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PURPOSE To describe the quality assurance (QA) program and early toxicities in the phase III randomized trial BONBIS (NCT00907868) on the role of a localized radiation boost in ductal carcinoma in situ (DCIS). MATERIALS AND METHODS From November 2008 to July 2014, 2004 patients were randomized in arm A (only whole breast radiotherapy, WBRT) and arm B (WBRT + boost). The QA program involved 44 participant centers that performed the dummy run (DR). Compliance and uniformity of clinical target volume (CTV) delineations, and dose prescription and delivery according to the BONBIS trial radiotherapy guidelines were analyzed. Acute toxicities (during and up to 3 months after radiotherapy completion, NCI-CTCAE v3.0 classification) were evaluated in 1929 patients. RESULTS The differences in whole breast CTV (CTV1) and planning target volume (PTV1) were ≤10%, and the differences in boost CTV (CTV2) and PTV (PTV2) were ≥20% compared with the reference DR values; 95% of the prescribed dose encompassed 98.7% and 100% of the median CTV1 and CTV2. Grade ≥2 breast erythema (38.3% vs. 22.4% of grade 2 and 5.4% vs. 2.1% of grade 3, p

Adjuvant radiotherapy is an essential component of the treatment of breast cancer. 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. A boost dose over the tumour bed is required if the patient is younger than 50 years-old. Partial breast irradiation could be routinely proposed as an alternative to whole breast irradiation, but only in 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 neoadjuvant 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 infraclavicular 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). Hypofractionation regimens (42.5Gy in 16 fractions, or 41,6Gy en 13 or 40Gy en 15) are equivalent to conventional irradiation and must prescribe after tumorectomy in selected patients. 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 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 or after radiotherapy.

Purpose/objective: The association of 3D Conformal External Beam Radiotherapy (3D-CEBRT) with adjuvant Androgen Deprivation Therapy (ADT) proved to treat patients with intermediate- and high-risk localized prostate cancer (IR and HR). However, older patients were underrepresented in literature. We aimed to report the oncological results and morbidity 3D-CEBRT +ADT in &ge, 80 years patients. Material and Methods: From June 1998 to July 2017, 101 patients &ge, 80 years were included in a tertiary center. The median age was 82 years. ADT was initiated 3 months prior 3D-CEBRT in all patients, with a total duration of 6 months for IR prostate cancer (group A, n = 41) and 15 months for HR prostate cancer (group B, n = 60). Endpoints included overall survival (OS), metastasis-free survival (DMFS), biochemical recurrence-free survival (BRFS) and toxicity. Results: Five years-OS was 95% and 86.7% in groups A and B, respectively. Cardiovascular events occurred in 22.8% of &ge, 80 years patients with no impact on OS. In the multivariate analysis, age &lt, 82 years, Karnofsky index and normalization of testosterone levels were significantly associated with better OS. Conclusion: Age &ge, 80 years should not be a limitation for the treatment of IR and HR prostate cancer patients with 3D-CEBRT and ADT, but cardiovascular monitoring and prevention are mandatory.

International audience; Although the PIG-A gene mutation frequency (MF) is considered a good proxy to evaluate the somatic MF in animals, evidence remains scarce in humans. In this study, a granulocyte PIG-A-mutant assay was evaluated in patients undergoing radiation therapy (RT) for breast cancer. Breast cancer patients undergoing adjuvant RT were prospectively enrolled. RT involved the whole breast, with (WBNRT) or without (WBRT) nodal area irradiation. Blood samples were obtained from participants before (T0) RT, and T1, T2, and T3 samples were collected 3 weeks after the initiation of RT, at the end of RT, and at least 10 weeks after RT discontinuation, respectively. The MF was assessed using a flow cytometry protocol identifying PIG-A-mutant granulocytes. Cytokinesis-blocked micronucleated lymphocyte (CBML) frequencies were also evaluated. Thirty patients were included, and five of them had received chemotherapy prior to RT. The mean (±SD) PIG-A MFs were 7.7 (±12.1) per million at T0, 5.2 (±8.6) at T1, 6.4 (±8.0) at T2 and 3.8 (±36.0) at T3. No statistically significant increases were observed between the PIG-A MF at T0 and the MFs at other times. RT significantly increased the CBML frequencies: 7.9 ‰ (±3.1‰) versus 33.6‰ (±17.2‰) (p < .0001). By multivariate analysis, the CBML frequency was correlated with age at RT initiation (p = .043) and irradiation volume at RT discontinuation (p = .0001) but not with chemotherapy. RT for breast cancer therapy failed to induce an increase in the PIG-A MF. The PIG-A assay in humans needs further evaluation, in various genotoxic exposures and including various circulating human cells.

Gene mutations are not directly detected by current genotoxicity assays and most of them need a cell culture step. The whole blood PIG-A assay consists in the detection of the mutation frequency within the PIG-A sentinel gene by identification of glycosyl-phosphatidyl-inositol (GPI-) deficient cells. PIG-A mutated/GPI-deficient cells can be detected by flow cytometry as they no longer express surface fluorescence for GPI-linked markers. The last researches have focused on cell enrichment techniques leading to increased throughput and sensitivity. The results of this new and promising biomarker of mutagenesis, performed in humans or rodents, are now available within 2 hours after blood collection.

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.

Resume Objectif de l’etude Evaluer retrospectivement la tolerance, la faisabilite et l’efficacite d’une chimioradiotherapie concomitante apres chimiotherapie d’induction par docetaxel, cisplatine et 5-fluoro-uracile pour les cancers de la tete et du cou localement evolues. Patients et methodes Les donnees de patients de trois centres de radiotherapie du sud-est de la France, atteints de cancers de la tete et du cou localement evolues et pris en charge entre decembre 2007 et juillet 2013 par chimioradiotherapie concomitante, apres chimiotherapie d’induction par docetaxel, cisplatine et 5-fluoro-uracile, ont ete analysees. Les effets indesirables ont ete evalues selon la Common Terminology Criteria for Adverse Events v3.0. Les survies globales et sans maladie ont ete calculees selon la methode de Kaplan-Meier. Resultats Cent soixante-huit patients, majoritairement atteints d’une tumeur de stade T4 (46 %) et N2 (54 %) de l’oropharynx (38 %) ont recu apres chimiotherapie d’induction par docetaxel, cisplatine et 5-fluoro-uracile, une chimioradiotherapie concomitante a base de platine ou cetuximab de 66 a 70 Gy. Les effets indesirables de grade 3-4 etaient moins frequents dans le groupe de patients ayant recu du cisplatine (avec ou sans 5-fluoro-uracile) a la dose de 100 mg/m2 tous les 21 jours par rapport au cetuximab (radiomucite : 32,5 % contre 61 %, p = 0,018 ; radioepitheliite : 13 % contre 61 %, p 1 ; p = 0,006 ; survie sans maladie : 66 % si N Conclusion L’association de chimiotherapie d’induction par docetaxel, cisplatine et 5-fluoro-uracile et de chimioradiotherapie concomitante a donne des resultats satisfaisants au prix d’une toxicite acceptable. Les modalites de la chimiopotentialisation ainsi que sa superiorite par rapport a une chimioradiotherapie concomitante exclusive restent encore a etre precisees.

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.

Resume Objectif de l’etude Les carcinomes adenoides kystiques representent 1 % des cancers ORL. Malgre une croissance lente, leur recidive est frequente. La place de la radiotherapie est debattue. Cette etude retrospective multicentrique du cercle des oncologues radiotherapeutes du Sud porte sur 169 patients. Patients et methodes Sur 169 cylindromes ORL inclus entre 1982 et 2010, 135 n’avaient jamais ete traites et 34 etaient en situation de recidive. Le site tumoral etait la parotide pour 48 patients, la glande sous-maxillaire pour 22, les cavites sinusiennes pour 22, le palais pour 21, ailleurs pour 56. Le stade etait T1 pour 12,4 % des patients, T2 pour 14,2 %, T3 pour 12,4 %, T4 pour 41,4 % et Tx pour 19,5 %, 13 % des tumeurs atteignaient les ganglions et 8,9 % etaient metastatiques. Dix-sept cylindromes parotidiens etaient responsables d’une paralysie faciale. Il a ete realise une chirurgie seule pour 27 patients, une chirurgie suivie de radiotherapie pour 89, une chirurgie suivie de chimioradiotherapie pour 12, une chimioradiotherapie exclusive pour 13, une radiotherapie exclusive pour 14, une autre association pour cinq, une abstention pour sept. La radiotherapie a ete delivree 119 fois par photons, six fois par neutrons et quatre fois par photons et neutrons. La dose mediane delivree a la tumeur etait de 65 Gy, et celle aux ganglions de 50 Gy. Resultats Le suivi moyen etait 58 mois. Les probabilites de survie globale et de survie sans maladie etaient respectivement de 72 % et 72 % a cinq ans, 53 % et 32 % a dix ans. Celle de survie sans rechute locale etait de 81 % a cinq ans, 52 % a dix ans. En analyse multifactorielle, la survie sans maladie etait liee a la chirurgie (p Conclusion Dans cette serie de cylindromes ORL localement evolues, recidivants ou metastatiques, la probabilite de survie globale a dix ans etait de plus de 50 %. La radiotherapie n’a pas influe le pronostic.

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

No study on side effects had showed that conformal radiation therapy for prostate cancer is more harmful in patients older than 70 years to patients younger. The aim of this study was to evaluate acute and late toxicities of conformal radiotherapy, with high dose for localized prostate cancer in patients older than 70 years and compared to patients younger than 70 years. Between 1996 and 2009, 104 patients were treated with radiation therapy and hormonal therapy for localized cancer prostate. Median follow-up was 105 months (9-300). Acute (occurred at ≤ three months) and late side effects of 55 patients older than 70 years (median age: 75 [71-92]) were graded according to the CTCAE 3.0 criteria and compared to the younger population. Median dose to the prostate was 75.6 Gy (67-80) in both groups. There were no significant differences in acute and late side effects between age groups. For patients above 70 years, the incidence of grade II or higher acute and late side effects were respectively 27 and 22% for urologic symptoms and 13 and 16% for rectal symptoms. The frequency of grade III late symptoms was low and ranged between 0 and 6% for the evaluated symptoms, irrespective of age group. Older patients had a better biochemical recurrence-free survival than younger patients (86 versus 77% at four years, P=ns). High dose 3D conformal radiotherapy for localized prostate cancer was well tolerated in patients older than 70 years. Age is not a limiting factor for conformal radiation therapy and hormonotherapy for older patients.

Resume Objectif de l’etude La chirurgie est le traitement de reference des sarcomes uterins localises. Nous avons mene une etude retrospective pour definir les facteurs pronostiques dans cette pathologie. Patientes et methodes Nous avons etudie 111 dossiers de patientes traitees par irradiation postoperatoire pour un sarcome uterin dans sept centres. Le recul median etait de 31 mois. Nous avons effectue une analyse unifactorielle afin d’identifier les facteurs de recidive locale. Les facteurs statistiquement significatifs ont ete etudies en analyse multifactorielle selon le modele de Cox. Resultats L’âge moyen des patientes etait de 60 ans et la dose mediane de radiotherapie externe de 45 Gy. Quarante-trois pour cent des patientes ont eu une curietherapie du fond vaginal et 21 % une chimiotherapie. Seulement 6,3 % des patientes ont souffert de complications aigues de grade III et 8,1 % de sequelles a long terme de la radiotherapie. Le taux de survie a cinq ans etait de 74,6 %. On notait 12,6 % de recidives locoregionales isolees, 29,7 % de recidives a distance. Les facteurs correles avec le risque de rechute locoregionale etaient le statut menopausique (p = 0,045) et les tranches de section chirurgicales non saines (p = 0,0095). La chimiotherapie n’ameliorait pas la probabilite de survie globale, ni celle de survie sans recidive. Conclusion La radiotherapie postoperatoire permet un bon taux de controle local dans cette pathologie. La curietherapie n’ameliore pas le taux de controle local. La chimiotherapie n’est pas un standard au stade de tumeur localisee mais le taux de recidive metastatique plaide en faveur du developpement de strategies associant un traitement systemique a la radiotherapie.

Introduction The most common female cancer is breast cancer. Classically performed in 3D conformational technique (RC3D) on a linear accelerator, it can also be performed on other machines such as Tomotherapy, mainly in case of treatment of both breasts or funnel breast. To use this treatment method for more indications of breast cancer requires a comparative study of ballistics from a linear accelerator with those of Tomotherapy. Methods The treatment delivery on Tomotherapy can be performed helically (”TomoHelical”) or using fixed beams (”TomoDirect 3DCRT” and ”TomoDirect IMRT”). A state of the art of the methods used supported by a comparative dosimetric study will enable us to associate a privileged treatment technique for each indication. Results At the time of writing this summary, the first results follow the publications: for breasts with or without tumor bed, TD-IMRT enable to cover the PTV with a better conformation and save better the organs at risk compared to the conventional technique. Nevertheless, it causes a higher inhomogeneity (hot spots) in the target volume. For complete breasts (with nodes and internal breast chain), double breasts and chest walls, the helical technique reduces the pulmonary and/ or cardiac dose. Conclusions The ballistics performed in Tomotherapy have proven to be mostly equivalent or better than those made in 3D. TD-IMRT appears to be a great technique for the treatment of a breast cancer with or without a tumor bed. The helical technique is adapted for the treatment of complete breasts and chest walls.

Resume Objectif de l’etude Determiner les facteurs responsables d’echec de mastectomie avec reconstruction immediate et de retraction capsulaire chez des patientes ayant beneficie d’une reconstruction immediate en deux temps par expandeur et implant suivie de radiotherapie pour un cancer du sein opere par mastectomie. Il s’agit d’une etude prospective multicentrique non randomisee. Patientes et methodes De fevrier 1998 a septembre 2006, l’evaluation a concerne 141 patientes qui ont beneficie de 141 implants apres mastectomie suivie d’une radiotherapie de la paroi thoracique a 46 a 50 Gy en 23 a 25 fractions. La radiotherapie a ete delivree au decours de la mastectomie avec reconstruction immediate. L’evaluation a ete faite cliniquement par un binome oncologue radiotherapeute et chirurgien de 24 a 36 mois apres le traitement. Un questionnaire de satisfaction et de qualite de vie leur a ete remis a la date des dernieres nouvelles. Resultats La duree mediane de suivi etait de 37 mois et 67,5 % des patientes etaient atteintes d’une retraction capsulaire de grade 1 ou 2 et 32,5 % de grade 3 et/ou 4. Il y a eu 32 echecs de reconstruction necessitant une chirurgie. En analyse unifactorielle, les facteurs suivants etaient associes a une retraction capsulaire de stade de Baker 3 et 4 : le chirurgien, l’hormonotherapie et le tabac. Un seul etait significatif en analyse multifactorielle : le chirurgien. Trois facteurs sont associes a un echec de la mastectomie avec reconstruction immediate dans une analyse en regression logistique multiple : le stade T3 ou T4 ; le tabac et l’atteinte ganglionnaire axillaire. Conclusion Mastectomie, reconstruction immediate par expandeur puis implant et radiotherapie doivent etre consideres quand la chirurgie conservatrice est contre-indiquee. Les patientes pouvant beneficier de cette technique avec un taux d’echec minimum peuvent etre selectionnees en fonction de la presence de ces trois facteurs.

Rationale: Issues have been reported with aromatase inhibitors (AI) compliance in adjuvant breast cancer. The present study was performed in order to better assess patient (pt) compliance, and to test whether educational material (EM) can improve compliance rate. Methods: This 2-year observational study (NCT00681122) was conducted on 2,758 patients in 18 countries, and completed in March 2009. Pts were allocated to Standard Therapy AI (anastrozole or letrozole), Group A, or to Standard Therapy + EM (Group B) following a 1:1 randomisation. EM consisted of a range of information on breast cancer-related topics. Primary endpoint was compliance rate for AI: patient is defined as being compliant if she took more than 80% of her tablets during the last year. Secondary endpoints were: persistence rate at 1 and 2 years (patient is classified as a persistent user of adjuvant AI medication when the data supports the persistent intake of adjuvant AI medication during the one-year period), and reasons for and time to AI discontinuation. Specialised questionnaires were used to evaluate pt compliance and behaviour (EORTC-INPATSAT-32, OPTIMA-X, GHQ-12, FACT-ES, compliance questionnaire and EM feedback in Group B).Results: 711 pts were randomised in France, 348 in Groupe A and 363 in Groupe B. Pt characteristics were well balanced across randomised arms. Mean age was 65 years, mean BMI was 26, 20% of pts had received hormone replacement therapy, and 68% had associated co-morbidities, including musculoskeletal disorders in 12%. Preliminary analysis showed that compliance rate at 1 year was only 74%, with no difference between the 2 groups (73% in Group A vs. 74% in Group B). Persistence rates were also similar (77% vs.78%). AI discontinuations were mainly attributed to AI related side effects. Prognostic factor analysis showed no baseline characteristics associated with compliance behaviours.Conclusion: At 1 year, Cariatide preliminary analysis showed that compliance rate of adjuvant AI in France does not exceed 74%, and is not improved by EM. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-11-06.

Ductal carcinoma in situ is defined as breast cancer confined to the ducts of the breast without evidence of penetration of the basement membrane. Local treatment quality represents one of the most prognostic factors as half of recurrences are invasive diseases. The main goal of adjuvant radiotherapy after conservative surgery is to decrease local recurrences and to permit breast conservation with low treatment-induced sequelae. Several randomized trials have established the impact of 50 Gy to the whole breast in terms of local control. Nevertheless, no randomized trial is still available concerning the role of the boost in this disease. In this review, we present updated results of the literature and we detail the French multicentric randomized trial evaluating the impact of a 16 Gy boost after 50 Gy delivered to the whole breast in 25 fractions and 33 days. This protocol will start inclusions in October 2008.

Retrospectively evaluate the safety, feasibility and efficacy of concomitant chemoradiotherapy after induction chemotherapy by docetaxel, cisplatin and 5-fluoro-uracil for locally advanced head and neck cancers.Patients' data from three radiotherapy centres in South of France, with locally advanced head and neck cancers, and treated between December 2007 and July 2013 by concomitant chemoradiotherapy, after induction chemotherapy by docetaxel, cisplatin and 5-fluoro-uracil, were analysed. Adverse effects were graduated according to CTCAE v3.0 criteria. Overall survival and disease-free survival were calculated according to Kaplan-Meier method.One hundred and sixty-eight patients, mostly oropharynx (38%) T4 (46%) N2 (54%) tumors, received, after induction chemotherapy by docetaxel, cisplatin and 5-fluoro-uracil, a concomitant chemoradiotherapy with platin or cetuximab, which delivered 66 to 70Gy. Grade 3-4 adverse effects were less frequent in the group of patients who received cisplatin (with or withour 5-fluoro-uracil) at 100mg/m(2) each 21 days compared to cetuximab (radiomucositis: 32.5% vs 61%, P=0.018; radioepithelitis: 13% vs 61 %, P0.0001). Chemopotentiation was incomplete for 21% of patients without impacting survival. Two years overall survival and disease-free survival were respectively of 81% and 64%. Lymph nodes status and WHO status significantly influenced these survivals (overall survival 84% if N3 vs 56% if N3, P=0.017 and 85 % if WHO status ≤ 1 vs 50% if WHO status1, P=0.006; disease-free survival 66% if N3 vs 47% if N3, P=0.046).The association of induction chemotherapy by docetaxel, cisplatin and 5-fluoro-uracil and concomitant chemoradiotherapy shows satisfying results with an acceptable toxicity. The terms of the chemopotentiation and its superiority to a single concomitant chemoradiotherapy treatment still remain to be clarified.

Purpose and Objective: Late rectal bleeding is a potentially dose limiting complication of three-dimensional conformal radiotherapy (3D-CRT) for prostate cancer. The frequency of late rectal bleeding has been shown to increase as the prescription dose rises above 70 Gy. The purpose of this study is to identify features of the cumulative dose–volume histogram (DVH) for the rectal wall that correlate with late rectal bleeding after 3D-CRT for prostate cancer. Methods and Materials: Follow-up information on rectal bleeding is available for 261 and 315 patients treated using 3D-CRT at Memorial Sloan-Kettering Cancer Center for Stage T1c-T3 prostate cancer with minimum target doses of 70.2 and 75.6 Gy, respectively. All patients in this study were treated with a coplanar 6-field technique (2 lateral and 4 oblique fields). Patients were classified as having rectal bleeding if they bled (≥ Grade 2) before 30 months, and nonbleeding (⩽ Grade 1) if they were without bleeding at 30 months, using the RTOG morbidity scale. Rectal bleeding was observed in 13 and 38 of the patients treated at 70.2 and 75.6 Gy, respectively. Treatment plans were analyzed for 39 nonbleeding and 13 bleeding patients receiving 70.2 Gy, and 83 nonbleeding and 36 bleeding patients receiving 75.6 Gy. Dose–volume histograms (DVHs) for the anatomic rectal wall were calculated. Average DVHs of the bleeding and nonbleeding patients were generated, and a permutation test was used to assess the significance of differences between them, for each dose group. The confounding effect of total rectal wall volume (VRW) was removed by calculating the average differences in DVHs between all combinations of bleeding and nonbleeding patients with similar VRWs. Finally, multivariate analysis using logistic regression was performed to test the significance of the DVH variables in the presence of anatomic, geometric, and medical variables previously found to correlate with rectal bleeding in a companion analysis of the same patients. Results: The area under the average percent volume DVH for the rectal wall of patients with bleeding was significantly higher than those of patients without bleeding in both dose groups (p = 0.02, 70.2 Gy; p < 0.0001, 75.6 Gy). However, small VRWs were associated with rectal bleeding (p = 0.06, 70.2 Gy; p < 0.01, 75.6 Gy), resulting in an increase in average percent volumes exposed to all doses for patients with rectal bleeding. For patients with similar VRWs, rectal bleeding was significantly correlated with the volumes exposed to 46 Gy in both dose groups (p = 0.02, 70.2 Gy; p = 0.005, 75.6 Gy, tolerance in VRW: 5 ccs). For the 75.6 Gy dose group, the percent volume receiving 77 Gy was significantly correlated with rectal bleeding (p < 0.005). Bivariate analysis using logistic regression, including VRW together with a single DVH variable, showed good agreement with the above analysis. Multivariate analysis revealed a borderline significant correlation of the percent volume receiving 71 Gy in the 70.2 Gy dose group. It also showed that the DVH variables were highly correlated with geometric and dosimetric variables previously found to correlate with rectal bleeding in multivariate analysis. Conclusion: Significant volume effects were found in the probability of late rectal bleeding for patients undergoing 3D-CRT for prostate cancer with prescription doses of 70.2 and 75.6 Gy. The percent volumes exposed to 71 and 77 Gy in the 70.2 and 75.6 Gy dose groups respectively were significantly correlated with rectal bleeding. The independent correlation of small VRW with rectal bleeding may indicate the existence of a functional reserve for the rectum. The independent association with larger percent volumes exposed to intermediate doses (∼ 46 Gy) seen in both dose groups may indicate that a large surrounding region of intermediate dose may interfere with the ability to repair the effects of a central high dose region.

Purpose: To evaluate the feasibility of dose escalation in a multi-institutional study in prostate cancer patients. Methods and Materials: Between October 1995 and October 1998, 164 patients with localized adenocarcinoma of the prostate were treated with 3-dimensional conformal radiotherapy at one of five French institutions. The dose of radiation was escalated from 66 to 80 Gy (ICRU point). The maximum dose to the rectal wall was limited to 75 Gy. Results: Results were compared in two groups, one (group 1) receiving the standard dose ( n = 46 patients; 66 to 70 Gy) and the other (group 2) receiving the escalated dose ( n = 118 patients; 74 to 80 Gy). There was no difference in the characteristics of patients between the two groups. The mean follow-up time was 32 months in group 1 and 17.5 months in group 2. No statistical difference between the two groups was observed in the incidence of late gastrointestinal and urinary toxicities. The probability of achieving a posttreatment prostate-specific antigen nadir of ≤1 ng/mL in the 120 patients who did not receive neoadjuvant androgen-deprivation therapy was significantly higher in the dose-escalation group and was directly related to the dose of radiation given. Conclusion: This multi-institutional study demonstrated the feasibility of escalating the dose of radiation to 80 Gy in prostate cancer patients.

The purpose of this paper is to use the outcome of a dose escalation protocol for three-dimensional conformal radiation therapy (3D-CRT) of prostate cancer to study the dose-response for late rectal toxicity and to identify anatomic, dosimetric, and clinical factors that correlate with late rectal bleeding in multivariate analysis.Seven hundred forty-three patients with T1c-T3 prostate cancer were treated with 3D-CRT with prescribed doses of 64.8 to 81.0 Gy. The 5-year actuarial rate of late rectal toxicity was assessed using Kaplan-Meier statistics. A retrospective dosimetric analysis was performed for patients treated to 70.2 Gy (52 patients) or 75.6 Gy (119 patients) who either exhibited late rectal bleeding (RTOG Grade 2/3) within 30 months after treatment (i.e., 70.2 Gy-13 patients, 75. 6 Gy-36 patients) or were nonbleeding for at least 30 months (i.e., 70.2 Gy-39 patients, 75.6 Gy-83 patients). Univariate and multivariate logistic regression was performed to correlate late rectal bleeding with several anatomic, dosimetric, and clinical variables.A dose response for/= Grade 2 late rectal toxicity was observed. By multivariate analysis, the following factors were significantly correlated with/= Grade 2 late rectal bleeding for patients prescribed 70.2 Gy: 1) enclosure of the outer rectal contour by the 50% isodose on the isocenter slice (i.e., Iso50) (p0.02), and 2) smaller anatomically defined rectal wall volume (p0.05). After 75.6 Gy, the following factors were significant: 1) smaller anatomically defined rectal wall volume (p0.01), 2) higher rectal D(max) (p0.01), 3) enclosure of rectal contour by Iso50 (p0.01), 4) patient age (p = 0.02), and 5) history of diabetes mellitus (p = 0.04). In addition to these five factors, acute rectal toxicity was also significantly correlated (p = 0.05) with late rectal bleeding when patients from both dose groups were combined in multivariate analysis.A multivariate logistic regression model is presented which describes the probability of developing late rectal bleeding after conformal irradiation of prostate cancer. Late rectal bleeding correlated with factors which may indicate that a greater fractional volume of rectal wall was exposed to high dose, such as smaller rectal wall volume, inclusion of the rectum within the 50% isodose on the isocenter slice, and higher rectal D(max).

Summary Background: Shared decision-making is increasingly advocated as an ideal model. However, very few studies have tested the feasibility of giving patients the opportunity to participate in the choice of treatment. Patients and methods: Women, with non-metastatic breast cancer, eligible for non-intensified adjuvant chemotherapy attending our hospital were proposed two administrations of chemotherapy and radiotherapy: a sequential and a concomitant one. Two patient-questionnaires were used to elicit motivations for their choice and their degree of comfort with the process of decision-making and one questionnaire to test physicians'ability to predict patients'choice. Results: Participation rate in the study was 75.3% (n = 64). Majority (64%) of patients chose the concomitant treatment. Multivariate analysis revealed that patients with a lower level of education, who discussed the choice with social circle, and who most feared side-effects were more likely to choose the sequential treatment. Physicians were able to predict patients' choice in 66% of cases. 89% of patients declared that they were ifully satisfiedi with having participated in the choice of treatment and 79% supported shared decision-making. Conclusions: Results are in favour of promoting active participation of cancer-patients in medical decision-making. The adequate degree of such participation remains however to be elicited and tested for therapeutic choices implying more difficult trade-offs between quantity and quality of life.

Resume Le recours a l'irradiation dans les stades avances de la maladie de Hodgkin reste controverse. Les bases de son utilisation reposent sur son efficacite aux stades initiaux de la maladie mais egalement en situation de rechute, sur la localisation des recidives apres chimiotherapie exclusive qui surviennent au niveau de territoires non irradies dans 75 % des cas, et sur une amelioration de la survie sans recidive documentee dans de nombreux travaux prospectifs. Malheureusement, la majorite des essais randomises n'ont pas montre d'amelioration de la survie globale chez les patients recevant une irradiation en raison d'une part, de ses complications tardives et, d'autre part, de la mauvaise definition des patients susceptibles d'en tirer benefice. En situation adjuvante, l'irradiation trouve probablement ses meilleures indications dans le stade III plutot que IV, dans l'histologie de type scleronodulaire, et chez les patients ayant une atteinte mediastinale en situation de remission complete apres chimiotherapie. La diminution des doses delivrees, une rigueur technique constante, et une meilleure definition des volumes cibles en association avec une chimiotherapie optimale devraient permettre une amelioration de la survie dans des populations selectionnees.

With an effective telescope area of order $10^4$ m$^2$ for TeV neutrinos, a threshold near $\sim$50 GeV and a pointing accuracy of 2.5 degrees per muon track, the AMANDA detector represents the first of a new generation of high energy neutrino telescopes, reaching a scale envisaged over 25 years ago. We describe early results on the calibration of natural deep ice as a particle detector as well as on AMANDA's performance as a neutrino telescope., Comment: 12 pages, Latex2.09, uses espcrc2.sty and epsf.sty, 13 postscript files included. Talk presented at the 18th International Conference on Neutrino Physics and Astrophysics (Neutrino 98), Takayama, Japan, June 1998

Resume Objectif de l'etude. Les cancers du col uterin de stade limite sont tres souvent traites en France par une association radio-chirurgicale incluant apres curietherapie uterovaginale, une hysterectomie radicale identique a celle pratiquee en cas de chirurgie premiere. L'analyse prospective presentee concerne les resultats d'une association de curietherapie et d'hysterectomie vaginale non elargie chez des patientes qui avaient les facteurs pronostiques les plus favorables. Patientes et methodes. Apres lymphadenectomie percœlioscopique n'ayant pas objective d'envahissement ganglionnaire sur un nombre median de 12 ganglions lymphatiques preleves, 22 patientes dont la mediane de la dimension tumorale maximale etait de 1 cm (trois de stade Ia2 avec emboles et 19 de stade Ib1) ont beneficie d'une hysterectomie simple par voie basse 6 semaines apres une curietherapie uterovaginale. Resultats. Deux complications peroperatoires ont ete observees, une hemorragie veineuse de 100 mL lors de la lymphadenectomie avec hemostase par cœlioscopie et une plaie vesicale lors de l'hysterectomie suturee par voie basse. Une seule complication tardive a ete observee, une complication vesicale de grade G2 (b). Avec un suivi median de 29 mois (extremes: 20–48 mois), aucune recidive n'a ete deploree. Conclusion. Sous reserve d'une confirmation avec un effectif plus important, il semble qu'une hysterectomie vaginale non elargie apres curietherapie uterovaginale soit suffisante pour traiter ces formes les plus favorables des cancers du col uterin. © 1998, Elsevier, Paris.

The importance of dose-intensity has been suggested in breast cancer. The aim of this study was to evaluate the feasability of a high-dose intensity doxorubicin-cyclophosphamide regimen with supporting G-CSF and blood stem cells. Twenty-five patients with non-metastatic breast cancer received four cycles of doxorubicin (75 mg/m 2 ) and cyclophosphamide (3000 mg/m 2 ) at 3 week intervals. Apheresis was performed after the first cycle and if necessary after the second cycle. Stem cells were reinfused after the third and fourth cycles. G-CSF was started on day 3 of each cycle (5 μg/kg/day) and was stopped the day before the last apheresis or when absolute neutrophil count was above 0.5 x 10 9 /l. Median received dose-intensity was respectively 25 mg/m 2 /week (range 22-26) and 1000 mg/m 2 /week (range 904-1065) for doxorubicin and cyclophosphamide. Grade IV thrombocytopenia occurred in 8% of cycles. Two patients needed platelets and 12 red cell transfusion. Fifteen patients were readmitted for a median duration of 4 days (range 1-7). We have established a safe, outpatient, high-dose intensity doxorubicin-cyclophosphamide regimen with supporting G-CSF and blood stem cells which can be submitted for comparison with the current standards.

Resume But de l'etude Les myelofibroses (MF) et les leucemies myeloides chroniques (LMC) sont des maladies au cours desquelles apparait frequemment une splenomegalie, temoin d'une importante metaplasie splenique. Des irradiations spleniques sont pratiquees en pareil cas depuis fort longtemps, mais les donnees exploitables demeurent peu nombreuses et les modalites optimales de ces traitements restent a definir. Les resultats de l'irradiation splenique dans les hemopathies myeloides ont fait l'objet d'une analyse retrospective. Patients et methodes Il s'agissait de 24 patients dont 15 atteints de MF et neuf de LMC. Les doses totales d'irradiation medianes delivrees etaient respectivement de 9,8 et 7,7 Gy. Resultats La toxicite hematologique a ete moderee (hormis la toxicite plaquettaire survenue chez des patients en phase aigue de leur maladie). Aucune autre toxicite n'a ete observee. Nous avons mis en evidence certains facteurs predictifs de reponse a l'irradiation. Ainsi, dans les MF, il apparait necessaire, si possible, de delivrer une dose totale d'irradiation d'environ 14 Gy et d'initier l'irradiation avant d'etre confronte a des besoins transfusionnels trop importants. Dans les LMC, il est preferable d'exclure les splenomegalies tres volumineuses des indications d'irradiation ; il faut probablement tenter de delivrer des doses suffisantes d'au moins 10 Gy, mais notre travail ne nous permet pas de conclure. Conclusion Des etudes prospectives de phase Il restent a mettre en place afin d'etudier l'interet d'une radio-chimiotherapie et d'apprehender les mecanismes biologiques de radiosensibilite dans les MF.

The Tutoring Network is a nonprofit organization that emphasizes rigorous screening of educational therapists and careful matching of their expertise with the needs of learning-disabled students. It operates a clearinghouse for information pertinent to learning disabilities and strives to facilitate better communication among professionals concerned with the learning-disabled. This paper chronicles the birth and growth of The Tutoring Network and explores possibilities for replication.

The total synthesis of the highly oxygenated quassinoid, 14β,15β-dihydroxyklaineanone has been achieved thus confirming the structural assignment which was based on spectroscopic data.

There is a paucity of information on functional benefits of inpatient rehabilitation of patients with end-stage renal disease (ESRD). This study examined admission and discharge Functional Independence Measure (FIM) scores of 45 ESRD patients admitted over a 33-month span to determine if these patients made functional gains similar to 2,324 concurrently admitted general rehabilitation patients without ESRD. FIM scores were transformed and reported as scaled (0 to 100) motor and cognitive subscores by the Rasch method. FIM scores were compared using multiple linear regression to control for differences in rehabilitation diagnosis and other confounding factors between the ESRD and other patients. ESRD subgroups were compared using one-way analysis of variance. The mean discharge motor FIM score unadjusted for confounders was lower in ESRD than general rehabilitation patients (45.18 vs 50.63), and the difference after regression analysis (7.63 points lower in the ESRD group) was significant (p < .01). The mean motor FIM score gain after regression analysis for the two groups showed only a near significant (p = .06) difference, with the gain among ESRD patients being 3.15 points lower. Discharge settings were similar, with 89% of ESRD patients and 87% of patients without ESRD being discharged home. ESRD patients on hemodialysis had similar FIM scores to patients with renal transplantation. ESRD patients with stroke had significantly lower (p < .05) discharge motor and cognitive scores than ESRD patients with generalized weakness or amputation. In addition, stroke patients with ESRD showed significantly lower motor FIM score gains than stroke patients without ESRD (5.09 vs 11.08; p = .002).(ABSTRACT TRUNCATED AT 250 WORDS)

Between 1979 and 1990, 149 patients with non-metastatic thymomas were treated in ten French cancer centers. Patients were staged according to the 'GETT' classification, derived from that of Masaoka. There were 13 stage I patients, 46 stage II, 58 stage III and 32 stage IVA. Gross total resections were performed in 63 cases, subtotal resections in 31 cases and in 55 cases a biopsy alone was performed. All patients received radiotherapy and 74 were given post-operative chemotherapy. Median follow-up was 7.7 years. Local control was achieved in 117 cases (78.5%) and was influenced by the stage of the disease (p < 0.01) and the extent of surgery (p < 0.01). Twenty-six patients developed metastatis after a median period of 9 months. Five- and ten-year disease-free survival rates were 59.5% (51-67%) and 49.5% (39-60%), respectively, and were influenced by the stage of the disease (p < 0.01), the extent of surgery (p < 0.001) and a mediastinal compression on presentation (p = 5 x 10(-6)). Four factors could predict a worse overall survival in the multivariate analysis: mediastinal compression on presentation (p < 0.001), absence of chemotherapy (p < 0.001), biopsy alone (p = 0.003), and young age (p = 0.013). A worse DFS was predicted by mediastinal compression on presentation (p < 0.001), absence of chemotherapy (p < 0.001), young age (p = 0.006), and stages III-IVA (p = 0.04). Future therapeutic strategies are discussed and the literature is reviewed.

In patients with locally advanced cervical cancer, most of the treatment failures occur within the pelvis. In an attempt to improve local control, 40 patients with bulky tumors (stage IB > 5 era, stage IIB with distal parametrial invasion, and stage III-IVA) were treated between 1988 and 1992 with concurrent chemoradiation (CCR). The whole pelvis received a midplane dose of 45 Gy over 33 days. Daily radiation dose was 1.8 Gy, with twice-daily fractionation in the last 20 patients. Chemotherapy was administered on the 1st and 21st days of radiation therapy (RT) consisting of cisplatin (60 mg/m 2 ), followed by 5-fluorouracil (600 mg/m 2 /day continuous iv infusion) over 96 hr (and decreased to 40 and 400 mg/m 2 , respectively, in the last 23 patients). CCR was first followed by a single intracavitary application and then by a parametrial boost in stage IIB-III patients and in stage IVA patients with disease reaching the pelvis side wall. Then surgery (colpohysterectomy with lymphadenectomy or pelvic exenteration) was performed in 35 patients. Median follow-up time was 2.6 years (0.6-5.6 years). Acute toxicity (WHO grade 3-4 diarrhea) in 13 patients led to 6 RT interruptions and 4 incomplete RTs. One patient died of a septic episode without leukopenia after completion of CCR. Five postexenteration complications required a second surgical procedure, of which one patient died with tumor and small bowel fistula. One patient developed small bowel late complication and another patient developed urinary late complications. No postoperative or late complications were observed in patients treated with twice-daily fractionation. Pelvic control was achieved in 32 of 40 patients (81 and 74% in stage IB-IIB and stage III-IVA, respectively). Sites of failure were the pelvis (6 cases), metastases (7 cases), and both (2 cases). Two-year survival and DFS rates were 61 and 66%, respectively, in stage IB-IIB and 77 and 65% in stage III-IVA. High SCC-TA4 values significantly worsened DFS rates. In patients with stage III-IVA tumors, additional surgery could be an important component of this treatment strategy and may be compatible with CCR using twice-daily fractionation radiotherapy. However, these results must be confirmed by a large-scale prospective study.

Medulloblastoma (MB) is the most common malignant pediatric brain tumor and a rare adulthood tumor. Twenty percent to 30% of patients relapses and displays a poor prognosis. The management of recurrent disease represents a medical challenge as salvage therapy with high-dose chemotherapy is disappointing. We report a pilot study of reirradiation and concomitant metronomic temozolomide of MB focal recurrence. Five patients from 10 to 27 years old at time of first diagnosis were treated initially with upfront radiation therapy at full dose. They relapsed focally and progressed under chemotherapy with a time recurrence ranged from 2 to 15 years after initial diagnosis. Patients were then treated with 3-dimensional conformal reirradiation focused on the relapsed disease with a median dose of 28 Gy (1.8 Gy per fraction) and concomitant temozolomide (75 mg/m/d) alone or as part of a multidrug metronomic regimen. Five complete responses were obtained at the end of metronomic radiochemotherapy. The median follow-up was 28 months. At last follow-up, 3 patients progressed outside radiation field under maintenance chemotherapy, and 1 is free of disease. Only 1 patient relapsed in the reirradiation field. No neurological toxicity was observed. These results indicate a possible radiosensitizing effect of concomitant metronomic temozolomide with radiation therapy. This association could play a role in the management of high-risk MB patient with oligometastasis disease to increase local control.

Adenoid cystic carcinoma represents 1% of head and neck cancers. Adenoid cystic carcinomas are slow growing tumours with high potential for local recurrence. Treatment usually associates radiotherapy and surgery, but the role of radiotherapy remains unclear. We report a retrospective multicentric study of the management and prognostic factors of 169 adenoid cystic carcinomas of head and neck.Between 1982 and 2010, 169 patients with adenoid cystic carcinoma of the head and neck were referred to the Cercle des oncologues radiothérapeutes du Sud departments of radiotherapy either for primary untreated tumour (n=135) or for a recurrence of previously treated tumour (n=34). The site of adenoid cystic carcinoma was: parotid gland (n=48, 28.4%), minor salivary gland (n=35, 20.7%), submandibular gland (n=22, 13%), sinus cavities (n=22, 13%), other (n=42, 24.9%). Tumour stages were: T1 (12.4%); T2 (14.2%); T3 (12.4%); T4 (41.4%) and Tx (19.5%). Lymph node involvement was 13% and distant metastasis 8.9%. For adenoid cystic carcinomas of the parotid gland, major nerve involvement was evaluated. Preferential site of metastasis was the lung (87.5%). Treatments were: surgery alone (n=27), surgery and adjuvant radiotherapy (n=89), surgery and adjuvant chemoradiotherapy (n=12), exclusive chemoradiotherapy (n=13), exclusive radiotherapy (n=14), other associations (n=5) and no treatment (n=7). Radiotherapy was delivered through photons (n=119), neutrons (n=6), both (n=4). Two patients had a brachytherapy boost. Median prescribed doses to T and N were respectively 65 Gy and 50 Gy for the 119 photons treated patients.Mean follow-up was 58 months (range 1-250 months). As of December 1, 2010, 83 patients were alive with no evolutive disease (49%), 35 alive and had recurred, 18 had uncontrolled evolutive disease, 28 had died of adenoid cystic carcinoma and 5 of intercurrent disease. Overall survival and disease free survival were respectively 72% and 72% at 5 years, 53% and 32% at 10 years; 5 and 10-year freedom from local recurrence were 81% and 52% respectively. Nerve involvement was found in 17/48 parotid gland adenoid cystic carcinomas. The Cox model including all patients, showed that surgery (P0.001), surgical margins (P=0.015), nerve involvement (P=0.0079), length of radiotherapy (P=0.018), and tumour location (P=0.041) were associated with disease free survival.In this large series of adenoid cystic carcinoma of head and neck with a majority of T3-T4 tumours, 10-year survivals were achieved for 50% of patients. Radiotherapy did not impact survival.

No study on side effects had showed that conformal radiation therapy for prostate cancer is more harmful in patients older than 70 years to patients younger. The aim of this study was to evaluate acute and late toxicities of conformal radiotherapy, with high dose for localized prostate cancer in patients older than 70 years and compared to patients younger than 70 years. Between 1996 and 2009, 104 patients were treated with radiation therapy and hormonal therapy for localized cancer prostate. Median follow-up was 105 months (9-300). Acute (occurred at ≤ three months) and late side effects of 55 patients older than 70 years (median age: 75 [71-92]) were graded according to the CTCAE 3.0 criteria and compared to the younger population. Median dose to the prostate was 75.6 Gy (67-80) in both groups. There were no significant differences in acute and late side effects between age groups. For patients above 70 years, the incidence of grade II or higher acute and late side effects were respectively 27 and 22% for urologic symptoms and 13 and 16% for rectal symptoms. The frequency of grade III late symptoms was low and ranged between 0 and 6% for the evaluated symptoms, irrespective of age group. Older patients had a better biochemical recurrence-free survival than younger patients (86 versus 77% at four years, P=ns). High dose 3D conformal radiotherapy for localized prostate cancer was well tolerated in patients older than 70 years. Age is not a limiting factor for conformal radiation therapy and hormonotherapy for older patients.

The syntheses of 5a'-homo-vinblastine (3a) and its C-20' methyl congener 62a were achieved. In contrast to vinblastine, these compounds did not allow isolation of atropisomers because of their lower conformational inversion barrier. However, annelation of a six-membered ring to the conformationally mobile D'-piperidine ring provided an isolated atropisomer 81a, which could be converted to its lower energy conformation 65a on heating. The 5a'-homo-vinblastine congeners 3a, 62a, and 65a showed vinblastine-like inhibition of tubulin polymerization and cytotoxicity to L1210 leukemia cells, albeit at lower potency for the latter activity, than that found with the corresponding compounds in the vinblastine series.

International audience; The objective is to prospectively determine the factors responsible for reconstruction failure and capsular contracture in mastectomized breast cancer patients who underwent immediate two-stage breast reconstruction with a tissue expander and implant, followed by radiotherapy. This is a multicenter, prospective, non-randomized study. Between February 1998 and September 2006, we prospectively examined 141 consecutive patients, each of which received an implant after mastectomy, followed by chest wall radiotherapy at 46-50 Gy in 23-25 fractions. Radiotherapy was delivered during immediate post-mastectomy reconstruction. Patients were evaluated by both a radiation oncologist and a surgeon 24-36 months after treatment. The median follow-up duration was 37 months. According to Baker's classification, capsular contracture was grade 0, 1, or 2 in 67.5% of cases; it was grade 3 or 4 in 32.5% of cases. In total, 32 breast reconstruction failures required surgery. In univariate analysis, the following factors were associated with Baker grade 3 and 4 capsular contraction: adjuvant hormone therapy ( = 0.02), the surgeon ( = 0.04), and smoking ( = 0.05). Only one factor was significant in multivariate analysis: the surgeon ( = 0.009). Three factors were associated with immediate post-mastectomy breast reconstruction failure in multiple logistic regression analysis: T3 or T4 tumors ( = 0.0005), smoking ( = 0.001), and pN+ axillary status ( = 0.004). Patients with none, 1, 2, or all 3 factors have a probability of failure equal to 7, 15.7, 48.3, and 100%, respectively ( = 3.6 × 10). The model accurately predicts 80% of failures. Mastectomy, immediate reconstruction (expander followed by implant), and radiotherapy should be considered when conservative surgery is contraindicated. Three factors may be used to select patients likely to benefit from this technique with a low failure rate.

Marginally vitamin C-deficient guinea-pigs treated with the diabetogenic agent streptozotocin were compared with those liberally supplied with vitamin C, for functional indices of vitamin C status, particularly in the eye lens. Weanling male Dunkin–Hartley guinea-pigs were fed on diets with 0.1 g vitamin C/kg (marginally deficient), or 5 g/kg (liberally supplied), and some received intraperitoneal streptozotocin (two doses of 150 mg/kg body-weight). About half the streptozotocin-treated animals had high urinary glucose following an oral glucose dose; these animals also grew more slowly than the others. At 4 months after streptozotocin the animals were killed for measurement of tissue vitamin C, glucose and sorbitol. Streptozotocin moderately increased the concentration of glucose in plasma, lens and aqueous humour. Lens sorbitol levels increased only in the group exposed to streptozotocin plus marginal vitamin C. There was a significant (P < 0.02) positive correlation between urinary glucose and lens sorbitol levels overall. Liberal vitamin C intake may thus counteract the effect of streptozotocin diabetes on lens sorbitol, suggesting a new function of vitamin C, possibly related to cataractogenesis and to the biochemical lesions associated with diabetes.

Surgery is the treatment of choice for localized uterine sarcomas. We conducted a retrospective study to define prognostic factors.We studied 111 cases of patients treated by adjuvant radiotherapy for uterine sarcoma in seven French centers. The median decline was 31 months. We conducted a univariate analysis to identify factors correlated with local recurrence. The statistically significant factors were studied in multivariate analysis by Cox model.The median dose of external beam radiotherapy was 45 Gy. Forty-three percent of patients had vaginal vault brachytherapy and 21 % chemotherapy. Only 6.3 % of patients had complications of acute grade III and 8.1 % of long-term sequelae of radiotherapy. The survival rate at 5 years was 74.6 %. They noted 12.6 % of isolated locoregional recurrences, against 29.7 % for distant recurrences, 80 % were pulmonary. Factors correlated with the risk of locoregional relapse were menopausal status (P = 0.045) and surgical margins suspicious or not healthy (P = 0.0095). The chemotherapy did not improve overall survival or disease free survival but the numbers were low.The postoperative radiotherapy provides good local control in this disease. Brachytherapy is sometimes done, but it does not improve local control. Chemotherapy is not a standard localized stage but the rate of metastatic recurrence calls for the development of strategies involving systemic treatment with radiotherapy.

To determine prospectively the factors associated with reconstruction failure (i.e. requiring expander removal) and capsular contracture in patients undergoing mastectomy and immediate two-stage breast reconstruction with a tissue expander and implant, and radiotherapy for breast cancer. This is a multi-institutional prospective nonrandomized trial.Between 2/1998 and 9/2006, we prospectively evaluated 141 consecutive patients who received 141 implants after mastectomy and underwent chest wall radiotherapy (46 to 50 Gy in 23 to 25 fractions). Patients were evaluated after 24 to 36 months by two senior physicians (radiation oncologist and surgeon).Medical follow-up was 37 months. Baker 1 and 2 capsular contracture was observed in 67.5% of patients, Baker 3 and 4 in 32.5%. There were 32 reconstruction failures. In a univariate analysis, the following factors were associated with Baker 3 and 4 capsular contracture: surgeon, use of hormonotherapy and smoking, of which only one remained in the multivariate analysis: surgeon. In a univariate analysis, the following factors were associated with reconstruction failure: tumor size T3 or T4, smoking, pN+ axilla. Three factors remained associated with reconstruction failure in a multiple logistic regression: large tumors T3/T4, smoking and pN+ axilla.Mastectomy, radiotherapy and immediate breast reconstruction with a tissue expander and implant should be considered when breast conserving surgery has been denied. Adequate patients can be easily selected by using three factors of favourable outcome.

Axillary bud proliferation of Zinnia elegans Jacq. was accomplished from vegetative bud explants of greenhouse-grown plants. Photoperiod extension via metalarc lamps in the greenhouse stock plant environment significantly increased both the quantity and quality of explants. Shoot cultures initiated from axillary buds of identified male sterile plants proliferated best on a medium with 1μM BAP. Microshoots exhibited 80% rooting on media without growth regulators, and 100% acclimatization of rooted plantlets was accomplished in a lighted, high humidity chamber. In vitro- produced male sterile plants were more compact, more heavily branched, and demonstrated earlier flowering than seed-propagated plants. These male steriles were cross pollinated to male fertile lines to verify their ability to serve as a uniform female parent.

Resume Des etudes recentes suggerent que la radiotherapie pourrait etre abandonnee dans les stades avances de la maladie de Hodgkin en raison de sa toxicite et de l'absence de gain de survie (voire meme une perte). Nous presentons ces donnees de facon synthetique et encourageons le lecteur interesse a se reporter aux articles references.

Ductal carcinoma in situ is defined as breast cancer confined to the ducts of the breast without evidence of penetration of the basement membrane. Local treatment quality represents one of the most prognostic factors as half of recurrences are invasive diseases. The main goal of adjuvant radiotherapy after conservative surgery is to decrease local recurrences and to permit breast conservation with low treatment-induced sequelae. Several randomized trials have established the impact of 50 Gy to the whole breast in terms of local control. Nevertheless, no randomized trial is still available concerning the role of the boost in this disease. In this review, we present updated results of the literature and we detail the French multicentric randomized trial evaluating the impact of a 16 Gy boost after 50 Gy delivered to the whole breast in 25 fractions and 33 days. This protocol will start inclusions in October 2008.

De nombreux progres ont ete realises dans le cancer du sein au cours des dernieres annees. La radiotherapie postoperatoire du sein en totalite diminue le risque de recidive locale et une meta-analyse a montre qu’elle ameliorait meme la survie (1, 2, 3). Dans le meme temps grâce aux progres des traitements adjuvants, la mortalite du cancer du sein a diminue (4). La morbidite a egalement pu etre reduite grâce a l’equivalence demontree entre traitements conservateurs et mastectomie pour le sein, et entre curage axillaire et ganglion sentinelle pour les creux axillaires non envahis.

L’informatique et l’imagerie ont permis de redistribuer la dose physique en epargnant les tissus sains ce qui a considerablement reduit les complications. Les reactions aigues de survenue precoces sont des effets secondaires. Les complications tardives (au-dela de 3 mois) peuvent affecter l’intestin (stenose), la vessie (petite vessie fibreuse), le rectum (rectorragie par rupture de telangiectasie au passage des selles). Les complications vaginales entrainent souvent des sequelles sexuelles: synechie, stenose, rigidite responsable de dyspareunie.