This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gerard, J.-P. Articles by Adeleine, P. Search for Related Content PubMed PubMed Citation Articles by Gerard, J.-P. Articles by Adeleine, P. Social Bookmarking                            What's this?

Improved Sphincter Preservation in Low Rectal Cancer With High-Dose Preoperative Radiotherapy: The Lyon R96-02 Randomized Trial

From the Department of Radiotherapy, Centre Antoine-Lacassagne, Nice; Department of Radiotherapy and Department of General Surgery CHU Lyon Sud, Pierre Bênite; Department of Biostatistics, Department of General Surgery, Hôpital Croix Rousse, Hôpital Edouard Herriot, CHU Lyon, and Clinique Charcot, Sainte Foy, Lyon; Clinique Saint-Jean, Lyon; Clinique Denis, MÂcon; Department of Radiotherapy, Centre George-François Leclerc, Dijon; Department of Radiotherapy, Centre René Gauducheau, Nantes; Clinique Trenel, Vienne; Clinique Sainte Marie-Thérèse, Bron, France

Address reprint requests to Jean-Pierre Gérard, MD, Centre Antoine-Lacassagne, 33 Avenue de Valombrose, 06189 Nice Cedex 2, France; e-mail: jean-pierre.gerard{at}cal.nice.fnclcc.fr

	ABSTRACT

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... REFERENCES

 
PURPOSE: The potential advantage of high-dose preoperative radiotherapy to increase tumor response and improve the chance of sphincter preservation for low rectal cancer remains controversial. The aim of this trial was to evaluate the role of escalating the dose of preoperative radiation to increase sphincter-saving procedures.

PATIENTS AND METHODS: Patients with rectal carcinoma located in the lower rectum, staged T2 or T3, Nx, or M0 with endorectal sonography, and not involving more than two-thirds circumference, were randomly assigned to one of two groups: preoperative external-beam radiotherapy (EBRT; 39 Gy in 13 fractions over 17 days) versus the same EBRT with boost (85 Gy in three fractions) using endocavitary contact x-ray.

RESULTS: Between 1996 and 2001, 88 patients were enrolled onto the study. A significant improvement was seen in favor of the contact x-ray boost for complete clinical response (24% v 2%) and for a complete or near-complete sterilization of the operative specimen (57% v 34%). A significant increase in sphincter preservation was observed in the boost group (76% v 44%; P = .004). At a median follow-up of 35 months, there was no difference in morbidity, local relapse, and 2-year overall survival.

CONCLUSION: A dose escalation with endocavitary irradiation provides increased tumor response and sphincter preservation with no detrimental effect on treatment toxicity and early clinical outcome.

	INTRODUCTION

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... REFERENCES

 
The standard treatment of T2-T3 rectal adenocarcinoma is surgery with total mesorectal excision (TME).1 The Dutch Colorectal Cancer Group Trial2 duplicated the Swedish preoperative trial3 with the introduction of TME surgery and pathological examination according to the Quirke procedure.4 The Dutch Colorectal Cancer Group Trial has confirmed that a short course of radiotherapy (25 Gy, five fractions, five days) was reducing the rate of local pelvic recurrence at 3 years, from 10.1% to 3.4%. Meta-analysis of 19 randomized trials including preoperative radiotherapy tends to show that it provides a gain of three percent at 5 years in overall survival.5 One important question is whether preoperative radiotherapy can improve the success of any sphincter-saving procedure (SSP). Only randomized trials can give a somewhat objective response to this question.6 Many randomized trials in the literature are comparing surgery alone with preoperative radiotherapy and immediate surgery.2,3,7,8 None of these trials show any difference in the rate of SSP. The next hypothesis was to assess if preoperative radiotherapy and long interval before surgery, taking advantage of tumor response could improve the rate of sphincter salvage. The Lyon R90-01 randomized trial comparing a short versus a long interval demonstrated an increase in tumor response with long interval (sterilized operative specimen 15 versus 5%) and a trend toward more SSP in low rectal cancer (41 versus 22%).9

The present Lyon R96-02 randomized trial was designed to determine if a dose escalation using contact x-ray (CXR) boost in addition to external-beam radiotherapy (EBRT) could further increase tumor response and sphincter preservation.

	PATIENTS AND METHODS

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... REFERENCES

 
Eligibility and Random Assignment
To be eligible, patients had to present histologically confirmed adenocarinoma of the rectum without evidence of distant metastases, and the inferior edge of the tumor had to be located not further than 6 cm from the anal verge. Only International Union Against Cancer (UICC) T2 or T3 tumors staged with endorectal sonography were included. The tumor should not involve more than two-thirds of the rectal circumference to be accessible to CXR therapy. There was no age limit, and the patient had to be fit for surgery.

After written consent, patients were randomly assigned to preoperative EBRT alone (control group) or to the same EBRT with a CXR boost dose escalation (experimental group). Random assignment was performed at the central trial office and was based on permuted random blocks. There was no stratification. The trial was approved by the Lyon II Medical Ethics Committee.

Sample Size
The main end point of this trial was sphincter preservation. To detect an increase in the rate of sphincter salvage from 40% to 65%, with 90% probability and a 5% significance level, it was calculated that a total of 90 patients had to be recruited.

Patient Work-Up
All patients underwent a work-up with careful digital rectal examination and rigid proctoscopy in the knee-chest position, and endorectal sonography with a flexible probe. A metastatic work-up was performed using abdominal sonography, computed tomography, chest x-ray, serum carcinoembryonic antigen serum level, and liver function tests.

Irradiation Technique
EBRT. The protocol called for a three-field wedge technique with the patient in a prone position and use of an 18-MV photon beam. The target volume included the primary rectal tumor, the perirectal nodes, the mesorectum up to the level of the upper border of the first sacral vertebra, and the lymph nodes along the internal iliac vessels. The anal canal was not irradiated, except in those patients who had tumor invading the upper part of the anus. The mean field size was 14 x 12 cm and 14 x 11 cm for the posterior and lateral fields, respectively. The dose per fraction was 3 Gy, specified at the International Commission on Radiation Units point. The total dose of EBRT was 39 Gy in 13 fractions delivered over 17 days.

CXR. CXR was performed using a RT50 Philips unit delivering a beam of 50 kV with 0.5-mm aluminum filtration and a dose rate at 4 cm source-surface distance of 20 Gy per minute.10 The CXR treatment was started 2 weeks before EBRT. Three fractions of 35 Gy, 30 Gy, and 20 Gy were delivered on days 1, 8, and 21. The day-21 fraction was given at the end of the first week of EBRT. A total dose of 85 GY in three fractions of CXR was prescribed.

Brachytherapy. After a complete clinical response (CR) 4 weeks after the end of EBRT, a final boost irradiation could be given to the tumor bed using an interstitial iridium-192 brachytherapy implant. If the tumor was between 4 and 6 cm from the anal verge, a "fork" implant was used made of two iridium-192 wires 4 cm long and 1.6 cm apart delivering 25 Gy in 24 to 36 hours according to the Paris dosimetric system. In case of tumor of the rectum below 4 cm from the anal verge, a perineal template was used with 5- to 6-cm-long iridium 192 wires, 1 cm apart, also delivering 25 Gy over 24 to 36 hours.10

Surgery
All surgery was performed following the rules of sharp dissection under direct vision with resection of the total mesorectum. Two major types of surgery were defined: abdominoperineal resection with a permanent colostomy and low anterior resection with colorectal or usually coloanal anastomosis. Diverting stoma was left to the surgeon's decision. Delayed coloanal anastomosis was used in one surgical department.11 Endoanal local excision was an alternative in case of complete CR. Surgery was planned after a minimum interval of 5 weeks following the end of EBRT.

No adjuvant chemotherapy was foreseen in the protocol, but in case of locally advanced evolutive cancer in the operative specimen, adjuvant chemotherapy with fluorouracil and folinic acid was possible and was left to the responsible clinician's decision.

Histopathologic Examination
In all cases, the circumferential resection margin was determined on a transverse or coronal dissection of the specimen. The circumferential resection margin was considered positive where tumor tissue approaches the inked resection margin within 1 mm or less. The operative specimen was classified as pathologic CR when no cancer cells were found, or as "few residual cells" when only a small cluster of cells was detected in any of the rectal layers. The operative specimen was staged according to the 1987 UICC pTNM staging system.

Follow-Up
Patients were evaluated 4 weeks after the end of EBRT by the surgeon. A clinical CR was defined as the total disappearance of the tumor on digital rectal examination and proctoscopy. After surgery or irradiation alone, patient follow-up was performed every 3 months during the first 3 years. Clinical examination with rigid proctoscopy was performed each time. Relevant radiologic or biologic examinations were performed according to presenting symptoms or signs. At each examination, sphincter function was evaluated by patient interview using the Memorial Sloan-Kettering Cancer Center score.12

Statistical Analysis
The significance of associations for the two treatment groups and dichotomous data were calculated with the Fisher's exact test, and the significance of differences between means, with the Student's t test. P < .05 was considered to indicate statistical significance. Analyses of response and survival were based on all eligible patients. Comparison between the treatment groups was made on the intention-to-treat principle. Survival probabilities, local relapse-free rate, and curves of distribution were calculated with the Kaplan and Meier method and compared by log-rank test. A multivariate analysis of SSP according to randomized treatment was performed using a logistic regression model. Age, sex, circumference extension, distance from anal verge, TN stage, and treatment group were included as covariables. Circumferential extension was grouped, and distance from anal verge was analyzed as a continuous variable.

	RESULTS

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... REFERENCES

 
Patients
A total of 90 patients was randomly assigned to one of the two treatment groups between April 1996 and June 2001. Two patients were not eligible for analysis (one in each treatment group) because they had undergone surgery without preoperative irradiation. The characteristics of the 88 eligible patients were similar in the two treatment groups (Table 1).

Treatment
Radiotherapy. In 81 patients, EBRT was given according to the protocol. In seven patients, some variations were found (four field techniques in five patients, and a dose of 45 Gy in 50 fractions over 5 weeks in two patients). Forty-five patients of the combined EBRT + CXR group received a CXR boost with a mean dose of 85 Gy (range, 50 to 135 Gy) in three sessions (range, 2 to 5 sessions). In six patients with CR after EBRT, an iridium-192 implant was performed. In four cases, a perineal template technique was used, and in two cases, a "fork" implant was performed. The mean dose delivered was 25 Gy (range, 20 to 30 Gy).

Surgery. Seven patients did not undergo surgery. For all patients in the experimental group (six of them because after complete CR), it was decided that surgery be cancelled, and that we perform a boost with brachytherapy. One patient presented with a peritoneal carcinosis found during surgery, and as the local response was complete, the surgeon decided not to perform any rectal resection. A total of 81 patients underwent surgery—all the 43 patients of the control group and 38 in the experimental group. Table 2 shows the various types of surgery performed. In three cases, an endoanal local excision was performed. In two patients, the CR was complete, and no residual tumor was found in the operative specimen. In one frail, 79-year-old patient with a partial response and suspicion of lung metastases, the surgeon decided to perform a full-thickness R0 endoanal excision. The pathological specimen showed adenocarcinoma invading the perirectal fat with few residual cells. None of these three patients thus far had local recurrence with a follow-up between 18 and 40 months.

Adjuvant chemotherapy. In 23 patients (control group, n = 12; experimental group, n = 11), adjuvant chemotherapy was given. The protocol in all cases was a combination of fluorouracil and leucovorin for four or six cycles.

Clinical and Pathologic Response
Four to 6 weeks after the end of EBRT, a complete CR was found in 11 patients in the experimental group, and in only one from the control group (P < .05).

An operative specimen could be examined in all of the 43 patients of the EBRT group and in 38 patients of the EBRT + CXR group. The maximum tumor diameter was smaller in the experimental group, and there were significantly more operative specimens with few residual cells or a complete sterilization in this experimental group. There was no difference for the rate of perirectal lymph node involvement. Surgical margins were found positive in one patient with EBRT + CXR (distal margin), and in three patients with EBRT (circumferential margin; Table 3).

Toxicity
There was no difference in the early acute reaction of EBRT in both groups. All the patients could receive the prescribed dose. Brachytherapy was well tolerated, and none of the seven patients treated with exclusive irradiation developed grade 3 or higher late anorectal toxicity. The surgical complications were similar in both groups (Table 4). The rate of anastomotic fistula, reoperation, and postoperative toxicity (abcess, peritonitis, myocardial infarction, thrombophlebitis) appears to be within usual range. The anorectal function was analyzed using the MSKCC score in the patients with a sphincter-saving surgery. No significant difference was found between both groups (Table 5).

	DISCUSSION

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... REFERENCES

There are limitations to this study that includes only 88 patients. Some patients (23 of 88) received adjuvant chemotherapy. Although these patients were evenly distributed in both arms of the trial and probably did not change the results, the use of chemotherapy is a potentially confounding factor that must be considered. In addition, some patients (six of 88) were treated with brachytherapy. Although this was standard treatment in the design of the trial, the decision to perform this brachytherapy was arbitrary, and is, therefore, a potential confounding factor.

These results can be compared with those of other trials. There are three randomized trials that can be analyzed to answer the question of the role of preoperative radiotherapy and delayed surgery to increase sphincter preservation. Two randomized trials compared preoperative chemoradiotherapy with delayed surgery, versus the same regimen in a postoperative situation. In the National Surgical Adjuvant Breast and Bowel Project R03 trial, the 5-year sphincter-saving surgery rate with no evidence of disease was significantly increased in the preoperative arm (44% v 34%).13 In the German CAO/ARO/AIO trial for patients with low rectal cancer, the rate of SSP was significantly increased from 18% (13 of 74 patients) in the postoperative group, to 35% (26 of 75 patients) in the preoperative group.14 Conversely, a Polish trial came to an opposite conclusion.15 This randomized trial of low rectal cancer compared Dutch preoperative short-course irradiation (25 Gy, five fractions, 5 days) with immediate surgery, with the German regimen of concurrent chemoradiotherapy and delayed surgery. After inclusion of 311 patients, the rate of sphincter preservation was 61.3% in the immediate surgery group, versus 58.3% in the delayed group. This absence of improvement in SSP was observed, despite a significant increase in the tumor response in the delayed group with concurrent chemoradiotherapy (mean largest tumor diameter on the operative specimen, 29 mm v 48 mm). A hypothesis can be proposed to explain the negative results of this trial: the surgeons were asked before irradiation to specify the type of surgery they would propose if no radiation was given; it is possible that for conceptual oncological reasons they decided not to change their choice whatever the tumor response was at time of delayed surgery in the chemoradiotherapy group. Conversely, in breast cancers larger than 3 cm16 and in T3 laryngeal or hypopharyngeal cancers17, a first-line radiotherapy and/or chemotherapy has proven in randomized trials to be able to increase tumor response and organ preservation. In such situations, surgeons have accepted to change their technique of operation.

It is clearly demonstrated in all the aforementioned trials that preoperative irradiation and delayed surgery produce a significant tumor response. This end point, when evaluated on the operative specimen, depends heavily on the care taken by the pathologists to critically perform the microscopic examination.18 The Lyon trial shows a significant increase in the pathological primary tumor response with dose escalation, but no impact on the pN stage as the dose fall-off with the 50 kV x-ray beam delivered by the contact unit is too sharp to influence tumor deposit at few centimeters from the primary tumor.

Although CXR technique is accessible to any radiation oncologist with clinical expertise in rectal cancer, it is not widely used. There are only two or three centers in the United States and 10 in Europe that can perform this technique, mainly because the 50 kV machine is not manufactured any more, which limits the present applicability of this approach. Alternative possibilities to take advantage of an endocavitary approach is the use of long source-skin distance with a 50-kV beam19 or high-dose rate-conformal endoluminal brachytherapy.20 The role of concurrent chemoradiaton to increase tumor response and SSP is also of importance, but is beyond the scope of this article.

In conclusion, this trial brings strong support for a radiation dose-tumor response relationship in rectal adenocarcinoma.21 It is also reasonable that, according to the present data, a colorectal surgeon could adapt their surgical decisions and technical approach in accord with the importance of rectal tumor response, to increase the chance of organ preservation.

This trial brings data in favor of the use of high-dose preoperative radiotherapy and delayed surgery to increase anorectal SSPs in the management of low rectal cancer.

	Authors' Disclosures of Potential Conflicts of Interest

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... REFERENCES

 
The authors indicated no potential conflicts of interest.

	NOTES

 
Presented at the 45^th Annual Meeting of the American Society of Therapeutic Radiology and Oncology, Salt Lake City, UT, October 21, 2003.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

	REFERENCES

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... REFERENCES

 
1. Heald RJ, Moran BJ, Ryall RD, et al: Rectal cancer: The Basingstoke experience of total mesorectal excision, 1978–1997. Arch Surg 133:894-899, 1998[Abstract/Free Full Text]

2. Kapiteijn E, Marijnen CAM, Nagtegaal ID, et al: Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med 345:638-646, 2001[Abstract/Free Full Text]

3. Swedish Rectal Cancer Trial: Improved survival with preoperative radiotherapy in resectable rectal cancer. N Engl J Med 336:980-987, 1997[Abstract/Free Full Text]

4. Quirke P, Durdey P, Dixon MF, et al: Local recurrence of rectal adenocarcinoma due to inadequate surgical resection: Histopathological study of lateral tumor spread and surgical excision. Lancet 2:996-999, 1986[CrossRef][Medline]

5. Colorectal Cancer Collaborative Group. Adjuvant radiotherapy for rectal cancer: A systematic overview of 8507 patients from 22 randomized trials. Lancet 358:1291-1304, 2001[CrossRef][Medline]

6. Minsky B: Sphincter preservation for rectal cancer: Fact or fiction? J Clin Oncol 20:1971-1972, 2002[Free Full Text]

7. Gérard A, Buyse M, Nordlinger B, et al: Preoperative radiotherapy in Duke's B and C carcinoma of the rectum and rectosigmoid: A randomized multicenter study. Ann Surg 208:606-614, 1988[Medline]

8. Medical Research Council Rectal Cancer Working Party: Randomized trial of surgery alone versus radiotherapy followed by surgery for potentially operable locally advanced rectal cancer. Lancet 348:1605-1610, 1996[CrossRef][Medline]

9. François Y, Nemoz C, Baulieux J, et al: Influence of the interval between preoperative radiation therapy and surgery on downstaging and on the rate of sphincter saving surgery for rectal cancer: The Lyon R 90.01 randomized trial. J Clin Oncol 17:2396-2402, 1999[Abstract/Free Full Text]

10. Gérard JP, Romestaing P, Ardiet JM, et al: Endocavitary radiotherapy. Semin Radiat Oncol 8:13-23, 1998[CrossRef][Medline]

11. Olagne E, Baulieux J, De Laroche E, et al: Functional results of delayed coloanal anastomosis after preoperative radiotherapy for lower third rectal cancer. J Am Coll Surg 191:643-649, 2000[CrossRef][Medline]

12. Minsky BD, Cohen AM, Enker WE, et al: Phase I/II trial of preoperative radiation therapy and coloanal anastomosis in distal invasive resectable rectal cancer. Int J Radiat Oncol Biol Phys 23:387-392, 1992[Medline]

13. Hyam SDM, Mamounas EP, Petrelli N, et al: A clinical trial to evaluate the worth of preoperative multimodality therapy in patients with operable carcinoma of the rectum: A progress report of NSABP Protocol R-03. Dis Colon Rectum 40:131-139, 1997[CrossRef][Medline]

14. Sauer R, Fietkau R, Rödel C, et al: Adjuvant and neoadjuvant radiochemotherapy for advanced rectal cancer: First results of the German multicenter phase III trial (CAO/ARO/AIO-94) cancer. Radiother Oncol 64:115-139, 2002 (suppl 1)

15. Bujko K, Nowacki MP, Bebenek M, et al: Randomized trial comparing high dose per fraction preoperative radiochemotherapy with delayed surgery for patients with low rectal cancer. Radiother Oncol 64:140-147, 2002 (suppl 1)

16. Mauriac L, Durand M, Avril A: Effects of primary chemotherapy in conservative treatment of breast cancer patients with operable tumors larger than 3 cm: Results of a randomized trial in a single centre. Ann Oncol 2:347-354, 1991[Abstract/Free Full Text]

17. The Department of Veterans Affairs Laryngeal Cancer Study Group. Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. N Engl J Med 324:1685-1690, 1991[Abstract]

18. Roedel C, Grabenhaeur G, Papadopoulos T, et al: Apoptosis as a cellular predictor for histopathologic response to neoadjuvant radiochemotherapy in patients with rectal cancer. Int J Radiat Oncol Biol Phys 52:294-303, 2002[CrossRef][Medline]

19. Coffey CW, Morris R, Martin J, et al: Dosimetric evaluation of a variable energy superifical x-ray machine with applications for endocavitary radiotherapy techniques. Int J Radiat Oncol Biol Phys 16:849-855, 1989[Medline]

20. Vuong T, Belliveau RJ, Michel RP, et al: Conformal preoperative endorectal brachytherapy treatment for locally advanced rectal cancer: Early results of a phase I/II study. Dis Colon Rectum 45:1486-1495, 2002[CrossRef][Medline]

21. Gérard JP, Chapet O, Ramaioli A, et al: Long-term control of T2–T3 rectal adenocarinoma with radiotherapy alone. Int J Radiat Oncol Biol Phys 54:142-149, 2002[Medline]

Submitted August 25, 2003; accepted April 7, 2004.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				B D P O'NEILL, G SALERNO, K THOMAS, D M TAIT, and G BROWN MR vs CT imaging: low rectal cancer tumour delineation for three-dimensional conformal radiotherapy Br. J. Radiol., June 1, 2009; 82(978): 509 - 513. [Abstract] [Full Text] [PDF]

				J Murphy, D Boyle, C Bhan, and N S Williams Letter in response to 'Unacceptable variation in abdominoperineal excision rates for rectal cancer: time to intervene?' Gut, January 1, 2009; 58(1): 146 - 146. [Full Text] [PDF]

				B. S. Min, Y. J. Choi, H. R. Pyo, H. Kim, J. Seong, H. C. Chung, S. Y. Rha, and N. K. Kim Cyclooxygenase-2 Expression in Pretreatment Biopsy as a Predictor of Tumor Responses After Preoperative Chemoradiation in Rectal Cancer Arch Surg, November 1, 2008; 143(11): 1091 - 1097. [Abstract] [Full Text] [PDF]

				R. Glynne-Jones and M. Harrison Locally Advanced Rectal Cancer: What Is the Evidence for Induction Chemoradiation? Oncologist, November 1, 2007; 12(11): 1309 - 1318. [Abstract] [Full Text] [PDF]

				J.-P. Gerard, T. Conroy, F. Bonnetain, O. Bouche, O. Chapet, M.-T. Closon-Dejardin, M. Untereiner, B. Leduc, E. Francois, J. Maurel, et al. Preoperative Radiotherapy With or Without Concurrent Fluorouracil and Leucovorin in T3-4 Rectal Cancers: Results of FFCD 9203 J. Clin. Oncol., October 1, 2006; 24(28): 4620 - 4625. [Abstract] [Full Text] [PDF]

				F. A. Calvo, F. J. Serrano, J. A. Diaz-Gonzalez, M. Gomez-Espi, E. Lozano, R. Garcia, D. de la Mata, J. A. Arranz, P. Garcia-Alfonso, G. Perez-Manga, et al. Improved incidence of pT0 downstaged surgical specimens in locally advanced rectal cancer (LARC) treated with induction oxaliplatin plus 5-fluorouracil and preoperative chemoradiation Ann. Onc., July 1, 2006; 17(7): 1103 - 1110. [Abstract] [Full Text] [PDF]

				R. Rengan, P. Paty, W. D. Wong, J. Guillem, M. Weiser, L. Temple, L. Saltz, and B. D. Minsky Distal cT2N0 Rectal Cancer: Is There an Alternative to Abdominoperineal Resection? J. Clin. Oncol., August 1, 2005; 23(22): 4905 - 4912. [Abstract] [Full Text] [PDF]

				I. Zlobec, R. Steele, N. Nigam, and C. C. Compton A Predictive Model of Rectal Tumor Response to Preoperative Radiotherapy Using Classification and Regression Tree Methods Clin. Cancer Res., August 1, 2005; 11(15): 5440 - 5443. [Abstract] [Full Text] [PDF]

				C. A.M. Marijnen, C. J.H. van de Velde, H. Putter, M. van den Brink, C. P. Maas, H. Martijn, H. J. Rutten, T. Wiggers, E. K. Kranenbarg, J.-W. H. Leer, et al. Impact of Short-Term Preoperative Radiotherapy on Health-Related Quality of Life and Sexual Functioning in Primary Rectal Cancer: Report of a Multicenter Randomized Trial J. Clin. Oncol., March 20, 2005; 23(9): 1847 - 1858. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gerard, J.-P. Articles by Adeleine, P. Search for Related Content PubMed PubMed Citation Articles by Gerard, J.-P. Articles by Adeleine, P. Social Bookmarking                            What's this?