Preoperative Radiotherapy In Rectal Carcinoma Research Articles

Pre-operative radiotherapy for rectal carcinoma? Has the case really been made for short course pre-operative radiotherapy if surgical standards for rectal carcinoma are optimal?

Recent publications on early results of the Dutch trial on pre-operative radiotherapy combined with total mesorectal excision (TME) for resectable rectal cancer have initiated a major swing towards routine radiotherapy of this type. However, detailed analysis of the data so far published shows 23.3% microscopic margin involvement and 23.9% macroscopically poor specimens in a sample group. Since only mobile tumours were selected these figures are too high to validate the claim that the whole series represents 'standardized TME surgery'. The role of pre-operative radiotherapy for resectable rectal cancer undergoing optimal surgery therefore remains open. It may be expected that in future the individual indication for pre-operative radiotherapy will be based on the findings of pre-operative modern fine slice high resolution magnetic resonance imaging (MRI).

Prophylaxis for venous thromboembolism during treatment for cancer: questionnaire survey

Venous thromboembolism is common in patients with cancer and is often the cause of death.1 Patients receiving treatment for cancer are at even greater risk of thromboembolism. Thromboembolism occurs in...

Prognostic values of radiation-induced p53 in adjacent normal mucosa and p21WAF1/CIP1 expression in rectal cancer patients

DNA damage induces p53-mediated cell cycle arrest in which p21WAF1/CIP1, a cyclin-dependent kinase inhibitor, may play a critical role by being regulated via wild-type p53. Although adjuvant preoperative radiotherapy in rectal carcinoma is generally believed to improve the prognosis, it remains unclear which factors control the response. We investigated the interactions between the underlying mechanisms of cell cycle perturbation in response to radiotherapy, and local recurrence and distant metastasis in patients undergoing radical surgery for rectal carcinoma. A retrospective review was carried out in which 63 cases of Dukes' B or C, well or moderately differentiated rectal carcinomas in the lower two-thirds of the rectum, with or without preoperative radiotherapy, were immunohistochemically analyzed using antibodies to p53 and p21WAF1/CIP1. Induced p53 expression in adjacent normal mucosa, as seen in seven of 35 cases with radiotherapy, and mutually exclusive p21WAF1/CIP1 immunoreactivity, was strongly associated with local recurrence (P=0.0001). Furthermore, high p21WAF1/CIP1 expression was associated with a lack of distant metastasis (P=0.032). Our data suggest that there are some cases in which p53 overexpression in adjacent normal mucosa induced by radiotherapeutic treatment might heighten the risk of local recurrence, and that p21WAF1/CIP1 induction independent of the status of the p53 gene showing radiosensitivity might lead to a less distant metastasis.

The Stockholm II trial on preoperative radiotherapy in rectal carcinoma: long-term follow-up of a population-based study

BACKGROUND The Stockholm II trial is a population-based prospective randomized trial on preoperative radiotherapy in rectal carcinoma. METHODS Eligibility criteria were age younger than 80 years and biopsy-proven adenocarcinoma of the rectum judged resectable for cure with an abdominal procedure. Between 1987 and 1993, 557 patients were included. Patients were randomized to preoperative radiotherapy (RT+) followed by surgery within a week (n = 272) or surgery alone (RT−; n = 285). Radiotherapy was given with 25 grays in 1 week to the rectum and pararectal tissues. Curative resection was performed in 481 patients (86%). Median follow-up was 8.8 years. RESULTS Among patients who underwent curative surgery, the incidence of pelvic recurrence was 12% (RT+) and 25% (RT−), respectively (P < 0.001). The overall survival rate in irradiated patients who underwent curative surgery was improved (46%) versus (39%; P < 0.03). For all included patients, the difference was 39% (RT+) compared with 36% (RT−; P = 0.2). Within 6 months of surgery, 13 of 272 (5%) of the irradiated patients died of intercurrent disease versus 4 of 285 (1%) of the nonirradiated (P = 0.02). Cardiovascular death was the main cause of intercurrent death and occurred in 35 of 272 (13%) of the irradiated patients compared with 20 of 285 (7%) among the nonirradiated (P = 0.07). CONCLUSIONS Preoperative short-term radiotherapy reduces the risk of pelvic recurrence and can improve survival after curative surgery for rectal carcinoma. An increased risk of intercurrent death may reduce the benefit especially in elderly patients. Cancer 2001;92:896–902. © 2001 American Cancer Society.

Prognostic value of P53 mutations in rectal carcinoma.

The influence of p53 mutations on the response to ionizing radiation and survival was retrospectively evaluated in patients treated with preoperative radiotherapy for rectal carcinoma. From 1989 to 1991, 86 rectal cancer patients treated by preoperative radiotherapy were included in this series. For all patients, endorectal sonography (to define ultrasonography TNM [uTNM]) was performed before treatment; 19 patients were classified as stage 1, 27 as stage 2 and 40 as stage 3. Response to radiotherapy (39 Gy in 13 fractions delivered in 17 days) was assessed by comparing the uT and the T obtained by histologic examination of the resected specimen (TNM classification). A rectal cancer biopsy was performed before treatment and enabled the search for p53 mutations by denaturing gradient gel electrophoresis (DGGE) and sequencing. The status of the p53 gene was correlated with the response to radiotherapy and survival. Forty-nine percent of the tumors presented abnormal DGGE profiles. The prevalence of p53 mutations was significantly higher in patients who did not respond to radiotherapy (63%) than in those who did respond (34%) (p < 0.01). Presence of a p53 mutation was associated with significantly shorter 5-year survival compared to patients without mutations (p < 0.02). In a multivariate analysis, p53 mutation status remained a prognostic factor independent of tumor posttreatment staging (p < 0.05). p53 status is an independent prognostic factor of response to radiotherapy and survival in rectal carcinoma.

Five fractions of preoperative radiotherapy for selected cases of rectal carcinoma: long-term tumor control and tolerance to treatment

Background: Randomized Swedish studies demonstrate the efficacy of a 5-fraction course of preoperative radiotherapy for rectal carcinoma. The present study evaluates the results in a single U.S. institution over a 20-year period with a similar regimen. Methods and Materials: During the period of 1975–1995, 83 patients received pelvic radiotherapy of 20 Gy/5 fractions, followed by immediate surgery for rectal cancer. These patients represented 21% of cases receiving preoperative treatment; the remainder received 45–50 Gy preoperatively. The 5-fraction course was used for lesions deemed readily resectable but too bulky for conservative endocavitary treatment. Since 1990, it has been our policy to administer postoperative chemotherapy to medically fit patients who prove to have pathologic Stage II or III disease. Patient characteristics including age (mean 65 years, range 23–90), gender (45% male), and location within the rectum were comparable to our previously reported cases that received 45 Gy/25 fractions preoperatively. However, the group selected for 5 fractions preoperatively had relatively fewer lesions that were tethered (20% vs. 61%), circumferential (11% vs. 20%), or near obstructing (1% vs. 16%). Results: With a post treatment follow-up of 1–15 years (mean 4.7), there have been 3 local failures and 12 distant failures, with an actuarial local control of 95%, and disease-specific survival of 77% at 5 and 10 years. Grade ≥ 3 perioperative or late toxicity occurred in 11 cases (13%), including 3 (3.5%) late bowel obstructions. Stage II or III disease was found in 56% of the cases, 74% of which were free of disease at last follow-up. However, patients with Stage II or III lesions that were significantly tethered or fixed had a 40% greater likelihood of recurring than similar stage lesions that were, at most, slightly tethered. Sphincter-preserving surgery was possible in 60% of the patients. In recent years, postoperative chemotherapy has been administered to 16 patients with Stage II or III disease; this has been well tolerated, with only 1 late toxicity (cystitis managed medically). When compared with a matched group of cases receiving conventionally fractionated preoperative radiation, there were no significant differences in perioperative morbidity and nonradiotherapeutic cost generating factors (length of hospital stay, duration of postoperative antibiotics, blood loss at surgery). Conclusion: Patients with resectable rectal cancer who received 20 Gy/5 fractions preoperative radiotherapy to the pelvis had excellent local and distant control of disease. These patients were able to undergo sphincter-preserving surgery and postoperative chemotherapy. It would be of interest to conduct a randomized trial comparing short course with longer course (45 or 50 Gy) preoperative radiotherapy for resectable T3 lesions. The results of this study suggest that, in general, differences in toxicity, local control, and disease-free survival would probably be < 10%. However, since the results of this study suggest that patients with significantly tethered lesions may be better served with the higher dose and longer duration course of radiation, clinical degree of fixation should be included as a stratification parameter, and stopping criteria should be included for tethered lesions.

Designing the optimal surgery for rectal carcinoma

CancerVolume 78, Issue 9 p. 1847-1850 EditorialFree Access Designing the optimal surgery for rectal carcinoma Warren E. Enker M.D., Corresponding Author Warren E. Enker M.D. Department of Surgery, and Division of Colorectal Surgery, Beth Israel Medical Center, New York, New York.350 East 17th Street, Baird Hall 1622, New York, NY 10003===Search for more papers by this author Warren E. Enker M.D., Corresponding Author Warren E. Enker M.D. Department of Surgery, and Division of Colorectal Surgery, Beth Israel Medical Center, New York, New York.350 East 17th Street, Baird Hall 1622, New York, NY 10003===Search for more papers by this author First published: 1 November 1996 https://doi.org/10.1002/(SICI)1097-0142(19961101)78:9<1847::AID-CNCR1>3.0.CO;2-CCitations: 23AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat References 1 Enker WE, Laffer UT, Block GE. Enhanced survival of patients with colon and rectal cancer is based upon wide anatomic resection. Ann Surg 1979; 190: 350– 60. 2 Heald RJ. A new approach to rectal cancer. Br J Hosp Med 1979; 277. 3 Sugihara K, Moriya Y, Akasu T, Fujita S. Pelvic autonomic nerve preservation for patients with rectal carcinoma: oncologic and functional outcome. Cancer 1996; 78: 1871– 80. 4 Church JM, Raudkivi PJ, Hill GL. The surgical anatomy of the rectum: a review with particular relevance to the hazards of rectal mobilization. Int J Colorectal Dis 1987; 2: 158– 66. 5 Beart RW, Steele GD, Menck HR, Chmiel JS, Ocwieja KE, Winchester DP. Management and survival of patients with adenocarcinoma of the colon and rectum: a national survey of the Commission on Cancer. J Am Coll Surg 1995; 181: 225– 36. 6 Enker WE, Thaler HT, Cranor ML, Polyak T. Total mesorectal excision in the operative treatment of rectal cancer. J Am Coll Surg 1995; 181: 335– 46. 7 Heald RJ, Husband EM, Ryall RDH. The mesorectum in rectal cancer surgery: the clue to pelvic recurrence. Br J Surg 1982; 69: 613– 6. 8 Quirke P, Durdey P, Dixon MF, Williams NS. Local recurrence of rectal adenocarcinoma due to inadequate surgical resection. Histopathological study of lateral tumor spread and surgical excision. Lancet 1986; 1: 996– 9. 9 Adam IJ, McHamdee MO, Martin IG. et al. Role of circumferential margin involvement in the local recurrence of rectal cancer. Lancet 1994; 344: 707– 11. 10 Paty PB, Enker WE, Cohen AM, Lauwers GY. Treatment of rectal cancer by low anterior resection with coloanal anastomosis. Ann Surg 1994; 219: 365– 73. 11 MacFarlane J, Ryall RDH, Heald RJ. Mesorectal excision for rectal cancer. Lancet 1993; 341: 457– 60. 12 Enker WE. Potency, cure, and local control in the operative treatment of rectal cancer. Arch Surg 1992; 127: 1396– 1402. 13 Havenga K, Enker WE, McDermott K, Cohen AM, Minsky BD, Guillem J. Male and female sexual and urinary function after total mesorectal excision with autonomic nerve preservation for carcinoma of the rectum. J Am Coll Surg 1996; 182: 495– 502. 14 Minsky BD. Preoperative combined modality treatment for rectal cancer. Oncology 1994; 8: 53– 8. 15 Swedish Rectal Cancer Trial. Local recurrence rates in a randomized multiculture trial of preoperative radiotherapy compared with operation alone in resectable rectal carcinoma. Eur J Surg 1996; 162: 397– 402. 16 Stockholm Colorectal Cancer Study Group. Randomized study on preoperative radiotherapy in rectal carcinoma. Ann Surg Oncology 1996; 3: 423– 30. 17 Dutch Colorectal Cancer Group. Total mesorectal excision (TME) with or without preoperative readiotherapy in the treatment of primary rectal cancer. A multicenter phase III study. January 1996. 18 Norstein J, Bergan A, Langmark F. Risk factors for local recurrence after radical surgery for rectal carcinoma: a prospective multicentre study. Br J Surg 1993; 80 (Suppl): 22. 19 Quirke P. The pathologist's role in the evaluation of local recurrence in rectal cancer. In: Surgical Workshop and Prosection Course, Royal College of Surgeons of London, London, United Kingdom, April 25–26, 1995. Citing Literature Volume78, Issue91 November 1996Pages 1847-1850 ReferencesRelatedInformation

Randomized study on preoperative radiotherapy in rectal carcinoma

Background: A population based prospective randomized trial on preoperative radiotherapy in operable rectal cancer was conducted in Stockholm, Sweden. Five hundred fifty-seven patients from 12 institutions were included with histologically proven, clinically resectable rectal adenocarcinoma. Patients planned for local excision or previously irradiated to the pelvis were excluded. Methods: A total of 272 patients were allocated to preoperative irradiation with 25 Gy in five cycles during 5–7 days to the rectum and the pararectal tissues (RT+ group) and 285 patients were allocated to surgery only (RT− group). The median follow-up time was 50 months. No patient was lost to follow-up. Surgery was considered curative in 479 patients (86%). Results: Locoregional recurrence occurred in 10% of the patients in the RT+ group versus 21% in the RT− group (p<0.01). Among the curatively operated patients, distant metastases occurred in 19% in the RT+ group versus 26% in the RT− group (p=0.02). The overall survival was improved in the irradiated patients (p=0.02). Postoperative complications were more common after irradiation but were usually mild. The postoperative mortality was low in both groups. Conclusion: Preoperative short-term, high-dose radiotherapy as given in this trial reduces the risk of local and distant recurrence and improves survival after curative surgery for rectal carcinoma.

Preoperative radiotherapy in rectal carcinoma—Aspects of acute adverse effects and radiation technique

Purpose : To explain a possible association between treatment technique and postoperative mortality adter preoperative radiotherapy of rectal carcinoma, the dose distributions were compared in model experiments. Methods and Materials : Preoperative radiotherapy with a three-beam technique delivered in five fractions to 25 effects of this treatment, both acute and late, have been low. In a parallel trial using an identical fractionation schedule and total dose but with a two-beam technique, the postoperative mortality was higher. Two-, three-, and four-beam techniques were analyzed in 20 patients with computed tomography based, three-dimensional dose planning. Dose distributions and dose-volume histograms in the planning target volume (PTV) and in the organs at risk were considered. A numerical “biological” model was used to compare the techniques. Results : The two-beam and the four-beam box techniques give the most homogeneous distributions in the PTV, although all techniques results in dose distributions that would be considered adequate, provided 16 MV or higher photon energies are used. Three- and four-beam techniques show advantages over the two-beam technique with respect to organs at risk, particularly the small bowel. With the two-beam technique and the upper beam limit at mid-L4, the volume of the bowel that receives >95% of the prescribed dose, and hence, is included in the treated volume (TV), is more twice as large as that with three- and four-beam techniques, and that of the total body between 1.5 and 2 times as large. The results of the analyses using the biological model indicate that the three- and four-beam techniques result in less small bowel complication rates than the two-bowel technique. The integral energy to the total body is similar for all treatment modalities compared. Conclusions : The volume of bowel included in the TV, rather than the energy imparted to the body, influences postoperative mortality, and emphasizes the importance of precise radiotherapy planing to minimize normal tissue toxicity.

Preoperative radiotherapy for rectal carcinoma

Preoperative radiotherapy for rectal carcinoma