[show abstract][hide abstract] ABSTRACT: To determine whether increased duration of radiation therapy (RT) and overall treatment (RX) time has a detrimental effect in anal cancer.
Data from Radiation Therapy Oncology Group (RTOG) 87-04 and RTOG 98-11 trials were combined to form three treatment groups: RT/fluorouracil (FU)/mitomycin (n = 472), RT/FU/cisplatin (n = 320), and RT/FU (n = 145). Cox proportional hazards models were used with the following variables: RT duration, RT intensity, RX duration, treatment group, age, sex, Karnofsky performance score (KPS), T stage, N stage, and RT dose.
In the univariate analysis, there was a significant association between RX duration and colostomy failure (CF; hazard ratio [HR] = 1.51; 95% CI, 1.07 to 2.14; P = .02), local failure (HR = 1.52; 95% CI, 1.14 to 2.03; P = .005), locoregional failure (HR = 1.51; 95% CI, 1.15 to 1.98; P = .003), and time to failure (HR = 1.40; 95% CI, 1.10 to 1.79; P = .007). The significance of RX duration was maintained after adjusting for treatment group. In multivariate modeling there was a trend toward an association between RX duration and CF (HR = 1.57; 95% CI, 0.98 to 2.50; P = .06) and a statistically significant association with local failure (HR = 1.96; 95% CI, 1.34 to 2.87; P = .0006). Age, sex, KPS, T stage, N stage, and RT dose, but not RT duration, RT intensity, or RX duration, were found to be statistically significant predictors of OS and colostomy-free survival.
Total treatment time, but not duration of radiation therapy, seems to have a detrimental effect on local failure and colostomy rate in anal cancer. Induction chemotherapy may contribute to local failure by increasing total treatment time.
Journal of Clinical Oncology 10/2010; 28(34):5061-6. · 18.04 Impact Factor
[show abstract][hide abstract] ABSTRACT: Radiation Therapy Oncology Group (RTOG) 92-08 began as a single arm, Phase II trial for patients with anal cancer consisting of radiation (RT) + 5-flourouracil + mitomycin-C with a mandatory 2-week break and was amended after completion to evaluate the same treatment regimen without a treatment break. Long-term efficacy and late toxicity reporting are the specific aims of this study.
Survivals were estimated with the Kaplan-Meier method. Overall survival (OS) was compared with RTOG 87-04 with the log-rank test. Time to local failure, regional failure, locoregional failure (LRF), distant metastases, second primary, and colostomy failure were estimated by the cumulative incidence method. LRF was compared with RTOG 87-04 using the Gray's test.
Forty-seven patients entered in the mandatory treatment break cohort. The study was reopened in 1995 to the no mandatory treatment break cohort completing accrual with 20 patients in 1996. Of 67 total patients, 1 patient in the mandatory treatment break portion of the study did not receive any protocol treatment and is excluded from analyses. After adjusting for tumor size, neither cohort showed a statistically significant difference in OS or LRF compared with the RTOG 87-04 mitomycin-C arm. No patient in either cohort experienced a Grade 3 or higher late toxicity.
No statistically significant differences were seen in OS or LRF when compared to the mitomycin-C arm of RTOG 87-04, but the sample sizes for the mandatory break cohort and the no mandatory break cohort are small. Late toxicity was low and similar for the treatment cohorts.
International Journal of Radiation OncologyBiologyPhysics 06/2008; 72(1):114-8. · 4.52 Impact Factor
[show abstract][hide abstract] ABSTRACT: It is common belief that patients failing chemoradiation therapy (CRT) for squamous cell cancer of the anus (SCCA) can be salvaged with subsequent surgery. The aim of this study was to examine our experience with abdominoperineal resection (APR) in cases of persistent or recurrent SCCA with an emphasis on survival and morbidity. All patients between 1985 and 2001 undergoing salvage APR were reviewed. Details of CRT, surgery, tumor characteristics, postoperative complications, and survival were obtained from medical records. There were 22 patients (13 women, 9 men) with a mean age of 62 years (range=42-87). Initial tumors were AJCC stage 2 (16 cases), 3A (3 cases), and 4 (1 case). Mean radiation dose was 47.6 Gy (30-60) and most received concomitant 5-FU. In 20 patients, APR was felt to be "curative" but only 13 (65%) had negative margins on final pathology. Thirteen (59%) perineal wounds broke down with a median time to healing of 7 months. Tumor differentiation (p=0.02) and positive resection margins (p=0.004) were significantly associated with DFS (5-year DFS of 37%). Salvage APR in patients with poorly differentiated tumors or positive resection margins has a high morbidity and poor survival and may warrant a planned APR after CRT instead.
Journal of Gastrointestinal Surgery 01/2008; 11(12):1744-51. · 2.36 Impact Factor
[show abstract][hide abstract] ABSTRACT: Because of increased toxicity, full doses of gemcitabine and radiation therapy cannot routinely be given concurrently. The purpose of the present study was to determine the toxicity and response to treatment with full-dose gemcitabine given between cycles of split-course radiation therapy (nonconcurrent treatment) for inoperable periampullary adenocarcinoma. Treatment consisted of 3 6 week courses for a total of 18 weeks: 1000 mg/m gemcitabine intravenous bolus once a week x 2 weeks; 1 week break; 2 weeks of radiation therapy (1.8 Gy per fraction); 1 week break x 3. The total dose of radiation consisted of 45 Gy to the tumor + regional nodes followed by a 5.4-Gy boost. Patients were restaged at week 15 and at the completion of all treatment. Patients underwent resection if there was sufficient response. A total of 42 patients (40 pancreatic, 1 gallbladder, 1 biliary tract) were enrolled between March 1999 and July 2002. All but 2 medically inoperable patients had evidence of major vessel involvement. Median age was 63 years (range, 40-80 years). All patients were evaluable for response. There were 10 objective partial responses (24%). Six responders underwent resection with a mean survival of 18 months. Mean survival for all 42 patients was 10.3 months (range, 2.0-32.5 months; median, 9.5 months). Four patients experienced grade 3 or 4 gastrointestinal toxicity. Alternating cycles of split-course radiotherapy and gemcitabine chemotherapy permits the delivery of full doses of both modalities with acceptable tolerance. Despite the prolongation in radiation treatment time because of split-course treatment, patients with sufficient response were able to undergo resection.
American journal of clinical oncology 07/2005; 28(3):234-41. · 2.21 Impact Factor
[show abstract][hide abstract] ABSTRACT: Some patients with colon cancer have a high risk of local recurrence postoperatively. This trial was undertaken to determine whether radiation therapy added to an adjuvant chemotherapy regimen improves outcome in high-risk patients.
Patients with resected colon cancer with tumor adherence or invasion of surrounding structures, or with T3N1 or T3N2 tumors of the ascending or descending colon were randomly assigned to receive fluorouracil and levamisole therapy with or without radiation therapy. Patients who received chemotherapy and radiation therapy (chemoRT) received 45 to 50.4 Gy in 25 to 28 fractions beginning 28 days after starting chemotherapy. Patient enrollment was terminated because of slow accrual after 222 patients enrolled (original goal was 700 patients); 187 patients were assessable.
Overall 5-year survival was 62% for chemotherapy patients and 58% for chemoRT patients (P >.50); 5-year disease-free survival was 51% for both groups (P >.50). Toxicity (>/= grade 3) occurred in 42% of chemotherapy patients and 54% of chemoRT patients (P =.04). Leukopenia (>/= grade 3) occurred in 10% of chemotherapy patients and 22% of chemoRT patients (P =.02). No significant difference in nonhematologic toxicity (>/= grade 3) was observed between chemoRT and chemotherapy patients (35% v 44%; P =.26).
Patients who received chemotherapy or chemoRT had similar overall survival and disease-free survival. Toxicity was higher among chemoRT patients. These results must be interpreted with caution because of the high number of ineligible patients and the limited power of the study to detect potentially meaningful differences.
Journal of Clinical Oncology 08/2004; 22(16):3277-83. · 18.04 Impact Factor
[show abstract][hide abstract] ABSTRACT: The role of 3-dimensional treatment planning in the management of rectal cancer is not well defined. This report reviews technical guidelines for simulation, defining target volumes, and suggested beam configurations. Outcome from pilot clinical trials, with emphasis on the impact of volume and dose on tumor response and treatment morbidity is discussed.
Seminars in Radiation Onchology 11/2003; 13(4):433-40. · 3.97 Impact Factor
[show abstract][hide abstract] ABSTRACT: To improve the resectability and long-term local control of locally advanced rectal cancer, we have initiated a radiation dose-escalation trial. It is hoped that the radioprotector amifostine will sufficiently reduce rectal morbidity (without also reducing tumor response) to permit increasing radiation doses. Only 6 patients have been treated at the first dose level (45 Gy with a 9-Gy boost and concurrent continuous infusion of 5-fluorouracil). During treatment, daily stool frequency improved or was stable. There was one case of transitory severe proctitis/enteritis. Four of the six patients achieved objective responses to preoperative treatment. These very early results suggest that the use of amifostine does not interfere with tumor response and that it may facilitate the delivery of higher boost doses to the rectum.
[show abstract][hide abstract] ABSTRACT: Rectal adenocarcinoma almost invariably requires extirpative surgery to be cured. Although radiation therapy and concurrent chemotherapy often will elicit dramatic responses, the treatment morbidity limits the tolerable dose of radiation to about 45 to 50 Gy. Strategies to reduce procto/enteritis may permit higher doses of radiation to be delivered. This report reviews a recently activated radiation dose-escalation study that combines the radioprotector amifostine (Ethyol, WR-2721) with 3-dimensionally planned radiation therapy and concurrent infusional 5-fluorouracil chemotherapy.