Jean-Christophe Faivre1, Didier Peiffert2, Véronique Vendrely3, Claire Lemanski4, Jean-Michel Hannoun-Levi5, Xavier Mirabel6, Trevor Stanbury7, Julia Salleron8, Francis Guillemin9. 1. Radiation Department, Institut de Cancérologie de Lorraine Alexis-Vautrin, Vandœuvre-lès-Nancy, France; EA 4360 APEMAC, Université de Lorraine, Nancy, France. Electronic address: jeanchristophe.faivre@gmail.com. 2. Radiation Department, Institut de Cancérologie de Lorraine Alexis-Vautrin, Vandœuvre-lès-Nancy, France; EA 4360 APEMAC, Université de Lorraine, Nancy, France. 3. Radiation Department, Centre Hospitalier Universitaire de Bordeaux - Hôpital Haut-Lévêque, Pessac, France. 4. Department of Radiation Oncology, Institut de Cancérologie de Montpellier - Val d'Aurelle, University of Montpellier, France. 5. Radiation Department, Centre Antoine Lacassagne, Nice, France; Université de Nice, Sophia Antipolis, France. 6. Radiation Department, Centre Oscar Lambret, Lille, France. 7. Unicancer, Paris, France. 8. Biostatistics and Epidemiology Department, Institut de Cancérologie de Lorraine - Alexis-Vautrin, Vandœuvre-lès-Nancy, France. 9. EA 4360 APEMAC, Université de Lorraine, Nancy, France; Inserm CIC 1433 Clinical Epidemiology, and Centre Hospitalier Régional Universitaire de Nancy, Vandoeuvre-lès-Nancy, France.
Abstract
BACKGROUND: To carry out a prognosis study of the prospective studies KANAL 2 and ACCORD 03 in order to highlight new prognostic factors of colostomy-free survival in patients with locally advanced anal canal carcinoma. PATIENTS AND METHODS: KANAL 2 and ACCORD 03 were phase 2 and phase 3 multicenter trials with same inclusion criteria: anal canal squamous cell carcinoma of ≥4 cm or pelvic node involvement treated withconformal radiotherapy (45 Gy/25 fractions plus a boost) and concomitant fluorouracyl and cisplatin at weeks 1 and 5. A multivariate analysis of potential factors (patients, tumors, and treatments) was carried out through Cox proportional hazard model. Results were presented as hazard ratio (HR). RESULTS:387 patients were included. In multivariate analysis, age over 55 years (HR = 0.62, p = 0.013), the increase of circumferential tumor spread (between 1/3 and 2/3 and more than 2/3 compared to less than 1/3) (respectively 1.97, p = 0.015 and 2.94, p < 0.001), the skin ulceration (1.57, p = 0.03), the inguinal node involvement (1,98, p < 0.001) and the total radiotherapy dose above 60 Gy (between 60 and 65 Gy (HR = 0.37, p < 0.001) and >65 Gy (HR = 0.61, p = 0.028)) were associated with colostomy-free survival. CONCLUSION: Our study highlights new favorable prognostic factors such as circumferential tumor damage of less than two thirds, age over 55 years, dose escalation boost irradiation and possibly a total radiation dose between 60 and 65 Gy (but the BED dose depends on the overall treatment time). These results could be considered for better selection or stratification of the target population in future trials.
RCT Entities:
BACKGROUND: To carry out a prognosis study of the prospective studies KANAL 2 and ACCORD 03 in order to highlight new prognostic factors of colostomy-free survival in patients with locally advanced anal canal carcinoma. PATIENTS AND METHODS: KANAL 2 and ACCORD 03 were phase 2 and phase 3 multicenter trials with same inclusion criteria: anal canal squamous cell carcinoma of ≥4 cm or pelvic node involvement treated with conformal radiotherapy (45 Gy/25 fractions plus a boost) and concomitant fluorouracyl and cisplatin at weeks 1 and 5. A multivariate analysis of potential factors (patients, tumors, and treatments) was carried out through Cox proportional hazard model. Results were presented as hazard ratio (HR). RESULTS: 387 patients were included. In multivariate analysis, age over 55 years (HR = 0.62, p = 0.013), the increase of circumferential tumor spread (between 1/3 and 2/3 and more than 2/3 compared to less than 1/3) (respectively 1.97, p = 0.015 and 2.94, p < 0.001), the skin ulceration (1.57, p = 0.03), the inguinal node involvement (1,98, p < 0.001) and the total radiotherapy dose above 60 Gy (between 60 and 65 Gy (HR = 0.37, p < 0.001) and >65 Gy (HR = 0.61, p = 0.028)) were associated with colostomy-free survival. CONCLUSION: Our study highlights new favorable prognostic factors such as circumferential tumor damage of less than two thirds, age over 55 years, dose escalation boost irradiation and possibly a total radiation dose between 60 and 65 Gy (but the BED dose depends on the overall treatment time). These results could be considered for better selection or stratification of the target population in future trials.
Authors: Eleonor Rivin Del Campo; Oscar Matzinger; Karin Haustermans; Didier Peiffert; Robert Glynne-Jones; Kathryn A Winter; Andre A Konski; Jaffer A Ajani; Jean-François Bosset; Jean-Michel Hannoun-Levi; Marc Puyraveau; A Bapsi Chakravarthy; Helen Meadows; John Northover; Laurence Collette; Melissa Christiaens; Philippe Maingon Journal: Eur J Cancer Date: 2019-09-28 Impact factor: 9.162