Sphincter-sparing Surgery Research Articles

METHOD OF INTESTINAL DECOMPRESSION IN TREATMENT OF RECTAL CANCER COMPLICATED BY INTESTINAL OBSTRUCTION

Stoma surgery in patients with obstructive rectal cancer is not a rare case. That is why we studied a possibility of conservative treatment with large bowel obstruction (LBO) using the method of endoscopic recanalization. Material and methods. We enrolled 117 rectal cancer patients with acute or partial LBO. Fifty-eight patients were treated with endoscopic recanalization of lumen. After achieving intestinal decompression, the patients received preoperative chemoradiotherapy (40–60 Gy, tegafur 300 mg/м2, 1–28 days) followed by surgery. The control group consisted of 59 patients who were treated with surgery followed by chemoradiotherapy. Results. Decompression was successful in 48 patients (82.7 %). Partial recanalization was observed in 8 patients, but it was not obstacle to perform chemoradiotherapy. Two patients developed complications (paracolic abscess), requiring unplanned emergency surgery. The frequency of sphincter-preserving surgical procedures was 82.6 % in the study group and 28.8 % in the control group, p<0.001. Conclusion. The proposed method of intestinal decompression allowed the number of sphincter-sparing surgery to be increased without worsening the disease prognosis.

Role of magnetic resonance imaging in assessment of rectal neoplasms

BackgroundMRI examination of the rectum has evolved as the standard technique in the assessment of cancer rectum having multiplaner capabilities and high tissue contrast imaging. Aim of the workThe aim of this study is to evaluate the role of MRI in assessment of rectal neoplasm. Patients and methodsIn this work, 42 patients were studied as preoperative evaluation and staging that known to have or highly suspected clinically to have rectal neoplasms. They were subjected to assessment by MRI using pelvic phased array coil with IV contrast (Gadolinium) and rectal gel administration. ResultsMRI was proved to have high accuracy in the assessment of the rectal wall infiltration and pelvic organ involvement which is about 93% and also has high accuracy in the assessment of peri-rectal lymph nodes involvement which is about 91% as compared to the post-operative pathological results. ConclusionOur study results demonstrate that high resolution MRI has pivotal role in accurate staging of rectal cancer and predicting involvement of the perirectal and pelvic lymph nodes as well as planning of the sphincter sparing surgery.

Psychiatric Illness is a Disparity in the Surgical Management of Rectal Cancer.

Psychiatric disorders are common in the US and represent a major health disparity but little is known about their impact on surgical management and outcomes in cancer. The aim of this study was to determine whether rectal cancer patients with psychiatric diagnoses have fewer sphincter-preserving procedures and higher postoperative complications. Overall, 23,914 patients from the Nationwide Inpatient Sample (NIS) who underwent surgery for rectal cancer from 2004 to 2011 were identified. Patients with comorbid common psychiatric diagnoses were identified by International Classification of Diseases, Ninth Revision (ICD-9) codes. Main outcomes were measured by operation performed, length of stay (LOS), postoperative complications, and discharge disposition. Twenty percent of patients had a psychiatric diagnosis, with substance use being the most common psychiatric disorder (63 %). Patients with psychiatric diagnoses were more likely to be younger, White, have lower income, and have Medicaid insurance (p < 0.001) than those without. In a logistic regression model, patients with any psychiatric diagnosis were less likely to have sphincter-sparing surgery, controlling for patient sociodemographics, Charlson score, hospital procedure volume, and year (odds ratio 0.77; 95 % CI 0.72-0.83). LOS and postoperative complications were similar among the cohorts. Patients with psychiatric disorders were more likely to have home health care at discharge (p < 0.001). Fewer sphincter-sparing procedures were performed on rectal cancer patients with psychiatric diagnoses. However, no significant differences in postoperative complications were observed.

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

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. 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. 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. 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.

OC-0610: Quality of life in patients undergoing radiotherapy and sphincter sparing surgery or rectal amputation

OC-0610: Quality of life in patients undergoing radiotherapy and sphincter sparing surgery or rectal amputation

The results of seton drainage combined with anti-TNFα therapy for anal fistula in Crohn's disease.

Combined infliximab and sphincter-sparing surgery can be effective in perianal fistula associated with Crohn's disease (CD). This study aimed to assess the efficacy of local surgery combined with infliximab on sustained fistula closure and to identify predictive factors for response after this combined treatment. Between 2000 and 2010, 81 patients with fistulising perianal CD were included in this observational study. Drainage with a loose seton was followed by infliximab therapy. The primary end-points were the rate of complete fistula closure and time required for this to occur. The fistula was complex in 71 (88%) of the 81 patients. Local proctological surgery was carried out in 77 (95%), including seton drainage in 62 (80.5%) of these. This was continued for a median duration of 3.8months and the patient then received infliximab therapy. The median follow-up after treatment was 64months (2-263). Initial complete closure of the fistula occurred in 71 (88%) cases at a median interval of 12.4months (1-147) from the start of treatment. Recurrence was observed in 29 (41%) patients at a median interval of 38.5months (2-48) from the start of treatment. They were treated again with combined treatment with successful closure in 19 (65.5%) patients. The total rate of closure of the fistula was 75.3%. Female gender, anal stenosis, rectovaginal and complex fistula formation were factors independently associated with failure of combined treatment. Seton drainage for several months combined with infliximab therapy is effective in closing the fistula in 75% of patients with complex perianal fistula formation associated with CD.

The neoadjuvant treatment of rectal cancer: a review.

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, especially in the curative setting. 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. We review both pivotal trial data that has shaped the current standard of care, fluoropyrimidine-based chemoradiotherapy, while also presenting results from more recent studies, which aim to outperform this standard. Strategies combining 5FU radiotherapy with oxaliplatin, VEGF inhibition, EGFR inhibition, other targeted agents, and/or use of induction chemotherapy hold promise but thus far have failed to improve outcomes in randomized trials. Results of studies such as the ongoing PROSPECT trial may help further define our current therapeutic algorithm for stage II and III rectal cancer.

Is There a Role for Adjuvant Chemotherapy in Rectal Cancer?

Adjuvant chemoradiotherapy trials demonstrated a reduction in local failure and an increase in survival of patients with locally advanced rectal cancer submitted to upfront surgery. The standard-of-care shifted to neoadjuvant chemoradiotherapy when the German Rectal Cancer Study Group Trial demonstrated the benefit of neoadjuvant compared to adjuvant fluoropyrimidine chemoradiotherapy in lower rates of local failure, lower toxicity in patients optimally resected with total mesorectal excision (TME), and higher rate of sphincter-sparing surgery. Overall survival (OS) was equivalent in both arms. The benefit of adjuvant chemotherapy after preoperative chemoradiotherapy has not been clearly demonstrated in randomized trials. This review will discuss the role of fluoropyrimidine-based and oxaliplatin-based adjuvant chemotherapy in patients treated with neoadjuvant chemoradiotherapy.

Comparative Effectiveness of Sphincter-Sparing Surgery Versus Abdominoperineal Resection in Rectal Cancer

National Surgical Adjuvant Breast and Bowel Project (NSABP) R-04 was a randomized controlled trial of neoadjuvant chemoradiotherapy in patients with resectable stage II-III rectal cancer. We hypothesized that patients who underwent abdominoperineal resection (APR) would have a poorer quality of life than those who underwent sphincter-sparing surgery (SSS). To obtain patient-reported outcomes (PROs) we administered two symptom scales at baseline and 1 year postoperatively: the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) and the European Organization for the Research and Treatment of Cancer module for patients with Colorectal Cancer Quality of Life Questionnaire (EORTC QLQ-CR38). Scoring was stratified by nonrandomly assigned definitive surgery (APR vs SSS). Analyses controlled for baseline scores and stratification factors: age, sex, stage, intended surgery, and randomly assigned chemoradiotherapy. Of 1,608 randomly assigned patients, 987 had data for planned analyses; 62% underwent SSS; 38% underwent APR. FACT-C total and subscale scores were not statistically different by surgery at 1 year. For the EORTC QLQ-CR38 functional scales, APR patients reported worse body image (70.3 vs 77.0, P = 0.0005) at 1 year than did SSS patients. Males undergoing APR reported worse sexual enjoyment (43.7 vs 54.7, P = 0.02) at 1 year than did those undergoing SSS. For the EORTC QLQ-CR38 symptom scale scores, APR patients reported worse micturition symptoms than the SSS group at 1 year (26.9 vs 21.5, P = 0.03). SSS patients reported worse gastrointestinal tract symptoms than did the APR patients (18.9 vs 15.2, P < 0.0001), as well as weight loss (10.1 vs 6.0, P = 0.002). Symptoms and functional problems were detected at 1 year by EORTC QLQ-CR38, reflecting different symptom profiles in patients who underwent APR than those who underwent SSS. Information from these PROs may be useful in counseling patients anticipating surgery for rectal cancer.

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

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.

Oral fluorpyrimidines in preoperative chemoradiotherapy for operable rectal cancer

Background. The aim of this study was to compare short and long-term outcomes after neoadjuvant short-course chemoradiotherapy with capecitabine ot tegafur for operable rectal cancer. Materials and methods. Patients with histologycally verified Т3N0M0, Т2–3N1–2M0 rectal cancer, who underwent 5 × 5 Gy neoadjuvant radiotherapy with local 41–45 °C hyperthermia on days 3–5 and metronidazole 10 g/m2 per rectum days 3, 5 were randomized to receive capecitabine 1000 mg/m2 bid per os days 1–14 or tegafur 400 mg/m2 bid per os days 1–21. Toxicity, tumor regression, sphincter preservation rate and long-term outcomes were analyzed. Results. During 2011–2013 26 patients were included in the tegafur group and 30 – in capecitabine group. Overall toxicity was 50 % in the tegafur arm and 36.7 % in the capecitabine arm (p = 0.42), grade III–IV toxicity (diarrhoea was the most common grade 3+ event) was observed in 23.1 % and 6.7 % (p = 0.13) patients accordingly. Grade III–IV tumor regression was observed in 34.6 % patients, who received tegafur and 53.3 % (p = 0.12) patients who received capecitabine. Sphincter-sparing surgery was performed in 84.6 % and 100 % (p = 0.04) patients who received tegafur and capecitabine accordingly. Median follow-up was 31.6 and 32.2 months accordingly. 3-year overall survival in capecitabine and tegafur arms was 95.4 and 82.1 % (р = 0.13), 3-year disease-free survival – 91 and 74 % (р = 0.029). Conclusions. Both fluorpyrimidines demonstrated comparable short-term outcomes with a tendency to better results in the capecitabine arm.

Future of Radiotherapy Delivery in Rectal Cancer—European and US Approaches

Neoadjuvant radiation therapy is integral in the management of patients with localized rectal cancer. In parts of Europe, patients with operable rectal cancer are treated with short-course radiation therapy delivered in five daily, 5 Gy fractions to a total dose of 25 Gy, followed by surgery within 1 week. In the US, the standard for locally advanced rectal cancer is neoadjuvant chemoradiotherapy. This approach is principally based on the results of the German Rectal Cancer Study Group trial evaluating preoperative compared with postoperative chemoradiation. Surgery is typically performed at 4–8 weeks following completion of long-course chemoradiotherapy, facilitating tumor downstaging, and potential sphincter sparing surgery. No significant difference in clinical outcomes has been observed between these two approaches in two randomized clinical trials; however, further follow-up of these studies and new results from ongoing trials are anticipated to further clarify the optimal neoadjuvant treatment strategy.

297. Multimodal approach to stage IV rectal cancer treatment

297. Multimodal approach to stage IV rectal cancer treatment

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

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

The adequacy of the distal resection margin after preoperative chemoradiotherapy for rectal cancer

The study aimed to determine the adequacy of the distal margin in patients having preoperative chemoradiotherapy (CRT) followed by restorative surgery for rectal cancer. A total of 368 patients with locally advanced rectal cancer treated for cure at our institution between July 1999 and March 2009 were included in the study. All underwent preoperative CRT and sphincter-sparing surgery. The distal margin and other factors were examined for their effect on recurrence and survival. The median duration of follow-up was 48months. The length of distal margin ranged from 0 to 9.0cm (median 1.5cm). The pelvic control and disease-free survival rates at 5years for patients with a margin of ≤3mm were no different from those in whom it was >3mm (P=0.6 and 0.8). The 5-year pelvic control rates between the ≤3mm and >3mm groups were 66.7 and 86.2% in patients with a ypT3-4 tumour (P=0.049) and 70.0 and 89.1% in patients who showed no response to CRT (P=0.039). The results suggest that a distal margin of <3mm in the surgical specimen after preoperative CRT is associated with a lower rate of pelvic tumour control at 5years in patients with Stage ypT3-4 tumours or in those who do not respond to CRT.

Capecitabine and oxaliplatin in the preoperative multimodality treatment of rectal cancer: surgical end points from National Surgical Adjuvant Breast and Bowel Project trial R-04.

The optimal chemotherapy regimen administered concurrently with preoperative radiation therapy (RT) for patients with rectal cancer is unknown. National Surgical Adjuvant Breast and Bowel Project trial R-04 compared four chemotherapy regimens administered concomitantly with RT. Patients with clinical stage II or III rectal cancer who were undergoing preoperative RT (45 Gy in 25 fractions over 5 weeks plus a boost of 5.4 Gy to 10.8 Gy in three to six daily fractions) were randomly assigned to one of the following chemotherapy regimens: continuous intravenous infusional fluorouracil (CVI FU; 225 mg/m(2), 5 days per week), with or without intravenous oxaliplatin (50 mg/m(2) once per week for 5 weeks) or oral capecitabine (825 mg/m(2) twice per day, 5 days per week), with or without oxaliplatin (50 mg/m(2) once per week for 5 weeks). Before random assignment, the surgeon indicated whether the patient was eligible for sphincter-sparing surgery based on clinical staging. The surgical end points were complete pathologic response (pCR), sphincter-sparing surgery, and surgical downstaging (conversion to sphincter-sparing surgery). From September 2004 to August 2010, 1,608 patients were randomly assigned. No significant differences in the rates of pCR, sphincter-sparing surgery, or surgical downstaging were identified between the CVI FU and capecitabine regimens or between the two regimens with or without oxaliplatin. Patients treated with oxaliplatin experienced significantly more grade 3 or 4 diarrhea (P < .001). Administering capecitabine with preoperative RT achieved similar rates of pCR, sphincter-sparing surgery, and surgical downstaging compared with CVI FU. Adding oxaliplatin did not improve surgical outcomes but added significant toxicity. The definitive analysis of local tumor control, disease-free survival, and overall survival will be performed when the protocol-specified number of events has occurred.

Primary anorectal malignant melanoma treated with neoadjuvant chemoradiotherapy and sphincter-sparing surgery: A case report.

Primary anorectal (PA) malignant melanoma (MM) is a rare disease associated with a high mortality rate. The most appropriate treatment strategy for PAMM remains controversial. A 55-year-old female patient, who was misdiagnosed with locally advanced rectal carcinoma, was treated with preoperative radiotherapy and concurrent oral capecitabine. During the therapy, grade 1 leukopenia occurred, however, there was no interruption to treatment. Following chemoradiotherapy, a computer tomography scan identified that the tumor had shrunk significantly and the original enlarged lymph nodes had disappeared. Eight weeks after completion of chemoradiotherapy, sphincter-sparing surgery was performed on the patient and based on the postoperative pathological result, MM was diagnosed. At the time of writing, the patient has survived disease-free for 15 months and at the most recent follow-up examination the Karnofsky Performance Scale score was 100. The therapeutic regimen of neoadjuvant concurrent chemoradiotherapy together with sphincter-sparing surgery is considered to be an optimal choice for patients with PAMM. However, further studies are required to evaluate the efficacy and clinical utility of this therapeutic regimen.

Association of radiation therapy with overall survival in patients undergoing surgery for T3N0M0 adenocarcinoma of the rectum.

528 Background: The standard treatment for locally advanced rectal cancer is neoadjuvant chemoradiation followed by surgery, but many physicians question the benefit of multimodality therapy in patients with stage T3N0M0 disease. We aimed to determine the impact of radiation therapy (RT) on overall survival (OS) in this group of patients. Methods: We used the Surveillance, Epidemiology, and End Results database to identify patients undergoing surgery for T3N0M0 adenocarcinoma of the rectum from 2004 to 2010. The Kaplan-Meier method was used to compare OS for patients receiving RT vs. no RT, along with for pre-op vs. post-op RT among patients that received RT. Multivariable analysis (MVA) using a Cox proportional hazards model was performed to assess the association of RT with OS after adjusting for patient age, gender, race, tumor grade, carcinoembryonic antigen, type of surgery, and circumferential margin status. The analysis was repeated separately on patients that underwent total colectomy (TC) vs. sphincter-sparing surgery. Results: The cohort included 8,679 patients, including 4,705 who received RT and 3,974 who did not. Median age was 66 years. Five year OS was 76.5% in patients who received RT, compared to 60.0% in patients who did not receive RT (p &lt;0.001). Five year OS was 76.9% for patients receiving pre-op RT vs. 75.7% in patients receiving post-op RT (p = 0.247). In patients undergoing TC, five year OS was 74.7% for patients receiving RT, compared to 47.5% in patients not receiving RT (p &lt;0.001). In patients undergoing sphincter-sparing surgery, five year OS was 77.7% in patients receiving RT, compared to 62.9% in patients not receiving RT (p &lt;0.001). Use of RT was significantly associated with OS on MVA, both in the entire cohort (HR 0.70 [95% CI 0.60-0.81]; p&lt;0.001) and in subsets of patients undergoing TC (HR 0.55 [95% CI 0.38-0.79]; p=0.001) and sphincter-sparing surgery (HR 0.70 [95% CI 0.59-0.84]; p&lt;0.001). Conclusions: The use of RT is associated with superior OS in patients undergoing surgery for T3N0M0 adenocarcinoma of the rectum. This benefit is demonstrated in both the pre-op and post-op settings and applies to patients undergoing both TC and sphincter-sparing surgery.

Neoadjuvant therapy for rectal cancer: Mature results from NSABP protocol R-04.

390 Background: The primary aims were to: 1) compare capecitabine (Cape) and continuous intravenous infusion (CVI) 5-FU combined with pelvic radiation therapy (RT) given preoperatively for patients (pts) with stage II or III rectal cancer; 2) determine whether the addition of oxaliplatin (Ox) would improve pt outcomes. Preliminary results focusing on pathologic complete response, sphincter-sparing surgery, surgical downstaging, and toxicity were presented at ASCO 2011 (Roh: J Clin Oncol 29: 2011 Ab 3503). Methods: Pts with clinical stage II or III rectal cancer undergoing preoperative RT (4,500cGy in 25 fractions over 5 wks + boost of 540cGy-1080cGy in 3-6 daily fractions) were randomly assigned to one of four chemotherapy regimens in a 2x2 design: CVI 5-FU (225mg/m2 5 days/wk), with or without intravenous Ox (50mg/m2 /wk x 5) or oral Cape (825 mg/m2 BID 5 days/wk), with or without Ox (50mg/m2/wk x 5). The primary endpoint of local-regional (L-R) tumor control included L-R tumor recurrence, less than an R0 resection (complete surgical resection), and no surgery. Results: From July 2004 to August 2010, 1608 patients were randomly assigned and 99.2% were eligible. There were no significant differences in L-R tumor control, DFS, or OS between regimens for either the 5-FU-Cape (L-R p=0.98) or the Ox-none (L-R p=0.70) comparisons. The addition of Ox was associated with significantly more grade 3-4 diarrhea (p&lt;0.0001). Analysis of the primary endpoint showed 3-yr rates of L-R tumor control ranged from 87.4%-88.2%. 3-yr rates of L-R recurrence among pts who underwent R0 resection ranged from 2-4 % for stage II pts, and from 4-11% for stage III pts. 16% of stage II and 26% of stage III pts developed distant metastases by 5 yrs. From 84% to 97% of pts received &gt;80% of the ideal chemotherapy dose in combination with preoperative RT. Conclusions: CVI 5-FU or oral Cape combined with RT produced similar outcomes and toxicity profiles. Because use of oral Cape avoids the need for central venous catheters and ambulatory infusion pumps, it can be considered a new standard of care in this setting. The addition of Ox provided no improvement in outcomes but did add significant toxicity. Clinical trial information: NCT00058474.

Future of Radiotherapy Delivery in Rectal Cancer— European and US Approaches

Neoadjuvant radiation therapy is integral in the management of patients with localized rectal cancer. In parts of Europe, patients with operable rectal cancer are treated with short-course radiation therapy delivered in five daily, 5 Gy fractions to a total dose of 25 Gy, followed by surgery within 1 week. In the US, the standard for locally advanced rectal cancer is neoadjuvant chemoradiotherapy. This approach is principally based on the results of the German Rectal Cancer Study Group trial evaluating preoperative compared with postoperative chemoradiation. Surgery is typically performed at 4–8 weeks following completion of long-course chemoradiotherapy, facilitating tumor downstaging, and potential sphincter sparing surgery. No significant difference in clinical outcomes has been observed between these two approaches in two randomized clinical trials; however, further follow-up of these studies and new results from ongoing trials are anticipated to further clarify the optimal neoadjuvant treatment strategy.