Purpose. - To assess the efficacy and the tolerance of a split course hypofractionated (SCH) radiotherapy (RT) protocol in head and neck cancer (HNC) for eldery and/or unfit patients (pts). Patients and methods. - Pts with HNC treated by SCH-RT in two institutions were included retrospectively. The main SCH RT regimen was two courses of 30 grays (Gy)/10 fractions separated by 2-4 weeks, without any systemic therapy. Results. - Between February 2012 and January 2019, 75 consecutive patients were analyzed. The median age was 80 years (range: 45.7-98.2) and 53 (70.7%) were men. Sixty-one (81.3%) pts had stage III/IV disease and 54 (72%) had at least two comorbidities. All of them were treated with intensity-modulated radiotherapy. Median follow-up was 10.6 months (range: 3.1-58.3). Local control at 12 and 24 months was 72.8% IC95%[62-85.5] and 51.7% IC95%[38.1-70.1] respectively. Progression free survival (PFS) at 12 and 24 months were 47.7% IC95%[37.4-60.8] and 41% IC95%[15-36.4] respectively, with a median of 11.5 months IC95%[8.9-17]. OS at 12 and 24 months were 60.4% IC95%[50-73.1] and 41% IC95%[30.6-54.9] respectively, with a median of 19.3 months IC95%[11.9-25.8]. Acute and late grade 3 or higher toxicities occurred for 6 (8%) and 3 (4%) pts. Conclusion. - The present SCH-RT regimen seems effective, well-tolerated and could represent an alternative to palliative strategies for pts deemed unfit for standard exclusive RT. (C) 2020 Societe francaise de radiotherapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.

BACKGROUND AND PURPOSE:Few data are available concerning the safety of bevacizumab (B) in combination with locoregional radiation therapy (RT). The objective of this study was to evaluate the 5-year late toxicity of concurrent B and RT in non-metastatic breast cancer.MATERIALS AND METHODS:This multicentre prospective study included non-metastatic breast cancer patients enrolled in phase 3 clinical trials evaluating B with concurrent RT versus RT alone. All patients received neoadjuvant or adjuvant chemotherapy and normofractionated breast or chest wall RT, with or without regional lymph node RT. B was administered at an equivalent dose of 5 mg/kg once a week for 1 year. The safety profile was evaluated 1, 3 and 5 years after completion of radiotherapy.RESULTS:A total of 64 patients were included between November 2007 and April 2010. Median follow-up was 60 months (12-73) and 5-year late toxicity data were available for 46 patients. The majority of tumours were triple-negative (68.8%), tumour size <2cm (41.3%) with negative nodal status (50.8%). Median total dose of B was 15,000mg and median duration was 11.2 months. No grade ≥3 toxicity was observed. Only 8 patients experienced grade 1-2 toxicities: n = 3 (6.5%) grade 1 lymphedema, n = 2 (4.3%) grade 1 pain, n = 1 (2.2%) grade 2 lymphedema, n = 1 (2.2%) grade 1 fibrosis. Five-year overall survival was 93.8%, disease-free survival was 89% and locoregional recurrence-free survival was 93.1%.CONCLUSION:Concurrent B and locoregional RT are associated with acceptable 5-year toxicity in patients with non-metastatic breast cancer. No grade ≥3 toxicity was observed.

Abstract Background and Purpose: Recent phase 3 clinical trials have evaluated the addition of bevacizumab (B) to standard chemotherapy in the treatment of patients with non-metastatic breast cancer. But few data are available about the tolerance of B with locoregional radiation therapy (RT). The objective was to evaluate the 5 years late toxicities of the concurrent B and RT in non-metastatic breast cancer. Material and methods: This is a multicenter prospective study including non-metastatic breast cancer patients enrolled in phase 3 clinical trials evaluating B with concurrent RT (BEATRICE, BETH, BEVERLY 1, BERVERLY 2) versus RT alone. All patients received neo-adjuvant or adjuvant chemotherapy and normo-fractionated breast or chest wall RT, with or without regional lymph nodes RT. B was administrated as an equivalent of 5 mg/kg every week for 1 year. The safety profile (using the Common Terminology Criteria for Adverse Events version 3.0) was evaluated at 1, 3 and 5 years after the completion of radiotherapy. Results: From October 2007 to January 2012, 151 patients totally included. Median follow-up was 60 months (36-84) and 5 years late toxicities were available for 104 patients (46 with B and RT, 58 with RT alone). Median age was 51 (22-81). 61% of patients received regional lymph nodes RT. The majority of tumor was triple negative (65.6%), tumor size <2cm (50%) and nodal status negative (63.8%). Median total dose of B was 15000 mg (13200 – 18550) and median duration was 11.2 months (11-12.6). No grade ≥3 toxicity was observed. Only 16 patients had grade 1-2 toxicities (8 treated with B and RT, 8 with RT alone): n=4 (3.8%) had grade 1 pain, n=5 (4.8%) had grade 1-2 fibrosis, n=1 (1%) had grade 2 telangiectasia and n=5 (4.8%) had grade 1-2 lymphoedema. No significant difference between the 2 arms was observed. One patient of 46 evaluated had Left Ventricular Ejection Fraction inferior to 50%. At 5 years, overall survival was 93.8%, disease free-survival 89% and locoregional free-survival 93.1 %. Conclusion: Concurrent B and locoregional RT provides acceptable 5-years toxicities in patients with non-metastatic breast cancer. No grade ≥3 toxicity was observed. Citation Format: Clément-Zhao A, Tanguy M-L, Cottu P, De La Lande B, Bontemps P, Lemanski C, Baumann P, Levy C, Peignaux K, Reynaud-Bougnoux A, Gobillion A, Kirova Y. TOxicities of Locoregional Radiotherapy Associated with Bevacizumab in patients with non-metastatic breast cancer (TOLERAB): Final long-term evaluation [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-12-06.

S730 ESTRO 37 Results Median age was 53, 9 years (range 23-90).Classification with VNPI in all patients was high risk depending on: size tumor, grade tumor, age patient and margins.After median follow-up of 112 months, recurrence occurred in 18 patients (10,3%), including 5 patients DCIS ipsilateral recurrence (2,8%), 6 patients ipsilateral invasive carcinoma recurrence (3,5%), 3 patients locoregional recurrence (1,7%) and 4 patients distant metastases (2,3%).Predictive factors for recurrence were identified: presentation, margins and endocrine therapy; clinical presentation (p=0,002), close (<1-9mm) margins (p=0,01) and endocrine adjuvant therapy (p=0,05) were associated to recurrence by univariate analysis.Other factors were analyzed but were not significant in statistical analysis.The 5-year overall survival (OS) was 96.55%.Conclusion Clinical presentation, close margins in tumor and endocrine treatment was identified as predictive factors of recurrence for DCIS treated with mastectomy.In this cases we need consider evaluate radiotherapy as local adjuvant treatment.

Purpose. - To determine the 3 years late toxicity among patients with non-metastatic breast cancer who received concurrent bevacizumab and locoregional radiotherapy. Material and methods. - This is a single-arm, multicentre, prospective study, of the toxicity of adjuvant concomitant association of bevacizumab and radiotherapy in patients with breast cancer. Toxicity was assessed by the Common Terminology Criteria for Adverse Events version 3.0 during the radiotherapy and follow-up clinics at 12 and 36 months after its completion. The study was designed to evaluate the toxicity at one year, 3 years and 5 years. Results. - Sixty-four patients were included from October 2007 to August 2010. All of them received concurrent adjuvant radiotherapy and bevacizumab (in 24 cases after primary systemic treatment). All patients received non-fractionated radiotherapy to breast or chest wall with or without irradiation of regional lymph nodes. Early toxicity has been previously reported. Median follow-up was 46.4 months (range: 18-77 months). Median age was 53 years old (range: 23-68 years). The 3-years overall survival was 93% (range: 87-100%). Evaluation of the toxicity at 3 years was available for 67% of the patients. There was a low rate of toxicity: 14% grade 1 pain, 9% grade 1 fibrosis, 2% grade 1 telangiectasia, 2% grade 1 paresis, 7% grade 1 lymphedema and 2% grade 3 lymphedema. No grade 4 toxicity was observed. No patient had a left ventricular ejection fraction below 50% at 3 years. Conclusions. - Concurrent bevacizumab with locoregional radiotherapy is associated with acceptable 3-years toxicity in patients with breast cancer. (C) 2018 Societe francaise de radiotherapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.

Évaluer l’efficacité et la tolérance d’une radiothérapie hypofractionnée en split course des cancers de la tête et du cou chez 58 patients (âgés ou en mauvais état général). L’étude incluait, à Montbéliard et à Besançon, les cancers de la tête et du cou traités par irradiation hypofractionnée en split course consécutivement de janvier 2012 à décembre 2017. Le schéma principal de traitement était : irradiation conformationnelle avec modulation d’intensité délivrant 30 Gy en dix fractions sur deux semaines (PTV1 = CTV1 + 5 mm/CTV1 = GTV T + N + 5–10 mm + premiers relais ganglionnaires), puis 30 Gy en dix fractions sur 2 semaines (PTV2 = CTV2 + 5 mm/CTV2 = GTV T + N + 5 mm), à 2–4 semaines d’intervalle (GTV : volume tumoral macroscopique ; CTV : volume cible anatomoclinique ; PTV : volume cible prévisionnel). Aucune chimiothérapie n’était associée. Cinquante-huit patients ont été inclus, dont 56 (97 %) atteints de carcinome épidermoïde. L’âge moyen était de 78 ans (extrêmes : 45–94 ans). Quarante-neuf tumeurs (84,5 %) étaient de stade III/IV selon l’ American Joint Committe on Cancer (AJCC) et 26 (45 %) avaient un indice de performance de 2–3. Vingt tumeurs (34,5 %) étaient localisés à la cavité buccale, 17 (29,3 %) à l’oropharynx, dix (17,3 %) à l’hypopharynx, 6 (10,3 %) au larynx et cinq (8,6 %) diverses. Le suivi moyen était de 18,4 mois (extrêmes : 3,1–45,9 mois). Six mois après la radiothérapie, on retrouvait 35 rémissions complètes (60,4 %), 3 réponses partielles (5,2 %), une stabilité (1,7 %) et 19 progressions (32,7 %), incluant des réponses dissociées et décès de toutes causes. La survie globale médiane et à 12 mois étaient respectivement de 23,2 mois (intervalle de confiance à 95 % [IC95 %] : 14,9–26,0) et 67,1 % (IC95 % : 0,56–0,81). Le traitement a été globalement bien suivi et toléré : trois patients étaient non compliants (5,2 %) et il y a eu huit hospitalisations (13,8 %) en cours de radiothérapie. Une toxicité aiguë de grade 1–2 selon le RTOG a été rapportée pour 40 patients (69 %), contre sept (12,1 %) souffrant d’une toxicité grade 3–4. Aucun décès lié au traitement n’a été observé. Il n’y a eu aucune toxicité tardive pour 47 patients (81 %), sept de grade 1–2 (12,1 %) et quatre de grade 3–4 (6,9 %), majoritairement de type dysphagie-dénutrition. La radiothérapie conformationnelle avec modulation d’intensité hypofractionnée en split course (30 + 30 Gy) semble une option curative efficace avec une toxicité acceptable pour des patients âgés et fragiles atteints d’un cancer de la tête et du cou localement évolué.

Purpose/Objectives The purpose of this study was to determine early and late toxicities among patients with non-metastatic breast cancer (BC) receiving concurrent bevacizumab (BV) and radiation therapy (RT). Materials/Methods Multicentre, prospective study, of the toxicity of adjuvant concomitant association of BV and RT in patients with non-metastatic BC enrolled in Phase 3 BEATRICE, BEVERLY and BETH trial. Early and late toxicities were assessed by the Common Terminology Criteria for Adverse Events v. 3.0 during RT, 12 months and 36 months after its completion. Results Sixty-four patients were included from october 2007 to august 2010. They all received adjuvant RT and BV concomitant treatment, plus neo-adjuvant BV for 24 patients. RT was adjuvant and normo-fractionated. Twelve months toxicity was available for 60 patients and 36 months toxicity was available for 43 patients. Median follow-up was 46 months (18-77). Median age was 51 years old (23-68). Among 63 evaluated patients during RT, acute radiation dermatitis was observed in 48 (76%) patients : Grade 1 for 27 (43%), grade 2 for 17 (27%), grade 3 for 4 patients (6%). Grade 2 acute oesophagitis was observed in 1 patient. At 3 years, few toxicities were observed : 6 patients (14%) had grade 1 pain, 4 (9%) had grade 1 fibrosis, one (2%) had grade 1 telangiectasis, one (2%) had grade 1 paresis, 3 (7%) had grade 1 lymphoedema and one grade 3 lymphoedema. No grade 4 toxicity was observed. At 12 months, only one evaluated patient had a LVEF Conclusions Concurrent bevacizumab with locoregional RT is associated with acceptable early and late 3-years toxicities in patients with BC. Determination of late toxicity at 60 months is currently underway. Citation Format: Dautruche A, Belin L, Cottu P, Bontemps P, Lemanski C, De La Lande B, Baumann P, Missohou F, Levy C, Peignaux K, Reynaud-Bougnoux A, Denis F, Gobillion A, Ady Vago N, Fourquet A, Kirova Y. Radiotherapy associated with concurrent bevacizumab in patients with non-metastatic breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-10-17.

OBJECTIVE:To evaluate the safety of the concurrent combination of bevacizumab with adjuvant radiotherapy (B-RT) in breast cancer (BC).METHODS:Multicentre, prospective study, of the toxicity of adjuvant radiotherapy (RT) alone or B-RT in patients with non-metastatic BC enrolled in randomized Phase 3 BEATRICE trial. Early and late toxicities were assessed by the Common Terminology Criteria for Adverse Events v. 3.0 during and 12 months after the completion of RT.RESULTS:From 2007 to 2012, 39 females received adjuvant B-RT and 45 received adjuvant RT alone. Median follow-up was 21.5 months. All patients had triple-negative non-metastatic BC and received adjuvant chemotherapy followed by RT. 90% of the 39 females treated by concurrent B-RT received whole breast irradiation (WBI) with a boost and 4 (10%) received post-mastectomy RT. Lymph node RT was delivered in 49% of the females with internal mammary chain irradiation. The mean duration of bevacizumab was 11.7 months. 38 (84%) females treated by RT alone received WBI with a boost and 16% of the females received post-mastectomy RT. Lymph node RT was delivered in 47% of the females with internal mammary chain RT in 31%. Grade 3 acute dermatitis was observed in 9% of patients receiving B-RT and 5% of patients receiving RT alone with no significant difference. 1 year after the completion of RT, the most common late grade 1-2 toxicities in the B-RT group were pain (18%), fibrosis (8%) and telangiectasia (5%).CONCLUSION:The concurrent bevacizumab with locoregional RT is associated with acceptable early and late 1-year toxicities in patients with BC.ADVANCES IN KNOWLEDGE:The largest series of this association.

The purpose of this multicenter prospective and descriptive study was to determine late toxicities and outcomes among patients with non-metastatic breast cancer receiving concurrent bevacizumab (BV) and radiation therapy (RT) in the clinical trials. Early and late toxicities were assessed and evaluation was available for 63 patients (pts) at 12 months. Acute radiation dermatitis was observed in 48 (76%): grade 1 for 27, grade 2 for 17 and grade 3 for 4 pts. Grade 2 acute oesophagitis was observed in one patient (2%). Little toxicity was described 1 year after the completion of RT: 7 pts (12%): grade 1-2 pain, 3 (5%) presented grade 1 fibrosis, and 2 pts (4%) - telangiectasia. One patient (2%) experienced grade 1 dyspnoea. Five grade 1-2 lymphoedema occurred. Only one patient experienced a LEVF value less than 50% one year after the end of RT. In conclusion, the concurrent BV with locoregional RT provides acceptable toxicities.

Après chirurgie conservatrice et radiothérapie adjuvante pour un cancer du sein, le traitement de référence de la récidive locale est une mastectomie. En présence de facteurs de pronostic favorable, une radiothérapie adjuvante peut être indiquée. L’objectif de l’étude était d’évaluer la faisabilité d’une réirradiation de la paroi thoracique délivrée selon un mode hyperfractionné après mastectomie de rattrapage pour récidive locale, en termes de tolérance immédiate et à long terme. Étude rétrospective monocentrique conduite chez des patientes traitées entre 2007 et 2013. Les critères d’indication de radiothérapie étaient une tumeur classée au moins T3, des emboles lymphatiques ou vasculaires, une invasion cutanée ou de la paroi thoracique, le caractère R1 de la résection, une invasion ganglionnaire massive. Il a été délivré 55 Gy en 50 fractions de 1,1 Gy, à raison de deux fractions quotidiennes espacées de 8h00 par une technique classique tridimensionnelle par des faisceaux tangentiels de 6 MV (avec ou sans bolus). Sur les dix patientes, le taux de contrôle local était de 78 % pour une durée médiane de suivi de 27 mois après la réirradiation (13–68). Seules deux patientes (33 %) ont été atteintes de nouvelles récidives locales, à respectivement 12 et 24 mois. Sept patientes (77 %) ont été atteintes d’une toxicité cutanée aiguë de grade 2 et une patiente d’une toxicité cutanée de grade 3. Trois patientes (33 %) ont été atteintes d’une toxicité cutanée tardive de grade 2, une fibrose et des télangiectasies Aucune patientes n’a souffert de toxicité pulmonaire ou cardiaque. Ce schéma thérapeutique de réirradiation semble bien toléré. Sa validation sur un plus grand effectif est nécessaire.

Purpose/Objective(s)Even if bevacizumab is not approved for the treatment of early breast cancer (BC), few data are available regarding the safety of the concurrent combination of bevacizumab with adjuvant radiation therapy (RT), especially in terms of late toxicity. The aim of this study was to determine early and late loco-regional toxicity among patients with non-metastatic BC treated with this combination in several clinical trials.Materials/MethodsIn our multicenter prospective study, we analyzed toxicities of adjuvant RT in patients with non-metastatic BC receiving concurrent bevacizumab in several clinical trials. Early and late toxicities were assessed by the Common Terminology Criteria for Adverse Events (v3.0). Evaluation was done during RT and 12 months after the end of RT. All patients provided written informed consent before enrollment.ResultsFrom October 2007 to August 2010, 65 women with BC receiving concurrent bevacizumab with adjuvant RT were enrolled in our study. Median follow-up was 21.5 months (range, 1.4-46.8 months). Evaluation at 12 months was available for 62 patients. Mean age was 51 years. Among tumors, 6% were luminal BC, 24% HER2+ and 70% triple negative. A total of 55 patients had an invasive ductal carcinoma. Eighteen patients were stage I (29%), 21 patients stage II (34%), and 22 patients stage IIIB (35%) without patients stage IV (no data for one patient). A total of 23 patients (37%) received neoadjuvant chemotherapy plus bevacizumab followed by surgery then RT, whereas 39 patients (63%) had surgery followed by adjuvant chemotherapy plus bevacizumab then RT. A total of 27 patients (44%) achieved post mastectomy RT and 35 patients (56%) had a whole breast RT with a boost in the surgical bed. Lymph node RT was performed in 42 patients (68%) with internal mammary chain RT in 25 patients (40%). Concurrent trastuzumab with RT and bevacizumab was performed in 14 patients (22%). Mean time of bevacizumab treatment was 10.2 months (range, 2-13 months) and mean total dose of bevacizumab was 15,085 mg (range, 960-28,080 mg). For patients with neoadjuvant bevacizumab, the mean interval between breast surgery and RT was 1.6 months (range, 1-4 months). Early dermatitis occurred in 48 patients: 56% grade 1, 35% grade 2, and 8% grade 3. Grade 2 esophagitis occurred in one patient. One year after the end of the RT, the most common late toxicities were grade 1-2 pain (11%), grade 1 arm lymphedema (6%), grade 2 arm lymphedema (2%), and grade 1 fibrosis (5%). No patients were identified to have grade ≥3 late toxicity. Two patients had cardiovascular events: one with a grade 1 arterial hypertension and one with a grade 1 ventricular extrasystoles.ConclusionsOur results indicate that concurrent bevacizumab with loco-regional RT provide acceptable early and late toxicities after one year in patients with non-metastatic BC. Purpose/Objective(s)Even if bevacizumab is not approved for the treatment of early breast cancer (BC), few data are available regarding the safety of the concurrent combination of bevacizumab with adjuvant radiation therapy (RT), especially in terms of late toxicity. The aim of this study was to determine early and late loco-regional toxicity among patients with non-metastatic BC treated with this combination in several clinical trials. Even if bevacizumab is not approved for the treatment of early breast cancer (BC), few data are available regarding the safety of the concurrent combination of bevacizumab with adjuvant radiation therapy (RT), especially in terms of late toxicity. The aim of this study was to determine early and late loco-regional toxicity among patients with non-metastatic BC treated with this combination in several clinical trials. Materials/MethodsIn our multicenter prospective study, we analyzed toxicities of adjuvant RT in patients with non-metastatic BC receiving concurrent bevacizumab in several clinical trials. Early and late toxicities were assessed by the Common Terminology Criteria for Adverse Events (v3.0). Evaluation was done during RT and 12 months after the end of RT. All patients provided written informed consent before enrollment. In our multicenter prospective study, we analyzed toxicities of adjuvant RT in patients with non-metastatic BC receiving concurrent bevacizumab in several clinical trials. Early and late toxicities were assessed by the Common Terminology Criteria for Adverse Events (v3.0). Evaluation was done during RT and 12 months after the end of RT. All patients provided written informed consent before enrollment. ResultsFrom October 2007 to August 2010, 65 women with BC receiving concurrent bevacizumab with adjuvant RT were enrolled in our study. Median follow-up was 21.5 months (range, 1.4-46.8 months). Evaluation at 12 months was available for 62 patients. Mean age was 51 years. Among tumors, 6% were luminal BC, 24% HER2+ and 70% triple negative. A total of 55 patients had an invasive ductal carcinoma. Eighteen patients were stage I (29%), 21 patients stage II (34%), and 22 patients stage IIIB (35%) without patients stage IV (no data for one patient). A total of 23 patients (37%) received neoadjuvant chemotherapy plus bevacizumab followed by surgery then RT, whereas 39 patients (63%) had surgery followed by adjuvant chemotherapy plus bevacizumab then RT. A total of 27 patients (44%) achieved post mastectomy RT and 35 patients (56%) had a whole breast RT with a boost in the surgical bed. Lymph node RT was performed in 42 patients (68%) with internal mammary chain RT in 25 patients (40%). Concurrent trastuzumab with RT and bevacizumab was performed in 14 patients (22%). Mean time of bevacizumab treatment was 10.2 months (range, 2-13 months) and mean total dose of bevacizumab was 15,085 mg (range, 960-28,080 mg). For patients with neoadjuvant bevacizumab, the mean interval between breast surgery and RT was 1.6 months (range, 1-4 months). Early dermatitis occurred in 48 patients: 56% grade 1, 35% grade 2, and 8% grade 3. Grade 2 esophagitis occurred in one patient. One year after the end of the RT, the most common late toxicities were grade 1-2 pain (11%), grade 1 arm lymphedema (6%), grade 2 arm lymphedema (2%), and grade 1 fibrosis (5%). No patients were identified to have grade ≥3 late toxicity. Two patients had cardiovascular events: one with a grade 1 arterial hypertension and one with a grade 1 ventricular extrasystoles. From October 2007 to August 2010, 65 women with BC receiving concurrent bevacizumab with adjuvant RT were enrolled in our study. Median follow-up was 21.5 months (range, 1.4-46.8 months). Evaluation at 12 months was available for 62 patients. Mean age was 51 years. Among tumors, 6% were luminal BC, 24% HER2+ and 70% triple negative. A total of 55 patients had an invasive ductal carcinoma. Eighteen patients were stage I (29%), 21 patients stage II (34%), and 22 patients stage IIIB (35%) without patients stage IV (no data for one patient). A total of 23 patients (37%) received neoadjuvant chemotherapy plus bevacizumab followed by surgery then RT, whereas 39 patients (63%) had surgery followed by adjuvant chemotherapy plus bevacizumab then RT. A total of 27 patients (44%) achieved post mastectomy RT and 35 patients (56%) had a whole breast RT with a boost in the surgical bed. Lymph node RT was performed in 42 patients (68%) with internal mammary chain RT in 25 patients (40%). Concurrent trastuzumab with RT and bevacizumab was performed in 14 patients (22%). Mean time of bevacizumab treatment was 10.2 months (range, 2-13 months) and mean total dose of bevacizumab was 15,085 mg (range, 960-28,080 mg). For patients with neoadjuvant bevacizumab, the mean interval between breast surgery and RT was 1.6 months (range, 1-4 months). Early dermatitis occurred in 48 patients: 56% grade 1, 35% grade 2, and 8% grade 3. Grade 2 esophagitis occurred in one patient. One year after the end of the RT, the most common late toxicities were grade 1-2 pain (11%), grade 1 arm lymphedema (6%), grade 2 arm lymphedema (2%), and grade 1 fibrosis (5%). No patients were identified to have grade ≥3 late toxicity. Two patients had cardiovascular events: one with a grade 1 arterial hypertension and one with a grade 1 ventricular extrasystoles. ConclusionsOur results indicate that concurrent bevacizumab with loco-regional RT provide acceptable early and late toxicities after one year in patients with non-metastatic BC. Our results indicate that concurrent bevacizumab with loco-regional RT provide acceptable early and late toxicities after one year in patients with non-metastatic BC.

Abstract Purpose/Objectives Few data are available regarding the safety of the concurrent combination of bevacizumab with adjuvant radiotherapy (RT) in breast cancer, especially in terms of late toxicity. The aim of this study was to determine early and late loco-regional toxicities among patients with non-metastatic breast cancer treated with this combination. Materials/Methods In our prospective and descriptive study, we analyzed loco-regional toxicities of adjuvant RT in patients with non-metastatic breast cancer receiving either concurrent bevacizumab or not in the randomized trial BEATRICE. Early and late toxicities were assessed by the Common Terminology Criteria for Adverse Events (v3.0). Evaluation was done during RT and 12 months after the end of RT. All patients provided written informed consent before enrollment. Statistical analysis was performed to analyze toxicity between the two groups. Results From September 2007 to July 2009, we included 84 patients from the randomized trial BEATRICE which evaluate the efficacy and safety of the addition of bevacizumab to standard adjuvant therapy in patients with triple negative breast cancer; 39 women received an adjuvant RT with concurrent bevacizumab and 45 women received an adjuvant RT alone. Evaluation at 12 months was available for all the patients. All patients had a triple negative non-metastatic breast cancer and had an adjuvant chemotherapy then RT. Among patients receiving concurrent bevacizumab with RT, a total of 35 patients (90%) achieved a whole breast irradiation (median dose: 50 Gy) with a boost in the surgical bed (median dose: 16 Gy) and 4 patients (10%) had a post mastectomy RT (median dose 50 Gy); lymph node RT was performed in 19 patients (49%) with internal mammary chain RT in 12 patients (31%). Mean time of bevacizumab treatment was 11.7 months [2.1-12.6] and mean total dose of bevacizumab was 15000 mg [3330-28080]. Among patients receiving RT alone, 38 patients (84%) achieved a whole breast irradiation (median dose: 50 Gy) with a boost in the surgical bed (median dose: 16 Gy) and 7 patients (16%) had a post mastectomy RT (median dose 50 Gy); lymph node RT was performed in 21 patients (47%) with internal mammary chain RT in 14 patients (31%). Radiation treatment parameters were not significantly different between the two groups. Incidence of acute grade 3 dermatitis was 10% in patients receiving bevacizumab associated with RT and 6% in patients receiving RT alone without significant difference. One year after the end of RT, the most common late toxicities in the group receiving bevacizumab and RT were grade 1-2 pain (18%), grade 1-2 fibrosis (8%), grade 1-2 arm lymphedema (8%) and grade 1-2 telangiectasia (6%).There was no significant difference in pain, radiation fibrosis, telangiectasia, arm lymphedema and dyspnea between the two groups. No patient experienced grade 3-4 toxicity in the two groups. Conclusions Our results indicate that concurrent bevacizumab with loco-regional RT provide acceptable early and late toxicities after one year in patients with non-metastatic breast cancer. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-14-11.

L'augmentation de l'incidence du cancer du sein et son taux élevé de mortalité ont justifié la mise en place d'un dépistage mammographique. Dans le Doubs, département français de 500 000 habitants, le dépistage individuel a été généralisé dans les années 1990, il a été suivi par la mise en place du programme de dépistage organisé en 2003.

TPS131 Background: Ductal carcinoma in situ is defined as breast cancer confined to the ducts of the breast without evidence of penetration of the basement membrane. Local treatment quality represents one of the most prognostic factors as half of recurrences are invasive diseases. The main goal of adjuvant radiotherapy after conservative surgery is to decrease local recurrences and to permit breast conservation with low treatment-induced sequelae. Several randomized trials have established the impact of 50 Gy to the whole breast (WB) in terms of local control. Nevertheless, no randomized trial is still available concerning the role of the boost in this disease. The phase III randomized trial "BONBIS" is elaborated to evaluate the impact of a 16-Gy boost after 50 Gy delivered to the whole breast in 25 fractions and 33 days.METHODSA total of 1,950 DCIS breast cancer patients are planned to be enrolled in this trial. Patients will receive the following treatment: (A) WB radiotherapy of 50 Gy in 25 fractions vs. (B) WB radiotherapy of 50 Gy in 25 fractions plus a localized 16-Gy in 8 fractions. The primary endpoint is local-relapse free survival (LRFS). This trial is designed to detect an expected rate in control arm of 7% and 4 % in experimental arm. With 90% power and a=0.05, 137 events are necessary to achieve the main goal. An interim analysis is planned after 50% of observed event. Stratifications are made based on recognized prognostic factors: age, hormonal treatment, differentiation, circumstance of diagnosis, surgical margin, centre. Secondary endpoints are relapse free survival, overall survival, acute and late toxicities, cosmetic results, and quality of life. Translational researches are also planned to identify intrinsic radiosensitivity of normal tissues (radiation-induced apoptosis assay, genome-wide association study) but also predictive models of tumor recurrences. Inclusions have started in November 2008 and correspond to the planned estimation. This trial is supported by the French National Cancer Institute (PHRC 2008).

PURPOSE:This randomized phase III trial investigated the potential benefit of concurrent re-irradiation, fluorouracil and hydroxyurea versus methotrexate for patients treated with palliative intent for recurrent or second primary head and neck squamous cell carcinoma (HNSCC) in previously irradiated area.PATIENTS AND METHODS:Patients with recurrent HNSCC or a second primary not amenable to curative-intent treatment were randomized to the R-RT arm (concurrent re-irradiation, fluorouracil and hydroxyurea) or to the Ch-T arm (methotrexate). The primary endpoint was overall survival (OS). Due to a very slow accrual, the trial was closed after inclusion of 57 patients.RESULTS:Fifty-seven patients were included. All patients died in the two arms with a maximal follow-up of 5years. Although four complete responses were achieved in R-RT arm, (none in Ch-T arm) re-irradiation did not improve OS compared with methotrexate (23% versus 22% at 1year, NS). Sixteen patients experienced clinical grade ⩾3 late toxicities (>6months), 11 in R-RT arm and five in Ch-T arm.CONCLUSIONS:Premature discontinuation of the trial did not allow us to draw firm conclusions. However, there was no suggestion that concurrent re-irradiation, fluorouracil and hydroxyurea improved OS compared to methotrexate alone in patients treated with palliative intent for a recurrent or second primary HNSCC.

Abstract Background Ductal carcinoma in situ is defined as breast cancer confined to the ducts of the breast without evidence of penetration of the basement membrane. Local treatment quality represents one of the most prognostic factors as half of recurrences are invasive diseases. The main goal of adjuvant radiotherapy after conservative surgery is to decrease local recurrences and to permit breast conservation with low treatment-induced sequelae. Several randomized trials have established the impact of 50 Gy to the whole breast (WB) in terms of local control. Nevertheless, no randomized trial is still available concerning the role of the boost in this disease. The phase III randomized trial “BONBIS” is elaborated to evaluate the impact of a 16-Gy boost after 50 Gy delivered to the whole breast in 25 fractions and 33 days. Methods: A total of 1950 patients DCIS breast cancer patients are planned to be enrolled in this trial. Patients will receive the following treatment: (A) WB radiotherapy of 50 Gy in 25 fractions vs. (B) WB radiotherapy of 50 Gy in 25 fractions plus a localized 16-Gy boost in 8 fractions. The primary endpoint is local-relapse free survival (LRFS). This trial is designed to detect an expected rate in control arm of 7% and 4 % in experimental arm. With 90% power and a=0.05, 137 events are necessary to achieve the main goal. An interim analysis is planned after 50% of observed event. Stratifications are made based on recognized prognostic factors: age, hormonal treatment, differentiation, circumstance of diagnosis, surgical margin, centre. Secondary endpoints are relapse free survival, overall survival, acute and late toxicities, cosmetic results, and quality of life. Translational researches are also planned to identify intrinsic radiosensitivity of normal tissues (radiation-induced apoptosis assay, genome-wide association study) but also predictive models of tumor recurrences. Inclusions have started in November 2008 and are not so far than the planned estimation. This trial is granted by the French National Cancer Institute (PHRC 2008) and supported by the French National Society of Radiation Oncology (SFRO). Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT2-06-01.