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Purpose: A gene expression signature, predictive for local recurrence after breast-conserving treatment, has previously been identified from a series of 165 young patients with breast cancer. We evaluated this signature on both another platform and an independent series, compared its performance with other published gene-sets, and investigated the gene expression profile of a larger data set.Experimental Design: Gene expression tumor profiles were obtained on 148 of the initial 165 Dutch patients and on an independent validation series of 195 French patients. Both unsupervised and supervised classifications were used to study the gene expression profile of the 343 breast cancers and to identify subgroups that differ for their risk of local recurrence.Results: The previous local recurrence signature was validated across platforms. However, when applied to the French patients, the signature did not reproduce its reported performance and did not better classify the patients than other published gene sets. Hierarchical clustering of all 343 breast cancers did not show any grouping reflecting local recurrence status. Genes related to proliferation were found differentially expressed between patients with or without local recurrence only in triple-negative tumors. Supervised classification revealed no significant gene set predictive for local recurrence or able to outperform classification based on clinical variables.Conclusions: Although the previously identified local recurrence signature was robust on another platform, we were neither able to validate it on an independent data set, nor able to define a strong gene expression classifier for local recurrence using a larger data set. We conclude that there are no significant differences in gene expression pattern in tumors from patients with and without local recurrence after breast-conserving treatment. Clin Cancer Res; 18(6); 1704–15. ©2012 AACR.

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Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is a rare disease which is often associated with Helicobacter pylori (H. pylori) infection. First-line treatment of stage IE and IIE localized gastric MALT lymphoma is based on the eradication of H. pylori. The presence of H. pylori resistance factors such as translocation t (11;18), peri-gastric lymph node involvement and the degree of tumor infiltration of the gastric wall; or lack of response to antibiotic therapy are two main indications to treat with definitive radiotherapy (RT). RT is an effective treatment in localized gastric MALT lymphoma. A moderate dose of 30 Gy allows a high cure rate while being well tolerated. After treatment, regular gastric endoscopic follow-up is necessary to detect a potential occurrence of gastric adenocarcinoma.

Objective The severity of breakthrough cancer pain (BTcP) impacts patients' quality of life, increases the risk of anxiety and depression, lowers functional capacities, and may lead to poor compliance with cancer treatments. The aim of the current study was to assess, in a real-life setting, patient satisfaction with a fentanyl-pectin-nasal-spray (FPNS) for BTcP management in head and neck (H&N) cancer patients treated by radiotherapy. Materials and Methods This non-interventional, prospective study was conducted in 92 adult H&N-cancer patients undergoing radiotherapy and who started FPNS treatment for BTcP. Throughout the radiotherapy period, the patients completed self-diaries to assess their BTcP episodes, FPNS use, satisfaction on FPNS efficiency (primary outcome), tolerability and ease of use. Results Prior to FPNS treatment, 86% of the patients were experiencing ≤4 BTcP episodes/day. During the radiotherapy period, the BTcP episodes were treated with a median dose of 100µg of FPNS. Patients were "satisfied/very-satisfied" with the efficiency (73% of assessments), ease of use (87% of assessments) and tolerability (87% of assessments) of FPNS. In total, 27% of patients reported at least one adverse event related to FPNS and 4% of patients discontinued treatment due to adverse events. None of the adverse events were serious. Patient quality of life was maintained throughout the radiotherapy period. Conclusion This study showed, in a real-life setting, that a clear majority of H&N cancer patients treated with FPNS for BTcP throughout radiotherapy expressed satisfaction with this analgesic treatment.

Simple Summary Neoadjuvant fluoropyrimidine (5FU or capecitabine)-based chemoradiotherapy (CRT) has been considered the standard of care for locally advanced rectal cancer (LARC). Our Meta-analysis showed that the combining oxaliplatin with capecitabine or 5FU in preoperative chemoradiotherapy or perioperative chemotherapy seems beneficial significantly and improved DFS. It remains necessary to identify which patients benefit most from the addition of oxaliplatin. Abstract Background: Neoadjuvant fluoropyrimidine (5FU or capecitabine)-based chemoradiotherapy (CRT) has been considered the standard of care for locally advanced rectal cancer (LARC). Whether addition of oxaliplatin (OXP) will further improve clinical outcomes is still unclear. Methods: To identify clinical trials combining oxaliplatin in preoperative CRT or perioperative chemotherapy for LARC published until March 2021, we searched PubMed and the Cochrane Library. We also searched for relevant ASCO conference abstracts. The primary endpoint was disease-free survival (DFS). Data were extracted from every study to perform a meta-analysis using Review Manager (version 5.3). Results: A total of seven randomized clinical trials (ACCORD-12, CARO-AIO-04, FOWARC, JIAO, NSABP, PETACC-6, and STAR-01) with 5782 stage II or III rectal cancer patients were analyzed, including 2727 patients with OXP + 5FU regimen and 3055 patients with 5FU alone. Compared with the 5FU alone group, the OXP + 5FU regimen improved DFS (HR = 0.90, 95% CI: 0.81–0.99, p = 0.03) and pathologic complete response (pCR) (OR = 1.21, 95% CI: 1.07–1.37, p = 0.002). Patients treated with the OXP + 5FU regimen had significantly less metastatic progression (OR = 0.79; 95% CI, 0.67 to 0.94; p = 0.007). Considering adverse events (AEs), there was more grade 3–4 diarrhea with OXP + 5FU (OR = 2.41, 95% CI: 1.74–3.32, p < 0.00001). However, there were no significant differences grade 3–4 hematologic AEs (OR = 1.16, 95% CI: 0.87–1.57, p = 0.31). Conclusions: Our meta-analysis with long-term results from the randomized studies showed a benefit of the addition of OXP + 5FU regiment in terms of DFS, metastatic progression, and pCR rate that did not translate to improved OS.

Introduction et but de l’etude La photobiomodulation est recommandee pour prevenir la mucite orale au cours du cancer de la tete et du cou traite par irradiation et a montre des resultats encourageants sur la radiodermite au cours du cancer du sein. Les dispositifs actuels ne permettent pas une administration reproductible ni standardisee. CareMin650 permet l’illumination des tissus par des applicateurs souples, faits de fibres optiques tissees, places au contact des tissus (peau ou muqueuse), delivrant une lumiere rouge a 650nm. Materiel et methodes Il s’agissait d’une etude francaise multicentrique prospective chez des patients pris en charge par radiotherapie pour un cancer de la tete et du cou (cohorte A) ou du sein (cohorte B), en situation preventive (A1 et B1) ou curative (A2 et B2). Une prophylaxie (3j/cm2) a ete debutee a j1 de la radiotherapie (trois a cinq seances par semaine), un traitement curatif (6j/cm2, cinq seances par semaine) a ete debute a l’apparition d’une lesion, les seances ont ete realisees juste avant ou apres la radiotherapie. Le critere principal etait la tolerance (CTCAEv4). Les criteres secondaires etaient l’efficacite, la satisfaction du patient et de l’operateur. Resultats et analyse statistique Soixante-douze patients ont ete inclus dans l’analyse en ITT (22 A1, neuf A2, 23 B1 et 18 B2) pour un total de 1312 sessions de CareMin650. Il y a eu 17 sorties prematurees de l’etude, principalement liees a la pandemie de covid-19. Les traitements sont resumes dans le Tableau 1. La tolerance etait tres bonne, aucun evenement indesirable lie au dispositif n’a ete observe. Le Tableau 2 resume les donnees des patients ayant recu le traitement prophylactique. En ce qui concerne l’efficacite (population per protocole), en situation preventive, le delai median d’apparition des lesions etait de 20jours (intervalle : 3–50jours). En situation curative, le nombre median etait de deux lesions (intervalle : 1–4) en debut de traitement, de grade maximal 1 (70,4 %), 2 (25,9 %) ou 3 (3,7 %). A la fin de la radiotherapie, il etait observe pour une majorite de patients une stabilisation (52 %) ou une amelioration (19 %). En ce qui concerne la satisfaction, la majorite des patients ont trouve le traitement non contraignant (81,3 %), non douloureux (87,5 %), satisfaisant (93,6 %) et 89,1 % ont pu tenir les applicateurs seuls pendant les sessions. La satisfaction globale des operateurs etait de 96 %. Conclusion CareMin650 est un nouveau dispositif tres bien tolere et simple d’utilisation qui peut ameliorer la faisabilite de la photobiomodulation chez les patients recevant un traitement pour un cancer.

BackgroundIn this prospective phase 2 trial, we assessed the efficacy of trastuzumab-emtansine (T-DM1) in HER2-negative metastatic breast cancer (MBC) patients with HER2-positive CTC.MethodsMain inclusion criteria for screening were as follows: women with HER2-negative MBC treated with ≥ 2 prior lines of chemotherapy and measurable disease. CTC with aHER2/CEP17 ratio of ≥ 2.2 by fluorescent in situ hybridization (CellSearch) were considered to beHER2-amplified (HER2amp). Patients with ≥ 1HER2ampCTC were eligible for the treatment phase (T-DM1 monotherapy). The primary endpoint was the overall response rate.ResultsIn 154 screened patients, ≥ 1 and ≥ 5 CTC/7.5 ml of blood were detected inN = 118 (78.7%) andN = 86 (57.3%) patients, respectively. ≥1HER2ampCTC was found in 14 patients (9.1% of patients with ≥ 1 CTC/7.5 ml). Among 11 patients treated with T-DM1, one achieved a confirmed partial response. Four patients had a stable disease as best response. Median PFS was 4.8 months while median OS was 9.5 months.ConclusionsCTC withHER2amplification can be detected in a limited subset of HER2-negative MBC patients. Treatment with T-DM1 achieved a partial response in only one patient.Trial registrationNCT01975142, Registered 03 November 2013

Purpose Morbidity and mortality review (MMR) meetings in radiation therapy (RT) departments aim to monitor radiation-induced toxicities and identify potential factors that may be correlated with their development and severity, particularly treatment planning errors. The aims of the Prospective Registration of Morbidity and Mortality, Individual Radiosensitivity and Radiation Technique (PROUST) survey were to make an inventory of existing MMR procedures and to describe their procedures. Methods and materials The link to the web-based questionnaire of the PROUST survey was sent to 351 radiation oncologists working at 172 centers. The questionnaire included items related to organization, frequency, membership, governance, reasons for nonimplementation of MMR, and interest in its creation. Results As of July 2017, 108 responses had been received from the 172 centers, of which 107 responses were completed for analysis. All centers declared that they had initiated a quality assurance program in their department, including implementation of feedback committees dedicated to the registration, analysis, and correction of precursor events. Less than half of the centers (47%) had implemented MMR procedures. However, there was significant confusion regarding feedback committees in a majority of the centers. MMRs were organized every 6 and 12 months in 21% and 15%, respectively, of the centers. In 60% of the centers, toxicity grade ≥3 was the main reason for the MMR initiation. In routine practice, contouring and dosimetry files were reviewed by 66% and 83%, respectively, of centers practicing MMR. However, only 40% of the centers enrolled data in a registry dedicated to surveillance. Finally, 78% of centers expressed interest in initiating a consensual procedure. Conclusions MMRs are not systematically implemented in RT departments worldwide. In France and in Europe, few departments with quality assurance programs have implemented MMRs. This survey showed that a large majority of centers are interested in implementing an MMR with a formalized procedure. Our project could help increase the interest of the RT community worldwide in this topic.

In breast cancer, radiotherapy is an essential component of the treatment. After conservative surgery for an infiltrating carcinoma, radiotherapy must be systematically performed, regardless of the characteristics of the disease, because it decreases the rate of local recurrence and by this way, specific mortality. Partial breast irradiation could not be proposed routinely but only in very selected and informed patients. For ductal carcinoma in situ, adjuvant radiotherapy must be also systematically performed after lumpectomy. After mastectomy, chest wall irradiation is required for pT3-T4 tumours and if there is an axillary nodal involvement, whatever the number of involved lymph nodes. After neo-adjuvant chemotherapy and mastectomy, in case of pN0 disease, chest wall irradiation is recommended if there is a clinically or radiologically T3-T4 or node positive disease before chemotherapy. Axillary irradiation is recommended only if there is no axillary surgical dissection and a positive sentinel lymph node. Supra and infra-clavicular irradiation is advised in case of positive axillary nodes. Internal mammary irradiation must be discussed case by case, according to the benefit/risk ratio (cardiac toxicity). Dose to the chest wall or the breast must be between 45-50Gy with a conventional fractionation. A boost dose over the tumour bed is required if the patient is younger than 60 years old. Hypofractionation (42.5 Gy in 16 fractions, or 41.6 Gy en 13 or 40 Gy en 15) is possible after tumorectomy and if a nodal irradiation is not mandatory. Delineation of the breast, the chest wall and the nodal areas are based on clinical and radiological evaluations. 3D-conformal irradiation is the recommended technique, intensity-modulated radiotherapy must be proposed only in case of specific clinical situations. Respiratory gating could be useful to decrease the cardiac dose. Concomitant administration of chemotherapy in unadvised, but hormonal treatment could be start with radiotherapy.

Several algorithms exist to perform quality assurance for volumetric‐modulated arc therapy (VMAT) treatments based on electronic portal imaging devices (EPID). These algorithms are used to compare doses (convert into water, GLAaS) and fluences (in amorphous silicon (aSi), Varian portal dosimetry). The aim of this study is to compare the two methods using clinical data. In this study, Varian portal dosimetry (VPD) and Epiqa solutions were compared. We used a same set of patient images data treated with 6 MV and 20 MV photon energies and different locations. The response of the portal imaging device was also investigated with different field sizes, monitor units, dose rates, sag effect, and linac daily output. All images were acquired on an electronic portal imaging device (EPID) positioned at source detector distance (SDD) of 100 cm. A virtual water phantom was used for Epiqa to calculate the dose matrices at the maximum depth doses dmax. The 2D gamma evaluation index (GAI) was performed to quantitatively compare the results given by the two solutions. The response of the EPID gave a good agreement with Epiqa (deviation less than 1%) for MU greater than 20 for both 6 MV and 20 MV photon energies. For VPD, the upward sloping trend showed a good agreement for MU higher than 50. Dose rate evaluations for both methods gave a deviation of, respectively, 0.4 and 0.5 % for 6 MV and 20 MV. The gamma criteria of 3 mm for distance to agreement and 3 % for dose difference was, as mean ±1 SD, 99.81%±1.48% and 99.42%±0.97% for VPD and Epiqa, respectively, for 6 MV photon energy. The mean values of the gamma criteria for the collected data using 20 MV photon energy were, respectively, 98.33%±2.41% and 98.12%±1.99% for VPD and Epiqa. The output constancy deviation correction (a 10×10 cm2 reference field plan to obtain absorbed dose despite the linac monitor daily variations) showed a mean deviation of, respectively, 0.07%±0.57% and 0.16%±1.38% for 6 MV and 20 MV photon energies. For sag effect, a slight improvement was noticed for realignment of the integrated image and was 0.25%±0.69% for 6 MV and 0.40%±0.57% for 20 MV. The clinical data were used for pretreatment QA with the two systems, both VPD and Epiqa software, showed acceptable and similar results for low and high energies. Furthermore, Epiqa shows better linearity response for low MU. PACS number: 87.53.Bn, 87.55.km, 87.57.uq

Aim To assess the safety and tolerability of adjuvant subcutaneous trastuzumab (Herceptin ® SC, H SC), delivered from an H SC Vial via hand-held syringe (Cohort A) or single-use injection device (Cohort B), with or without chemotherapy, for human epidermal growth factor receptor 2 (HER2)-positive stage I to IIIC early breast cancer (EBC) in the phase III SafeHer study (NCT01566721). Methods Patients received 600 mg fixed-dose H SC every 3 weeks for 18 cycles. The chemotherapy partner was at the investigators' discretion (H SC monotherapy was limited to ≤10% of the population). Data from the first H SC dose until 28 days (plus a 5-day window) after the last dose are presented. Results are descriptive. Results In the overall population, 2282/2573 patients (88.7%) experienced adverse events (AEs). Of the above, 128 (5.0%) patients experienced AEs leading to study drug discontinuation; 596 (23.2%) experienced grade ≥ 3 AEs and 326 (12.7%) experienced serious AEs. Grade ≥ 3 cardiac disorders were reported in 24 patients (0.9%), including congestive heart failure in eight (0.3%). As expected, the AE rates varied according to the timing of chemotherapy in both cohorts, with higher rates in concurrent versus sequential chemotherapy subgroups. In the concurrent chemotherapy subgroup, AEs were more common during the actual period of concurrent chemotherapy compared with the period when patients did not receive concurrent chemotherapy. Conclusion SafeHer confirms the safety and tolerability of the H SC 600 mg fixed dose for 1 year (every 3 weeks for 18 cycles) as adjuvant therapy with concurrent or sequential chemotherapy for HER2-positive EBC. These primary analysis results are consistent with the known safety profile for intravenous H and H SC.

Aim To identify predictors for infiltrating carcinoma and lymph node involvement, before immediate breast reconstructive surgery, in patients with an initial diagnosis of extensive pure ductal carcinoma in situ of the breast (DCIS). Patients and methods Between January 2000 and December 2009, 241 patients with pure extensive DCIS in preoperative biopsy had underwent mastectomy. Axillary staging (sentinel node and/or axillary dissection) was performed in 92% ( n = 221) of patients. Patients with micro-invasive lesions at initial diagnosis, recurrence or contralateral breast cancer were excluded. Results Respectively 14% and 21% of patients had a final diagnosis of micro-invasive carcinoma (MIC) and invasive ductal carcinoma (IDC). Univariate analysis showed that the following variables at diagnosis were significantly correlated with the presence of either MIC or IDC in the mastectomy specimen: palpable tumor ( p = 0.002), high grade DCIS ( p = 0.002) and detection of an opacity by mammography ( p = 0.019). Axillary lymph node (ALN) involvement was reported in 9% of patients. Univariate analysis suggested that a body mass index higher than 25 ( p = 0.007), a palpable tumor ( p = 0.012) and the detection of an opacity by mammography ( p = 0.044) were associated with an increased rate of ALN involvement. Conclusion Skin-sparing mastectomy and immediate breast reconstruction (IBRS) has become increasingly popular, especially for patients with extended DCIS of the breast. This study confirmed that extended DCIS is associated with a substantial risk of finding MIC or IDC on the surgical specimen but also ALN involvement. Adjuvant systemic treatment and/or radiotherapy could be indicated for some of these patients after the surgery. Patients should be informed of the rate of 1) complications associated to IBRS that will potentially delay the introduction of systemic or local therapy 2) complications associated to radiotherapy after IBRS.

Introduction et but de l’etude L’objectif de cette etude etait d’evaluer la faisabilite, l’efficacite et les complications liees a l’implantation et au suivi de marqueurs fiduciels dans le cadre de traitements par de radiotherapie stereotaxique de localisation extracrânienne avec le CyberKnife®. Materiel et methodes Il s’agit d’une etude observationnelle retrospective monocentrique qui a collecte les donnees de tous les patients traites entre juin 2014 et novembre 2017, par irradiation stereotaxique extracrânienne avec suivi des marqueurs fiduciels. Les informations concernant la procedure d’implantation, la toxicite liee a l’implantation, le nombre de marqueurs implantes et suivis pendant le traitement ont ete recueillis. Les toxicites ont ete evalues selon les Common Terminology Criteria for Adverse Events (CTCAE v4). Le taux de reussite technique a ete evalue et etait base sur la possibilite de suivre de maniere optimale la cible pendant toutes les fractions de traitement. Resultats et analyse statistique En tout, 2505 patients ont ete traites par irradiation stereotaxique, dont 25 % avec suivi de marqueurs fiduciels. Le nombre total de procedures d’implantation etait de 616 et 1 543 marqueurs ont ete implantes. Les taux de complications liees aux differentes procedures d’implantation etaient de 3 %, avec 16 evenements de grade 1 et quatre de grade 2. Les 1295 marqueurs ont finalement ete suivis sur l’ensemble des fractions des differents traitements avec un taux de reussite technique de 84 %. La difference entre le nombre de marqueurs implantes et le nombre de marqueurs suivis pendant le traitement a significativement diminuee au cours du temps. Conclusion L’implantation de marqueurs fiduciels est bien toleree et le suivi de ces marqueurs semblent techniquement efficace pour le traitement par irradiation stereotaxique de tumeurs extracrâniennes.

Objective: In previous studies we developed a radiosensitivity molecular signature (RSI) that has been independently validated in multiple disease sites (n = 652) including breast cancer 1-3. Here, we test whether RSI can be utilized to identify sub-populations in breast cancer that benefit from RT dose intensification (boost). Methods: RSI was tested in two published breast cancer datasets (n = 342) 4. Patients were selected if they had experienced a local recurrence within the first 10 years after primary treatment or were free of local recurrence for a minimum of 10 years after treatment. Primary treatment was initial breast-conserving surgery plus whole breast RT with/without a boost (no boost, n = 94, low boost < = 66 Gy, n = 148, high boost >66 Gy, n = 100). Patients were treated between January 1984 and November 2002. RSI was generated as previously described 1-3. Time to local recurrence was used as the endpoint for the study. Results: Increased RT dose (>66 Gy vs. < = 66 Gy) resulted in a slight decrease in local recurrence risk that did not reach statistical significance (p = 0.11). As hypothesized, RSI-high patients (more radioresistant) were sensitive to increased RT dose (high RT-boost) which resulted in a decrease in local recurrence (HR = 0.3418, CI 0.1195-0.9777, p = 0.036). In contrast, RSI-low and intermediate patients had similar local recurrence risk independent of RT dose (RSI-low HR = 0.7687, CI 0.3404-1.736, p = 0.53, RSI-intermediate, HR = 0.9115, CI 0.5125-1.621, p = 0.75). Importantly, there were no statistical differences in the distribution of known prognostic variables between RSI-determined sub-populations (RSI-low, intermediate, high) including age, T-stage, margin status, nodal status, adjuvant chemotherapy, hormonal therapy, grade and molecular subtype. Conclusions: RSI identifies a sub-population of breast cancer patients that benefit from increased RT-dose. RSI may be utilized to support RT-based decisions (high boost vs. low boost vs. no boost) in breast cancer. 1. Eschrich S, Fulp WJ, Pawitan Y, et al: Validation of a Radiosensitivity Molecular Signature in Breast Cancer. Clin Cancer Res, 2012 2. Eschrich S, Zhang H, Zhao H, et al: Systems biology modeling of the radiation sensitivity network: a biomarker discovery platform. Int J Radiat Oncol Biol Phys 75:497-505, 2009 3. Eschrich SA, Pramana J, Zhang H, et al: A gene expression model of intrinsic tumor radiosensitivity: prediction of response and prognosis after chemoradiation. Int J Radiat Oncol Biol Phys 75:489-96, 2009 4. Servant N, Bollet MA, Halfwerk H, et al: Search for a gene expression signature of breast cancer local recurrence in young women. Clin Cancer Res 18:1704-15, 2012. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-11-11.

Resume Objectif Etude prospective monocentrique de la toxicite liee a l’administration concomitante du trastuzumab a la radiotherapie mammaire. Patientes et methodes Cent soixante-treize patientes ont ete traitees entre juin 2003 et mars 2009 par trastuzumab concomitant a une radiotherapie normofractionnee. Le trastuzumab etait delivre toutes les trois semaines (8 mg/kg a la premiere injection puis 6 mg/kg) pendant une duree mediane de 12 mois (2–62). La fraction d’ejection ventriculaire gauche a ete mesuree par echocardiographie ou scintigraphie cardiaque au moment du diagnostic, avant et apres la radiotherapie, tous les trois mois pendant un an puis annuellement. Une fraction d’ejection ventriculaire gauche strictement inferieure a 55 % etait consideree comme alteree. La toxicite a ete evaluee selon la Common Terminology Criteria for Adverse Effects version 3.0. Resultats Le suivi median etait de 52 mois (17–88). L’âge median etait de 52 ans (25–83). Cent trente-quatre patientes (77,5 %) ont recu une radiotherapie de la chaine mammaire interne. Une epitheliite aigue de grades 1, 2 et 3 a ete decrite chez respectivement 132 (76,3 %), 32 (18,5 %) et six patientes (3,4 %). Avec un recul median de 23 mois, une fibrose de grades 1 et 2 a ete observee chez respectivement 31 et huit patientes (18,8 et 4,6 %). La fraction d’ejection ventriculaire gauche etait normale pour 159 patientes (91,9 %) avant la radiotherapie. Elle etait alteree chez ces patientes 18 fois (11,3 %), dont huit (5,0 %) au terme de la radiotherapie. Une insuffisance cardiaque congestive symptomatique est survenue chez une patiente (0,6 %). Conclusion La toxicite en rapport avec l’association du trastuzumab a la radiotherapie mammaire s’est averee moderee. Un suivi prolonge est necessaire.

Resume Objectif de l’etude L’objectif de notre etude etait d’evaluer les caracteristiques des cancers du sein survenant apres un lymphome hodgkinien et notamment le pronostic apres chirurgie conservatrice. Patientes et methodes Il s’agit d’une etude retrospective concernant 72 femmes qui ont vu se developper un cancer du sein in situ ou invasif de stade I–III apres un lymphome de Hodgkin, entre 1978 et 2009. Resultats L’âge median au moment du diagnostic du lymphome de Hodgkin etait de 23 ans. La dose totale mediane recue par le mediastin etait de 40 Gy, principalement par une technique en mantelet. Les cancers du sein sont survenus apres un intervalle median de 21 ans apres le lymphome de Hodgkin. Les carcinomes canalaires infiltrants et in situ representaient respectivement 71 % et 19 % des cas. Le traitement locoregional des cancers du sein a comporte une mastectomie avec (3) ou sans (36) radiotherapie adjuvante chez 39 patientes et une tumorectomie avec (30) ou sans (2) ou sans radiotherapie adjuvante chez 32 patientes. La technique de decubitus lateral isocentrique a ete utilisee chez 17 patientes (57 %). Avec un suivi en mediane de sept ans, les taux de survie globale et de controle locoregional a cinq ans etaient respectivement de 74,5 % et 82 % pour les cancers invasifs et de 100 % et 92 % pour les cancers in situ. Treize patientes sont decedees d’une progression du cancer du sein et un cancer du sein controlateral a ete diagnostique chez dix patientes (14 %). Conclusions La chirurgie conservatrice peut etre une option pour les cancers du sein survenant apres lymphome de Hodgkin, malgre l’irradiation thoracique anterieure. Elle doit associer une mastectomie partielle et une irradiation avec utilisation d’une technique adequate telle que le lateral isocentrique.

Purpose To report clinical and pathologic characteristics and outcome of breast cancer (BC) after irradiation for Hodgkin's lymphoma (HL) in women treated at the Institut Curie, with a special focus on the breast-conserving option. Methods and Materials Medical records of 72 women who developed either ductal carcinoma in situ or Stage I–III invasive carcinoma of the breast after HL between 1978 and 2009 were retrospectively reviewed. Results Median age at HL diagnosis was 23 years (range, 14–53 years). Median total dose received by the mediastinum was 40 Gy, mostly by a mantle-field technique. Breast cancers occurred after a median interval of 21 years (range, 5–40 years). Ductal invasive carcinoma and ductal carcinoma in situ represented, respectively, 51 cases (71%) and 14 cases (19%). Invasive BCs consisted of 47 cT0–2 tumors (82%), 5 cN1–3 tumors (9%), and 20 Grade 3 tumors (35%). Locoregional treatment for BCs consisted of mastectomy with (3) or without (36) radiotherapy in 39 patients and lumpectomy with (30) or without (2) 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% (95% confidence interval [CI], 64–88%) and 82% (95% CI, 72–93%) for invasive carcinoma and 100% (95% CI, 100 –100%) and 92% (95% CI, 79–100%) for in situ carcinoma. In patients with invasive tumors, the 5-year distant disease-free survival rate was 79% (95% CI, 69–91%), and 13 patients died of progressive BC. Contralateral BC was diagnosed in 10 patients (14%). Conclusions Breast-conserving treatment can be an option for BCs that occur after HL, 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, to protect the underlying heart and lung.

Purpose This phase II trial aimed to investigate the efficacy of concurrent radio- (RT) and chemotherapy (CT) in the preoperative setting for operable, non-metastatic breast cancer (BC) not amenable to initial breast-conserving surgery (BCS). Patients and methods From 2001 to 2003, 59 women were included. CT consisted of four cycles of 5-FU, 500 mg/m2/d, continuous infusion (d1–d5) and vinorelbine, 25 mg/m2 (d1 and d6). Starting concurrently with the second cycle, RT delivered 50 Gy to the breast and 46 Gy to the internal mammary and supra/infra-clavicular areas. Breast surgery and lymph node dissection were then performed. Adjuvant treatment consisted of a 16 Gy boost to the tumor bed after BCS, FEC (four cycles of fluorouracil 500 mg/m2, cyclophosphamide 500 mg/m2, and epirubicin 100 mg/m2, d1; d21) for pN1-3 and hormone-therapy for positive hormone receptors BC. Results The in-breast pathological complete response rate was 27%. BCS was performed in 41 (69%) pts. Overall and distant-disease free survivals at 5 years were respectively 88% [95% CI 80–98] and 83% [95% CI 74–93] whereas locoregional and local controls were 90% [95% CI 82–97] and 97% [95% CI 92–100]. Late toxicity (CTCAE-V3) was assessed in 51 pts (86%) with a median follow-up of 7 years [5–8]. Four (8%) experienced at least one grade III toxicities (one telangectasia and three fibroses). Cosmetic results, assessed in 35 of the 41 pts (85%) who retained their breasts, were poor in four pts (11%). Conclusion Preoperative concurrent administration of RT and CT is an effective regimen. Long-term toxicity is moderate. This association deserves further evaluations in prospective trials.

Purpose To evaluate the effect of postmastectomy radiotherapy (PMRT) in Stage II-III breast cancer patients with negative lymph nodes (pN0) after neoadjuvant chemotherapy (NAC). Patients and Materials Of 1,054 breast cancer patients treated with NAC at our institution between 1990 and 2004, 134 had pN0 status after NAC and mastectomy. The demographic data, tumor characteristics, metastatic sites, and treatments were prospectively recorded. The effect of PMRT on locoregional recurrence-free survival and overall survival (OS) was evaluated by multivariate analysis, including known prognostic factors. Results Of the 134 eligible patients, 78 (58.2%) received PMRT and 56 (41.8%) did not. At a median follow-up time of 91.4 months, the 5-year locoregional recurrence-free survival and OS rate was 96.2% and 88.3% with PMRT and 92.5% and 94.3% without PMRT, respectively ( p = NS). The corresponding values at 10 years were 96.2% and 77.2% with PMRT and 86.8% and 87.7% without PMRT ( p = NS). On multivariate analysis, PMRT had no effect on either locoregional recurrence-free survival (hazard ratio, 0.37; 95% confidence interval, 0.09–1.61; p = .18) or OS (hazard ratio, 2.06; 95% confidence interval, 0.71–6; p = .18). This remained true in the subgroups of patients with clinical Stage II or Stage III disease at diagnosis. A trend was seen toward poorer OS among patients who had not had a pathologic complete in-breast tumor response after NAC (hazard ratio, 6.65; 95% confidence interval, 0.82–54.12; p = .076). Conclusions The results from the present retrospective study showed no increase in the risk of distant metastasis, locoregional recurrence, or death when PMRT was omitted in breast cancer patients with pN0 status after NAC and mastectomy. Whether the omission of PMRT is acceptable for these patients should be addressed prospectively.

Resume Objectif de l’etude Evaluer le benefice de la chirurgie mammaire chez les patientes traitees pour un cancer du sein inflammatoire. Patientes et methodes Cette etude retrospective a ete basee sur 232 patientes traitees pour des cancers du sein inflammatoire. Toutes les patientes ont recu une chimiotherapie premiere suivie soit de radiotherapie exclusive (118 patientes, 51 %) soit de chirurgie avec ou sans radiotherapie (114 patientes, 49 %). La duree mediane de surveillance etait de 11 ans. Resultats Les deux groupes etaient comparables en dehors de l’existence d’un plus petit nombre de tumeurs de moins de 70 mm (43 % contre 33 %, p = 0,003), un plus grand taux de tumeurs classees N2 cliniquement (15 % contre 5 %, p = 0,04) et un plus petit nombre de tumeurs de grade 3 (46 % contre 61 %, p Conclusion L’analyse des resultats indique que la chirurgie associee a la chimiotherapie et a la radiotherapie augmente le taux de controle local chez les patientes traitees pour un cancer du sein inflammatoire.

Resume Objectifs La chimiotherapie neoadjuvante peut entrainer un down-staging tumoral et remettre en question les indications d’irradiation adjuvante. Cette etude retrospective a evalue l’interet de l’irradiation apres une mastectomie chez les patientes atteintes d’un cancer du sein sans envahissement ganglionnaire (pN0) apres chimiotherapie neoadjuvante. Patientes et methodes Chez les 1054 patientes ayant recu une chimiotherapie neoadjuvante pour un cancer du sein entre 1990 et 2004, 134 de ces cancers (23,6 %) ont ete classes pN0 apres chimiotherapie neoadjuvante, mastectomie et lymphadenectomie axillaire. L’ensemble des caracteristiques demographiques, anatomocliniques et therapeutiques ont ete recueillies prospectivement. L’impact de la radiotherapie sur les survies sans rechute locoregionale et globale a ete evalue en analyse multifactorielle tenant compte des principaux facteurs pronostiques. Resultats Parmi les 134 patientes, 78 (58,2 %) ont ete irradiees apres la mastectomie. Apres un suivi median de 91,4 mois, les probabilites de survie sans recidive locoregionale et de survie globale a dix ans etaient respectivement de 96,2 % et 77,2 % apres irradiation et 86,8 % et 87,7 % sans irradiation ( p = NS). En analyse multifactorielle, seule l’absence de reponse histologique complete de la tumeur primitive etait associee a une tendance a une probabilite de survie globale moindre ( hazard ratio [HR] de deces = 6,65 ; intervalle de confiance a 95 % [IC95 %], 0,82–54,12 ; p = 0,076). La radiotherapie delivree apres la mastectomie n’a pas eu d’impact significatif sur la probabilite de survie sans recidive locale (HR : 0,37 ; IC95 % : 0,09–1,61 ; p = 0,18) ni sur celle de survie globale (HR : 2,06 ; IC95 % : 0,71–6 ; p = 0,18). Conclusion Sous reserve de la nature retrospective des donnees, la radiotherapie delivree apres la mastectomie ne semble pas avoir eu d’impact sur la survie de patientes atteintes d’un cancer du sein sans envahissement ganglionnaire apres chimiotherapie neoadjuvante. Une confirmation prospective de ces donnees est necessaire.

Introduction: AdjuvantOnline is a web-based application designed to provide 10 years survival probability patients with breast cancer. Few validation studies have underlined some limitations, particularly an overestimation of the prognosis among certain subgroups of patients. Moreover, several predictors such as HER2 over expression status and proliferation markers have not been assessed in Adjuvant! original study. We provide the validation of AdjuvantOnline algorithm on two breast cancer datasets collected from two large European cancer centres, and we determined whether the accuracy of AdjuvantOnline is improved by others well known prognostic factors. Material and Methods: The French data set is composed of 456 women with early breast cancer, treated at the Institut Curie between 1995 and 1996. The dutch data set is composed of 295 women less that 52 years treated at the Netherlands Cancer Institute between 1984 and 1995. Agreement between observation and Adjuvant! prediction was checked by testing that the calibration slope was equal to 1. Logistic models were performed to evaluate whether risk factors adds significant prognostic information, including AdjuvantOnline a priori information as an offset. Results: Ten years survival status was known for 383 patients in the French data set and 247 patients in the Dutch data set. Adjuvant! prediction was globally well calibrated in the French data set (observed survival 86%, predicted survival 85%), but was overestimated in high grade, HER2 positive and Ki67 > 20% subgroups. HER2 status, Mitotic Index, Ki67 and treatment type were strongly associated with 10-year survival, even considering AdjuvantOnline a priori information. In the Dutch data set, the overall 10-year survival was overestimated by AdjuvantOnline (observed 66%, predicted 79%), particularly in patients less than 40 years old. Conclusion: AdjuvantOnline needs to be updated to adjust overoptimistic results in young and high grade patients, and should consider candidates, such as Ki67, HER2 and Mitotic Index. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-09-13.

Purpose Radio-induced early skin reactions still remain a clinical challenge. Preliminary results with Hyaluronic acid, one of the most recent topical products used in this indication are proving interesting. To evaluate the efficacy of Hyaluronic acid compared to placebo. Material and methods Breast cancer patients with grade 1–2 radio-induced dermatitis during postoperative radiotherapy were eligible. They were randomised to receive either hyaluronic acid (A) or a simple emollient (B). The primary endpoint was the clinical evaluation of the erythema (success versus failure). Secondary endpoints were the evaluation of skin colorimetry, pain, and quality of life. Results Two-hundred patients were enroled (A = 99, B = 101). Ninety-five patients per treatment arm could be evaluated. Failures occurred in 23 patients (24%) in the hyaluronic acid arm, and 32 (34%) in the emollient arm (p = 0.15). Seventy-three patients (36.5%) prematurely stopped the treatment without any ensuing difference between the two arms. Body mass index and the size of the epithelitis were both independently associated with the failure of the local treatment. The relative reduction of colorimetric levels was 20% in the hyaluronic acid group, and 13% in the emollient group (p = 0.46). Concerning the quality of life assessment, there was a trend towards a lower level of pain in patients receiving hyaluronic acid (p = 0.053). Conclusions The present study showed no significant difference between hyaluronic acid and simple emollient in the treatment of acute radio-induced dermatitis. There was however a trend towards an improvement in both pain level and skin colorimetry.

Resume Objectif de l’etude L’indication d’une radiotherapie externe est parfois posee chez des patients porteurs d’un stimulateur cardiaque. Ce traitement peut occasionner des dysfonctionnements lies soit a l’effet ionisant des rayons, soit a des interferences electromagnetiques. Nous avons repris le cas de patientes atteintes d’un cancer du sein traitees par une irradiation mammaire ou parietale, parfois aussi des aires ganglionnaires de drainage, pour evaluer la tolerance et les repercussions de la radiotherapie par rapport au stimulateur cardiaque. Patientes et methodes Plus de 900 patientes ont ete traitees par irradiation externe pour un cancer du sein de novembre 2008 a decembre 2009 dans notre departement par un accelerateur lineaire de haute energie (par photons X de 4 a 6 MV et electrons). Parmi ces dernieres, sept etaient porteuses d’un stimulateur cardiaque. Toutes les patientes ont ete irradiees dans le sein, la paroi thoracique ou les aires ganglionnaires. La dose totale prescrite etait de 50 Gy en 25 fractions dans le sein ou la paroi thoracique et de 46 Gy en 23 fractions dans les aires ganglionnaires. Un boost de 16 Gy en huit fractions etait indique chez certaines patientes traitees par chirurgie conservatrice. Le rythme cardiaque de toutes les patientes etait monitore pendant les seances et surveille par un medecin oncologue radiotherapeute. Tous les stimulateurs cardiaques ont ete controles par le cardiologue des patientes avant et apres l’irradiation. Resultats Sept patientes ont ete adressees dans notre departement pour radiotherapie postoperatoire dans le cadre d’un cancer du sein. Parmi ces sept patientes, seule une finalement s’est vue recuser la radiotherapie et a beneficie d’une mastectomie. Dans quatre cas, le stimulateur cardiaque a ete repositionne avant le debut de la radiotherapie. Six patientes âgees de 48 a 84 ans ont ete traitees par irradiation pour leur cancer du sein. Quatre patientes ont ete traitees par chirurgie conservatrice suivie d’une irradiation mammaire et deux par mastectomie suivie d’une irradiation de la paroi thoracique et des aires ganglionnaires sus- et sous-claviculaire et mammaire interne. La dose au stimulateur cardiaque a ete calculee et etait toujours inferieure a 2 Gy. Il n’a ete observe aucun dysfonctionnement des stimulateurs cardiaques pendant la radiotherapie. Conclusion La prise en charge multidisciplinaire incluant un eventuel changement de positionnement du stimulateur cardiaque avant radiotherapie et le monitoring quotidien ont permis le deroulement sans incident de la radiotherapie pour nos patientes. Il est neanmoins necessaire de mettre a jour des recommandations precisant la dose maximale tolerable aux differents constituants du stimulateur cardiaque.

Resume Objectifs Le but de cette etude est de rapporter la tolerance et la reponse de l’association concomitante de radiotherapie a l’ensemble de l’encephale et de trastuzumab pour des metastases encephaliques de cancer du sein. Patientes et methodes Nous avons realise une etude retrospective de 31 patientes irradiees pour metastases cerebrales d’un cancer du sein avec surexpression Her2 et qui ont recu une irradiation cerebrale en association concomitante avec le trastuzumab. La dose delivree etait de 30 Gy en dix fractions dans la majorite des cas. Toutes les patientes ont beneficie d’un suivi hebdomadaire afin d’evaluer la tolerance. Toutes les patientes ont poursuivi le trastuzumab apres la radiotherapie. Resultats L’âge moyen au moment du diagnostic de la metastase cerebrale etait de 55 ans (38 a 73 ans) avec un etat general conserve ( performance status selon OMS : 0-2). Le delai median avant la progression etait de 10,5 mois. L’evolution clinique etait marquee par une reponse chez 27 patientes (87,1 %) avec, pour 23 d’entre elles, une disparition complete des symptomes (74,2 %). Une remission radiologique complete etait notee chez six patientes (19,4 %), et partielle chez 17 (54,8 %). Le traitement a ete bien tolere, seules sept patientes (23 %) ont presente des nausees grades 1 et 2, une asthenie ou des cephalees. Conclusion Nos resultats suggerent que la poursuite du trastuzumab pendant la radiotherapie des metastases cerebrales est bien toleree. Le taux de reponse est encourageant mais il est necessaire d’evaluer ces resultats par des etudes prospectives comparant la radiotherapie seule a l’association radiotherapie-trastuzumab.

Resume Objectif de l’etude Evaluer la radiotherapie exclusive comme option therapeutique apres reponse clinique complete a une chimiotherapie neoadjuvante pour des cancers du sein de stade II-IIIA. Patientes et methodes Entre 1985 et 1999, 1477 patients ont recu une chimiotherapie neoadjuvante pour un cancer du sein de stade II-IIIA considere trop volumineux pour etre opere de facon conservatrice. Parmi les 165 patientes en situation d’une reponse clinique complete apres la chimiotherapie neoadjuvante, 65 ont ete traitees par chirurgie mammaire et irradiation et 100 par irradiation exclusive. Resultats Les deux groupes etaient comparables en termes de caracteristiques initiales, excepte pour le diametre tumoral au diagnostic (plus grand dans le groupe exclusivement irradie). Aucune difference statistiquement significative n’a ete observee en termes de survie globale, de survie sans maladie ni de survie sans metastase. Les taux de survie globale a cinq et dix ans etaient respectivement de 91 et 77 % dans le groupe exclusivement irradie et de 82 et 79 % dans le groupe opere et irradie ( p = 0,9). Cependant, une tendance en faveur d’un taux plus eleve de recidive locoregionale a ete observee dans le groupe exclusivement irradie (31 contre 17 % a dix ans ; p = 0,06). Chez les patientes en situation de remission complete d’apres la mammographie et/ou l’echographie, il n’y avait pas de difference statistiquement significative de taux de recidive locoregionale (a dix ans : 21 dans le groupe opere et irradie contre 26 % dans le groupe exclusivement irradie, p = 0,45). Aucune difference n’a ete observee en termes de toxicite cutanee, cardiaque et pulmonaire. Conclusion La chirurgie est une etape incontournable du traitement locoregional des cancers du sein ayant repondu completement a une chimiotherapie neoadjuvante.

Phyllodes tumors are a rare distinctive fibroepithelial tumors of the breast and their management continues to be questioned. The aim of our study was to examine the treatment and outcome of 165 patients with phyllodes tumors and to review the options for surgical management. This is a retrospective study of 165 patients who presented to the Institut Curie between January 1994 and November 2008 for benign, borderline or malignant phyllodes tumors. The median follow-up was 12.65 months [range 0-149.8]. The median age at diagnosis was 44 years [range 17-79]. One hundred and sixty patients (97%) had breast-conserving treatment, of whom 3 patients (1.8%) had oncoplastic breast surgery. Younger women had a significantly higher chance of having a benign phyllodes tumor (p = 0.0001) or a tumor of small size (p < 0.0001). Histologic examination showed 114 benign (69%), 37 borderline (22%) and 14 malignant tumors (9%). The median tumor size was 30 mm [range 5-150]. The tumor margins were considered incomplete (< 10 mm) in 46 out of 165 cases (28%) with 52% revision surgery. Only the tumor grade was a significant risk factor for incomplete tumor margins (p = 0.005). Fifteen patients developed local recurrence (10%) and two, metastases. In univariate analysis, the histologic grade (p = 0.008), and tumor size (p = 0.02) were significative risk factors for local recurrence with an accentuated risk for "borderline" tumors and tumors of large size.).Similar results were obtained using multivariate analysis (p = 0.07). The mainstay of treatment for phyllodes tumors remains excision with a safe surgical margin, taking advantage breast conserving surgery where amenable. For borderline or malignant phyllodes tumors or in cases of local tumor recurrence, mastectomy, and immediate breast reconstruction may become the preferred option. Genetic analysis will potentially supplement classical histologic examination in order to improve our management of these tumors. The role of adjuvant treatments is unproven and must be considered on a case-by-case basis.

Introduction: The aim of our study was to identify predictive factors of infiltrating carcinoma and lymph node involvement in patients with an initial diagnosis of extended pure ductal carcinoma in situ (DCIS) of the breast. Material and Methods: 241 patients diagnosed with extended pure ductal carcinoma in situ (DCIS) underwent treatment at the Institut Curie (2000-2009) consisting of mastectomy with or without immediate breast reconstruction (IMR). Axillary staging (sentinel node and/or standard procedure) was performed in 92% of patients. Patients with micro-invasive lesions at diagnosis, recurrence or contralateral breast cancer were excluded. Differences between groups were analysed by Chi-square or Fisher Exact tests for categorical variables and Student's t-test for continuous variables. Survival analyses were performed using KaplanMeier, with comparisons using the logrank test and hazard ratios estimated using the Cox proportional hazard model. P-values were considered significant when below 0.05. Results: Respectively 15% and 20%of patients had a final diagnosis of micro-invasive (MIC) and invasive ductal carcinoma (IDC). The median sizes of the DCIS and IDC were respectively 40mm [0-95] and 6mm [2-50] according to final histological assessment. Univariate analysis showed that the following variables at diagnosis were significantly correlated to the presence of either MIC or IDC in the mastectomy specimen; palpable tumor (p=0.02), high grade DCIS (p=0.02), detection of an opacity on mammography (p=0.01). Axillary lymph node involvement was reported in 9% of patients. In univariate analysis a BMI>25 (p=0.007), a palpable tumor (p=0.01), the detection of an opacity (p=0.04) were associated with an increase rate of lymph node involvement. A IMR was performed in 69% of patients. These patients were younger (P25 (p=0.06), a palpable tumor (p=0.0004), an opacity (p=0.01) and extended microcalcifications (p=0.02) were associated with a higher rate of loco-regional recurrence. Immediate breast reconstruction was not a significant risk factor for loco-regional recurrence (p=0.31). Conclusion: Extended pure ductal carcinoma of the breast on preoperative biopsies is associated with a substantial risk of finding not only micro-invasive or invasive carcinoma on the mastectomy specimen but also axillary lymph node involvement. Some risk factors have been identified and should be used to exclude patients from immediate reconstruction surgery due to an increased risk of getting adjuvant systemic treatment and radiotherapy. Immediate breast reconstructive surgery was not associated with an increased risk of loco regional recurrence in our series. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-14-18.

Purpose To evaluate the accuracy of a boost technique. Methods and Materials Twenty-two patients underwent tumorectomy with placement of two or more clips in the surgical cavity before breast remodeling. Preoperative and postoperative computed tomography scans, with match-point registration, were performed on all patients. The relationship between the location of the gross tumor volume (GTV), defined on the preoperative scan, and clip clinical target volume (CTV) (clips with a 5-mm margin on the postoperative scan) was then studied, by use of commercial volume analysis software. Results Of the patients, 4 had two clips, 2 had three clips, 8 had four clips, and 8 had five clips. The median GTV was 1.06 mL (range, 0.2–5.3 mL); clip CTV ranged from 2.4 to 21.5 mL. Volumetric analysis showed that in 7 cases (32%), there was no intersection between the GTV and the clip CTV, with the following distribution: 4 patients with two clips, 1 patient with three clips, 1 patient with four clips, and 1 patient with five clips. The common contoured volume was defined as the percent ratio between the intersection of the GTV and clip CTV and the GTV. It was found to be significantly increased if three or more clips were used vs. only two clips (common contoured volume, 35.45% vs. 0.73%; p = 0.028). Finally, the GTV and clip CTV volume relationship can be presented as follows: 12.5% to 33% overlap in 8 patients (36.4%), 50% to 75% in 5 patients (22.7%), and greater than 90% in 2 patients (9%). Conclusions The use of three or more clips during tumorectomy increases the accuracy of tumor bed delineation.

Background: Elston-Ellis grading (EE) is one of the key criteria for adjuvant therapy decision in ER+/HER2-/pN0/pT1 -2 tumors. The genomic grade index (GGI) is a 97-gene micro-array assay able to identify tumors of high or low genomic grade. GGI has been developed in order to improve the prognosis determination, especially in EE2 tumors which represent a significant proportion of breast carcinomas and where the inter-assessor variability is the highest. The aim of the present study was to model the influence of the GGI on adjuvant treatment decision in EE2 patients, using a cohort of ER+/HER2-/pN0/pT1-2 tumors. Methods: A randomly selected series of pT1-2, pN0 breast cancers from the Institut Curie 1995-1996 cohort was profiled using Affymetrix HGU133 Plus 2.0 gene chips. The GGI was calculated using Ipsogen Mapßuant Dx®. Treatment decisions were made for EE2 cases based on the Institut Curie adjuvant treatment guidelines (www.curie.fr). The treatment decision algorithm was firstly run using the grade as defined by Elston Ellis, and secondly using the GGI (undetermined cases were classified as grade2). Results: Out of 72 EE2 tumors, 35 were classified as GGI-1 (49%) and 13 (18%) as GGI-3. Based on EE, 7% of patients would have received adjuvant chemotherapy (ACT) alone (all were ER-/PR-), 50% adjuvant hormonal therapy (AHT) alone, and 43% both. Using the GGI, 7% (n=5) of patients would have been spared AHT and 10% (n=7) ACT. In the ER+/HER2- subgroup of 62 pts, 58% of patients would have received AHT alone and 42% AHT+ACT based on EE; GGI would have lead to a 14% reduction in AHT prescription and to a 26% reduction in ACT prescription. Conclusion: Applying the Genomic Grade Index instead of the Elston Ellis Grade to determine the adjuvant treatment strategy in a series of EE2/ER+/HER2-/pN0/pT1-2 breast carcinomas would lead to a 14% and 27% reduction in the administration of, respectively, adjuvant hormone-therapy and chemotherapy. Adjuvant treatment decision: models based on Elston-Ellis or Genomic Grading Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-13-11.

Aim:The aim of our study was to examine the treatment and outcome of 165 patients with phyllodes tumours and to review the options for surgical management. Patients and Methods: This is a retrospective study of 165 patients who presented to the Institut Curie between January 1994 and November 2008 for benign, borderline or malignant phyllodes tumours. Results: The median follow-up was 12.65 months [range 0 to 149.8]. The median age at diagnosis was 44 years [range 17 to 79]. One hundred and sixty patients (97%) had breast conserving treatment, of whom 3 patients (1. 8%) had oncoplastic breast surgery. Younger women had a significantly higher chance of having a benign phyllodes tumor (p = 0.0001) or a tumour of small size (< 0.0001). Histological examination showed 114 benign (69%), 37 borderline (22%) and 14 malignant tumours (9%). The median tumour size was 30 mm [range 5 to 150]. The tumour margins were considered incomplete (< 10 mm) in 46 out of 165 cases (28%) with 52% revision surgery. Only the tumour grade was a significant risk factor for incomplete tumour margins (p = 0.005). Fifteen patients developed local recurrence (10%) and two, metastases. In univariate analysis, the histological grade (p = 0.008) and tumour size (p=0.02) were significative risk factors for local recurrence with an accentuated risk for borderline tumours and tumours of large size. Similar results were obtained using multivariate analysis (p=0.07) Conclusion: The mainstay of treatment for phyllodes tumours remains excision with a safe surgical margin, taking advantage breast conserving surgery where amenable. For borderline or malignant phyllodes tumours or in cases of local tumour recurrence, mastectomy and immediate breast reconstruction may become the preferred option.Genetic analysis will potentially supplement classical histological examination in order to improve our management of these tumours. The role of adjuvant treatments is unproven and must be considered on a case-by-case basis. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-14-12.

The aim of this study was to present the simplified rules of delineation of lymph node (LN) volumes in breast irradiation. Practical rules of delineation of LN areas were developed in the Department of Radiation Oncology of the Institut Curie. These practical guidelines of delineation were based on different specific publications in the field of breast and LN anatomy. The principal characteristic of these rules is their clearly established relationship with anatomical structure, which is easy to find on CT slices. The simplified rules of delineation have been published in pocket format as the illustrated atlas “Help of delineation for breast cancer treatment”. In this small pocket guide, delineation using the practical rules is illustrated, with examples from anatomical CT slices. It is shown that there is an improvement in delineation after the use of these simplified rules and the guide. In conclusion, this small guide is useful for improving everyday practice and decreasing the differences in target delineation for breast irradiation between institutions and observers.

Breast cancer is a rare disease in young women. Its incidence has remained remarkably constant over the last decades, contrary to what has happened in older patients. Age is a major prognostic factor for local control after breast-conserving treatments, which does not seem to be entirely explained by the poor prognostic features that are more commonly associated with breast cancers in young women. A better knowledge of the prognostic factors for local control, and, whenever possible, those pertaining specifically to the young age group, is key, not only to better select the patients who would benefit the most from a breast-conserving approach but also to enhance the local control when this option has been elected. These prognostic factors can be related to the patient, the tumor and the treatment they receive. Finally, we will present a perspective of what the future could hold, both in terms of the selection of the patients and of a more customized therapeutic approach.

Poly(ADP-ribosyl)ation is a ubiquitous protein modification found in mammalian cells that modulates many cellular responses, including DNA repair. The poly(ADP-ribose) polymerase (PARP) family catalyze the formation and addition onto proteins of negatively charged ADP-ribose polymers synthesized from NAD(+). The absence of PARP-1 and PARP-2, both of which are activated by DNA damage, results in hypersensitivity to ionizing radiation and alkylating agents. PARP inhibitors that compete with NAD(+) at the enzyme's activity site are effective chemo- and radiopotentiation agents and, in BRCA-deficient tumors, can be used as single-agent therapies acting through the principle of synthetic lethality. Through extensive drug-development programs, third-generation inhibitors have now entered clinical trials and are showing great promise. However, both PARP-1 and PARP-2 are not only involved in DNA repair but also in transcription regulation, chromatin modification, and cellular homeostasis. The impact on these processes of PARP inhibition on long-term therapeutic responses needs to be investigated.

Depuis plus de dix ans, le developpement continu de nouvelles technologies d’analyse a haut debit offre aux scientifiques la possibilite d’etudier la biologie du vivant en general et des cancers en particulier par des voies aussi differentes que complementaires. Ainsi, les alterations de la structure de l’ADN (amplification, deletion, gain), les pertes d’heterozygotie (LOH), les alterations du niveau d’expression des genes, les alterations du controle posttranscriptionnelle des microARN, l’activation des complexes proteiques peuvent etre analysees simultanement a l’echelle du genome humain. Nous presentons ici un resume des decouvertes obtenues par l’analyse a haut debit du profil d’expression des cancers du sein, en insistant particulierement sur l’impact majeur de ces travaux sur la connaissance et la prise en charge clinique de ces patientes. Les terabytes de donnees biologiques accumulees par les scientifiques depuis plus de dix ans ne repondent pas simplement a une lubie technologique mais sont au contraire des outils determinants de la dissection moderne de ces tumeurs. L’amelioration du pronostic des patientes atteintes de cancer du sein passe necessairement par l’utilisation de ces technologies.

To evaluate the dosimetry of helical tomotherapy (HT) and three-dimensional conformal radiotherapy (3D-CRT) in breast cancer patients undergoing whole breast radiation with simultaneous integrated boost (SIB) of the tumor bed.Thirteen patients with breast cancer treated by lumpectomy and requiring whole breast radiotherapy with tumor bed boost were planned using both HT and 3D-CRT using the field-in-field technique. The whole breast and tumor bed were prescribed 50.68 Gy and 64.4 Gy, respectively, in 28 fractions. Dosimetries for both techniques were compared.Coverage of the whole breast was adequate with both techniques (V(95%)=96.22% vs. 96.25%, with HT and 3D-CRT, respectively; p=0.64). Adequate tumor bed coverage was also achieved, although it was significantly lower with HT (V(95%)=97.18% vs. 99.72%; p0.001). Overdose of the breast volume outside the tumor bed was significantly lower with HT (V(54.23 Gy)=12.47% vs. 30.83%; p0.001). Ipsilateral lung V(20 Gy) (6.34% vs. 10.17%; p0.001), V(5 Gy) (16.54% vs. 18.53%; p0.05) and mean dose (4.05 Gy vs. 6.36 Gy; p0.001) were significantly lower with HT. In patients with left-sided tumors, heart V(30 Gy) (0.03% vs. 1.14%; p0.05) and mean dose (1.35 Gy vs. 2.22 Gy; p0.01) were significantly lower with HT, but not V(5 Gy). Contralateral breast V(5 Gy) (0.27% vs. 0.00%; p0.01) and maximum dose were significantly increased with HT.In breast cancer treated with SIB, both HT and 3D-CRT provided adequate target volume coverage and low heart doses. Tumor bed coverage was slightly lower with HT, but HT avoided unnecessary breast overdosage while improving ipsilateral lung dosimetry.

Resume Objectif de l’etude La rarete des tumeurs phyllodes malignes du sein (ou tumeur phyllode de grade 3) et le caractere debattu de leur prise en charge justifie la realisation d’etudes retrospectives des pratiques institutionnelles. Patientes et methodes Etude retrospective avec relecture anatomopathologique des dossiers des 25 patientes traitees a l’institut Curie entre 1969 et 2006 pour une tumeur phyllode maligne, non metastatique d’emblee. Le suivi median etait de 65 mois (7–257 mois). Resultats L’âge median lors du diagnostic etait de 52 ans (20–64 ans). La chirurgie a ete conservatrice (tumorectomie) chez cinq patientes (20 %). Les marges etaient larges (> 10 mm), etroites, envahies ou inconnues chez respectivement 17 (68 %), trois (12 %), trois (12 %) et deux (8 %) patientes. La taille tumorale mediane etait de 65 mm (12–250 mm). Une radiotherapie postoperatoire a ete delivree a sept patientes (deux apres tumorectomie, cinq apres mastectomie) et une chimiotherapie adjuvante a base d’anthracyclines a 13 patientes (52 %). Le taux de survie globale a cinq ans etait de 91 % (intervalle de confiance a 95 % : 80–100 %). Cinq patientes (20 %) ont ete atteintes de metastases (dont une apres chimiotherapie) et trois (12 %) de rechute locoregionale (une apres tumorectomie et marge inconnue sans radiotherapie, deux apres mastectomie et tranches de section atteintes et radiotherapie). Conclusion Le traitement des tumeurs phyllodes malignes non metastatiques repose sur une chirurgie large (≥ 10 mm) qui, dans des cas selectionnes, peut etre conservatrice. La determination des places respectives des traitements adjuvants systemiques et de la radiotherapie necessite la poursuite d’etudes cliniques mais aussi la recherche de nouveaux facteurs pronostiques et predictifs pour la sensibilite tumorale.

Resume Objectif de l’etude Etude prospective monocentrique de la tolerance cutanee et cardiaque de l’association concomitante de trastuzumab et de radiotherapie pour le cancer du sein. Patientes et methodes De fevrier 2004 a janvier 2007, 57 patientes ont recu l’association concomitante de trastuzumab et d‘une radiotherapie normalement fractionnee du sein ou de la paroi, avec ou sans les aires ganglionnaires. La fraction d’ejection du ventricule gauche, mesuree avant l’administration de trastuzumab, avant celle de la radiotherapie, apres la radiotherapie puis tous les quatre a six mois par echographie ou scintigraphie, etait normale si d’au moins 50 % ou consideree comme telle par le cardiologue. Toute fraction d’ejection du ventricule gauche devait etre normale avant l’administration de trastuzumab. La toxicite cutanee a ete evaluee selon la Common Terminology Criteria for Adverse Events, version 3.0 . L’âge median etait de 49 ans (25–80). La chimiotherapie comportait des anthracyclines dans 84 % des cas, pour une dose totale de 300 mg/m 2 . Toutes les patientes sauf une, irradiee une fois par semaine, ont recu le trastuzumab toutes les trois semaines a la dose de 8 mg/kg puis 6 mg/kg, pour une duree mediane de 12 mois (2–33). La chaine mammaire interne a ete irradiee dans 88 % des cas. Resultats La fraction d’ejection du ventricule gauche etait normale avant la radiotherapie pour 54 patientes (100 %, trois donnees manquantes), apres la radiotherapie pour 56 (98 %, aucune donnee manquante) et aux dernieres nouvelles pour 53 (95 %, une donnee manquante). L’epidermite a ete cotee de grade 0, 1 ou 2 pour respectivement deux, 44 et 11 patientes. Pour les 27 patientes vues apres six mois, la toxicite cutanee a ete cotee de grade 0, 1 et 2 chez respectivement 22, quatre et une. Conclusion Avec une technique adaptee, la tolerance cutanee et cardiaque precoce de l’association de trastuzumab et de radiotherapie s’est averee bonne. Le suivi plus long d’un plus grand nombre de patientes reste cependant indispensable.

Definition of nodal volumes in breast cancer treatment and segmentation guidelines. Purpose. To assist in the determination of breast and nodal volumes in the setting of radiotherapy for breast cancer and establish segmentation guidelines. Materials and methods. Contrast metarial enhanced CT examinations were obtained in the treatment position in 25 patients to clearly define the target volumes. The clinical target volume (CTV) including the breast, internal mammary nodes, supraclavicular and subclavicular regions and axxilary region were segmented along with the brachial plexus and interpectoral nodes. The following critical organs were also segmented : heart, lungs, contralateral breast, thyroid, esophagus and humeral head. Results. A correlation between clinical and imaging findings and meeting between radiation oncologists and breast specialists resulted in a better definition of irradiation volumes for breast and nodes with establishement of segmentation guidelines and creation of an anatomical atlas. Conclusion. A practical approach, based on anatomical criteria, is proposed to assist in the segmentation of breast and node volumes in the setting of breast cancer treatment along with a definition of irradiation volumes.

Resume Objectif Evaluer les reactions cutanees aigues d’un schema d’irradiation adjuvante hypofractionnee du sein et leur delai d’apparition. Patientes et methodes Un recueil prospectif de toutes les observations des patientes traitees pour un cancer du sein par irradiation du sein de 42,9 Gy en 13 fractions et cinq semaines a ete effectue au sein du departement de radiotherapie. Les reactions cutanees aigues de 81 patientes ont ete evaluees au cours d’un examen clinique hebdomadaire selon le National Cancer Institute-Common Toxicity Criteria scoring system, version 3. Les facteurs favorisants tels que le tabagisme, l’obesite et le diabete ont egalement ete recueillis. Resultats Les 81 patientes, âgees de 40 a 83 ans (mediane : 70 ans), ont toutes beneficie d’une irradiation du sein apres chirurgie conservatrice de 42,9 Gy en 13 fractions et cinq semaines sans irradiation des aires ganglionnaires. Aucune patiente n’a recu en concomitance de chimiotherapie, ni d’hormonotherapie. Dix-sept patientes on ete traitees en decubitus dorsal et 64 (79 %) en decubitus lateral avec une technique isocentrique precedemment decrite. Durant la radiotherapie, il a ete observe une radiodermite de grade 1 chez 34 patientes (42 %) et aucune chez 47 patientes (58 %). A la consultation de fin de traitement, il y avait 66 radiodermites (81 %), dont 59 de grade I et sept de grade II. Quinze patientes (19 %) n’avaient aucune reaction cutanee. La tolerance cutanee immediate de ce schema hypofractionne a donc ete consideree comme excellente, mais dans les deux semaines apres la fin de l’irradiation, 20 patientes (25 %) ont demande a etre vues en consultation en urgence par un oncologue radiotherapeute du fait d’une aggravation des effets secondaires cutanes. Toutes ont ete examinees par leur oncologue radiotherapeute et/ou une infirmiere. Neuf d’entre eux avaient une radiodermite de grade I et 11 de grade II, avec necessite de soins locaux. Une consultation systematique a ete instauree dix a 14 jours apres la fin de la radiotherapie pour les patientes irradiees selon ce schema. Conclusion L’efficacite et la bonne tolerance du schema d’irradiation adjuvante du sein de 42,9 Gy en 13 fractions ont deja ete prouvees. Le suivi prospectif de ce groupe homogene de patientes a mis en evidence la possibilite de reactions cutanees aigues retardees. Une consultation complementaire au decours du traitement semble necessaire pour diagnostiquer et traiter ces reactions.

Several meta-analyses of the effects of radiotherapy in breast cancer were published. Methodological quality varied largely in these studies, from simply gathering data from published studies or even published abstracts, to more rigorous studies gathering individual data from each patient having participated in the trials analysed. A model of the latter is represented by the successive meta-analyses from the Early Breast Cancer Trialists' Cooperative Group (EBCTCG). These studies have had a strong impact on the clinical practice of radiotherapy in breast cancer, by demonstrating its long-term potential toxic effects, but also its ability to decrease the long-term breast-cancer mortality, regardless of the effects of other breast-cancer treatments. Therefore, it has contributed to the continuous improvement in the techniques of radiotherapy, as well as to its use in the multidisciplinary management of breast-cancer patients.

Purpose To describe a new procedure for breast radiotherapy that will improve tumor bed localization and radiotherapy treatment using a multidisciplinary approach. Patients and Methods This pilot study was conducted by departments of radiation oncology, surgery, and radiology. A new procedure has been implemented, summarized as eight steps: from pre-surgery contrast CT to surgery, tumor bed planning target volume (PTV) determination, and finally breast and tumor bed irradiation. Results Twenty patients presenting with T1N0M0 tumors were enrolled in the study. All patients underwent lumpectomy with the placement of surgical clips in the tumor bed region. During surgery, 1 to 5 clips were placed in the lumpectomy cavity before the plastic procedure. All patients underwent pre- and postoperative CT scans in the treatment position. The two sets of images were registered with a match-point registration. All volumes were contoured and the results evaluated. The PTV included the clips region, the gross tumor volume, and the surgical scar, with an overall margin of 5–10 mm in all directions, corresponding to localization and setup uncertainties. For each patient the boost PTV was discussed and compared with our standard forward-planned PTV. Conclusions We demonstrate the feasibility of a tumor bed localization and treatment procedure that seems adaptable to routine practice. Our study shows the advantages of a multidisciplinary approach for tumor bed localization and treatment. The use of more than 1 clip associated with pre- to postoperative CT image registration allows better definition of the PTV boost volume.

The literature reports low rates of breast conservation after neoadjuvant chemotherapy for operable breast cancers not amenable to initial breast-conserving surgery. This study aims to compare the outcome of lobular vs ductal carcinomas after neoadjuvant chemotherapy. Between 1989 and 1999, 750 patients with clinical stage II/IIIA ductal (672) or lobular (78) invasive breast carcinomas were treated at the Institut Curie with primary anthracycline-based polychemotherapy followed by either breast conservation (surgery and/or radiotherapy) or mastectomy. Median follow-up was 10 years. Clinical response to primary chemotherapy was significantly worse for lobular than for ductal carcinomas (47 vs 60%; P=0.04), but only histological grade remained predictive in multivariate analysis. Breast conservation was high for both ductal and lobular carcinomas (65 and 54%; P=0.07), due, in part, to the use of radiotherapy, either exclusive or preoperative, for respectively 26 and 40% of patients. The lobular type had no adverse effect, neither on locoregional control nor on overall survival, even in the group of patients treated with breast conservation.

Introduction This study aimed to evaluate responses and outcome of hormone-therapy (HT) and radiotherapy (RT) given concurrently for large breast cancers in post-menopausal women. Material and methods Forty-two breast carcinomas in 41 women were treated with HT and concurrent RT to the breast ± lymph node bearing areas. For 30 tumours this was followed by breast surgery (with axillary lymph node dissection when the axilla had not been irradiated). RT delivered a median dose to the tumour of 50 Gy (48–66) and 75 Gy (65–84) for, respectively, preoperative and exclusive RT–HT. Median follow-up was 64 months. Results Out of 42 clinically assessable tumours (after a mean dose of 50 Gy), 9 tumours (21%) had complete clinical responses, 24 (57%) partial responses, 9 (21%) stable disease. Breast-conserving surgery or exclusive RT–HT was possible in 74% of tumours. For 29 patients who underwent breast surgery, the rate of pathological complete responses was 17%. At 50 Gy no skin toxicity higher than grade 2 occurred. Five year OS, RFS and local control were, respectively, 85%, 84% and 97%. Lymphoedema occurred in one patient. Conclusion Concurrent association of RT–HT demonstrated good efficacy, both in terms of clinical and pathological complete responses. It allowed breast conservation with acceptable tolerance and good 5-year local control.

Purpose Electron beam radiotherapy of the chest wall with or without lymph node irradiation has been used at the Institut Curie for >20 years. The purpose of this report was to show the latest improvements of our technique developed to avoid hot spots and improve the homogeneity. Methods and Materials The study was split into two parts. A new electron irradiation technique was designed and compared with the standard one (dosimetric study). The dose distributions were calculated using our treatment planning software ISIS (Technologie Diffusion). The dose calculation was performed using the same calculation parameters for the new and standard techniques. Next, the early skin toxicity of our new technique was evaluated prospectively in the first 25 patients using Radiation Therapy Oncology Group criteria (clinical study). Results The maximal dose found on the five slices was 53.4 ± 1.1 Gy for the new technique and 59.1 ± 2.3 Gy for the standard technique. The hot spots of the standard technique plans were situated at the overlap between the internal mammary chain and chest wall fields. The use of one unique field that included both chest wall and internal mammary chain volumes solved the problem of junction. To date, 25 patients have been treated with the new technique. Of these patients, 12% developed Grade 0, 48% Grade 1, 32% Grade 2, and 8% Grade 3 toxicity. Conclusions This report describes an improvement in the standard postmastectomy electron beam technique of the chest wall. This new technique provides improved target homogeneity and conformality compared with the standard technique. This treatment was well tolerated, with a low rate of early toxicity events.

The characteristics of ipsilateral breast tumour recurrences (IBTRs) relative to those of their primary tumours (PTs) remain scarcely studied. Of 70 young (or =40 years) premenopausal women with IBTRs, we studied a series of 63 with paired histological data. Median follow-up since IBTR was 10 years. Rates of histological types, grades or hormonal receptors were not significantly different in PTs and in IBTRs. The concordance between IBTRs and their PTs was good for histological types. IBTRs with conserved histological types tended to occur more locally, but not significantly sooner than others. These IBTRs had good concordance for hormone receptors. In discordant cases there were as many losses as appearances of the receptors. The concordance was weak for grades, with equivalent numbers of IBTRs graded lower as higher than their PTs. The 10-year overall survival rate was 70%. Neither the conservation of histological type, location, nor of the two combined were associated with deaths. Early (2 years) IBTRs, tended to be associated with poorer survival (HR=2.24 (0.92-5.41); P=0.08). IBTRs did not display features of higher aggressiveness than PTs. Neither clinical nor histological definition of a true recurrence could be established other than the conservation of the histological type.