To assess the possibility and safety of a boost delivery up to74 Gy, based on lung tumour early response to on-treatment FDG-PET /CT (42 Gy), in inoperable patients with stage III non-small-cell lung cancer (NSCLC)treated with concomitant radio-chemotherapy (RCT). 158 patients were prospectively included in a multicentre phase II-III study. Patients were randomized into two groups: patients from arm A (experimental) with residual metabolism on FDG-PET2 at 42 Gy received a radiation boost (74 Gy), while patients without residual uptake on FDG-PET2 at 42 Gy and patients in arm B (standard) received a standard radiotherapy (RT) dose (66 Gy). Local control rate (LCR%), median overall survival (OS, months), and progression-free survival (PFS) were analysed for three years after the end of RCT. FDG-PET parameters were measured at baseline (PET1), 42 Gy (PET2), and 6 months post-RCT (PET3). All patients were evaluated with the RECIST 1.1 criteria. The main objective was the LCR at 1 year after RCT. Patient demographic characteristics and FDG-PET parameters were similar between the two arms (A vs. B). The mean age was 62.3 years; 53.2% of lesions were stage IIIA and 45.6% were stage IIIB. The mean radiation dose was 71.65 Gy for experimental arm and 66 Gy for standard arm (p < 0.001). The median follow-up time was 45.1 months. The LCR at 1 year after RCT was 77.6% [95% CI: 67.6% – 87.6%] in arm A and 71.2% [95% CI : 60.8% - 81.6%] in arm B. The median OS and the PFS (months) were respectively NR [95% CI: 40.9 – NR] in arm A and 43.3 [95% CI: 33.4 - NR] in arm B, and 22.3 [95% CI: 14.8 – 33.7] in arm A and 12.3 [95% CI : 9.4 – 23.3] in arm B. Using multivariate analysis, ΔSUVmax > 66% (p < 0.01), Δ metabolic tumoral volume (MTV) > 100% (p = 0.04) between PET1 and PET3, and the boost realization (p = 0.05) were the only predictors of PFS. There were less acute or late toxicity in boost radiation arm. Boost at 74 Gy based on interim FDG-PET is feasible and safe during thoracic RCT, without acute or late toxicity. Boost administration, ΔSUVmax, ΔMTV seem to be prognostic factors in patients with stage III inoperable NSCLC.

PURPOSE:To report characteristics and outcome of breast cancer after irradiation for Hodgkin lymphoma with special focus on breast conservation surgery. PATIENTS AND METHODS:Medical records of 72 women who developed either ductal carcinoma in situ or stage I-III invasive carcinoma of the breast after Hodgkin lymphoma between 1978 and 2009 were retrospectively reviewed. RESULTS:Median age at Hodgkin lymphoma diagnosis was 23 years old. Median total dose received by the mediastinum was 40 Gy, mostly by a mantle field technique. Breast cancer occurred after a median time interval of 21 years. Ductal invasive carcinoma and ductal carcinoma in situ represented respectively 71% and 19% of the cases. Locoregional treatment for breast cancer consisted of mastectomy with or without radiotherapy in 39 patients and of lumpectomy with or without adjuvant radiotherapy in 32 patients. The isocentric lateral decubitus radiation technique was used in 17 patients after breast conserving surgery (57%). With a median follow-up of 7 years, 5-year overall survival rate and locoregional control rate were respectively 74.5% and 82% for invasive carcinoma and 100% and 92% for in situ carcinoma. Thirteen patients died of progressive breast cancer and contralateral breast cancer was diagnosed in ten patients (14%). CONCLUSIONS:Breast conserving treatment can be an option for breast cancers that occur after Hodgkin lymphoma despite prior thoracic irradiation. It should consist of lumpectomy and adjuvant breast radiotherapy with use of adequate techniques, such as the lateral decubitus isocentric position.

581 Background: To evaluate the influence of loco-regional radiotherapy and adjuvant chemotherapy on the outcome of breast cancer patients with axillary lymph node micrometastases (MMTS) or isolated tumor cells (ITC). Methods: Between 1995 and 2005, 10,296 breast cancer patients were treated in our institution, 177 of them for unilateral breast cancer with MMTS (147) or ITC (30) by breast-conserving surgery or total mastectomy. The impact of chemotherapy and irradiation on overall survival (OS), disease-free survival (DFS) and metastases-free survival (MFS) were studied. Results: Median follow-up time was 77 months (mean 83.2 months), OS at 5 years 94.1 (89.2- 96.9), DFS 90.1 (84.4–93.9). No improvement in OS, DFS nor MFS were found in patients treated by supraclavicular irradiation (127/177), internal mammary lymph nodes (IMLN) irradiation (103/177) or axillary region irradiation (52/177). The OS, DFS and MFS were similar in patients with (93) or without (84) chemotherapy. Conclusions: Neither loco-regional radiotherapy nor adjuvant chemotherapy influenced the outcome of breast patients with MMTS or ITC. No significant financial relationships to disclose.

Purpose. - Neoadjuvant chemotherapy generally induces significant changes in the pathological extent of disease. This potential down-staging challenges the standard indications of adjuvant radiation therapy. We assessed the utility of lymph node irradiation in breast cancer patients with pathological N0 status (pN0) after neoadjuvant chemotherapy and breast-conserving surgery.Patients and materials. - Among 1054 breast cancer patients treated with neoadjuvant chemotherapy in our institution between 1990 and 2004, 248 patients with clinical N0 or N1-N2 lymph node status at diagnosis had pN0 status after neoadjuvant chemotherapy and breast-conserving surgery. Cox regression analysis was used to identify factors influencing locoregional recurrence-free survival, disease-free survival and overall survival.Results. - All 248 patients received breast irradiation, and 158 patients (63.7%) also received lymph node irradiation. With a median follow-up of 88 months, the 5-year locoregional recurrence-free survival and overall survival rates were respectively 89.4% and 88.7% with lymph node irradiation and 86.2% and 92% without lymph node irradiation (no significant difference). Survival was poorer among patients who did not have a pathological complete primary tumor response (pCR) (hazards ratio [HR] = 3.05; 95% Cl, 1.17 to 7.99) and in patients with N1-N2 clinical status at diagnosis ([HR] = 2.24; 95% Cl, 1.15 to 4.36). Lymph node irradiation did not significantly affect survival.Conclusions. - Relative to combined breast and local lymph node irradiation, isolated breast irradiation does not appear to be associated with a higher risk of locoregional relapse or death among breast cancer patients with pN0 status after neoadjuvant chemotherapy. These results need to be confirmed in a prospective study. (C) 2010 Societe francaise de radiotherapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.

Le down-staging tumoral après chimiothérapie néoadjuvante pourrait modifier les indications d’irradiation adjuvante des aires ganglionnaires. L’objectif était d’évaluer l’intérêt de l’irradiation des aires ganglionnaires chez les patientes atteintes d’un cancer du sein sans envahissement ganglionnaire (pN0) après chimiothérapie néoadjuvante et chirurgie mammaire conservatrice. Parmi 1054 patientes prises en charge entre 1990 et 2004 par chimiothérapie néoadjuvante pour un cancer du sein, 248 (23,5 %) étaient indemnes d’envahissement ganglionnaire après chimiothérapie néoadjuvante et chirurgie mammaire conservatrice. Les survies sans récidive locorégionale, sans maladie et globale ont été analysées en fonction de l’irradiation ou non des aires ganglionnaires. Toutes les patientes (248) ont reçu une irradiation mammaire, associée pour 158 (63,7 %) d’entre elles à une irradiation adjuvante des aires ganglionnaires. Après un suivi médian de 88 mois, les taux de survie sans récidive locorégionale et de survie globale à cinq ans étaient respectivement de 89,4 % et 88,7 % avec irradiation adjuvante des aires ganglionnaires et 86,2 % et 92 % sans irradiation adjuvante des aires ganglionnaires (NS). En analyse multifactorielle, l’absence de réponse histologique complète de la tumeur (hazard ratio [HR] = 3,05 ; intervalle de confiance à 95 % [IC 95 %], 1,17 à 7,99 ; p = 0,023) et le statut cN1-N2 lors du diagnostic (HR = 2,24 ; IC 95 %, 1,15 à 4,36 ; p = 0,017) étaient associés à une diminution de la survie globale. L’absence d’irradiation adjuvante des aires ganglionnaires n’avait d’effet délétère ni sur la survie sans maladie ni sur la survie globale. Nos résultats suggèrent que l’irradiation mammaire seule ne serait pas associée à un risque plus élevé de récidive locorégionale ou de décès chez les patientes atteintes d’un cancer du sein classé pN0 après chimiothérapie néoadjuvante. Neoadjuvant chemotherapy generally induces significant changes in the pathological extent of disease. This potential down-staging challenges the standard indications of adjuvant radiation therapy. We assessed the utility of lymph node irradiation in breast cancer patients with pathological N0 status (pN0) after neoadjuvant chemotherapy and breast-conserving surgery. Among 1054 breast cancer patients treated with neoadjuvant chemotherapy in our institution between 1990 and 2004, 248 patients with clinical N0 or N1-N2 lymph node status at diagnosis had pN0 status after neoadjuvant chemotherapy and breast-conserving surgery. Cox regression analysis was used to identify factors influencing locoregional recurrence-free survival, disease-free survival and overall survival. All 248 patients received breast irradiation, and 158 patients (63.7%) also received lymph node irradiation. With a median follow-up of 88 months, the 5-year locoregional recurrence-free survival and overall survival rates were respectively 89.4% and 88.7% with lymph node irradiation and 86.2% and 92% without lymph node irradiation (no significant difference). Survival was poorer among patients who did not have a pathological complete primary tumor response (pCR) (hazards ratio [HR] = 3.05; 95% CI, 1.17 to 7.99) and in patients with N1-N2 clinical status at diagnosis ([HR] = 2.24; 95% CI, 1.15 to 4.36). Lymph node irradiation did not significantly affect survival. Relative to combined breast and local lymph node irradiation, isolated breast irradiation does not appear to be associated with a higher risk of locoregional relapse or death among breast cancer patients with pN0 status after neoadjuvant chemotherapy. These results need to be confirmed in a prospective study.

The value of lymph node irradiation (LNI) for breast cancer (BC) patients with pathologic N0 status (pN0) after neoadjuvant chemotherapy (NAC) and breast-conservative surgery (BCS) is unknown. We compared the outcomes of pN0 patients following NAC and BCS who received breast radiotherapy (BRT) with or without LNI. Among 1,054 BC patients treated with NAC between 1990 and 2004, 248 patients (23.5%) had pN0 status after NAC and BCS. We limited our study to the patients who were treated with BCS as all patients who were selected for postmastectomy irradiation had LNI. Demographic data, tumor characteristics, and treatments were prospectively recorded. Outcome was assessed in relation to locoregional recurrence-free survival (LRR-FS), disease-free survival (DFS), and overall survival (OS). Among 248 patients (T1–T2: 193 patients, T3: 41 patients, T4: 14 patients, cN0: 164 patients, cN1–N2: 84 patients), 158 (63.7%) received BRT and LNI and 90 (36.3%) received BRT alone. Younger age (p = 0.005), N1–N2 clinical lymph node status at diagnosis (p = 0.0001) and internal or central localizations (p < 0.00001) were associated with LNI. With a median follow-up of 88 months (15–218), 2 patients experienced nodal recurrence in the BRT and LNI group compared with 3 patients in the BRT group. The 5-year LRR-FS rates were 89.4% in the BRT and LNI group compared with 86.2% in the BRT group (p > 0.5). Among 164 cN0 pN0 patients, the 5-year DFS and OS rates were 83% and 89.3% vs. 85% and 94.5%, respectively, according to whether they received LNI (n = 89) or not (n = 75; p > 0.05). Among 84 cN1–N2 pN0 patients, the 5-year DFS and OS rates were 72% and 87.9% vs. 79.4% and 80%, respectively, according to whether they received LNI (n = 69) or not(n = 15; p > 0.05). In a multivariate analysis, absence of pathologic complete response of the tumor (hazard ratio [HR] = 3.05; 95% CI, 1.17–7.99; p = 0.023) and N1–N2 clinical status at diagnosis (HR, 2.24; 95% CI, 1.15–4.36; p = 0.017) were associated with worse survival. Omission of LNI had no effect on either DFS (HR, 1.18; 95% CI, 0.64–2.15) or OS (HR, 1.19; 95% CI, 0.48–2.94). Our results suggest that BRT alone is not associated with a higher risk of LRR or death in BC patients with pN0 status after NAC. Whether this allows the omission of LNI for such strategy should be addressed prospectively.

Dans l’approche therapeutique conservatrice du cancer du sein, un des buts de la radiotherapie est celui d’obtenir une dose homogene dans la totalite de la glandemammaire (et dans les aires ganglionnaires, lorsque cela est indique), en evitant les surdosages qui pourraient engendrer des reactions aigues ou tardives, et les sous-dosages qui pourraient etre a l’origine des recidives. Les organes a risque, dont la protection est necessaire, sont les poumons et le cœur (particulierement pour l’irradiation du sein gauche). Les techniques visant a reduire les toxicites cardiaques de la radiotherapie, sont d’autant plus recommandees lorsque d’autres traitements cardiotoxiques lui sont associes (anthracyclines et / ou trastuzumab).

10513 Background: To determine overall survival and independent prognostic factors for patients with brain metastases from breast carcinoma treated with whole brain radiation therapy (WBRT). Methods: From January 1998 through December 2003, 132 patients with brain metastases (BM) from breast carcinoma were treated with WBRT (median dose: 3000 cGy/ 10 fractions). We analyzed a number of potential predictors of survival after WBRT: age, presence of other systemic metastases, performance status, RTOG recursive partition analysis (RPA) class (1–2 vs 3), total dose of WBRT, number of brain metastases, interval between primary tumor and brain metastases, SBR score, tumor receptor hormonal (RH) status, lymphocyte count (< 700 vs ≥ 700 G/L), serum lactate dehydrogenase and HER-2 overexpression. The survival time with BM was defined as the time from the date of BM to the date of death or date of last of follow-up. Multivariate analysis was used to determine the effect of prognostic factors on overall survival using the Cox proportional hazard model. Results: One hundred and seventeen patients received exclusive WBRT. Surgery was followed by WBRT in 14 patients and stereotactic radiosurgery was followed by WBRT in 1. The median survival with BM was 6 months (range: 0–52). The 1-year and 2-years survival rates were 31% (CI95%: 23.5–39.8) and 16% (CI95%: 9.8–24.9). In multivariate analysis, RTOG RPA class III, lymphopenia (<700) and negative tumor RH status were independent prognostic factors for poor survival. Moreover, analysis of Her-2 overexpression was performed in 53 patients and 43% BM patients overexpressed Her-2. In preliminary analysis, Her-2 status was not a prognostic factor of survival. A complete analysis is ongoing and will be presented at the meeting. Conclusions: This large study confirms the value of established prognostic factors such as the RTOG RPA score and some less-well recognized factors such as lymphopenia and tumor RH status. No significant financial relationships to disclose.

Purpose: Prospective analysis of local tumor control, survival, and treatment complications in 44 consecutive patients, treated with fractionated photon and proton radiation for a chordoma or chondrosarcoma of the skull base.Methods and Materials : Between December 1995 and December 1998, 45 patients with a median age of 55 years (14-85) were treated using a 201-MeV proton beam at the Centre de Protontherapie d'Orsay. 34 for a chordoma and 11 for a chondrosarcoma. Irradiation combined high-energy photons and protons. Photons represented two-thirds of the total dose and protons one-third. The median total dose delivered within the gross tumor volume was 67 cobalt Gray equivalent (CGE) (range: 60-70).Results: With a mean follow-up of 30.5 months (range: 2-56), the 3-year local control rates for chordomas and chondrosarcomas were 83.1% and 90%, respectively, and 3-year overall survival rates were 91% and 90%, respectively. Eight patients (18%) failed locally (7 within the clinical tumor volume and 1 unknown). Four patients died of tumor and 2 others of intercurrent disease. In univariate analysis, young age at time of radiotherapy influenced local control positively (p < 0.03), but not in multivariate analysis. Only 2 patients presented Grade 3 or 4 complications.Conclusion: In skull-base chordomas and chondrosarcomas, the combination of photons with a proton boost of one-third the total dose offers an excellent chance of cure at the price of an acceptable toxicity. These results should be confirmed with a longer follow-up. (C) 2001 Elsevier Science Inc.