the treatment of prostate cancer. Because patients were treated in prone position, the air cavity was situated superiorly to the target. The treatment used a serial tomotherapy technique with the Multivane Intensity Modulating Collimator (MIMiC) in arc treatment mode. Rectal toxicity was assessed in 116 patients treated with IMRT to a mean dose of 76 Gy over 35 fractions (2.17-Gy fraction size). They were treated in the prone position, immobilized using a Vac-Loktrade mark bag and carrier-box system. Rectal balloon inflated with 100 cc of air was used for prostate gland immobilization during daily treatment. Rectal toxicity was assessed using modifications of the Radiation Therapy Oncology Group (RTOG) and late effects Normal Tissue Task Force (LENT) scales systems. DVH of the rectum was also evaluated. From film dosimetry, there was a dose reduction at the distal air-tissue interface as much as 60% compared with the same geometry without the air cavity for 15-MV photon beam and 2x2-cm field size. The dose beyond the

  19. Causes and outcomes of emergency presentation of rectal cancer.

    PubMed

    Comber, Harry; Sharp, Linda; de Camargo Cancela, Marianna; Haase, Trutz; Johnson, Howard; Pratschke, Jonathan

    2016-09-01

    Emergency presentation of rectal cancer carries a relatively poor prognosis, but the roles and interactions of causative factors remain unclear. We describe an innovative statistical approach which distinguishes between direct and indirect effects of a number of contextual, patient and tumour factors on emergency presentation and outcome of rectal cancer. All patients diagnosed with rectal cancer in Ireland 2004-2008 were included. Registry information, linked to hospital discharge data, provided data on patient demographics, comorbidity and health insurance; population density and deprivation of area of residence; tumour type, site, grade and stage; treatment type and optimality; and emergency presentation and hospital caseload. Data were modelled using a structural equation model with a discrete-time survival outcome, allowing us to estimate direct and mediated effects of the above factors on hazard, and their inter-relationships. Two thousand seven hundred and fifty patients were included in the analysis. Around 12% had emergency presentations, which increased hazard by 80%. Affluence, private patient status and being married reduced hazard indirectly by reducing emergency presentation. Older patients had more emergency presentations, while married patients, private patients or those living in less deprived areas had fewer than expected. Patients presenting as an emergency were less likely to receive optimal treatment or to have this in a high caseload hospital. Apart from stage, emergency admission was the strongest determinant of poor survival. The factors contributing to emergency admission in this study are similar to those associated with diagnostic delay. The socio-economic gradient found suggests that patient education and earlier access to endoscopic investigation for public patients could reduce emergency presentation.

  20. New approach to adjuvant radiotherapy in rectal cancer

    SciTech Connect

    Mohiuddin, M.; Dobelbower, R.R.; Kramer, S.

    1980-02-01

    A sandwich technique of adjuvant radiotherapy was used to treat twenty-three patients with rectal cancer. In this technique, low dose preoperative irradiation (500 rad in one treatment) was given to all patients followed by immediate surgery (usually an A-P resection); on the basis of histopathological findings, patients with stage B/sub 2/ and C rectal cancer were selectively given 4500 rad post-operative irradiation in 5 weeks. Nine patients had early lesions (stage A and B/sub 1/) and did not receive postoperative irradiation. Thirteen patients had stage B/sub 2/ and C disease and hence received the full course of postoperative irradiation. One patient was found to have liver metastasis at the time of surgery, and hence received only palliative therapy. Follow-up of these twenty-three patients ranges from 10 months to 24 months with a median follow-up of 15 months. Treatment was well-tolerated with few side effects. Only two of the twenty-two patients who were treated for cure have failed to date. Both patients had stage C/sub 2/ disease; one patient developed an anterior abdominal wall recurrence in the surgical scar 3 months post-treatment and the second patient developed brain and bone metastases. No patients have failed in the pelvis. We feel this technique of adjuvant therapy is a logical approach to the treatment of rectal cancer and has potential for improving survival. The rationale for this approach to adjuvant radiotherapy is discussed together with implications for survival.

  1. Causes and outcomes of emergency presentation of rectal cancer.

    PubMed

    Comber, Harry; Sharp, Linda; de Camargo Cancela, Marianna; Haase, Trutz; Johnson, Howard; Pratschke, Jonathan

    2016-09-01

    Emergency presentation of rectal cancer carries a relatively poor prognosis, but the roles and interactions of causative factors remain unclear. We describe an innovative statistical approach which distinguishes between direct and indirect effects of a number of contextual, patient and tumour factors on emergency presentation and outcome of rectal cancer. All patients diagnosed with rectal cancer in Ireland 2004-2008 were included. Registry information, linked to hospital discharge data, provided data on patient demographics, comorbidity and health insurance; population density and deprivation of area of residence; tumour type, site, grade and stage; treatment type and optimality; and emergency presentation and hospital caseload. Data were modelled using a structural equation model with a discrete-time survival outcome, allowing us to estimate direct and mediated effects of the above factors on hazard, and their inter-relationships. Two thousand seven hundred and fifty patients were included in the analysis. Around 12% had emergency presentations, which increased hazard by 80%. Affluence, private patient status and being married reduced hazard indirectly by reducing emergency presentation. Older patients had more emergency presentations, while married patients, private patients or those living in less deprived areas had fewer than expected. Patients presenting as an emergency were less likely to receive optimal treatment or to have this in a high caseload hospital. Apart from stage, emergency admission was the strongest determinant of poor survival. The factors contributing to emergency admission in this study are similar to those associated with diagnostic delay. The socio-economic gradient found suggests that patient education and earlier access to endoscopic investigation for public patients could reduce emergency presentation. PMID:27087482

  2. Clarifying margins in the multidisciplinary management of rectal cancer: the MERCURY experience.

    PubMed

    Salerno, G; Daniels, I R; Moran, B J; Wotherspoon, A; Brown, G

    2006-11-01

    The Magnetic Resonance Imaging and Rectal Cancer European Equivalence Study (MERCURY) was an observational prospective study involving 11 European centres, to evaluate equivalence between magnetic resonance imaging and histopathology in measuring depth of tumour invasion beyond the bowel and involvement of the circumferential resection margin in rectal cancer specimens. PMID:17018303

  3. YpT1-2N0 rectal cancer after neoadjuvant chemoradiation has lower survival compared with pT1-2N0 rectal cancer

    PubMed Central

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

    2015-01-01

    Pathologic T1-2N0 rectal cancer shows an excellent prognosis without preoperative or postoperative chemoradiation. However, oncologic outcome of ypT1-2N0 remains unclear and undetermined. Thus, the aim of this study was to compare the survival of ypT1-2 and pT1-2 rectal cancer patients after radical resection and identify risk factors of ypT1-2 rectal cancer in Surveillance, Epidemiology, and End Results Program (SEER)-registered rectal cancer patients. The results showed that ypT1-2N0 rectal cancer after neoadjuvant chemoradiation has lower survival compared with pT1-2N0 rectal cancer and mucinous/signet-ring cancer and less than 12 lymph nodes retrieval were two risk factors in ypT1-2 patients. These results suggest that ypT1-2 patients with one or two risk factors may benefit from postoperative adjuvant chemotherapy. PMID:26517674

  4. 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

  5. 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

  6. Lymphangiogenesis in Regional Lymph Nodes Is an Independent Prognostic Marker in Rectal Cancer Patients after Neoadjuvant Treatment

    PubMed Central

    Jakob, Christiane; Aust, Daniela E.; Liebscher, Birgit; Baretton, Gustavo B.; Datta, Kaustubh; Muders, Michael H.

    2011-01-01

    One of the major prognostic factors in rectal cancer is lymph node metastasis. The formation of lymph node metastases is dependent on the existence of a premetastatic niche. An important factor preceding metastasis are lymph vessels which are located in the lymph node. Accordingly, the occurrence of intranodal lymphangiogenesis is thought to indicate distant metastasis and worse prognosis. To evaluate the significance of lymph node lymphangiogenesis, we studied formalin fixed, paraffin embedded adenocarcinomas and regional lymph nodes of 203 rectal cancer patients who were treated with neoadjuvant radiochemotherapy and consecutive curative surgery with cancer free surgical margins (R0). Regional lymph node lymph vessels were detected by immunohistochemistry for podoplanin (D2-40). Our results show that the presence of lymphatic vessels in regional lymph nodes significantly affects the disease-free survival in univariate and multivariate analyses. In contrast, there was no correlation between peritumoral or intratumoral lymph vessel density and prognosis. Indeed, our study demonstrates the importance of lymphangiogenesis in regional lymph nodes after neoadjuvant radiochemotherapy and consecutive surgery as an independent prognostic marker. Staining for intranodal lymphangiogenesis and methods of intravital imaging of lymphangiogenesis and lymphatic flow may be a useful strategy to predict long-term outcome in rectal cancer patients. Furthermore, addition of VEGF-blocking agents to standardized neoadjuvant treatment schemes might be indicated in advanced rectal cancer. PMID:22087309

  7. Re-Staging Following Long-Course Chemoradiotherapy For Rectal Cancer: Does It Influence Management?

    PubMed Central

    McCallion, K; Moorehead, RJ; McAllister, I; Mulholland, K; Gilliland, R; Campbell, WJ

    2016-01-01

    Background 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. Methods 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. Results 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

  8. Re-Staging Following Long-Course Chemoradiotherapy For Rectal Cancer: Does It Influence Management?

    PubMed Central

    McCallion, K; Moorehead, RJ; McAllister, I; Mulholland, K; Gilliland, R; Campbell, WJ

    2016-01-01

    Background 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. Methods 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. Results 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

  9. Preoperative infusional chemoradiation therapy for stage T3 rectal cancer

    SciTech Connect

    Rich, T.A.; Skibber, J.M.; Ajani, J.A.

    1995-07-15

    To evaluate preoperative infusional chemoradiation for patients with operable rectal cancer. Preoperative chemoradiation therapy using infusional 5-fluorouracil (5-FU), (300 mg/m{sup 2}/day) together with daily irradiation (45 Gy/25 fractions/5 weeks) was administered to 77 patients with clinically Stage T3 rectal cancer. Endoscopic ultrasound confirmed the digital rectal exam in 63 patients. Surgery was performed approximately 6 weeks after the completion of chemoradiation therapy and included 25 abdominoperineal resections and 52 anal-sphincter-preserving procedures. Posttreatment tumor stages were T1-2, N0 in 35%, T3, N0 in 25%, and T1-3, N1 in 11%; 29% had no evidence of tumor. Local tumor control after chemoradiation was seen in 96% (74 out of 77); 2 patients had recurrent disease at the anastomosis site and were treated successfully with abdominoperineal resection. Overall, pelvic control was obtained in 99% (76 out of 77). The survival after chemoradiation was higher in patients without node involvement than in those having node involvement (p = n.s.). More patients with pathologic complete responses or only microscopic foci survived than did patients who had gross residual tumor (p = 0.07). The actuarial survival rate was 83% at 3 years; the median follow-up was 27 months, with a range of 3 to 68 months. Acute, perioperative, and late complications were not more numerous or more severe with chemoradiation therapy than with traditional radiation therapy (XRT) alone. Excellent treatment response allowed two-thirds of the patients to have an anal-sphincter-sparing procedure. Gross residual disease in the resected specimen indicates a poor prognosis, and therapies specifically targeting these patients may improve survival further. 22 refs., 2 figs., 3 tabs.

  10. Pre-operative Neutrophils/Lymphocyte Ratio in Rectal Cancer Patients with Preoperative Chemoradiotherapy

    PubMed Central

    Lino-Silva, Leonardo S.; Salcedo-Hernández, Rosa A.; Ruiz-García, Erika B.; García-Pérez, Leticia; Herrera-Gómez, Ángel

    2016-01-01

    Background: Several studies have reported that an elevation in neutrophils/lymphocyte ratio (NLR) is correlated with poor survival in patients with colorectal cancer, but in rectal cancer (RC), it has been reported only in a few studies. It is necessary to separate colon cancer and rectal cancer to clarify the prognostic significance of NLR, especially in patients who received chemoradiotherapy. Methods: It is a comparative, observational retrospective study of a cohort of 175 patients. We grouped the patients into two based on their NLR (0-3 vs. > 3) to correlate with disease-specific survival (DSS) and pathologic complete response (pCR). Results: The average NLR was 2.65 + 1.32 (range 0.58-6.89), and 144 (82.3%) patients had an NLR of 0-3. The median follow-up was 33.53 months. There were no differences in pCR between the two groups. The 5-year DSS was 78.8%. NLR did not correlate with survival. Mesorectal quality, pT3-4 tumors, lymph node metastasis, lymphovascular invasion, perineural invasion, positive margins and recurrence were statistically significant predictors of increased mortality in univariate analysis. In multivariate analysis, only overall recurrence correlated with poor survival. The analysis of the association of NLR with outcomes with different cut points (2.0, 2.5, 4 and 5) did not show differences in DSS and pCR. Conclusion: In our cohort, the NLR did not serve as a prognostic marker in patients with locally advanced rectal cancer and who received chemoradiotherapy and did not correlate with pCR as well. PMID:27703284

  11. Intra-tumor Genetic Heterogeneity in Rectal Cancer

    PubMed Central

    Hardiman, Karin M.; Ulintz, Peter J.; Kuick, Rork; Hovelson, Daniel H.; Gates, Christopher M.; Bhasi, Ashwini; Grant, Ana Rodrigues; Liu, Jianhua; Cani, Andi K.; Greenson, Joel; Tomlins, Scott; Fearon, Eric R.

    2015-01-01

    Colorectal cancer arises in part from the cumulative effects of multiple gene lesions. Recent studies in selected cancer types have revealed significant intra-tumor genetic heterogeneity and highlighted its potential role in disease progression and resistance to therapy. We hypothesized the existence of significant intra-tumor genetic heterogeneity in rectal cancers involving variations in localized somatic mutations and copy number abnormalities. Two or three spatially disparate regions from each of six rectal tumors were dissected and subjected to next-generation whole exome DNA sequencing, Oncoscan SNP arrays, and targeted confirmatory sequencing and analysis. The resulting data were integrated to define subclones using SciClone. Mutant-allele tumor heterogeneity (MATH) scores, mutant allele frequency correlation, and mutation percent concordance were calculated, and copy number analysis including measurement of correlation between samples was performed. Somatic mutations profiles in individual cancers were similar to prior studies, with some variants found in previously reported significantly mutated genes and many patient-specific mutations in each tumor. Significant intra-tumor heterogeneity was identified in the spatially disparate regions of individual cancers. All tumors had some heterogeneity but the degree of heterogeneity was quite variable in the samples studied. We found that 67–97% of exonic somatic mutations were shared among all regions of an individual’s tumor. The SciClone computational method identified 2 to 8 shared and unshared subclones in the spatially disparate areas in each tumor. MATH scores ranged from 7 to 41. Allele frequency correlation scores ranged from R2 = 0.69 to 0.96. Measurements of correlation between samples for copy number changes varied from R2 = 0.74 to 0.93. All tumors had some heterogeneity, but the degree was highly variable in the samples studied. The occurrence of significant intra-tumor heterogeneity may allow

  12. Robotic Versus Laparoscopic Resection for Mid and Low Rectal Cancers

    PubMed Central

    Salman, Bulent; Yuksel, Osman

    2016-01-01

    Background and Objectives: The current study was conducted to determine whether robotic low anterior resection (RLAR) has real benefit over laparoscopic low anterior resection (LLAR) in terms of surgical and early oncologic outcomes. Methods: We retrospectively analyzed data from 35 RLARs and 28 LLARs, performed for mid and low rectal cancers, from January 2013 through June 2015. Results: A total of 63 patients were included in the study. All surgeries were performed successfully. The clinicopathologic characteristics were similar between the 2 groups. Compared with the laparoscopic group, the robotic group had less intraoperative blood loss (165 vs. 120 mL; P < .05) and higher mean operative time (252 vs. 208 min; P < .05). No significant differences were observed in the time to flatus passage, length of hospital stay, and postoperative morbidity. Pathological examination of total mesorectal excision (TME) specimens showed that both circumferential resection margin and transverse (proximal and distal) margins were negative in the RLAR group. However, 1 patient each had positive circumferential resection margin and positive distal transverse margin in the LLAR group. The mean number of harvested lymph nodes was 27 in the RLAR group and 23 in the LLAR group. Conclusions: In our study, short-term outcomes of robotic surgery for mid and low rectal cancers were similar to those of laparoscopic surgery. The quality of TME specimens was better in the patients who underwent robotic surgery. However, the longer operative time was a limitation of robotic surgery. PMID:27081292

  13. 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

  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. High-dose-rate pre-operative endorectal brachytherapy for patients with rectal cancer

    PubMed Central

    Devic, Slobodan

    2015-01-01

    High-dose-rate endorectal brachytherapy (HDREBT) is an image guided brachytherapy treatment for patients with rectal cancer. It is based on tumor imaging with magnetic resonance in particular, which is used to choose eligible patients and improve tumor visualization. Treatment planning is performed using 3D CT simulation and treatment planning. The treatment is given on an outpatient basis and requires minimal local anesthesia. The validation of the technique was carried out through a preoperative study and is now explored as part of a radical treatment for early rectal cancer or as a boost modality. We describe technical aspects of the HDREBT and we discuss the ongoing institutional review board approved studies exploring the clinical applications of this treatment modality for patients with rectal cancer: 1) as a neoadjuvant treatment for patients with operable rectal tumor; 2) as a option to improve local control in patients with newly diagnosed rectal cancer but with previous pelvic radiation. PMID:26034500

  16. 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

  17. 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.

  18. Prognosis Can Be Predicted More Accurately Using Pre- and Postchemoradiotherapy Carcinoembryonic Antigen Levels Compared to Only Prechemoradiotherapy Carcinoembryonic Antigen Level in Locally Advanced Rectal Cancer Patients Who Received Neoadjuvant Chemoradiotherapy

    PubMed Central

    Sung, SooYoon; Son, Seok Hyun; Kay, Chul Seung; Lee, Yoon Suk

    2016-01-01

    Abstract We aimed to evaluate the prognostic value of a change in the carcinoembryonic antigen (CEA) level during neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer. A total of 110 patients with clinical T3/T4 or node-positive disease underwent nCRT and curative total mesorectal resection from February 2006 to December 2013. Serum CEA level was measured before nCRT, after nCRT, and then again after surgery. A cut-off value for CEA level to predict prognosis was determined using the maximally selected log-rank test. According to the test, patients were classified into 3 groups, based on their CEA levels (Group A: pre-CRT CEA ≤3.2; Group B: pre-CRT CEA level >3.2 and post-CRT CEA ≤2.8; and Group C: pre-CRT CEA >3.2 and post-CRT CEA >2.8). The median follow-up time was 31.1 months. The 3-year disease-free survival (DFS) rates of Group A and Group B were similar, while Group C showed a significantly lower 3-year DFS rate (82.5% vs. 89.5% vs. 55.1%, respectively, P = 0.001). Other clinicopathological factors that showed statistical significance on univariate analysis were pre-CRT CEA, post-CRT CEA, tumor distance from the anal verge, surgery type, downstage, pathologic N stage, margin status and perineural invasion. The CEA group (P = 0.001) and tumor distance from the anal verge (P = 0.044) were significant prognostic factors for DFS on multivariate analysis. Post-CRT CEA level may be a useful prognostic factor in patients whose prognosis cannot be predicted exactly by pre-CRT CEA levels alone in the neoadjuvant treatment era. Combined pre-CRT CEA and post-CRT CEA levels enable us to predict prognosis more accurately and determine treatment and follow-up policies. Further large-scale studies are necessary to validate the prognostic value of CEA levels. PMID:26962798

  19. 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

  20. Ropidoxuridine in Treating Patients With Advanced Gastrointestinal Cancer Undergoing Radiation Therapy

    ClinicalTrials.gov

    2016-06-17

    Bile Duct Carcinoma; Stage III Pancreatic Cancer; Stage IIIA Colon Cancer; Stage IIIA Gastric Cancer; Stage IIIA Rectal Cancer; Stage IIIA Small Intestinal Cancer; Stage IIIB Colon Cancer; Stage IIIB Gastric Cancer; Stage IIIB Rectal Cancer; Stage IIIB Small Intestinal Cancer; Stage IIIC Colon Cancer; Stage IIIC Gastric Cancer; Stage IIIC Rectal Cancer; Stage IV Gastric Cancer; Stage IV Pancreatic Cancer; Stage IV Small Intestinal Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

  1. Predictors of pathologic complete response after preoperative concurrent chemoradiotherapy of rectal cancer: a single center experience

    PubMed Central

    Choi, Euncheol; Kim, Jin Hee; Kim, Ok Bae; Kim, Mi Young; Oh, Young Ki; Baek, Sung Gyu

    2016-01-01

    Purpose: To identify possible predictors of pathologic complete response (pCR) of rectal cancer after preoperative concurrent chemoradiotherapy (CCRT). Materials and Methods: We conducted a retrospective review of 53 patients with rectal cancer who underwent preoperative CCRT followed by radical surgery at a single center between January 2007 and December 2012. The median radiotherapy dose to the pelvis was 54.0 Gy (range, 45.0 to 63.0 Gy). Five-fluorouracil-based chemotherapy was administered via continuous infusion with leucovorin. Results: The pCR rate was 20.8%. The downstaging rate was 66%. In univariate analyses, poor and undifferentiated tumors (p = 0.020) and an interval of ≥7 weeks from finishing CCRT to surgery (p = 0.040) were significantly associated with pCR, while female gender (p = 0.070), initial carcinoembryonic antigen concentration of <5.0 ng/dL (p = 0.100), and clinical stage T2 (p = 0.100) were marginally significant factors. In multivariate analysis, an interval of ≥7 weeks from finishing CCRT to surgery (odds ratio, 0.139; 95% confidence interval, 0.022 to 0.877; p = 0.036) was significantly associated with pCR, while stage T2 (odds ratio, 5.363; 95% confidence interval, 0.963 to 29.877; p = 0.055) was a marginally significant risk factor. Conclusion: We suggest that the interval from finishing CCRT to surgery is a predictor of pCR after preoperative CCRT in patients with rectal cancer. Stage T2 cancer may also be an important predictive factor. We hope to perform a robust study by collecting data during treatment to obtain more advanced results. PMID:27306776

  2. Total mesorectal excision for the treatment of rectal cancer

    PubMed Central

    Zedan, Ali; Salah, Tareq

    2015-01-01

    Introduction In the surgical treatment of rectal cancer, a clear circumferential resection margin and distal resection margin should be obtained. The aim of this study was to determine the morbidity, mortality, survival outcome, and local failure after total mesorectal excision (TME) in the surgical treatment of rectal cancer. Methods This retrospective study was conducted on 101 patients treated for rectal cancer using low anterior resection (LAR), abdominoperinial resection (APR), or Hartmaan’s technique. In all operative procedures, total mesorectal excisions (TMEs) were done. The patients were treated from November 2000 to April 2011 in the South Egypt Cancer Institute (SECI) of Assuit University (Egypt). Neo-adjuvant therapy was given to those patients with serosalin filtration, lymph node involvement, and sexual and urinary function impairment. Data were analyzed using IBM-SPSS version 21, and survival rates were estimated using the Kaplan-Meier method. Results One hundred one patients were evaluable (61 males, 40 females). Regarding the operative procedure used, it was: (APR), LAR, Hartmaan’s technique in 15.8%, 71.3%, and 12.9% of patients, respectively. Operation-related mortality during the 30 days after surgery was 3%. The operations resulted in morbidity in 25% of the patients, anastomotic site leak in 5.9% of the patients, urinary dysfynction in 9.9% of the patients, and erectile dysfunction in 15.8% of the male patients. Regarding safety margin, the median distances were distal/radial margin, 23/12 mm, distal limit 7 cm. Median lymph nodes harvest 19 nodes. Primary tumor locations were anteriorly 23.8%, laterally 13.9%, posteriorly 38.6%, and circumferential 23.8%. Protective stoma 16.8%. Primary Tumor TNM classification (T1, T2, T3, and T4; 3, 28.7, 55.4, and 12.9%, respectively). Nodes Metastases (N0, N1, and N2; 57.4, 31.7, and 10.9%, respectively). TNM staging (I, II, III, and IV; 15.8, 29.7, 46.5, and 7.9%, respectively). Chemotherapy was

  3. 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.

  4. 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).

  5. 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

  6. 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.

  7. [A Patient with Recurrent Ulcerative Colitis-Associated Rectal Cancer Attaining a Complete Response with FOLFIRI plus Bevacizumab].

    PubMed

    Iseki, Yasuhito; Maeda, Kiyoshi; Shibutani, Masatsune; Nagahara, Hisashi; Ikeya, Tetsuro; Tamura, Tatsuro; Ohira, Go; Sakurai, Katsunobu; Yamazoe, Sadaaki; Kimura, Kenjiro; Toyokawa, Takahiro; Kubo, Naoshi; Tanaka, Hiroaki; Muguruma, Kazuya; Hirakawa, Kosei

    2015-11-01

    A 60-year-old man underwent laparoscopic total proctocolectomy with ileostomy for advanced ulcerative colitis-associated rectal cancer. The final diagnosis was advanced cancer pT3, pN2 and M0 (pStage Ⅲb). Adjuvant therapy with XELOX was performed. However, abdominal CT revealed a liver metastasis and lymph node metastases in the pelvis 6 months after surgery. The patient was treated with FOLFIRI plus bevacizumab. After 20 courses of chemotherapy, the patient was considered to have experienced a clinical CR, which has been maintained for 3 years 5 months. PMID:26805312

  8. [A Patient with Recurrent Ulcerative Colitis-Associated Rectal Cancer Attaining a Complete Response with FOLFIRI plus Bevacizumab].

    PubMed

    Iseki, Yasuhito; Maeda, Kiyoshi; Shibutani, Masatsune; Nagahara, Hisashi; Ikeya, Tetsuro; Tamura, Tatsuro; Ohira, Go; Sakurai, Katsunobu; Yamazoe, Sadaaki; Kimura, Kenjiro; Toyokawa, Takahiro; Kubo, Naoshi; Tanaka, Hiroaki; Muguruma, Kazuya; Hirakawa, Kosei

    2015-11-01

    A 60-year-old man underwent laparoscopic total proctocolectomy with ileostomy for advanced ulcerative colitis-associated rectal cancer. The final diagnosis was advanced cancer pT3, pN2 and M0 (pStage Ⅲb). Adjuvant therapy with XELOX was performed. However, abdominal CT revealed a liver metastasis and lymph node metastases in the pelvis 6 months after surgery. The patient was treated with FOLFIRI plus bevacizumab. After 20 courses of chemotherapy, the patient was considered to have experienced a clinical CR, which has been maintained for 3 years 5 months.

  9. [Research hotspot and progress of preoperative chemoradiotherapy for rectal cancer].

    PubMed

    Peng, Jianhong; Pan, Zhizhong

    2016-06-01

    Preoperative chemoradiotherapy (CRT) has become an important component of comprehensive treatment for rectal cancer. Although local recurrent risk has been remarkably reduced by CRT, distant metastasis remains the main cause of therapeutic failure. Therefore, more and more studies focused on controlling distant metastasis in order to prolong long-term survival. Recently, CRT has achieved certain progression in rectal cancer: (1)Patients with stage T3 should be classified into specific subgroups to formulate individualized treatment regimen. For stage T3a, it is feasible to perform surgery alone or administrate low intensity preoperative CRT; for stage T3b and T3c, conventional preoperative CRT should be performed in order to reduce the risk of recurrence postoperatively. (2)With regard to combined regimen for chemotherapy, oral capecitabine superiors to intravenous bolus 5-fluorouracil (5-FU) and is comparable to continuous intravenous infusion 5-FU with a better safety. Therefore, capecitabine is recommended for older patients and those with poor tolerance to chemotherapy. Compared to single 5-FU concurrent CRT, addition of oxaliplatin into preoperative CRT may result in a higher survival benefit in Chinese patients. As to the application of irinotecan, bevacizumab or cetuximab, unless there are more evidence to confirm their efficacy and safety from randomized controlled trial, they should not be recommended for adding to preoperative CRT routinely. (3)On the optimization in CRT pattern, the application values of induction chemotherapy before concurrent CRT, consolidation chemotherapy after concurrent CRT, neoadjuvant sandwich CRT, neoadjuvant chemotherapy alone and short-course preoperative radiotherapy remain further exploration. (4)On the treatment strategy for clinical complete response (cCR) after CRT, whether "wait and see" strategy is able to be adopted, it is still a hot topic with controversy. PMID:27353093

  10. Late rectal complications after prostate brachytherapy for localized prostate cancer: incidence and management.

    PubMed

    Phan, Jack; Swanson, David A; Levy, Lawrence B; Kudchadker, Rajat J; Bruno, Teresa L; Frank, Steven J

    2009-05-01

    This review of the literature on late rectal complications after prostate brachytherapy indicated that it is a highly effective treatment modality for patients with clinically localized prostate cancer but can cause chronic radiation proctitis. The most common manifestation of chronic radiation proctitis was anterior rectal wall bleeding, which often occurred within the first 2 years after brachytherapy. It is interesting to note that the rates of late rectal morbidity appear to have declined over time, which may reflect improvements in implantation techniques and imaging. Rectal biopsy as part of the workup to evaluate rectal bleeding can lead to rectal fistula and the need for colostomy, a rare but major complication. The authors recommend 1) screening colonoscopy before brachytherapy for patients who have not had a screening colonoscopy within the preceding 3 years to rule out colorectal malignancies and, thus, facilitate conservative management should rectal bleeding occur; 2) lifestyle modifications during treatment to limit exposure of the rectum to radiation; and 3) conservative management for rectal bleeding that occurs within 2 years after brachytherapy. Cancer 2009. (c) 2009 American Cancer Society.

  11. Rectal cancer staging: Multidetector-row computed tomography diagnostic accuracy in assessment of mesorectal fascia invasion

    PubMed Central

    Ippolito, Davide; Drago, Silvia Girolama; Franzesi, Cammillo Talei; Fior, Davide; Sironi, Sandro

    2016-01-01

    , as compared to the reference magnetic resonance images. The difference in accuracy was statistically significant (P = 0.02). CONCLUSION: 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. PMID:27239115

  12. [Conversion Therapy of Initially Unresectable Rectal Cancer with Perforation via FOLFOX4 Chemotherapy].

    PubMed

    Yamada, Chizu; Ishikawa, Fumihiko; Nitta, Hiroshi; Fujita, Yoshihisa; Omoto, Hideyuki; Kamata, Shigeyuki; Ito, Hiroshi

    2015-11-01

    We describe a case of perforated rectal cancer that became curatively resectable after FOLFOX4 chemotherapy. An 81- year-old woman was transferred to our hospital with a diagnosis of bowel perforation. She underwent emergency transverse colostomy, peritoneal lavage, and the insertion of indwelling drainage tubes, because the perforated rectal cancer was considered unresectable. After recuperation, she received chemotherapy consisting of FOLFOX4 and bevacizumab. Owing to a good response to the treatment after 4 months, rectal resection was achieved curatively. Wound dehiscence occurred as a postoperative complication. The patient chose not to receive adjuvant chemotherapy. Currently, she has been alive for more than 1 year 3 months after resection without recurrence.

  13. The outcomes of therapeutic decision in lower 3rd rectal cancer patients.

    PubMed

    Chen, Chien-Hsin; Wei, Po-Li; Hsieh, Mao-Chih; Lin, En-Kwang; Chiou, Jeng-Fong; Lu, Yen-Jung; Wu, Szu-Yuan

    2016-09-01

    To investigate the outcomes of the selective neoadjuvant concurrent chemoradiotherapy (CCRT) in lower 3rd rectal cancer patients in different groups (with or without neoadjuvant CCRT), especially in survival rate, local recurrence rate, and sphincter preservation rate.From January 1999 to December 2012, 69 consecutive patients who had histologically proven adenocarcinoma of lower 3rd rectum, defined preoperatively as lower tumor margin within 7 cm from the anal verge as measured by rigid sigmoidoscopy, received total mesorectum excision (TME). Our inclusion criteria of neoadjuvant CCRT are lower 3rd rectal cancer, stage II/III, and large (diameter >5 cm or >1/2 of circumference). Neoadjuvant concurrent CCRT had begun to apply lower 3rd rectal cancer patients or not. The radiation techniques of neoadjuvant CCRT for lower 3rd rectal cancer patients were all conventional fraction intensity modulated radiotherapy (IMRT) and concurrent fluoropyrimidine chemotherapy.Five-year overall survival rate, disease-free survival rate, and local recurrence rate for lower 3rd rectal cancer patients in group I were 51%, 45%, and 25%, respectively. On the contrary, 5-year overall survival rate, disease-free survival rate, and local recurrence rate for lower rectal cancer patients in group II were 70%, 70%, and 3%, respectively. The 5-year sphincter sparing rate was increased from 38.2% to 100% after the beginning of neoadjuvant CCRT. Analyzing local recurrence, overall survival rate, disease-specific survival rate, and sphincter sparing rate in group II were statistically significant superior to group I.Five-year overall survival rate, disease-free survival rate, and sphincter sparing rate for lower 3rd rectal cancer patients were improved after the addition of neoadjuvant CCRT. No unacceptable toxicity was noted after conventional fraction IMRT and concurrent fluoropyrimidine chemotherapy. Our study showed neoadjuvant CCRT could be valuable for lower 3rd rectal cancer patients

  14. A Prospective Pathologic Analysis Using Whole-Mount Sections of Rectal Cancer Following Preoperative Combined Modality Therapy

    PubMed Central

    Guillem, Jose G.; Chessin, David B.; Shia, Jinru; Suriawinata, Arief; Riedel, Elyn; Moore, Harvey G.; Minsky, Bruce D.; Wong, W Douglas

    2007-01-01

    Objective: The aims of this study were to use a comprehensive whole-mount pathologic analysis to characterize microscopic patterns of residual disease, as well as circumferential and distal resection margins, in rectal cancer treated with preoperative CMT; and to identify clinicopathologic factors associated with residual disease. Summary Background Data: Recent studies have shown that preoperative combined modality therapy (CMT) for rectal cancer enhances rates of sphincter preservation. However, the efficacy of preoperative CMT in conjunction with a total mesorectal excision (TME)-based resection, in terms of resection margins using whole-mount sections, has not been reported. Furthermore, since patterns of residual disease and extent of distal spread following preoperative CMT are largely unknown, intraoperative determination of distal rectal transection remains a surgical challenge. Methods: We prospectively accrued 109 patients with endorectal ultrasound (ERUS)-staged, locally advanced rectal cancer (T2–T4 and/or N1), located a median distance of 7 cm from the anal verge, requiring preoperative CMT, and undergoing a TME-based resection. Comprehensive whole-mount pathologic analysis was performed, with particular emphasis on extent of residual disease, margin status, and intramural tumor extension. Clinicopathologic factors associated with residual disease were identified. Results: A sphincter-preserving resection was feasible in 87 patients (80%), and in all 109 patients, distal margins were negative (median, 2.1 cm; range, 0.4–10 cm). Intramural extension beyond the gross mucosal edge of residual tumor was observed in only 2 patients (1.8%), both ≤0.95 cm. There were no positive circumferential margins (median, 10 mm; range, 1–28 mm), although 6 were less than or equal to 1 mm. On multivariate analysis, residual disease was observed more frequently in distally located tumors (distance from anal verge <5 cm) (P = 0.03). Conclusion: Our comprehensive

  15. 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.

  16. Proteogenomic characterization of human colon and rectal cancer

    PubMed Central

    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.

    2014-01-01

    Summary We analyzed proteomes of colon and rectal tumors previously characterized by the Cancer Genome Atlas (TCGA) and performed integrated proteogenomic analyses. Somatic variants displayed reduced protein abundance compared to germline variants. mRNA transcript abundance did not reliably predict protein abundance differences between tumors. Proteomics identified five proteomic subtypes in the TCGA cohort, two of which overlapped with the TCGA “MSI/CIMP” 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, TOMM34 and SRC. Integrated proteogenomic analysis provides functional context to interpret genomic abnormalities and affords a new paradigm for understanding cancer biology. PMID:25043054

  17. 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 all pelvic dimensions defined as deep and narrow pelvis, while PCRT was related to higher rate of permanent stoma in shorter transverse diameter and interspinous distance. On logistic regression analysis, PCRT was not shown to influence both sphincter preservation and permanent stoma, while longer transverse diameter and interspinous distance were associated with lower rate of permanent stoma. PCRT had

  18. Variation in the CYP19A1 gene and risk of colon and rectal cancer

    PubMed Central

    Slattery, Martha L.; Lundgreen, Abbie; Herrick, Jennifer S.; Kadlubar, Susan; Caan, Bette J.; Potter, John D.; Wolff, Roger K.

    2011-01-01

    CYP19A1, or aromatase, influences estrogen-metabolizing enzymes and may influence cancer risk. We examine variation in the CYP19A1 gene and risk of colorectal cancer using data from population-based case–control studies (colon n = 1,574 cases, 1,970 controls; rectal n = 791 cases, 999 controls). Four SNPs were statistically significantly associated with colon cancer and four were associated with rectal cancer. After adjustment for multiple comparisons, the AA genotype of rs12591359 was associated with an increased risk of colon cancer (OR 1.44 95% CI 1.16–1.80) and the AA genotype of rs2470144 was associated with a reduced risk of rectal cancer (OR 0.65 95% CI 0.50–0.84). Variants of CYP19A1 were associated with CIMP+ and CIMP+/KRAS2-mutated tumors. CT/TT genotypes of rs1961177 were significantly associated with an increased likelihood of a MSI+ colon tumor (OR 1.77 95% CI 1.26–2.37). We observed statistically significant interactions between genetic variation in NFκB1 and CYP19A1 for both colon and rectal cancer. Our data suggest the importance of CYP19A1 in the development of colon and rectal cancer and that estrogen may influence risk through an inflammation-related mechanism. PMID:21479914

  19. Intratumoral Heterogeneity of MicroRNA Expression in Rectal Cancer

    PubMed Central

    Andersen, Rikke Fredslund; Nielsen, Boye Schnack; Sørensen, Flemming Brandt; Appelt, Ane Lindegaard; Jakobsen, Anders; Hansen, Torben Frøstrup

    2016-01-01

    Introduction An increasing number of studies have investigated microRNAs (miRNAs) as potential markers of diagnosis, treatment and prognosis. So far, agreement between studies has been minimal, which may in part be explained by intratumoral heterogeneity of miRNA expression. The aim of the present study was to assess the heterogeneity of a panel of selected miRNAs in rectal cancer, using two different technical approaches. Materials and Methods The expression of the investigated miRNAs was analysed by real-time quantitative polymerase chain reaction (RT-qPCR) and in situ hybridization (ISH) in tumour specimens from 27 patients with T3-4 rectal cancer. From each tumour, tissue from three different luminal localisations was examined. Inter- and intra-patient variability was assessed by calculating intraclass correlation coefficients (ICCs). Correlations between RT-qPCR and ISH were evaluated using Spearman’s correlation. Results ICCsingle (one sample from each patient) was higher than 50% for miRNA-21 and miRNA-31. For miRNA-125b, miRNA-145, and miRNA-630, ICCsingle was lower than 50%. The ICCmean (mean of three samples from each patient) was higher than 50% for miRNA-21(RT-qPCR and ISH), miRNA-125b (RT-qPCR and ISH), miRNA-145 (ISH), miRNA-630 (RT-qPCR), and miRNA-31 (RT-qPCR). For miRNA-145 (RT-qPCR) and miRNA-630 (ISH), ICCmean was lower than 50%. Spearman correlation coefficients, comparing results obtained by RT-qPCR and ISH, respectively, ranged from 0.084 to 0.325 for the mean value from each patient, and from -0.085 to 0.515 in the section including the deepest part of the tumour. Conclusion Intratumoral heterogeneity may influence the measurement of miRNA expression and consequently the number of samples needed for representative estimates. Our findings with two different methods suggest that one sample is sufficient for adequate assessment of miRNA-21 and miRNA-31, whereas more samples would improve the assessment of miRNA-125b, miRNA-145, and miRNA-630

  20. Preoperative Therapy for Lower Rectal Cancer and Modifications in Distance From Anal Sphincter

    SciTech Connect

    Gavioli, Margherita Losi, Lorena; Luppi, Gabriele; Iacchetta, Francesco; Zironi, Sandra; Bertolini, Federica; Falchi, Anna Maria; Bertoni, Filippo; Natalini, Gianni

    2007-10-01

    Purpose: To assess the frequency and magnitude of changes in lower rectal cancer resulting from preoperative therapy and its impact on sphincter-saving surgery. Preoperative therapy can increase the rate of preserving surgery by shrinking the tumor and enhancing its distance from the anal sphincter. However, reliable data concerning these modifications are not yet available in published reports. Methods and Materials: A total of 98 cases of locally advanced cancer of the lower rectum (90 Stage uT3-T4N0-N+ and 8 uT2N+M0) that had undergone preoperative therapy were studied by endorectal ultrasonography. The maximal size of the tumor and its distance from the anal sphincter were measured in millimeters before and after preoperative therapy. Surgery was performed 6-8 weeks after therapy, and the histopathologic margins were compared with the endorectal ultrasound data. Results: Of the 90 cases, 82.5% showed tumor downsizing, varying from one-third to two-thirds or more of the original tumor mass. The distance between the tumor and the anal sphincter increased in 60.2% of cases. The median increase was 0.73 cm (range, 0.2-2.5). Downsizing was not always associated with an increase in distance. Preserving surgery was performed in 60.6% of cases. It was possible in nearly 30% of patients in whom the cancer had reached the anal sphincter before the preoperative therapy. The distal margin was tumor free in these cases. Conclusion: The results of our study have shown that in very low rectal cancer, preoperative therapy causes tumor downsizing in >80% of cases and in more than one-half enhances the distance between the tumor and anal sphincter. These modifications affect the primary surgical options, facilitating or making sphincter-saving surgery possible.

  1. [What will determine the first-line treatment of a patient with rectal cancer?].

    PubMed

    Lepistö, Anna; Kouri, Mauri; Savolainen, Ritja; Ristimäki, Ari

    2016-01-01

    Treatment of a rectal cancer patient is devised by a multidisciplinary expert team. The first thing to be solved is whether a curative treatment, one slowing the progression of the disease, or a symptomatic treatment is aimed at. The extent of the disease is assessed by using whole body CT scan and MR imaging of the rectum. When aiming at curative treatment, the need for preoperative radiation therapy and the surgical technique is assessed on the basis of MRI and clinical examination. The patient's physical condition, associated diseases or pelvic radiotherapy previously applied due to other diseases may restrict the choice of treatment. In an advanced disease, cytostatic chemotherapy is usually the first-line therapy, unless the tumor is obstructing the bowel. PMID:27483636

  2. Distal intramural spread of rectal cancer after preoperative radiotherapy: The results of a multicenter randomized clinical study

    SciTech Connect

    Chmielik, Ewa; Bujko, Krzysztof . E-mail: bujko@coi.waw.pl; Nasierowska-Guttmejer, Anna; Nowacki, Marek P.; Kepka, Lucyna; Sopylo, Rafal; Wojnar, Andrzej; Majewski, Przemyslaw; Sygut, Jacek; Karmolinski, Andrzej; Huzarski, Tomasz; Wandzel, Piotr

    2006-05-01

    Purpose: To evaluate the extent of distal intramural spread (DIS) after preoperative radiotherapy for rectal cancer. Methods and Materials: A total of 316 patients with T{sub 3-4} primary resectable rectal cancer were randomized to receive either preoperative 5x5 Gy radiation with immediate surgery or chemoradiation (50.4 Gy, 1.8 Gy per fraction plus boluses of 5-fluorouracil and leucovorin) with delayed surgery. The slides of the 106 patients who received short-course radiation and of the 86 who received chemoradiation were available for central microscopic evaluation of DIS. Results: The length of DIS did not differ significantly (p = 0.64) between the short-course group and the chemoradiation group and was 0 in 47% vs. 49%; 1 to 5 mm in 41% vs. 42%; 6 to 10 mm in 8% vs. 9%, and greater than 10 mm in 4% vs. 0, respectively. Among the 11 clinically complete responders, DIS was found 1 to 5 mm from the microscopically detected ulceration of the mucosa in 5 patients. The discontinuous DIS was more frequent in the chemoradiation group as compared with the short-course group (i.e., 57% vs. 16% of cases, p < 0.001). Conclusions: Approximately 1 out of 10 advanced rectal cancers after preoperative radiotherapy or radiochemotherapy was characterized by DIS of over 5 mm. No significant difference was seen in the length of DIS between the 2 groups.

  3. The radiation-induced changes in rectal mucosa: Hyperfractionated vs. hypofractionated preoperative radiation for rectal cancer

    SciTech Connect

    Starzewski, Jacek J.; Pajak, Jacek T.; Pawelczyk, Iwona; Lange, Dariusz; Golka, Dariusz . E-mail: dargolka@wp.pl; Brzeziska, Monika; Lorenc, Zbigniew

    2006-03-01

    Purpose: The purpose of the study was the qualitative and quantitative evaluation of acute radiation-induced rectal changes in patients who underwent preoperative radiotherapy according to two different irradiation protocols. Patients and Methods: Sixty-eight patients with rectal adenocarcinoma underwent preoperative radiotherapy; 44 and 24 patients underwent hyperfractionated and hypofractionated protocol, respectively. Fifteen patients treated with surgery alone served as a control group. Five basic histopathologic features (meganucleosis, inflammatory infiltrations, eosinophils, mucus secretion, and erosions) and two additional features (mitotic figures and architectural glandular abnormalities) of radiation-induced changes were qualified and quantified. Results: Acute radiation-induced reactions were found in 66 patients. The most common were eosinophilic and plasma-cell inflammatory infiltrations (65 patients), erosions, and decreased mucus secretion (54 patients). Meganucleosis and mitotic figures were more common in patients who underwent hyperfractionated radiotherapy. The least common were the glandular architectural distortions, especially in patients treated with hypofractionated radiotherapy. Statistically significant differences in morphologic parameters studied between groups treated with different irradiation protocols were found. Conclusion: The system of assessment is a valuable tool in the evaluation of radiation-induced changes in the rectal mucosa. A greater intensity of regenerative changes was found in patients treated with hyperfractionated radiotherapy.

  4. Predictive Factors and Management of Rectal Bleeding Side Effects Following Prostate Cancer Brachytherapy

    SciTech Connect

    Price, Jeremy G.; Stone, Nelson N.; Stock, Richard G.

    2013-08-01

    Purpose: To report on the incidence, nature, and management of rectal toxicities following individual or combination brachytherapy following treatment for prostate cancer over a 17-year period. We also report the patient and treatment factors predisposing to acute ≥grade 2 proctitis. Methods and Materials: A total of 2752 patients were treated for prostate cancer between October 1990 and April 2007 with either low-dose-rate brachytherapy alone or in combination with androgen depletion therapy (ADT) or external beam radiation therapy (EBRT) and were followed for a median of 5.86 years (minimum 1.0 years; maximum 19.19 years). We investigated the 10-year incidence, nature, and treatment of acute and chronic rectal toxicities following BT. Using univariate, and multivariate analyses, we determined the treatment and comorbidity factors predisposing to rectal toxicities. We also outline the most common and effective management for these toxicities. Results: Actuarial risk of ≥grade 2 rectal bleeding was 6.4%, though notably only 0.9% of all patients required medical intervention to manage this toxicity. The majority of rectal bleeding episodes (72%) occurred within the first 3 years following placement of BT seeds. Of the 27 patients requiring management for their rectal bleeding, 18 underwent formalin treatment and nine underwent cauterization. Post-hoc univariate statistical analysis revealed that coronary artery disease (CAD), biologically effective dose, rectal volume receiving 100% of the prescription dose (RV100), and treatment modality predict the likelihood of grade ≥2 rectal bleeding. Only CAD, treatment type, and RV100 fit a Cox regression multivariate model. Conclusions: Low-dose-rate prostate brachytherapy is very well tolerated and rectal bleeding toxicities are either self-resolving or effectively managed by medical intervention. Treatment planning incorporating adjuvant ADT while minimizing RV100 has yielded the best toxicity-free survival following

  5. Rectal cancer profiling identifies distinct subtypes in India based on age at onset, genetic, epigenetic and clinicopathological characteristics.

    PubMed

    Laskar, Ruhina Shirin; Ghosh, Sankar Kumar; Talukdar, Fazlur Rahman

    2015-12-01

    Rectal cancer is a heterogeneous disease that develops through multiple pathways characterized by genetic and epigenetic alterations. India has a comparatively higher proportion of rectal cancers and early-onset cases. We analyzed genetic (KRAS, TP53 and BRAF mutations, and MSI), epigenetic alterations (CpG island methylation detection of 10 tumor-related genes/loci), the associated clinicopathological features and survival trend in 80 primary rectal cancer patients from India. MSI was detected using BAT 25 and BAT 26 mononucleotide markers and mutation of KRAS, TP53, and BRAF V600E was detected by direct sequencing. Methyl specific polymerase chain reaction was used to determine promoter methylation status of the classic CIMP panel markers (P16, hMLH1, MINT1, MINT2, and MINT31) as well as other tumor specific genes (DAPK, RASSF1, BRCA1, and GSTP1). MSI and BRAF mutations were uncommon but high frequencies of overall KRAS mutations (67.5%); low KRAS codon 12 and a novel KRAS G15S mutation with concomitant RASSF1 methylation in early onset cases were remarkable. Hierarchical clustering as well as principal component analysis identified three distinct subgroups of patients having discrete age at onset, clinicopathological, molecular and survival characteristics: (i) a KRAS associated CIMP-high subgroup; (ii) a significantly younger MSS, CIMP low, TP53 mutant group having differential KRAS mutation patterns, and (iii) a CIMP-negative, TP53 mutated group. The early onset subgroup exhibited the most unfavorable disease characteristics with advanced stage, poorly differentiated tumors and had the poorest survival compared to the other subgroups. Genetic and epigenetic profiling of rectal cancer patients identified distinct subtypes in Indian population.

  6. N-acetyltransferase 1 in colon and rectal cancer cases from an industrialized area.

    PubMed

    Roemer, Hermann C; Weistenhofer, Wobbeke; Lohlein, Dietrich; Geller, Frank; Blomeke, Brunhilde; Golka, Klaus

    2008-01-01

    Colon and rectal cancers are both associated with genetic as well as nutritional, occupational, and environmental factors. Aromatic amines and heterocyclic amines are established colorectal carcinogens. The polymorphic enzyme N-acetyltransferase 1 (NAT1) contributes to heterocyclic amine metabolism in the human colon. Thereby, NAT1 may influence the risk for development of colorectal cancer. The distribution of NAT1 genotypes was determined in 107 colon cancer cases, 77 rectal cancer cases, and 185 controls (suffering from nonmalignant diseases) by standard methods. In addition, possible occupational and nonoccupational risk factors were determined by a personal interview. Cancer cases and controls were derived from an area of former coal, iron, and steel industries, which is known for elevated colon cancer mortality. The proportions of NAT1*4/*4 genotype were 72% in controls, 75% in rectal cancer cases, and 72% in colon cancer cases. The proportions of the NAT1*4/*10 genotype were 17.8% in controls, 12.9% in rectal cancer cases, and 14% in colon cancer cases. Combinations of the determined NAT1 alleles *3/*3, *3/*10, *4/*3, *4/*11, *10/*10 and *11/*11 contributed to 10.2% of the genotypes in controls, 12.1% in rectal cancer cases, and 14% in colon cancer cases. In contrast to another study on healthy German volunteers, the NAT1*4/*4 genotype (wild type) is overrepresented. This might be due to the variation in the proportion of NAT1 alleles in the general population. The present study does not support a relevant impact of the NAT1 genotype on colorectal cancer risk development in the study area.

  7. Dose Constraint for Minimizing Grade 2 Rectal Bleeding Following Brachytherapy Combined With External Beam Radiotherapy for Localized Prostate Cancer: Rectal Dose-Volume Histogram Analysis of 457 Patients

    SciTech Connect

    Shiraishi, Yutaka; Yorozu, Atsunori; Ohashi, Toshio; Toya, Kazuhito; Seki, Satoshi; Yoshida, Kayo; Kaneda, Tomoya; Saito, Shiro; Nishiyama, Toru; Hanada, Takashi; Shigematsu, Naoyuki

    2011-11-01

    Purpose: To determine the rectal tolerance to Grade 2 rectal bleeding after I-125 seed brachytherapy combined with external beam radiotherapy (EBRT), based on the rectal dose-volume histogram. Methods and Materials: A total of 458 consecutive patients with stages T1 to T3 prostate cancer received combined modality treatment consisting of I-125 seed implantation followed by EBRT to the prostate and seminal vesicles. The prescribed doses of brachytherapy and EBRT were 100 Gy and 45 Gy in 25 fractions, respectively. The rectal dosimetric factors were analyzed for rectal volumes receiving >100 Gy and >150 Gy (R100 and R150) during brachytherapy and for rectal volumes receiving >30 Gy to 40 Gy (V30-V40) during EBRT therapy in 373 patients for whom datasets were available. The patients were followed from 21 to 72 months (median, 45 months) after the I-125 seed implantation. Results: Forty-four patients (9.7%) developed Grade 2 rectal bleeding. On multivariate analysis, age (p = 0.014), R100 (p = 0.002), and V30 (p = 0.001) were identified as risk factors for Grade 2 rectal bleeding. The rectal bleeding rate increased as the R100 increased: 5.0% (2/40 patients) for 0 ml; 7.5% (20/267 patients) for >0 to 0.5 ml; 11.0% (11/100 patients) for >0.5 to 1 ml; 17.9% (5/28 patients) for >1 to 1.5 ml; and 27.3% (6/22 patients) for >1.5 ml (p = 0.014). Grade 2 rectal bleeding developed in 6.4% (12/188) of patients with a V30 {<=}35% and in 14.1% (26/185) of patients with a V30 >35% (p = 0.02). When these dose-volume parameters were considered in combination, the Grade 2 rectal bleeding rate was 4.2% (5/120 patients) for a R100 {<=}0.5 ml and a V30 {<=}35%, whereas it was 22.4% (13/58 patients) for R100 of >0.5 ml and V30 of >35%. Conclusion: The risk of rectal bleeding was found to be significantly volume-dependent in patients with prostate cancer who received combined modality treatment. Rectal dose-volume analysis is a practical method for predicting the risk of development of

  8. Discrimination of rectal cancer through human serum using surface-enhanced Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Li, Xiaozhou; Yang, Tianyue; Li, Siqi; Zhang, Su; Jin, Lili

    2015-05-01

    In this paper, surface-enhanced Raman spectroscopy (SERS) was used to detect the changes in blood serum components that accompany rectal cancer. The differences in serum SERS data between rectal cancer patients and healthy controls were examined. Postoperative rectal cancer patients also participated in the comparison to monitor the effects of cancer treatments. The results show that there are significant variations at certain wavenumbers which indicates alteration of corresponding biological substances. Principal component analysis (PCA) and parameters of intensity ratios were used on the original SERS spectra for the extraction of featured variables. These featured variables then underwent linear discriminant analysis (LDA) and classification and regression tree (CART) for the discrimination analysis. Accuracies of 93.5 and 92.4 % were obtained for PCA-LDA and parameter-CART, respectively.

  9. Rectal cancer with disseminated carcinomatosis of the bone marrow: report of a case.

    PubMed

    Nakashima, Yuichiro; Takeishi, Kazuki; Guntani, Atsushi; Tsujita, Eiji; Yoshinaga, Keiji; Matsuyama, Ayumi; Hamatake, Motoharu; Maeda, Takashi; Tsutsui, Shinichi; Matsuda, Hiroyuki; Fujihara, Megumu; Ishida, Teruyoshi

    2014-01-01

    We report a rare case of disseminated carcinomatosis of the bone marrow from rectal cancer with disseminated intravascular coagulation (DIC). A 65-year-old man was admitted with melena and low back pain at rest. X-ray examination showed rectal cancer with multiple bone metastases. Laboratory examination showed severe anemia and DIC. Histologic examination showed disseminated carcinomatosis of the bone marrow. The DIC was considered to be caused by disseminated carcinomatosis of the bone marrow from rectal cancer, and we immediately started treatment with anti-DIC therapy and anticancer chemotherapy with the modified FOLFOX6 regimen (mFOLFOX6). After some response to therapy, the patient's general condition deteriorated, and he died 128 days after admission. This is the first English report showing disseminated carcinomatosis of the bone marrow from colorectal cancer treated with mFOLFOX6.

  10. Rectal cancer: future directions and priorities for treatment, research and policy in New Zealand.

    PubMed

    Jackson, Christopher; Ehrenberg, Nieves; Frizelle, Frank; Sarfati, Diana; Balasingam, Adrian; Pearse, Maria; Parry, Susan; Print, Cristin; Findlay, Michael; Bissett, Ian

    2014-06-06

    New Zealand has one of the highest incidences of rectal cancer in the world, and its optimal management requires a multidisciplinary approach. A National Rectal Cancer Summit was convened in August 2013 to discuss management of rectal cancer in the New Zealand context, to highlight controversies and discuss domestic priorities for the future. This paper summarises the priorities for treatment, research and policy for rectal cancer services in New Zealand identified as part of the Summit in August. The following priorities were identified: - Access to high-quality information for service planning, review of outcomes, identification of inequities and gaps in provision, and quality improvement; - Engagement with the entire sector, including private providers; - Focus on equity; - Emerging technologies; - Harmonisation of best practice; - Importance of multidisciplinary team meetings. In conclusion, improvements in outcomes for patients with rectal cancer in New Zealand will require significant engagement between policy makers, providers, researchers, and patients in order to ensure equitable access to high quality treatment, and strategic incorporation of emerging technologies into clinical practice. A robust clinical information framework is required in order to facilitate monitoring of quality improvements and to ensure that equitable care is delivered.

  11. [Total mesorectal excision with ultrasonic coagulation knife ("UltraCision") in surgery of rectal cancer].

    PubMed

    Balogh, A; Zöllei, I; Varga, L; Tiszlavicz, L; Lázár, G; Bagi, R; Palkó, A; Nagy, F

    2000-02-20

    The authors report a total of 62 middle and low third rectal cancer cases operated on by total mesorectal excision by the method of Heald. The oncological basis of this procedure is the horizontal regional metastatization of rectal cancer. The total mesorectal excision facilitates, the low anterior resections and preservation of sphincter with an ultra-low colorectal, or coloanal anastomosis using the double stapling technique. In the authors' experience, the "UltraCision" cutting-coagulating device permits an atraumatic, bloodless and oncologically correct dissection. Using the double stapling technique, we succeeded in 60% of our middle- and low-third rectal cancer patients to perform a sphincter preserving low anterior resection. In 9 (28%) of the low third rectal cancer patients, preservation of the sphincter was possible with oncologically correct anterior resection and an ultra-low colo-anal anastomosis. Three anastomotic insufficiencies occurred, two of them healed on lotion-suction drainage, and one on the application of transient protective ileostomy. The literature data suggest a lower local recurrency rate after radical rectal cancer surgery, if total mesorectal excision is performed.

  12. Anatomic basis of sharp pelvic dissection for curative resection of rectal cancer.

    PubMed

    Kim, Nam Kyu

    2005-12-31

    The optimal goals in the surgical treatment of rectal cancer are curative resection, anal sphincter preservation, and preservation of sexual and voiding functions. The quality of complete resection of rectal cancer and the surrounding mesorectum can determine the prognosis of patients and their quality of life. With the emergence of total mesorectal excision in the field of rectal cancer surgery, anatomical sharp pelvic dissection has been emphasized to achieve these therapeutic goals. In the past, the rates of local recurrence and sexual/voiding dysfunction have been high. However, with sharp pelvic dissection based on the pelvic anatomy, local recurrence has decreased to less than 10%, and the preservation rate of sexual and voiding function is high. Improved surgical techniques have created much interest in the surgical anatomy related to curative rectal cancer surgery, with particular focus on the fascial planes and nerve plexuses and their relationship to the surgical planes of dissection. A complete understanding of rectum anatomy and the adjacent pelvic organs are essential for colorectal surgeons who want optimal oncologic outcomes and safety in the surgical treatment of rectal cancer.

  13. Knowledge, Attitudes, and Practices Related to Preoperative Chemoradiotherapy in Rectal Cancer Patients

    PubMed Central

    Chen, Xingxing; Lin, Ruifang; Li, Huifang; Su, Meng; Zhang, Wenyi; Deng, Xia; Zhang, Ping

    2016-01-01

    Background. The aim of this study is to assess the knowledge, attitudes, and practices related to pre-CRT in patients of stage II/III rectal cancer. Materials and Methods. Questionnaires regarding the knowledge, attitudes, and practices of pre-CRT were mailed to 145 rectal cancer patients in II/III stage between January 2012 and December 2014, and 111 agreed to participate and returned completed questionnaires to the researcher. Logistic regression model was used to compare sociodemographic characteristics, knowledge, and attitude with practice, respectively. Results. A total of 145 patients were approached for interview, of which 111 responded and 48.6% (54) had undergone pre-CRT. Only 31.5% of the participants knew that CRT is a treatment of rectal cancer and 39.6% were aware of the importance of CRT. However, the vast majority of participants (68.5%) expressed a positive attitude toward rectal cancer. Multivariate logistic regression analysis revealed that knowledge level (p = 0.006) and attitudes (p = 0.001) influence the actual practice significantly. Furthermore, age, gender, and income were potential predictors of practice (all p < 0.05). Conclusion. This study shows that, despite the fact that participants had suboptimal level of knowledge on rectal cancer, their attitude is favorable to pre-CRT. Strengthening the professional health knowledge and realizing the importance of attitudes may deepen patients' understanding of preoperative therapy. PMID:27761141

  14. [Three Cases of Stage Ⅳ Low Rectal Cancer with Lateral Pelvic Lymph Node Metastasis].

    PubMed

    Tamura, Hiroshi; Shimada, Yoshifumi; Yagi, Ryoma; Tajima, Yosuke; Okamura, Takuma; Nakano, Masato; Ishikawa, Takashi; Sakata, Jun; Kobayashi, Takashi; Kameyama, Hitoshi; Kosugi, Shin-ichi; Wakai, Toshifumi; Nogami, Hitoshi; Maruyama, Satoshi; Takii, Yasumasa

    2015-11-01

    Case 1: A 61-year-old man who had a diagnosis of low rectal cancer with lateral pelvic lymph node (LPLN) metastasis and multiple liver metastases underwent low anterior resection with LPLN dissection. The initial surgery was followed by chemotherapy, and then an extended right hepatectomy with partial resection of the liver was performed. Subsequently, a lung metastasis was detected, and the lung was partially resected. The patient was alive 9 years and 6 months after the initial operation. Case 2: A 53-year-old man had a diagnosis of low rectal cancer. After 5 courses of mFOLFOX6 plus bevacizumab, he underwent low anterior resection with LPLN dissection and resection of the peritoneal metastasis. The patient was alive 6 years and 3 months after the surgery without any signs of recurrence. Case 3: A 48-year-old man had a diagnosis of low rectal cancer and multiple liver metastases. He underwent low anterior resection with LPLN dissection and right hepatic lobectomy. He subsequently showed liver and lung metastases. The patient received systemic chemotherapy, and is alive with recurrent disease. We report 3 cases of Stage Ⅳ low rectal cancer with LPLN metastasis, and propose that LPLN dissection is important as a part of R0 resection for Stage Ⅳ low rectal cancer. PMID:26805345

  15. A functional biological network centered on XRCC3: a new possible marker of chemoradiotherapy resistance in rectal cancer patients.

    PubMed

    Agostini, Marco; Zangrando, Andrea; Pastrello, Chiara; D'Angelo, Edoardo; Romano, Gabriele; Giovannoni, Roberto; Giordan, Marco; Maretto, Isacco; Bedin, Chiara; Zanon, Carlo; Digito, Maura; Esposito, Giovanni; Mescoli, Claudia; Lavitrano, Marialuisa; Rizzolio, Flavio; Jurisica, Igor; Giordano, Antonio; Pucciarelli, Salvatore; Nitti, Donato

    2015-01-01

    Preoperative chemoradiotherapy is widely used to improve local control of disease, sphincter preservation and to improve survival in patients with locally advanced rectal cancer. Patients enrolled in the present study underwent preoperative chemoradiotherapy, followed by surgical excision. Response to chemoradiotherapy was evaluated according to Mandard's Tumor Regression Grade (TRG). TRG 3, 4 and 5 were considered as partial or no response while TRG 1 and 2 as complete response. From pretherapeutic biopsies of 84 locally advanced rectal carcinomas available for the analysis, only 42 of them showed 70% cancer cellularity at least. By determining gene expression profiles, responders and non-responders showed significantly different expression levels for 19 genes (P < 0.001). We fitted a logistic model selected with a stepwise procedure optimizing the Akaike Information Criterion (AIC) and then validated by means of leave one out cross validation (LOOCV, accuracy = 95%). Four genes were retained in the achieved model: ZNF160, XRCC3, HFM1 and ASXL2. Real time PCR confirmed that XRCC3 is overexpressed in responders group and HFM1 and ASXL2 showed a positive trend. In vitro test on colon cancer resistant/susceptible to chemoradioterapy cells, finally prove that XRCC3 deregulation is extensively involved in the chemoresistance mechanisms. Protein-protein interactions (PPI) analysis involving the predictive classifier revealed a network of 45 interacting nodes (proteins) with TRAF6 gene playing a keystone role in the network. The present study confirmed the possibility that gene expression profiling combined with integrative computational biology is useful to predict complete responses to preoperative chemoradiotherapy in patients with advanced rectal cancer.

  16. A rare presentation of breast cancer: near obstructing rectal mass and gastric outlet obstruction.

    PubMed

    Martin, Rachel; Mathews, Winn; Scarcliff, Steven

    2016-01-01

    Breast cancer metastasizes to the gastrointestinal (GI) tract are exceedingly rare. The low incidence and vague presentation of GI metastasizes often cause delay in diagnosis and treatment. Here, we present a case of metastatic breast cancer causing gastric outlet obstruction and rectal obstruction. PMID:27672104

  17. Study shows colon and rectal tumors constitute a single type of cancer

    Cancer.gov

    The pattern of genomic alterations in colon and rectal tissues is the same regardless of anatomic location or origin within the colon or the rectum, leading researchers to conclude that these two cancer types can be grouped as one, according to The Cancer

  18. A rare presentation of breast cancer: near obstructing rectal mass and gastric outlet obstruction

    PubMed Central

    Martin, Rachel; Mathews, Winn; Scarcliff, Steven

    2016-01-01

    Breast cancer metastasizes to the gastrointestinal (GI) tract are exceedingly rare. The low incidence and vague presentation of GI metastasizes often cause delay in diagnosis and treatment. Here, we present a case of metastatic breast cancer causing gastric outlet obstruction and rectal obstruction.

  19. A rare presentation of breast cancer: near obstructing rectal mass and gastric outlet obstruction

    PubMed Central

    Martin, Rachel; Mathews, Winn; Scarcliff, Steven

    2016-01-01

    Breast cancer metastasizes to the gastrointestinal (GI) tract are exceedingly rare. The low incidence and vague presentation of GI metastasizes often cause delay in diagnosis and treatment. Here, we present a case of metastatic breast cancer causing gastric outlet obstruction and rectal obstruction. PMID:27672104

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

    SciTech Connect

    Dipetrillo, Tom; Pricolo, Victor; Lagares-Garcia, Jorge; Vrees, Matt; Klipfel, Adam; Cataldo, Tom; Sikov, William; McNulty, Brendan; Shipley, Joshua; Anderson, Elliot; Khurshid, Humera; Oconnor, Brigid; Oldenburg, Nicklas B.E.; Radie-Keane, Kathy; Husain, Syed; Safran, Howard

    2012-01-01

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

  1. A New Laparoscopic Surgical Procedure to Achieve Sufficient Mesorectal Excision in Upper Rectal Cancer

    PubMed Central

    Ohigashi, Seiji; Taketa, Takashi; Sudo, Kazuki; Shiozaki, Hironori; Onodera, Hisashi

    2011-01-01

    Objective. Mesorectal excision corresponding to the location of a tumor, termed tumor-specific mesorectal excision (TSME), is commonly performed for resection of upper rectal cancer. We devised a new laparoscopic procedure for sufficient TSME with rectal transection followed by mesorectal excision. Operative Technique. After mobilization of the sigmoid colon and ligation of inferior mesenteric vessels, we dissected the mesorectum along the layer of the planned total mesorectal excision. The rectal wall was carefully separated from the mesorectum at the appropriate anal side from the tumor. After the rectum was isolated and transected using an endoscopic linear stapler, the rectal stump drew immediately toward the anal side, enabling the mesorectum to be identified clearly. In this way, sufficient TSME can be performed easily and accurately. This technique has been successfully conducted on 19 patients. Conclusion. This laparoscopic technique is a feasible and reliable procedure for achieving sufficient TSME. PMID:22312519

  2. Total Mesorectal Excision, an erroneous anatomical term for the gold standard in rectal cancer treatment.

    PubMed

    Rodríguez-Luna, María Rita; Guarneros-Zárate, Joaquín E; Tueme-Izaguirre, Jorge

    2015-11-01

    In 1986 Professor R J Heald published in The Lancet his new technique which he called Total Mesorectal Excision; today this is the gold standard for the surgical management of rectal cancer. In Total Mesorectal Excision (TME), the mesorectum is the term used to describe all the peri-rectal connective tissue including the posterior sheath of the endopelvic fascia containing the peri-rectal neurovascular structures. However, the mesenterium is a defined structure composed of a double layer of peritoneum which does not include the endopelvic fascia and the lateral rectal stalks, so these should not be included in the term 'mesorectum'. In our globalized medical culture it is important to use anatomic terms approved by the International Federation of Associations of Anatomists, as contained in the Terminologia Anatomica produced by the Federative International Programme for Anatomical Terminology (FIPAT). The term mesorectum is not listed in the Terminologia Anatomica. PMID:26409653

  3. Sparing Sphincters and Laparoscopic Resection Improve Survival by Optimizing the Circumferential Resection Margin in Rectal Cancer Patients

    PubMed Central

    Keskin, Metin; Bayraktar, Adem; Sivirikoz, Emre; Yegen, Gülcin; Karip, Bora; Saglam, Esra; Bulut, Mehmet Türker; Balik, Emre

    2016-01-01

    Abstract The goal of rectal cancer treatment is to minimize the local recurrence rate and extend the disease-free survival period and survival. For this aim, obtainment of negative circumferential radial margin (CRM) plays an important role. This study evaluated predictive factors for positive CRM status and its effect on patient survival in mid- and distal rectal tumors. Patients who underwent curative resection for rectal cancer were included. The main factors were demographic data, tumor location, surgical technique, neoadjuvant therapy, tumor diameter, tumor depth, lymph node metastasis, mesorectal integrity, CRM, the rate of local recurrence, distant metastasis, and overall and disease-free survival. Statistical analyses were performed by using the Chi-squared test, Fisher exact test, Student t test, Mann–Whitney U test and the Mantel–Cox log-rank sum test. A total of 420 patients were included, 232 (55%) of whom were male. We observed no significant differences in patient characteristics or surgical treatment between the patients who had positive CRM and who had negative CRM, but a higher positive CRM rate was observed in patients undergone abdominoperineal resection (APR) (P < 0.001). Advanced T-stage (P < 0.001), lymph node invasion (P = 0.001) and incomplete mesorectum (P = 0.007) were encountered significantly more often in patients with positive CRM status. Logistic regression analysis revealed that APR (P < 0.001) and open resection (P = 0.046) were independent predictors of positive CRM status. Moreover, positive CRM was associated with decreased 5-year overall and disease-free survival (P = 0.002 and P = 0.004, respectively). This large single-institution series demonstrated that APR and open resection were independent predictive factors for positive CRM status in rectal cancer. Positive CRM independently decreased the 5-year overall and disease-free survival rates. PMID:26844498

  4. Sparing Sphincters and Laparoscopic Resection Improve Survival by Optimizing the Circumferential Resection Margin in Rectal Cancer Patients.

    PubMed

    Keskin, Metin; Bayraktar, Adem; Sivirikoz, Emre; Yegen, Gülcin; Karip, Bora; Saglam, Esra; Bulut, Mehmet Türker; Balik, Emre

    2016-02-01

    The goal of rectal cancer treatment is to minimize the local recurrence rate and extend the disease-free survival period and survival. For this aim, obtainment of negative circumferential radial margin (CRM) plays an important role. This study evaluated predictive factors for positive CRM status and its effect on patient survival in mid- and distal rectal tumors.Patients who underwent curative resection for rectal cancer were included. The main factors were demographic data, tumor location, surgical technique, neoadjuvant therapy, tumor diameter, tumor depth, lymph node metastasis, mesorectal integrity, CRM, the rate of local recurrence, distant metastasis, and overall and disease-free survival. Statistical analyses were performed by using the Chi-squared test, Fisher exact test, Student t test, Mann-Whitney U test and the Mantel-Cox log-rank sum test.A total of 420 patients were included, 232 (55%) of whom were male. We observed no significant differences in patient characteristics or surgical treatment between the patients who had positive CRM and who had negative CRM, but a higher positive CRM rate was observed in patients undergone abdominoperineal resection (APR) (P < 0.001). Advanced T-stage (P < 0.001), lymph node invasion (P = 0.001) and incomplete mesorectum (P = 0.007) were encountered significantly more often in patients with positive CRM status. Logistic regression analysis revealed that APR (P < 0.001) and open resection (P = 0.046) were independent predictors of positive CRM status. Moreover, positive CRM was associated with decreased 5-year overall and disease-free survival (P = 0.002 and P = 0.004, respectively).This large single-institution series demonstrated that APR and open resection were independent predictive factors for positive CRM status in rectal cancer. Positive CRM independently decreased the 5-year overall and disease-free survival rates.

  5. Reporting Late Rectal Toxicity in Prostate Cancer Patients Treated With Curative Radiation Treatment

    SciTech Connect

    Faria, Sergio L. Souhami, Luis; Joshua, Bosede; Vuong, Te; Freeman, Carolyn R.

    2008-11-01

    Purpose: Long-term rectal toxicity is a concern for patients with prostate cancer treated with curative radiation. However, comparing results of late toxicity may not be straightforward. This article reviews the complexity of reporting long-term side effects by using data for patients treated in our institution with hypofractionated irradiation. Methods and Materials: Seventy-two patients with localized prostate cancer treated with hypofractionated radiotherapy alone to a dose of 66 Gy in 22 fractions were prospectively assessed for late rectal toxicity according to the Common Toxicity Criteria, Version 3, scoring system. Ninety percent of patients had more than 24 months of follow-up. Results are compared with data published in the literature. Results: We found an actuarial incidence of Grade 2 or higher late rectal toxicity of 27% at 30 months and a crude incidence of Grade 2 or higher late rectal toxicity of 18%. This was mostly severe toxicity documented during follow-up. The incidence of Grade 3 rectal toxicity at the last visit was 3% compared with 13% documented at any time during follow-up. Conclusion: Comparison of late toxicity after radiotherapy in patients with prostate cancer must be undertaken with caution because many factors need to be taken into consideration. Because accurate assessment of late toxicity in the evaluation of long-term outcome after radiotherapy in patients with localized prostate cancer is essential, there is a need to develop by consensus guidelines for assessing and reporting late toxicity in this group of patients.

  6. Prediction of Response to Preoperative Chemoradiotherapy in Rectal Cancer by Multiplex Kinase Activity Profiling

    SciTech Connect

    Folkvord, Sigurd; Flatmark, Kjersti; Dueland, Svein

    2010-10-01

    Purpose: Tumor response of rectal cancer to preoperative chemoradiotherapy (CRT) varies considerably. In experimental tumor models and clinical radiotherapy, activity of particular subsets of kinase signaling pathways seems to predict radiation response. This study aimed to determine whether tumor kinase activity profiles might predict tumor response to preoperative CRT in locally advanced rectal cancer (LARC). Methods and Materials: Sixty-seven LARC patients were treated with a CRT regimen consisting of radiotherapy, fluorouracil, and, where possible, oxaliplatin. Pretreatment tumor biopsy specimens were analyzed using microarrays with kinase substrates, and the resulting substrate phosphorylation patterns were correlated with tumor response to preoperative treatment as assessed by histomorphologic tumor regression grade (TRG). A predictive model for TRG scores from phosphosubstrate signatures was obtained by partial-least-squares discriminant analysis. Prediction performance was evaluated by leave-one-out cross-validation and use of an independent test set. Results: In the patient population, 73% and 15% were scored as good responders (TRG 1-2) or intermediate responders (TRG 3), whereas 12% were assessed as poor responders (TRG 4-5). In a subset of 7 poor responders and 12 good responders, treatment outcome was correctly predicted for 95%. Application of the prediction model on the remaining patient samples resulted in correct prediction for 85%. Phosphosubstrate signatures generated by poor-responding tumors indicated high kinase activity, which was inhibited by the kinase inhibitor sunitinib, and several discriminating phosphosubstrates represented proteins derived from signaling pathways implicated in radioresistance. Conclusions: Multiplex kinase activity profiling may identify functional biomarkers predictive of tumor response to preoperative CRT in LARC.

  7. Tumor Volume Reduction Rate Measured by Magnetic Resonance Volumetry Correlated With Pathologic Tumor Response of Preoperative Chemoradiotherapy for Rectal Cancer

    SciTech Connect

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

    2010-09-01

    Purpose: To determine whether the tumor volume reduction rate (TVRR) measured using three-dimensional region-of-interest magnetic resonance volumetry correlates with the pathologic tumor response after preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer. Methods and Materials: The study included 405 patients with locally advanced rectal cancer (cT3-T4) who had undergone preoperative CRT and radical proctectomy. The tumor volume was measured using three-dimensional region-of-interest magnetic resonance volumetry before and after CRT but before surgery. We analyzed the correlation between the TVRR and the pathologic tumor response in terms of downstaging and tumor regression grade (TRG). Downstaging was defined as ypStage 0-I (ypT0-T2N0M0), and the TRG proposed by Dworak et al. was used. Results: The mean TVRR was 65.0% {+-} 22.3%. Downstaging and complete regression occurred in 167 (41.2%) and 58 (14.3%) patients, respectively. The TVRRs according to ypT classification (ypT0-T2 vs. ypT3-T4), ypN classification (ypN0 vs. ypN1-N2), downstaging (ypStage 0-I vs. ypStage II-III), good regression (TRG 3-4 vs. TRG 1-2), and complete regression (TRG 4 vs. TRG 1-3) were all significantly different (p <.05). When the TVRR was categorized into three groups (<60%, 60-80%, and >80%), the rates of ypT0-T2, ypN0, downstaging, and good regression were all significantly greater for patients with a TVRR of {>=}60%, as was the complete regression rate for patients with a TVRR >80% (p <.05). Conclusion: The TVRR measured using three-dimensional region-of-interest magnetic resonance volumetry correlated significantly with the pathologic tumor response in terms of downstaging and TRG after preoperative CRT for locally advanced rectal cancer.

  8. Advances in cancer control

    SciTech Connect

    Anderson, P.N. ); Engstrom, P.F. ); Mortenson, L.E. )

    1989-01-01

    This book contains the proceedings of the sixth annual meeting on Advances in Cancer Control. Included are the following articles: Barriers and facilitators to compliance with routine mammographic screening, Preliminary report of an intervention to improve mammography skills of radiologists.

  9. Predominance of CIN versus MSI in the development of rectal cancer at young age

    PubMed Central

    Fernebro, Eva; Halvarsson, Britta; Baldetorp, Bo; Nilbert, Mef

    2002-01-01

    Background Development of proximal and distal colorectal cancers involve partly different mechanisms associated with the microsatellite instability (MSI) and the chromosomal instability (CIN) pathways. Colorectal cancers in patients under 50 years of age represent about 5% of the total number of tumors and have been associated with an increased frequency of MSI tumors. However, MSI and CIN may play different roles in the development of colon cancer and rectal cancer, and we have specifically investigated their contribution to the development of rectal cancer at young age. Methods Thirty rectal cancers diagnosed before the age of 50 were characterized for DNA-ploidy, MSI, mutations of KRAS and CTNNB1 and immunohistochemical expression of p53, β-catenin and of the mismatch repair (MMR) proteins MLH1 and MSH2. Results DNA aneuploidy was detected in 21/30 tumors, KRAS mutations in 6 tumors, no mutations of CTNNB1 were detected but immunohistochemical staining for β-catenin showed nuclear staining in 6 tumors, and immunohistochemical expression of p53 was detected in 18 tumors. MSI was detected in 3/30 tumors, all of which showed and immunohistochemical loss of staining for the MMR protein MSH2, which strongly indicates a phenotype associated with hereditary nonpolyposis colorectal cancer (HNPCC). Conclusions MSI occurs only in a small fraction of the tumors from young patients with rectal cancer, but when present it strongly indicates an underlying HNPCC-causing mutation, and other mechanisms than HNPCC thus cause rectal cancer in the majority of young patients. PMID:12379157

  10. Rectal Disorders

    MedlinePlus

    The rectum is the lower part of your large intestine where your body stores stool. Problems with rectum are common. They include hemorrhoids, abscesses, incontinence and cancer. Many people are embarrassed to talk about rectal ...

  11. Pathological Assessment of Rectal Cancer after Neoadjuvant Chemoradiotherapy: Distribution of Residual Cancer Cells and Accuracy of Biopsy

    PubMed Central

    Xiao, Lin; Yu, Xin; Deng, Wenjing; Feng, Huixia; Chang, Hui; Xiao, Weiwei; Zhang, Huizhong; Xi, Shaoyan; Liu, Mengzhong; Zhu, Yujia; Gao, Yuanhong

    2016-01-01

    We investigated the distribution of residual cancer cells (RCCs) within different layers of the bowel wall in surgical specimens and the value of biopsies of primary rectal lesion after preoperative volumetric modulated arc therapy (VMAT) with concurrent chemotherapy in patients with rectal cancer. Between April 2011 and April 2013, 178 patients with rectal cancer who received preoperative VMAT, concurrent chemotherapy, and surgery were evaluated; 79 of the patients received a biopsy of the primary lesion after chemoradiotherapy and prior to surgery. The distribution of RCCs in the surgical specimens and the sensitivity and specificity of the biopsy of primary rectal lesions for pathological response were evaluated. Fifty-two patients had a complete pathological response in the bowel wall. Of the 120 patients with ypT2-4, the rate of detection of RCCs in the mucosa, submucosa, and muscularis propria was 20%, 36.7%, 69.2%, respectively. The sensitivity and specificity of biopsies of primary rectal lesions was 12.9% and 94.1%, respectively. After chemoradiotherapy, the RCCs were primarily located in the deeper layers of the bowel wall, and the biopsy results for primary rectal lesions were unreliable due to poor sensitivity. PMID:27721486

  12. Cross-Linked Hyaluronan Gel Reduces the Acute Rectal Toxicity of Radiotherapy for Prostate Cancer

    SciTech Connect

    Wilder, Richard B.; Barme, Greg A.; Gilbert, Ronald F.; Holevas, Richard E.; Kobashi, Luis I.; Reed, Richard R.; Solomon, Ronald S.; Walter, Nancy L.; Chittenden, Lucy; Mesa, Albert V.; Agustin, Jeffrey; Lizarde, Jessica; Macedo, Jorge; Ravera, John; Tokita, Kenneth M.

    2010-07-01

    Purpose: To prospectively analyze whether cross-linked hyaluronan gel reduces the mean rectal dose and acute rectal toxicity of radiotherapy for prostate cancer. Methods and Materials: Between September 2008 and March 2009, we transperitoneally injected 9mL of cross-linked hyaluronan gel (Hylaform; Genzyme Corporation, Cambridge, MA) into the anterior perirectal fat of 10 early-stage prostate cancer patients to increase the separation between the prostate and rectum by 8 to 18mm at the start of radiotherapy. Patients then underwent high-dose rate brachytherapy to 2,200cGy followed by intensity-modulated radiation therapy to 5,040cGy. We assessed acute rectal toxicity using the National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 grading scheme. Results: Median follow-up was 3 months. The anteroposterior dimensions of Hylaform at the start and end of radiotherapy were 13 {+-} 3mm (mean {+-} SD) and 10 {+-} 4mm, respectively. At the start of intensity-modulated radiation therapy, daily mean rectal doses were 73 {+-} 13cGy with Hylaform vs. 106 {+-} 20cGy without Hylaform (p = 0.005). There was a 0% incidence of National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 Grade 1, 2, or 3 acute diarrhea in 10 patients who received Hylaform vs. a 29.7% incidence (n = 71) in 239 historical controls who did not receive Hylaform (p = 0.04). Conclusions: By increasing the separation between the prostate and rectum, Hylaform decreased the mean rectal dose. This led to a significant reduction in the acute rectal toxicity of radiotherapy for prostate cancer.

  13. Early Proctoscopy is a Surrogate Endpoint of Late Rectal Toxicity in Prostate Cancer Treated With Radiotherapy

    SciTech Connect

    Ippolito, Edy; Massaccesi, Mariangela; Digesu, Cinzia; Deodato, Francesco; Macchia, Gabriella; Pirozzi, Giuseppe Antonio; Cilla, Savino; Cuscuna, Daniele; Di Lallo, Alessandra; Mattiucci, Gian Carlo; Mantini, Giovanna; Pacelli, Fabio; Valentini, Vincenzo; Cellini, Numa; Ingrosso, Marcello; Morganti, Alessio Giuseppe

    2012-06-01

    Purpose: To predict the grade and incidence of late clinical rectal toxicity through short-term (1 year) mucosal alterations. Methods and Materials: Patients with prostate adenocarcinoma treated with curative or adjuvant radiotherapy underwent proctoscopy a year after the course of radiotherapy. Mucosal changes were classified by the Vienna Rectoscopy Score (VRS). Late toxicity data were analyzed according to the Kaplan-Meier method. Comparison between prognosis groups was performed by log-rank analysis. Results: After a median follow-up time of 45 months (range, 18-99), the 3-year incidence of grade {>=}2 rectal late toxicity according to the criteria of the European Organization for Research and Treatment of Cancer and the Radiation Therapy Oncology Group was 24%, with all patients (24/24; 100%) experiencing rectal bleeding. The occurrence of grade {>=}2 clinical rectal late toxicity was higher in patients with grade {>=}2 (32% vs. 15 %, p = 0.02) or grade {>=}3 VRS telangiectasia (47% vs. 17%, p {<=} 0.01) and an overall VRS score of {>=}2 (31% vs. 16 %, p = 0.04) or {>=}3 (48% vs. 17%, p = 0.01) at the 1-year proctoscopy. Conclusions: Early proctoscopy (1 year) predicts late rectal bleeding and therefore can be used as a surrogate endpoint for late rectal toxicity in studies aimed at reducing this frequent complication.

  14. Systemic release of osteoprotegerin during oxaliplatin-containing induction chemotherapy and favorable systemic outcome of sequential radiotherapy in rectal cancer

    PubMed Central

    Meltzer, Sebastian; Kalanxhi, Erta; Hektoen, Helga Helseth; Dueland, Svein; Flatmark, Kjersti; Redalen, Kathrine Røe; Ree, Anne Hansen

    2016-01-01

    In colorectal cancer, immune effectors may be determinative for disease outcome. Following curatively intended combined-modality therapy in locally advanced rectal cancer metastatic disease still remains a dominant cause of failure. Here, we investigated whether circulating immune factors might correlate with outcome. An antibody array was applied to assay changes of approximately 500 proteins in serial serum samples collected from patients during oxaliplatin-containing induction chemotherapy and sequential chemoradiotherapy before final pelvic surgery. Array data was analyzed by the Significance Analysis of Microarrays software and indicated significant alterations in serum osteoprotegerin (TNFRSF11B) during the treatment course, which were confirmed by osteoprotegerin measures using a single-parameter immunoassay. Patients experiencing increase in circulating osteoprotegerin during the chemotherapy had significantly better 5-year progression-free survival than those without increase (78% versus 48%; P = 0.009 by log-rank test). Hence, systemic release of this soluble tumor necrosis factor decoy receptor following the induction phase of neoadjuvant therapy was associated with favorable long-term outcome in patients given curatively intended chemoradiotherapy and surgery but with metastatic disease as the main adverse event. This finding suggests that osteoprotegerin may mediate or reflect systemic anti-tumor immunity invoked by combined-modality therapy in locally advanced rectal cancer. PMID:27145458

  15. New technique of transanal proctectomy with completely robotic total mesorrectal excision for rectal cancer.

    PubMed

    Gómez Ruiz, Marcos; Palazuelos, Carlos Manuel; Martín Parra, José Ignacio; Alonso Martín, Joaquín; Cagigas Fernández, Carmen; del Castillo Diego, Julio; Gómez Fleitas, Manuel

    2014-05-01

    Anterior resection with total mesorectal excision is the standard method of rectal cancer resection. However, this procedure remains technically difficult in mid and low rectal cancer. A robotic transanal proctectomy with total mesorectal excision and laparoscopic assistance is reported in a 57 year old male with BMI 32 kg/m2 and rectal adenocarcinoma T2N1M0 at 5 cm from the dentate line. Operating time was 420 min. Postoperative hospital stay was 6 days and no complications were observed. Pathological report showed a 33 cm specimen with ypT2N0 adenocarcinoma at 2 cm from the distal margin, complete TME and non affected circumferential resection margin. Robotic technology might reduce some technical difficulties associated with TEM/TEO or SILS platforms in transanal total mesorectal excision. Further clinical trials will be necessary to assess this technique. PMID:24589418

  16. New technique of transanal proctectomy with completely robotic total mesorrectal excision for rectal cancer.

    PubMed

    Gómez Ruiz, Marcos; Palazuelos, Carlos Manuel; Martín Parra, José Ignacio; Alonso Martín, Joaquín; Cagigas Fernández, Carmen; del Castillo Diego, Julio; Gómez Fleitas, Manuel

    2014-05-01

    Anterior resection with total mesorectal excision is the standard method of rectal cancer resection. However, this procedure remains technically difficult in mid and low rectal cancer. A robotic transanal proctectomy with total mesorectal excision and laparoscopic assistance is reported in a 57 year old male with BMI 32 kg/m2 and rectal adenocarcinoma T2N1M0 at 5 cm from the dentate line. Operating time was 420 min. Postoperative hospital stay was 6 days and no complications were observed. Pathological report showed a 33 cm specimen with ypT2N0 adenocarcinoma at 2 cm from the distal margin, complete TME and non affected circumferential resection margin. Robotic technology might reduce some technical difficulties associated with TEM/TEO or SILS platforms in transanal total mesorectal excision. Further clinical trials will be necessary to assess this technique.

  17. Significance of Cox-2 expression in rectal cancers with or without preoperative radiotherapy

    SciTech Connect

    Pachkoria, Ketevan; Zhang Hong; Adell, Gunnar; Jarlsfelt, Ingvar; Sun Xiaofeng . E-mail: xiao-feng.sun@ibk.liu.se

    2005-11-01

    Purpose: Radiotherapy has reduced local recurrence of rectal cancers, but the result is not satisfactory. Further biologic factors are needed to identify patients for more effective radiotherapy. Our aims were to investigate the relationship of cyclooxygenase-2 (Cox-2) expression to radiotherapy, and clinicopathologic/biologic variables in rectal cancers with or without radiotherapy. Methods and Materials: Cox-2 expression was immunohistochemically examined in distal normal mucosa (n = 28), in adjacent normal mucosa (n = 107), in primary cancer (n = 138), lymph node metastasis (n = 30), and biopsy (n = 85). The patients participated in a rectal cancer trial of preoperative radiotherapy. Results: Cox-2 expression was increased in primary tumor compared with normal mucosa (p < 0.0001), but there was no significant change between primary tumor and metastasis. Cox-2 positivity was or tended to be related to more p53 and Ki-67 expression, and less apoptosis (p {<=} 0.05). In Cox-2-negative cases of either biopsy (p = 0.01) or surgical samples (p = 0.02), radiotherapy was related to less frequency of local recurrence, but this was not the case in Cox-2-positive cases. Conclusion: Cox-2 expression seemed to be an early event involved in rectal cancer development. Radiotherapy might reduce a rate of local recurrence in the patients with Cox-2 weakly stained tumors, but not in those with Cox-2 strongly stained tumors.

  18. Simultaneous resection for rectal cancer with synchronous liver metastasis is a safe procedure

    PubMed Central

    Silberhumer, Gerd R.; Paty, Philip B.; Temple, Larissa K.; Araujo, Raphael L. C.; Denton, Brian; Gonen, Mithat; Nash, Garret M.; Allen, Peter J.; DeMatteo, Ronald P.; Guillem, Jose; Weiser, Martin R.; D'Angelica, Michael I.; Jarnagin, William R.; Wong, W. Douglas; Fong, Yuman

    2015-01-01

    OBJECTIVE To examine the outcome of simultaneous resection for rectal cancer with synchronous liver metastases. BACKGROUND One quarter of colorectal cancer patients will present with liver metastasis at the time of diagnosis. Recent studies have shown that simultaneous resections are safe and feasible for stage IV colon cancer. Limited data are available for simultaneous surgery in stage IV rectal cancer patients. METHODS One hundred ninety-eight patients underwent surgical treatment for stage IV rectal cancer. In 145 (73%) patients, a simultaneous procedure was performed. Fifty-three (27%) patients underwent staged liver resection. A subpopulation of 69 (35%) patients underwent major liver resection (3 segments or more) and 30 (44%) patients with simultaneous surgery. RESULTS The demographics of the 2 groups were similar. Complication rates were comparable for simultaneous or staged resections, even in the group subjected to major liver resection. Total hospital stay was significantly shorter for the simultaneously resected patients (P < .01). CONCLUSIONS Simultaneous resection of rectal primaries and liver metastases is a safe procedure in carefully selected patients at high-volume institutions, even if major liver resections are required. PMID:25601556

  19. Remission of Unresectable Lung Metastases from Rectal Cancer After Herbal Medicine Treatment: A Case Report.

    PubMed

    Kim, Kyungsuk; Lee, Sanghun

    2016-01-01

    Lung metastasis is frequent in rectal cancer patients and has a poor prognosis, with an expected three-year survival rate of about 10%. Though western medicine has made great strides in the curative resection of liver metastases, resection of lung metastases has lagged far behind. Many preclinical studies have suggested that herbal treatments block metastasis, but few clinical studies have addressed this topic. We present the case of a 57-year-old Asian male with lung metastases from rectal cancer. He first underwent resection of the primary lesion (stage IIA, T3N0M0) and six cycles of adjuvant chemotherapy. Unfortunately, lung metastases were confirmed about one year later. Palliative chemotherapy was begun, but his disease continued to progress after three cycles and chemotherapy was halted. The patient was exclusively treated with herbal medicine-standardized allergen-removed Rhus verniciflua stokes extract combined with Dokhwaljihwang-tang (Sasang constitutional medicine in Korea). After seven weeks of herbal medicine treatment, the lung metastases were markedly improved. Regression of lung metastases has continued; also, the patient's rectal cancer has not returned. He has been receiving herbal medicine for over two years and very few side effects have been observed. We suggest that the herbal regimen used in our patient is a promising candidate for the treatment of lung metastases secondary to rectal cancer, and we hope that this case stimulates further investigation into the efficacy of herbal treatments for metastatic colorectal cancer patients.

  20. Efficacy Endpoints of RTOG 0247: A Randomized Phase II Study of Neoadjuvant Radiation Therapy Plus Concurrent Capecitabine and Irinotecan or Capecitabine and Oxaliplatin for Patients with Locally Advanced Rectal Cancer

    PubMed Central

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

    2015-01-01

    Purpose/Objectives Primary endpoint analysis of RTOG 0247 demonstrated preoperative RT with capecitabine plus oxaliplatin achieved a pCR pre-specified threshold (21%) to merit further study, whereas the RT with capecitabine plus irinotecan arm did not (10%). Secondary efficacy endpoints are reported here. Methods and Materials A randomized phase II trial evaluated preoperative RT (50.4 Gy in 1.8 Gy fractions) with two concurrent chemotherapy regimens: 1—capecitabine (1200 mg/m2/d M-F) plus irinotecan (50 mg/m2 /week × 4); and 2—capecitabine (1650 mg/m2/d M-F) plus oxaliplatin (50 mg/m2 /week × 5) for clinical T3 or T4 rectal cancer. Surgery was performed 4-8 weeks following chemoradiation, then 4-6 weeks later, adjuvant chemotherapy (oxaliplatin 85 mg/m2; leucovorin 400 mg/m2; 5FU 400 mg/m2; 5FU 2400 mg/m2) every 2 weeks × 9. Disease-free survival (DFS) and overall survival (OS) were estimated univariately by the Kaplan-Meier method. Local-regional failure (LRF), distant failure (DF), and second primary failure (SP) were estimated by the cumulative incidence method. No statistical comparisons were made between arms as each was evaluated individually. Results 104 patients (median age 57) were treated; characteristics were similar for both arms. Median follow-up for RT with capecitabine/irinotecan arm was 3.77 years and for RT with capecitabine/oxaliplatin arm was 3.97 years. Four-year DFS, OS, LRF, DF, and SP estimates for capecitabine/irinotecan arm are 68%, 85%, 16%, 24%, and 2%, respectively. The 4-year DFS, OS, LRF, DF, and SP failure estimates for capecitabine/oxaliplatin arm are 62%, 75%, 18%, 30%, and 6%, respectively. Conclusions Efficacy results for both arms are similar to other reported studies but suggest that pCR is an unsuitable surrogate for traditional survival metrics of clinical outcome. While it remains uncertain if the addition of a second cytotoxic agent enhances the effectiveness of fluorouracil plus RT, these results suggest further

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

    SciTech Connect

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

    2015-01-01

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

  2. Dynamic contrast-enhanced magnetic resonance imaging of radiation therapy-induced microcirculation changes in rectal cancer

    SciTech Connect

    Lussanet, Quido G. de . E-mail: qdlu@rdia.azm.nl; Backes, Walter H.; Griffioen, Arjan W.; Padhani, Anwar R.; Baeten, Coen I.; Baardwijk, Angela van; Lambin, Philippe; Beets, Geerard L.; Engelshoven, Jos van; Beets-Tan, Regina G.H.

    2005-12-01

    Purpose: Dynamic contrast-enhanced T1-weighted magnetic resonance imaging (DCE-MRI) allows noninvasive evaluation of tumor microvasculature characteristics. This study evaluated radiation therapy related microvascular changes in locally advanced rectal cancer by DCE-MRI and histology. Methods and Materials: Dynamic contrast-enhanced-MRI was performed in 17 patients with primary rectal cancer. Seven patients underwent 25 fractions of 1.8 Gy radiation therapy (RT) (long RT) before DCE-MRI and 10 did not. Of these 10, 3 patients underwent five fractions of 5 Gy RT (short RT) in the week before surgery. The RT treated and nontreated groups were compared in terms of endothelial transfer coefficient (K{sup PS}, measured by DCE-MRI), microvessel density (MVD) (scored by immunoreactivity to CD31 and CD34), and tumor cell and endothelial cell proliferation (scored by immunoreactivity to Ki67). Results: Tumor K{sup PS} was 77% (p = 0.03) lower in the RT-treated group. Histogram analyses showed that RT reduced both magnitude and intratumor heterogeneity of K{sup PS} (p = 0.01). MVD was significantly lower (37%, p 0.03) in tumors treated with long RT than in nonirradiated tumors, but this was not the case with short RT. Endothelial cell proliferation was reduced with short RT (81%, p = 0.02) just before surgery, but not with long RT (p > 0.8). Tumor cell proliferation was reduced with both long (57%, p < 0.001) and short RT (52%, p = 0.002). Conclusion: Dynamic contrast-enhanced-MRI-derived K{sup PS} values showed significant radiation therapy related reductions in microvessel blood flow in locally advanced rectal cancer. These findings may be useful in evaluating effects of radiation combination therapies (e.g., chemoradiation or RT combined with antiangiogenesis therapy), to account for effects of RT alone.

  3. Preliminary analysis of risk factors for late rectal toxicity after helical tomotherapy for prostate cancer.

    PubMed

    Tomita, Natsuo; Soga, Norihito; Ogura, Yuji; Hayashi, Norio; Shimizu, Hidetoshi; Kubota, Takashi; Ito, Junji; Hirata, Kimiko; Ohshima, Yukihiko; Tachibana, Hiroyuki; Kodaira, Takeshi

    2013-09-01

    The purpose of this study is to examine risk factors for late rectal toxicity for localized prostate cancer patients treated with helical tomotherapy (HT). The patient cohort of this retrospective study was composed of 241 patients treated with HT and followed up regularly. Toxicity levels were scored according to the Radiation Therapy Oncology Group grading scale. The clinical and dosimetric potential factors increasing the risk of late rectal toxicity, such as age, diabetes, anticoagulants, prior abdominal surgery, prescribed dose, maximum dose of the rectum, and the percentage of the rectum covered by 70 Gy (V70), 60 Gy (V60), 40 Gy (V40) and 20 Gy (V20) were compared between ≤ Grade 1 and ≥ Grade 2 toxicity groups using the Student's t-test. Multivariable logistic regression analysis of the factors that appeared to be associated with the risk of late rectal toxicity (as determined by the Student's t-test) was performed. The median follow-up time was 35 months. Late Grade 2-3 rectal toxicity was observed in 18 patients (7.4%). Age, the maximum dose of the rectum, V70 and V60 of the ≥ Grade 2 toxicity group were significantly higher than in those of the ≤ Grade 1 toxicity group (P = 0.00093, 0.048, 0.0030 and 0.0021, respectively). No factor was significant in the multivariable analysis. The result of this study indicates that the risk of late rectal toxicity correlates with the rectal volume exposed to high doses of HT for localized prostate cancer. Further follow-up and data accumulation may establish dose-volume modeling to predict rectal complications after HT.

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

    SciTech Connect

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

    2006-10-01

    Purpose: Epidermal growth factor receptor (EGFR) has been associated with radioresistance in solid tumors. Recently a polymorphism in the Sp1 recognition site of the EGFR promoter region was identified. The present study investigated the predictive value of this polymorphism for the outcome of chemoradiation in locally advanced rectal cancer. Methods and Materials: The study included 77 patients with locally advanced T3 rectal tumors. Treatment consisted of preoperative radiation therapy at a total tumor dose of 65 Gy and concomitant chemotherapy with Uftoral. Blood samples from 63 patients were evaluated for Sp1 -216 G/T polymorphism by polymerase chain reaction analysis. Forty-eight primary tumor biopsies were available for EGFR immunostaining. Patients underwent surgery 8 weeks after treatment. Pathologic response evaluation was performed according to the tumor regression grade (TRG) system. Results: Forty-nine percent had major response (TRG1-2) and 51% moderate response (TRG 3-4) to chemoradiation. The rates of major response were 34% (10/29) in GG homozygote patients compared with 65% (22/34) in patients with T containing variants (p = 0.023). Fifty-eight percent of biopsies were positive for EGFR expression (28/48). The major response rates with regard to EGFR immunostaining were not significantly different. EGFR-positive tumors were found in 83% of the GG homozygote patients compared with 38% of patients with TT or GT variants (p = 0.008). Conclusions: There was a significant correlation between EGFR Sp1 -216 G/T polymorphism and treatment response to chemoradiation in locally advanced rectal cancer. Further investigations of a second set of patient and other treatment schedules are warranted.

  5. Quantitative analysis of rectal cancer by spectral domain optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Zhang, Q. Q.; Wu, X. J.; Tang, T.; Zhu, S. W.; Yao, Q.; Gao, Bruce Z.; Yuan, X. C.

    2012-08-01

    To quantify OCT images of rectal tissue for clinic diagnosis, the scattering coefficient of the tissue is extracted by curve fitting the OCT signals to a confocal single model. A total of 1000 measurements (half and half of normal and malignant tissues) were obtained from 16 recta. The normal rectal tissue has a larger scattering coefficient ranging from 1.09 to 5.41 mm-1 with a mean value of 2.29 mm-1 (std:±0.32), while the malignant group shows lower scattering property and the values ranging from 0.25 to 2.69 mm-1 with a mean value of 1.41 mm-1 (std:±0.18). The peri-cancer of recta has also been investigated to distinguish the difference between normal and malignant rectal tissue. The results demonstrate that the quantitative analysis of the rectal tissue can be used as a promising diagnostic criterion of early rectal cancer, which has great value for clinical medical applications.

  6. Caveolin-1 as a Prognostic Marker for Local Control After Preoperative Chemoradiation Therapy in Rectal Cancer

    SciTech Connect

    Roedel, Franz Capalbo, Gianni; Roedel, Claus; Weiss, Christian

    2009-03-01

    Purpose: Caveolin-1 is a protein marker for caveolae organelles and has an essential impact on cellular signal transduction pathways (e.g., receptor tyrosine kinases, adhesion molecules, and G-protein-coupled receptors). In the present study, we investigated the expression of caveolin-1 in patients with rectal adenocarcinoma and correlated its expression pattern with the risk for disease recurrences after preoperative chemoradiation therapy (CRT) and surgical resection. Methods and Materials: Caveolin-1 mRNA and protein expression were evaluated by Affymetrix microarray analysis (n = 20) and immunohistochemistry (n = 44) on pretreatment biopsy samples of patients with locally advanced adenocarcinoma of the rectum, and were correlated with clinical and histopathologic characteristics as well as with 5-year rates of local failure and overall survival. Results: A significantly decreased median caveolin-1 intracellular mRNA level was observed in tumor biopsy samples as compared with noncancerous mucosa. Individual mRNA levels and immunohistologic staining, however, revealed an overexpression in 7 of 20 patients (35%) and 17 of 44 patients (38.6%), respectively. Based on immunohistochemical evaluation, local control rates at 5 years for patients with tumors showing low caveolin-1 expression were significantly better than for patients with high caveolin-1-expressing carcinoma cells (p = 0.05; 92%, 95% confidence interval [95% CI] = 82-102% vs. 72%, 95% CI = 49-84%). A low caveolin-1 protein expression was also significantly related to an increased overall survival rate (p = 0.05; 45%, 95% CI 16-60% vs. 82%, 95% CI = 67-97%). Conclusion: Caveolin-1 may provide a novel prognostic marker for local control and survival after preoperative CRT and surgical resection in rectal cancer.

  7. Vaccine Therapy With or Without Sargramostim in Treating Patients With Advanced or Metastatic Cancer

    ClinicalTrials.gov

    2013-01-24

    Adenocarcinoma of the Colon; Adenocarcinoma of the Gallbladder; Adenocarcinoma of the Pancreas; Adenocarcinoma of the Rectum; Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Gallbladder; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Male Breast Cancer; Mixed Adenocarcinoma of the Stomach; Ovarian Endometrioid Adenocarcinoma; Paget Disease of the Breast With Intraductal Carcinoma; Paget Disease of the Breast With Invasive Ductal Carcinoma; Recurrent Adult Primary Liver Cancer; Recurrent Breast Cancer; Recurrent Colon Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Salivary Gland Cancer; Salivary Gland Adenocarcinoma; Stage II Malignant Testicular Germ Cell Tumor; Stage II Pancreatic Cancer; Stage III Colon Cancer; Stage III Gastric Cancer; Stage III Malignant Testicular Germ Cell Tumor; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Salivary Gland Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IV Breast Cancer; Stage IV Colon Cancer; Stage IV Gastric Cancer; Stage IV Pancreatic Cancer; Stage IV Rectal Cancer; Stage IV Salivary Gland Cancer; Thyroid Gland Medullary Carcinoma; Unresectable Gallbladder Cancer

  8. [Application of radiotherapy in perioperative comprehensive treatment for the elderly with rectal cancer].

    PubMed

    Cai, Xin; Zhang, Zhen

    2016-05-01

    Considered that most of the phase II or III clinical trials contain less elderly patients or only contain those who had good health status, these results might not be applied in those elderly patients with some complex status. The patients of 70 years old or more usually have complications or worse organ function, thus the standard treatment for them becomes a gray zone. In rectal cancer patients, the rate of elderly patients receiving standard chemoradiotherapy (CRT) is obviously lower than that of the younger ones. More and more retrospective studies found that the prognosis of the elderly (≥70) who received neo-adjuvant or adjuvant CRT was better than that of those who received surgery or radiotherapy only, and the outcome of the above-mentioned elderly was similar to those of other phase III trial or younger patients with good tolerance. In addition, some studies revealed patients with good status, less or slight complications had a better prognosis. The advance of radiation therapy, such as Image-guided Radiation Therapy (IGRT), Intensity-modulated Radiation Therapy (IMRT), Stereotactic Body Radiation Therapy (SBRT), brachytherapy and particle therapy, will benefit the elderly cancer patients. We think that treatments recommended to the elderly will become more personalized.

  9. Role of Peroxiredoxin I in Rectal Cancer and Related to p53 Status

    SciTech Connect

    Chen, Miao-Fen; Lee, Kuan-Der; Yeh, Chung-Hung; Chen, Wen-Cheng; Huang, Wen-Shih; Chin, Chih-Chien; Lin, Paul- Yang; Wang, Jeng-Yi

    2010-11-01

    Background: Neoadjuvant chemoradiotherapy is widely accepted for the treatment of localized rectal cancer. Although peroxiredoxin I (PrxI) and p53 have been implicated in carcinogenesis and cancer treatment, the role of PrxI and its interaction with p53 in the prognosis and treatment response of rectal cancer remain relatively unstudied. Methods and Materials: In the present study, we examined the levels of PrxI and p53 in rectal cancer patients using membrane arrays and compared them with normal population samples. To demonstrate the biologic changes after manipulation of PrxI expression, we established stable transfectants of HCT-116 (wild-type p53) and HT-29 (mutant p53) cells with a PrxI silencing vector. The predictive capacities of PrxI and p53 were also assessed by relating the immunohistochemical staining of a retrospective series of rectal cancer cases to the clinical outcome. Results: The membrane array and immunochemical staining data showed that PrxI, but not p53, was significantly associated with the tumor burden. Our immunochemistry findings further indicated that PrxI positivity was linked to a poor response to neoadjuvant therapy and worse survival. In cellular and animal experiments, the inhibition of PrxI significantly decreased tumor growth and sensitized the tumor to irradiation, as indicated by a lower capacity to scavenge reactive oxygen species and more extensive DNA damage. The p53 status might have contributed to the difference between HCT-116 and HT-29 after knockdown of PrxI. Conclusion: According to our data, the level of PrxI combined with the p53 status is relevant to the prognosis and the treatment response. We suggested that PrxI might be a new biomarker for rectal cancer.

  10. Rectal cancer mortality and total hardness levels in Taiwan's drinking water.

    PubMed

    Yang, C Y; Tsai, S S; Lai, T C; Hung, C F; Chiu, H F

    1999-05-01

    The possible association between the risk of rectal cancer and hardness levels in drinking water from municipal supplies was investigated in a matched case-control study in Taiwan. All eligible rectal cancer deaths (986 cases) of Taiwan residents from 1990 through 1994 were compared with deaths from other causes (986 controls), and the hardness levels of the drinking water used by these residents were determined. Data on water hardness throughout Taiwan were collected from Taiwan Water Supply Corporation (TWSC). The control group consisted of people who died from other causes and the controls were pair matched to the cases by sex, year of birth, and year of death. The results show a significant negative relationship between drinking water hardness and rectal cancer mortality. Odds ratio and 95% confidence intervals were 1.24 (1.01-1. 55) and 1.38 (1.10-1.73), respectively, for exposure to moderately hard water and soft water compared with the use of hard water. Trend analyses showed an increasing odds ratio for rectal cancer with decreasing levels of hardness in drinking water. This is an important finding for the Taiwan water industry and human health.

  11. [Current situation and outlook of transanal total mesorectum excision in rectal cancer].

    PubMed

    Kang, Liang; Wang, Jianping

    2016-08-25

    Since the characteristics of metastasis and invasion of rectal cancer are confirmed gradually, the aim of surgical treatment in rectal cancer is to protect anal and reproductive function, and to minimize the damage of patients. With prominent advantages of identified lower tumor resection margin, enough circumference resection margin, more minimally invasive procedure and faster recovery, transanal total mesorectal excision(taTME) integrated with natural canal theory, transanal minimally invasive technique and TME can effectively solve the difficulties of transabdominal procedure and becomes the research hotspot in rectal cancer surgery worldwide. Though taTME is still at the initial stage and has certain problems, such as the definition of operational procedure, careful performance of standard operation, further summary of operational detail and skill, observation of long-term efficacy and optimization design of operational instruments, it will be supported by high-level evidence based on increasing cases, maturation of procedure, and clinical multicenter cohort researches. TaTME has a good application prospect and may become one of the main procedures of colorectal surgery to treat the middle or low rectal cancer.

  12. Analysis of Risk Factors and Management of Anastomotic Leakage After Rectal Cancer Surgery: An Indian Series.

    PubMed

    Jatal, Sudhir; Pai, Vishwas D; Demenezes, Jean; Desouza, Ashwin; Saklani, Avanish P

    2016-03-01

    The primary objective of this study was to determine whether sphincter preservation is possible among patients who develop anastomotic leakage after rectal cancer surgery. The secondary objective was to determine the factors that may contribute to anastomotic leakage. This is a retrospective review of a prospectively maintained database. All patients with rectal cancer who underwent restorative proctectomy over 1 year were included in the study. The parameters analyzed were age, preoperative hemoglobin and albumin, neoadjuvant therapy, type of surgery, level of ligation of inferior mesenteric pedicle, technique of anastomosis, and defunctioning proximal stoma. In this study, 176 cases of anterior resection were included,of which15 (8.5 %) had anastomotic leakage. None of the factors contributing to anastomotic leakage reached statistical significance on univariate analysis. Among the patients who had proximal defunctioning ileostomy (n = 9), five (56 %) required re-surgery whereas other four were managed with antibiotics and presacral drainage alone (44 %). Among the patients who didnot have proximal defunctioning ileostomy (n = 6), all (100 %) required re-surgery. Among the 12 eligible patients, stoma reversal was successful in eight (67 %) patients. This study highlights the importance of defunctioning proximal stoma in reducing the incidence and severity of anastomotic leakage as well as the need and extent of re-surgery for low rectal cancer. Sphincter preservation is possible in majority of patients who develop anastomotic leakage after rectal cancer surgery.

  13. [Current situation and outlook of transanal total mesorectum excision in rectal cancer].

    PubMed

    Kang, Liang; Wang, Jianping

    2016-08-25

    Since the characteristics of metastasis and invasion of rectal cancer are confirmed gradually, the aim of surgical treatment in rectal cancer is to protect anal and reproductive function, and to minimize the damage of patients. With prominent advantages of identified lower tumor resection margin, enough circumference resection margin, more minimally invasive procedure and faster recovery, transanal total mesorectal excision(taTME) integrated with natural canal theory, transanal minimally invasive technique and TME can effectively solve the difficulties of transabdominal procedure and becomes the research hotspot in rectal cancer surgery worldwide. Though taTME is still at the initial stage and has certain problems, such as the definition of operational procedure, careful performance of standard operation, further summary of operational detail and skill, observation of long-term efficacy and optimization design of operational instruments, it will be supported by high-level evidence based on increasing cases, maturation of procedure, and clinical multicenter cohort researches. TaTME has a good application prospect and may become one of the main procedures of colorectal surgery to treat the middle or low rectal cancer. PMID:27545460

  14. Image-guided intensity-modulated radiotherapy for prostate cancer: Dose constraints for the anterior rectal wall to minimize rectal toxicity

    SciTech Connect

    Peterson, Jennifer L.; Buskirk, Steven J.; Heckman, Michael G.; Diehl, Nancy N.; Bernard, Johnny R.; Tzou, Katherine S.; Casale, Henry E.; Bellefontaine, Louis P.; Serago, Christopher; Kim, Siyong; Vallow, Laura A.; Daugherty, Larry C.; Ko, Stephen J.

    2014-04-01

    Rectal adverse events (AEs) are a major concern with definitive radiotherapy (RT) treatment for prostate cancer. The anterior rectal wall is at the greatest risk of injury as it lies closest to the target volume and receives the highest dose of RT. This study evaluated the absolute volume of anterior rectal wall receiving a high dose to identify potential ideal dose constraints that can minimize rectal AEs. A total of 111 consecutive patients with Stage T1c to T3a N0 M0 prostate cancer who underwent image-guided intensity-modulated RT at our institution were included. AEs were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. The volume of anterior rectal wall receiving 5 to 80 Gy in 2.5-Gy increments was determined. Multivariable Cox regression models were used to identify cut points in these volumes that led to an increased risk of early and late rectal AEs. Early AEs occurred in most patients (88%); however, relatively few of them (13%) were grade ≥2. At 5 years, the cumulative incidence of late rectal AEs was 37%, with only 5% being grade ≥2. For almost all RT doses, we identified a threshold of irradiated absolute volume of anterior rectal wall above which there was at least a trend toward a significantly higher rate of AEs. Most strikingly, patients with more than 1.29, 0.73, or 0.45 cm{sup 3} of anterior rectal wall exposed to radiation doses of 67.5, 70, or 72.5 Gy, respectively, had a significantly increased risk of late AEs (relative risks [RR]: 2.18 to 2.72; p ≤ 0.041) and of grade ≥ 2 early AEs (RR: 6.36 to 6.48; p = 0.004). Our study provides evidence that definitive image-guided intensity-modulated radiotherapy (IG-IMRT) for prostate cancer is well tolerated and also identifies dose thresholds for the absolute volume of anterior rectal wall above which patients are at greater risk of early and late complications.

  15. Collaborative case conferences in rectal cancer: case series in a tertiary care centre

    PubMed Central

    Eskicioglu, C.; Forbes, S.; Tsai, S.; Francescutti, V.; Coates, A.; Grubac, V.; Sonnadara, R.; Simunovic, M.

    2016-01-01

    Background In many hospitals, resource barriers preclude the use of preoperative multidisciplinary cancer conferences (mccs) for consecutive patients with cancer. Collaborative cancer conferences (cccs) are modified mccs that might overcome such barriers. Methods We established a ccc at an academic tertiary care centre to review preoperative plans for patients with rectal cancer. Attendees included only surgeons who perform colorectal cancer procedures and a radiologist with expertise in cross-sectional imaging. Individual reviews began with the primary surgeon presenting the case information and initial treatment recommendations. Cross-sectional images were then reviewed, the case was discussed, and consensus on ccc-treatment recommendations was achieved. Outcomes for the present study were changes in treatment recommendations defined as “major” (that is, redirection of patient to preoperative radiation from straight-to-surgery or uncertain plan, or redirection of the patient to straight-to-surgery from preoperative radiation or plan uncertain) or as “minor” (that is, referral to a multidisciplinary cancer clinic, request additional tests, change type of neoadjuvant therapy, change type of surgery). Chart reviews provided relevant patient, tumour, and treatment information. Results Between September 2011 and September 2012, 101 rectal cancer patients were discussed at a ccc. Of the 35 management plans (34.7%) that were changed as a result, 8 had major changes, and 27 had minor changes. Available patient and tumour factors did not predict for a change in treatment recommendation. Conclusions Preoperative cccs at a tertiary-care centre changed treatment recommendations for one third of patients with rectal cancer. Given that no specific factor predicted for a treatment plan change, it is likely prudent that all rectal cancer patients undergo some form of collaborative review. PMID:27122982

  16. Robotic surgery for rectal cancer: current immediate clinical and oncological outcomes.

    PubMed

    Araujo, Sergio Eduardo Alonso; Seid, Victor Edmond; Klajner, Sidney

    2014-10-21

    Laparoscopic rectal surgery continues to be a challenging operation associated to a steep learning curve. Robotic surgical systems have dramatically changed minimally invasive surgery. Three-dimensional, magnified and stable view, articulated instruments, and reduction of physiologic tremors leading to superior dexterity and ergonomics. Therefore, robotic platforms could potentially address limitations of laparoscopic rectal surgery. It was aimed at reviewing current literature on short-term clinical and oncological (pathological) outcomes after robotic rectal cancer surgery in comparison with laparoscopic surgery. A systematic review was performed for the period 2002 to 2014. A total of 1776 patients with rectal cancer underwent minimally invasive robotic treatment in 32 studies. After robotic and laparoscopic approach to oncologic rectal surgery, respectively, mean operating time varied from 192-385 min, and from 158-297 min; mean estimated blood loss was between 33 and 283 mL, and between 127 and 300 mL; mean length of stay varied from 4-10 d; and from 6-15 d. Conversion after robotic rectal surgery varied from 0% to 9.4%, and from 0 to 22% after laparoscopy. There was no difference between robotic (0%-41.3%) and laparoscopic (5.5%-29.3%) surgery regarding morbidity and anastomotic complications (respectively, 0%-13.5%, and 0%-11.1%). Regarding immediate oncologic outcomes, respectively among robotic and laparoscopic cases, positive circumferential margins varied from 0% to 7.5%, and from 0% to 8.8%; the mean number of retrieved lymph nodes was between 10 and 20, and between 11 and 21; and the mean distal resection margin was from 0.8 to 4.7 cm, and from 1.9 to 4.5 cm. Robotic rectal cancer surgery is being undertaken by experienced surgeons. However, the quality of the assembled evidence does not support definite conclusions about most studies variables. Robotic rectal cancer surgery is associated to increased costs and operating time. It also seems to be

  17. Robotic surgery for rectal cancer: current immediate clinical and oncological outcomes.

    PubMed

    Araujo, Sergio Eduardo Alonso; Seid, Victor Edmond; Klajner, Sidney

    2014-10-21

    Laparoscopic rectal surgery continues to be a challenging operation associated to a steep learning curve. Robotic surgical systems have dramatically changed minimally invasive surgery. Three-dimensional, magnified and stable view, articulated instruments, and reduction of physiologic tremors leading to superior dexterity and ergonomics. Therefore, robotic platforms could potentially address limitations of laparoscopic rectal surgery. It was aimed at reviewing current literature on short-term clinical and oncological (pathological) outcomes after robotic rectal cancer surgery in comparison with laparoscopic surgery. A systematic review was performed for the period 2002 to 2014. A total of 1776 patients with rectal cancer underwent minimally invasive robotic treatment in 32 studies. After robotic and laparoscopic approach to oncologic rectal surgery, respectively, mean operating time varied from 192-385 min, and from 158-297 min; mean estimated blood loss was between 33 and 283 mL, and between 127 and 300 mL; mean length of stay varied from 4-10 d; and from 6-15 d. Conversion after robotic rectal surgery varied from 0% to 9.4%, and from 0 to 22% after laparoscopy. There was no difference between robotic (0%-41.3%) and laparoscopic (5.5%-29.3%) surgery regarding morbidity and anastomotic complications (respectively, 0%-13.5%, and 0%-11.1%). Regarding immediate oncologic outcomes, respectively among robotic and laparoscopic cases, positive circumferential margins varied from 0% to 7.5%, and from 0% to 8.8%; the mean number of retrieved lymph nodes was between 10 and 20, and between 11 and 21; and the mean distal resection margin was from 0.8 to 4.7 cm, and from 1.9 to 4.5 cm. Robotic rectal cancer surgery is being undertaken by experienced surgeons. However, the quality of the assembled evidence does not support definite conclusions about most studies variables. Robotic rectal cancer surgery is associated to increased costs and operating time. It also seems to be

  18. Meta-analysis of robotic and laparoscopic surgery for treatment of rectal cancer

    PubMed Central

    Lin, Shuang; Jiang, Hong-Gang; Chen, Zhi-Heng; Zhou, Shu-Yang; Liu, Xiao-Sun; Yu, Ji-Ren

    2011-01-01

    AIM: To conduct a meta-analysis to determine the relative merits of robotic surgery (RS) and laparoscopic surgery (LS) for rectal cancer. METHODS: A literature search was performed to identify comparative studies reporting perioperative outcomes for RS and LS for rectal cancer. Pooled odds ratios and weighted mean differences (WMDs) with 95% confidence intervals (95% CIs) were calculated using either the fixed effects model or random effects model. RESULTS: Eight studies matched the selection criteria and reported on 661 subjects, of whom 268 underwent RS and 393 underwent LS for rectal cancer. Compared the perioperative outcomes of RS with LS, reports of RS indicated favorable outcomes considering conversion (WMD: 0.25; 95% CI: 0.11-0.58; P = 0.001). Meanwhile, operative time (WMD: 27.92, 95% CI: -13.43 to 69.27; P = 0.19); blood loss (WMD: -32.35, 95% CI: -86.19 to 21.50; P = 0.24); days to passing flatus (WMD: -0.18, 95% CI: -0.96 to 0.60; P = 0.65); length of stay (WMD: -0.04; 95% CI: -2.28 to 2.20; P = 0.97); complications (WMD: 1.05; 95% CI: 0.71-1.55; P = 0.82) and pathological details, including lymph nodes harvested (WMD: 0.41, 95% CI: -0.67 to 1.50; P = 0.46), distal resection margin (WMD: -0.35, 95% CI: -1.27 to 0.58; P = 0.46), and positive circumferential resection margin (WMD: 0.54, 95% CI: 0.12-2.39; P = 0.42) were similar between RS and LS. CONCLUSION: RS for rectal cancer is superior to LS in terms of conversion. RS may be an alternative treatment for rectal cancer. Further studies are required. PMID:22215947

  19. Future directions in combined modality therapy for rectal cancer: reevaluating the role of total mesorectal excision after chemoradiotherapy

    PubMed Central

    Solanki, Abhishek A; Chang, Daniel T; Liauw, Stanley L

    2013-01-01

    Most patients who develop rectal cancer present with locoregionally advanced (T3 or node-positive) disease. The standard management of locoregionally advanced rectal cancer is neoadjuvant concurrent chemoradiotherapy (nCRT), followed by radical resection (low-anterior resection or abdominoperineal resection with total mesorectal excision). Approximately 15% of patients can have a pathologic complete response (pCR) at the time of surgery, indicating that some patients can have no detectable residual disease after nCRT. The actual benefit of surgery in this group of patients is unclear. It is possible that omission of surgery in these patients, termed selective nonoperative management, can limit the toxicities associated with standard, multimodal combined modality therapy without compromising disease control. In this review, we discuss the clinical experiences to date using selective nonoperative management and various attempts at escalation of nCRT to improve the number of patients who have a pCR. We also explore several clinical, laboratory, imaging, histopathologic, and genetic biomarkers that have been tested as tools to predict which patients are most likely to have a pCR after nCRT. PMID:23983475

  20. [Current status and novel approach of robotic surgery for rectal cancer].

    PubMed

    Du, Xiaohui

    2015-08-01

    With the development of minimally invasive surgery, laparoscopic technique is now widely used in rectal surgery because of its advantages in terms of pain control, recovery of bowel function, length of hospital stay, short- and long-term outcomes. Total mesorectal excision(TME) is recommended as the standard procedure for rectal cancer. Laparoscopic TME, however, can be challenging due to its two-dimensional vision, restricted instrument movements, and a prolonged learning curve. Robotic surgery overcomes these intrinsic limitations by superior three-dimensional magnified optics, stable retraction platform, and 7 degrees of freedom of instrument movements, and offers an easier operation and shorter learning curve. This review summarizes the advantages as well as the current status of robotic rectal surgery, and explores the novel approach and new techniques with the related literature and the author's own experience. PMID:26303685

  1. [Current status and novel approach of robotic surgery for rectal cancer].

    PubMed

    Du, Xiaohui

    2015-08-01

    With the development of minimally invasive surgery, laparoscopic technique is now widely used in rectal surgery because of its advantages in terms of pain control, recovery of bowel function, length of hospital stay, short- and long-term outcomes. Total mesorectal excision(TME) is recommended as the standard procedure for rectal cancer. Laparoscopic TME, however, can be challenging due to its two-dimensional vision, restricted instrument movements, and a prolonged learning curve. Robotic surgery overcomes these intrinsic limitations by superior three-dimensional magnified optics, stable retraction platform, and 7 degrees of freedom of instrument movements, and offers an easier operation and shorter learning curve. This review summarizes the advantages as well as the current status of robotic rectal surgery, and explores the novel approach and new techniques with the related literature and the author's own experience.

  2. Pretreatment Evaluation of Microcirculation by Dynamic Contrast-Enhanced Magnetic Resonance Imaging Predicts Survival in Primary Rectal Cancer Patients

    SciTech Connect

    DeVries, Alexander Friedrich; Piringer, Gudrun; Kremser, Christian; Judmaier, Werner; Saely, Christoph Hubert; Lukas, Peter; Öfner, Dietmar

    2014-12-01

    Purpose: To investigate the prognostic value of the perfusion index (PI), a microcirculatory parameter estimated from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), which integrates information on both flow and permeability, to predict overall survival and disease-free survival in patients with primary rectal cancer. Methods and Materials: A total of 83 patients with stage cT3 rectal cancer requiring neoadjuvant chemoradiation were investigated with DCE-MRI before start of therapy. Contrast-enhanced dynamic T{sub 1} mapping was obtained, and a simple data analysis strategy based on the calculation of the maximum slope of the tissue concentration–time curve divided by the maximum of the arterial input function was used as a measure of tumor microcirculation (PI), which integrates information on both flow and permeability. Results: In 39 patients (47.0%), T downstaging (ypT0-2) was observed. During a mean (±SD) follow-up period of 71 ± 29 months, 58 patients (69.9%) survived, and disease-free survival was achieved in 45 patients (54.2%). The mean PI (PImean) averaged over the group of nonresponders was significantly higher than for responders. Additionally, higher PImean in age- and gender-adjusted analyses was strongly predictive of therapy nonresponse. Most importantly, PImean strongly and significantly predicted disease-free survival (unadjusted hazard ratio [HR], 1.85 [ 95% confidence interval, 1.35-2.54; P<.001)]; HR adjusted for age and sex, 1.81 [1.30-2.51]; P<.001) as well as overall survival (unadjusted HR 1.42 [1.02-1.99], P=.040; HR adjusted for age and sex, 1.43 [1.03-1.98]; P=.034). Conclusions: This analysis identifies PImean as a novel biomarker that is predictive for therapy response, disease-free survival, and overall survival in patients with primary locally advanced rectal cancer.

  3. Random Forests to Predict Rectal Toxicity Following Prostate Cancer Radiation Therapy

    SciTech Connect

    Ospina, Juan D.; Zhu, Jian; Chira, Ciprian; Bossi, Alberto; Delobel, Jean B.; Beckendorf, Véronique; Dubray, Bernard; Lagrange, Jean-Léon; Correa, Juan C.; and others

    2014-08-01

    Purpose: To propose a random forest normal tissue complication probability (RF-NTCP) model to predict late rectal toxicity following prostate cancer radiation therapy, and to compare its performance to that of classic NTCP models. Methods and Materials: Clinical data and dose-volume histograms (DVH) were collected from 261 patients who received 3-dimensional conformal radiation therapy for prostate cancer with at least 5 years of follow-up. The series was split 1000 times into training and validation cohorts. A RF was trained to predict the risk of 5-year overall rectal toxicity and bleeding. Parameters of the Lyman-Kutcher-Burman (LKB) model were identified and a logistic regression model was fit. The performance of all the models was assessed by computing the area under the receiving operating characteristic curve (AUC). Results: The 5-year grade ≥2 overall rectal toxicity and grade ≥1 and grade ≥2 rectal bleeding rates were 16%, 25%, and 10%, respectively. Predictive capabilities were obtained using the RF-NTCP model for all 3 toxicity endpoints, including both the training and validation cohorts. The age and use of anticoagulants were found to be predictors of rectal bleeding. The AUC for RF-NTCP ranged from 0.66 to 0.76, depending on the toxicity endpoint. The AUC values for the LKB-NTCP were statistically significantly inferior, ranging from 0.62 to 0.69. Conclusions: The RF-NTCP model may be a useful new tool in predicting late rectal toxicity, including variables other than DVH, and thus appears as a strong competitor to classic NTCP models.

  4. A case of capecitabine-induced coronary microspasm in a patient with rectal cancer

    PubMed Central

    Arbea, Leire; Coma-Canella, Isabel; Martinez-Monge, Rafael; García-Foncillas, Jesús

    2007-01-01

    5-Fluorouracil (5-FU) is the most frequently used chemotherapy agent concomitant with radiotherapy in the management of patients with rectal cancer. Capecitabine is an oral fluoropyrimidine that mimics the pharmaconkinetics of infusional 5-FU. This new drug is replacing 5-FU as a part of the combined-modality treatment of a number of gastrointestinal cancers. While cardiac events associated with the use of 5-FU are a well known side effect, capecitabine-induced cardiotoxicity has been only rarely reported. Here, we reviewed the case of a patient with rectal cancer who had a capecitabine-induced coronary vasospasm. The most prominent mutation of the dihydropyrimidine dehydrogenase gene was also analyzed. PMID:17465463

  5. [Composite resection of sciatic nerve for local recurrence of rectal cancer].

    PubMed

    Kameyama, M; Nakamori, S; Imaoka, S; Hinakawa, M; Sasaki, Y; Ishikawa, O; Kabuto, T; Furukawa, H; Iwanaga, T; Ueda, T

    1993-08-01

    Three patients with local recurrence of rectal cancer involving the sciatic nerve underwent radical pelvic exenteration combined with sciatic nerve resection. This surgical procedure resulted in complete relief of intolerable cancer pain in all patients. After the rehabilitation, all could walk unassisted by wearing only a below-the-knee leg brace. The first patient died 16 months postoperatively due to multiple liver metastasis, but no local recurrence was documented. The second patient is alive 13 months postoperatively with bone and liver metastasis and pelvic wall recurrence. The third patient is alive 7 months postoperatively with no evidence of disease. Composite resection of lateral sciatic nerve improved the quality of life in patients who had local recurrence of rectal cancer with sciatic nerve involvement.

  6. Expression of PRL proteins at invasive margin of rectal cancers in relation to preoperative radiotherapy

    SciTech Connect

    Wallin, Asa R.; Svanvik, Joar; Adell, Gunnar; Sun Xiaofeng . E-mail: xiasu@ibk.liu.se

    2006-06-01

    Purpose: PRL-3 (phosphatase of regenerating liver) is involved in metastasis of colorectal cancer; however, its therapeutic implication in cancer patients has not been studied. We investigated the relationships of PRL expression to radiotherapy (RT) in rectal cancer patients. Methods and Materials: Phosphatase of regenerating liver expression was immunohistochemically examined in distant (n = 36) and adjacent (n = 82) normal mucosa, primary tumor (n = 125), biopsy specimens (n = 96), and lymph node metastasis (n = 30) from rectal cancer patients participating in a clinical trial of preoperative RT. Results: Phosphatase of regenerating liver expression was increased from the distant to adjacent mucosa and to the primary tumor (p < 0.05). PRL was highly expressed at the invasive margin in 28% of the primary tumors and 26% of the metastases. In the RT group, strong PRL expression at the invasive margin was related to distant recurrence (p 0.006) and poor survival (p = 0.01), but not in the non-RT group. The survival significance remained even after adjusting for Dukes' stage and differentiation (p = 0.02). Additional multivariate analyses showed that the correlation with prognostic significance of PRL differed between the RT and non-RT groups (p = 0.01). Conclusion: Phosphatase of regenerating liver expression (rather than PRL-3 alone) at the invasive margin predicted resistance to RT and unfavorable survival in rectal cancer patients with preoperative RT.

  7. Increased expression of FERM domain-containing 4A protein is closely associated with the development of rectal cancer

    PubMed Central

    FAN, YONGTIAN; LI, DECHUAN; QIAN, JUN; LIU, YONG; FENG, HAIYANG; LI, DECHUAN

    2016-01-01

    The aim of the present study was to detect the expression levels of FERM domain-containing 4A (FRMD4A) in rectal cancer tissues and peripheral blood and to investigate the correlation between FRMD4A and cancer development. A total of 78 consecutive patients were enrolled in this study. Thirty healthy individuals were used as the control group. The expression of FRMD4A in rectal cancer and the corresponding normal adjacent tissues was detected by immunohistochemistry and western blotting. The expression of FRMD4A mRNA in peripheral blood was detected by reverse transcription-quantitative polymerase chain reaction. The expression of FRMD4A in rectal cancer tissues was found to be negatively correlated with the degree of differentiation, depth of invasion and Dukes' stage. A negative correlation was identified between FRMD4A and epithelial cadherin expression. The expression of FRMD4A in the peripheral blood of patients with rectal cancer was significantly increased compared with that in the control group (P<0.05). Expression of FRMD4A in the peripheral blood in the patients with lymph node metastasis was significantly increased compared with that in the patients without lymph node metastasis (P<0.05). These results indicate that the expression of FRMD4A is significantly increased in rectal cancer tissues and the peripheral blood of patients with rectal cancer, and the expression levels of FRMD4A are closely associated with differentiation, invasion of rectal cancer and Dukes' stage. In conclusion, the findings of the present study suggest that FRMD4A may be used as a target for the diagnosis and treatment of rectal cancer. PMID:26893625

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

    SciTech Connect

    Dzhugashvili, Maia; Luengo-Gil, Ginés; García, Teresa; González-Conejero, Rocío; Conesa-Zamora, Pablo; Escolar, Pedro Pablo; Calvo, Felipe; Vicente, Vicente; Ayala de la Peña, Francisco

    2014-11-01

    Purpose: To investigate whether polymorphisms of genes related to inflammation are associated with pathologic response (primary endpoint) in patients with rectal cancer treated with primary chemoradiation therapy (PCRT). Methods and Materials: Genomic DNA of 159 patients with locally advanced rectal cancer treated with PCRT was genotyped for polymorphisms rs28362491 (NFKB1), rs1213266/rs5789 (PTGS1), rs5275 (PTGS2), and rs16944/rs1143627 (IL1B) using TaqMan single nucleotide polymorphism genotyping assays. The association between each genotype and pathologic response (poor response vs complete or partial response) was analyzed using logistic regression models. Results: The NFKB1 DEL/DEL genotype was associated with pathologic response (odds ratio [OR], 6.39; 95% confidence interval [CI], 0.78-52.65; P=.03) after PCRT. No statistically significant associations between other polymorphisms and response to PCRT were observed. Patients with the NFKB1 DEL/DEL genotype showed a trend for longer disease-free survival (log-rank test, P=.096) and overall survival (P=.049), which was not significant in a multivariate analysis that included pathologic response. Analysis for 6 polymorphisms showed that patients carrying the haplotype rs28362491-DEL/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G (13.7% of cases) had a higher response rate to PCRT (OR, 8.86; 95% CI, 1.21-64.98; P=.034) than the reference group (rs28362491-INS/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G). Clinically significant (grade ≥2) acute organ toxicity was also more frequent in patients with that same haplotype (OR, 4.12; 95% CI, 1.11-15.36; P=.037). Conclusions: Our results suggest that genetic variation in NFKB-related inflammatory pathways might influence sensitivity to primary chemoradiation for rectal cancer. If confirmed, an inflammation-related radiogenetic profile might be used to select patients with rectal cancer for preoperative combined-modality treatment.

  9. Predictive Response Value of Pre- and Postchemoradiotherapy Variables in Rectal Cancer: An Analysis of Histological Data

    PubMed Central

    Santos, Marisa D.; Silva, Cristina; Rocha, Anabela; Nogueira, Carlos; Matos, Eduarda; Lopes, Carlos

    2016-01-01

    Background. Neoadjuvant chemoradiotherapy (nCRT) followed by curative surgery in locally advanced rectal cancer (LARC) improves pelvic disease control. Survival improvement is achieved only if pathological response occurs. Mandard tumor regression grade (TRG) proved to be a valid system to measure nCRT response. Potential predictive factors for Mandard response are analyzed. Materials and Methods. 167 patients with LARC were treated with nCRT and curative surgery. Tumor biopsies and surgical specimens were reviewed and analyzed regarding mitotic count, necrosis, desmoplastic reaction, and inflammatory infiltration grade. Surgical specimens were classified according to Mandard TRG. The patients were divided as “good responders” (Mandard TRG1-2) and “bad responders” (Mandard TRG3-5). According to results from our previous data, good responders have better prognosis than bad responders. We examined predictive factors for Mandard response and performed statistical analysis. Results. In univariate analysis, distance from anal verge and ten other postoperative variables related with nCRT tumor response had predictive value for Mandard response. In multivariable analysis only mitotic count, necrosis, and differentiation grade in surgical specimen had predictive value. Conclusions. There is a lack of clinical and pathological preoperative variables able to predict Mandard response. Only postoperative pathological parameters related with nCRT response have predictive value. PMID:26885438

  10. Complete Response after Chemoradiotherapy in Rectal Cancer (Watch-and-Wait): Have we Cracked the Code?

    PubMed

    Glynne-Jones, R; Hughes, R

    2016-02-01

    Patients with locally advanced rectal cancer receive preoperative chemoradiation as the standard of care, producing a pathological complete response in 10-20% and a complete clinical response (CCR) in 20-30%. Small observational studies suggest a selective non-operative management with rigorous surveillance is an option and is increasingly being advocated in many parts of the world for patients who achieve a CCR or near CCR. The assumption is that oncological outcomes for good responders, who are observed, compare favourably with patients subjected to radical surgery. Late regrowth of the primary is rare, almost invariably endoluminal and, hence, can be salvaged. However, concerns remain among some surgeons and oncologists regarding the reproducibility of published results in routine practice. We have previously reviewed this topic. The aim of this brief overview was to re-assess the feasibility and safety of a non-operative approach based on the currently available literature. We make recommendations as to the quality of care required to undertake this management. Significant heterogeneity remains in the initial inclusion criteria, staging and restaging methods, study design, timing of assessment, duration and rigour of follow-up of the trials reviewed - all of which obscure the validity of the results.

  11. [A Case Report of a Pathological Complete Response of Rectal Cancer to Preoperative Chemoradiotherapy with Tegafur].

    PubMed

    Morikawa, Tatsuya; Teraishi, Fuminori; Shima, Yasuo; Iwata, Jun

    2016-03-01

    We report the case of a patient with advanced rectal cancer who achieved a pathological complete response to preoperative chemoradiotherapy (CRT). A 65-year-old man was diagnosed as having a two-thirds circumferential well-to moderately differentiated tumor (Rb-P, type 2). To control local recurrence, we treated the patient with CRT. Radiotherapy was administered in fractions of 2 Gy/day (total, 40 Gy). Concurrently, S-1 was administered orally at a fixed daily dose of 80 mg/m2 for 20 days. Withdrawal and/or dose reduction of S-1 was not necessary in spite of Grade 1 or 2 toxic effects, including diarrhea and periproctitis, occurring on day 7. Laparoscopic abdominoperineal resection was performed 6 weeks after the final dose of chemotherapy was administered. The histopathological regression grade was Grade 3. No recurrence was detected on enhanced CT more than 5 years after surgery. This case suggests that the regimen was both effective and tolerated, and that preoperative chemoradiotherapy may be effective for tumor suppression to prevent local recurrence. PMID:27067861

  12. The effect of preoperative chemoradiotherapy on lymph nodes harvested in TME for rectal cancer

    PubMed Central

    2013-01-01

    Background Adequate lymph nodes resection in rectal cancer is important for staging and local control. This retrospective analysis single center study evaluated the effect of neoadjuvant chemoradiation on the number of lymph nodes in rectal carcinoma, considering some clinicopathological parameters. Methods A total of 111 patients undergone total mesorectal excision for rectal adenocarcinoma from July 2005 to May 2012 in our center were included. No patient underwent any prior pelvic surgery or radiotherapy. Chemoradiotherapy was indicated in patients with rectal cancer stage II or III before chemoradiation. Results One-hundred and eleven patients were considered. The mean age was 67.6 yrs (range 36 – 84, SD 10.8). Fifty (45.0%) received neoadjuvant therapy before resection. The mean number of removed lymph nodes was 13.6 (range 0–39, SD 7.3). In the patients who received neoadjuvant therapy the number of nodes detected was lower (11.5, SD 6.5 vs. 15.3, SD 7.5, p = 0.006). 37.4% of patients with preoperative chemoradiotherapy had 12 or more lymph nodes in the specimen compared to the 63.6% of those who had surgery at the first step (p: 0.006). Other factors associated in univariate analysis with lower lymph nodes yield included stage (p 0.005) and grade (p 0.0003) of the tumour. Age, sex, tumor site, type of operation, surgeons and pathologists did not weight upon the number of the removed lymph nodes. Conclusion In TME surgery for rectal cancer, preoperative CRT results into a reduction of lymph nodes yield in univariate analisys and linear regression. PMID:24246069

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

    PubMed Central

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

    2016-01-01

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

  14. New Perspectives on Predictive Biomarkers of Tumor Response and Their Clinical Application in Preoperative Chemoradiation Therapy for Rectal Cancer

    PubMed Central

    Hur, Hyuk

    2015-01-01

    Preoperative chemoradiation therapy (CRT) is the standard treatment for patients with locally advanced rectal cancer (LARC) and can improve local control and survival outcomes. However, the responses of individual tumors to CRT are not uniform and vary widely, from complete response to disease progression. Patients with resistant tumors can be exposed to irradiation and chemotherapy that are both expensive and at times toxic without benefit. In contrast, about 60% of tumors show tumor regression and T and N down-staging. Furthermore, a pathologic complete response (pCR), which is characterized by sterilization of all tumor cells, leads to an excellent prognosis and is observed in approximately 10-30% of cases. This variety in tumor response has lead to an increased need to develop a model predictive of responses to CRT in order to identify patients who will benefit from this multimodal treatment. Endoscopy, magnetic resonance imaging, positron emission tomography, serum carcinoembryonic antigen, and molecular biomarkers analyzed using immunohistochemistry and gene expression profiling are the most commonly used predictive models in preoperative CRT. Such modalities guide clinicians in choosing the best possible treatment options and the extent of surgery for each individual patient. However, there are still controversies regarding study outcomes, and a nomogram of combined models of future trends is needed to better predict patient response. The aim of this article was to review currently available tools for predicting tumor response after preoperative CRT in rectal cancer and to explore their applicability in clinical practice for tailored treatment. PMID:26446626

  15. CXCL10 mRNA expression predicts response to neoadjuvant chemoradiotherapy in rectal cancer patients.

    PubMed

    Li, Cong; Wang, Zhimin; Liu, Fangqi; Zhu, Ji; Yang, Li; Cai, Guoxiang; Zhang, Zhen; Huang, Wei; Cai, Sanjun; Xu, Ye

    2014-10-01

    Chemoradiotherapy has been commonly used as neoadjuvant therapy for rectal cancer to allow for less aggressive surgical approaches and to improve quality of life. In cancer, it has been reported that CXCL10 has an anti-tumor function. However, the association between CXCL10 and chemoradiosensitivity has not been fully investigated. We performed this study to investigate the relationship between CXCL10 expression and chemoradiosensitivity in rectal cancer patients. Ninety-five patients with rectal cancer who received neoadjuvant chemoradiotherapy (NCRT) were included. Clinical parameters were compared with the outcome of NCRT and CXCL10 messenger RNA (mRNA) expression between the pathological complete response (pCR) group and non-pathological complete response (npCR) group. CXCL10 mRNA and protein expressions between groups were analyzed using the Student's t test and chi-square test. The mean mRNA level of CXCL10 in the pCR group was significantly higher than that in the npCR group (p = 0.010). In the pCR group, 73.7 % of the patients had high CXCL10 mRNA expression, and 61.4 % of the patients in the npCR group had low CXCL10 mRNA expression. Subjects with high CXCL10 mRNA expression demonstrated a higher sensitivity to NCRT (p = 0.011). The receiver operating characteristic curve showed that the diagnostic performance of CXCL10 mRNA expression had an area under the curve of 0.720 (95 % confidence interval, 0.573-0.867). There were no differences between the pCR and npCR groups in CXCL10 protein expression (p > 0.05). High CXCL10 mRNA expression is associated with a better tumor response to NCRT in rectal cancer patients and may predict the outcome of NCRT in this malignancy.

  16. Low or Ultralow Anterior Resection of Rectal Cancer Without Diverting Stoma: Experience with 28 Patients.

    PubMed

    Soltani, E; Jangjoo, A; Saremi, E

    2015-12-01

    A diverting temporary stoma is frequently used to decrease the chance of anastomosis leakage in the middle and lower rectum cancer surgeries, but its role in preventing the leakage is still doubtful. This study has been designed to evaluate any possible anastomosis complications after a rectum resection and a low or ultralow anastomosis when no diverting stoma is applied in patients with rectal cancer. Twenty-eight patients suffering from rectal cancer were treated by a low anterior resection between the years 2005 and 2008 in Imam Reza University Hospital, Mashhad, Iran. Out of the 28 patients, 6 patients had already undergone a course of neoadjuvant radiotherapy. Anastomosis was performed manually in 23 patients, using a stapler in 5 of them. None of the patients had a diverting stoma. Then, the outcome was evaluated. Fecal incontinence occurred in one of the patients (6.7 %) who had already undergone a course of radiotherapy preoperatively and had a stapler used for anastomosis. No leakage was detected in any of them. The very low incidence of complications in this study, such as those not preventable by a diverting stoma, suggest a very low chance of leakage in low or ultralow anastomosis in patients with rectal cancer and in those who were treated with neoadjuvant radiotherapy. PMID:26730038

  17. In rectal cancer, the type of desmoplastic response after preoperative chemoradiotherapy is associated with prognosis.

    PubMed

    Ueno, Hideki; Shinto, Eiji; Hashiguchi, Yojiro; Shimazaki, Hideyuki; Kajiwara, Yoshiki; Sueyama, Takahiro; Yamamoto, Junji; Hase, Kazuo

    2015-06-01

    Although the essential contribution of the desmoplastic reaction (DR) to aggressive tumor behavior is increasingly recognized, its prognostic value has not been investigated in rectal cancer after preoperative chemoradiotherapy. We retrospectively analyzed 101 consecutive patients with rectal cancer treated with short-course chemoradiotherapy followed by surgery (2001-2007). The DR in the resected primary tumor was pathologically classified into three patterns on the basis of products of cancer-associated fibroblasts (CAFs): mature (multilayered fibrotic), intermediate (keloid-like hyalinized), and immature (mostly myxoid). We classified 46 tumors as mature, 30 as intermediate, and 25 as immature DR. In addition, immunostaining of CD8(+) and FoxP3(+) cells was performed to characterize the immune response accompanying DR. Mature DR correlated with higher density of CD8(+) and FoxP3(+) cells in both resected surgical and pretreatment biopsy specimens. A significant association with DR category was observed for T stage, lymphatic invasion, and venous invasion (P ≤ 0.0001-0.0006). Mature DR was significantly associated with higher grade of pathological response (P = 0.0350). The 5-year disease-free survival (DFS) rates were 82, 72, and 47 % for mature, intermediate, and immature DR, respectively (P = 0.0055). On multivariate analysis, DR category and ypN were independently predictive of DFS. The pattern of the DR in rectal cancers after chemoradiotherapy treatment might have a prognostic value, as it likely reflects pretreatment desmoplastic environment.

  18. [Endorectal echotomography in assessing the spread of rectal cancer].

    PubMed

    Bilenko, A A; Didarchuk, S P

    1998-01-01

    Endorectal echotomography is one of modern methods to diagnose rectal carcinoma spreading. On the basis of examination of 56 patients with the above pathology the authors have studied the ultrasonic semiotics of tumourous lesion of rectum and its regional lymphatic apparatus during different stages of the illness. The article contains an outline of the methods of investigation. The findings from ultrasonic diagnosis were compared with the results of clinical, endoscopic investigations and histological analysis of the operative material. A high diagnostic value was shown of the method in the assessment of local spread of the tumor: sensitivity--94.6%, specificity--83.3%, general precision--91.8%. Endorectal ultrasonic tomography permits the enlarged pararectal lymphatic nodes to be visualized but the method's demerit is lack of ultrasonic criteria in the differential diagnosis between the metastatic lesion of the lymphatic node and inflammatory type changes.

  19. Influence of image slice thickness on rectal dose-response relationships following radiotherapy of prostate cancer

    NASA Astrophysics Data System (ADS)

    Olsson, C.; Thor, M.; Liu, M.; Moissenko, V.; Petersen, S. E.; Høyer, M.; Apte, A.; Deasy, J. O.

    2014-07-01

    When pooling retrospective data from different cohorts, slice thicknesses of acquired computed tomography (CT) images used for treatment planning may vary between cohorts. It is, however, not known if varying slice thickness influences derived dose-response relationships. We investigated this for rectal bleeding using dose-volume histograms (DVHs) of the rectum and rectal wall for dose distributions superimposed on images with varying CT slice thicknesses. We used dose and endpoint data from two prostate cancer cohorts treated with three-dimensional conformal radiotherapy to either 74 Gy (N = 159) or 78 Gy (N = 159) at 2 Gy per fraction. The rectum was defined as the whole organ with content, and the morbidity cut-off was Grade ≥2 late rectal bleeding. Rectal walls were defined as 3 mm inner margins added to the rectum. DVHs for simulated slice thicknesses from 3 to 13 mm were compared to DVHs for the originally acquired slice thicknesses at 3 and 5 mm. Volumes, mean, and maximum doses were assessed from the DVHs, and generalized equivalent uniform dose (gEUD) values were calculated. For each organ and each of the simulated slice thicknesses, we performed predictive modeling of late rectal bleeding using the Lyman-Kutcher-Burman (LKB) model. For the most coarse slice thickness, rectal volumes increased (≤18%), whereas maximum and mean doses decreased (≤0.8 and ≤4.2 Gy, respectively). For all a values, the gEUD for the simulated DVHs were ≤1.9 Gy different than the gEUD for the original DVHs. The best-fitting LKB model parameter values with 95% CIs were consistent between all DVHs. In conclusion, we found that the investigated slice thickness variations had minimal impact on rectal dose-response estimations. From the perspective of predictive modeling, our results suggest that variations within 10 mm in slice thickness between cohorts are unlikely to be a limiting factor when pooling multi-institutional rectal dose data that include slice thickness

  20. Genotypic characteristics of resistant tumors to pre-operative ionizing radiation in rectal cancer

    PubMed Central

    Ramzan, Zeeshan; Nassri, Ammar B; Huerta, Sergio

    2014-01-01

    Due to a wide range of clinical response in patients undergoing neo-adjuvant chemoradiation for rectal cancer it is essential to understand molecular factors that lead to the broad response observed in patients receiving the same form of treatment. Despite extensive research in this field, the exact mechanisms still remain elusive. Data raging from DNA-repair to specific molecules leading to cell survival as well as resistance to apoptosis have been investigated. Individually, or in combination, there is no single pathway that has become clinically applicable to date. In the following review, we describe the current status of various pathways that might lead to resistance to the therapeutic applications of ionizing radiation in rectal cancer. PMID:25024812

  1. [The role of cross-sectional imaging in staging of rectal cancer].

    PubMed

    Schäfer, A O; Langer, M; Baumann, T

    2012-05-01

    The ongoing diversification of treatment strategies for rectal cancer justifies the demand for highly specialized radiological imaging. Currently, numerous studies have underlined the ability of magnetic resonance imaging (MRI) to determine those parameters that are critical for therapeutic decision-making and prognosis in rectal cancer. Computed tomography (CT) does not meet the criteria of a first line diagnostic procedure with regard to local staging but will remain the workhorse in the search for distant metastases. The increasing acceptance of extended MRI-based concepts will, however, improve cost-effectiveness and simplify patient management. Response evaluation and detection of recurrent disease are the major indications for positron emission tomography (PET)/CT, which is currently not routinely recommended.

  2. Underlying anatomy for CTV contouring and lymphatic drainage in rectal cancer radiation therapy.

    PubMed

    Arcangeli, Stefano; Valentini, Vincenzo; Nori, Stefania L; Fares, Claudia; Dinapoli, Nicola; Gambacorta, Maria Antonierrta

    2003-01-01

    Despite the low local recurrence rate that can be achieved by adequate surgery (total mesorectal excision--TME), radiation therapy was shown to play a significant role in reducing this risk. The widespread use of TME in many European Centers has introduced a new terminology and the need to identify the area at major risk for local failure using this surgical procedure. In the surgical series where extended extra-mesorectal surgery was performed, the role of lymphatic spread was evidenced, especially for low rectal cancer, through the pelvic parietal fascia and lateral pelvic spaces. The aim of this study was to better define some anatomic concepts and the main risk factors which impact on CTV contouring and field conformation in rectal cancer treatment. This information helps formulating guidelines for CTV contouring in daily radiotherapy practice, in order to define the best therapy, according to the tumor stage and location. PMID:15018321

  3. Reduced Acute Bowel Toxicity in Patients Treated With Intensity-Modulated Radiotherapy for Rectal Cancer

    SciTech Connect

    Samuelian, Jason M.; Callister, Matthew D.; Ashman, Jonathan B.; Young-Fadok, Tonia M.; Borad, Mitesh J.; Gunderson, Leonard L.

    2012-04-01

    Purpose: We have previously shown that intensity-modulated radiotherapy (IMRT) can reduce dose to small bowel, bladder, and bone marrow compared with three-field conventional radiotherapy (CRT) technique in the treatment of rectal cancer. The purpose of this study was to review our experience using IMRT to treat rectal cancer and report patient clinical outcomes. Methods and Materials: A retrospective review was conducted of patients with rectal cancer who were treated at Mayo Clinic Arizona with pelvic radiotherapy (RT). Data regarding patient and tumor characteristics, treatment, acute toxicity according to the Common Terminology Criteria for Adverse Events v 3.0, tumor response, and perioperative morbidity were collected. Results: From 2004 to August 2009, 92 consecutive patients were treated. Sixty-one (66%) patients were treated with CRT, and 31 (34%) patients were treated with IMRT. All but 2 patients received concurrent chemotherapy. There was no significant difference in median dose (50.4 Gy, CRT; 50 Gy, IMRT), preoperative vs. postoperative treatment, type of concurrent chemotherapy, or history of previous pelvic RT between the CRT and IMRT patient groups. Patients who received IMRT had significantly less gastrointestinal (GI) toxicity. Sixty-two percent of patients undergoing CRT experienced {>=}Grade 2 acute GI side effects, compared with 32% among IMRT patients (p = 0.006). The reduction in overall GI toxicity was attributable to fewer symptoms from the lower GI tract. Among CRT patients, {>=}Grade 2 diarrhea and enteritis was experienced among 48% and 30% of patients, respectively, compared with 23% (p = 0.02) and 10% (p = 0.015) among IMRT patients. There was no significant difference in hematologic or genitourinary acute toxicity between groups. In addition, pathologic complete response rates and postoperative morbidity between treatment groups did not differ significantly. Conclusions: In the management of rectal cancer, IMRT is associated with a

  4. Radiotherapy for Rectal Cancer Is Associated With Reduced Serum Testosterone and Increased FSH and LH

    SciTech Connect

    Bruheim, Kjersti Svartberg, Johan; Carlsen, Erik; Dueland, Svein; Haug, Egil; Skovlund, Eva; Tveit, Kjell Magne; Guren, Marianne G.

    2008-03-01

    Purpose: It is known that scattered radiation to the testes during pelvic radiotherapy can affect fertility, but there is little knowledge on its effects on male sex hormones. The aim of this study was to determine whether radiotherapy for rectal cancer affects testosterone production. Methods and Materials: All male patients who had received adjuvant radiotherapy for rectal cancer from 1993 to 2003 were identified from the Norwegian Rectal Cancer Registry. Patients treated with surgery alone were randomly selected from the same registry as control subjects. Serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and sex hormone binding globulin (SHBG) were analyzed, and free testosterone was calculated (N = 290). Information about the radiotherapy treatment was collected from the patient hospital charts. Results: Serum FSH was 3 times higher in the radiotherapy group than in the control group (median, 18.8 vs. 6.3 IU/L, p <0.001), and serum LH was 1.7 times higher (median, 7.5 vs. 4.5 IU/l, p <0.001). In the radiotherapy group, 27% of patients had testosterone levels below the reference range (8-35 nmol/L), compared with 10% of the nonirradiated patients (p <0.001). Irradiated patients had lower serum testosterone (mean, 11.1 vs. 13.4 nmol/L, p <0.001) and lower calculated free testosterone (mean, 214 vs. 235 pmol/L, p <0.05) than control subjects. Total testosterone, calculated free testosterone, and gonadotropins were related to the distance from the bony pelvic structures to the caudal field edge. Conclusions: Increased serum levels of gonadotropins and subnormal serum levels of testosterone indicate that curative radiotherapy for rectal cancer can result in permanent testicular dysfunction.

  5. Salvage high-dose-rate interstitial brachytherapy for locally recurrent rectal cancer*

    PubMed Central

    Pellizzon, Antônio Cássio Assis

    2016-01-01

    For tumors of the lower third of the rectum, the only safe surgical procedure is abdominal-perineal resection. High-dose-rate interstitial brachytherapy is a promising treatment for local recurrence of previously irradiated lower rectal cancer, due to the extremely high concentrated dose delivered to the tumor and the sparing of normal tissue, when compared with a course of external beam radiation therapy. PMID:27403021

  6. Robotic surgery for rectal cancer: A systematic review of current practice

    PubMed Central

    Mak, Tony Wing Chung; Lee, Janet Fung Yee; Futaba, Kaori; Hon, Sophie Sok Fei; Ngo, Dennis Kwok Yu; Ng, Simon Siu Man

    2014-01-01

    AIM: To give a comprehensive review of current literature on robotic rectal cancer surgery. METHODS: A systematic review of current literature via PubMed and Embase search engines was performed to identify relevant articles from january 2007 to november 2013. The keywords used were: “robotic surgery”, “surgical robotics”, “laparoscopic computer-assisted surgery”, “colectomy” and “rectal resection”. RESULTS: After the initial screen of 380 articles, 20 papers were selected for review. A total of 1062 patients (male 64.0%) with a mean age of 61.1 years and body mass index of 24.9 kg/m2 were included in the review. Out of 1062 robotic-assisted operations, 831 (78.2%) anterior and low anterior resections, 132 (12.4%) intersphincteric resection with coloanal anastomosis, 98 (9.3%) abdominoperineal resections and 1 (0.1%) Hartmann’s operation were included in the review. Robotic rectal surgery was associated with longer operative time but with comparable oncological results and anastomotic leak rate when compared with laparoscopic rectal surgery. CONCLUSION: Robotic colorectal surgery has continued to evolve to its current state with promising results; feasible surgical option with low conversion rate and comparable short-term oncological results. The challenges faced with robotic surgery are for more high quality studies to justify its cost. PMID:24936229

  7. Multidrug resistance-associated protein 3 confers resistance to chemoradiotherapy for rectal cancer by regulating reactive oxygen species and caspase-3-dependent apoptotic pathway.

    PubMed

    Yu, Zhiqi; Zhang, Chang; Wang, Hao; Xing, Junjie; Gong, Haifeng; Yu, Enda; Zhang, Wei; Zhang, Xiaoqing; Cao, Guangwen; Fu, Chuangang

    2014-10-28

    This study aimed to clarify the role of multidrug resistance-associated protein 3 (MRP3) in resistance to neoadjuvant chemoradiotherapy and long-term prognosis of advanced rectal cancer. Immunohistochemistry was used to measure MRP3 expression in biopsy specimens of 144 stage II-III rectal cancer patients who received preoperative chemoradiotherapy. The effect of MRP3 expression on short-term pathological response and postoperative long-term prognosis were assessed using the Cox proportional hazards model. Short interfering RNAs targeting MRP3 were synthesized and used to transfect human colorectal carcinoma cell lines. The effect of MRP3 down-regulation on cell proliferation and apoptosis in response to 5-fluorouracil and/or irradiation were examined in vitro and in xenograft mouse models, respectively. The content of intracellular reactive oxygen species and the activity of caspase-3-dependent apoptotic pathway in response to irradiation were further evaluated. High expression (immunoreactive score > 6) of MRP3 significantly predicted poor pathological response to chemoradiotherapy (tumor regression grade ≤ 2 vs. ≥3, p = 0.002) in univariate analysis and unfavorable long-term prognosis (5-year overall survival: HR = 1.612, 95% CI, 1.094-2.375, p = 0.016; 5-year disease-free survival: HR = 1.513, 95% CI, 1.041-2.200, p = 0.030) in multivariate Cox analysis. MRP3 down-regulation significantly increased 5-fluorouracil or irradiation-induced cell apoptosis and attenuated tumor growth following irradiation in animal models. MRP3 inhibition significantly reduced intracellular reactive oxygen species exporting from cells following irradiation, and increased expression of cleaved poly ADP-ribose polymerase and caspase-3. Aberrant expression of MRP3 in rectal cancer confers chemo-radioresistance. MRP3 might be a predictive factor and an attractive target in treating advanced rectal cancer.

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

    SciTech Connect

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

    2009-09-01

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

  9. Transanal Tube as a Means of Prevention of Anastomotic Leakage after Rectal Cancer Surgery

    PubMed Central

    Adamova, Zuzana

    2014-01-01

    Background Anastomotic leaks after low anterior resection for rectal cancer remain the most feared complication. The aim of our study was to investigate whether the use of a transanal tube could reduce the leakage rate after this surgical procedure. Methods This is a retrospective analysis of a single-institution experience. The study includes 66 patients who underwent low anterior resection for rectal cancer without stoma creation between January 2008 and June 2013. Patients were divided into two groups, i.e. those with a transanal drainage tube (TT; n = 9) and those without tube (NTT; n = 57), and evaluated for clinically evident anastomotic leakage and postoperative complications. Results The postoperative anastomotic leakage appeared in 5 patients (9%) in the NTT group while no single case was observed within the TT group. Despite the disadvantageous background in the TT group (a transanal stent was used in the most high-risk patients), these patients had no postoperative complications. In the NTT group, 23% had some kind of postoperative complications, and 5% died. The difference between the two groups is not significant. Conclusions Our study showed that the use of a transanal tube in low anterior resection for rectal cancer could potentially be a simple and effective method of reducing anastomotic leakage. In order to prove our observations, larger prospective randomized studies should be performed. PMID:26288609

  10. Preoperative chemoradiotherapy followed by local excision in clinical T2N0 rectal cancer

    PubMed Central

    Shin, Young Seob; Yoon, Yong sik; Lim, Seok-Byung; Yu, Chang Sik; Kim, Tae Won; Chang, Heung Moon; Park, Jin-hong; Ahn, Seung Do; Lee, Sang-Wook; Choi, Eun Kyung; Kim, Jin Cheon; Kim, Jong Hoon

    2016-01-01

    Purpose To investigate whether preoperative chemoradiotherapy (PCRT) followed by local excision (LE) is feasible approach in clinical T2N0 rectal cancer patients. Materials and Methods Patients who received PCRT and LE because of clinical T2 rectal cancer within 7 cm from anal verge between January 2006 and June 2014 were retrospectively analyzed. LE was performed in case of a good clinical response after PCRT. Patients’ characteristics, treatment record, tumor recurrence, and treatment-related complications were reviewed at a median follow-up of 49 months. Results All patients received transanal excision or transanal minimally invasive surgery. Of 34 patients, 19 patients (55.9%) presented pathologic complete response (pCR). The 3-year local recurrence-free survival and disease free-survival were 100.0% and 97.1%, respectively. There was no recurrence among the patients with pCR. Except for 1 case of grade 4 enterovesical fistula, all other late complications were mild and self-limiting. Conclusion PCRT followed by an LE might be feasible as an alternative to total mesorectal excision in good responders with clinical T2N0 distal rectal cancer. PMID:27730804

  11. Tumor infiltrating lymphocytes (TILs) before and after neoadjuvant chemoradiotherapy and its clinical utility for rectal cancer

    PubMed Central

    Teng, Feifei; Mu, Dianbin; Meng, Xiangjiao; Kong, Li; Zhu, Hui; Liu, Sujing; Zhang, Jianbo; Yu, Jinming

    2015-01-01

    Backgrounds: Radiotherapy (RT) and chemotherapy (CT) can potentiate systemic antitumor immune effect. However, immunomodulation during RT or CT and their clinical implications in rectal cancer have not been thoroughly investigated. Methods: We investigated alterations in the densities of tumor infiltrating lymphocytes (TILs) during chemoradiation and their clinical utilities in patients with rectal cancer. We analyzed 136 rectal cancer patients who underwent neoadjuvant RT, CT or chemoradiotherapy (CRT), followed by radical resection retrospectively. Pretreatment biopsy specimens and posttreatment resected specimens of all patients were immunostained for CD3 and CD8. The predictive value of TILs to neoadjuvant treatment and prognosis were examined. Results: Densities of CD3+ and CD8+TILs in posttreatment specimens after RT, CT or CRT were all significantly higher than those in pretreatment specimens. There were no significant differences between each two of these three groups. High pretreatment CD3+ and CD8+TILs were associated with good response (TRG ≥ 3) after neoadjuvant treatments (P = 0.033 and 0.021). High CD3+TILs and CD8+TILs in pretreatment biopsy specimens were significantly associated with favorable disease free survival (DFS) (P = 0.010 and P = 0.022) and overall survival (OS) (P = 0.019 and P = 0.003). Conclusions: We may, thus, conclude that chemoradiation can enhance local immune response by increased TILs. High TILs densities before treatment are associated with good response to neoadjuvant chemoradiotherapy and a favorable prognosis. PMID:26269765

  12. Intraoperative fluorescence imaging to localize tumors and sentinel lymph nodes in rectal cancer.

    PubMed

    Handgraaf, Henricus J M; Boogerd, Leonora S F; Verbeek, Floris P R; Tummers, Quirijn R J G; Hardwick, James C H; Baeten, Coen I M; Frangioni, John V; van de Velde, Cornelis J H; Vahrmeijer, Alexander L

    2016-01-01

    Tumor involvement at the resection margin remains the most important predictor for local recurrence in patients with rectal cancer. A careful description of tumor localization is therefore essential. Currently, endoscopic tattooing with ink is customary, but visibility during laparoscopic resections is limited. Near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) could be an improvement. In addition to localize tumors, ICG can also be used to identify sentinel lymph nodes (SLNs). The feasibility of this new technique was explored in five patients undergoing laparoscopic low anterior resection for rectal cancer. Intraoperative tumor visualization was possible in four out of five patients. Fluorescence signal could be detected 32 ± 18 minutes after incision, while ink could be detected 42 ± 21 minutes after incision (p = 0.53). No recurrence was diagnosed within three months after surgery. Ex vivo imaging identified a mean of 4.2 ± 2.7 fluorescent lymph nodes, which were appointed SLNs. One out of a total of 83 resected lymph nodes contained a micrometastasis. This node was not fluorescent. This technical note describes the feasibility of endoscopic tattooing of rectal cancer using ICG:nanocolloid and NIR fluorescence imaging during laparoscopic resection. Simultaneous SLN mapping was also feasible, but may be less reliable due to neoadjuvant therapy.

  13. JAK/STAT/SOCS-signaling pathway and colon and rectal cancer

    PubMed Central

    Slattery, Martha L.; Lundgreen, Abbie; Kadlubar, Susan A.; Bondurant, Kristina L.; Wolff, Roger K.

    2012-01-01

    The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway is involved in immune function and cell growth. We evaluated the association between genetic variation in JAK1 (10 SNPs), JAK2 (9 SNPs), TYK2 (5 SNPs), SOCS1 (2 SNPs), SOCS2 (2 SNPs), STAT1 (16 SNPs), STAT2 (2 SNPs), STAT3 (6 SNPs), STAT4 (21 SNPs), STAT5A (2 SNPs), STAT5B (3 SNPs), STAT6 (4 SNPs) with risk of colorectal cancer. We used data from population-based case-control studies (colon cancer n=1555 cases, 1956 controls; rectal cancer n=754 cases, 959 controls). JAK2, SOCS2, STAT1, STAT3, STAT5A, STAT5B, and STAT6 were associated with colon cancer; STAT3, STAT4, STAT6, and TYK2 were associated with rectal cancer. Given the biological role of the JAK/STAT-signaling pathway and cytokines, we evaluated interaction with IFNG, TNF, and IL6; numerous statistically significant associations after adjustment for multiple comparisons were observed. The following statistically significant interactions were observed: TYK2 with aspirin/NSAID use; STAT1, STAT4, and TYK2 with estrogen status; and JAK2, STAT2, STAT4, STAT5A, STAT5B, and STAT6 with smoking status and colon cancer risk; JAK2, STAT6, and TYK2 with aspirin/NSAID use; JAK1 with estrogen status; STAT2 with cigarette smoking and rectal cancer. JAK2, SOCS1, STAT3, STAT5, and TYK2 were associated with colon cancer survival (HRR of 3.3 95% CI 2.01, 5.42 for high mutational load). JAK2, SOCS1, STAT1, STAT4, and TYK2 were associated with rectal cancer survival (HRR 2.80 95 %CI 1.63, 4.80). These data support the importance of the JAK/STAT-signaling pathway in colorectal cancer and suggest targets for intervention. PMID:22121102

  14. Panitumumab and Chemotherapy in Patients With Advanced Colorectal Cancer After Prior Therapy With Bevacizumab

    ClinicalTrials.gov

    2016-03-14

    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

  15. Adoption of Preoperative Radiation Therapy for Rectal Cancer From 2000 to 2006: A Surveillance, Epidemiology, and End Results Patterns-of-Care Study

    SciTech Connect

    Mak, Raymond H.; McCarthy, Ellen P.; Das, Prajnan; Hong, Theodore S.; Mamon, Harvey J.

    2011-07-15

    study, there was widespread, rapid adoption of preoperative RT for locally advanced rectal cancer. However, preoperative RT may be underused in certain sociodemographic groups.

  16. A case-control study of diet and colo-rectal cancer in northern Italy.

    PubMed

    La Vecchia, C; Negri, E; Decarli, A; D'Avanzo, B; Gallotti, L; Gentile, A; Franceschi, S

    1988-04-15

    The relation between dietary factors and the risk of colorectal cancer was investigated in a case-control study conducted in Northern Italy on 339 cases of colon cancer, 236 cases of rectal cancer and 778 controls admitted to hospital for acute, non-neoplastic or digestive disorders. Consistent positive associations were observed with more frequent consumption of starchy foods (pasta or rice) (relative risk, RR = 3.0 for colon and 1.8 for rectum for highest vs. lowest tertile) and beef/veal meats (RR = 2.1 for colon, 2.3 for rectum), whereas reduced relative risks were observed in subjects reporting more frequent green vegetable consumption (RR = 0.5 for highest vs. lowest tertile), a few specific vegetable or fruit items, and coffee (RR = 0.6 for highest vs. lowest tertile). Various fats in seasonings were positively, but inconsistently, related to intestinal cancer risk, whereas no association was evident with measures of whole grain foods or alcohol intake. For both intestinal sites, a 4- to 5-fold difference in risk was evident between the extreme quintiles of a simple score obtained by algebraic sum of the 4 major groups of foods. These findings could not be explained in terms of confounding by socio-economic status or other major potential distorting factors, are in agreement with the results from previous studies of colo-rectal cancer in Southern Europe, and are consistent with various aspects of the descriptive epidemiology of intestinal cancer in Italy.

  17. Predictors of Pathologic Complete Response in Rectal Cancer Patients Undergoing Total Mesorectal Excision After Preoperative Chemoradiation.

    PubMed

    Han, Yoon Dae; Kim, Woo Ram; Park, Seung Wan; Cho, Min Soo; Hur, Hyuk; Min, Byung Soh; Baik, Seung Hyuk; Lee, Kang Young; Kim, Nam Kyu

    2015-11-01

    Preoperative chemoradiotherapy (CRT) is the standard of care for patients with stage II and III rectal cancer. This strategy leads to pathologic complete response (pCR) in a significant number of patients. Factors predictive of pCR are currently being extensively investigated. The aim of this study was to analyze clinical factors that might be predictive of pCR.This study was a retrospective analysis of rectal cancer patients from January 2004 through December 2012. A total of 332 stage II and III patients with middle and low rectal cancer (≤10 cm) who received CRT and underwent curative total mesorectal excision were eligible. The median radiation dose was 50.4 Gy, and 72.6% of patients received infusional 5-fluorouracil with leucovorin, whereas 19.6% of patients received TS-1 with irinotecan, and 7.8% of patients received xeloda only. Pathologic complete response was confirmed by using pathologic specimens and analyzed based on predictive clinical factors.Among the 332 patients, 27.4% (n = 91) achieved pCR. Age, sex, body mass index, clinical T and N stages, tumor differentiation, the chemotherapy agent for CRT, and the time interval between CRT and surgery did not differ between the pCR and non-pCR groups. Carcinoembryogenic antigen (CEA) levels before CRT were 4.61 ± 7.38 ng/mL in the pCR group and 10.49 ± 23.83 ng/mL in the non-pCR group (P = 0.035). Post-CRT CEA levels were 1.4 ± 1.07 ng/mL in the pCR group and 2.16 ± 2.8 ng/mL in the non-pCR group (P = 0.014), and the proportion of middle rectal cancer patients was higher in pCR group (54.9%, P = 0.028). The results from multivariate logistic regression analysis indicated that higher tumor location (odds ratio 2.151; P = 0.003) and low post-CRT CEA level (odds ratio 0.789; P = 0.04) were independent predictive factors for pCR.Tumor location and post-CRT CEA level were predictive factors in pCR for rectal cancer patients. Therefore, these factors may

  18. Patients’ Expectations of Functional Outcomes Following Rectal Cancer Surgery: a Qualitative Study

    PubMed Central

    Park, Jason; Neuman, Heather B.; Bennett, Antonia V.; Polskin, Lily; Phang, P. Terry; Wong, W. Douglas; Temple, Larissa K.

    2014-01-01

    Background Rectal cancer patients’ expectations of health and function may affect their disease- and treatment-related experience, but how patients form expectations of post-surgery function has received little study. Objective We used a qualitative approach to explore patients’ expectations of outcomes related to bowel function following sphincter-preserving surgery (SPS) for rectal cancer. Design and Setting Individual telephone interviews with patients who were about to undergo SPS for rectal cancer. Patients 26 patients (14 men, 12 women) with clinical stage (cTNM) I to III disease. Main Outcome Measures The semi-structured interview script contained open-ended questions on patients’ expectations of post-operative bowel function and its perceived impact on daily function and life. Two researchers analyzed the interview transcripts for emergent themes using a grounded theory approach. Results Participants’ expectations of bowel function reflected three major themes: (1) information sources, (2) personal attitudes, and (3) expected outcomes. The expected outcomes theme contained references to specific symptoms and participants’ descriptions of the certainty, importance and imminence of expected outcomes. Despite multiple information sources and attempts at maintaining a positive personal attitude, participants expressed much uncertainty about their long term bowel function. They were more focused on what they considered more important and imminent concerns about being cancer-free and getting through surgery. Limitations This study is limited by context in terms of the timing of interviews (relative to the treatment course). The transferability to other contexts requires further study. Conclusions Patients’ expectations of long term functional outcomes cannot be considered outside of the overall context of the cancer-experience and the relative importance and imminence of cancer- and treatment-related events. Recognizing the complexities of the

  19. The benchmark analysis of gastric, colorectal and rectal cancer pathways: toward establishing standardized clinical pathway in the cancer care.

    PubMed

    Ryu, Munemasa; Hamano, Masaaki; Nakagawara, Akira; Shinoda, Masayuki; Shimizu, Hideaki; Miura, Takeshi; Yoshida, Isao; Nemoto, Atsushi; Yoshikawa, Aki

    2011-01-01

    Most clinical pathways in treating cancers in Japan are based on individual physician's personal experiences rather than on an empirical analysis of clinical data such as benchmark comparison with other hospitals. Therefore, these pathways are far from being standardized. By comparing detailed clinical data from five cancer centers, we have observed various differences among hospitals. By conducting benchmark analyses, providing detailed feedback to the participating hospitals and by repeating the benchmark a year later, we strive to develop more standardized clinical pathways for the treatment of cancers. The Cancer Quality Initiative was launched in 2007 by five cancer centers. Using diagnosis procedure combination data, the member hospitals benchmarked their pre-operative and post-operative length of stays, the duration of antibiotics administrations and the post-operative fasting duration for gastric, colon and rectal cancers. The benchmark was conducted by disclosing hospital identities and performed using 2007 and 2008 data. In the 2007 benchmark, substantial differences were shown among five hospitals in the treatment of gastric, colon and rectal cancers. After providing the 2007 results to the participating hospitals and organizing several brainstorming discussions, significant improvements were observed in the 2008 data study. The benchmark analysis of clinical data is extremely useful in promoting more standardized care and, thus in improving the quality of cancer treatment in Japan. By repeating the benchmark analyses, we can offer truly clinical evidence-based higher quality standardized cancer treatment to our patients.

  20. Expression of the p73 protein in rectal cancers with or without preoperative radiotherapy

    SciTech Connect

    Pfeifer, Daniella; Gao Jingfang; Adell, Gunnar; Sun Xiaofeng . E-mail: xiasu@ibk.liu.se

    2006-07-15

    Purpose: To investigate p73 expression in normal mucosa, primary tumor, and metastasis in relation to radiotherapy (RT) response and clinicopathologic/biologic variables in rectal cancers. Methods and Materials: p73 was immunohistochemically examined on biopsies (unirradiated, n = 102), distant (from the large bowel, n = 82), and adjacent (adjacent to primary tumor, n = 89) normal mucosa samples, primary tumors (n = 131), and lymph node metastasis (n = 32) from rectal cancer patients participating in a clinical trial of preoperative RT. Seventy-four patients received surgery alone and 57 received additional RT. Results: Cytoplasmic p73 was increased in the primary tumor compared with the distant or adjacent mucosa (p {<=} 0.0001). Nuclear (p = 0.02) and cytoplasmic (p = 0.003) p73 was higher in irradiated distant mucosa samples than in unirradiated ones, and nuclear p73 tended to be increased in irradiated primary tumors compared with unirradiated ones (p = 0.06). p73 was positively related to cyclooxygenase-2 expression in irradiated tumors (p = 0.03). p73-negative tumors tended to have a lower local recurrence after RT compared with unirradiated cases (p 0.06). Conclusions: Normal epithelial cells seem more sensitive to RT than tumor cells regarding p73 expression. Patients with p73-negative rectal tumors may have a lower risk of local recurrence after RT.

  1. Low rectal cancer: Sphincter preserving techniques-selection of patients, techniques and outcomes

    PubMed Central

    Dimitriou, Nikoletta; Michail, Othon; Moris, Dimitrios; Griniatsos, John

    2015-01-01

    Low rectal cancer is traditionally treated by abdominoperineal resection. In recent years, several new techniques for the treatment of very low rectal cancer patients aiming to preserve the gastrointestinal continuity and to improve both the oncological as well as the functional outcomes, have been emerged. Literature suggest that when the intersphincteric resection is applied in T1-3 tumors located within 30-35 mm from the anal verge, is technically feasible, safe, with equal oncological outcomes compared to conventional surgery and acceptable quality of life. The Anterior Perineal PlanE for Ultra-low Anterior Resection technique, is not disrupting the sphincters, but carries a high complication rate, while the reports on the oncological and functional outcomes are limited. Transanal Endoscopic MicroSurgery (TEM) and TransAnal Minimally Invasive Surgery (TAMIS) should represent the treatment of choice for T1 rectal tumors, with specific criteria according to the NCCN guidelines and favorable pathologic features. Alternatively to the standard conventional surgery, neoadjuvant chemo-radiotherapy followed by TEM or TAMIS seems promising for tumors of a local stage T1sm2-3 or T2. Transanal Total Mesorectal Excision should be performed only when a board approved protocol is available by colorectal surgeons with extensive experience in minimally invasive and transanal endoscopic surgery. PMID:26191350

  2. Erlotinib Hydrochloride in Treating Patients With Stage I-III Colorectal Cancer or Adenoma

    ClinicalTrials.gov

    2014-12-22

    Adenomatous Polyp; Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage I Colon Cancer; Stage I 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

  3. Phase I-II Study of Fluorouracil in Combination With Phenylbutyrate in Advanced Colorectal Cancer

    ClinicalTrials.gov

    2013-01-31

    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

  4. Two-marker protein profile predicts poor prognosis in patients with early rectal cancer

    PubMed Central

    Zlobec, I; Baker, K; Terracciano, L; Peter, S; Degen, L; Beglinger, C; Lugli, A

    2008-01-01

    The aim of this study was to establish an immunohistochemical protein profile to complement preoperative staging and identify rectal cancer patients at high-risk of adverse outcome. Immunohistochemistry was performed on a tissue microarray including 482 rectal cancers for APAF-1, EphB2, MST1, Ki67, p53, RHAMM, RKIP and CD8+ tumour infiltrating lymphocytes (TILs). After resampling of the data and multivariable analysis, the most reproducible markers were combined and prognosis evaluated as stratified by pT and pN status. In multivariable analysis, only positive RHAMM (P<0.001; HR=1.94 (1.44–2.61)) and loss of CD8+ TILs (P=0.006; HR=0.63 (0.45–0.88)) were independent prognostic factors. The 5-year cancer-specific survival rate for RHAMM+/TIL− patients was 30% (95% CI 21–40%) compared to 76% (95% CI: 66–84%) for RHAMM−/TIL+ patients (P<0.001). The 5-year cancer-specific survival of T1/T2/RHAMM+/TIL− patients was 48% (20–72%) and significantly worse compared to T3/T4/RHAMM−/TIL+ patients (71% 95% CI 56–82%); P=0.039). Stratifying by nodal status, only N+/RHAMM+/TIL− patients demonstrated a significantly worse prognosis than N0/RHAMM+/TIL− patients (P=0.005). Loss of CD8+ TILs was predictive of local recurrence in RHAMM+ tumours (P=0.009) only. RHAMM and CD8+ TILs may assist in identifying early stage rectal cancer patients facing a particularly poor prognosis and who may derive a benefit from preoperative therapy. PMID:18985041

  5. Second St. Gallen European Organisation for Research and Treatment of Cancer Gastrointestinal Cancer Conference: consensus recommendations on controversial issues in the primary treatment of rectal cancer.

    PubMed

    Lutz, Manfred P; Zalcberg, John R; Glynne-Jones, Rob; Ruers, Theo; Ducreux, Michel; Arnold, Dirk; Aust, Daniela; Brown, Gina; Bujko, Krzysztof; Cunningham, Christopher; Evrard, Serge; Folprecht, Gunnar; Gerard, Jean-Pierre; Habr-Gama, Angelita; Haustermans, Karin; Holm, Torbjörn; Kuhlmann, Koert F; Lordick, Florian; Mentha, Gilles; Moehler, Markus; Nagtegaal, Iris D; Pigazzi, Alessio; Puciarelli, Salvatore; Roth, Arnaud; Rutten, Harm; Schmoll, Hans-Joachim; Sorbye, Halfdan; Van Cutsem, Eric; Weitz, Jürgen; Otto, Florian

    2016-08-01

    Primary treatment of rectal cancer was the focus of the second St. Gallen European Organisation for Research and Treatment of Cancer (EORTC) Gastrointestinal Cancer Conference. In the context of the conference, a multidisciplinary international expert panel discussed and voted on controversial issues which could not be easily answered using published evidence. Main topics included optimal pretherapeutic imaging, indication and type of neoadjuvant treatment, and the treatment strategies in advanced tumours. Here we report the key recommendations and summarise the related evidence. The treatment strategy for localised rectal cancer varies from local excision in early tumours to neoadjuvant radiochemotherapy (RCT) in combination with extended surgery in locally advanced disease. Optimal pretherapeutic staging is a key to any treatment decision. The panel recommended magnetic resonance imaging (MRI) or MRI + endoscopic ultrasonography (EUS) as mandatory staging modalities, except for early T1 cancers with an option for local excision, where EUS in addition to MRI was considered to be most important because of its superior near-field resolution. Primary surgery with total mesorectal excision was recommended by most panellists for some early tumours with limited risk of recurrence (i.e. cT1-2 or cT3a N0 with clear mesorectal fascia on MRI and clearly above the levator muscles), whereas all other stages were considered for multimodal treatment. The consensus panel recommended long-course RCT over short-course radiotherapy for most clinical situations where neoadjuvant treatment is indicated, with the exception of T3a/b N0 tumours where short-course radiotherapy or even no neoadjuvant therapy were regarded to be an option. In patients with potentially resectable tumours and synchronous liver metastases, most panel members did not see an indication to start with classical fluoropyrimidine-based RCT but rather favoured preoperative short-course radiotherapy with systemic

  6. Second St. Gallen European Organisation for Research and Treatment of Cancer Gastrointestinal Cancer Conference: consensus recommendations on controversial issues in the primary treatment of rectal cancer.

    PubMed

    Lutz, Manfred P; Zalcberg, John R; Glynne-Jones, Rob; Ruers, Theo; Ducreux, Michel; Arnold, Dirk; Aust, Daniela; Brown, Gina; Bujko, Krzysztof; Cunningham, Christopher; Evrard, Serge; Folprecht, Gunnar; Gerard, Jean-Pierre; Habr-Gama, Angelita; Haustermans, Karin; Holm, Torbjörn; Kuhlmann, Koert F; Lordick, Florian; Mentha, Gilles; Moehler, Markus; Nagtegaal, Iris D; Pigazzi, Alessio; Puciarelli, Salvatore; Roth, Arnaud; Rutten, Harm; Schmoll, Hans-Joachim; Sorbye, Halfdan; Van Cutsem, Eric; Weitz, Jürgen; Otto, Florian

    2016-08-01

    Primary treatment of rectal cancer was the focus of the second St. Gallen European Organisation for Research and Treatment of Cancer (EORTC) Gastrointestinal Cancer Conference. In the context of the conference, a multidisciplinary international expert panel discussed and voted on controversial issues which could not be easily answered using published evidence. Main topics included optimal pretherapeutic imaging, indication and type of neoadjuvant treatment, and the treatment strategies in advanced tumours. Here we report the key recommendations and summarise the related evidence. The treatment strategy for localised rectal cancer varies from local excision in early tumours to neoadjuvant radiochemotherapy (RCT) in combination with extended surgery in locally advanced disease. Optimal pretherapeutic staging is a key to any treatment decision. The panel recommended magnetic resonance imaging (MRI) or MRI + endoscopic ultrasonography (EUS) as mandatory staging modalities, except for early T1 cancers with an option for local excision, where EUS in addition to MRI was considered to be most important because of its superior near-field resolution. Primary surgery with total mesorectal excision was recommended by most panellists for some early tumours with limited risk of recurrence (i.e. cT1-2 or cT3a N0 with clear mesorectal fascia on MRI and clearly above the levator muscles), whereas all other stages were considered for multimodal treatment. The consensus panel recommended long-course RCT over short-course radiotherapy for most clinical situations where neoadjuvant treatment is indicated, with the exception of T3a/b N0 tumours where short-course radiotherapy or even no neoadjuvant therapy were regarded to be an option. In patients with potentially resectable tumours and synchronous liver metastases, most panel members did not see an indication to start with classical fluoropyrimidine-based RCT but rather favoured preoperative short-course radiotherapy with systemic

  7. Tumor vascularity evaluated by transrectal color Doppler US in predicting therapy outcome for low-lying rectal cancer

    SciTech Connect

    Barbaro, Brunella . E-mail: a.leonemd@tiscalinet.it; Valentini, Vincenzo; Coco, Claudio; Mancini, Anna Paola; Gambacorta, Maria Antonietta; Vecchio, Fabio Maria; Bonomo, Lorenzo

    2005-12-01

    Purpose: To evaluate the impact on T downstaging of the vasculature supplying blood flow to rectal cancer evaluated by color Doppler ultrasound. Methods and Materials: Color Doppler images were graded in 29 T3-staged rectal carcinoma patients sonographically just before chemoradiation. Any arterial vessels detected in rectal masses were assigned one of two grades: vascularity was considered as grade 1 for vessels feeding the periphery and as grade 2 for vessels coursing in all rectal masses within its peripheral and central portions. The pulsatility indices (PI = peak systolic velocity - end-diastolic velocity/time-averaged maximum velocity) were calculated in the central and peripheral portions. Results: The pathologic observations showed a change in stage in 15 of the 23 patients graded 2, positive predictive value 65.2% (p = 0.047), and in one of the six rectal cancers graded 1 (negative predictive value, 83.3%). The minimal peripheral PI values in rectal cancer graded 2 were higher in nonresponding (2.2 {+-} 1.3) than in responding lesions (1.6 {+-} 0.7) p = 0.01. Conclusion: Vascularity graded 2 associated with low peripheral PI values are indicators of therapy outcome. Vascularity graded 1 and high peripheral PI values in graded 2 have negative predictive value.

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

    SciTech Connect

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

    2013-07-01

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

  9. SPARCL1 Expression Increases With Preoperative Radiation Therapy and Predicts Better Survival in Rectal Cancer Patients

    SciTech Connect

    Kotti, Angeliki Holmqvist, Annica; Albertsson, Maria; Sun, Xiao-Feng

    2014-04-01

    Purpose: The secreted protein acidic and rich in cysteine-like 1 (SPARCL1) is expressed in various normal tissues and many types of cancers. The function of SPARCL1 and its relationship to a patient's prognosis have been studied, whereas its relationship to radiation therapy (RT) is not known. Our aim was to investigate the expression of SPARCL1 in rectal cancer patients who participated in a clinical trial of preoperative RT. Methods and Materials: The study included 136 rectal cancer patients who were randomized to undergo preoperative RT and surgery (n=63) or surgery alone (n=73). The expression levels of SPARCL1 in normal mucosa (n=29), primary tumor (n=136), and lymph node metastasis (n=35) were determined by immunohistochemistry. Results: Tumors with RT had stronger SPARCL1 expression than tumors without RT (P=.003). In the RT group, strong SPARCL1 expression was related to better survival than weak expression in patients with stage III tumors, independent of sex, age, differentiation, and margin status (P=.022; RR = 18.128; 95% confidence interval, 1.512-217.413). No such relationship was found in the non-RT group (P=.224). Further analysis of interactions among SPARCL1 expression, RT, and survival showed statistical significance (P=.024). In patients with metastases who received RT, strong SPARCL1 expression was related to better survival compared to weak expression (P=.041) but not in the non-RT group (P=.569). Conclusions: SPARCL1 expression increases with RT and is related to better prognosis in rectal cancer patients with RT but not in patients without RT. This result may help us to select the patients best suited for preoperative RT.

  10. Late Side Effects and Quality of Life After Radiotherapy for Rectal Cancer

    SciTech Connect

    Bruheim, Kjersti; Guren, Marianne G.; Skovlund, Eva; Hjermstad, Marianne J.; Dahl, Olav; Frykholm, Gunilla; Carlsen, Erik; Tveit, Kjell Magne

    2010-03-15

    Purpose: There is little knowledge on long-term morbidity after radiotherapy (50 Gy) and total mesorectal excision for rectal cancer. Therefore, late effects on bowel, anorectal, and urinary function, and health-related quality of life (QoL), were studied in a national cohort (n = 535). Methods and Materials: All Norwegian patients who received pre- or postoperative (chemo-)radiotherapy for rectal cancer from 1993 to 2003 were identified. Patients treated with surgery alone served as controls. Patients were without recurrence or metastases. Bowel and urinary function was scored with the LENT SOMA scale and the St. Marks Score for fecal incontinence and QoL with the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30). Results: Median time since surgery was 4.8 years. Radiation-treated (RT+) patients (n = 199) had increased bowel frequency compared with non-radiation-treated (RT-) patients (n = 336); 19% vs. 6% had more than eight daily bowel movements (p < 0.001). In patients without stoma, a higher proportion of RT+ (n = 69) compared with RT- patients (n = 240), were incontinent for liquid stools (49% vs. 15%, p < 0.001), needed a sanitary pad (52% vs. 13%, p < 0.001), and lacked the ability to defer defecation (44% vs. 16%, p < 0.001). Daily urinary incontinence occurred more frequently after radiotherapy (9% vs. 2%, p = 0.001). Radiation-treated patients had worse social function than RT- patients, and patients with fecal or urinary incontinence had impaired scores for global quality of life and social function (p < 0.001). Conclusions: Radiotherapy for rectal cancer is associated with considerable long-term effects on anorectal function, especially in terms of bowel frequency and fecal incontinence. RT+ patients have worse social function, and fecal incontinence has a negative impact on QoL.

  11. Transcriptomics and proteomics show that selenium affects inflammation, cytoskeleton, and cancer pathways in human rectal biopsies.

    PubMed

    Méplan, Catherine; Johnson, Ian T; Polley, Abigael C J; Cockell, Simon; Bradburn, David M; Commane, Daniel M; Arasaradnam, Ramesh P; Mulholland, Francis; Zupanic, Anze; Mathers, John C; Hesketh, John

    2016-08-01

    Epidemiologic studies highlight the potential role of dietary selenium (Se) in colorectal cancer prevention. Our goal was to elucidate whether expression of factors crucial for colorectal homoeostasis is affected by physiologic differences in Se status. Using transcriptomics and proteomics followed by pathway analysis, we identified pathways affected by Se status in rectal biopsies from 22 healthy adults, including 11 controls with optimal status (mean plasma Se = 1.43 μM) and 11 subjects with suboptimal status (mean plasma Se = 0.86 μM). We observed that 254 genes and 26 proteins implicated in cancer (80%), immune function and inflammatory response (40%), cell growth and proliferation (70%), cellular movement, and cell death (50%) were differentially expressed between the 2 groups. Expression of 69 genes, including selenoproteins W1 and K, which are genes involved in cytoskeleton remodelling and transcription factor NFκB signaling, correlated significantly with Se status. Integrating proteomics and transcriptomics datasets revealed reduced inflammatory and immune responses and cytoskeleton remodelling in the suboptimal Se status group. This is the first study combining omics technologies to describe the impact of differences in Se status on colorectal expression patterns, revealing that suboptimal Se status could alter inflammatory signaling and cytoskeleton in human rectal mucosa and so influence cancer risk.-Méplan, C., Johnson, I. T., Polley, A. C. J., Cockell, S., Bradburn, D. M., Commane, D. M., Arasaradnam, R. P., Mulholland, F., Zupanic, A., Mathers, J. C., Hesketh, J. Transcriptomics and proteomics show that selenium affects inflammation, cytoskeleton, and cancer pathways in human rectal biopsies. PMID:27103578

  12. The neutrophil to albumin ratio as a predictor of pathological complete response in rectal cancer patients following neoadjuvant chemoradiation.

    PubMed

    Tawfik, Bernard; Mokdad, Ali A; Patel, Prachi M; Li, Hsiao C; Huerta, Sergio

    2016-10-01

    Pathological complete response (pCR) following neoadjuvant chemoradiotherapy (nCRT) and total mesorectal excision (TME), in patients with locally advanced rectal cancer, occurs in 15-27% of patients. Because blood cell counts and albumin are a direct indicator of the host environment, a response to nCRT might be predicted by these markers. This study was carried out to determine whether the neutrophil to albumin ratio (NAR) was predictive of pCR in veteran patients. Ninety-eight patients with rectal cancer who underwent standard nCRT, followed by TME were analyzed. Pre-nCRT and post-nCRT hematologic data were collected. Univariate and multivariate analyses were carried out. Kaplan-Meier curves were constructed with our primary endpoint of pCR. Male patients (99%), age 62.4±9.1 years, BMI=27.4±5.9 kg/m, rectal cancer distance from anal verge=7.1±4.5 cm (SD), interval between nCRT and TME=8 weeks, 55% patients=low anterior resection, 95% received 5-fluorouracil, and all patients received radiation, with 15% achieving a pCR. Univariate analysis showed that pre-nCRT carcinoembryonic antigen (15.8±45.1 vs. 3.5±5.3 ng/dl; P=0.002) and the pre-nCRT NAR (16.4±4.8 vs. 14.2±1.6; P=0.002) were associated with pCR. On multivariate analysis, pre-nCRT carcinoembryonic antigen (odds ratio=0.41, 95% confidence interval 0.22-0.77) and pre-nCRT NAR (odds ratio=0.76, 95% confidence interval 0.60-0.97) remained independent predictors of pCR. Overall survival between nonresponders and pCR patients at 1, 5, and 10 years was 96, 62, and 44% versus 93, 85, and 61%, P=0.13, and disease-free survival was 95, 60, and 47% versus 93, 85, and 61%, P=0.17; respectively. Our study shows that the pre-nCRT NAR is an independent predictor of pCR. These findings should be applied to other cohorts to determine its validity and reliability for use as a potential predictor of pCR.

  13. Total mesorectal excision for mid and low rectal cancer: Laparoscopic vs robotic surgery

    PubMed Central

    Feroci, Francesco; Vannucchi, Andrea; Bianchi, Paolo Pietro; Cantafio, Stefano; Garzi, Alessia; Formisano, Giampaolo; Scatizzi, Marco

    2016-01-01

    AIM: To compare the short- and long-term outcomes of laparoscopic and robotic surgery for middle and low rectal cancer. METHODS: This is a retrospective study on a prospectively collected database containing 111 patients who underwent minimally invasive rectal resection with total mesorectal excision (TME) with curative intent between January 2008 and December 2014 (robot, n = 53; laparoscopy, n = 58). The patients all had a diagnosis of middle and low rectal adenocarcinoma with stage I-III disease. The median follow-up period was 37.4 mo. Perioperative results, morbidity a pathological data were evaluated and compared. The 3-year overall survival and disease-free survival rates were calculated and compared. RESULTS: Patients were comparable in terms of preoperative and demographic parameters. The median surgery time was 192 min for laparoscopic TME (L-TME) and 342 min for robotic TME (R-TME) (P < 0.001). There were no differences found in the rates of conversion to open surgery and morbidity. The patients who underwent laparoscopic surgery stayed in the hospital two days longer than the robotic group patients (8 d for L-TME and 6 d for R-TME, P < 0.001). The pathologic evaluation showed a higher number of harvested lymph nodes in the robotic group (18 for R-TME, 11 for L-TME, P < 0.001) and a shorter distal resection margin for laparoscopic patients (1.5 cm for L-TME, 2.5 cm for R-TME, P < 0.001). The three-year overall survival and disease-free survival rates were similar between groups. CONCLUSION: Both L-TME and R-TME achieved acceptable clinical and oncologic outcomes. The robotic technique showed some advantages in rectal surgery that should be validated by further studies. PMID:27053852

  14. Feasibility of transanal endoscopic total mesorectal excision for rectal cancer: results of a pilot study

    PubMed Central

    Oh, Jae Hwan; Park, Sung Chan; Kim, Min Jung; Park, Byung Kwan; Hyun, Jong Hee; Chang, Hee Jin; Han, Kyung Su

    2016-01-01

    Purpose To evaluate the feasibility of transanal total mesorectal excision (TME) in patients with rectal cancer. Methods This study enrolled 12 patients with clinically node negative rectal cancer located 4–12 cm from the anal verge who underwent transanal endoscopic TME with the assistance of single port laparoscopic surgery between September 2013 and August 2014. The primary endpoint was TME quality; secondary endpoints included number of harvested lymph nodes and postoperative complications within 30 days (NCT01938027). Results The 12 patients included 7 males and 5 females, of median age 59 years and median body mass index 24.2 kg/m2. Tumors were located on average 6.7 cm from the anal verge. Four patients (33.3%) received preoperative chemoradiotherapy. Median operating time was 195 minutes and median blood loss was 50 mL. There were no intraoperative complications and no conversions to open surgery. TME was complete or nearly complete in 11 patients (91.7%). Median distal resection and circumferential resection margins were 18.5 mm and 10 mm, respectively. Median number of harvested lymph nodes was 15. Median length of hospital stay was 9 days. There were no postoperative deaths. Six patients experienced minor postoperative complications, including urinary dysfunction in 2, transient ileus in 3, and wound abscess in 1. Conclusion This pilot study showed that high-quality TME was possible in most patients without serious complications. Transanal TME for patients with rectal cancer may be feasible and safe, but further investigations are necessary to evaluate its long-term functional and oncologic outcomes and to clarify its indications. PMID:27757396

  15. Patterns of Locoregional Recurrence After Surgery and Radiotherapy or Chemoradiation for Rectal Cancer

    SciTech Connect

    Yu, T.-K.; Bhosale, Priya R.; Crane, Christopher H.; Iyer, Revathy B.; Skibber, John M. M.D.; Rodriguez-Bigas, Miguel A.; Feig, Barry W.; Chang, George J.; Eng, Cathy; Wolff, Robert A.; Janjan, Nora A.; Delclos, Marc E.; Krishnan, Sunil; Das, Prajnan

    2008-07-15

    Purpose: To identify patterns of locoregional recurrence in patients treated with surgery and preoperative or postoperative radiotherapy or chemoradiation for rectal cancer. Methods and Materials: Between November 1989 and October 2001, 554 patients with rectal cancer were treated with surgery and preoperative (85%) or postoperative (15%) radiotherapy, with 95% receiving concurrent chemotherapy. Among these patients, 46 had locoregional recurrence as the first site of failure. Computed tomography images showing the site of recurrence and radiotherapy simulation films were available for 36 of the 46 patients. Computed tomography images were used to identify the sites of recurrence and correlate the sites to radiotherapy fields in these 36 patients. Results: The estimated 5-year locoregional control rate was 91%. The 36 patients in the study had locoregional recurrences at 43 sites. There were 28 (65%) in-field, 7 (16%) marginal, and 8 (19%) out-of-field recurrences. Among the in-field recurrences, 15 (56%) occurred in the low pelvis, 6 (22%) in the presacral region, 4 (15%) in the mid-pelvis, and 2 (7%) in the high pelvis. Clinical T stage, pathologic T stage, and pathologic N stage were significantly associated with the risk of in-field locoregional recurrence. The median survival after locoregional recurrence was 24.6 months. Conclusions: Patients treated with surgery and radiotherapy or chemoradiation for rectal cancer had a low risk of locoregional recurrence, with the majority of recurrences occurring within the radiation field. Because 78% of in-field recurrences occur in the low pelvic and presacral regions, consideration should be given to including the low pelvic and presacral regions in the radiotherapy boost field, especially in patients at high risk of recurrence.

  16. Robotic versus conventional laparoscopic surgery for rectal cancer: systematic review and meta-analysis

    PubMed Central

    Lee, Seon Heui; Lim, Sungwon; Kim, Jin Hee

    2015-01-01

    Purpose Robotic surgery (RS) overcomes the limitations of previous conventional laparoscopic surgery (CLS). Although meta-analyses have been published recently, our study evaluated the latest comparative surgical, urologic, and sexual results for rectal cancer and compares RS with CLS in patients with rectal cancer only. Methods We searched three foreign databases (Ovid-MEDLINE, Ovid-Embase, and Cochrane Library) and five Korean databases (KoreaMed, KMbase, KISS, RISS, and KisTi) during July 2013. The Cochrane Risk of Bias and the Methodological Index for Non-Randomized were utilized to evaluate quality of study. Dichotomous variables were pooled using the risk ratio (RR), and continuous variables were pooled using the mean difference (MD). All meta-analyses were conducted with Review Manager, V. 5.3. Results Seventeen studies involving 2,224 patients were included. RS was associated with a lower rate of intraoperative conversion than that of CLS (RR, 0.28; 95% confidence interval [CI], 0.15-0.54). Time to first flatus was short (MD, -0.13; 95% CI, -0.25 to -0.01). Operating time was longer for RS than that for CLS (MD, 49.97; 95% CI, 20.43-79.52, I2 = 97%). International Prostate Symptom Score scores at 3 months better RS than CLS (MD, -2.90; 95% CI, -5.31 to -0.48, I2 = 0%). International Index of Erectile Function scores showed better improvement at 3 months (MD, -2.82; 95% CI, -4.78 to -0.87, I2 = 37%) and 6 months (MD, -2.15; 95% CI, -4.08 to -0.22, I2 = 0%). Conclusion RS appears to be an effective alternative to CLS with a lower conversion rate to open surgery, a shorter time to first flatus and better recovery in voiding and sexual function. RS could enhance postoperative recovery in patients with rectal cancer. PMID:26448918

  17. Circadian gene expression predicts patient response to neoadjuvant chemoradiation therapy for rectal cancer.

    PubMed

    Lu, Haijie; Chu, Qiqi; Xie, Guojiang; Han, Hao; Chen, Zheng; Xu, Benhua; Yue, Zhicao

    2015-01-01

    Preoperative neoadjuvant chemoradiation therapy may be useful in patients with operable rectal cancer, but treatment responses are variable. We examined whether expression levels of circadian clock genes could be used as biomarkers to predict treatment response. We retrospectively analyzed clinical data from 250 patients with rectal cancer, treated with neoadjuvant chemoradiation therapy in a single institute between 2011 and 2013. Gene expression analysis (RT-PCR) was performed in tissue samples from 20 patients showing pathological complete regression (pCR) and 20 showing non-pCR. The genes analyzed included six core clock genes (Clock, Per1, Per2, Cry1, Cry2 and Bmal1) and three downstream target genes (Wee1, Chk2 and c-Myc). Patient responses were analyzed through contrast-enhanced pelvic MRI and endorectal ultrasound, and verified by histological assessment. pCR was defined histologically as an absence of tumor cells. Among the 250 included patients, 70.8% showed regression of tumor size, and 18% showed pCR. Clock, Cry2 and Per2 expressions were significantly higher in the pCR group than in the non-pCR group (P<0.05), whereas Per1, Cry1 and Bmal1 expressions did not differ significantly between groups. Among the downstream genes involved in cell cycle regulation, c-Myc showed significantly higher expression in the pCR group (P<0.05), whereas Wee1 and Chk2 expression did not differ significantly between groups. Circadian genes are potential biomarkers for predicting whether a patient with rectal cancer would benefit from neoadjuvant chemoradiation therapy. PMID:26617816

  18. Evaluation of Tumor Response after Short-Course Radiotherapy and Delayed Surgery for Rectal Cancer

    PubMed Central

    Rega, Daniela; Pecori, Biagio; Scala, Dario; Avallone, Antonio; Pace, Ugo; Petrillo, Antonella; Aloj, Luigi; Tatangelo, Fabiana; Delrio, Paolo

    2016-01-01

    Purpose Neoadjuvant therapy is able to reduce local recurrence in rectal cancer. Immediate surgery after short course radiotherapy allows only for minimal downstaging. We investigated the effect of delayed surgery after short-course radiotherapy at different time intervals before surgery, in patients affected by rectal cancer. Methods From January 2003 to December 2013 sixty-seven patients with the following characteristics have been selected: clinical (c) stage T3N0 ≤ 12 cm from the anal verge and with circumferential resection margin > 5 mm (by magnetic resonance imaging); cT2, any N, < 5 cm from anal verge; and patients facing tumors with enlarged nodes and/or CRM+ve who resulted unfit for chemo-radiation, were also included. Patients underwent preoperative short-course radiotherapy with different interval to surgery were divided in three groups: A (within 6 weeks), B (between 6 and 8 weeks) and C (after more than 8 weeks). Hystopatolgical response to radiotherapy was measured by Mandard’s modified tumor regression grade (TRG). Results All patients completed the scheduled treatment. Sixty-six patients underwent surgery. Fifty-three of which (80.3%) received a sphincter saving procedure. Downstaging occurred in 41 cases (62.1%). The analysis of subgroups showed an increasing prevalence of TRG 1–2 prolonging the interval to surgery (group A—16.7%, group B—36.8% and 54.3% in group C; p value 0.023). Conclusions Preoperative short-course radiotherapy is able to downstage rectal cancer if surgery is delayed. A higher rate of TRG 1–2 can be obtained if interval to surgery is prolonged to more than 8 weeks. PMID:27548058

  19. Robotic-assisted surgery versus open surgery in the treatment of rectal cancer: the current evidence

    PubMed Central

    Liao, Guixiang; Li, Yan-Bing; Zhao, Zhihong; Li, Xianming; Deng, Haijun; Li, Gang

    2016-01-01

    The aim of this meta-analysis was to comprehensively compare the safety and efficacy of robotic-assisted rectal cancer surgery (RRCS) and open rectal cancer surgery (ORCS). Electronic database (PubMed, EMBASE, Web of Knowledge, and the Cochrane Library) searches were conducted for all relevant studies that compared the short-term and long-term outcomes between RRCS and ORCS. Odds ratios (ORs), mean differences, and hazard ratios were calculated. Seven studies involving 1074 patients with rectal cancer were identified for this meta-analysis. Compared with ORCS, RRCS is associated with a lower estimated blood loss (mean difference [MD]: −139.98, 95% confidence interval [CI]: −159.11 to −120.86; P < 0.00001), shorter hospital stay length (MD: −2.10, 95% CI: −3.47 to −0.73; P = 0.003), lower intraoperative transfusion requirements (OR: 0.52, 95% CI: 0.28 to 0.99, P = 0.05), shorter time to flatus passage (MD: −0.97, 95% CI = −1.06 to −0.88, P < 0.00001), and shorter time to resume a normal diet (MD: −1.71.95% CI = −3.31 to −0.12, P = 0.04). There were no significant differences in surgery-related complications, oncologic clearance, disease-free survival, and overall survival between the two groups. However, RRCS was associated with a longer operative time. RRCS is safe and effective. PMID:27228906

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

    SciTech Connect

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

    2009-07-15

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

  1. Efficacy of Immunohistochemical Staining in Differentiating a Squamous Cell Carcinoma in Poorly Differentiated Rectal Cancer: Two Case Reports

    PubMed Central

    Rami, Sairafi; Han, Yoon Dae; Jang, Mi; Cho, Min Soo; Hur, Hyuk; Min, Byung Soh; Lee, Kang Young

    2016-01-01

    A rectal carcinoma, including primary an adenosquamous and a squamous cell carcinoma (SCC), is a very rare disease, accounting for 0.025% to 0.20% of all large-bowel malignant tumors. Because SCCs have a higher mortality than adenosquamous carcinomas, determining whether the primary rectal cancer exhibits an adenomatous component or a squamous component is important. While differentiating between these 2 components, especially in poorly differentiated rectal cancer, is difficult, specific immunohistochemical stains enable accurate diagnoses. Here, we report the use of immunohistochemical stains to distinguish between the adenomatous and the squamous components in 2 patients with low rectal cancer, a 58-year-old man and a 73-year-old woman, who were initially diagnosed using the histopathologic results for a poorly differentiated carcinoma. These data suggest that using these immunohistochemical stains will help to accurately diagnose the type of rectal cancer, especially for poorly differentiated carcinomas, and will provide important information to determine the proper treatment for the patient. PMID:27626026

  2. Efficacy of Immunohistochemical Staining in Differentiating a Squamous Cell Carcinoma in Poorly Differentiated Rectal Cancer: Two Case Reports

    PubMed Central

    Rami, Sairafi; Han, Yoon Dae; Jang, Mi; Cho, Min Soo; Hur, Hyuk; Min, Byung Soh; Lee, Kang Young

    2016-01-01

    A rectal carcinoma, including primary an adenosquamous and a squamous cell carcinoma (SCC), is a very rare disease, accounting for 0.025% to 0.20% of all large-bowel malignant tumors. Because SCCs have a higher mortality than adenosquamous carcinomas, determining whether the primary rectal cancer exhibits an adenomatous component or a squamous component is important. While differentiating between these 2 components, especially in poorly differentiated rectal cancer, is difficult, specific immunohistochemical stains enable accurate diagnoses. Here, we report the use of immunohistochemical stains to distinguish between the adenomatous and the squamous components in 2 patients with low rectal cancer, a 58-year-old man and a 73-year-old woman, who were initially diagnosed using the histopathologic results for a poorly differentiated carcinoma. These data suggest that using these immunohistochemical stains will help to accurately diagnose the type of rectal cancer, especially for poorly differentiated carcinomas, and will provide important information to determine the proper treatment for the patient.

  3. Efficacy of Immunohistochemical Staining in Differentiating a Squamous Cell Carcinoma in Poorly Differentiated Rectal Cancer: Two Case Reports.

    PubMed

    Rami, Sairafi; Han, Yoon Dae; Jang, Mi; Cho, Min Soo; Hur, Hyuk; Min, Byung Soh; Lee, Kang Young; Kim, Nam Kyu

    2016-08-01

    A rectal carcinoma, including primary an adenosquamous and a squamous cell carcinoma (SCC), is a very rare disease, accounting for 0.025% to 0.20% of all large-bowel malignant tumors. Because SCCs have a higher mortality than adenosquamous carcinomas, determining whether the primary rectal cancer exhibits an adenomatous component or a squamous component is important. While differentiating between these 2 components, especially in poorly differentiated rectal cancer, is difficult, specific immunohistochemical stains enable accurate diagnoses. Here, we report the use of immunohistochemical stains to distinguish between the adenomatous and the squamous components in 2 patients with low rectal cancer, a 58-year-old man and a 73-year-old woman, who were initially diagnosed using the histopathologic results for a poorly differentiated carcinoma. These data suggest that using these immunohistochemical stains will help to accurately diagnose the type of rectal cancer, especially for poorly differentiated carcinomas, and will provide important information to determine the proper treatment for the patient. PMID:27626026

  4. Colon and rectal cancer incidence and water trihalomethane concentrations in New South Wales, Australia

    PubMed Central

    2014-01-01

    Background There is evidence, although inconsistent, that long term exposure to disinfection by products (DBPs) increases the risk of bowel cancer. No study has been conducted in Australia to examine this association and due to difference in the methods of disinfection the risk can vary across geographical regions and. This study was conducted to analyse the association of trihalomethanes (THMs) in water with colon and rectal cancer in NSW Australia. Methods Average yearly concentrations of total and individual species of THMs were obtained for 50 local government areas (LGAs). Indirectly-standardized incidence rates of colon and rectal cancers in LGAs for the period 1995 to 2001 were regressed against mean THM concentrations lagged five years, adjusting for socioeconomic status, high risk drinking, smoking status, usual source of water and year of diagnosis, including local and global random effects within a Bayesian framework. The incidence rate ratios (IRRs) for an interquartile range (IQR) increase in THMs were estimated. Results Using five year lag of exposure there was a positive association between bromoform concentration and CRC in men (IRR = 1.025, 95% CI 1.010, 1.040) but not in women (IRR = 1.003, 95% CI 0.987, 1.018). The association in men was mainly found in colon cancer with bromoform (IRR = 1.035, 95% CI 1.017, 1.053). There was no appreciable association of colorectal cancer with other species of THMs. Sensitivity analyses did not materially change the associations observed. Conclusion A positive association was observed between colon cancer and water bromoform concentrations in men. Given the potential population impact of such an association, further research into the relationship between THMs, particularly brominated species, and colorectal cancer is warranted. PMID:24938491

  5. Evaluation of preoperative serum markers for individual patient prognosis in stage I-III rectal cancer.

    PubMed

    Giessen, Clemens; Nagel, Dorothea; Glas, Maria; Spelsberg, Fritz; Lau-Werner, Ulla; Modest, Dominik Paul; Michl, Marlies; Heinemann, Volker; Stieber, Petra; Schulz, Christoph

    2014-10-01

    Several independent serum biomarkers have been proposed as prognostic and/or predictive markers for colorectal cancer (CRC). To this date, carcinoembryonic antigen (CEA) remains the only recommended serological CRC biomarker. The present retrospective analysis investigates the prognostic value of several serum markers. A total of 256 patients with rectal cancer underwent surgery for curative intent in a university cancer center between January 1988 and June 2007. Preoperative serum was retrospectively analyzed for albumin, alkaline phosphatase (aP), beta-human chorionic gonadotropin, bilirubin, CA 125, cancer antigen 19-9, cancer antigen 72-4 (CA 72-4), CEA, CRP, CYFRA 21-1, ferritin, gamma-glutamyl transpeptidase, glutamate oxaloacetate transanunase, glutamate pyruvate transaminase, hemoglobin, haptoglobin, interleukin-6, interleukin-8, creatinine, lactate-dehydrogenase, serum amyloid A (SAA), and 25-hydroxyvitamin D. Cancer-specific survival (CSS) and disease-free survival (DFS) were estimated. Median follow-up time was 8.4 years. Overall 3- and 5-year CSS was 88.6 and 78.9 %, respectively. DFS rates were 72.8 % (3 years) and 67.5 % (5 years). Univariate analysis of CSS indicated aP, CA 72-4, CEA, and SAA as prognostic factors, while aP, CEA, and SAA were also prognostic with regard to DFS. Multivariate analysis confirmed SAA together with T and N stage as prognostic factors. According to UICC stage, CEA and SAA add prognostic value in stages II and III with regard to DFS and CSS, respectively. The combined use of CEA and SAA is able to identify patients with favorable and poor prognosis. In addition to tumor baseline parameters, routine analysis of SAA together with CEA provided markedly improved prognostic value on CSS and DFS in resected rectal cancer. PMID:25027407

  6. Comprehensive molecular characterization of human colon and rectal cancer.

    PubMed

    2012-07-19

    To characterize somatic alterations in colorectal carcinoma, we conducted a genome-scale analysis of 276 samples, analysing exome sequence, DNA copy number, promoter methylation and messenger RNA and microRNA expression. A subset of these samples (97) underwent low-depth-of-coverage whole-genome sequencing. In total, 16% of colorectal carcinomas were found to be hypermutated: three-quarters of these had the expected high microsatellite instability, usually with hypermethylation and MLH1 silencing, and one-quarter had somatic mismatch-repair gene and polymerase ε (POLE) mutations. Excluding the hypermutated cancers, colon and rectum cancers were found to have considerably similar patterns of genomic alteration. Twenty-four genes were significantly mutated, and in addition to the expected APC, TP53, SMAD4, PIK3CA and KRAS mutations, we found frequent mutations in ARID1A, SOX9 and FAM123B. Recurrent copy-number alterations include potentially drug-targetable amplifications of ERBB2 and newly discovered amplification of IGF2. Recurrent chromosomal translocations include the fusion of NAV2 and WNT pathway member TCF7L1. Integrative analyses suggest new markers for aggressive colorectal carcinoma and an important role for MYC-directed transcriptional activation and repression. PMID:22810696

  7. Comprehensive Molecular Characterization of Human Colon and Rectal Cancer

    PubMed Central

    2012-01-01

    Summary To characterize somatic alterations in colorectal carcinoma (CRC), we conducted genome-scale analysis of 276 samples, analyzing exome sequence, DNA copy number, promoter methylation, mRNA and microRNA expression. A subset (97) underwent low-depth-of-coverage whole-genome sequencing. 16% of CRC have hypermutation, three quarters of which have the expected high microsatellite instability (MSI), usually with hypermethylation and MLH1 silencing, but one quarter has somatic mismatch repair gene mutations. Excluding hypermutated cancers, colon and rectum cancers have remarkably similar patterns of genomic alteration. Twenty-four genes are significantly mutated. In addition to the expected APC, TP53, SMAD4, PIK3CA and KRAS mutations, we found frequent mutations in ARID1A, SOX9, and FAM123B/WTX. Recurrent copy number alterations include potentially drug-targetable amplifications of ERBB2 and newly discovered amplification of IGF2. Recurrent chromosomal translocations include fusion of NAV2 and WNT pathway member TCF7L1. Integrative analyses suggest new markers for aggressive CRC and important role for MYC-directed transcriptional activation and repression. PMID:22810696

  8. Prognostic factors for disease-free survival in patients with T-4 or N+ rectal cancer treated with preoperative chemoradiation therapy, surgery, and intraoperative irradiation

    SciTech Connect

    Diaz-Gonzalez, Juan A.; Calvo, Felipe A.; Cortes, Javier; Garcia-Sabrido, Jose L.; Gomez-Espi, Marina; Valle, Emilio del; Munoz-Jimenez, Fernando; Alvarez, Emilio

    2006-03-15

    Purpose: Fluoropyrimidine-radiosensitizing agents in conjunction with preoperative radiotherapy have proven to induce tumor and nodal downstaging effects, sphincter preservation promotion, and mid-term favorable survival rates. Intraoperative electron beam radiation therapy may improve pelvic control in patients with locally advanced rectal cancer stages. Potential predictive factors for response and disease-free survival, with intense local multidisciplinary approach, are analyzed. Methods and Materials: One hundred fifteen patients with rectal cancer were treated with oral 5-fluorouracil or Tegafur with preoperative radiotherapy, surgery, and intraoperative electron beam radiation therapy to identify potential pre- and on-treatment characteristics that might be of prognostic value for disease outcome. Univariate and multivariate analyses were performed. Results: Older patients and those treated with Tegafur were more likely to achieve a major histologic response, categorized as persistence of minimal residual microscopic disease foci in the surgical specimen ('mic' response). Factors unfavorably associated with disease-free survival in the multivariate model were male gender and persistence of macroscopic disease in the rectal wall ('mac' response). Accordingly, 3-year disease-free survival rates in the groups of patients with 0, 1, or 2 of these risk factors were 100%, 81%, and 53%, respectively (p < 0.001). Conclusions: Females with an intense pathologic response (pT{sub mic} residue) to preoperative chemoradiotherapy have an excellent 3-year disease-free survival. This information might be of interest for stratification of patients in the development of adjuvant treatment trials.

  9. Gangrene of the penis, scrotum, and perineum, occurred after radiotherapy of rectal cancer

    PubMed Central

    Życzkowski, Marcin; Bryniarski, Piotr; Nowakowski, Krzysztof; Muskała, Bartosz; Paradysz, Andrzej

    2013-01-01

    We present a case of a 58-year-old man hospitalized because of gangrene of the penis and scrotum, after radiochemotherapy for rectal cancer. At the time of the admission the patient presented with extensive gangrene with necrosis affecting the scrotum and the penis. During the first day of hospitalization the patient was operated. Due to the progress of the disease he had to be operated again. The status of the patient, which initially was very bad, was gradually improving. He was discharged from the hospital after 59 days in a good general state with good wound healing. PMID:24707380

  10. Gangrene of the penis, scrotum, and perineum, occurred after radiotherapy of rectal cancer.

    PubMed

    Zyczkowski, Marcin; Bogacki, Rafał; Bryniarski, Piotr; Nowakowski, Krzysztof; Muskała, Bartosz; Paradysz, Andrzej

    2013-01-01

    We present a case of a 58-year-old man hospitalized because of gangrene of the penis and scrotum, after radiochemotherapy for rectal cancer. At the time of the admission the patient presented with extensive gangrene with necrosis affecting the scrotum and the penis. During the first day of hospitalization the patient was operated. Due to the progress of the disease he had to be operated again. The status of the patient, which initially was very bad, was gradually improving. He was discharged from the hospital after 59 days in a good general state with good wound healing.

  11. [Predictive factors for locally recurrent rectal cancer after primary curative surgery].

    PubMed

    Gao, Haoji; Zhang, Tao; Zhao, Ren

    2015-11-01

    Local recurrence is a major clinical challenge after primary rectal cancer surgery. Although there is a possibility that R0 resection can be achieved, the outcome is still not favorable due to the low R0 resection rate and complexity of the surgery. Therefore prevention has a higher priority over treatment afterwards. As TME principle is accepted worldwide, the local recurrence rate has been reduced dramatically. And there are other factors associated with local recurrence including CRM, operation type, staging and PNI. Proper chemoradiotherapy may reduce the risk, however benefit always comes with side effect, therefore risk stratification is important.

  12. [Predictive factors for locally recurrent rectal cancer after primary curative surgery].

    PubMed

    Gao, Haoji; Zhang, Tao; Zhao, Ren

    2015-11-01

    Local recurrence is a major clinical challenge after primary rectal cancer surgery. Although there is a possibility that R0 resection can be achieved, the outcome is still not favorable due to the low R0 resection rate and complexity of the surgery. Therefore prevention has a higher priority over treatment afterwards. As TME principle is accepted worldwide, the local recurrence rate has been reduced dramatically. And there are other factors associated with local recurrence including CRM, operation type, staging and PNI. Proper chemoradiotherapy may reduce the risk, however benefit always comes with side effect, therefore risk stratification is important. PMID:26616817

  13. Tolerability of Combined Modality Therapy for Rectal Cancer in Elderly Patients Aged 75 Years and Older

    SciTech Connect

    Margalit, Danielle N.; Mamon, Harvey J.; Ryan, David P.; Blaszkowsky, Lawrence S.; Clark, Jeffrey; Willett, Christopher G.; Hong, Theodore S.

    2011-12-01

    Purpose: To determine the rate of treatment deviations during combined modality therapy for rectal cancer in elderly patients aged 75 years and older. Methods and Materials: We reviewed the records of consecutively treated patients with rectal cancer aged 75 years and older treated with combined modality therapy at Massachusetts General Hospital and Brigham and Women's Hospital from 2002 to 2007. The primary endpoint was the rate of treatment deviation, defined as a treatment break, dose reduction, early discontinuation of therapy, or hospitalization during combined modality therapy. Patient comorbidity was rated using the validated Adult Comorbidity Evaluation 27 Test (ACE-27) comorbidity index. Fisher's exact test and the Mantel-Haenszel trend test were used to identify predictors of treatment tolerability. Results: Thirty-six eligible patients had a median age of 79.0 years (range, 75-87 years); 53% (19/36) had no or mild comorbidity and 47% (17/36) had moderate or severe comorbidity. In all, 58% of patients (21/36) were treated with preoperative chemoradiotherapy (CRT) and 33% (12/36) with postoperative CRT. Although 92% patients (33/36) completed the planned radiotherapy (RT) dose, 25% (9/36) required an RT-treatment break, 11% (4/36) were hospitalized, and 33% (12/36) had a dose reduction, break, or discontinuation of concurrent chemotherapy. In all, 39% of patients (14/36) completed {>=}4 months of adjuvant chemotherapy, and 17% (6/36) completed therapy without a treatment deviation. More patients with no to mild comorbidity completed treatment than did patients with moderate to severe comorbidity (21% vs. 12%, p = 0.66). The rate of deviation did not differ between patients who had preoperative or postoperative CRT (19% vs. 17%, p = 1.0). Conclusions: The majority of elderly patients with rectal cancer in this series required early termination of treatment, treatment interruptions, or dose reductions. These data suggest that further intensification of

  14. Phase I trial of cetuximab in combination with capecitabine, weekly irinotecan, and radiotherapy as neoadjuvant therapy for rectal cancer

    SciTech Connect

    Hofheinz, Ralf-Dieter . E-mail: ralf.hofheinz@med3.ma.uni-heidelberg.de; Horisberger, Karoline; Woernle, Christoph; Wenz, Frederik; Kraus-Tiefenbacher, Uta; Kaehler, Georg; Dinter, Dietmar; Grobholz, Rainer; Heeger, Steffen; Post, Stefan; Hochhaus, Andreas; Willeke, Frank

    2006-12-01

    Purpose: To establish the feasibility and efficacy of chemotherapy with capecitabine, weekly irinotecan, cetuximab, and pelvic radiotherapy for patients with locally advanced rectal cancer. Methods and materials: Twenty patients with rectal cancer (clinical Stage uT3-T4 or N+) received a standard dosing regimen of cetuximab (400 mg/m{sup 2} on Day 1 and 250 mg/m{sup 2} on Days 8, 15, 22, and 29) and escalating doses of irinotecan and capecitabine according to phase I methods: dose level I, irinotecan 40 mg/m{sup 2} on Days 1, 8, 15, 22, and 29 and capecitabine 800 mg/m{sup 2} on Days 1-38; dose level II, irinotecan 40 mg/m{sup 2} and capecitabine 1000 mg/m{sup 2}; and dose level III, irinotecan 50 mg/m{sup 2} and capecitabine 1000 mg/m{sup 2}. Radiotherapy was given to a dose of 50.4 Gy (45 Gy plus 5.4 Gy). Resection was scheduled 4-5 weeks after termination of chemoradiotherapy. Results: On dose level I, no dose-limiting toxicities occurred; however, Grade 3 diarrhea affected 1 of 6 patients on dose level II. Of 5 patients treated at dose level III, 2 exhibited dose-limiting toxicity (diarrhea in 2 and nausea/vomiting in 1). Therefore, dose level II was determined as the recommended dose for future studies. A total of 10 patients were treated on dose level II and received a mean relative dose intensity of 100% of cetuximab, 94% of irinotecan, and 95% of capecitabine. All patients underwent surgery. Five patients had a pathologically complete remission and six had microfoci of residual tumor only. Conclusion: Preoperative chemoradiotherapy with cetuximab, capecitabine, and weekly irinotecan is feasible and well tolerated. The preliminary efficacy is very promising. Larger phase II trials are ongoing.

  15. Acute small bowel toxicity and preoperative chemoradiotherapy for rectal cancer: Investigating dose-volume relationships and role for inverse planning

    SciTech Connect

    Tho, Lye Mun . E-mail: l.tho@beatson.gla.ac.uk; Glegg, Martin; Paterson, Jennifer; Yap, Christina; MacLeod, Alice; McCabe, Marie; McDonald, Alexander C.

    2006-10-01

    Purpose: The relationship between volume of irradiated small bowel (VSB) and acute toxicity in rectal cancer radiotherapy is poorly quantified, particularly in patients receiving concurrent preoperative chemoradiotherapy. Using treatment planning data, we studied a series of such patients. Methods and Materials: Details of 41 patients with locally advanced rectal cancer were reviewed. All received 45 Gy in 25 fractions over 5 weeks, 3-4 fields three-dimensional conformal radiotherapy with daily 5-fluorouracil and folinic acid during Weeks 1 and 5. Toxicity was assessed prospectively in a weekly clinic. Using computed tomography planning software, the VSB was determined at 5 Gy dose intervals (V{sub 5}, V{sub 1}, etc.). Eight patients with maximal VSB had dosimetry and radiobiological modeling outcomes compared between inverse and conformal three-dimensional planning. Results: VSB correlated strongly with diarrheal severity at every dose level (p < 0.03), with strongest correlation at lowest doses. Median VSB differed significantly between patients experiencing Grade 0-1 and Grade 2-4 diarrhea (p {<=} 0.05). No correlation was found with anorexia, nausea, vomiting, abdominal cramps, age, body mass index, sex, tumor position, or number of fields. Analysis of 8 patients showed that inverse planning reduced median dose to small bowel by 5.1 Gy (p = 0.008) and calculated late normal tissue complication probability (NTCP) by 67% (p = 0.016). We constructed a model using mathematical analysis to predict for acute diarrhea occurring at V{sub 5} and V{sub 15}. Conclusions: A strong dose-volume relationship exists between VSB and acute diarrhea at all dose levels during preoperative chemoradiotherapy. Our constructed model may be useful in predicting toxicity, and this has been derived without the confounding influence of surgical excision on bowel function. Inverse planning can reduce calculated dose to small bowel and late NTCP, and its clinical role warrants further

  16. Late Patient-Reported Toxicity After Preoperative Radiotherapy or Chemoradiotherapy in Nonresectable Rectal Cancer: Results From a Randomized Phase III Study

    SciTech Connect

    Braendengen, Morten; Tveit, Kjell Magne; Bruheim, Kjersti; Cvancarova, Milada; Berglund, Ake; Glimelius, Bengt

    2011-11-15

    Purpose: Preoperative chemoradiotherapy (CRT) is superior to radiotherapy (RT) in locally advanced rectal cancer, but the survival gain is limited. Late toxicity is, therefore, important. The aim was to compare late bowel, urinary, and sexual functions after CRT or RT. Methods and Materials: Patients (N = 207) with nonresectable rectal cancer were randomized to preoperative CRT or RT (2 Gy Multiplication-Sign 25 {+-} 5-fluorouracil/leucovorin). Extended surgery was often required. Self-reported late toxicity was scored according to the LENT SOMA criteria in a structured telephone interview and with questionnaires European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30), International Index of Erectile Function (IIEF), and sexual function -vaginal changes questionnaire (SVQ). Results: Of the 105 patients alive in Norway and Sweden after 4 to 12 years of follow-up, 78 (74%) responded. More patients in the CRT group had received a stoma (73% vs. 52%, p = 0.09). Most patients without a stoma (7 of 12 in CRT group and 9 of 16 in RT group) had incontinence for liquid stools or gas. No stoma and good anal function were seen in 5 patients (11%) in the CRT group and in 11 (30%) in the RT group (p = 0.046). Of 44 patients in the CRT group, 12 (28%) had had bowel obstruction compared with 5 of 33 (15%) in the RT group (p = 0.27). One-quarter of the patients reported urinary incontinence. The majority of men had severe erectile dysfunction. Few women reported sexual activity during the previous month. However, the majority did not have concerns about their sex life. Conclusions: Fecal incontinence and erectile dysfunction are frequent after combined treatment for locally advanced rectal cancer. There was a clear tendency for the problems to be more common after CRT than after RT.

  17. Assessment of quality of life in patients with rectal cancer treated by preoperative radiotherapy: A longitudinal prospective study

    SciTech Connect

    Allal, Abdelkarim S. . E-mail: abdelkarim.allal@hcuge.ch; Gervaz, Pascal; Gertsch, Philippe; Bernier, Jacques; Roth, Arnaud D.; Morel, Philippe; Bieri, Sabine

    2005-03-15

    Purpose: To assess prospectively the quality of life (QOL) of patients treated by preoperative radiotherapy (RT) and surgery for locally advanced rectal cancer. Methods and materials: We studied 53 patients treated with bi-fractionated RT (50 Gy in 40 fractions within 4 weeks) followed at a median interval of 45 days by abdominoperineal resection in 11 patients and low anterior resection in 42 patients. Their QOL was assessed using two self-rating questionnaires developed by the European Organization for Research and Treatment of Cancer (EORTC): one was cancer specific (EORTC QLQ-C30) and one was site specific (EORTC QLQ-C38). The questionnaires were completed before RT and 12-16 months after RT, at which time 17 patients had undergone colostomy. We hypothesized that at least some scores of the various scales would vary between the two analyses. Results: Compared with the pre-RT scores, at 1 year, patients reported statistically significant improvement in their emotional state (median 75 vs. 100, p <0.0001), perspective of the future (67 vs. 100, p = 0.0004), and their global QOL (75 vs. 83, p = 0.0008), as well as a decrease in GI symptoms (13 vs. 0, p = 0.002). However, the sexual dysfunction score increased significantly, particularly in men (17 vs. 83, p = 0.0045), and a trend toward a lower body image score was observed (100 vs. 89, p = 0.068). At 1 year, patients with colostomies reported similar or significantly improved symptom scores for fatigue, pain, GI problems, and sleep disturbance, but no such improvements were observed in patients without stomas. Conclusion: One year after combined treatment for locally advanced rectal cancer, patients exhibited statistically significant improvement in some important QOL outcomes, including global QOL, despite a decrease in sexual function and body image. Any additional improvement in QOL outcome may require refinements in the RT and surgical techniques to reduce late sequelae, particularly sexual dysfunction. Our

  18. Synergistic effects of AKAP95, Cyclin D1, Cyclin E1, and Cx43 in the development of rectal cancer

    PubMed Central

    Qi, Fengjie; Yuan, Yangyang; Zhi, Xuehong; Huang, Qian; Chen, Yuexin; Zhuang, Wenxin; Zhang, Dengcheng; Teng, Bogang; Kong, Xiangyu; Zhang, Yongxing

    2015-01-01

    Objective: To explore the expression of A-kinase anchor protein 95 (AKAP95), Cyclin D1, Cyclin E1, and Connexin43 (Cx43) in rectal cancer tissues and assess the associations between each of the proteins and pathological parameters, as well as their inter-relationships. Methods: AKAP95, Cyclin D1, Cyclin E1, and Cx43 protein expression rates were evaluated by immunohistochemistry in 50 rectal cancer specimens and 16 pericarcinoma tissues. Results: The positive rates of AKAP95, Cyclin E1, and Cyclin D1 proteins were 54.00 vs. 18.75%, 62.00 vs. 6.25%, and 72.00 vs. 31.25% in rectal cancer specimens and pericarcinoma tissues, respectively, representing statistically significant differences (P < 0.05). The positive rate of Cx43 protein expression in rectal cancer tissues was 44.00% and 62.50% in pericarcinoma tissues, and the difference between them was not significant (P > 0.05). No significant associations were found between protein expression of AKAP95, Cyclin E1, Cyclin D1, and Cx43, and the degree of differentiation, histological type, and lymph node metastasis of rectal cancer (P > 0.05). However, significant correlations were obtained between the expression rates of AKAP95 and Cyclin E1, Cyclin E1 and Cyclin D1, Cyclin E1 and Cx43 protein, and Cyclin D1 and Cx43, respectively (P < 0.05). Conclusion: AKAP95, Cyclin E1, and Cyclin D1 protein expression rates were significantly higher in rectal cancer tissues compared with pericarcinoma samples, suggesting an association between these proteins and the development and progression of rectal cancer. In addition, the significant correlations between the proteins (AKAP95 and Cyclin E1, Cyclin E1 and Cyclin D1, Cyclin E1 and Cx43 protein, and Cyclin D1 and Cx43) indicate the possible synergistic effects of these factors in the development and progression of rectal cancer. PMID:25973052

  19. Advances in Therapeutic Cancer Vaccines.

    PubMed

    Wong, Karrie K; Li, WeiWei Aileen; Mooney, David J; Dranoff, Glenn

    2016-01-01

    Therapeutic cancer vaccines aim to induce durable antitumor immunity that is capable of systemic protection against tumor recurrence or metastatic disease. Many approaches to therapeutic cancer vaccines have been explored, with varying levels of success. However, with the exception of Sipuleucel T, an ex vivo dendritic cell vaccine for prostate cancer, no therapeutic cancer vaccine has yet shown clinical efficacy in phase 3 randomized trials. Though disappointing, lessons learned from these studies have suggested new strategies to improve cancer vaccines. The clinical success of checkpoint blockade has underscored the role of peripheral tolerance mechanisms in limiting vaccine responses and highlighted the potential for combination therapies. Recent advances in transcriptome sequencing, computational modeling, and material engineering further suggest new opportunities to intensify cancer vaccines. This review will discuss the major approaches to therapeutic cancer vaccination and explore recent advances that inform the design of the next generation of cancer vaccines. PMID:26923002

  20. Effects of radiotherapy and chemotherapy on angiogenesis and leukocyte infiltration in rectal cancer

    SciTech Connect

    Baeten, Coen . E-mail: C.Baeten@surgery.azm.nl; Castermans, Karolien; Lammering, Guido; Hillen, Femke; Wouters, Bradly G.; Hillen, Harry; Griffioen, Arjan W.; Baeten, Cornelius G.M.I.

    2006-11-15

    Background: We and others have shown that angiogenesis and leukocyte infiltration are important prognostic factors in rectal cancer. However, little is known about its possible changes in response to radiotherapy (RTX), which is frequently given to rectal tumors as a neoadjuvant treatment to improve the prognosis. We therefore investigated the biologic effects of RTX on these parameters using fresh-frozen biopsy samples of tumor and normal mucosa tissue before and after RTX. Methods: Biopsy samples were taken from a total of 34 patients before and after either a short course or long course of RTX combined with chemotherapy. The following parameters were analyzed by immunohistochemistry, flow cytometry, or quantitative real-time polymerase chain reaction: Microvessel density, leukocyte infiltration, proliferating epithelial and tumor cells, proliferating endothelial cells, adhesion molecule expression on endothelial cells, and the angiogenic mRNA profile. Results: The tumor biopsy samples taken after RTX treatment demonstrated a significant decrease in microvessel density and the number of proliferating tumor cells and proliferating endothelial cells (p < 0.001). In contrast, the leukocyte infiltration, the levels of basic fibroblast growth factor in carcinoma tissue, and the adhesion molecule expression on endothelial cells in normal as well as carcinoma tissue increased significantly (p < 0.05). Conclusion: Our data show that together with an overall decrease in tumor cell and endothelial cell proliferation, RTX results in an increase in the expression of adhesion molecules that stimulate leukocyte infiltration. This suggests the possibility that, in addition to its direct cytotoxic effect, radiation may also stimulate an immunologic tumor response that could contribute to the documented improvement in local tumor control and distal failure rate of rectal cancers.

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

    SciTech Connect

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

    2009-07-01

    Purpose: Sacral insufficiency (SI) fractures can occur as a late side effect of pelvic radiation therapy. Our goal was to determine the incidence, risk factors, and clinical course of SI fractures in patients treated with preoperative chemoradiation for rectal cancer. Materials and Methods: Between 1989 and 2004, 562 patients with non-metastatic rectal adenocarcinoma were treated with preoperative chemoradiation followed by mesorectal excision. The median radiotherapy dose was 45 Gy. The hospital records and radiology reports of these patients were reviewed to identify those with pelvic fractures. Radiology images of patients with pelvic fractures were then reviewed to identify those with SI fractures. Results: Among the 562 patients, 15 had SI fractures. The 3-year actuarial rate of SI fractures was 3.1%. The median time to SI fractures was 17 months (range, 2-34 months). The risk of SI fractures was significantly higher in women compared to men (5.8% vs. 1.6%, p = 0.014), and in whites compared with non-whites (4% vs. 0%, p = 0.037). On multivariate analysis, gender independently predicted for the risk of SI fractures (hazard ratio, 3.25; p = 0.031). Documentation about the presence or absence of pain was available for 13 patients; of these 7 (54%) had symptoms requiring pain medications. The median duration of pain was 22 months. No patient required hospitalization or invasive intervention for pain control. Conclusions: SI fractures were uncommon in patients treated with preoperative chemoradiation for rectal cancer. The risk of SI fractures was significantly higher in women. Most cases of SI fractures can be managed conservatively with pain medications.

  2. Hyperfractionated Accelerated Radiotherapy for Rectal Cancer in Patients With Prior Pelvic Irradiation

    SciTech Connect

    Das, Prajnan; Delclos, Marc E.; Skibber, John M.; Rodriguez-Bigas, Miguel A.; Feig, Barry W.; Chang, George J.; Eng, Cathy; Bedi, Manpreet; Krishnan, Sunil; Crane, Christopher H.

    2010-05-01

    Purpose: To retrospectively determine rates of toxicity, freedom from local progression, and survival in rectal cancer patients treated with reirradiation. Methods and Materials: Between February 2001 and February 2005, 50 patients with a history of pelvic radiotherapy were treated with hyperfractionated accelerated radiotherapy for primary (n = 2 patients) or recurrent (n = 48 patients) rectal adenocarcinoma. Patients were treated with 150-cGy fractions twice daily, with a total dose of 39 Gy (n = 47 patients) if the retreatment interval was >=1 year or 30 Gy (n = 3) if the retreatment interval was <1 year. Concurrent chemotherapy was administered to 48 (96%) patients. Eighteen (36%) patients underwent surgical resection following radiotherapy. Results: Two patients had grade 3 acute toxicity and 13 patients had grade 3 to 4 late toxicity. The 3-year rate of grade 3 to 4 late toxicity was 35%. The 3-year rate of freedom from local progression was 33%. The 3-year freedom from local progression rate was 47% in patients undergoing surgery and 21% in those not undergoing surgery (p = 0.057). The 3-year overall survival rate was 39%. The 3-year overall survival rate was 66% in patients undergoing surgery and 27% in those not undergoing surgery (p = 0.003). The 3-year overall survival rate was 53% in patients with a retreatment interval of >2 years and 21% in those with a retreatment interval of <=2 years (p = 0.001). Conclusions: Hyperfractionated, accelerated reirradiation was well tolerated, with low rates of acute toxicity and moderate rates of late toxicity. Reirradiation may help improve pelvic control in rectal cancer patients with a history of pelvic radiotherapy.

  3. Age and Comorbid Illness Are Associated With Late Rectal Toxicity Following Dose-Escalated Radiation Therapy for Prostate Cancer

    SciTech Connect

    Hamstra, Daniel A.; Stenmark, Matt H.; Ritter, Tim; Litzenberg, Dale; Jackson, William; Johnson, Skyler; Albrecht-Unger, Liesel; Donaghy, Alex; Phelps, Laura; Blas, Kevin; Halverson, Schuyler; Marsh, Robin; Olson, Karin; Feng, Felix Y.

    2013-04-01

    Purpose: To assess the impacts of patient age and comorbid illness on rectal toxicity following external beam radiation therapy (EBRT) for prostate cancer and to assess the Qualitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) normal tissue complication probability (NTCP) model in this context. Methods and Materials: Rectal toxicity was analyzed in 718 men previously treated for prostate cancer with EBRT (≥75 Gy). Comorbid illness was scored using the Charlson Comorbidity Index (CCMI), and the NTCP was evaluated with the QUANTEC model. The influence of clinical and treatment-related parameters on rectal toxicity was assessed by Kaplan-Meier and Cox proportional hazards models. Results: The cumulative incidence of rectal toxicity grade ≥2 was 9.5% and 11.6% at 3 and 5 years and 3.3% and 3.9% at 3 and 5 years for grade ≥3 toxicity, respectively. Each year of age predicted an increasing relative risk of grade ≥2 (P<.03; hazard ratio [HR], 1.04 [95% confidence interval (CI), 1.01-1.06]) and ≥3 rectal toxicity (P<.0001; HR, 1.14 [95% CI,1.07-1.22]). Increasing CCMI predicted rectal toxicity where a history of either myocardial infarction (MI) (P<.0001; HR, 5.1 [95% CI, 1.9-13.7]) or congestive heart failure (CHF) (P<.0006; HR, 5.4 [95% CI, 0.6-47.5]) predicted grade ≥3 rectal toxicity, with lesser correlation with grade ≥2 toxicity (P<.02 for MI, and P<.09 for CHF). An age comorbidity model to predict rectal toxicity was developed and confirmed in a validation cohort. The use of anticoagulants increased toxicity independent of age and comorbidity. NTCP was prognostic for grade ≥3 (P=.015) but not grade ≥2 (P=.49) toxicity. On multivariate analysis, age, MI, CHF, and an NTCP >20% all correlated with late rectal toxicity. Conclusions: Patient age and a history of MI or CHF significantly impact rectal toxicity following EBRT for the treatment of prostate cancer, even after controlling for NTCP.

  4. Prostate cancer diagnosis in a resource-poor setting: the changing role of digital rectal examination.

    PubMed

    Ahmed, Muhammed

    2011-07-01

    We undertook this study in order to determine the current role of digital rectal examination (DRE) in the diagnosis of prostate cancer in a resource-poor setting. The diagnosis of prostate cancer has been revolutionized by the introduction of prostate-specific antigen (PSA), transrectal ultrasound (TRUS) for biopsy guidance and more efficient biopsy equipment, but they are not readily available in most developing countries. This is a prospective study of 131 patients with suspected prostate cancer based on clinical presentation, DRE and elevated PSA. The presence or absence of cancer was confirmed by biopsy and histologic examination. Patients with screen- or incidentally-detected prostate cancer were excluded. The most common symptom was the development of lower urinary tract symptoms (LUTS). All patients had abnormal DRE and indurated prostate was the most frequent finding (50%). The mean PSA was 33.9 ng/mL: of the 131 patients, 80 (61.1%) had a malignant histology following biopsy, 47 (35.9%) were benign and four (3.0%) were prostate intraepithelial neoplasia (PIN). The low specificity of DRE in the diagnosis of prostate cancer requires that it should be combined with other diagnostic modalities such as PSA and TRUS-guided prostate biopsy. Thus government and health-care providers in resource-poor countries must strive to make these facilities available in order to improve prostate cancer diagnosis.

  5. Long-term disease-free survival after surgical resection for multiple bone metastases from rectal cancer

    PubMed Central

    Choi, Seok Jin; Kim, Jong Hun; Lee, Min Ro; Lee, Chang Ho; Kuh, Ja Hong; Kim, Jung Ryul

    2011-01-01

    Bone metastasis of primary colorectal cancer is uncommon. When it occurs, it is usually a late manifestation of disease and is indicative of poor prognosis. We describe a patient with multiple metachronous bone metastases from lower rectal cancer who was successfully treated with multimodal treatment including surgical resections and has shown 32 mo disease-free survival. Surgical resection of metastatic bone lesion(s) from colorectal cancer may be a good treatment option in selected patients. PMID:21876853

  6. A common variant in MTHFR influences response to chemoradiotherapy and recurrence of rectal cancer

    PubMed Central

    Nikas, Jason B; Lee, Janet T; Maring, Elizabeth D; Washechek-Aletto, Jill; Felmlee-Devine, Donna; Johnson, Ruth A; Smyrk, Thomas C; Tawadros, Patrick S; Boardman, Lisa A; Steer, Clifford J

    2015-01-01

    An important determinant of the pathogenesis and prognosis of various diseases is inherited genetic variation. Single-nucleotide polymorphisms (SNPs), variations at a single base position, have been identified in both protein-coding and noncoding DNA sequences, but the vast majority of millions of those variants are far from being functionally understood. Here we show that a common variant in the gene MTHFR [rs1801133 (C>T)] not only influences response to neoadjuvant chemoradiotherapy in patients with rectal cancer, but it also influences recurrence of the disease itself. More specifically, patients with the homozygous ancestral (wild type) genotype (C/C) were 2.91 times more likely (291% increased benefit) to respond to neoadjuvant chemoradiotherapy {95% CI: [1.23, 6.89]; P=0.0150} and 3.25 times more likely (325% increased benefit) not to experience recurrence of the disease {95% CI: [1.37, 7.72]; P=0.0079} than patients with either the heterozygous (C/T) or the homozygous mutation (T/T) genotype. These results identify MTHFR as an important genetic marker and open up new, pharmacogenomic strategies in the treatment and management of rectal cancer. PMID:26693073

  7. Dealing with robot-assisted surgery for rectal cancer: Current status and perspectives

    PubMed Central

    Biffi, Roberto; Luca, Fabrizio; Bianchi, Paolo Pietro; Cenciarelli, Sabina; Petz, Wanda; Monsellato, Igor; Valvo, Manuela; Cossu, Maria Laura; Ghezzi, Tiago Leal; Shmaissany, Kassem

    2016-01-01

    The laparoscopic approach for treatment of rectal cancer has been proven feasible and oncologically safe, and is able to offer better short-term outcomes than traditional open procedures, mainly in terms of reduced length of hospital stay and time to return to working activity. In spite of this, the laparoscopic technique is usually practised only in high-volume experienced centres, mainly because it requires a prolonged and demanding learning curve. It has been estimated that over 50 operations are required for an experienced colorectal surgeon to achieve proficiency with this technique. Robotic surgery enables the surgeon to perform minimally invasive operations with better vision and more intuitive and precise control of the operating instruments, thus promising to overcome some of the technical difficulties associated with standard laparoscopy. It has high-definition three-dimensional vision, it translates the surgeon’s hand movements into precise movements of the instruments inside the patient, the camera is held and moved by the first surgeon, and a fourth robotic arm is available as a fixed retractor. The aim of this review is to summarise the current data on clinical and oncologic outcomes of robot-assisted surgery in rectal cancer, focusing on short- and long-term results, and providing original data from the authors’ centre. PMID:26811606

  8. Local Recurrence in Rectal Cancer: Anatomic Localization and Effect on Radiation Target

    SciTech Connect

    Syk, Erik Torkzad, Michael R.; Blomqvist, Lennart; Nilsson, Per J.; Glimelius, Bengt

    2008-11-01

    Purpose: To determine the sites of local recurrence after total mesorectal excision for rectal cancer in an effort to optimize the radiation target. Methods and Materials: A total of 155 patients with recurrence after abdominal resection for rectal cancer were identified from a population-based consecutive cohort of 2,315 patients who had undergone surgery by surgeons trained in the total mesorectal excision procedure. A total of 99 cross-sectional imaging studies were retrieved and re-examined by one radiologist. The clinical records were examined for the remaining patients. Results: Evidence of residual mesorectal fat was identified in 50 of the 99 patients. In 83 patients, local recurrence was identified on the imaging studies. All recurrences were within the irradiated volume if the patients had undergone preoperative radiotherapy or within the same volume if they had not. The site of recurrence was in the lower 75% of the pelvis, anatomically below the S1-S2 interspace for all patients. Only 5 of the 44 recurrences in patients with primary tumors >5 cm from the anal verge were in the lowest 20% of the pelvis. Six recurrences involved the lateral lymph nodes. Conclusion: These data suggest that a lowering of the upper limit of the clinical target volume could be introduced. The anal sphincter complex with surrounding tissue could also be excluded in patients with primary tumors >5 cm from the anal verge.

  9. Probiotics for Rectal Volume Variation During Radiation Therapy for Prostate Cancer

    SciTech Connect

    Ki, Yongkan; Kim, Wontaek; Nam, Jiho; Kim, Donghyun; Lee, Juhye; Park, Dahl; Jeon, Hosang; Ha, Honggu; Kim, Taenam; Kim, Dongwon

    2013-11-15

    Purpose: To investigate the effect of the probiotic Lactobacillus acidophilus on the percentage volume change of the rectum (PVC{sub R}), a crucial factor of prostate movement. Methods and Materials: Prostate cancer patients managed with tomotherapy as a radical treatment were enrolled in the study to take a probiotic capsule containing 1.0 × 10{sup 8} colony-forming units of L acidophilus or a placebo capsule twice daily. Radiation therapy was performed at a dose of 78 Gy in 39 fractions. The PVC{sub R}, defined as the difference in rectal volume between the planning computed tomographic (CT) and daily megavoltage CT images, was analyzed. Results: Forty patients were randomized into 2 groups. The L acidophilus group showed significantly lower median rectal volume and median PVC{sub R} values than the placebo group. L acidophilus showed a significant reduction effect on the PVC{sub R} (P<.001). However, the radiation therapy fraction number did not significantly influence the PVC{sub R}. Conclusions: L acidophilus was useful in reducing the PVC{sub R}, which is the most important determining factor of prostate position, during radiation therapy for prostate cancer.

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

    PubMed

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

    2016-07-01

    Following the introduction of total mesorectal excision (TME) in the curative treatment of rectal cancer, the role of neoadjuvant therapy has evolved. By improving the surgical technique the local recurrence rate could be reduced by TME surgery alone to below 8 %. Even if local control was further improved by additional preoperative irradiation this did not lead to a general survival benefit. Guidelines advocate that all patients in UICC stage II and III should be pretreated; however, the stage-based indications for neoadjuvant therapy have limitations. This is mainly attributable to the facts that patients with T3 tumors comprise a very heterogeneous prognostic group and preoperative lymph node diagnostics lack accuracy. In contrast, in recent years the circumferential resection margin (CRM) has become an important prognostic parameter. Patients with tumors that are very close to or infiltrate the pelvic fascia (positive CRM) have a higher rate of local recurrence and poorer survival. With high-resolution pelvic magnetic resonance imaging (MRI) examination in patients with rectal cancer, the preoperative CRM can be determined with a high sensitivity and specificity. Improved T staging and better prediction of the resection margins by pelvic MRI potentially facilitate the selection of patients for study-based treatment strategies omitting neoadjuvant radiotherapy. PMID:27339645

  11. Cost-Effectiveness of Robotic Surgery for Rectal Cancer Focusing on Short-Term Outcomes

    PubMed Central

    Kim, Chang Woo; Baik, Seung Hyuk; Roh, Yun Ho; Kang, Jeonghyun; Hur, Hyuk; Min, Byung Soh; Lee, Kang Young; Kim, Nam Kyu

    2015-01-01

    Abstract Although the total cost of robotic surgery (RS) is known to be higher than that of laparoscopic surgery (LS), the cost-effectiveness of RS has not yet been verified. The aim of the study is to clarify the cost-effectiveness of RS compared with LS for rectal cancer. From January 2007 through December 2011, 311 and 560 patients underwent totally RS and conventional LS for rectal cancer, respectively. A propensity score-matching analysis was performed with a ratio of 1:1 to reduce the possibility of selection bias. Costs and perioperative short-term outcomes in both the groups were compared. Additional costs due to readmission were also analyzed. The characteristics of the patients were not different between the 2 groups. Most perioperative outcomes were not different between the groups except for the operation time. Complications within 30 days of surgery were not significantly different. Total hospital charges and patients’ bill were higher in RS than in LS. The total hospital charges for patients who recovered with or without complications were higher in RS than in LS, although their short-term outcomes were similar. In patients with complications, the postoperative course after RS appeared to be milder than that of LS. Total hospital charges for patients who were readmitted due to complications were similar between the groups. RS showed similar short-term outcomes with higher costs than LS. Therefore, cost-effectiveness focusing on short-term perioperative outcomes of RS was not demonstrated. PMID:26039115

  12. STED Super-Resolution Microscopy of Clinical Paraffin-Embedded Human Rectal Cancer Tissue

    PubMed Central

    Wurm, Christian Andreas; Rüschoff, Josef; Ghadimi, B. Michael; Liersch, Torsten; Jakobs, Stefan

    2014-01-01

    Formalin fixed and paraffin-embedded human tissue resected during cancer surgery is indispensable for diagnostic and therapeutic purposes and represents a vast and largely unexploited resource for research. Optical microscopy of such specimen is curtailed by the diffraction-limited resolution of conventional optical microscopy. To overcome this limitation, we used STED super-resolution microscopy enabling optical resolution well below the diffraction barrier. We visualized nanoscale protein distributions in sections of well-annotated paraffin-embedded human rectal cancer tissue stored in a clinical repository. Using antisera against several mitochondrial proteins, STED microscopy revealed distinct sub-mitochondrial protein distributions, suggesting a high level of structural preservation. Analysis of human tissues stored for up to 17 years demonstrated that these samples were still amenable for super-resolution microscopy. STED microscopy of sections of HER2 positive rectal adenocarcinoma revealed details in the surface and intracellular HER2 distribution that were blurred in the corresponding conventional images, demonstrating the potential of super-resolution microscopy to explore the thus far largely untapped nanoscale regime in tissues stored in biorepositories. PMID:25025184

  13. Volvulus of the Sigmoid Colon Associated With Rectal Cancer: A Case Report

    PubMed Central

    Lee, Seung-Hyun; Ahn, Byung-Kwon; Baek, Sung-Uhn

    2015-01-01

    Sigmoid volvulus is one of the three most common causes of acute colonic obstruction. Predisposing factors include chronic constipation, adhesion from a prior abdominal surgery, and megacolon. However, concomitant presentation of volvulus of the sigmoid colon and rectal cancer is extremely rare. We report a case of a 50-year-old woman with coexisting volvulus of the sigmoid colon and rectal cancer. The patient presented with abdominal distension and pain for 2 days. On computed tomography, the whole colon was dilated with gas and feces. A whirl sign with rotation of the inferior mesenteric vessel was identified. The rectum had irregular wall thickening. Colonoscopy showed a circumscribed, ulcerofungating mass approximately 6 cm from the anal verge. The sigmoid colon was obstructed at a point approximately 25 cm from the anal verge. The mucosa was hyperemic and edematous with the pathognomonic spiral pattern. Endoscopic reduction was not successful. On laparotomy, the sigmoid colon was rotated around its mesentery. It was severely distended with edematous, hyperemic serosa. A tumor of the rectum was identified in the mid-rectum. The patient underwent low anterior resection and protective ileostomy. Pathologic findings confirmed adenocarcinoma of the rectum. The postoperative course was complicated by an ileus, which was managed with conservative treatment.

  14. Brachytherapy and Local Excision for Sphincter Preservation in T1 and T2 Rectal Cancer

    SciTech Connect

    Grimard, Laval Stern, Hartley; Spaans, Johanna N. M.Sc.

    2009-07-01

    Purpose: To report long-term results of brachytherapy after local excision (LE) in the treatment of T1 and T2 rectal cancer at risk of recurrence due to residual subclinical disease. Methods and Materials: Between 1989 and 2007, 32 patients undergoing LE and brachytherapy were followed prospectively for a mean of 6.2 years. Estimates of local recurrence (LR), disease-specific survival (DSS), and overall survival (OS) were generated. Treatment-related toxicity and the effect of known prognostic factors were determined. Results: There were 8 LR (3 T1, 5 T2), of which 5 were salvaged surgically. Median time to the 8 LR was 14 months, and the 5-year rate of local control was 76%. Although there have been 9 deaths to date, only 5 were from disease. Five-year DSS and OS rates were 85% and 78%, respectively. There were 4 cases of Grade 2-3 radionecrosis and 1 case of mild stool incontinence. The sphincter was preserved in 27 of 32 patients. Conclusion: Local excision and adjuvant brachytherapy for T1 and T2 rectal cancer is an appealing treatment alternative to immediate radical resection, particularly in the frail and elderly who are unable to undergo major surgery, as well as for patients wanting to avoid a permanent colostomy.

  15. Dietary influence on MAPK-signaling pathways and risk of colon and rectal cancer

    PubMed Central

    Slattery, Martha L.; Lundgreen, Abbie; Wolff, Roger K.

    2014-01-01

    Mitogen-activated protein kinase (MAPK) pathways regulate cellular functions including cell proliferation, differentiation, migration, and apoptosis. Associations between genes in the DUSP, ERK1/2, JNK, and p38 MAPK-signaling pathways and dietary factors associated with growth factors, inflammation, and oxidative stress and risk of colon and rectal cancer were evaluated. Data include colon cases (n=1555) and controls (n=1956) and rectal cases (n=754) and controls (n=959). Statistically significant interactions were observed for the MAPK-signaling pathways after adjustment for multiple comparisons. DUSP genes interacted with carbohydrates, mutagen index, calories, calcium, vitamin D, lycopene, dietary fats, folic acid, and selenium. MAPK1, MAPK3, MAPK1 and RAF1 within the ERK1/2 MAPK-signaling pathway interacted with dietary fats and cruciferous vegetables. Within the JNK MAPK-signaling pathway, interactions between MAP3K7 and protein, vitamin C, iron, folic acid, carbohydrates, and cruciferous vegetables; MAP3K10 and folic acid; MAP3K9 and lutein/zeaxanthin; MAPK8 and calcium; MAP3K3 and calcium and lutein; MAP3K1 and cruciferous vegetables. Interaction within the p38-signaling pathway included: MAPK14 with calories, carbohydrates saturated fat, selenium, vitamin C; MAP3K2 and carbohydrates, and folic acid. These data suggest that dietary factors involved in inflammation and oxidative stress interact with MAPK-signaling genes to alter risk of colorectal cancer. PMID:23859041

  16. Diffusion-Weighted Magnetic Resonance Imaging in Monitoring Rectal Cancer Response to Neoadjuvant Chemoradiotherapy

    SciTech Connect

    Barbaro, Brunella; Vitale, Renata; Valentini, Vincenzo; Illuminati, Sonia; Vecchio, Fabio M.; Rizzo, Gianluca; Gambacorta, Maria Antonietta; Coco, Claudio; Crucitti, Antonio; Persiani, Roberto; Sofo, Luigi; Bonomo, Lorenzo

    2012-06-01

    Purpose: To prospectively monitor the response in patients with locally advanced nonmucinous rectal cancer after chemoradiotherapy (CRT) using diffusion-weighted magnetic resonance imaging. The histopathologic finding was the reference standard. Methods and Materials: The institutional review board approved the present study. A total of 62 patients (43 men and 19 women; mean age, 64 years; range, 28-83) provided informed consent. T{sub 2}- and diffusion-weighted magnetic resonance imaging scans (b value, 0 and 1,000 mm{sup 2}/s) were acquired before, during (mean 12 days), and 6-8 weeks after CRT. We compared the median apparent diffusion coefficients (ADCs) between responders and nonresponders and examined the associations with the Mandard tumor regression grade (TRG). The postoperative nodal status (ypN) was evaluated. The Mann-Whitney/Wilcoxon two-sample test was used to evaluate the relationships among the pretherapy ADCs, extramural vascular invasion, early percentage of increases in ADCs, and preoperative ADCs. Results: Low pretreatment ADCs (<1.0 Multiplication-Sign 10{sup -3}mm{sup 2}/s) were correlated with TRG 4 scores (p = .0011) and associated to extramural vascular invasion with ypN+ (85.7% positive predictive value for ypN+). During treatment, the mean percentage of increase in tumor ADC was significantly greater in the responders than in the nonresponders (p < .0001) and a >23% ADC increase had a 96.3% negative predictive value for TRG 4. In 9 of 16 complete responders, CRT-related tumor downsizing prevented ADC evaluations. The preoperative ADCs were significantly different (p = .0012) between the patients with and without downstaging (preoperative ADC {>=}1.4 Multiplication-Sign 10{sup -3}mm{sup 2}/s showed a positive and negative predictive value of 78.9% and 61.8%, respectively, for response assessment). The TRG 1 and TRG 2-4 groups were not significantly different. Conclusion: Diffusion-weighted magnetic resonance imaging seems to be a promising

  17. A Phase I, Pharmacological, and Biological Study of OSI-774 in Combination With FOLFOX 4 (5-FU, Leucovorin, and Oxaliplatin) and Bevacizumab (Avastin) in Patients With Advanced Colorectal Cancer

    ClinicalTrials.gov

    2013-09-27

    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

  18. [Laparoscopic rectal resection technique].

    PubMed

    Anthuber, M; Kriening, B; Schrempf, M; Geißler, B; Märkl, B; Rüth, S

    2016-07-01

    The quality of radical oncological operations for patients with rectal cancer determines the rate of local recurrence and long-term survival. Neoadjuvant chemoradiotherapy for locally advanced tumors, a standardized surgical procedure for rectal tumors less than 12 cm from the anus with total mesorectal excision (TME) and preservation of the autonomous nerve system for sexual and bladder function have significantly improved the oncological results and quality of life of patients. The TME procedure for rectal resection has been performed laparoscopically in Germany for almost 20 years; however, no reliable data are available on the frequency of laparoscopic procedures in rectal cancer patients in Germany. The rate of minimally invasive procedures is estimated to be less than 20 %. A prerequisite for using the laparoscopic approach is implicit adherence to the described standards of open surgery. Available data from prospective randomized trials, systematic reviews and meta-analyses indicate that in the early postoperative phase the generally well-known positive effects of the minimally invasive approach to the benefit of patients can be realized without any long-term negative impact on the oncological results; however, the results of many of these studies are difficult to interpret because it could not be confirmed whether the hospitals and surgeons involved had successfully completed the learning curve. In this article we would like to present our technique, which we have developed over the past 17 years in more than 1000 patients. Based on our experiences the laparoscopic approach can be highly recommended as a suitable alternative to the open procedure. PMID:27277556

  19. Bevacizumab, Oxaliplatin, and Capecitabine With Radiation Therapy in Rectal Cancer: Phase I Trial Results

    SciTech Connect

    Czito, Brian G. . E-mail: czito001@mc.duke.edu; Bendell, Johanna C.; Willett, Christopher G.; Morse, Michael A.; Blobe, Gerard C.; Tyler, Douglas S.; Thomas, John; Ludwig, Kirk A.; Mantyh, Christopher R.; Ashton, Jill; Yu Daohai; Hurwitz, Herbert I.

    2007-06-01

    Purpose: The overexpression of vascular endothelial growth factor (VEGF) is associated with poor outcomes in colorectal cancer patients. Bevacizumab, a VEGF inhibitor, enhances the effects of chemotherapy and radiation therapy on tumor cytotoxicity in preclinical models, including colorectal cancer. A Phase I trial was undertaken to evaluate the combination of bevacizumab, capecitabine, oxaliplatin, and radiation therapy in patients with rectal cancer. Methods and Materials: Patients with pathologically confirmed adenocarcinoma of the rectum were eligible. Pretreatment staging included computerized tomography, endoscopic ultrasound, and surgical evaluation. Patients received 50.4 Gy of external beam radiation therapy (EBRT) to the tumor in 28 fractions. Capecitabine, oxaliplatin, and bevacizumab were administered concurrently with radiation therapy. After EBRT completion, patients were restaged and evaluated for surgery. Primary endpoints included the determination of dose-limiting toxicity and a recommended Phase II dose, non dose-limiting toxicity, and preliminary radiographic and pathologic response rates. Results: Eleven patients were enrolled. All were evaluable for toxicity and efficacy. Dose level 2 was associated with unacceptable toxicity (primarily diarrhea). Dose level 1 had an acceptable toxicity profile. The recommended Phase II dose in our study was bevacizumab 15 mg/kg Day 1 + 10 mg/kg Days 8 and 22, oxaliplatin 50 mg/m{sup 2} weekly, and capecitabine 625 mg/m{sup 2} bid during radiation days. Six patients had clinical responses. Two patients had a pathologic complete response, and 3 had microscopic disease only. One patient experienced a postoperative abscess, one a syncopal episode during adjuvant chemotherapy, and one a subclinical myocardial infarction during adjuvant chemotherapy. Conclusions: The combination of bevacizumab, capecitabine, oxaliplatin, and radiation therapy in rectal cancer was tolerable, with encouraging response rates. Further

  20. Prognostic Factors Affecting Locally Recurrent Rectal Cancer and Clinical Significance of Hemoglobin

    SciTech Connect

    Rades, Dirk Kuhn, Hildegard; Schultze, Juergen; Homann, Nils; Brandenburg, Bernd; Schulte, Rainer; Krull, Andreas; Schild, Steven E.; Dunst, Juergen

    2008-03-15

    Purpose: To investigate potential prognostic factors, including hemoglobin levels before and during radiotherapy, for associations with survival and local control in patients with unirradiated locally recurrent rectal cancer. Patients and Methods: Ten potential prognostic factors were investigated in 94 patients receiving radiotherapy for recurrent rectal cancer: age ({<=}68 vs. {>=}69 years), gender, Eastern Cooperative Oncology Group performance status (0-1 vs. 2-3), American Joint Committee on Cancer (AJCC) stage ({<=}II vs. III vs. IV), grading (G1-2 vs. G3), surgery, administration of chemotherapy, radiation dose (equivalent dose in 2-Gy fractions: {<=}50 vs. >50 Gy), and hemoglobin levels before (<12 vs. {>=}12 g/dL) and during (majority of levels: <12 vs. {>=}12 g/dL) radiotherapy. Multivariate analyses were performed, including hemoglobin levels, either before or during radiotherapy (not both) because these are confounding variables. Results: Improved survival was associated with better performance status (p < 0.001), lower AJCC stage (p = 0.023), surgery (p = 0.011), chemotherapy (p = 0.003), and hemoglobin levels {>=}12 g/dL both before (p = 0.031) and during (p < 0.001) radiotherapy. On multivariate analyses, performance status, AJCC stage, and hemoglobin levels during radiotherapy maintained significance. Improved local control was associated with better performance status (p = 0.040), lower AJCC stage (p = 0.010), lower grading (p = 0.012), surgery (p < 0.001), chemotherapy (p < 0.001), and hemoglobin levels {>=}12 g/dL before (p < 0.001) and during (p < 0.001) radiotherapy. On multivariate analyses, chemotherapy, grading, and hemoglobin levels before and during radiotherapy remained significant. Subgroup analyses of the patients having surgery demonstrated the extent of resection to be significantly associated with local control (p = 0.011) but not with survival (p = 0.45). Conclusion: Predictors for outcome in patients who received radiotherapy for

  1. Adjuvant chemotherapy for ypT0N0M0 rectal cancer following chemoradiotherapy and total mesorectal excision.

    PubMed

    Kainthla, Radhika; Huerta, Sergio

    2016-10-01

    The management of adenocarcinoma of the rectum is a dynamic field in oncology. The multidisciplinary approach to the management of this disease continues to evolve in each segment of its trimodality treatment. New scheduling regimens and radiosensitizing agents continue to emerge. Although total mesorectal excision continues to be the operation of choice for rectal cancers, what is done before and after surgery continues to evolve to maximize an ideal oncologic outcome with minimal morbidity. The achievement of a pathological complete response [pCR (i.e. ypT0N0)] in a fraction of patients undergoing neoadjuvant chemoradiation poses an interesting management dilemma. The cohort of patients who can achieve a pCR have superior oncologic outcomes compared to nonresponders. The present review addresses the need for adjuvant therapy in patients with a pCR. We discuss the evolution of the role of adjuvant therapy in patients with rectal cancer and the studies addressing the elimination of this strategy in all patients with rectal cancer with a goal of determining the current evidence that might result in the omission of adjuvant therapy for patients with ypT0N0 rectal cancer after chemoradiation and total mesorectal excision. PMID:27387144

  2. Laparoscopic restorative proctocolectomy with ileal pouch-anal anastomosis for Peutz-Jeghers syndrome with synchronous rectal cancer.

    PubMed

    Zhong, Min-Er; Niu, Bei-Zhan; Ji, Wu-Yang; Wu, Bin

    2016-06-14

    We report on a patient diagnosed with Peutz-Jeghers syndrome (PJS) with synchronous rectal cancer who was treated with laparoscopic restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA). PJS is an autosomal dominant syndrome characterized by multiple hamartomatous polyps in the gastrointestinal tract, mucocutaneous pigmentation, and increased risks of gastrointestinal and nongastrointestinal cancer. This report presents a patient with a 20-year history of intermittent bloody stool, mucocutaneous pigmentation and a family history of PJS, which together led to a diagnosis of PJS. Moreover, colonoscopy and biopsy revealed the presence of multiple serried giant pedunculated polyps and rectal adenocarcinoma. Currently, few options exist for the therapeutic management of PJS with synchronous rectal cancer. For this case, we adopted an unconventional surgical strategy and ultimately performed laparoscopic restorative proctocolectomy with IPAA. This procedure is widely considered to be the first-line treatment option for patients with ulcerative colitis or familial adenomatous polyposis. However, there are no previous reports of treating PJS patients with laparoscopic IPAA. Since the operation, the patient has experienced no further episodes of gastrointestinal bleeding and has demonstrated satisfactory bowel control. Laparoscopic restorative proctocolectomy with IPAA may be a safe and effective treatment for patients with PJS with synchronous rectal cancer. PMID:27298573

  3. Adjuvant therapy sparing in rectal cancer achieving complete response after chemoradiation

    PubMed Central

    García-Albéniz, Xabier; Gallego, Rosa; Hofheinz, Ralf Dieter; Fernández-Esparrach, Gloria; Ayuso-Colella, Juan Ramón; Bombí, Josep Antoni; Conill, Carles; Cuatrecasas, Miriam; Delgado, Salvadora; Ginés, Angels; Miquel, Rosa; Pagés, Mario; Pineda, Estela; Pereira, Verónica; Sosa, Aarón; Reig, Oscar; Victoria, Iván; Feliz, Luis; María de Lacy, Antonio; Castells, Antoni; Burkholder, Iris; Hochhaus, Andreas; Maurel, Joan

    2014-01-01

    AIM: To evaluate the long-term results of conventional chemoradiotherapy and laparoscopic mesorectal excision in rectal adenocarcinoma patients without adjuvant therapy. METHODS: Patients with biopsy-proven adenocarcinoma of the rectum staged cT3-T4 by endoscopic ultrasound or magnetic resonance imaging received neoadjuvant continuous infusion of 5-fluorouracil for five weeks and concomitant radiotherapy. Laparoscopic surgery was planned after 5-8 wk. Patients diagnosed with ypT0N0 stage cancer were not treated with adjuvant therapy according to the protocol. Patients with ypT1-2N0 or ypT3-4 or N+ were offered 5-fluorouracil-based adjuvant treatment on an individual basis. An external cohort was used as a reference for the findings. RESULTS: One hundred and seventy six patients were treated with induction chemoradiotherapy and 170 underwent total mesorectal excision. Cancer staging of ypT0N0 was achieved in 26/170 (15.3%) patients. After a median follow-up of 58.3 mo, patients with ypT0N0 had five-year disease-free and overall survival rates of 96% (95%CI: 77-99) and 100%, respectively. We provide evidence about the natural history of patients with localized rectal cancer achieving a complete response after preoperative chemoradiation. The inherent good prognosis of these patients will have implications for clinical trial design and care of patients. CONCLUSION: Withholding adjuvant chemotherapy after complete response following standard neoadjuvant chemoradiotherapy and laparoscopic mesorectal excision might be safe within an experienced multidisciplinary team. PMID:25400468

  4. Phase II Study of Preoperative Helical Tomotherapy With a Simultaneous Integrated Boost for Rectal Cancer

    SciTech Connect

    Engels, Benedikt; Tournel, Koen; Everaert, Hendrik; Hoorens, Anne; Sermeus, Alexandra; Christian, Nicolas; Storme, Guy; Verellen, Dirk; De Ridder, Mark

    2012-05-01

    Purpose: The addition of concomitant chemotherapy to preoperative radiotherapy is considered the standard of care for patients with cT3-4 rectal cancer. The combined treatment modality increases the complete response rate and local control (LC), but has no impact on survival or the incidence of distant metastases. In addition, it is associated with considerable toxicity. As an alternative strategy, we explored prospectively, preoperative helical tomotherapy with a simultaneous integrated boost (SIB). Methods and Materials: A total of 108 patients were treated with intensity-modulated and image-guided radiotherapy using the Tomotherapy Hi-Art II system. A dose of 46 Gy, in daily fractions of 2 Gy, was delivered to the mesorectum and draining lymph nodes, without concomitant chemotherapy. Patients with an anticipated circumferential resection margin (CRM) of less than 2 mm, based on magnetic resonance imaging, received a SIB to the tumor up to a total dose of 55.2 Gy. Acute and late side effects were scored using the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. Results: A total of 102 patients presented with cT3-4 tumors; 57 patients entered the boost group and 51 the no-boost group. One patient in the no-boost group developed a radio-hypersensitivity reaction, resulting in a complete tumor remission, a Grade 3 acute and Grade 5 late enteritis. No other Grade {>=}3 acute toxicities occurred. With a median follow-up of 32 months, Grade {>=}3 late gastrointestinal and urinary toxicity were observed in 6% and 4% of the patients, respectively. The actuarial 2-year LC, progression-free survival and overall survival were 98%, 79%, and 93%. Conclusions: Preoperative helical tomotherapy displays a favorable acute toxicity profile in patients with cT3-4 rectal cancer. A SIB can be safely administered in patients with a narrow CRM and resulted in a promising LC.

  5. Transanal Total Mesorectal Excision With Single-Incision Laparoscopy for Rectal Cancer

    PubMed Central

    Foo, Dominic Chi-chung; Choi, Hok Kwok; Wei, Rockson; Yip, Jeremy

    2016-01-01

    Background and Objectives: There has been great enthusiasm for the technique of transanal total mesorectal excision. Coupled with this procedure, we performed single-incision laparoscopic surgery for left colon mobilization. This is a description of our initial experience with the combined approach. Methods: Patients with distal or mid rectal cancer were included. The operation was performed by 2 teams: one team performed the single-incision mobilization of the left colon via the right lower quadrant ileostomy site, and the other team performed the total mesorectal excision with a transanal platform. Results: During the study period, 10 patients (5 men) with cancer of the rectum underwent the surgery. The mean age was 62.2 ± 11.1 years, and the mean body mass index was 23.4 ± 3.2 kg/m2. The tumor's mean distance from the anal verge was 5.1 ± 2.5 cm. The median operating time was 247.5 minutes (range, 188–462 minutes). The mean estimated blood loss was 124 ± 126 mL (range, 10–188 mL). Conversion to multiport laparoscopy was needed in one case (10%). Postoperative pain, as reflected by the pain score, was minimal. The mean number of lymph nodes harvested was 15.6 ± 3.8. All specimens had clear distal and circumferential radial margins. The overall complication rate was 10%. Conclusion: Our experience showed transanal total mesorectal excision with single-incision laparoscopy to be a feasible option for rectal cancer. Patients reported minimal postoperative pain. Further studies on the long-term outcome are warranted. PMID:27186068

  6. Anastomotic leakage in rectal cancer surgery: The role of blood perfusion

    PubMed Central

    Rutegård, Martin; Rutegård, Jörgen

    2015-01-01

    Anastomotic leakage after anterior resection for rectal cancer remains a common and often devastating complication. Preoperative risk factors for anastomotic leakage have been studied extensively and are used for patient selection, especially whether to perform a diverting stoma or not. From the current literature, data suggest that perfusion in the rectal stump rather than in the colonic limb may be more important for the integrity of the colorectal anastomosis. Moreover, available research suggests that the mid and upper rectum is considerably more vascularized than the lower part, in which the posterior compartment seems most vulnerable. These data fit neatly with the observation that anastomotic leaks are far more frequent in patients undergoing total compared to partial mesorectal excision, and also that most leaks occur dorsally. Clinical judgment has been shown to ineffectively assess anastomotic viability, while promising methods to measure blood perfusion are evolving. Much interest has recently been turned to near-infrared light technology, enhanced with fluorescent agents, which enables intraoperative perfusion assessment. Preliminary data are promising, but large-scale controlled trials are lacking. With maturation of such technology, perfusion measurements may in the future inform the surgeon whether anastomoses are at risk. In high colorectal anastomoses, anastomotic revision might be feasible, while a diverting stoma could be fashioned selectively instead of routinely for low anastomoses. PMID:26649151

  7. Quantification of Organ Motion During Chemoradiotherapy of Rectal Cancer Using Cone-Beam Computed Tomography

    SciTech Connect

    Chong, Irene; Hawkins, Maria; Hansen, Vibeke; Thomas, Karen; McNair, Helen; O'Neill, Brian; Aitken, Alexandra; Tait, Diana

    2011-11-15

    Purpose: There has been no previously published data related to the quantification of rectal motion using cone-beam computed tomography (CBCT) during standard conformal long-course chemoradiotherapy. The purpose of the present study was to quantify the interfractional changes in rectal movement and dimensions and rectal and bladder volume using CBCT and to quantify the bony anatomy displacements to calculate the margins required to account for systematic ({Sigma}) and random ({sigma}) setup errors. Methods and Materials: CBCT images were acquired from 16 patients on the first 3 days of treatment and weekly thereafter. The rectum and bladder were outlined on all CBCT images. The interfraction movement was measured using fixed bony landmarks as references to define the rectal location (upper, mid, and low), The maximal rectal diameter at the three rectal locations was also measured. The bony anatomy displacements were quantified, allowing the calculation of systematic ({Sigma}) and random ({sigma}) setup errors. Results: A total of 123 CBCT data sets were analyzed. Analysis of variance for standard deviation from planning scans showed that rectal anterior and lateral wall movement differed significantly by rectal location. Anterior and lateral rectal wall movements were larger in the mid and upper rectum compared with the low rectum. The posterior rectal wall movement did not change significantly with the rectal location. The rectal diameter changed more in the mid and upper than in the low rectum. No consistent relationship was found between the rectal and bladder volume and time, nor was a significant relationship found between the rectal volume and bladder volume. Conclusions: In the present study, the anterior and lateral rectal movement and rectal diameter were found to change most in the upper rectum, followed by the mid rectum, with the smallest changes seen in the low rectum. Asymmetric margins are warranted to ensure phase 2 coverage.

  8. Biopsy Specimens Obtained 7 Days After Starting Chemoradiotherapy (CRT) Provide Reliable Predictors of Response to CRT for Rectal Cancer

    SciTech Connect

    Suzuki, Toshiyuki; Sadahiro, Sotaro; Tanaka, Akira; Okada, Kazutake; Kamata, Hiroko; Kamijo, Akemi; Murayama, Chieko; Akiba, Takeshi; Kawada, Shuichi

    2013-04-01

    Purpose: Preoperative chemoradiation therapy (CRT) significantly decreases local recurrence in locally advanced rectal cancer. Various biomarkers in biopsy specimens obtained before CRT have been proposed as predictors of response. However, reliable biomarkers remain to be established. Methods and Materials: The study group comprised 101 consecutive patients with locally advanced rectal cancer who received preoperative CRT with oral uracil/tegafur (UFT) or S-1. We evaluated histologic findings on hematoxylin and eosin (H and E) staining and immunohistochemical expressions of Ki67, p53, p21, and apoptosis in biopsy specimens obtained before CRT and 7 days after starting CRT. These findings were contrasted with the histologic response and the degree of tumor shrinkage. Results: In biopsy specimens obtained before CRT, histologic marked regression according to the Japanese Classification of Colorectal Carcinoma (JCCC) criteria and the degree of tumor shrinkage on barium enema examination (BE) were significantly greater in patients with p21-positive tumors than in those with p21-negative tumors (P=.04 and P<.01, respectively). In biopsy specimens obtained 7 days after starting CRT, pathologic complete response, histologic marked regression according to both the tumor regression criteria and JCCC criteria, and T downstaging were significantly greater in patients with apoptosis-positive and p21-positive tumors than in those with apoptosis-negative (P<.01, P=.02, P=.01, and P<.01, respectively) or p21-negative tumors (P=.03, P<.01, P<.01, and P=.02, respectively). The degree of tumor shrinkage on both BE as well as MRI was significantly greater in patients with apoptosis-positive and with p21-positive tumors than in those with apoptosis-negative or p21-negative tumors, respectively. Histologic changes in H and E-stained biopsy specimens 7 days after starting CRT significantly correlated with pathologic complete response and marked regression on both JCCC and tumor

  9. Voiding and Sexual Function after Autonomic-Nerve-Preserving Surgery for Rectal Cancer in Disease-Free Male Patients

    PubMed Central

    Lee, Dong Kil; Song, Kanghyon; Park, Jong Wook; Moon, Sun-Mi

    2010-01-01

    Purpose We evaluated the effects of surgery for rectal cancer on postoperative voiding and sexual function over the course of time. Materials and Methods Data from 28 patients who underwent autonomic nerve preserving rectal cancer surgery were retrospectively analyzed. Operations were performed between October 2005 and July 2007 and all patients were followed-up for more than 3 years. Preoperatively, all patients underwent urodynamic studies including uroflowmetry, and filled out the International Prostate Symptom Score (IPSS). The evaluation of sexual function consisted of Erectile Function domain score in International Index of Erectile Function (IIEF-EFD) and Ejaculation domain score in Male Sexual Health Questionnaire (MSHQ-EjD). Data from uroflowmetry and questionnaires were examined. Results At 3 years postoperatively the prostate volume was similar to the preoperative value (p=0.727). There were no statistically significant postoperative changes in the average maximum flow rate (15.9 ml/s vs. 16.2 ml/s, p=0.637) and post-void residual urine volume (34.7 ml vs. 36.8 ml, p=0.809). No statistically significant differences were observed in the IPSS (13.2 vs. 12.2, p=0.374). However, although pelvic autonomic nerve preservation have been performed, a significant proportion of rectal cancer patients suffer from sexual dysfunction and the average of IIEF-EFD and MSHQ-EjD scores was decreased postoperatively until 3 years (25.1 vs. 16.1 and 28.3 vs. 14.2 respectively, p<0.001). Conclusions Voiding function was not affected after autonomic nerve-preserving rectal cancer surgery, however sexual function was significantly aggravated. We recommend that the baseline genitourinary function should be evaluated before the treatment for male rectal cancer patients, and penile rehabilitation is necessary for their quality of life after treatment. PMID:21221207

  10. Anatomical basis and clinical research of pelvic autonomic nerve preservation with laparoscopic radical resection for rectal cancer.

    PubMed

    Liu, Yan; Lu, Xiao-ming; Tao, Kai-xiong; Ma, Jian-hua; Cai, Kai-lin; Wang, Lin-fang; Niu, Yan-feng; Wang, Guo-bin

    2016-04-01

    The clinical effect of laparoscopic rectal cancer curative excision with pelvic autonomic nerve preservation (PANP) was investigated. This study evaluated the frequency of urinary and sexual dysfunction of 149 male patients with middle and low rectal cancer who underwent laparoscopic or open total mesorectal excision with pelvic autonomic nerve preservation (PANP) from March 2011 to March 2013. Eighty-four patients were subjected to laparoscopic surgery, and 65 to open surgery respectively. The patients were followed up for 12 months, interviewed, and administered a standardized questionnaire about postoperative functional outcomes and quality of life. In the laparoscopic group, 13 patients (18.37%) presented transitory postoperative urinary dysfunction, and were medically treated. So did 12 patients (21.82%) in open group. Sexual desire was maintained by 52.86%, un-ability to engage in intercourse by 47.15%, and un-ability to achieve orgasm and ejaculation by 34.29% of the patients in the laparoscopic group. Sexual desire was maintained by 56.36%, un-ability to engage in intercourse by 43.63%, and un-ability to achieve orgasm and ejaculation by 33.73% of the patients in the open group. No significant differences in urinary and sexual dysfunction between the laparoscopic and open rectal resection groups were observed (P>0.05). It was concluded that laparoscopic rectal cancer radical excision with PANP did not aggravate or improve sexual and urinary dysfunction. PMID:27072964

  11. COX-1 (PTGS1) and COX-2 (PTGS2) polymorphisms, NSAID interactions, and risk of colon and rectal cancer in two independent populations

    PubMed Central

    Makar, Karen W; Poole, Elizabeth M; Resler, Alexa J; Seufert, Brenna; Curtin, Karen; Kleinstein, Sarah E; Duggan, David; Kulmacz, Richard J; Hsu, Li; Whitton, John; Carlson, Christopher S; Rimorin, Christine F; Caan, Bette J; Baron, John A; Potter, John D; Slattery, Martha L; Ulrich, Cornelia M

    2014-01-01

    Purpose Nonsteroidal anti-inflammatory drugs (NSAIDs) target the prostaglandin H synthase enzymes, cyclooxygenase (COX)-1 and -2, and reduce colorectal cancer risk. Genetic variation in the genes encoding these enzymes may be associated with changes in colon and rectal cancer risk and in NSAID efficacy. Methods We genotyped candidate polymorphisms and tagSNPs in PTGS1 (COX-1) and PTGS2 (COX-2) in a population-based case-control study (Diet, Activity and Lifestyle Study, DALS) of colon cancer (n=1470 cases/1837 controls) and rectal cancer (n=583/775), and independently among cases and controls from the Colon Cancer Family Registry (CCFR; colon n= 959/1535, rectal n= 505/839). Results In PTGS2, a functional polymorphism (−765G>C; rs20417) was associated with a 2-fold increased rectal cancer risk (p=0.05) in the DALS study. This association replicated with a significant nearly 5-fold increased risk of rectal cancer in the CCFR study (ORCC vs GG=4.88; 95%CI=1.54–15.45; ORGC vs GG=1.36; 95%CI: 0.95–1.94). Genotype-NSAID interactions were observed in the DALS study for PTGS1 and rectal cancer risk, and for PTGS2 and colon cancer risk, but were no longer significant after correcting for multiple comparisons and did not replicate in the CCFR. No significant associations between PTGS1 polymorphisms and colon or rectal cancer risk were observed. Conclusions These findings suggest that polymorphisms in PTGS2 may be associated with rectal cancer risk and impact the protective effects of NSAIDs. PMID:24022467

  12. Moderately Low Alpha/Beta Ratio for Rectal Cancer May Best Explain the Outcome of Three Fractionation Schedules of Preoperative Radiotherapy

    SciTech Connect

    Suwinski, Rafal Wzietek, Iwona; Tarnawski, Rafal; Namysl-Kaletka, Agnieszka; Kryj, Mariusz; Chmielarz, Andrzej; Wydmanski, Jerzy

    2007-11-01

    Purpose: To estimate the {alpha}/{beta} ratio for rectal cancer according to the outcome of three fractionation schedules of preoperative radiotherapy. Methods and Materials: Between 1996 and 2002, 168 patients with locally advanced rectal cancer were treated as follows: 53 patients received 25 Gy in 5 Gy per fraction, 45 received 30 Gy in 3.0 Gy per fraction, and 70 were treated with accelerated hyperfractionation (42 Gy, 1.5 Gy per fraction, given twice daily). No patients received concurrent chemotherapy. The clinical characteristics of the groups were comparable. Surgery was performed shortly after radiotherapy. Crude data on locoregional tumor control were fitted directly using a linear-quadratic model, and the actuarial data were analyzed using Cox model. Results: A linear-quadratic model provided an {alpha} estimate of 0.339 (SE 0.115) and {beta} estimate of 0.067 (SE 0.027), which resulted in an {alpha}/{beta} ratio of 5.06 Gy (95% confidence interval -0.1 to 10.3). In all three schemes the overall radiation treatment time was short, which limits the rationales for incorporating time effect into the model. If, however, time was incorporated the {alpha}/{beta} ratio was 11.1 Gy and the dose increment required to compensate for repopulation was 0.15 Gy/day. The actuarial analysis provided similar {alpha}/{beta} estimates. Conclusion: Although because of the retrospective character of the study, nonrandomized selection of fractionation schedule, and uncontrolled quality of surgery the present results can be regarded as hypothesis generating only, the control rates obtained in the pelvis are consistent with a moderately low {alpha}/{beta} ratio for rectal cancer.

  13. Rectal cancer staging: focus on the prognostic significance of the findings described by high-resolution magnetic resonance imaging.

    PubMed

    Dieguez, Adriana

    2013-01-01

    High-resolution (HR) magnetic resonance imaging (MRI) has become an indispensable tool for multidisciplinary teams (MDTs) addressing rectal cancer. It provides anatomic information for surgical planning and allows patients to be stratified into different groups according to the risk of local and distant recurrence. One of the objectives of the MDT is the preoperative identification of high-risk patients who will benefit from neoadjuvant treatment. For this reason, the correct evaluation of the circumferential resection margin (CRM), the depth of tumor spread beyond the muscularis propria, extramural vascular invasion and nodal status is of the utmost importance. Low rectal tumors represent a special challenge for the MDT, because decisions seek a balance between oncologic safety, in the pursuit of free resection margins, and the patient's quality of life, in order to preserve sphincter function. At present, the exchange of information between the different specialties involved in dealing with patients with rectal cancer can rank the contribution of colleagues, auditing their work and incorporating knowledge that will lead to a better understanding of the pathology. Thus, beyond the anatomic description of the images, the radiologist's role in the MDT makes it necessary to know the prognostic value of the findings that we describe, in terms of recurrence and survival, because these findings affect decision making and, therefore, the patients' life. In this review, the usefulness of HR MRI in the initial staging of rectal cancer and in the evaluation of neoadjuvant treatment, with a focus on the prognostic value of the findings, is described as well as the contribution of HR MRI in assessing patients with suspected or confirmed recurrence of rectal cancer. PMID:23876415

  14. Localized volume effects for late rectal and anal toxicity after radiotherapy for prostate cancer

    SciTech Connect

    Peeters, Stephanie T.H.; Lebesque, Joos V. . E-mail: j.lebesque@nki.nl; Heemsbergen, Wilma D.; Putten, Wim L.J. van; Slot, Annerie; Dielwart, Michel F.H.; Koper, Peter C.M.

    2006-03-15

    Purpose: To identify dosimetric parameters derived from anorectal, rectal, and anal wall dose distributions that correlate with different late gastrointestinal (GI) complications after three-dimensional conformal radiotherapy for prostate cancer. Methods and Materials: In this analysis, 641 patients from a randomized trial (68 Gy vs. 78 Gy) were included. Toxicity was scored with adapted Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer (RTOG/EORTC) criteria and five specific complications. The variables derived from dose-volume histogram of anorectal, rectal, and anal wall were as follows: % receiving {>=}5-70 Gy (V5-V70), maximum dose (D{sub max}), and mean dose (D{sub mean}). The anus was defined as the most caudal 3 cm of the anorectum. Statistics were done with multivariate Cox regression models. Median follow-up was 44 months. Results: Anal dosimetric variables were associated with RTOG/EORTC Grade {>=}2 (V5-V40, D{sub mean}) and incontinence (V5-V70, D{sub mean}). Bleeding correlated most strongly with anorectal V55-V65, and stool frequency with anorectal V40 and D{sub mean}. Use of steroids was weakly related to anal variables. No volume effect was seen for RTOG/EORTC Grade {>=}3 and pain/cramps/tenesmus. Conclusion: Different volume effects were found for various late GI complications. Therefore, to evaluate the risk of late GI toxicity, not only intermediate and high doses to the anorectal wall volume should be taken into account, but also the dose to the anal wall.

  15. Biological Image-Guided Radiotherapy in Rectal Cancer: Challenges and Pitfalls

    SciTech Connect

    Roels, Sarah; Slagmolen, Pieter; Lee, John A.; Loeckx, Dirk; Maes, Frederik; Stroobants, Sigrid; Ectors, Nadine; Penninckx, Freddy; Haustermans, Karin

    2009-11-01

    Purpose: To investigate the feasibility of integrating multiple imaging modalities for image-guided radiotherapy in rectal cancer. Patients and Methods: Magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) were performed before, during, and after preoperative chemoradiotherapy (CRT) in patients with resectable rectal cancer. The FDG-PET signals were segmented with an adaptive threshold-based and a gradient-based method. Magnetic resonance tumor volumes (TVs) were manually delineated. A nonrigid registration algorithm was applied to register the images, and mismatch analyses were carried out between MR and FDG-PET TVs and between TVs over time. Tumor volumes delineated on the images after CRT were compared with the pathologic TV. Results: Forty-five FDG-PET/CT and 45 MR images were analyzed from 15 patients. The mean MRI and FDG-PET TVs showed a tendency to shrink during and after CRT. In general, MRI showed larger TVs than FDG-PET. There was an approximately 50% mismatch between the FDG-PET TV and the MRI TV at baseline and during CRT. Sixty-one percent of the FDG-PET TV and 76% of the MRI TV obtained after 10 fractions of CRT remained inside the corresponding baseline TV. On MRI, residual tumor was still suspected in all 6 patients with a pathologic complete response, whereas FDG-PET showed a metabolic complete response in 3 of them. The FDG-PET TVs delineated with the gradient-based method matched closest with pathologic findings. Conclusions: Integration of MRI and FDG-PET into radiotherapy seems feasible. Gradient-based segmentation is recommended for FDG-PET. Spatial variance between MRI and FDG-PET TVs should be taken into account for target definition.

  16. [Resection of a left obturator lymph node recurrence five years five months after surgery for rectal cancer].

    PubMed

    Takenoya, Takashi; Kobayashi, Yukari; Suda, Kouichi; Shimizu, Kazuki; Kikuichi, Masahiro

    2014-11-01

    A 62-year-old man with lower rectal cancer underwent abdominoperineal resection and dissection of the lateral pelvic lymph nodes. The cancer was staged at pT3pN0cM0, pStage II and did not show recurrence. Two years later, the patient had dysphagia and was diagnosed with esophageal cancer based on upper gastrointestinal endoscopy. Positron emission tomography-computed tomography (PET/CT) performed to detect distant metastasis revealed fluorodeoxyglucose (FDG) uptake in the left obturator lymph nodes, indicating rectal cancer recurrence. The patient received radiation therapy (60.4 Gy) for the recurrence. A PET/CT scan obtained 2 years 6 months after the initial rectal cancer resection revealed no FDG uptake. Uraciltegafur plus Leucovorin (UFT+LV) was started and continued for 6 months, but tumor enlargement was noted. Treatment was changed to LV, 5-fluorouracil, and irinotecan (FOLFIRI), but after 4 courses, the patient's carcinoembryonic antigen (CEA) levels rose. The patient then received 4 courses of bevacizumab plus FOLFIRI. A CT scan revealed tumor shrinkage, so the patient received 4 more courses of this regimen. Five years postoperatively, the patient's CEA levels rose again. A PET/CT scan 4 months later revealed FDG uptake in the left obturator lymph nodes, indicative of rectal cancer recurrence. One month later, the lymph nodes were resected. The patient was subsequently recurrence free. Tumor marker measurement and PET/CT helped to assess the patient's condition. When cancer recurs in the lateral pelvic lymph nodes with no involvement of the pelvis and R0 resection is possible, resection should be considered if the patient is capable of undergoing surgery.

  17. Predictors of Rectal Tolerance Observed in a Dose-Escalated Phase 1-2 Trial of Stereotactic Body Radiation Therapy for Prostate Cancer

    SciTech Connect

    Kim, D.W. Nathan; Cho, L. Chinsoo; Straka, Christopher; Christie, Alana; Lotan, Yair; Pistenmaa, David; Kavanagh, Brian D.; Nanda, Akash; Kueplian, Patrick; Brindle, Jeffrey; Cooley, Susan; Perkins, Alida; Raben, David; Xie, Xian-Jin; Timmerman, Robert D.

    2014-07-01

    Purpose: To convey the occurrence of isolated cases of severe rectal toxicity at the highest dose level tested in 5-fraction stereotactic body radiation therapy (SBRT) for localized prostate cancer; and to rationally test potential causal mechanisms to guide future studies and experiments to aid in mitigating or altogether avoiding such severe bowel injury. Methods and Materials: Clinical and treatment planning data were analyzed from 91 patients enrolled from 2006 to 2011 on a dose-escalation (45, 47.5, and 50 Gy in 5 fractions) phase 1/2 clinical study of SBRT for localized prostate cancer. Results: At the highest dose level, 6.6% of patients treated (6 of 91) developed high-grade rectal toxicity, 5 of whom required colostomy. Grade 3+ delayed rectal toxicity was strongly correlated with volume of rectal wall receiving 50 Gy >3 cm{sup 3} (P<.0001), and treatment of >35% circumference of rectal wall to 39 Gy (P=.003). Grade 2+ acute rectal toxicity was significantly correlated with treatment of >50% circumference of rectal wall to 24 Gy (P=.010). Conclusion: Caution is advised when considering high-dose SBRT for treatment of tumors near bowel structures, including prostate cancer. Threshold dose constraints developed from physiologic principles are defined, and if respected can minimize risk of severe rectal toxicity.

  18. Metachronous Bilateral Isolated Adrenal Metastasis from Rectal Adenocarcinoma: A Case Report

    PubMed Central

    Jabir, H.; Tawfiq, N.; Moukhlissi, M.; Akssim, M.; Guensi, A.; Kadiri, B.; Bouchbika, Z.; Taleb, A.; Benchekroun, N.; Jouhadi, H.; Sahraoui, S.; Zamiati, S.; Benider, A.

    2014-01-01

    We report a case of adrenal metastasis from colorectal cancer in a 54-year-old woman. Nine months after resection for advanced rectal carcinoma, a computed tomography scan revealed bilateral adrenal metastasis. The level of serum carcinoembryonic antigen was normal. A bilateral adrenalectomy was performed after chemotherapy. Histopathological examination showed adenocarcinoma, compatible with metastasis from the rectal cancer. Adrenal metastasis should be considered in the patients' follow-up for colorectal cancer. PMID:24860684

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

    SciTech Connect

    Yu, Stanley K.T.; Tait, Diana

    2013-11-01

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

  20. Carcinoembryonic antigen (CEA) level, CEA ratio, and treatment outcome of rectal cancer patients receiving pre-operative chemoradiation and surgery

    PubMed Central

    2013-01-01

    Background To investigate serum carcinoembryonic antigen (CEA) as a prognostic factor for rectal cancer patients receiving pre-operative chemoradiotherapy (CRT). Methods Between 2000 and 2009, 138 patients with advanced rectal cancer receiving CRT before surgery at our hospital were retrospectively classified into 3 groups: pre-CRT CEA <6 ng/ml (group L; n = 87); pre-CRT CEA ≥ 6 ng/ml and post-CRT CEA <6 ng/ml (group H-L; n = 32); and both pre- and post-CRT CEA ≥ 6 ng/ml (group H-H; n = 19). CEA ratio (defined as post-CRT CEA divided by pre-CRT CEA), post-CRT CEA level and other factors were reviewed for prediction of pathologic complete response (pCR). Results Five-year disease-free survival (DFS) was better in groups L (69.0%) and H-L (74.5%) than in group H-H (44.9%) (p = 0.024). Pathologic complete response was observed in 19.5%, 21.9% and 5.3% of groups L, H-L and H-H respectively (p = 0.281). Multivariate analysis showed that ypN stage and pCR were independent prognostic factors for DFS and that post-CRT CEA level was independently predictive of pCR. As a whole, post-CRT CEA <2.61 ng/ml predicted pCR (sensitivity 76.0%; specificity 58.4%). For those with pre-CRT CEA ≥6 ng/ml, post-CRT CEA and CEA ratio both predicted pCR (sensitivity 87.5%, specificity 76.7%). Conclusions In patients with pre-CRT serum CEA ≥6 ng/ml, those with “normalized” CEA levels after CRT may have similar DFS to those with “normal” (<6 ng/ml) pre-CRT values. Post-CRT CEA level is a predictor for pCR, especially in those with pre-CRT CEA ≥6 ng/ml. PMID:23452434

  1. Pharmacogenetic Study in Rectal Cancer Patients Treated With Preoperative Chemoradiotherapy: Polymorphisms in Thymidylate Synthase, Epidermal Growth Factor Receptor, GSTP1, and DNA Repair Genes

    SciTech Connect

    Paez, David; Salazar, Juliana; Pare, Laia; Pertriz, Lourdes; Targarona, Eduardo; Rio, Elisabeth del; Barnadas, Agusti; Marcuello, Eugenio; Baiget, Montserrat

    2011-12-01

    Purpose: Several studies have been performed to evaluate the usefulness of neoadjuvant treatment using oxaliplatin and fluoropyrimidines for locally advanced rectal cancer. However, preoperative biomarkers of outcome are lacking. We studied the polymorphisms in thymidylate synthase, epidermal growth factor receptor, glutathione S-transferase pi 1 (GSTP1), and several DNA repair genes to evaluate their usefulness as pharmacogenetic markers in a cohort of 128 rectal cancer patients treated with preoperative chemoradiotherapy. Methods and Materials: Blood samples were obtained from 128 patients with Stage II-III rectal cancer. DNA was extracted from the peripheral blood nucleated cells, and the genotypes were analyzed by polymerase chain reaction amplification and automated sequencing techniques or using a 48.48 dynamic array on the BioMark system. The germline polymorphisms studied were thymidylate synthase, (VNTR/5 Prime UTR, 2R G>C single nucleotide polymorphism [SNP], 3R G>C SNP), epidermal growth factor receptor (Arg497Lys), GSTP1 (Ile105val), excision repair cross-complementing 1 (Asn118Asn, 8092C>A, 19716G>C), X-ray repair cross-complementing group 1 (XRCC1) (Arg194Trp, Arg280His, Arg399Gln), and xeroderma pigmentosum group D (Lys751Gln). The pathologic response, pathologic regression, progression-free survival, and overall survival were evaluated according to each genotype. Results: The Asterisk-Operator 3/ Asterisk-Operator 3 thymidylate synthase genotype was associated with a greater response rate (pathologic complete remission and microfoci residual tumor, 59% in Asterisk-Operator 3/ Asterisk-Operator 3 vs. 35% in Asterisk-Operator 2/ Asterisk-Operator 2 and Asterisk-Operator 2/ Asterisk-Operator 3; p = .013). For the thymidylate synthase genotype, the median progression-free survival was 103 months for the Asterisk-Operator 3/ Asterisk-Operator 3 patients and 84 months for the Asterisk-Operator 2/ Asterisk-Operator 2 and Asterisk-Operator 2/ Asterisk

  2. Uptake of an innovation in surgery: observations from the cluster-randomized Quality Initiative in Rectal Cancer trial

    PubMed Central

    Simunovic, Marko; Coates, Angela; Smith, Andrew; Thabane, Lehana; Goldsmith, Charles H.; Levine, Mark N.

    2013-01-01

    Background Theory suggests the uptake of a medical innovation is influenced by how potential adopters perceive innovation characteristics and by characteristics of potential adopters. Innovation adoption is slow among the first 20% of individuals in a target group and then accelerates. The Quality Initiative in Rectal Cancer (QIRC) trial assessed if rectal cancer surgery outcomes could be improved through surgeon participation in the QIRC strategy. We tested if traditional uptake of innovation concepts applied to surgeons in the experimental arm of the trial. Methods The QIRC strategy included workshops, access to opinion leaders, intra-operative demonstrations, postoperative questionnaires, and audit and feedback. For intraoperative demonstrations, a participating surgeon invited an outside surgeon to demonstrate optimal rectal surgery techniques. We used surgeon timing in a demonstration to differentiate early and late adopters of the QIRC strategy. Surgeons completed surveys on perceptions of the strategy and personal characteristics. Results Nineteen of 56 surgeons (34%) requested an operative demonstration on their first case of rectal surgery. Early and late adopters had similar perceptions of the QIRC strategy and similar characteristics. Late adopters were less likely than early adopters to perceive an advantage for the surgical techniques promoted by the trial (p = 0.023). Conclusion Most traditional diffusion of innovation concepts did not apply to surgeons in the QIRC trial, with the exception of the importance of perceptions of comparative advantage. PMID:24284150

  3. Downstage migration after neoadjuvant chemoradiotherapy for rectal cancer: the reverse of the Will Rogers phenomenon?

    PubMed

    Fokas, Emmanouil; Liersch, Torsten; Fietkau, Rainer; Hohenberger, Werner; Hess, Clemens; Becker, Heinz; Sauer, Rolf; Wittekind, Christian; Rödel, Claus

    2015-06-01

    Downstaging after neoadjuvant treatment is increasingly used as a prognostic factor and surrogate endpoint in clinical trials. However, in recent trials of neoadjuvant 5-fluorouracil-based chemoradiotherapy for rectal cancer, downstaging did not translate into a benefit with regard to either disease-free survival (DFS) or overall survival. By analyzing the 10-year outcome data of the German CAO/ARO/AIO-94 phase 3 trial, the authors demonstrated that significantly fewer patients had poor prognostic features (eg, ypT3-4, ypN1-2) after preoperative 5-fluorouracil-based chemoradiotherapy. Nevertheless, these patients with International Union for Cancer Control stage II disease were found to be at a higher risk of developing distant metastases and had poorer DFS compared with patients with corresponding TNM tumor (sub)groups in the postoperative treatment arm, whereas patients with International Union for Cancer Control stage III disease demonstrated a nonsignificant trend toward a worse outcome after preoperative treatment. Overall, DFS remained identical in both treatment arms. Thus, "downstage migration" after neoadjuvant treatment resembles the reverse of the Will Rogers phenomenon and therefore may not be a reliable endpoint for long-term outcomes.

  4. Pharmacogenetics Biomarkers and Their Specific Role in Neoadjuvant Chemoradiotherapy Treatments: An Exploratory Study on Rectal Cancer Patients

    PubMed Central

    Dreussi, Eva; Cecchin, Erika; Polesel, Jerry; Canzonieri, Vincenzo; Agostini, Marco; Boso, Caterina; Belluco, Claudio; Buonadonna, Angela; Lonardi, Sara; Bergamo, Francesca; Gagno, Sara; De Mattia, Elena; Pucciarelli, Salvatore; De Paoli, Antonino; Toffoli, Giuseppe

    2016-01-01

    Background: Pathological complete response (pCR) to neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC) is still ascribed to a minority of patients. A pathway based-approach could highlight the predictive role of germline single nucleotide polymorphisms (SNPs). The primary aim of this study was to define new predictive biomarkers considering treatment specificities. Secondary aim was to determine new potential predictive biomarkers independent from radiotherapy (RT) dosage and cotreatment with oxaliplatin. Methods: Thirty germ-line SNPs in twenty-one genes were selected according to a pathway-based approach. Genetic analyses were performed on 280 LARC patients who underwent fluoropyrimidine-based CRT. The potential predictive role of these SNPs in determining pathological tumor response was tested in Group 1 (94 patients undergoing also oxaliplatin), Group 2 (73 patients treated with high RT dosage), Group 3 (113 patients treated with standard RT dosage), and in the pooled population (280 patients). Results: Nine new predictive biomarkers were identified in the three groups. The most promising one was rs3136228-MSH6 (p = 0.004) arising from Group 3. In the pooled population, rs1801133-MTHFR showed only a trend (p = 0.073). Conclusion: This exploratory study highlighted new potential predictive biomarkers of neoadjuvant CRT and underlined the importance to strictly define treatment peculiarities in pharmacogenetic analyses. PMID:27608007

  5. Advances in cancer immunology and cancer immunotherapy.

    PubMed

    Voena, Claudia; Chiarle, Roberto

    2016-02-01

    After decades of setbacks, cancer immunology is living its Golden Age. Recent advances in cancer immunology have provided new therapeutic approaches to treat cancer. The objective clinical response observed in patients treated with antibodies that block the immune checkpoints, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell-death protein 1 (PD-1)/programmed cell-death 1 ligand 1 (PD-L1) pathways, has led to their FDA approval for the treatment of melanoma in 2011 and in 2014, respectively. The anti-PD-1 antibody nivolumab has received the FDA-approval in March 2015 for squamous lung cancer treatment. In addition, antibodies targeting PD-1 or PD-L1 have demonstrated their efficacy and safety in additional tumors, including non-small cell lung carcinoma (NSCLC), renal cell carcinoma (RCC), bladder cancer, and Hodgkin's lymphoma. Almost at the same time, the field of adoptive cell transfer has exploded. The chimeric antigen receptor (CAR) T technology has provided strong evidence of efficacy in the treatment of B cell malignancies, and different T cell based treatments are currently under investigation for different types of tumors. In this review we will discuss the latest advances in cancer immunology and immunotherapy as well as new treatments now under development in the clinic and potential strategies that have shown promising results in preclinical models. PMID:27011048

  6. A pilot study of fiberscopy-guided local injection of anti-cancer drugs bound to carbon particles for control of rectal cancer.

    PubMed

    Hagiwara, A; Hirata, Y; Takahashi, T

    1998-04-01

    Rectal cancer patients with contra-indicatory risks may not be able to undergo surgery. In these cases the preferred treatment is chemotherapy. The present dosage formulation, consisting of an anti-cancer drug bound to activated carbon particles, was designed to deliver the anti-cancer drug at high concentration selectively to the injection site as well as to the regional lymph nodes and to improve survival of mice bearing cancer with nodal metastases, as compared to the same dose of aqueous anti-cancer drug in animal experiments. The present clinical trial includes two patients with histologically confirmed adenocarcinoma of the rectum and who had risks contra-indicating surgery. Carbon particles adsorbing anti-cancer drugs totaling 400 mg of methotrexate and 32 mg of mitomycin C in one patient and 100 mg of methotrexate and 8 mg of mitomycin C in another patient were injected into the cancer tissue under guidance of a colono-fiberscope. The rectal cancers were successfully reduced in size and controlled over 2 years or 6 months until the patients died from other causes. Side effect was mild. Local injection of this dosage formulation will be useful for the control of rectal cancer in patients who cannot undergo surgery. PMID:9635928

  7. Preoperative Radiation Therapy With Concurrent Capecitabine, Bevacizumab, and Erlotinib for Rectal Cancer: A Phase 1 Trial

    SciTech Connect

    Das, Prajnan; Eng, Cathy; Rodriguez-Bigas, Miguel A.; Chang, George J.; Skibber, John M.; You, Y. Nancy; Maru, Dipen M.; Munsell, Mark F.; Clemons, Marilyn V.; Kopetz, Scott E.; Garrett, Christopher R.; Shureiqi, Imad; Delclos, Marc E.; Krishnan, Sunil; Crane, Christopher H.

    2014-02-01

    Purpose: The goal of this phase 1 trial was to determine the maximum tolerated dose (MTD) of concurrent capecitabine, bevacizumab, and erlotinib with preoperative radiation therapy for rectal cancer. Methods and Materials: Patients with clinical stage II to III rectal adenocarcinoma, within 12 cm from the anal verge, were treated in 4 escalating dose levels, using the continual reassessment method. Patients received preoperative radiation therapy with concurrent bevacizumab (5 mg/kg intravenously every 2 weeks), erlotinib, and capecitabine. Capecitabine dose was increased from 650 mg/m{sup 2} to 825 mg/m{sup 2} orally twice daily on the days of radiation therapy; erlotinib dose was increased from 50 mg orally daily in weeks 1 to 3, to 50 mg daily in weeks 1 to 6, to 100 mg daily in weeks 1 to 6. Patients underwent surgery at least 9 weeks after the last dose of bevacizumab. Results: A total of 19 patients were enrolled, and 18 patients were considered evaluable. No patient had grade 4 acute toxicity, and 1 patient had grade 3 acute toxicity (hypertension). The MTD was not reached. All 18 evaluable patients underwent surgery, with low anterior resection in 7 (39%), proctectomy with coloanal anastomosis in 4 patients (22%), posterior pelvic exenteration in 1 (6%), and abdominoperineal resection in 6 (33%). Of the 18 patients, 8 (44%) had pathologic complete response, and 1 had complete response of the primary tumor with positive nodes. Three patients (17%) had grade 3 postoperative complications (ileus, small bowel obstruction, and infection). With a median follow-up of 34 months, 1 patient developed distant metastasis, and no patient had local recurrence or died. The 3-year disease-free survival was 94%. Conclusions: The combination of preoperative radiation therapy with concurrent capecitabine, bevacizumab, and erlotinib was well tolerated. The pathologic complete response rate appears promising and may warrant further investigation.

  8. Comparison Between Perfusion Computed Tomography and Dynamic Contrast-Enhanced Magnetic Resonance Imaging in Rectal Cancer

    SciTech Connect

    Kierkels, Roel G.J.; Backes, Walter H.; Janssen, Marco H.M.; Buijsen, Jeroen; Beets-Tan, Regina G.H.; Lambin, Philippe; Lammering, Guido; Oellers, Michel C.; Aerts, Hugo J.W.L.

    2010-06-01

    Purpose: To compare pretreatment scans with perfusion computed tomography (pCT) vs. dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in rectal tumors. Methods and Materials: Nineteen patients diagnosed with rectal cancer were included in this prospective study. All patients underwent both pCT and DCE-MRI. Imaging was performed on a dedicated 40-slice CT-positron emission tomography system and a 3-T MRI system. Dynamic contrast enhancement was measured in tumor tissue and the external iliac artery. Tumor perfusion was quantified in terms of pharmacokinetic parameters: transfer constant K{sup trans}, fractional extravascular-extracellular space v{sub e}, and fractional plasma volume v{sub p}. Pharmacokinetic parameter values and their heterogeneity (by 80% quantile value) were compared between pCT and DCE-MRI. Results: Tumor K{sup trans} values correlated significantly for the voxel-by-voxel-derived median (Kendall's tau correlation, tau = 0.81, p < 0.001) and 80% quantile (tau = 0.54, p = 0.04), as well as for the averaged uptake (tau = 0.58, p = 0.03). However, no significant correlations were found for v{sub e} and v{sub p} derived from the voxel-by-voxel-derived median and 80% quantile and derived from the averaged uptake curves. Conclusions: This study demonstrated for the first time that pCT provides K{sup trans} values comparable to those of DCE-MRI. However, no correlation was found for the v{sub e} and v{sub p} parameters between CT and MRI. Computed tomography can serve as an alternative modality to MRI for the in vivo evaluation of tumor angiogenesis in terms of the transfer constant K{sup trans}.

  9. Voxel-based population analysis for correlating local dose and rectal toxicity in prostate cancer radiotherapy

    NASA Astrophysics Data System (ADS)

    Acosta, Oscar; Drean, Gael; Ospina, Juan D.; Simon, Antoine; Haigron, Pascal; Lafond, Caroline; de Crevoisier, Renaud

    2013-04-01

    The majority of current models utilized for predicting toxicity in prostate cancer radiotherapy are based on dose-volume histograms. One of their main drawbacks is the lack of spatial accuracy, since they consider the organs as a whole volume and thus ignore the heterogeneous intra-organ radio-sensitivity. In this paper, we propose a dose-image-based framework to reveal the relationships between local dose and toxicity. In this approach, the three-dimensional (3D) planned dose distributions across a population are non-rigidly registered into a common coordinate system and compared at a voxel level, therefore enabling the identification of 3D anatomical patterns, which may be responsible for toxicity, at least to some extent. Additionally, different metrics were employed in order to assess the quality of the dose mapping. The value of this approach was demonstrated by prospectively analyzing rectal bleeding (⩾Grade 1 at 2 years) according to the CTCAE v3.0 classification in a series of 105 patients receiving 80 Gy to the prostate by intensity modulated radiation therapy (IMRT). Within the patients presenting bleeding, a significant dose excess (6 Gy on average, p < 0.01) was found in a region of the anterior rectal wall. This region, close to the prostate (1 cm), represented less than 10% of the rectum. This promising voxel-wise approach allowed subregions to be defined within the organ that may be involved in toxicity and, as such, must be considered during the inverse IMRT planning step.

  10. Effect of particle beam radiotherapy on locally recurrent rectal cancer: Three case reports

    PubMed Central

    MOKUTANI, YUKAKO; YAMAMOTO, HIROFUMI; UEMURA, MAMORU; HARAGUCHI, NAOTSUGU; TAKAHASHI, HIDEKAZU; NISHIMURA, JUNICHI; HATA, TAISHI; TAKEMASA, ICHIRO; MIZUSHIMA, TSUNEKAZU; DOKI, YUICHIRO; MORI, MASAKI

    2015-01-01

    Surgical resection is the most effective therapy for locally recurrent rectal cancer (LRRC); however, it often necessitates invasive procedures that may lead to major complications. Particle beam radiotherapy (RT), including carbon ion RT (C-ion RT) and proton beam RT, is a promising new modality that exhibits considerable efficacy against various types of human cancer. C-ion RT reportedly offers a therapeutic alternative for LRRC. In the present study, we describe three cases of LRRC treated by particle beam RT. In all the cases, LRRC was diagnosed by computed tomography, magnetic resonance imaging and positron emission tomography imaging. No serious adverse effects were observed during RT. One patient experienced re-recurrence of LRRC, but survived for 6 years following particle beam RT; the second patient remains recurrence-free after a 2-year follow-up; and the third patient has developed recurrence at different sites in the pelvis but, to date, has survived for 4 years following particle beam RT. Therefore, LRRC was controlled by particle beam RT in two of the three cases, suggesting that particle beam RT is a safe alternative treatment for patients with LRRC. PMID:26171176

  11. [A Case of Radical Resection of Rectal Cancer with Multiple Liver and Lung Metastases after Preoperative Chemotherapy].

    PubMed

    Yamashita, Shinya; Shimizu, Yosuke; Tominaga, Harumi; Kimura, Yuri; Odagiri, Kazuki; Kurokawa, Tomoaki; Yamaguchi, Megumi; Takahashi, Gen; Sawada, Genta; Moon, JeongHo; Inoue, Masashi; Irei, Toshimitsu; Nakahira, Shin; Hatanaka, Nobutaka

    2015-10-01

    We report a case of radical resection of rectal cancer with multiple liver and lung metastases after preoperative chemotherapy. A 54-year-old woman presented with abdominal pain and loss of body weight due to rectal cancer with multiple liver and lung metastases. Therefore, the patient received 14 courses of bevacizumab+mFOLFOX6, and 7 courses of panitumumab+FOLFIRI. After the chemotherapy, the size of the distant metastases reduced by 62% on computed tomography, according to RECIST. Due to the reduction in size, a conversion surgery was attempted. First, an abdominal operation with laparoscopy was performed, and 2 months later an operation to resect the lung metastases via thoracoscopy was performed. Currently, 3 months after surgery, the patient is alive, without recurrence.

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

    SciTech Connect

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

    2015-03-01

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

  13. Impact of age on efficacy of postoperative oxaliplatin-based chemotherapy in patients with rectal cancer after neoadjuvant chemoradiotherapy

    PubMed Central

    Song, Yong-xi; Sun, Jing-xu; Chen, Xiao-wan; Zhao, Jun-hua; Ma, Bin; Wang, Jun; Wang, Zhen-ning

    2016-01-01

    Background Clinical practice guidelines focusing on age-related adjuvant chemotherapy for rectal cancer are currently limited. The present study aimed to explore the impact of age on the efficacy of adjuvant oxaliplatin-based chemotherapy in patients with rectal cancer after neoadjuvant chemoradiotherapy. Methods We performed a retrospective cohort analysis using data from the Surveillance, Epidemiology, and End Results-Medicare-linked database from 1992–2009. We enrolled patients with yp stages I–III rectal cancer who received neoadjuvant chemoradiotherapy and underwent curative resection. The age-related survival benefit of adding oxaliplatin to adjuvant 5-fluorouracil (5-FU) chemotherapy was evaluated using Kaplan–Meier survival analysis with propensity score-matching and Cox proportional hazards models. Results Comparing the oxaliplatin group with the 5-FU group, there were significant interactions between age and chemotherapy efficacy in terms of overall survival (OS) (p for interaction = 0.017) among patients with positive lymph nodes (ypN+). Adding oxaliplatin to 5-FU could prolong survival in patients aged < 73 years and ypN+ category, and but did not translate into survival benefits in patients aged ≥ 73 years and ypN+ category. No significant interactions were observed among ypN− patients, and oxaliplatin did not significantly improve OS, regardless of age. Conclusions In patients with rectal cancer who have already received neoadjuvant chemoradiotherapy and undergone curative resection, adding oxaliplatin to 5-FU could prolong OS in patients aged < 73 years and ypN+ category. However, adding oxaliplatin did not translate into survival benefits in patients age ≥ 73 years and ypN+ category, or in ypN− patients. PMID:26910371

  14. Radiation-Induced Thymidine Phosphorylase Upregulation in Rectal Cancer Is Mediated by Tumor-Associated Macrophages by Monocyte Chemoattractant Protein-1 From Cancer Cells

    SciTech Connect

    Kim, Tae-Dong; Li Ge; Song, Kyoung-Sub; Kim, Jin-Man; Kim, Jun-Sang; Kim, Jong-Seok; Yun, Eun-Jin; Park, Jong-Il; Park, Hae-Duck; Hwang, Byung-Doo; Lim, Kyu Yoon, Wan-Hee

    2009-03-01

    Purpose: The mechanisms of thymidine phosphorylase (TP) regulation induced by radiation therapy (XRT) in various tumors are poorly understood. We investigated the effect and mechanisms of preoperative XRT on TP expression in rectal cancer tissues. Methods and Materials: TP expression and CD68 and monocyte chemoattractant protein-1 (MCP-1) levels in rectal cancer tissues and cancer cell lines were evaluated before and after XRT in Western blotting, immunohistochemistry, enzyme-linked immunoassay, and reverse transcription-polymerase chain reaction studies. Isolated peripheral blood monocytes were used in the study of chemotaxis under the influence of MCP-1 released by irradiated colon cancer cells. Results: Expression of TP was significantly elevated by 9 Gy of XRT in most rectal cancer tissues but not by higher doses of XRT. In keeping with the close correlation of the increase in both TP expression and the number of tumor-associated macrophages (TAMs), anti-TP immunoreactivity was found in the CD68-positive TAMs and not the neoplastic cells. Expression of MCP-1 was increased in most cases after XRT, and this increase was strongly correlated with TP expression. However, this increase in MCP-1 expression occurred in tumor cells and not stromal cells. The XRT upregulated MCP-1 mRNA and also triggered the release of MCP-1 protein from cultured colon cancer cells. The supernatant of irradiated colon cancer cells showed strong chemotactic activity for monocyte migration, but this activity was completely abolished by neutralizing antibody. Conclusions: Use of XRT induces MCP-1 expression in cancer cells, which causes circulating monocytes to be recruited into TAMs, which then upregulate TP expression in rectal cancer tissues.

  15. Subtypes of fruit and vegetables, variety in consumption and risk of colon and rectal cancer in the European Prospective Investigation into Cancer and Nutrition.

    PubMed

    Leenders, Max; Siersema, Peter D; Overvad, Kim; Tjønneland, Anne; Olsen, Anja; Boutron-Ruault, Marie-Christine; Bastide, Nadia; Fagherazzi, Guy; Katzke, Verena; Kühn, Tilman; Boeing, Heiner; Aleksandrova, Krasimira; Trichopoulou, Antonia; Lagiou, Pagona; Klinaki, Eleni; Masala, Giovanna; Grioni, Sara; Santucci De Magistris, Maria; Tumino, Rosario; Ricceri, Fulvio; Peeters, Petra H M; Lund, Eiliv; Skeie, Guri; Weiderpass, Elisabete; Quirós, J Ramón; Agudo, Antonio; Sánchez, María-José; Dorronsoro, Miren; Navarro, Carmen; Ardanaz, Eva; Ohlsson, Bodil; Jirström, Karin; Van Guelpen, Bethany; Wennberg, Maria; Khaw, Kay-Tee; Wareham, Nick; Key, Timothy J; Romieu, Isabelle; Huybrechts, Inge; Cross, Amanda J; Murphy, Neil; Riboli, Elio; Bueno-de-Mesquita, H Bas

    2015-12-01

    Previously, a lower risk of colorectal cancer was observed with fruit and vegetable consumption in the European Prospective Investigation into Cancer and Nutrition within a follow-up period of 9 years which was not fully supported by a recent meta-analysis. Therefore, we were interested in the relation with extended follow-up, also focusing on single subtypes and a variety of intake of fruit and vegetables. Fruit and vegetable consumption was assessed at baseline. After an average of 13 years of follow-up, 3,370 participants were diagnosed with colon or rectal cancer. Diet diversity scores were constructed to quantify variety in fruit and vegetable consumption. A lower risk of colon cancer was observed with higher self-reported consumption of fruit and vegetable combined (HR Q4 vs. Q1 0.87, 95% CI 0.75-1.01, p for trend 0.02), but no consistent association was observed for separate consumption of fruits and vegetables. No associations with risk of rectal cancer were observed. The few observed associations for some fruit and vegetable subtypes with colon cancer risk may have been due to chance. Variety in consumption of fruits and vegetables was not associated with a lower risk of colon or rectal cancer. Although a lower risk of colon cancer is suggested with high consumption of fruit and vegetables, this study does not support a clear inverse association between fruit and vegetable consumption and colon or rectal cancer beyond a follow-up of more than 10 years. Attenuation of the risk estimates from dietary changes over time cannot be excluded, but appears unlikely. PMID:26077137

  16. Subtypes of fruit and vegetables, variety in consumption and risk of colon and rectal cancer in the European Prospective Investigation into Cancer and Nutrition.

    PubMed

    Leenders, Max; Siersema, Peter D; Overvad, Kim; Tjønneland, Anne; Olsen, Anja; Boutron-Ruault, Marie-Christine; Bastide, Nadia; Fagherazzi, Guy; Katzke, Verena; Kühn, Tilman; Boeing, Heiner; Aleksandrova, Krasimira; Trichopoulou, Antonia; Lagiou, Pagona; Klinaki, Eleni; Masala, Giovanna; Grioni, Sara; Santucci De Magistris, Maria; Tumino, Rosario; Ricceri, Fulvio; Peeters, Petra H M; Lund, Eiliv; Skeie, Guri; Weiderpass, Elisabete; Quirós, J Ramón; Agudo, Antonio; Sánchez, María-José; Dorronsoro, Miren; Navarro, Carmen; Ardanaz, Eva; Ohlsson, Bodil; Jirström, Karin; Van Guelpen, Bethany; Wennberg, Maria; Khaw, Kay-Tee; Wareham, Nick; Key, Timothy J; Romieu, Isabelle; Huybrechts, Inge; Cross, Amanda J; Murphy, Neil; Riboli, Elio; Bueno-de-Mesquita, H Bas

    2015-12-01

    Previously, a lower risk of colorectal cancer was observed with fruit and vegetable consumption in the European Prospective Investigation into Cancer and Nutrition within a follow-up period of 9 years which was not fully supported by a recent meta-analysis. Therefore, we were interested in the relation with extended follow-up, also focusing on single subtypes and a variety of intake of fruit and vegetables. Fruit and vegetable consumption was assessed at baseline. After an average of 13 years of follow-up, 3,370 participants were diagnosed with colon or rectal cancer. Diet diversity scores were constructed to quantify variety in fruit and vegetable consumption. A lower risk of colon cancer was observed with higher self-reported consumption of fruit and vegetable combined (HR Q4 vs. Q1 0.87, 95% CI 0.75-1.01, p for trend 0.02), but no consistent association was observed for separate consumption of fruits and vegetables. No associations with risk of rectal cancer were observed. The few observed associations for some fruit and vegetable subtypes with colon cancer risk may have been due to chance. Variety in consumption of fruits and vegetables was not associated with a lower risk of colon or rectal cancer. Although a lower risk of colon cancer is suggested with high consumption of fruit and vegetables, this study does not support a clear inverse association between fruit and vegetable consumption and colon or rectal cancer beyond a follow-up of more than 10 years. Attenuation of the risk estimates from dietary changes over time cannot be excluded, but appears unlikely.

  17. A case report of pathologically complete response of a huge rectal cancer after systemic chemotherapy with mFOLFOX6.

    PubMed

    Okoshi, Kae; Nagayama, Satoshi; Furu, Moritoshi; Mori, Yukiko; Yoshizawa, Akihiko; Toguchida, Junya; Sakai, Yoshiharu

    2009-08-01

    A 54-year-old man was referred to our hospital because of a huge, unresectable rectal cancer occupying his entire pelvic space with a solitary liver metastasis. He had undergone a laparotomy for surgical resection, but ended up with a sigmoid colostomy due to possible invasion into the urinary bladder and pelvic wall. At the completion of seven cycles of FOLFOX regimen, radiographic examination revealed remarkable reduction of the primary rectal tumor and regional lymph nodes, and also a complete response (CR) of the liver metastasis. The tumor was extirpated without any macroscopic residues by a low anterior resection of the rectum, along with a partial resection of the urinary bladder and seminal vesicles. Since pathological and immunohistochemical examinations showed no viable cancer cells in any parts of the resected specimens, the lesion was regarded as a pathologically CR. Analysis for single-nucleotide polymorphisms in the genes involved in nucleotide excision repair, excision repair cross-complementing group 1 and xeroderma pigmentosum group D, showed a genotypic pattern sensitive to oxaliplatin. To our knowledge, this is a rare case of an initially unresectable primary rectal cancer, which was down-staged to a pathologically CR by FOLFOX chemotherapy instead of chemoradiotherapy.

  18. PET-Based Treatment Response Evaluation in Rectal Cancer: Prediction and Validation

    SciTech Connect

    Janssen, Marco H.M.; Oellers, Michel C.; Stiphout, Ruud G.P.M. van; Riedl, Robert G.; Bogaard, Jorgen van den; Buijsen, Jeroen; Lambin, Philippe; Lammering, Guido

    2012-02-01

    Purpose: To develop a positron emission tomography (PET)-based response prediction model to differentiate pathological responders from nonresponders. The predictive strength of the model was validated in a second patient group, treated and imaged identical to the patients on which the predictive model was based. Methods and Materials: Fifty-one rectal cancer patients were prospectively included in this study. All patients underwent fluorodeoxyglucose (FDG) PET-computed tomography (CT) imaging both before the start of chemoradiotherapy (CRT) and after 2 weeks of treatment. Preoperative treatment with CRT was followed by a total mesorectal excision. From the resected specimen, the tumor regression grade (TRG) was scored according to the Mandard criteria. From one patient group (n = 30), the metabolic treatment response was correlated with the pathological treatment response, resulting in a receiver operating characteristic (ROC) curve based cutoff value for the reduction of maximum standardized uptake value (SUV{sub max}) within the tumor to differentiate pathological responders (TRG 1-2) from nonresponders (TRG 3-5). The applicability of the selected cutoff value for new patients was validated in a second patient group (n = 21). Results: When correlating the metabolic and pathological treatment response for the first patient group using ROC curve analysis (area under the curve = 0.98), a cutoff value of 48% SUV{sub max} reduction was selected to differentiate pathological responders from nonresponders (specificity of 100%, sensitivity of 64%). Applying this cutoff value to the second patient group resulted in a specificity and sensitivity of, respectively, 93% and 83%, with only one of the pathological nonresponders being false positively predicted as pathological responding. Conclusions: For rectal cancer, an accurate PET-based prediction of the pathological treatment response is feasible already after 2 weeks of CRT. The presented predictive model could be used to

  19. Automated functional image-guided radiation treatment planning for rectal cancer

    SciTech Connect

    Ciernik, Ilja Frank . E-mail: ciernik@usz.ch; Huser, Marius; Burger, Cyrill; Davis, J. Bernard; Szekely, Gabor

    2005-07-01

    Purpose: Computer tomography-based (CT-based) tumor-volume definition is time consuming and is subject to clinical interpretation. CT is not accessible for standardized algorithms for the purpose of treatment-volume planning. We have evaluated the accuracy of target-volume definition based on the positron emission tomography (PET) data from an integrated PET/CT system with 2-[{sup 18}F]fluoro-2-deoxy-D-glucose (FDG) for standardized target-volume delineation. Materials and Methods: Eleven patients with rectal cancer who were undergoing preoperative radiation therapy (RT) were studied. A standardized region-growing algorithm was tested to replace the CT-derived gross tumor volume by the PET-derived gross tumor volume (PET-GTV) or the biologic target volume (BTV). A software tool was developed to automatically delineate the appropriate tumor volume as defined by the FDG signal, the PET-GTV, and the planning target volume (PTV). The PET-derived volumes were compared with the target volumes from CT. Results: The BTV defined for appropriate GTV assessment was set at a single peak threshold of 40% of the signal of interest. Immediate treatment volume definition based on the choice of a single-tumor volume-derived PET-voxel resulted in a tumor volume that strongly correlated with the CT-derived GTV (r {sup 2} = 0.84; p < 0.01) and the volume as assessed on subsequent anatomic-pathologic analysis (r {sup 2} = 0.77; p < 0.01). In providing sufficient extension margins from the CT-derived GTV and the PET-derived GTV, to PTV, respectively, the correlation of the CT-derived and PET-derived PTV was sufficiently accurate for PTV definition for external-beam therapy (r {sup 2} = 0.96; p < 0.01). Conclusion: Automated segmentation of the PET signal from rectal cancer may allow immediate and sufficiently accurate definition of a preliminary working PTV for preoperative RT. If required, correction for anatomic precision and geometric resolution may be applied in a second step

  20. Interstitial curietherapy in the conservative treatment of anal and rectal cancers

    SciTech Connect

    Papillon, J.; Montbarbon, J.F.; Gerard, J.P.; Chassard, J.L.; Ardiet, J.M. )

    1989-12-01

    Conservative treatment has become a valid alternative to radical surgery in most cases of cancer of the anal canal and in selected cases of cancer of the low rectum. In this strategy interstitial curietherapy has an appreciable role to play. The results of a series of 369 patients followed more than 3 years indicate that implantation of Iridium-192 is effective not as sole treatment but as a booster dose 2 months after a course of external beam or intracavitary irradiation. The dose delivered did not exceed 20 to 30 Gy and the implantations were always performed in one plane using either a plastic template or a steel fork. Three groups of cases must be considered: (a) among 221 patients with epidermoid carcinoma of the anal canal, the rate of death related to treatment failures was 20% and among the patients cured more than 90% retained normal sphincter function. (b) In 90 patients with T1-T2 invasive adenocarcinoma of the rectum, Iridium-192 was carried out after four applications of contact X ray therapy. The rate of control was 84%. (c) In 62 elderly, poor risk patients with T2-T3 tumor of the low rectum initially suitable for an abdomino-perineal resection, a tentative extension of the field of conservation was made using a split-course protocol combining a short course of external beam irradiation at a dose of 30-35 Gy in 10 fractions over 12 days and an Iridium-192 implant. The rate of death due to treatment failures was 14.5% and among the patients controlled 97% had a normal anal function. These results show that implantations of Iridium-192 may contribute to the control of anal and rectal cancers and may spare many patients a permanent colostomy, but the treatment requires great care in patient selection, treatment protocol, technical details, and follow-up. This treatment policy must be conceived as a team work of radiation oncologists and surgeons.

  1. Association between Irrigation Fluids, Washout Volumes and Risk of Local Recurrence of Anterior Resection for Rectal Cancer: A Meta-Analysis of 427 Cases and 492 Controls

    PubMed Central

    Li, Juan; Wang, Ke; He, Jianjun; Chen, Wuke; Liu, Peijun

    2014-01-01

    Background Rectal washout can prevent local recurrence after anterior resection of rectal cancer. Few studies have focused particularly on the association between irrigation fluids volume or agents and the risk of local recurrence after anterior resection of rectal cancer. Objective To estimate the association between irrigation fluids types, volumes of rectal washout and risk of local recurrence after anterior resection for cancer. Data Sources Relevant studies were identified by a search of Medline, Embase, Wiley Online Library, China National Knowledge Infrastructure, Cochrane Oral Health Group Specialized Register, Wanfang databases and Google Website from their inception until October 18,2013. Study Selection Studies reporting the association between rectal washout types and volumes and risk of local recurrence after anterior resection for cancer were included. Interventions Eligible studies used rectal washout. Control groups were defined as no washout. Study Appraisal and Synthesis Methods Random-effects model were used to obtain summary estimates of RR and 95% CI, with Stata version 11 and RevMan 5.2.5 softwares used. The quality of report was appraised in reference to the MINORS item. Results Of the 919 rectal cancer patients in 8 included studies, a total of 61(6.64%) cases of local recurrence were reported, with a pooled RR 0.51 (95%CI = 0.28–0.92, P = 0.03). The RRs 0.37 and 0.39 in normal saline and washout volume (≥1500 ml normal saline) subgroup, respectively, indicated that rectal washout with normal saline, or ≥1500 ml in volume could significantly reduce local recurrence (LR) rate (95% CI = 0.17–0.79, P = 0.01; 95% CI = 0.18–0.87, P = 0.02) after anterior resection for cancer. Limitation The included studies were non-randomized observational studies, with diversity of study designs. Conclusion Rectal washout with normal saline alone can reduce the risk of local recurrence in patients with resectable rectal cancer

  2. Significance and prognostic value of increased serum direct bilirubin level for lymph node metastasis in Chinese rectal cancer patients

    PubMed Central

    Gao, Chun; Fang, Long; Li, Jing-Tao; Zhao, Hong-Chuan

    2016-01-01

    AIM: To determine the significance of increased serum direct bilirubin level for lymph node metastasis (LNM) in Chinese rectal cancer patients, after those with known hepatobiliary and pancreatic diseases were excluded. METHODS: A cohort of 469 patients, who were treated at the China-Japan Friendship Hospital, Ministry of Health (Beijing, China), in the period from January 2003 to June 2011, and with a pathological diagnosis of rectal adenocarcinoma, were recruited. They included 231 patients with LNM (49.3%) and 238 patients without LNM. Follow-up for these patients was taken through to December 31, 2012. RESULTS: The baseline serum direct bilirubin concentration was (median/inter-quartile range) 2.30/1.60-3.42 μmol/L. Univariate analysis showed that compared with patients without LNM, the patients with LNM had an increased level of direct bilirubin (2.50/1.70-3.42 vs 2.10/1.40-3.42, P = 0.025). Multivariate analysis showed that direct bilirubin was independently associated with LNM (OR = 1.602; 95%CI: 1.098-2.338, P = 0.015). Moreover, we found that: (1) serum direct bilirubin differs between male and female patients; a higher concentration was associated with poor tumor classification; (2) as the baseline serum direct bilirubin concentration increased, the percentage of patients with LNM increased; and (3) serum direct bilirubin was associated with the prognosis of rectal cancer patients and higher values indicated poor prognosis. CONCLUSION: Higher serum direct bilirubin concentration was associated with the increased risk of LNM and poor prognosis in our rectal cancers. PMID:26937145

  3. Correlation Between Dosimetric Parameters and Late Rectal and Urinary Toxicities in Patients Treated With High-Dose-Rate Brachytherapy Used as Monotherapy for Prostate Cancer

    SciTech Connect

    Konishi, Koji; Yoshioka, Yasuo; Isohashi, Fumiaki; Sumida, Iori; Kawaguchi, Yoshifumi; Kotsuma, Tadayuki; Adachi, Kana; Morimoto, Masahiro; Fukuda, Shoichi; Inoue, Takehiro

    2009-11-15

    Purpose: To evaluate the correlation between dosimetric parameters and late rectal and urinary toxicities in high-dose-rate brachytherapy (HDR-BT) used as monotherapy for prostate cancer. Methods and Materials: The data of 83 patients treated with HDR-BT alone for prostate cancer from 2001 through 2005 at Osaka University Hospital were analyzed. Median follow-up time was 36 months (range, 18-70). The total prescribed dose was 54 Gy in nine fractions over 5 days. Correlation between dosimetric parameters and late toxicities was examined. Results: The means of V30, V40, V50, V60, V70, D1cc, D2cc, D5cc, and D10cc of the rectum were significantly higher in 18 patients who presented with late rectal toxicity (Grades 1-3 rectal bleeding) than in the other 65 patients who did not. A significant difference was observed for D1cc-10cc but not for D5-90. The statistically most significant difference was observed for V40 and D5cc. Late rectal toxicity rate was significantly higher for patients with rectal V40 >= 8 cc than those with the rectal V40 < 8 cc (42% vs. 8%; p < 0.001), as well as for patients with rectal D5cc >= 27 Gy compared with those with rectal D5cc < 27 Gy (50% vs. 11%; p < 0.001). Dosimetric parameters of the urethra of 15 patients with late urinary toxicity were not significantly different from the 68 patients without toxicity. Conclusion: Rectal V40 < 8 cc and D5cc < 27 Gy may be dose-volume constraints in HDR-BT used as monotherapy for prostate cancer.

  4. SU-D-BRA-04: Fractal Dimension Analysis of Edge-Detected Rectal Cancer CTs for Outcome Prediction

    SciTech Connect

    Zhong, H; Wang, J; Hu, W; Shen, L; Wan, J; Zhou, Z; Zhang, Z

    2015-06-15

    Purpose: To extract the fractal dimension features from edge-detected rectal cancer CTs, and to examine the predictability of fractal dimensions to outcomes of primary rectal cancer patients. Methods: Ninety-seven rectal cancer patients treated with neo-adjuvant chemoradiation were enrolled in this study. CT images were obtained before chemoradiotherapy. The primary lesions of the rectal cancer were delineated by experienced radiation oncologists. These images were extracted and filtered by six different Laplacian of Gaussian (LoG) filters with different filter values (0.5–3.0: from fine to coarse) to achieve primary lesions in different anatomical scales. Edges of the original images were found at zero-crossings of the filtered images. Three different fractal dimensions (box-counting dimension, Minkowski dimension, mass dimension) were calculated upon the image slice with the largest cross-section of the primary lesion. The significance of these fractal dimensions in survival, recurrence and metastasis were examined by Student’s t-test. Results: For a follow-up time of two years, 18 of 97 patients had experienced recurrence, 24 had metastasis, and 18 were dead. Minkowski dimensions under large filter values (2.0, 2.5, 3.0) were significantly larger (p=0.014, 0.006, 0.015) in patients with recurrence than those without. For metastasis, only box-counting dimensions under a single filter value (2.5) showed differences (p=0.016) between patients with and without. For overall survival, box-counting dimensions (filter values = 0.5, 1.0, 1.5), Minkowski dimensions (filter values = 0.5, 1.5, 2.0, 2,5) and mass dimensions (filter values = 1.5, 2.0) were all significant (p<0.05). Conclusion: It is feasible to extract shape information by edge detection and fractal dimensions analysis in neo-adjuvant rectal cancer patients. This information can be used to prognosis prediction.

  5. [Prevention of intraoperative incidental injuries during sphincter-preserving surgery for rectal cancer and management of postoperative complication].

    PubMed

    Han, Fanghai; Li, Hongming

    2016-06-01

    Prevention of intraoperative incidental injuries during radical operation for rectal cancer and management of postoperative complication are associated with successful operation and prognosis of patients. This paper discusses how to prevent such intraoperative incidental injuries and how to manage postoperative complication. (1) Accurate clinical evaluation should be performed before operation and reasonable treatment decision should be made, including determination of the distance from transection to lower margin of the tumor, T and M staging evaluated by MRI, fascia invasion of mesorectum, metastasis of lateral lymph nodes, metastatic station of mesentery lymph node, association between levator ani muscle and anal sphincter, course and length of sigmoid observed by Barium enema, length assessment of pull-through bowel. Meanwhile individual factors of patients and tumors must be realized accurately. (2) Injury of pelvic visceral fascia should be avoided during operation. Negative low and circumference cutting edge must be ensured. Blood supply and adequate length of pull-down bowel must be also ensured. Urinary system injury, pelvic bleeding and intestinal damage should be avoided. Team cooperation and anesthesia procedure should be emphasized. Capacity of handling accident events should be cultivated for the team. (3) intraoperative incidental injuries during operation by instruments should be avoided, such as poor clarity of camera due to spray and smog, ineffective instruments resulted from repeated usage. (4) As to the prevention and management of postoperative complication of rectal cancer operation, prophylactic stoma should be regularly performed for rectal cancer patients undergoing anterior resection, while drainage tube placement does not decrease the morbidities of anastomosis and other complications. After sphincter-preserving surgery for rectal cancer, attentions must be paid to the occurrence of anastomotic bleeding, pelvic bleeding, anastomotic

  6. Preoperative CT versus diffusion weighted magnetic resonance imaging of the liver in patients with rectal cancer; a prospective randomized trial

    PubMed Central

    Løgager, Vibeke B.; Skjoldbye, Bjørn; Møller, Jakob M.; Lorenzen, Torben; Rasmussen, Vera L.; Thomsen, Henrik S.; Mollerup, Talie H.; Okholm, Cecilie; Rosenberg, Jacob

    2016-01-01

    Introduction. Colorectal cancer is one of the most frequent cancers in the world and liver metastases are seen in up to 19% of patients with colorectal cancers. Detection of liver metastases is not only vital for sufficient treatment and survival, but also for a better estimation of prognosis. The aim of this study was to evaluate the feasibility of diffusion weighted MRI of the liver as part of a combined MR evaluation of patients with rectal cancers and compare it with the standard preoperative evaluation of the liver with CT. Methods. Consecutive patients diagnosed with rectal cancers were asked to participate in the study. Preoperative CT and diffusion weighted MR (DWMR) were compared to contrast enhanced laparoscopic ultrasound (CELUS). Results. A total of 35 patients were included, 15 patients in Group-1 having the standard CT evaluation of the liver and 20 patients in Group-2 having the standard CT evaluation of the liver and DWMR of the liver. Compared with CELUS, the per-patient sensitivity/specificity was 50/100% for CT, and for DWMR: 100/94% and 100/100% for Reader 1 and 2, respectively. The per-lesion sensitivity of CT and DWMR were 17% and 89%, respectively compared with CELUS. Furthermore, one patient had non-resectable metastases after DWMR despite being diagnosed with resectable metastases after CT. Another patient was diagnosed with multiple liver metastases during CELUS, despite a negative CT-scan. Discussion. DWMR is feasible for preoperative evaluation of liver metastases. The current standard preoperative evaluation with CT-scan results in disadvantages like missed metastases and futile operations. We recommend that patients with rectal cancer, who are scheduled for MR of the rectum, should have a DWMR of the liver performed at the same time. PMID:26793420

  7. Characteristics and Prognostic Significance of Preoperative Magnetic Resonance Imaging-Assessed Circumferential Margin in Rectal Cancer.

    PubMed

    Ma, Xiaoji; Li, Xinxiang; Xu, Linghui; Shi, Debing; Tong, Tong; Huang, Dan; Ding, Ying; Cai, Sanjun; Peng, Junjie

    2015-01-01

    Purpose. To study the characteristics and prognostic significance of preoperative magnetic resonance imaging- (MRI-) assessed circumferential margin (CRM) in rectal cancer. Methods. Patients underwent preoperative high resolution pelvic MRI, followed by resection of primary tumor. The relationship between MRI-assessed CRM and pathological CRM (pCRM) was studied, and survival analysis was used to determine the prognostic significance of MRI-assessed CRM. Results. Of all the 203 patients, the total accuracy of MRI-assessed CRM for predicting involvement of pCRM was 84.2%, sensitivity was 50%, and specificity was 86.8%. Anterior tumors were more possible to assess involvement of CRM by MRI, while the false positive rate was significantly higher than lateral or posterior tumor (87.5% versus 50%, p = 0.0002). The 3-year local recurrence, disease-free survival, and overall survival rates were 35.6%, 58.1%, and 85.2% in patients with involved mrCRM, compared with 8.9%, 78.9%, and 92.3% in patients with clear mrCRM. In multivariate analysis, MRI-assessed CRM found an independent risk factor for local recurrence, with a hazard ratio of 3.49 (p = 0.003). Conclusions. High resolution MRI was accurate to assess CRM preoperatively, while anterior tumor should be assessed more cautiously. Involvement of mrCRM was significantly associated with local recurrence regardless of pCRM status.

  8. Clinical Parameters Predicting Pathologic Tumor Response After Preoperative Chemoradiotherapy for Rectal Cancer

    SciTech Connect

    Yoon, Sang Min; Kim, Dae Yong Kim, Tae Hyun; Jung, Kyung Hae; Chang, Hee Jin; Koom, Woong Sub; Lim, Seok-Byung; Choi, Hyo Seong; Jeong, Seung-Yong; Park, Jae-Gahb

    2007-11-15

    Purpose: To identify pretreatment clinical parameters that could predict pathologic tumor response to preoperative chemoradiotherapy (CRT) for rectal cancer. Methods and Materials: The study involved 351 patients who underwent preoperative CRT followed by surgery between October 2001 and July 2006. Tumor responses to preoperative CRT were assessed in terms of tumor downstaging and tumor regression. Statistical analyses were performed to identify clinical factors associated with pathologic tumor response. Results: Tumor downstaging (defined as ypT2 or less) was observed in 167 patients (47.6%), whereas tumor regression (defined as Dworak's Regression Grades 3 or 4) was observed in 103 patients (29.3%) and complete regression in 51 patients (14.5%). Multivariate analysis found that predictors of downstaging were pretreatment hemoglobin level (p = 0.045), cN0 classification (p < 0.001), and serum carcinoembryonic antigen (CEA) level (p < 0.001), that predictors of tumor regression were cN0 classification (p = 0.044) and CEA level (p < 0.001), and that the predictor of complete regression was CEA level (p = 0.004). Conclusions: The data suggest that pretreatment CEA level is the most important clinical predictor of pathologic tumor response. It may be of benefit in the selection of treatment options as well as the assessment of individual prognosis.

  9. Combining bevacizumab and chemoradiation in rectal cancer. Translational results of the AXEBeam trial

    PubMed Central

    Verstraete, M; Debucquoy, A; Dekervel, J; van Pelt, J; Verslype, C; Devos, E; Chiritescu, G; Dumon, K; D'Hoore, A; Gevaert, O; Sagaert, X; Van Cutsem, E; Haustermans, K

    2015-01-01

    Background: This study characterises molecular effect of bevacizumab, and explores the relation of molecular and genetic markers with response to bevacizumab combined with chemoradiotherapy (CRT). Methods: From a subset of 59 patients of 84 rectal cancer patients included in a phase II study combining bevacizumab with CRT, tumour and blood samples were collected before and during treatment, offering the possibility to evaluate changes induced by one dose of bevacizumab. We performed cDNA microarrays, stains for CD31/CD34 combined with α-SMA and CA-IX, as well as enzyme-linked immunosorbent assay (ELISA) for circulating angiogenic proteins. Markers were related with the pathological response of patients. Results: One dose of bevacizumab changed the expression of 14 genes and led to a significant decrease in microvessel density and in the proportion of pericyte-covered blood vessels, and a small but nonsignificant increase in hypoxia. Alterations in angiogenic processes after bevacizumab delivery were only detected in responding tumours. Lower PDGFA expression and PDGF-BB levels, less pericyte-covered blood vessels and higher CA-IX expression were found after bevacizumab treatment only in patients with pathological complete response. Conclusions: We could not support the ‘normalization hypothesis' and suggest a role for PDGFA, PDGF-BB, CA-IX and α-SMA. Validation in larger patient groups is needed. PMID:25867261

  10. [Techniques of autonomic nerve preservation in laparoscopic radical resection for rectal cancer].

    PubMed

    Wei, Hongbo; Zheng, Zongheng

    2015-06-01

    Pelvic autonomic nerve is a three-dimensional structure surrounding the rectum. There are several key points related to nerve injury during laparoscopic radical resection for rectal cancer. Hypogastric nerve has close relation with the upper and middle part of the rectum. Combined with S2-S4 pelvic splanchnic nerve, hypogastric nerve forms pelvic plexus. Incorrect operation in pelvic parietal peritoneum during dissection of upper rectum will lead to nerve injury. When performing dissection of inferior mesenteric artery, bilateral nerve tracts should be pushed to posterior abdominal wall and anterior fascia of the abdominal aorta should be well protected to avoid nerve injury. Pelvic plexus fibers located lateral to the rectum of pelvic floor, as well as neurovascular bundle closed to Denonvillier's fascia, also have close relations with nerve injury. Dissection of either lateral or anterior wall of rectum should be performed behind the Denonvillier's fascia and in front of the proper fascia of rectum. Sharp dissection should be performed closed to the mesorectum to protect branches of pelvic plexus.

  11. High dose rate endorectal brachytherapy as a neoadjuvant treatment for patients with resectable rectal cancer.

    PubMed

    Vuong, T; Devic, S; Podgorsak, E

    2007-11-01

    In the era of total mesorectal surgery, the issue of radiation toxicity is raised. A novel endocavitary brachytherapy technique was tested as a neoadjuvant treatment for patients with resectable rectal cancer. The objectives of the study were to evaluate the treatment-related toxicity and effects on local recurrence. A dose of 26 Gy was prescribed to the gross tumour volume and intramesorectal deposits seen on magnetic resonance imaging and given over four daily treatments, using the high dose rate delivery system followed by surgery 6-8 weeks later. The study included 93 T3, four T4 and three T2 tumours. Acute proctitis of grade 2 was observed in all patients, but one required transfusion. At a median follow-up time of 60 months, the 5-year actual local recurrence rate was 5%, disease-free survival was 65%, and overall survival was 70%. High dose rate endorectal brachytherapy seems to prevent local recurrence and has a favourable toxicity pattern compared with external beam radiotherapy. PMID:17714925

  12. Screening prostate cancer using a portable near infrared scanning imaging unit with an optical fiber-based rectal probe

    NASA Astrophysics Data System (ADS)

    Pu, Yang; Wang, Wubao; Tang, Guichen; Budansky, Yury; Sharonov, Mikhail; Xu, Min; Achilefu, Samuel; Eastham, James A.; Alfano, Robert R.

    2012-01-01

    A portable near infrared scanning polarization imaging unit with an optical fiber-based rectal probe, namely Photonic Finger, was designed and developed o locate the 3D position of abnormal prostate site inside normal prostate tissue. An inverse algorithm, Optical Tomography using Independent Component Analysis (OPTICA) was improved particularly to unmix the signal from targets (cancerous tissue) embedded in a turbid medium (normal tissue) in the backscattering imaging geometry. Photonic Finger combined with OPTICA was tested to characterize different target(s) inside different tissue medium, including cancerous prostate tissue embedded by large piece of normal tissue.

  13. Meat intake, cooking methods and risk of proximal colon, distal colon and rectal cancer: the Norwegian Women and Cancer (NOWAC) cohort study.

    PubMed

    Parr, Christine L; Hjartåker, Anette; Lund, Eiliv; Veierød, Marit B

    2013-09-01

    Red and processed meat intake is an established risk factor for colorectal cancer (CRC), but epidemiological evidence by subsite and sex is still limited. In the population-based Norwegian Women and Cancer cohort, we examined associations of meat intake with incident proximal colon, distal colon and rectal cancer, in 84,538 women who completed a validated food frequency questionnaire (FFQ) during 1996-1998 or 2003-2005 (baseline or exposure update) at age 41-70 years, with follow-up by register linkages through 2009. We also examined the effect of meat cooking methods in a subsample (n = 43,636). Multivariable hazard ratios (HRs) were estimated by Cox regression. There were 459 colon (242 proximal and 167 distal), and 215 rectal cancer cases with follow-up ≥ 1 (median 11.1) year. Processed meat intake ≥60 vs. <15 g/day was associated with significantly increased cancer risk in all subsites with HRs (95% confidence interval, CI) of 1.69 (1.05-2.72) for proximal colon, 2.13 (1.18-3.83) for distal colon and 1.71 (1.02-2.85) for rectal cancer. Regression calibration of continuous effects based on repeated 24-hr dietary recalls, indicated attenuation due to measurement errors in FFQ data, but corrected HRs were not statistically significant due to wider CIs. Our study did not support an association between CRC risk and intake of red meat, chicken, or meat cooking methods, but a high processed meat intake was associated with increased risk of proximal colon, distal colon and rectal cancer. The effect of processed meat was mainly driven by the intake of sausages.

  14. Postoperative radiation therapy for rectal cancer. An interim analysis of a prospective, randomized multicenter trial in The Netherlands.

    PubMed

    Treurniet-Donker, A D; van Putten, W L; Wereldsma, J C; Bruggink, E D; Hoogenraad, W J; Roukema, J A; Snijders-Keilholz, A; Meijer, W S; Meerwaldt, J H; Wijnmaalen, A J

    1991-04-15

    The authors assessed the potential benefit of postoperative radiation therapy for rectal cancer in a two-arm, prospective multicenter trial. One hundred seventy-two patients who had undergone surgical resection for rectal adenocarcinoma were randomly assigned to either treatment consisting of external irradiation to a dose of 5000 cGy in 5 weeks or a control group (no adjuvant therapy). It was assumed that the number of cells remaining after radical surgery would be low and that the dose of 5000 cGy would be adequate in eradicating the majority of those cells. The number of local recurrences was lower in the treated group of patients, but the difference was