Préoperative hyperfractionated accelerated radiotherapy (HART) in locally advanced rectal cancer (LARC) immediately followed by surgery. A prospective trial.
Coucke, Philippe ; ; et al
in Radiotherapy & Oncology (2006), 79
Abstract Background and purpose: We aim to report on local control in a phase II trial on preoperative hyperfractionated and accelerated radiotherapy schedule (HART) in locally advanced resectable rectal ... [more ▼]
Abstract Background and purpose: We aim to report on local control in a phase II trial on preoperative hyperfractionated and accelerated radiotherapy schedule (HART) in locally advanced resectable rectal cancer (LARC). This fractionation schedule was designed to keep the overall treatment time (OTT) as short as possible. Patients and methods: This is a prospective trial on patients with UICC stages II and III rectal cancer. The patients were submitted to a total dose of 41.6 Gy, delivered in 2.5 weeks at 1.6 Gy per fraction twice a day with a 6-h interfraction interval. Surgery was performed within 1 week after the end of irradiation. Adjuvant chemotherapy was delivered in a subset of patients. Results: Two hundred and seventy nine patients were entered and 250 are fully assessable, with a median follow-up of 39 months. The 5-years actuarial local control (LC) rate is 91.7%. The overall survival (OS) is 59.6%. The freedom from disease relapse (FDR) is 71.5%. Downstaging was observed in 38% of the tumors. Conclusion: The actuarial LC at 5 years is 91.7%, although we are dealing with stages II–III LARC, mainly located in the lower rectum (median distanceZ5 cm). The pattern of failure is dominated by distant metastases and treatment intensification will obviously require a systemic approach. q 2006 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 79 (2006) 52–58. [less ▲]Detailed reference viewed: 43 (1 ULg)
CPT-11 and concomitant hyperfractionated accelerated radiotherapy induce efficient local control in rectal cancer patients: results from a phase II
; ; et al
in British Journal of Cancer (2006), 95
Patients with rectal cancer are at high risk of disease recurrence despite neoadjuvant radiochemotherapy with 5-Fluorouracil (5FU), a <br />regimen that is now widely applied. In order to develop a ... [more ▼]
Patients with rectal cancer are at high risk of disease recurrence despite neoadjuvant radiochemotherapy with 5-Fluorouracil (5FU), a <br />regimen that is now widely applied. In order to develop a regimen with increased antitumour activity, we previously established the <br />recommended dose of neoadjuvant CPT-11 (three times weekly 90 mgm 2) concomitant to hyperfractionated accelerated <br />radiotherapy (HART) followed by surgery within 1 week. Thirty-three patients (20 men) with a locally advanced adenocarcinoma of <br />the rectum were enrolled in this prospective phase II trial (1 cT2, 29 cT3, 3 cT4 and 21 cNþ). Median age was 60 years (range 43– <br />75 years). All patients received all three injections of CPT-11 and all but two patients completed radiotherapy as planned. Surgery <br />with total mesorectal excision (TME) was performed within 1 week (range 2–15 days). The preoperative chemoradiotherapy was <br />overall well tolerated, 24% of the patients experienced grade 3 diarrhoea that was easily manageable. At a median follow-up of 2 <br />years no local recurrence occurred, however, nine patients developed distant metastases. The 2-year disease-free survival was 66% <br />(95% confidence interval 0.48–0.83). Neoadjuvant CPT-11 and HART allow for excellent local control; however, distant relapse <br />remains a concern in this patient population. [less ▲]Detailed reference viewed: 14 (1 ULg)
Preoperative hyperfractionated acclerated radiotherapy (HART) and concomittant CPT-11 in advanced rectal carcinoma. A phase I study.
; ; et al
in International Journal of Radiation, Oncology, Biology, Physics (2003), 56(5), 1288-1294
Purpose: Patients with locally advanced rectal carcinoma are at risk for both local recurrence and distant metastases. We demonstrated the efficacy of preoperative hyperfractionated accelerated ... [more ▼]
Purpose: Patients with locally advanced rectal carcinoma are at risk for both local recurrence and distant metastases. We demonstrated the efficacy of preoperative hyperfractionated accelerated radiotherapy (HART). In this Phase I trial, we aimed at introducing chemotherapy early in the treatment course with both intrinsic antitumor activity and a radiosensitizer effect. Methods and Materials: Twenty-eight patients (19 males; median age 63, range 28–75) with advanced rectal carcinoma (cT3: 24; cT4: 4; cN : 12; M1: 5) were enrolled, including 8 patients treated at the maximally tolerated dose. Escalating doses of CPT-11 (30–105 mg/m2/week) were given on Days 1, 8, and 15, and concomitant HART (41.6 Gy, 1.6 Gy bid 13 days) started on Day 8. Surgery was to be performed within 1 week after the end of radiochemotherapy. Results: Twenty-six patients completed all preoperative radiochemotherapy as scheduled; all patients underwent surgery. Dose-limiting toxicity was diarrhea Grade 3 occurring at dose level 6 (105 mg/m2). Hematotoxicity was mild, with only 1 patient experiencing Grade 3 neutropenia. Postoperative complications (30 days) occurred in 7 patients, with an anastomotic leak rate of 22%. Conclusions: The recommended Phase II dose of CPT-11 in this setting is 90 mg/m2/week. Further Phase II exploration at this dose is warranted. © 2003 Elsevier Inc. [less ▲]Detailed reference viewed: 19 (2 ULg)
Predictive factors in locally advanced rectal cancer treated with preoperative hyperfractionated and accelerated radiotherapy.
; ; et al
in Human Pathology (2003), 34(6), 541-548
This study examines the prognostic significance of pathologic factors in patients with primary locally advanced rectal cancer treated prospectively with preoperative radiotherapy. From 1992 to 1998, 104 ... [more ▼]
This study examines the prognostic significance of pathologic factors in patients with primary locally advanced rectal cancer treated prospectively with preoperative radiotherapy. From 1992 to 1998, 104 patients with rectal cancer of grades T3 or T4 and any N underwent preoperative radiotherapy followed by surgical resection. Survival curves were estimated according to the Kaplan-Meier method. Correlation of outcome with clinicopathologic variables (pathologic tumor and lymph node staging, histology, radial resection margin [RRM], clearance, vessel involvement, and tumor regression grade [TRG], quantitated in 5 grades) was evaluated using the Cox proportional hazards model. None of the patients achieved a histologically confirmed complete pathologic response, but 79% of the patients showed partial tumor regression (TRG2–4) and 21% did not show any tumor regression (TRG5). Among the tumors, 22% were of a mucinous type. The RRM was free of tumor in 76% of the surgical specimens. The median clearance was 2 mm. Vascular invasion was present in 37 cases (36%). In the univariate analysis, lymph node metastases, absence of tumor regression, positive RRM, and vascular invasion were correlated with adverse overall survival and diseasefree survival; absence of tumor regression, positive RRM, and clearance <2 mm were correlated with local recurrences; and advanced pT stage was correlated only with disease-free survival. However, in the multivariate analysis, only lymph node metastases and RRM were independent prognostic factors for overall survival and disease-free survival, and clearance <2 mm was an independent prognostic factor for local control. Pathologic parameters remain strong determinants of local recurrence and survival in locally advanced rectal cancer, treated preoperatively with hyperfractionated and accelerated radiotherapy. We show that patients with advanced pT, positive lymph nodes, vascular invasion, positive RRM, clearance <2 mm, or absence of tumor regression are known to have poor clinical outcome. HUM PATHOL 34:541-548. © 2003 Elsevier Inc. All rights reserved. Abbreviations: , computed tomography; DFS, disease-free survival; HART, hyperfractionated accelerated radiotherapy; OS, overall survival; RRM, radial resection margin; TRG, tumor regression grade. [less ▲]Detailed reference viewed: 22 (4 ULg)