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Purpose To determine prospectively the efficacy and to assess potential side effects of melphalan selective ophthalmic artery chemotherapy (SOAC) as first-line treatment for unilateral retinoblastoma. Design Phase 2 nonrandomized, prospective study. Participants Patients with unilateral retinoblastoma group B, C, or D of the International Classification for Intraocular Retinoblastoma (IRC). Group D eyes with massive vitreous seeding were not eligible. Methods Melphalan SOAC associated with diode laser thermotherapy, cryotherapy, or both at 4-week intervals (3–6 cycles). For persistent vitreous seeding, intravitreal melphalan chemotherapy also was used. Main Outcome Measures The primary outcome was globe preservation rate. Secondary outcomes were tumor relapse rate, occurrence of ocular or systemic adverse events, and measurement of the dose area product (DAP). Results Between 2012 and 2017, 39 patients (39 eyes) with unilateral retinoblastoma were included prospectively. Three included patients did not receive SOAC (2 catheterization failures and 1 case of viral syndrome) and were considered failures. At diagnosis, IRC groups for the 36 treated patients were: B, n = 4 (11%); C, n = 13 (36%); and D, n = 19 (53%); median age was 21.5 months (range, 3.2–61.6 months). Median number of SOAC cycles was 3.9 (range, 1–6 cycles), and median melphalan dose was 4.9 mg/procedure. The median DAP was 1.24 Gy.cm2/procedure. Median follow-up was 63 months (range, 34–93 months). SOAC was associated with local treatments for 31 patients (86%): diode laser thermotherapy for all of them and cryotherapy or intravitreal chemotherapy for 10 (32%) and 9 patients (25%), respectively. SOAC treatment was interrupted in 5 patients because of severe ophthalmic (ptosis, n = 2; retinal ischemia, n = 2) or systemic (hypotension, n = 1) adverse events. At the cutoff date analysis, all patients were alive without metastasis. The 18-month eye preservation rate was 80% (range, 68.6%–94.6%). After a follow-up of at least 30 months, the ocular preservation rate was 69% (n = 24 preservations). Conclusions This first prospective trial demonstrated that SOAC with melphalan alone as first-line treatment for retinoblastoma is efficient and well tolerated with no metastatic events, although ocular ischemic complications were observed.

Outcomes for adults with soft tissue sarcoma are better when managed at referral centers. Care guidelines advise for 5 main criteria: 1-Imaging before biopsy; 2-Tumor biopsy before surgery; 3-Multidiscipinary team discussion (MTD) before biopsy; 4-Biopsy in "expert centers"; 5-Somatic molecular biology feasible. The aim is to describe and assess the prognostic impact of initial management of STS according to the type of referring centers and the number of optimal criteria.Monocentric retrospective analysis of the management of 127 youths (0-25 years) with localized STS treated from 2006 to 2015.Median age at diagnosis was 9.6 years (range: 025). Overall, only 41% patients had 5/5, 28% 3-4, 31% ≤2. No adequate imaging was performed before surgery/biopsy for 18% patients, no biopsy before treatment for 29%. Patients referred by "expert centers" had higher compliance to guidelines (P = 0.025). Upfront surgery was performed in 59/127 patients. Immediate re-operation was inversely related to the number of criteria (0% when 5 criteria vs. 14% for 3-4, 46% if ≤ 2; P 0.001). For malignant tumors, outcome was better when 5 criteria were reached: 5 year EFS 90.8% (81.4-100.0%) vs. 71.6 for (60.4-84.9%; ≤4 criteria; p = 0.033), OS 93.6% (85.5-100%) vs. 79.5% (68.9-91.8%; p = 0.11), and LRFFS 90.6% (81.0-100.0) vs. 73.1% (62.0-86.3%; p = 0.047).Less than half of the youths with STS are initially managed according to international guidelines, highlighting the need for better information about optimal management. These results plead for immediate management in reference centers to reduce initial burden of therapy.

Background Primary central nervous system lymphomas (PCNSLs) are mainly diffuse large B-cell lymphomas (DLBCLs) of the non-germinal center B-cell (non-GCB) subtype. This study aimed to determine the efficacy of rituximab plus lenalidomide (R2) in DLBCL–PCNSL. Patients and methods Patients with refractory/relapsed (R/R) DLBCL–PCNSL or primary vitreoretinal lymphoma (PVRL) were included in this prospective phase II study. The induction treatment consisted of eight 28-day cycles of R2 (rituximab 375/m2 i.v. D1; lenalidomide 20mg/day, D1-21 for cycle 1; and 25mg/day, D1-21 for the subsequent cycles); in responding patients, the induction treatment was followed by a maintenance phase comprising 12 28-day cycles of lenalidomide alone (10mg/day, D1-21). The primary end point was the overall response rate (ORR) at the end of induction (P0=10%; P1=30%). Results Fifty patients were included. Forty-five patients (PCNSL, N=34; PVRL, N=11) were assessable for response. The ORR at the end of induction was 35.6% (95% CI 21.9–51.2) in assessable patients and 32.0% (95% CI 21.9–51.2) in the intent-to-treat analysis, including 13 complete responses (CR)/unconfirmed CR (uCR; 29%) and 3 partial responses (PR; 7%). The best responses were 18 CR/uCR (40%) and 12 PR (27%) during the induction phase. The maintenance phase was started and completed by 18 and 5 patients, respectively. With a median follow-up of 19.2months (range 1.5–31), the median progression-free survival (PFS) and overall survival (OS) were 7.8months (95% CI 3.9–11.3) and 17.7months (95% CI 12.9 to not reached), respectively. No unexpected toxicity was observed. The peripheral baseline CD4/CD8 ratio impacted PFS [median PFS=9.5months (95% CI, 8.1–14.8] for CD4/CD8≥1.6; median PFS=2.8months, [95% CI, 1.1–7.8) for CD4/CD8 Conclusions The R2 regimen showed significant activity in R/R PCNSL and PVRL patients. These results support assessments of the efficacy of R2 combined with methotrexate-based chemotherapy as a first-line treatment of PCNSL. Clinical trials number NCT01956695.

Context Advance care planning is essential to enable informed medical decisions to be made and to reduce aggressiveness in end-of-life (EOL) care. Objectives This study aimed to explore whether a question prompt list (QPL) adapted to French language and culture could promote discussions, particularly on prognosis and EOL issues, among advanced cancer patients attending outpatient palliative care (PC) consultations. Methods In this multicenter randomized study, patients assigned to the intervention arm received a QPL to help them prepare for the next consultation one month later. The main inclusion criteria were advanced cancer patients referred to the PC team with an estimated life expectancy of less than one year. The primary endpoint was the number of questions raised, globally and by topic. The secondary objectives were the impact of the QPL on psychological symptoms, quality of life, satisfaction with care, and coping styles at two months. Results Patients (n = 71) in the QPL arm asked more questions (mean 21.8 vs. 18.2, P = 0.03) than patients in the control arm (n = 71), particularly on PC (5.6 vs. 3.7, P = 0.012) and EOL issues (2.2 vs. 1, P = 0.018) but not on prognosis (4.3 vs. 3.6, not specified). At two months, there was no change in anxiety, depression, or quality of life in either arm; patient satisfaction with doctors' technical skills was scored higher (P = 0.024), and avoidance coping responses were less frequent (self-distraction, P = 0.015; behavioral disengagement, P = 0.025) in the QPL arm. Conclusion Questions on PC and EOL issues in outpatient PC consultations were more frequent, and patient satisfaction was better when a QPL was made available before the consultation.

To analyse long-term overall survival, relapse-free survival and late toxicities in a series of 675 patients treated between 1999 and 2003, with a median follow-up of 132 months.The cohort included low-risk patients and a selection of "favourable-intermediate" risk patients. All patients were homogeneously treated using an intraoperative dynamic planning prostate brachytherapy technique, with loose 125 iodine seeds. Hormone therapy, consisting most often of an anti-androgen alone, was given in 393 patients (58%).The 10-year overall survival was 92% (95% confidence interval [CI]: 90-94) without a significant difference between the low and the select intermediate-risk groups (P=0.17). The 10-year relapse-free survival rate for the entire cohort was 82% (95% CI: 79-85), and was significantly higher in the low-risk group than in the intermediate one (87 vs 71%; P0.0001). Twenty-six percent of the relapses observed in this series occurred after more than 10 years of follow-up. The 10-year cumulative incidence of grade 3-4 urinary toxicity (whatever the delay and the recovery) was 5.78%. The cumulative incidence of grades 3-4 rectal toxicity in the present series was 1.65% at 10 years. As for sexual toxicity, 61% of our patients retained an erectile capacity at 10 years (with or without oral medication), with age being a major factor.With a median follow-up of more than 11 years, this series appears to confirm the excellent long-term results of low-dose rate prostate brachytherapy, both in terms of survival and in terms of toxicity.

Background: There is a lack of information as to which molecular processes, present at diagnosis, favor tumour escape from standard-of-care treatments in cervical cancer (CC). RAIDs consortium (www.raids-fp7.eu), conducted a prospectively monitored trial, [BioRAIDs (NCT02428842)] with the objectives to generate high quality samples and molecular assessments to stratify patient populations and to identify molecular patterns associated with poor outcome. Methods: Between 2013-2017, RAIDs collected a prospective CC sample and clinical dataset involving 419 participant patients from 18 centers in seven EU countries. Next Generation Sequencing has so far been carried out on a total of 182 samples from 377 evaluable (48%) patients, allowing to define dominant genetic alterations. Reverse phase protein expression arrays (RPPA) was applied to group patients into clusters. Activation of key genetic pathways and protein expression signatures were tested for associations with outcome. Findings: At a median FU of 22 months, progression-free survival rates of this FIGO stage IB1-IV population, treated predominantly (87%) by chemoradiation, were 65*4% [CI95%: 60*2-71.1]. Dominant oncogenic alterations were seen in PIK3CA (40%), while dominant suppressor gene alterations were seen in KMT2D (15%) and KMT2C (16%). Cumulative frequency of loss-of-function (LOF) mutations in any epigenetic modulatorgene alteration was 47% and it was associated with PIK3CA gene alterations in 32%. Patients with tumours harbouring alterations in both pathways had a significantly poorer PFS. A new finding was the detection of a high frequency of gains of TLR4 gene amplifications (10%), as well as amplifications, mutations, and non-frame-shift deletions of Androgen receptor (AR) gene in 7% of patients. Finally, RPPA protein expression analysis defined three expression clusters. Interpretation: Our data suggests that patient population may be stratified into four different treatment strategies based on molecular markers at the outset. Funding: European Union's Seventh Program grant agreement No 304810. Declaration of Interest: All authors declared: No conflict of interest. Ethical Approval: Ethical review was conducted according to national requirements and in accordance with the Declaration of Helsinki. All tumour and serum samples and clinical data were registered in a common database using a unique barcode system assuring data privacy.

Introduction Dans le cadre d’une etude retrospective de patients atteints d’un cancer et exposes au cours de leur suivi a des dispositifs medicaux implantables (DMI), nous nous interessons a l’analyse de l’impact d’une exposition dependante du temps sur le risque de deces. Les modeles comme le modele de Cox ou exponentiel par morceaux (Em) font l’hypothese que le risque instantane d’evenement a l’instant t ne depend que de l’exposition a t et non des expositions recues jusqu’a t−. Le modele WCE (« Weighted Cumulative Exposure ») permet de prendre en compte les expositions passees et d’en etudier l’effet cumule en estimant une courbe ponderant les valeurs de ces expositions [1] . Ce modele est semi-parametrique, comme le modele de Cox et contrairement au modele Em qui suppose une fonction de risque instantane de base constante par morceaux. Il permet le calcul d’hazard ratios associes a differentes trajectoires d’expositions. Methodes L’objectif de ce travail est de comparer, a l’aide de simulations, le modele WCE au modele de Cox et au modele Em avec : – application de differentes courbes de ponderation definissant l’influence des expositions passees sur le risque instantane a l’instant t, allant d’une influence faible (ce cas de figure se rapprochant de l’hypothese faite par les modeles de Cox et Em) a une influence importante ; – le taux de censure variant entre 0 % et 80 % ; – la fonction de risque instantane de base des temps d’evenements qui est soit issue d’une loi uniforme, soit parametree par une fonction constante par morceaux. Dans ce dernier cas, deux modeles Em ont ete appliques, correctement et incorrectement specifies. La metrique utilisee pour les modeles de Cox et Em est le biais entre l’effet estime par ces modeles et la vraie valeur de l’effet de l’exposition a l’instant t sur le risque instantane a t ; la metrique utilisee pour le modele WCE est l’ecart moyen entre les courbes de poids estimees et la vraie courbe de ponderation. Suite aux resultats de ces simulations, le modele le plus interessant a ete applique aux donnees de l’etude retrospective. Resultats Le modele WCE est performant quel que soit le niveau d’influence des expositions passees sur le risque instantane d’evenement. Les modeles de Cox et Em surestiment l’effet de l’exposition recue a l’instant t lorsque les expositions passees ont une influence importante. Nous avons donc applique le modele WCE aux donnees de l’etude. Aucun effet significatif de l’effet cumule des expositions aux differents types de DMI sur le risque de deces n’a pu etre mis en evidence. Conclusion Le modele WCE semble etre approprie lorsqu’il n’existe pas de connaissance a priori sur la dynamique de l’exposition etudiee. Il reste cependant plus complexe a interpreter qu’un modele de Cox et il est par consequent preferable d’utiliser ce dernier lorsque qu’il existe une connaissance clinique fiable de l’absence d’effet cumule des expositions passees.

Purpose To report the efficacy of Hydrosorb® versus control (water based spray) as topical treatment of grade 1–2 radiodermatitis in patients (pts) treated for early stage breast cancer (BC) with normo fractionated radiotherapy (RT). Patients and methods BC pts were randomized to receive either Hydrosorb® (A) or water based spray (B). The primary endpoint was local treatment failure defined as interruption of RT because of skin radiotoxicity or change of local care because of skin alteration. Secondary endpoints were: evaluation of skin colorimetry, pain, quality of life. Results Two-hundred seventy-eight pts were enrolled. There were 186 successfully treated pts. There were 60 "failures" in the Hydrosorb® arm, and 62 in the control arm ( p =0.72), but mostly without interruption of the RT. Twenty-four pts stopped RT for local care. The average absolute reduction of colorimetric levels between day 28 and day 0 was 4 in the Hydrosorb®, and 4.2 in the water spray groups, respectively ( p =0.36). Forty-eight patients in the Hydrosorb® arm had a VAS >2 versus 51 pts in the placebo arm, i.e. 34% and 38%, respectively ( p =0.45). A significant reduction of pain was observed on D 7 and D 21 in the Hydrosorb® arm. Conclusions The present study showed no significant difference between Hydrosorb® and simple water spray in the treatment of acute radio-induced dermatitis even if there was a trend to an improvement in pain at the first weeks after the treatment. Systematic prevention measures and modern breast cancer radiotherapy techniques now allow excellent tolerability, but the place of topical treatment to optimize this tolerability has yet to be defined. It seems that the most important part of the skin care is the prevention of skin reactions using new adapted techniques, as well as strict hygiene.

Summary Introduction To describe the results of retinoblastoma treatment from 1995–2009 in a single institution. Material and methods Retrospective review of the charts of patients treated for retinoblastoma. Clinical characteristics at diagnosis, treatments and outcomes in terms of survival and ocular preservation are described. Results During the study period 826 children were referred for retinoblastoma and 730 were managed in our institution. Four hundred and eleven children presented with unilateral retinoblastoma and 319 with bilateral retinoblastoma. Median follow-up is of 93 months. Global survival is 98.5% of children, 10 children presented with second tumors, 11 children died (6 of tumor-related causes). Of the 411 children with unilateral retinoblastoma enucleation was needed at diagnosis for 324 (78.8%). Conservative treatments were attempted for 87 patients (21.2%) and ocular preservation obtained for 65 patients (74% of eyes). Three hundred and nineteen patients presented with bilateral retinoblastoma. Three hundred and ten could be treated conservatively for at least one eye. Initial intravenous chemotherapy was necessary for 75% of them. Ocular preservation without external beam radiation was possible for 221 patients (70%). The use of EBR decreased significantly after 2004 (9.1% of eyes vs 25.1%: P Discussion Management and treatment of retinoblastoma are complex, adapted to the extent of the disease. Survival is good. Enucleation is still required for extensive ocular disease, especially for unilateral patients. Intravenous chemotherapy allows good tumor control and eye preservation and decrease the need of EBR. Conclusions Retinoblastoma treatment with intravenous chemotherapy and ocular adjuvant therapies is very effective on the local tumor control and eye preservation.

Background To improve the therapeutic index of whole-brain radiation therapy (WBRT) in the treatment of brain metastases (BM) from breast cancer, we investigated the efficacy and safety of WBRT combined with temozolomide (TMZ) in this population. Patients and methods This phase II multicenter prospective randomized study included patients with newly diagnosed intraparenchymal BMs from breast cancer, unsuitable for surgery or radiosurgery. All patients received conformal WBRT (3 Gy × 10–30 Gy), with or without concomitant TMZ administered at a dosage of 75 mg/m2/day during the irradiation period. The primary end point was objective response rate (ORR) 6 weeks after the end of treatment, defined as a partial or complete response on systematic brain MRI (modified WHO criteria). Secondary end points were progression-free survival (PFS) and overall survival (OS), neurologic symptoms, and tolerability. Results Between February 2008 and November 2010, 100 patients were enrolled in the study (50 in the WBRT + TMZ arm, 50 in the WBRT arm). Median age was 55 years (29–79). Median follow-up was 9.4 months [1.0–68.1]. ORRs at 6 weeks were 36% in the WBRT arm and 30% in the WBRT + TMZ arm (NS). In the WBRT arm, median PFS was 7.4 months and median OS was 11.1 months. In the WBRT + TMZ arm, median PFS was 6.9 months and median OS was 9.4 months. Treatment was well tolerated in this arm: the most common ≥grade 2 acute toxicity was reversible lymphopenia. Conclusion WBRT combined with TMZ did not significantly improve local control and survival in patients with BMs from breast cancer. Clinicaltrials.gov NCT00875355.

Introduction In 2014, the RD IV should not be correlated to the output (OS) and affect the OS only indirectly through its effect on the treatment. We used “Activity level of FCCC”, which represents the number of cases in the whole database per contributing FCCC as IV with five strata. Analysis was carried out with the two-stage residual inclusion method (2SRI). For the quasi-trial analysis, the idea is to use a “superficial” randomized trial using variables, for example centers, reflecting a definite preferences for certain treatment options. Indeed, comparisons of results between centers can be informative and it is likely such differential preferences exist in real-life practice. In this study, we have considered the percentage of patients with bevacizumab + paclitaxel in each center, regardless of treatment arm. Results In the first analysis published by Delaloge and al., the OS adjusted for major prognostic factors was significantly longer in the paclitaxel and bevacizumab group compared with paclitaxel [hazard ratio (HR) 0.672, 95 % confidence interval (CI) 0.601–0.752] [1] . Using IV method to support these results seems difficult due to the lack of candidate variables. The level of activity of FCCC, with five strata, leads to different conclusions compared with those obtained in Delaloge's paper. Conclusion For the quasi-trial analysis, the percentage of patients with bevacizumab + paclitaxel had an independent and significant impact on OS [HR = 0.180, CI = 0.043–0.748]. Centers in which more than 50 % of the patients were reintroduced had an adjusted HR for OS of [HR = 0.735, CI = 0.645–0.837] compared with centers in which 50 % or less of patients were treated with bevacizumab + paclitaxel. These results consolidate those obtained with a conventional multivariate Cox model.

Introduction Functional residual capacity (FRC) and lung clearance index (LCI) are sensitive parameters for early detection of airway disease in infancy. The closed helium dilution method has been applied to assess lung volume and ventilation inhomogeneity (VI) in spontaneously breathing infants. Aims The aims of this study were as follows: (1) to assess applicability of the helium gas dilution technique in mechanically ventilated infants with high-risk congenital diaphragmatic hernia (CDH) and to evaluate changes in breathing patterns, lung volume, and VI during the first days of life before and after surgery, and (2) to analyze the possible correlation between changes in lung volume, cerebral hemodynamics, and oxygenation before and after surgical correction of CDH through near-infrared spectroscopy (NIRS) monitoring. Methods Lung function tests were performed by multibreath washout traces with an ultrasonic flowmeter and helium gas dilution technique. For all babies, three acceptable FRC and LCI measurements were collected for each test (mean and SD of three measurements were calculated) before surgery ( T 0 ), 24h after surgery ( T 1 ) during mechanical ventilation, and within 24h after extubation in spontaneous breathing ( T 2 ). Cerebral and splanchnic hemodynamics were continuously monitored by NIRS during mechanical ventilation to evaluate relationships between changes in lung volume and capillary–venous oxyhemoglobin saturation in tissues. Fraction of inspired oxygen delivered was adjusted to keep oxygen saturation between 90% and 95%. Results Thirteen CDH infants were studied; median GA=38weeks (range 35–41) and median BW=3000g (range 1850–3670). FRC and LCI significantly improved after extubation when compared with pre-surgical values. No differences were found in tidal volume (Vt) and NIRS monitoring before and after surgery and after extubation. Neither LCI nor FRC was correlated with NIRS values. Conclusions Helium gas dilution technique is an applicable and reliable technique to measure lung volumes and ventilation inhomogeneity also in ventilated infants. NIRS is a non-invasive technique to monitor tissue oxygenation during surgery and mechanical ventilation. In CDH newborns these preliminary data show an improvement in both FRC and LCI after extubation.

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 There is a scarce clinical experience about adjuvant helical tomotherapy (HT) in patients affected by malignant pleural mesothelioma (MPM) even though it appears as a useful technique to treat complex volume as the pleural cavity, and seems to have better dose distribution than the “classic” intensity modulated radiotherapy (IMRT). Methods and materials Twenty-four patients received adjuvant radiotherapy (RT) by HT from August 1st, 2007 to December 1st, 2009 at Curie Institute (Paris) and Rene Gauducheau Cancer Center (Nantes). Thirteen patients had neoadjuvant chemotherapy. Extrapleural pleuropneumonectomy (EPP) was done in 23 patients. Median dose to PTV was 50 Gy [48.7–55.9 Gy] (2 Gy/fraction). Acute and long term toxicities, disease free survival (DFS), overall survival (OS) and relapses are presented. Results Average follow up after RT was 7 months. The disease was staged mostly as T2–T3, N1–N2. Nineteen patients had epithelial type histology. Most patients tolerated radiotherapy with grade 1–2 side effects: redness of the skin, light cough or dyspnea, fatigue, nausea and odynophagia, mild increase of the post-operative thoracic pain. Grade 3 pneumonitis was suspected in 2 patients. Two grade 5 pneumonitis were also suspected. Eleven patients had a follow up of more than 6 months and no long term side effects related with HT were noted. At 24 months, 51.8% of patients were free of disease. Thirty percent of patients relapsed, with 2 patients presenting local relapses. Two patients died from recurrence. Conclusion With limited follow up, HT has comparable toxicity to those observed with traditional IMRT. Higher radiation dose and good coverage results in excellent local control.

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 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.

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.

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.

Purpose: To evaluate the accuracy of clinical examination and of three imaging modalities (ultrasound [US] scan, mammography, and magnetic resonance imaging [MRI]) to assess the tumor response of breast cancer to a preoperative regimen of concurrent radiochemotherapy for large breast cancers, using pathologic data as the reference. Methods and Materials: Sixty women were accrued. Treatment consisted of 4 cycles of (5-fluorouracil-vinorelbine) chemotherapy with, starting with the second cycle of chemotherapy, locoregional radiotherapy to the breast and the internal mammary and supraclavicular and infraclavicular lymph nodes. Breast surgery and axillary lymph node dissection were subsequently performed. Breast imaging assessments were performed both before chemotherapy and preoperatively. Results: The correlation coefficients between tumor dimension at imaging and pathology were statistically significant for US scan ( r = 0.4; p = 0.006) and MRI ( r = 0.4; p = 0.004) but not for clinical examination ( r = 0.2; p = 0.16) or mammography ( r = −0.15; p = 0.31). Furthermore, the area under the receiver operating characteristic curve for MRI was 0.81, compared with 0.67 for US scan. At the optimal threshold score, MRI performed with 81% sensitivity and 75% specificity. Conclusion: Compared with clinical examination, US scan, or mammography, MRI substantially improved the prediction of pathologic tumor response to preoperative concurrent radiochemotherapy for large breast cancers.

Phyllodes tumors are rare fibroepithelial tumors of the breast. The pathologic grading of phyllodes tumors based on the aspect of the stromal component, is divided into 2 or 3 grades according to the system used. To determine whether genetic markers could be of use for improving the classification of phyllodes tumors and to provide a better knowledge of the genetic alterations in these tumors, we analyzed chromosomal changes detected by comparative genomic hybridization (CGH) in comparison with histological data, in a series of 30 cases. Recurrent chromosome imbalances were observed in 55, 91 and 100% of benign, borderline and malignant phyllodes tumors, respectively. The mean number of chromosome changes was one in benign, six in borderline, and six in malignant phyllodes tumors. Most frequent genetic imbalances were +1q (12/30), -13q (7/30), -6q (9/30), +5 (9/30) and -10p (8/30). Gains of 1q, present in only one of nine benign tumors, were found in 11/21 (51%) borderline or malignant tumors. Losses of 13q have 13q14.2 as smallest region of overlap, suggesting that the RB1 gene could be the target of deletions. Amplifications of 12q14, involving the MDM2 locus, and of 8p24, involving the MYC gene, were observed in one case each. Borderline and malignant phyllodes tumors could not be differentiated on the basis of their genomic imbalances (presence and number of chromosomal changes, presence of 1q gain and/or 13q loss). Conversely, benign tumors could be significantly differentiated from the group composed of borderline and malignant tumors (P

BRCA1 and BRCA2 germline mutations are associated with a strong risk of breast cancer, which may preclude breast-conserving treatment in carriers. This study examined whether mutation status influenced the rate of breast cancer recurrence following breast-conserving treatment. BRCA1 and BRCA2 genes were screened for germline mutations in 131 patients with a family history of breast and/or ovarian cancer, who had been treated with breast-conserving surgery and radiotherapy. The 131 patients with familial history were matched to 261 patients without, according to age at diagnosis and year of treatment. The follow-up of controls was at least equal to the time-interval between diagnosis and genetic testing in familial cases. Matched cohorts were compared according to rates of breast cancer recurrence as first event and contralateral breast cancer using log-rank tests. BRCA1/2 mutations were found in 20.6% patients with a family history. Nineteen patients had a BRCA1 mutation and 8 had a BRCA2 mutation. Breast cancers in mutation carriers were more often grade III (p < 10-4) and oestrogen receptor negative (p = 0.005) than tumours in both non-carriers and controls. Median follow-up for all 392 patients was 8.75 years. No significant differences in breast cancer recurrence as first event were seen between BRCA1/2 tumours and controls (p = 0.47), carriers and non-carriers with a family history (p = 0.96), or non-carriers and controls (p = 0.10). On multivariate analysis, age was the most important factor significantly predicting for breast cancer recurrence. The rate of contralateral breast cancer was significantly increased in all patients with a family history: BRCA1/2 carriers versus controls (p = 0.0003), non-carriers versus controls (p = 0.0034) and carriers versus non-carriers (p = 0.02). At a 9-year median follow-up, the rate of ipsilateral breast cancer recurrence was not higher in BRCA1 and BRCA2 mutation carriers than in non-carriers with a family history or sporadic cases. These results support the hypothesis that breast tumours in BRCA carriers are more sensitive to radiation. Therefore, breast-conserving treatment can be offered to these patients. However, longer follow-up is needed to ensure that the rate of new primary cancer in the treated breast does not increase in the long-term.

Resume Objectifs. – Le but de ce travail etait d'etudier le nombre de grains migrants, les sites de migration et les eventuels facteurs de prediction de migration apres curietherapie de prostate par implantation de grains libres d'iode 125. Patients et methodes. – Les dossiers des 170 patients traites consecutivement par l'equipe de l'institut Curie–hopital Cochin–hopital Necker, du 1 er septembre 2001 au 31 aout 2002, ont ete analyses. Ont ete pris en compte les grains migrants pulmonaires visualises sur le cliche de thorax effectue systematiquement deux mois apres l'implantation, ainsi que les grains recuperes dans les urines (apres filtrage de ces dernieres) et le sperme (rapports proteges). Resultats. – Sur 12 179 grains implantes, 44 ont migre (0,36 %), la majorite (32/44, 73 %) vers les poumons. Ces migrations ont interesse 35 patients, soit 21 % des cas traites durant cette periode. Dans la grande majorite des cas (77 %), un seul grain a migre. Une relation significative ( p = 0,04) a ete retrouvee entre le nombre de grains migrants et le nombre de grains implantes (ou le volume prostatique, ces deux parametres etant lies de facon etroite). Plus specifiquement, une relation significative ( p = 0,02) a pu etre mise en evidence entre le nombre de grains implantes en peripherie et le nombre de grains migrants pulmonaires. Conclusion. – Le pourcentage de grains migrants dans cette serie reste l'un des plus bas de la litterature pour la technique des grains libres. La migration en general d'un seul grain n'a aucune consequence clinique, et aucun effet deletere (ou tres peu) sur la distribution de dose. Neanmoins, la nette predominance des migrations pulmonaires dans notre serie nous a pousse a modifier legerement notre technique d'implantation. Nous evitons actuellement dans toute la mesure du possible d'implanter les grains de facon trop peripherique, du fait du risque de migrations vers les plexus veineux periprostatiques, puis vers les poumons.

Purpose To report the technical aspects, complications, and outcomes concerning fine needle aspiration biopsy (FNAB) in uveal melanoma. Design Retrospective cohort study. Methods Patients with uveal melanoma who underwent transscleral or transvitreal FNAB at an ocular oncology center were retrospectively evaluated. FNAB was performed if the tumor was more than 5 mm in thickness. Array comparative genomic hybridization analysis was performed on biopsy samples with sufficient tissue. The main outcome measures were success (sample that gave a successful result for biomarker analysis) rate, complications, liver metastasis, and overall survival. Results There were 217 (114 male, 52%) consecutive study patients with a mean age of 56.7 (16–84) years. The mean follow-up period was 31 (range 3.6–61.3) months. Mean tumor thickness was 8.4 (range 5–12) mm. The overall success rate of the procedure was 169 patients (77.9%). Thirty-one patients (14.3%) experienced intravitreal hemorrhage, of whom 9 (4.1%) required vitreal surgery. There was no case of endophthalmitis, orbital dissemination, local recurrence, or rhegmatogenous retinal detachment. Thirty-two patients (14.7%) developed metastasis during the study, of whom 20 (9.2%) died. Of the 169 successful samples, 53 patients (31%) were classified as low risk, 41 (24%) as intermediate risk, and 54 (32%) as high risk. Fifteen patients (9%) did not have any detectable chromosomal abnormality and 6 (4%) could not be classified. Conclusion FNAB is a relatively safe and successful technique that can be routinely used to obtain tissue for molecular genomic analysis; such analysis helps determine the diagnosis and prognosis in uveal melanoma.

derived from several items in the FACT-Brain. Cognitive impairment was indicated by a patient’s cognitive function test score being 1.5 SD worse than a normative group in at least one major cognitive domain (e.g., memory, attention, language, executive function, or visuospatial skills). Patients were judged not to be demented based on the eligibility criterion of ECOG performance status equal to one non-memory deficit), and nonamnestic/multi-domain (> 2 non-memory deficits). Results: The sample was 91% white, 54% female, with median age of 55 years. Sixty-six percent had primary brain tumors, 27% brain metastases, and 8% PCI. Median time from radiation treatment to study enrollment was 38 months. Ninety-five percent had ECOG PS 0-1. One hundred fortysix of 197 (74%) patients met the criteria for MCI. Specifically, of those meeting the MCI criteria, 60% had amnestic/multi-domain MCI, 7% had amnestic/single domain MCI, 25% had non-amnestic/multi-domain MCI, and 8% had non-amnestic/single domain MCI. Fifty-one of 197 patients did not meet the MCI criteria, 20 (10%) met definition for early dementia based on presence of significant functional impairment. Conclusions: In the cohort of irradiated brain tumor survivors reported herein, three-quarters met the criteria for MCI, 10% for early dementia. Long-term follow-up will be needed to assess the utility of MCI typology in this patient population. Acknowledgment: This study was supported by NIH/NINR grant 5 R01 NR009675 and NIH/NCI grant 2 U10 CA 81851-09-13). Author Disclosure: E. Shaw: None. N. McKee: None. D. Case: None. J. Lawrence: None. G. Lesser: None. M. Naughton: None. A. Peiffer: None. M. Loghin: None. J. Giguere: None. V. Stieber: None. S. Rapp: None.