C Bourgier1, S Kerns2, S Gourgou3, C Lemanski4, M Gutowski5, P Fenoglietto4, G Romieu6, N Crompton7, J Lacombe8, A Pèlegrin8, M Ozsahin9, B Rosenstein10, D Azria11. 1. Inserm, U1194, Institut de Recherche en Cancérologie de Montpellier (IRCM), Cancer Institute ICM-Val d'Aurelle, Montpellier Department of Radiation Oncology, Montpellier Cancer Institute ICM-Val d'Aurelle, Montpellier, France. 2. University of Rochester Medical Centre, Rochester Icahn School of Medicine at Mount Sinai, New York, USA. 3. Biostatistics Unit, Cancer Institute ICM-Val d'Aurelle, Montpellier, France. 4. Department of Radiation Oncology, Montpellier Cancer Institute ICM-Val d'Aurelle, Montpellier, France. 5. Department of Surgery, Cancer Institute ICM-Val d'Aurelle, Montpellier, France. 6. Department of Medical Oncology, Cancer Institute ICM-Val d'Aurelle, Montpellier, France. 7. Laboratory of Non-invasive Imaging and Radiation Biology, Van Andel Research Institute, Grand Rapids, USA. 8. Inserm, U1194, Institut de Recherche en Cancérologie de Montpellier (IRCM), Cancer Institute ICM-Val d'Aurelle, Montpellier. 9. Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. 10. Mount Sinai School of Medicine and NYU School of Medicine, New York, USA. 11. Inserm, U1194, Institut de Recherche en Cancérologie de Montpellier (IRCM), Cancer Institute ICM-Val d'Aurelle, Montpellier Department of Radiation Oncology, Montpellier Cancer Institute ICM-Val d'Aurelle, Montpellier, France david.azria@icm.unicancer.fr.
Abstract
BACKGROUND: We present here final clinical results of the COHORT trial and both translational sub-studies aiming at identifying patients at risk of radiation-induced subcutaneous fibrosis (RISF): (i) radiation-induced lymphocyte apoptosis (RILA) and (ii) candidates of certain single-nucleotide polymorphisms (SNPs). PATIENTS AND METHODS: Post-menopausal patients with stage I-II breast cancer (n = 150) were enrolled and assigned to either concurrent (arm A) or sequential radiotherapy (RT)-letrozole (arm B). Among them, 121 were eligible for RILA and SNP assays. Grade ≥2 RISF were the primary end point. Secondary end points were lung and heart events and carcinologic outcome. RILA was performed to predict differences in RISF between individuals. A genome-wide association study was performed to identify SNPs associated with RILA and RISF. Analyses were done by intention to treat. RESULTS: After a median follow-up of 74 months, 5 patients developed a grade ≥2 RISF. No significant difference was observed between arms A and B. Neither grade ≥2 lung nor symptomatic cardiac toxicity was observed. Median RILA value of the five patients who had grade ≥2 RISF was significantly lower compared with those who developed grade ≤1 RISF (6.9% versus 13%, P = 0.02). Two SNPs were identified as being significantly associated with RILA: rs1182531 (P = 4.2 × 10(-9)) and rs1182532 (P = 3.6 × 10(-8)); both located within the PHACTR3 gene on chromosome 20q13.33. CONCLUSIONS: With long-term follow-up, letrozole can safely be delivered concomitantly with adjuvant breast RT. Translational sub-studies showed that high RILA values were correlated with patients who did not develop RISF. REGISTERED CLINICAL TRIAL: NCT00208273.
BACKGROUND: We present here final clinical results of the COHORT trial and both translational sub-studies aiming at identifying patients at risk of radiation-induced subcutaneous fibrosis (RISF): (i) radiation-induced lymphocyte apoptosis (RILA) and (ii) candidates of certain single-nucleotide polymorphisms (SNPs). PATIENTS AND METHODS: Post-menopausal patients with stage I-II breast cancer (n = 150) were enrolled and assigned to either concurrent (arm A) or sequential radiotherapy (RT)-letrozole (arm B). Among them, 121 were eligible for RILA and SNP assays. Grade ≥2 RISF were the primary end point. Secondary end points were lung and heart events and carcinologic outcome. RILA was performed to predict differences in RISF between individuals. A genome-wide association study was performed to identify SNPs associated with RILA and RISF. Analyses were done by intention to treat. RESULTS: After a median follow-up of 74 months, 5 patients developed a grade ≥2 RISF. No significant difference was observed between arms A and B. Neither grade ≥2 lung nor symptomatic cardiac toxicity was observed. Median RILA value of the five patients who had grade ≥2 RISF was significantly lower compared with those who developed grade ≤1 RISF (6.9% versus 13%, P = 0.02). Two SNPs were identified as being significantly associated with RILA: rs1182531 (P = 4.2 × 10(-9)) and rs1182532 (P = 3.6 × 10(-8)); both located within the PHACTR3 gene on chromosome 20q13.33. CONCLUSIONS: With long-term follow-up, letrozole can safely be delivered concomitantly with adjuvant breast RT. Translational sub-studies showed that high RILA values were correlated with patients who did not develop RISF. REGISTERED CLINICAL TRIAL: NCT00208273.
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