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ACR Appropriateness Criteria® Resectable Rectal Cancer
Radiation Oncologyvolume 7, Article number: 161 (2012)
The management of resectable rectal cancer continues to be guided by clinical trials and advances in technique. Although surgical advances including total mesorectal excision continue to decrease rates of local recurrence, the management of locally advanced disease (T3-T4 or N+) benefits from a multimodality approach including neoadjuvant concomitant chemotherapy and radiation. Circumferential resection margin, which can be determined preoperatively via MRI, is prognostic. Toxicity associated with radiation therapy is decreased by placing the patient in the prone position on a belly board, however for patients who cannot tolerate prone positioning, IMRT decreases the volume of normal tissue irradiated. The use of IMRT requires knowledge of the patterns of spreads and anatomy. Clinical trials demonstrate high variability in target delineation without specific guidance demonstrating the need for peer review and the use of a consensus atlas. Concomitant with radiation, fluorouracil based chemotherapy remains the standard, and although toxicity is decreased with continuous infusion fluorouracil, oral capecitabine is non-inferior to the continuous infusion regimen. Additional chemotherapeutic agents, including oxaliplatin, continue to be investigated, however currently should only be utilized on clinical trials as increased toxicity and no definitive benefit has been demonstrated in clinical trials.
The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every two years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
Summary of literature review
The American Cancer Society estimates there will be 103,170 new cases of colorectal cancer in 2012 with 40,290 of those being located in the rectum . Anatomically, the rectum begins above the dentate line, which marks the cephalad extent of the anal canal, and extends above the peritoneal reflection to the sigmoid colon. The location of the rectum deep in the pelvis with its tight confines complicates surgical resection, leading to an increased risk of local recurrence with surgical resection alone. Local and distant recurrence rates after non-total mesorectal excision (TME) surgery alone are as high as 40%-60% , thus warranting adjuvant therapy to improve local/regional control. Clinical trials have investigated the use of multimodality therapy to decrease the incidence of both local and distant recurrence. Historically, after surgical resection adjuvant therapy would be delivered if high-risk features were discovered upon pathologic examination of the surgical specimen. Subsequent investigation examined the role of neoadjuvant therapy, and most recently comparisons of these techniques have been published. This document summarizes the major clinical trials and the role for multimodality therapy.
In 2004, a randomized trial from Germany was published establishing a regimen of preoperative chemoradiotherapy and surgery followed by additional cycles of chemotherapy alone as the standard of care for clinical stages T3 or T4, or for node-positive rectal cancer . Other clinical studies from the United States, Europe, and Asia have also influenced the treatment strategies for operable rectal cancer, as various approaches using preoperative or postoperative radiotherapy, with or without chemotherapy, have been examined. A summary of the major randomized clinical trials spanning the past several decades is provided below.
Overall survival (OS) is most affected by the extent of disease, with increasing depth of rectal wall penetration and lymph node involvement being harbingers of worse outcome. Tumor location appears to be important in rectal cancer, with low-lying tumors having a greater propensity for local recurrence. Histological tumor grade is prognostic, with poorly differentiated tumors having a worse prognosis. The signet ring cell and mucinous varieties also portend a less favorable outcome. The mucinous variety can be visualized via magnetic resonance imaging (MRI) defined by greater than 50% mucin in the tumor, and this variety has recently been shown to respond less favorably to neoadjuvant chemoradiation. The pathologic circumferential resection margin (CRM) has been demonstrated to be prognostic, and at least one retrospective series confirms decreased cancer-specific survival with a CRM ≤2 mm [4, 5]. Additionally, the ypCRM status (after neoadjuvant chemoradiotherapy) is a significant risk factor for local recurrence . High-quality surgery with pathological evaluation of TME specimens is associated with a decreased risk of local recurrence. A pathological review of specimens from the Medical Research Council/United Kingdom (MRC CR07) trial, which required TME, clearly demonstrates that excellent surgical technique is directly related to local recurrence . Only 52% of the specimens demonstrated a “good” resection truly in the mesorectal plane, 34% were found to be “intermediate” in the intramesorectal plane, and 13% were “poor” involving the plane of the muscularis propria. The 3-year risk of local recurrence was directly related to quality of surgery, with high-quality surgery resulting in a lower recurrence. Importantly, all surgical groups, regardless of quality of resection, benefitted from neoadjuvant radiation therapy.
Preoperatively large radiotherapy portals covering the tumor, entire mesorectum, and lymph node regions at risk are typically treated to 45 Gy with a boost delivered to the tumor and presacral lymph nodes. The boost dose typically ranges in clinical trials from 5.4 to 9 Gy. The Radiation Therapy Oncology Group® (RTOG®) conducted a phase II study (R-0012) investigating combined-modality therapy with higher doses and hyperfractionation . Higher doses were associated with a similar pathologic complete response (pCR) rate at the cost of increased grade 3-4 acute toxicity; thus, the standard remains 50.4 to 54 Gy.
Postoperative radiotherapy with or without chemotherapy
Several classic trials have examined the use of postoperative irradiation alone or in combination with chemotherapy; conducted by the Gastrointestinal Tumor Study Group (GITSG), the North Central Cancer Treatment Group (NCCTG), and the Norwegian Adjuvant Rectal Cancer Project Group, radiotherapy delivered with concurrent chemotherapy improved both local control and survival [9–11]. Subsequently, studies R-01 and R-02 by the National Surgical Adjuvant Breast and Bowel Project (NSABP) demonstrated that the role of radiotherapy is primarily local control in the postoperative setting [12, 13].
The method of administrating chemotherapy appears to be important in obtaining optimal results. Protracted venous infusion of 5-fluorouracil (5-FU) was found to be superior to bolus 5-FU, with a 45%-50% decrease in hematologic toxicity  and is considered to be a standard adjuvant therapy; more recent studies have investigated alternate means of optimizing chemotherapy [14–16]. The choice of early versus late radiotherapy with respect to chemotherapy may also be important according to the preliminary results of a recent randomized study  and warrants further investigation. Because neoadjuvant chemoradiotherapy is superior to postoperative delivery, in cases where chemoradiation is clearly indicated, cT3-4 or N + neoadjuvant delivery is preferred. (See Table 1 and Table 2.)
Preoperative radiotherapy with or without chemotherapy
Exploring the role of preoperative radiotherapy alone (25 Gy in 5 fractions), a Swedish trial showed improvements in both local control and survival that persisted at 13 years of follow-up [18, 19]. Late toxicity with this hypofractionated regimen is substantial and includes an increased risk of small-bowel obstruction, abdominal pain, diarrhea, bleeding, and fistula formation [20, 21].
Both the MRC CR07 trial and the Dutch Colorectal Cancer Group (CKVO 95-04) investigated the role of radiation therapy with high-quality TME surgery. The Dutch study randomized 1,805 eligible patients to either surgery alone or short course radiation therapy (5 x 5 Gy) followed by surgery, and concluded that the addition of radiation significantly decreases the rate of local recurrence at 2 years even with high-quality surgery (P < 0.001) . The MRC CR07 study attempted to select high risk patients to selectively treat with radiation therapy; 1,350 patients were randomized to either neoadjuvant short-course radiation therapy (5 x 5 Gy) or selective postoperative concurrent chemoradiation therapy (45 Gy in 25 fractions with 5-FU) to those patients with CRM involvement (defined as ≤1 mm) . Patients with resectable rectal cancer who received preoperative radiation had a decreased rate of local recurrence at 3 years compared to patients who received adjuvant long-term radiation therapy. Together, the CKVO 95-04 and MRC CR07 studies confirm that radiation improves local control even with TME surgical technique. Because of the toxicity of long-term radiation treatment and the inability to safely combine the hypofractionated radiotherapy regimen with systemic chemotherapy, this approach is rarely used in the United States or Southern Europe, but it is more common in Northern Europe .
Importantly, two trials from Europe have examined the role of incorporating concurrent chemotherapy with preoperative irradiation using standard radiotherapy fractionation, in keeping with the postoperative combined chemoradiotherapy model. Two studies — one by the European Organisation for Research and Treatment of Cancer (EORTC 22921), the other by the Fondation Francaise de Cancerologie Digestive (FFCD 9203) — demonstrated a significant improvement in local control, in the absence of a survival or sphincter-preservation benefit, with the addition of chemotherapy [24, 25]. As expected, acute toxicity was increased with the addition of chemotherapy, as had been noted in the FFCD 9203 trial . (See Table 3.)
Preoperative versus postoperative chemoradiotherapy
The important question of comparing preoperative versus postoperative chemoradiotherapy, as noted above, was addressed by a randomized trial from Germany. The preoperative regimen, as published by Sauer et al , was associated with significantly improved local control and increased sphincter-preservation rates with no differences in disease-free or OS. As surgical technique continues to improve, it becomes increasingly difficult to demonstrate a benefit in disease-free or OS. Neoadjuvant delivery also resulted in decreased rates of acute and chronic treatment toxicity, when compared to the postoperative approach. Another randomized trial (NSABP R03) exploring the same question in the United States was terminated early due to poor accrual. This study did not require TME, but it did show a trend towards improved survival, with a significant improvement in recurrence-free survival and disease-free survival . Clinical response to the preoperative therapy was associated with significantly improved disease-free and OS . The current standard of care in the United States is, therefore, to provide preoperative chemoradiotherapy, using standard radiotherapy fractionation and concurrent fluorouracil for clinical stage T3 or T4 or for node-positive rectal cancer.
Physical positioning to displace the small bowel is a simple way of maximizing the therapeutic ratio. A comparative study shows that when a patient is placed prone, the use of a belly board combined with a full bladder reduces the volume of small bowel irradiated by 70% (about 100 cc) . Use of intensity-modulated radiation therapy (IMRT) with supine positioning potentially obviates the geometric benefit of placing the patient in the prone position on a belly board, which is uncomfortable and presumably more difficult for the patient to tolerate. A retrospective study comparing prone or supine setup with daily image guidance versus a no-action-level protocol confirmed that prone positioning leads to a greater systematic error. However, the study noted increased random error with the supine position. Error was decreased with either setup using increased frequency of image guidance . One study from the UK evaluated prone versus supine positioning in 19 consecutive patients and found the prone position did decrease dose to the small bowel, but primarily only in the low dose region of the dose-volume histogram . At doses above 20 Gy, there was no appreciable difference between supine and prone positioning, lending support to the notion of using the supine position in patients who may not tolerate lying prone with a full bladder.
Timing of surgery
One of the major differences in the adjuvant trials from Europe versus those from the United States has been regarding the timing of surgery after chemoradiotherapy. The short-course regimens from Europe with surgery 1 week after completing radiotherapy have not allowed adequate time for downstaging, yet it appears that with a longer interval from neoadjuvant therapy to surgery downstaging may occur. In a retrospective review of patients treated with neoadjuvant chemoradiation followed by surgery with a time interval ≤7 weeks versus >7 weeks, the longer interval before surgery demonstrated an improved pCR and near-pCR rates as well as increased disease-free survival interval . A primary concern with an extended interval from chemoradiotherapy to surgery is that tumor clonogens are afforded time for repopulation and potential spread. A delay to surgery beyond 12 weeks has been investigated in selected patients and appears to be safe without an increase in metastatic spread .
Infusional versus oral 5-FU
Since the advent of oral 5-FU, capecitabine, its equivalence has been called into question. A multitude of retrospective data exists with conflicting results. Several randomized phase III studies have recently been reported that add support to the use of capecitabine. NSABP R-04 is a randomized trial of radiotherapy with concurrent chemotherapy investigating four different chemotherapy regimens (5-FU or oral capecitabine with or without oxaliplatin). Preliminary results have recently been reported and show no significant difference between the arms with respect to pCR, sphincter preservation, or downstaging. However, the addition of oxalaplatin was associated with a notable increase in grade 3 and 4 gastrointestinal (GI) toxicity . Another randomized trial of 401 patients from Germany comparing infusional 5-FU versus oral capecitabine concurrent with neoadjuvant radiation therapy suggests different toxicity profiles between the two chemotherapy regimens with less leucopenia and increased hand-foot skin reactions associated with capecitabine. This noninferiority German study suggests that oral capecitabine is not inferior to infusional 5-FU, and is associated with an increased rate of ypN0 tumors demonstrating increased downstaging with the oral drug .
The role of neoadjuvant chemoradiotherapy in resectable rectal cancer has been established, but the possibility of increasing the therapeutic gain via newer chemotherapeutic agents exists. Two large trials, the French ACCORD and the Italian STAR trial, both evaluate the role of oxaliplatin, which increases the efficacy of fluorouracil-based chemotherapy in treating colon cancer [35, 36]. These trials clearly show an increase in toxicity with the addition of oxaliplatin with no apparent improvement in local response. This use of oxalaplatin is supported by the recent preliminary results from NSABP R-04, which showed no apparent benefit with the addition of oxalaplatin to neoadjuvant concurrent chemoradiotherapy. The use of IMRT with capecitabine and oxaliplatin is being examined in a phase II study (RTOG® 08-22), but the results are not yet available. The role of biologic agents in treating rectal cancer has not yet been established.
The role of additional adjuvant chemotherapy after chemoradiotherapy in either the neoadjuvant or adjuvant setting is also in question. Although it is clearly indicated with colon cancer, several large trials from Europe and a meta-analysis have failed to show any benefit. Adjuvant chemotherapy after either neoadjuvant or adjuvant chemoradiotherapy has remained the standard of care based on extrapolated data from colon cancer. A randomized trial was initiated to determine whether additional chemotherapy is necessary in rectal cancer, but unfortunately due to lack of clinical equipoise, the study failed to accrue and closed early. Analysis of the Surveillance, Epidemiology, and End Results (SEER) database comparing patients who received adjuvant chemotherapy with those who did not suggests that patients who are node positive may benefit from additional chemotherapy .
IMRT has a demonstrated benefit in the treatment of anal malignancies, with fewer treatment breaks presumed to be due to the decreased toxicity associated with more conformal dose delivery. The RTOG® launched a phase II study investigating the use of IMRT for T3-4N0-2 patients with capecitabine and oxaliplatin. The preliminary results, presented in abstract form only, revealed a trend towards decreased preoperative GI grade ≥2 toxicity when compared to RTOG® 0247 . A recent single-institution retrospective review comparing IMRT to classic 3-field conventional radiotherapy demonstrated a significant decrease in GI toxicity grade ≥2 for patients receiving IMRT . It is the consensus of the expert panel authoring this document that IMRT clearly decreases toxicity in the treatment of rectal cancer. Certain situations requiring larger treatment volumes such as postoperative therapy after an abdominoperineal resection (APR) or radiation of the inguinal nodes warrants a stronger recommendation for IMRT; however, there are concerns regarding delivery of IMRT outside the confines of a clinical trial. IMRT requires a greater knowledge of anatomic spread and understanding of the surrounding normal tissues and tolerances than the conventional 3-field pelvis treatment based on bony anatomy. This difficulty in contouring was clearly demonstrated in RTOG® 0529 where there were a significant number of inadequately contoured cases; however, due to a rapid review process, corrections were made prior to patient treatment. Multiple studies document the interobserver variability in target delineation with highly conformal therapy, and the need for guidance or aids in target delineation to avoid missing critical targets [40, 41]. The need for education regarding IMRT volumes in the pelvis was addressed by consensus panel of experts convened by RTOG® to create an anorectal contouring atlas that helps delineate targets . The preferred delivery for IMRT is via clinical trials; however, when being performed outside of a clinical trial, the atlas and peer review through colleagues or an established review process is strongly recommended.
Patients with low-lying rectal tumors extending below the dentate line and with extensive involvement of the anal canal receive treatment resembling that used for anal cancer, including treatment of the external iliac and inguinal nodes based on patterns of lymph node drainage. Retrospective data from MD Anderson Cancer Center suggests that the inguinal spread of rectal cancer, even with involvement of the anal canal, may be a rare event and that prophylactic radiotherapy to the groin may be unnecessary . This study defines patients having disease within 4 cm of the anal verge as having involvement of the anal canal, but it does not comment on extensive involvement with extension to the anal verge or margin. Further validation is necessary before omitting inguinal radiation therapy in patients with extensive involvement of the anal canal. (See Table 4.)
Need for future trial
Despite the published data from randomized trials that support the shift to preoperative chemoradiotherapy, a subset of patients will require surgical resection upfront for a variety of clinical reasons. A pooled analysis of five randomized clinical trials in the United States suggests that not all patients with resected tumors may require a trimodality (surgery, chemotherapy, radiotherapy) treatment approach. Patients with favorable or “intermediate-risk” (T3N0 or T1-2N1) tumors were found to have benefited equally from either postoperative chemoradiotherapy or chemotherapy alone [44, 45]. Other data from the Memorial Sloan-Kettering Cancer Center (MSKCC) suggests that understaging may be a significant problem, as 22% of the patients in the trial who were cT3N0 were found to be pN + at the time of surgery .
A risk-adapted approach, selecting patients for minimal surgery based on their response to preoperative chemoradiotherapy has been investigated. Preliminary results from a recently reported small phase II trial by the American College of Surgeons Oncology Group (ACOSOG Z6041) suggests select patients who have a small cT2N0 tumor may be candidates for preoperative chemoradiotherapy followed by local excision rather than proctectomy . The possibility of deferring or eliminating surgery for patients with a complete response to neoadjuvant chemoradiotherapy has also been suggested . A future clinical study is warranted to validate the appropriateness of such risk-adapted treatment-minimization strategies.
For additional information on ACR Appropriateness Criteria®, refer to http://www.acr.org/ac.
National Cancer Institute: Comprehensive Cancer Information. Accessed 5 January 2012 http://www.cancer.gov/cancertopics/types/colon-and-rectal
Rich T, Gunderson LL, Lew R, Galdibini JJ, Cohen AM, Donaldson G: Patterns of recurrence of rectal cancer after potentially curative surgery. Cancer 1983,52(7):1317-1329. 10.1002/1097-0142(19831001)52:7<1317::AID-CNCR2820520731>3.0.CO;2-6
Sauer R, Becker H, Hohenberger W, et al.: Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 2004,351(17):1731-1740. 10.1056/NEJMoa040694
Bernstein TE, Endreseth BH, Romundstad P, Wibe A: Circumferential resection margin as a prognostic factor in rectal cancer. Br J Surg 2009,96(11):1348-1357. 10.1002/bjs.6739
Tilney HS, Rasheed S, Northover JM, Tekkis PP: The influence of circumferential resection margins on long-term outcomes following rectal cancer surgery. Dis Colon Rectum 2009,52(10):1723-1729. 10.1007/DCR.0b013e3181b54fbd
Gosens MJ, Klaassen RA, Tan-Go I, et al.: Circumferential margin involvement is the crucial prognostic factor after multimodality treatment in patients with locally advanced rectal carcinoma. Clin Cancer Res 2007,13(22 Pt 1):6617-6623.
Quirke P, Steele R, Monson J, et al.: Effect of the plane of surgery achieved on local recurrence in patients with operable rectal cancer: a prospective study using data from the MRC CR07 and NCIC-CTG CO16 randomised clinical trial. Lancet 2009,373(9666):821-828. 10.1016/S0140-6736(09)60485-2
Mohiuddin M, Winter K, Mitchell E, et al.: Randomized phase II study of neoadjuvant combined-modality chemoradiation for distal rectal cancer: Radiation Therapy Oncology Group Trial 0012. J Clin Oncol 2006,24(4):650-655. 10.1200/JCO.2005.03.6095
Krook JE, Moertel CG, Gunderson LL, et al.: Effective surgical adjuvant therapy for high-risk rectal carcinoma. N Engl J Med 1991,324(11):709-715. 10.1056/NEJM199103143241101
Thomas PR, Lindblad AS: Adjuvant postoperative radiotherapy and chemotherapy in rectal carcinoma: a review of the Gastrointestinal Tumor Study Group experience. Radiother Oncol 1988,13(4):245-252. 10.1016/0167-8140(88)90219-8
Tveit KM, Guldvog I, Hagen S, et al.: Randomized controlled trial of postoperative radiotherapy and short-term time-scheduled 5-fluorouracil against surgery alone in the treatment of Dukes B and C rectal cancer. Norwegian Adjuvant Rectal Cancer Project Group. Br J Surg 1997,84(8):1130-1135. 10.1002/bjs.1800840827
Fisher B, Wolmark N, Rockette H, et al.: Postoperative adjuvant chemotherapy or radiation therapy for rectal cancer: results from NSABP protocol R-01. J Natl Cancer Inst 1988,80(1):21-29. 10.1093/jnci/80.1.21
Wolmark N, Wieand HS, Hyams DM, et al.: Randomized trial of postoperative adjuvant chemotherapy with or without radiotherapy for carcinoma of the rectum: National Surgical Adjuvant Breast and Bowel Project Protocol R-02. J Natl Cancer Inst 2000,92(5):388-396. 10.1093/jnci/92.5.388
Smalley SR, Benedetti JK, Williamson SK, et al.: Phase III trial of fluorouracil-based chemotherapy regimens plus radiotherapy in postoperative adjuvant rectal cancer: GI INT 0144. J Clin Oncol 2006,24(22):3542-3547. 10.1200/JCO.2005.04.9544
O'Connell MJ, Martenson JA, Wieand HS, et al.: Improving adjuvant therapy for rectal cancer by combining protracted-infusion fluorouracil with radiation therapy after curative surgery. N Engl J Med 1994,331(8):502-507. 10.1056/NEJM199408253310803
Tepper JE, O'Connell MJ, Petroni GR, et al.: Adjuvant postoperative fluorouracil-modulated chemotherapy combined with pelvic radiation therapy for rectal cancer: initial results of intergroup 0114. J Clin Oncol 1997,15(5):2030-2039.
Lee JH, Ahn JH, Bahng H, et al.: Randomized trial of postoperative adjuvant therapy in stage II and III rectal cancer to define the optimal sequence of chemotherapy and radiotherapy: a preliminary report. J Clin Oncol 2002,20(7):1751-1758. 10.1200/JCO.2002.07.037
Folkesson J, Birgisson H, Pahlman L, Cedermark B, Glimelius B, Gunnarsson U: Swedish Rectal Cancer Trial: long lasting benefits from radiotherapy on survival and local recurrence rate. J Clin Oncol 2005,23(24):5644-5650. 10.1200/JCO.2005.08.144
Improved survival with preoperative radiotherapy in resectable rectal cancer. Swedish Rectal Cancer Trial N Engl J Med 1997,336(14):980-987.
Birgisson H, Pahlman L, Gunnarsson U, Glimelius B: Adverse effects of preoperative radiation therapy for rectal cancer: long-term follow-up of the Swedish Rectal Cancer Trial. J Clin Oncol 2005,23(34):8697-8705. 10.1200/JCO.2005.02.9017
Birgisson H, Pahlman L, Gunnarsson U, Glimelius B: Late gastrointestinal disorders after rectal cancer surgery with and without preoperative radiation therapy. Br J Surg 2008,95(2):206-213.
Kapiteijn E, Marijnen CA, Nagtegaal ID, et al.: Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med 2001,345(9):638-646. 10.1056/NEJMoa010580
Sebag-Montefiore D, Stephens RJ, Steele R, et al.: Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial. Lancet 2009,373(9666):811-820. 10.1016/S0140-6736(09)60484-0
Bosset JF, Collette L, Calais G, et al.: Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med 2006,355(11):1114-1123. 10.1056/NEJMoa060829
Gerard JP, Conroy T, Bonnetain F, et al.: Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. J Clin Oncol 2006,24(28):4620-4625. 10.1200/JCO.2006.06.7629
Roh MS, Colangelo LH, O'Connell MJ, et al.: Preoperative multimodality therapy improves disease-free survival in patients with carcinoma of the rectum: NSABP R-03. J Clin Oncol 2009,27(31):5124-5130. 10.1200/JCO.2009.22.0467
Roh MS, Colangelo L, Wieand S, et al.: Response to preoperative multimodality therapy predicts survival in patients with carcinoma of the rectum. ASCO Meeting Abstracts 2004,22(14):3505.
Kim TH, Chie EK, Kim DY, et al.: Comparison of the belly board device method and the distended bladder method for reducing irradiated small bowel volumes in preoperative radiotherapy of rectal cancer patients. Int J Radiat Oncol Biol Phys 2005,62(3):769-775. 10.1016/j.ijrobp.2004.11.015
Siddiqui F, Shi C, Papanikolaou N, Fuss M: Image-guidance protocol comparison: supine and prone set-up accuracy for pelvic radiation therapy. Acta Oncol 2008,47(7):1344-1350. 10.1080/02841860802304564
Drzymala M, Hawkins MA, Henrys AJ, Bedford J, Norman A, Tait DM: The effect of treatment position, prone or supine, on dose-volume histograms for pelvic radiotherapy in patients with rectal cancer. Br J Radiol 2009,82(976):321-327.
Tulchinsky H, Shmueli E, Figer A, Klausner JM, Rabau M: An interval >7 weeks between neoadjuvant therapy and surgery improves pathologic complete response and disease-free survival in patients with locally advanced rectal cancer. Ann Surg Oncol 2008,15(10):2661-2667. 10.1245/s10434-008-9892-3
Habr-Gama A, Perez RO, Proscurshim I, et al.: Interval between surgery and neoadjuvant chemoradiation therapy for distal rectal cancer: does delayed surgery have an impact on outcome? Int J Radiat Oncol Biol Phys 2008,71(4):1181-1188. 10.1016/j.ijrobp.2007.11.035
Roh MS, Yothers GA, O'Connell MJ, et al.: The impact of capecitabine and oxaliplatin in the preoperative multimodality treatment in patients with carcinoma of the rectum: NSABP R-04. ASCO Meeting Abstracts 2011,29(15):3503.
Hofheinz R, Wenz FK, Post S, et al.: Capecitabine (Cape) versus 5-fluorouracil (5-FU)-based (neo)adjuvant chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC): Long-term results of a randomized, phase III trial. ASCO Meeting Abstracts 2011,29(15):3504.
Gerard JP, Azria D, Gourgou-Bourgade S, et al.: Comparison of two neoadjuvant chemoradiotherapy regimens for locally advanced rectal cancer: results of the phase III trial ACCORD 12/0405-Prodige 2. J Clin Oncol 2010,28(10):1638-1644. 10.1200/JCO.2009.25.8376
Valentini V, Coco C, Minsky BD, et al.: Randomized, multicenter, phase IIb study of preoperative chemoradiotherapy in T3 mid-distal rectal cancer: raltitrexed + oxaliplatin + radiotherapy versus cisplatin + 5-fluorouracil + radiotherapy. Int J Radiat Oncol Biol Phys 2008,70(2):403-412. 10.1016/j.ijrobp.2007.06.025
Kiran RP, Nisar PJ, Pelley RJ, Fazio VW, Lavery IC: Role of routine adjuvant chemotherapy after neoadjuvant chemoradiotherapy and resection in low-risk patients with rectal cancer. ASCO Meeting Abstracts 2011,29(15):e14032.
Garofalo M, Moughan J, Hong T, et al.: RTOG 0822: A Phase II Study of Preoperative (PREOP) Chemoradiotherapy (CRT) Utilizing IMRT in Combination with Capecitabine (C) and Oxaliplatin (O) for Patients with Locally Advanced Rectal Cancer. Int J Radiat Oncol Biol Phys 2011,81(2):S3-S4.
Samuelian JM, Callister MD, Ashman JB, Young-Fadok TM, Borad MJ, Gunderson LL: Reduced acute bowel toxicity in patients treated with intensity-modulated radiotherapy for rectal cancer. Int J Radiat Oncol Biol Phys 2012,82(5):1981-1987. 10.1016/j.ijrobp.2011.01.051
Fuller CD, Nijkamp J, Duppen JC, et al.: Prospective randomized double-blind pilot study of site-specific consensus atlas implementation for rectal cancer target volume delineation in the cooperative group setting. Int J Radiat Oncol Biol Phys 2011,79(2):481-489. 10.1016/j.ijrobp.2009.11.012
Fuller CD, Nijkamp J, Rasch CR, et al. Paper presented at: 2010 Gastrointestinal Cancers Symposium. Impact of rectal cancer target volume consensus atlas implementation in the cooperative group setting: Preliminary results from a prospective randomized double-blind pilot study 2010.
Myerson RJ, Garofalo MC, El Naqa I, et al.: Elective clinical target volumes for conformal therapy in anorectal cancer: a radiation therapy oncology group consensus panel contouring atlas. Int J Radiat Oncol Biol Phys 2009,74(3):824-830. 10.1016/j.ijrobp.2008.08.070
Taylor N, Crane C, Skibber J, et al.: Elective groin irradiation is not indicated for patients with adenocarcinoma of the rectum extending to the anal canal. Int J Radiat Oncol Biol Phys 2001,51(3):741-747. 10.1016/S0360-3016(01)01687-X
Gunderson LL, Sargent DJ, Tepper JE, et al.: Impact of T and N substage on survival and disease relapse in adjuvant rectal cancer: a pooled analysis. Int J Radiat Oncol Biol Phys 2002,54(2):386-396. 10.1016/S0360-3016(02)02945-0
Gunderson LL, Sargent DJ, Tepper JE, et al.: Impact of T and N stage and treatment on survival and relapse in adjuvant rectal cancer: a pooled analysis. J Clin Oncol 2004,22(10):1785-1796. 10.1200/JCO.2004.08.173
Guillem JG, Diaz-Gonzalez JA, Minsky BD, et al.: cT3N0 rectal cancer: potential overtreatment with preoperative chemoradiotherapy is warranted. J Clin Oncol 2008,26(3):368-373. 10.1200/JCO.2007.13.5434
Garcia-Aguilar J, Shi Q, Thomas CR Jr, et al.: A phase II trial of neoadjuvant chemoradiation and local excision for T2N0 rectal cancer: preliminary results of the ACOSOG Z6041 trial. Ann Surg Oncol 2012,19(2):384-391. 10.1245/s10434-011-1933-7
Habr-Gama A, Perez RO, Proscurshim I, et al.: Patterns of failure and survival for nonoperative treatment of stage c0 distal rectal cancer following neoadjuvant chemoradiation therapy. J Gastrointest Surg 2006,10(10):1319-1328. discussion 1328-1319 10.1016/j.gassur.2006.09.005
As of August 19, 2011, Joseph Herman, MD reported “Nucletron, Genentech”
As of June 27, 2011, Prajnan Das, MD reported “Research Support – Genentech”
For the remaining authors none were declared.
WJ, CT, JM, MW, NA, WB, PD, KG, TH, SK, AAK, ACK, MB, WS, JZ, WS. All authors read and approved the final manuscript.
The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through society representation on expert panels. Participation by representatives from collaborating societies on the expert panel does not necessarily imply individual or society endorsement of the final document.