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Les traitements utilisant des rayons X de basse energie continuent a etre realises mais en faible nombre. Le praticien se trouve en general pres du patient pour maintenir l’appareil et expose donc ses yeux. Avec la modification envisagee de la limite maximale d’exposition du cristallin, des mesures ont ete jugees necessaires pour mieux en connaitre l’exposition. Pour cela une simulation des traitements a ete realisee. Pour la dose d’un traitement superficiel de 42 Gy, l’exposition du cristallin derriere des verres radio attenuateurs se situe entre 130 et 43 μ Sv pour des distances entre 40 et 60 cm. Pour l’intra cavitaire les valeurs obtenues sont vingt fois plus faibles. L’attenuation par les verres est superieure a 90 %. Le port des lunettes avec verres radio attenuateurs permet de minimiser la dose au cristallin de facon significative. L’application de la nouvelle limite maximale n’aura pas d’impact sur le nombre de traitements.

Purpose Stereotactic body radiation therapy (SBRT) allows stereotactic irradiation of thoracic tumors. It may have a real impact on patients who may not otherwise qualify for breast-conserving surgery. We conducted a phase 1 trial that tested 5 dose levels of SBRT concomitant with neoadjuvant chemotherapy (NACT) before to surgery. The purpose of the current dose escalation study was to determine the maximum tolerable dose of SBRT in the treatment of breast cancer. Methods and Materials To define toxicity, we performed dermatologic examinations that included clinical examinations by 2 separate physicians and technical evaluations using colorimetry, dermoscopy, and skin ultrasonography. Dermatologic examinations were performed before NACT, 36 and 56 days after the beginning of NACT, and before surgery. Surgery was performed 4 to 8 weeks after the last chemotherapy session. Efficacy, the primary endpoint, was determined by the pathologic complete response (pCR) rate. Results Maximum tolerable dose was not reached. Only 1 case of dose-limiting toxicity was reported (grade 3 dermatologic toxicity), and SBRT was overall well tolerated. The pCR rate was 36%, with none being observed at the first 2 dose levels, and the highest rate being obtained at dose level 3 (25.5 Gy delivered in 3 fractions). Furthermore, the breast-conserving surgery rate was up to 92% compared with an 8% total mastectomy rate. No surgical complications were reported. Conclusions This study demonstrates that SBRT can be safely combined with NACT. Regarding the efficacy endpoints, this trial showed promising results in terms of pCR rate (36%) and breast-conserving rate (92%). The findings provide a strong rationale for extending the study into a phase 2 trial. In view of the absence of correlation between dose and pCR, and given that the data from dose level 3 met the statistical requirements, a dose of 25.5 Gy in 3 fractions should be used for the phase 2 trial.

Resume Objectifs La radiotherapie de contact 50 kV (CXRT) a fait la preuve de son service medical rendu pour les cancers du rectum et de la peau. Le but de cette recherche technologique est de developper un nouvel appareil (Papillon 50 tm) (P50) et ses applicateurs pour remplacer l’appareil Philips RT 50 arrive a obsolescence. Materiels et methodes Les caracteristiques du faisceau de rayons X produit par le P 50 fabrique en Angleterre ont ete etudies a l’aide de spectrometre, chambre d’ionisation, films Gafchromic et calcul Monte Carlo. Des applicateurs ont ete concus et realises a Nice. Les donnees dosimetriques de chaque applicateur ont ete evaluees. Des protocoles d’irradiation valides ont ete utilises pour traiter les patients. Resultats Entre septembre 2009 et novembre 2011, le bon fonctionnement du P50 a pu etre verifie avec un debit de dose voisin de 15 Gy/min selon les applicateurs. Les distributions de doses obtenues ont ete conformes aux objectifs. Les resultats observes sur 62 patients traites au centre Antoine-Lacassagne ont confirme l’efficacite de cette technique et sa bonne tolerance. Des resultats identiques ont ete obtenus au centre de Clatterbridge dans les cancers du rectum. Discussion Les resultats obtenus sont tres encourageants et doivent deboucher sur une commercialisation internationale de plusieurs appareils P50 et la mise au point de nouveaux appareils (Papillon Plus) destines a la radiotherapie peroperatoire et du fond vaginal. Conclusion Cette experience de recherche et developpement bien encadree par le programme TecSan montre que cette dynamique d’innovation technologique en radiotherapie doit etre encouragee et developpee.

Resume Objectif de l’etude Actuellement, la mastectomie represente le traitement de reference de la recidive locale du cancer du sein. Cependant, nous avons montre qu’un second traitement conservateur etait faisable en associant une nouvelle tumorectomie et une curietherapie interstitielle de bas debit de dose. Dans la presente etude, nous rapportons les resultats preliminaires d’un second traitement conservateur avec une curietherapie de haut debit de dose. Patientes et methodes De juin 2005 a juillet 2009, 42 patientes atteintes d’une recidive locale homolaterale d’un cancer du sein ont beneficie d’un second traitement conservateur. Apres tumorectomie et mise en place peroperatoire des tubes plastiques vecteurs, une scanographie dosimetrique a ete realisee pour delivrer une dose totale de 34 Gy en dix fractions et cinq jours dans le cadre d’un traitement ambulatoire. Le traitement systemique a ete discute au cas par cas. L’evaluation de la toxicite a utilise la Common Terminology Criteria for Adverse Events v3.0. Resultats Le suivi median etait de 21 mois (6–50 mois), l’âge median lors de la recidive etait de 65 ans (30–85 ans). Le delai median entre la tumeur primaire du sein et la recidive etait de 11 ans (1–35 ans). La recidive locale siegeait dans le lit tumoral dans 52 % des cas (22 patientes), dans le meme quadrant dans 33 % (14 patientes) et etait de siege inconnu dans 14 % (six patientes). La taille mediane de la recidive etait de 12 mm (2–30 mm). Les nombres medians de tubes plastiques vecteurs et de plans etaient respectivement de neuf (5–12) et deux (1–3). Le volume cible anatomoclinique (CTV) median etait de 68 cm3 (31,2–146 cm3). Le taux de second controle local etait de 97 %. Des effets secondaires ont ete notes chez 22 patientes (60 %). La fibrose cutanee et sous-cutanee representait 72 % de tous les effets secondaires observes. Conclusion Un second traitement conservateur radiochirurgical utilisant une curietherapie de haut debit de dose en cas de recidive locale homolaterale semble faisable, avec des taux de second controle local encourageants au prix d’une toxicite acceptable. Considerant qu’un essai randomise de non-inferiorite entre mastectomie et un second traitement conservateur serait difficilement realisable, quel niveau de preuve sera-t-il necessaire d’obtenir pour envisager un changement des pratiques ?

Background: Despite current treatment options, metastatic breast cancer (MBC) remains essentially incurable, requiring research on new drugs or combinations to improve survival and quality of life. Patients and Methods: This phase I study was designed to define the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT) and recommended dose of all-oral tegafur-uracil (UFT)/folinic acid combined with vinorelbine as chemotherapy for MBC. Starting doses were 40 mg/m2/week of oral vinorelbine administered continuously and 250 mg/m2/day of UFT plus 90 mg/day of folinic acid from day 1 to day 28, followed by a 1-week rest period. Results: Ten patients were included. Eight were evaluable for toxicity and antitumor response. The second dose level was shown to be the MTD. At this dose, 2 out of 5 patients receiving oral vinorelbine at 40 mg/m2/week and UFT at 300 mg/m2/day developed DLT consisting of grade 3 asthenia and grade 3nausea despite standard prophylaxis. Other toxicities were grade 1 diarrhea and anemia. There were no treatment-related deaths. Conclusions: The recommended dose for this combination seems to be the first dose level. A stable response was observed for 6 patients (average 33 weeks). This combination appears to be well-tolerated and offers an alternative to intravenous chemotherapy.

Since the prolongation of survival for patients treated by radiotherapy second primary cancers are not rare. Cumulative incidence of second primary malignancy after radiotherapy (SPMAR) 40 years after treatment can reach 20 % when patients were 40 years old at treatment time. Among SPMAR some of them can be promoted by irradiation. Relative risk (RR) analysis is the most common method used to estimate the proportion of such second cancers. Most of studies reported a RR around 1.1 in adult patients. In young patients RR is about 6, meaning that SPMAR attributable to irradiation is more elevated in this subgroup. Quantification of these events, biomolecular mechanisms, risk factors are complex and not yet fully understood. Information given to patients must be adapted and the cost/benefit ratio has to be justified regarding SPMAR risk. Irradiation technique optimisation is an important point especially in young patient and adults, in order to reduce at maximum the volume of organ at risk exposed while not compromising optimal dose given to the tumour volume, although no standard rules of irradiation are definitively established at the present time.

Acute skin toxicity is frequent during radiation therapy and can lead to temporary arrest of the treatment. Chronic toxicity can occur and conduct to cosmetic problems. Alopecia is the most frequent toxicity concerning hair and is most of the time reversible. Several factors linked to patients influence skin toxicity, such as undernutrition, old age, obesity, smoking, skin diseases, autoimmune diseases, failure of DNA reparation. Skin, hair and nail toxicities depend also on radiation schedule. Acute toxicity is greater when dose per fraction increases. Chronic and acute toxicities are more often when total dose increases. Under 45 Gy, the risk of severe skin toxicity is low, and begins above 50 Gy. Skin toxicity depends also on the duration of radiotherapy and split course schedules are associated with less toxicities. Irradiation surface seems to influence skin toxicity but interaction is more complex. Reirradiation is often feasible in case of cancer recurrence but with a risk of grade 3-4 toxicity above all in head and neck cancer. The benefit/risk ratio has to be always precisely evaluated. Permanent alopecia is correlated with the follicle dose. Modern techniques of radiation therapy allow to spare skin.

Resume Objectif de l’etude La radiotherapie par CyberKnife® est devenue un traitement cle dans la prise en charge multidisciplinaire des metastases, des tumeurs malignes primitives ou benignes localisees dans ou au contact des corps vertebraux et du cordon medullaire. Les objectifs sont pour les tumeurs spinales d’ameliorer la reponse clinique et le controle tumoral, y compris dans des cas de reirradiation. Patients et methodes Nous presentons les resultats obtenus chez les premiers patients traites par CyberKnife® entre le 1er decembre 2006 et le 31 decembre 2007 pour des tumeurs spinales ou paraspinales. Nos objectifs primaires etaient d’evaluer la faisabilite et la tolerance d’une irradiation stereotaxique utilisant le CyberKnife®. Nos objectifs secondaires etaient les taux de controle local precoces, de survie sans progression locale et de survie globale. L’evaluation a eu lieu tout les trois mois par un examen clinique et par une imagerie. Elle s’est faite selon les criteres RECIST. Resultats De decembre 2006 a decembre 2007, 16 patients ont ete traites avec le CyberKnife®. Treize patients avaient ete pretraites, dont trois irradies dans la moelle a des doses considerees comme maximales. Trois patients n’avaient jamais ete traites. L’âge median le jour du traitement etait de 58,6 ans (36–74). Les symptomes les plus frequents etaient la douleur (n = 8) et un deficit moteur (n = 4). La dose mediane delivree etait de 30 Gy (16–50). Le nombre de fractions median etait de trois (1–5). Des reactions aigues ont ete observees chez trois patients, mais aucun n’a ete atteint de myelite aigue. Le taux de survie globale a 18 mois etait 72 % et la duree moyenne de survie de 18,2 mois [intervalle de confiance a 95 % (IC 95 %) : 15,4–20,9]. Le taux de survie sans progression locale a 18 mois etait de 58 % et la duree moyenne de survie de 16,9 mois (IC 95 % : 13,6–20,2). Conclusion L’utilisation du CyberKnife® represente une avancee therapeutique majeure dans la prise en charge des tumeurs paramedullaires. La possibilite d’epargner au mieux le cordon medullaire et d’augmenter la dose dans le volume cible tumoral en sont les principaux avantages.

Le traitement des cancers du sein localises repose sur la chirurgie conservatrice et la radiotherapie. Le risque de ces traitements est la recidive locale. De nombreuses etudes ont retrouve un impact entre recidive locale et marges d’exereses insuffisantes ou envahies qui restent cependant un facteur controverse, que ce soit dans sa definition, que dans son impact ou de son implication clinique. L’analyse des marges d’exerese doit prendre plusieurs facteurs en compte: le risque de recidive locale depend outre de la distance des marges de securitemais aussi de la localisation des marges, de la presence de carcinome in situ, du type d’envahissement local ou diffus, de l’âge de la patiente et les traitements adjuvants associes. La marge communement admise est de 2 mm. La reprise chirurgicale est indispensable s’il persiste des cellules cancereuses au niveau des berges d’exerese.

Resume Objectif de l’etude Le CyberKnife® permet de realiser une radiotherapie stereotaxique des tumeurs du thorax grâce a une precision et un systeme de suivi de la cible en temps reel dont le potentiel est etabli pour le cancer du poumon classe T1-T2 N0. Cette technique n’a jamais ete utilisee pour traiter des tumeurs du sein, mais presente un interet potentiel dans cette localisation. Patientes et methode Dans le but de definir l’interet du traitement des tumeurs du sein par CyberKnife®, nous avons construit une etude de phase I d’escalade de dose qui additionne un traitement neodjuvant associant CyberKnife® et chimiotherapie, afin de permettre un traitement conservateur pour certaines tumeurs du sein dont la chirurgie conservatrice ne peut etre envisagee d’emblee. La chimiotherapie neoadjuvante comporte six cycles composes de trois cycles de docetaxel et trois 5-fluoro-uracile-epirubicine-cyclophosphamide (FEC). Le CyberKnife® est realise au cours du second cycle de chimiotherapie. La chirurgie du sein est realisee six a huit semaines apres le sixieme cycle de chimiotherapie. L’objectif principal est de definir la dose maximum toleree de la radiotherapie hypofractionnee concomitante a la chimiotherapie neoadjuvante pour les cancers du sein. La toxicite cutanee est le critere limitant l’etude. Les objectifs secondaires sont les resultats anatomopathologiques et la qualite de la chirurgie. Nous presentons les resultats preliminaires des trois premieres patientes. Cette etude participe au programme hospitalier de recherche clinique (PHRC). Resultats Aucune toxicite de grade I ou plus n’a ete retrouvee. La chirurgie a pu etre realisee avec la qualite habituelle et sans complication particuliere. L’anatomopathologiste a retrouve une reponse complete, une lymphangite carcinomateuse et une reponse partielle. Conclusion Ces resultats preliminaires sont encourageants mais doivent etre confirmes. Nous poursuivons l’etude d’escalade de dose.

The aim of this study was to evaluate the tolerance of topical application of the combination sucralfate / copper zinc salts in radiation dermatitis in women suffering from breast cancer and treated by radiotherapy. 47 patients (average age : 57,5 years) that have to be treated by radiation therapy on non lesional areas, were included into this open multicentric study. They had to apply Cicalfate cream twice a day, from the fi rst radiation therapy session and during 10 weeks. Patients were treated by photon- or electrontherapy (72 % et 28 %, respectively; cumulated total dose : 58,6Gy). Tolerance was considered to be excellent. The radiation dermatitis (score NCIC > or = 2) was noted at the 3rd week of radiotherapy only in 5 % of the subjects and in 53 % of the subjects, the last week of treatment. Pruritus was significantly increased at D21. Pain and discomfort were increased at D28, but remained low intensity. The soothing effect of the combination of sucralfate/ copper zinc salts were considered satisfying or very satisfying by investigators and patients during the study, varying from 94 to 100 % of satisfaction. The impact of radiation therapy on the patients'quality of life, assessed by DLQI, evaluated at the end of the study was not statistically different from the score calculated at D7 (DLQI=0,8 et D7 versus DLQI=1 at D70). Thus, topical application of the combination sucralfate / copper zinc salts can be used in the indication radiation dermatitis.

Purpose To evaluate early and late reactions, local control, disease-free survival, cause-specific survival, and overall survival of elderly breast cancer patients treated with adjuvant once-weekly hypofractionated radiotherapy (RT). Methods and materials Between 1987 and 1999, 150 patients (median age, 78 years) who presented with 151 nonmetastatic breast tumors were treated with surgery and then adjuvant hypofractionated RT. The clinical stage distribution was as follows: T1 in 47.7%, T2 in 43.2%, T3 in 6.1%, and T4 in 3.0%. Axillary lymph nodes were positive in 33.8% of cases. Estrogen receptors were present in 89.9%, and progesterone receptors in 77.3%. Conservative breast surgery was performed in 71.5% and total mastectomy in 28.5%. RT was delivered once weekly in five fractions of 6.5 Gy to a total dose of 32.5 Gy. A boost was delivered to the tumor bed in 33.1%. Adjuvant hormonal therapy was given in 76.2% of patients. The median follow-up was 65 months. Results The Kaplan-Meier rate of all grades of early skin reactions was 26.5%, and the rate of all late reactions was 45.5%, mainly Grades 1 and 2. Early and late reactions were greater in those who underwent boost RT. The long-term local recurrence rate was 2.3%. The 5-year and 10-year disease-free survival rate was 80% and 71.5%, respectively. The corresponding rates for cause-specific survival were 89.1% and 77.6%. The 5-year and 10-year overall survival rate was 71.6% and 46.5%, respectively. These endpoints were influenced by tumor size, lymph node status, and hormone receptor status to varying degrees; however, tumor size appeared to be a major determinant on multivariate analysis. Conclusions This hypofractionated RT scheme resulted in mild early reactions and acceptable late toxicity, in addition to providing excellent long-term local control. It can be proposed to patients who would have difficulties sustaining daily treatment because of old age or disabling associated disease.

Anaemia is frequently diagnosed in patients with cancer, yet it is difficult to identify a single cause due to its multifactorial aetiology. We conducted a systematic literature review (1996-2003) to produce evidence-based guidelines on the use of erythropoietic proteins in anaemic patients with cancer (see ). Level I evidence exists for a positive impact of erythropoietic proteins on haemoglobin (Hb) levels when administered to patients with chemotherapy-induced anaemia or anaemia of chronic disease, when used to prevent cancer anaemia, in patients undergoing cancer surgery and following allogeneic bone marrow transplantation. The Hb level at which erythropoietic protein therapy should be initiated is difficult to determine as it varied between studies; a large number of Level I studies in patients with chemotherapy-induced anaemia or anaemia of chronic disease enrolled patients with a Hb concentration/=105 g/L, but none compared the effect of different baseline Hb levels on the response to treatment. Similarly, several studies defined the target Hb concentration as 120-130 g/L following treatment with erythropoietic proteins, but none specifically addressed the correlation between target Hb level and clinical benefit in a randomised fashion. Level I evidence shows that red blood cell (RBC) transfusion requirements are significantly reduced with erythropoietic protein therapy in patients with chemotherapy-induced anaemia or when used to prevent cancer anaemia (approximately 20% reduction compared with controls). We found indirect Level I and III evidence that patients with chemotherapy-induced anaemia or anaemia of chronic disease initially classified as non-responders to standard doses proceed to respond to treatment following a dose increase (absolute increases in response rate ranged from 8% to 18%). However, none of these studies examined the effect on response rates of a longer treatment period at the lower dose, or performed a randomised comparison of a dose increase versus an unchanged dose. There is Level I evidence to show that quality-of-life (QOL) is significantly improved in patients with chemotherapy-induced anaemia and in those with anaemia of chronic disease, particularly in patients achieving a Hb response to erythropoietic protein therapy. There are insufficient data to determine the effect on survival following treatment with erythropoietic proteins in conjunction with chemotherapy or radiotherapy. There is Level I evidence that dosing of erythropoietic proteins less frequently than three times per week (TIW) is efficacious when used to treat chemotherapy-induced anaemia or prevent cancer anaemia. There is Level III evidence that initial doses of erythropoietic proteins considered to be higher than current standard practice produce higher haematological responses in patients with chemotherapy-induced anaemia or anaemia of chronic disease. Level I evidence demonstrates that several baseline patient parameters (e.g., low endogenous erythropoietin [EPO] concentration, age60 years, Hb concentration/=90 g/L) impact upon the response to erythropoietic proteins when used to treat chemotherapy-induced anaemia or prevent cancer anaemia. Evidence indicates that endogenous EPO concentration impacts on response in patients with lymphoproliferative malignancies, but is not a valid parameter in patients with solid tumours. There is Level I evidence that fixed doses of erythropoietic proteins can be used at the start of therapy to treat patients with chemotherapy-induced anaemia, but maintenance doses should be titrated individually. There is no evidence that pure red cell aplasia (PRCA) occurs following treatment with erythropoietic proteins in patients with chemotherapy-induced anaemia or when used prophylactically in patients with cancer. There is Level I evidence that the risk of thromboembolic events and hypertension are slightly elevated in patients with chemotherapy-induced anaemia receiving erythropoietic proteins. Level I evidence supports the effectiveness of erythropoietic proteins to prevenroteins to prevent anaemia in non-anaemic cancer patients receiving chemotherapy or radiotherapy or in those undergoing cancer surgery. However, these are non-licensed indications and we do not currently recommend the prophylactic use of erythropoietic proteins to prevent anaemia in patients who have normal Hb values at the start of treatment. Additional trials are warranted, especially on the issues of iron replacement and cost-effectiveness of erythropoietic protein therapy, as well as on tumour response/progression and survival.

Background. Approximately half of all breast cancer occurs after age 65. Several aspects for the treatment of early breast cancer may be influenced by patient age, including postoperative radiation therapy (RT), in order to prevent the risk of local recurrence (LR). Postoperative adjuvant RT, improving the chances of local control, is not always completed because of comorbidity-associated factors. Does an alternative exist between a 5-week radiotherapy regime and no irradiation after breast conservative surgery without burdening the overall therapeutic management? Methods. The authors review the literature regarding age-specific issues in the irradiation of breast cancer and the potential role of a partial breast irradiation (PBI) to prevent LR in the ipsilateral breast. Results. Phase II and III trials have been analyzed for feasibility, efficacy and toxicity. PBI may be delivered with low or high dose rate brachytherapy and intra operative, or external beam radiation therapy. PBI satisfies the control quality criteria. The majority of the teams provide PBI recurrence rates lower than 5% (0–4.4%) with a median follow-up varying between 8 and 72 months, associated with cosmetic results comparable to those achieved with conventional external beam. Conclusions. Breast cancer in elderly women represents a medical and economical problem. The recommended conservative treatment includes RT for 50 Gy over 5 weeks. Some subgroups of patients did not receive radiotherapy because of comorbidity-associated factors or more favorable tumor biology. PBI seems to be an acceptable alternative to adjuvant RT over 5 weeks and no irradiation. The evaluation of toxicity and efficacy, especially in terms of local control, is necessary and large multicentric phase III trials comparing the two irradiation approaches are needed, including quality of life, economic considerations and longer follow-up.

The aim of this study was to reexamine the prognostic role of tumor cell kinetics measured by S-phase fraction (SPF) and to establish its clinically relevant threshold values. SPF was determined by flow cytometry in a group of 920 consecutive breast cancer patients, all followed at our institute for 10 years (1988 to 1998). Mean age was 60.5 years (27–89 years). Median follow-up was 63 months (3–150 months). All patients had initial surgical treatment. SPF quartiles were: Q1=3.08%, median value = 5.98%, Q3=10.22%. A significant difference in overall specific survival was obtained between two populations divided by a cutoff at Q1 (p

This article describes the unique case of a female patient who presented distant melanoma metastasis on the breast while having irradiation therapy for breast cancer. This happened eight months after the initial treatment for a melanoma of the back (under the right scapula). Furthermore, this case report demonstrates the efficiency of Vemurafenib® as a treatment for late stage melanomas.The patient was a 47-year-old female that had a superficial spreading melanoma under the right scapula (Breslow 1.02mm) that was treated with 2cm skin excision and sentinel lymph node sampling that was negative. The melanoma was positive for the BRAF600E mutation. One month after this incident, the patient developed breast cancer that was treated with conservative surgery and radiotherapy. Three months after the end of the irradiation treatment, she developed multiple melanoma metastasis on the skin of the breast. Our multidisciplinary team decided to initiate a treatment with vemurafenib. The patient showed an excellent response, so the surgical team completed the treatment with a radical mastectomy and immediate reconstruction with a pedicled latissimus dorsi flap. The histologic report of the mastectomy specimen showed no sign of melanocytic proliferation, that demonstrates the efficacy of vemurafenib. The patient showed no relapse after two years of follow-up.The speed of development and location of cutaneous metastases in this case brought us to think about the effects of radiation therapy on the skin. Radiation therapy causes acute complications (radiodermatitis) by cellular and molecular mechanisms. Moreover, depressed immunity is found after irradiation. Association of these mecanisms could explain the appearance of these metastases in irradiation field. The efficiency of vemurafenib found in our case is consistent with what is described in literature, especially with the improvement in median overall survival.This case demonstrates a unique case of distant melanoma metastasis on the irradiation field of a breast cancer. It also demonstrates the efficacy of vemurafenib as well as the efficacy of a radical complementary surgical treatment in these patients.

Objective To evaluate clinical outcome after accelerated partial breast irradiation (APBI) in the elderly after high-dose-rate interstitial multi-catheter brachytherapy (HIBT). Methods and materials Between 2005 and 2013, 70 patients underwent APBI using HIBT. Catheter implant was performed intra or post-operatively (referred patients) after lumpectomy and axillary sentinel lymph node dissection. Once the pathological results confirmed the indication of APBI, planification CT-scan was performed to deliver 34 Gy/10f/5d or 32 Gy/8f/4d. Dose-volume adaptation was manually achieved (graphical optimization). Dosimetric results and clinical outcome were retrospectively analyzed. Physician cosmetic evaluation was reported. Results With a median follow-up of 60.9 months [4.6 – 90.1], median age was 80.7 years [62 – 93.1]. Regarding APBI ASTRO criteria, 61.4%, 18.6% and 20% were classified as suitable, cautionary and non-suitable respectively. Axillary sentinel lymph node dissection was performed in 94.3%; 8 pts (11.5%) presented an axillary involvement. A median dose of 34 Gy [32 – 35] in 8 to 10 fractions was delivered. Median CTV was 75.2 cc [16.9 – 210], median D90 EQD2 was 43.3 Gy [35 – 72.6] and median DHI was 0.54 [0.19 – 0.74]. One patient experienced ipsilateral recurrence (5-year local free recurrence rate: 97.6%. Five-year specific and overall survival rates were 97.9% and 93.2% respectively. Thirty-four patients (48%) presented 47 late complications classified grade 1 (80.8%) and grade 2 (19.2%) with no grade ≥ 3. Cosmetic results were considered excellent/good for 67 pts (95.7%). Conclusion APBI using HIBT and respecting strict rules of implantation and planification, represents a smart alternative between no post-operative irradiation and whole breast irradiation delivered over 6 consecutive weeks.

In developed countries, the cancer incidence is about 150 000 cases per year and half of people with cancer may die from the extension of the primary tumour in secondary deposits. This disaster costs more than 2 billion euro per year. People with cancer are often treated with surgery and/or radiotherapy of localized primary tumour and chemo-prevention of occult disseminated micrometastases. Since chemotherapy essentially targets cycling tumour cells, quiescent micrometastases which may contain only one cell may escape. We previously reported that human melanoma clones with high metastatic potential and low gangliosides content appeared very radiosensitive to low-dose ionizing radiation both in culture and in immunosuppressed animals. This exquisite radiosensitivity was observed with the highly metastatic single cells which were resting at the time of irradiation. These data are consistent with the dose–response relationship for the radiotherapy of secondary deposits which appears linear with no threshold. Highly metastatic cells at an early stage of growth also appear very sensitive to chemicals and activated immune cells. We propose the medical hypothesis according to which the spread of resting micrometastases should be prevented by a single fraction of total-body irradiation delivered at a dose sufficiently low (below 0.2 Gy) to avoid normal tissue radiotoxicity. Radio-prevention may complement standard treatments for patients with metastases and may be delivered even for patients in whom no distant metastases were detected on tumour diagnosis (M0 stage).

Resume Objectif de l’etude. – Les carcinomes epidermoides non resecables de l’oropharynx et de l’hypopharynx conservent un pronostic defavorable a court ou moyen terme. Plus de 70 % des patients decedent dans les cinq ans de part l’evolution locoregionale. Nous rapportons pour ces tumeurs l’experience du centre Antoine Lacassagne d'une association concomittante de radiotherapie bifractionnee non acceleree et chimiotherapie. L’observance, la toxicite, la reponse tumorale, la survie et la presence d’eventuels facteurs cliniques pronostiques associes a ce traitement ont ete evaluees. Patients et methodes. – Quatre-vingt douze patients consecutifs ont ete pris en charge par ce protocole de mai 1992 a fevrier 2000. Tous etaient atteints d’un carcinome epidermoide pharynge non resecable de stade IV. La radiotherapie de la tumeur primitive et des ganglions satellites a ete delivree par deux faisceaux paralleles opposes, par les photons d’un appareil de telecobaltherapie ou d’un accelerateur de 4 a 6 MV, a raison de deux fractions de 1,2 Gy/j, cinq jours par semaine, sans interruption en cours de traitement. Une dose totale de 80,4 Gy a ete delivree aux cancers de l’oropharynx en 46 jours et de 75,6 Gy en 44 jours a ceux de l’hypopharynx. La chimiotherapie a consiste en une administration de deux a trois cycles, tous les 21 jours, de cisplatine a la dose de 100 mg/m 2 , et de 5-fluoro-uracile en perfusion continue sur cinq jours a raison de 750 mg/m 2 /j (1 er cycle), 430 mg/m 2 /j (2 e et 3 e cycles). Une attention particuliere a ete accordee aux soins complementaires en cours de traitement, tels que la mise en place systematique d’une nutrition enterale et un traitement de la mucite par laser de basse energie. Resultats. – En dehors de deux deces precoces lies au traitement, la toxicite aigue, bien que significative (mucite de grades III et IV de l’OMS : 89 % dont 16 % de grades IV, epithelite de grade III de l’OMS : 72 %, neutropenie de grade III et IV : 61 %) n’a pas ete une cause d’interruption de traitement de plus d’une semaine, grâce notamment aux soins complementaires. Le taux de reponse complete a six mois etait de 74 %. Les taux actuariels de survie globale etaient respectivement a un et deux ans de 72 et 50 % avec un recul median de 17 mois. Les facteurs pronostiques de la survie globale etaient l’etat general (taux de survie globale a trois ans de 71 % si l’indice de Karnofsky du patient etait entre 90 et 100 %, 30 % s’il etait de 80 %, 0 % enfin s’il etait entre 60 et 70 %, p = 0,0001) et la localisation tumorale (taux de survie globale a trois ans de 28 % en cas de cancer de l’hypopharynx, 37 % en cas de cancer du panpharynx et 55 % en cas de cancer de l’oropharynx, p = 0,009). Conclusion. – L’analyse de ces resultats a confirme l’efficacite de la radiotherapie bifractionnee non acceleree concomitante a la chimiotherapie par cisplatine et 5-fluoro-uracile sur ce type de tumeur particulierement evoluee. Quant a l’etat general du patient avant traitement, seule une prise en charge nutritionnelle efficace peut conduire a une optimisation des conditions de realisation et de succes du protocole.

To determine the relative biological effectiveness (RBE) for initial and delayed inactivation of cells by a modulated proton beam suitable for the treatment of tumours of the eye, within the spread-out Bragg peak and in its distal declining edge.Human tumour SCC25 cells were irradiated with the 65 MeV proton beam at the Cyclotron Medicyc in Nice. Perspex plates of different thickness were used to simulate five positions along the beam line: 2mm corresponding to the entrance beam; 15.6 and 25 mm in the spread-out Bragg peak; 27.2 and 27.8mm for the distal edge. At each position clonogenic survival of the irradiated cells and of their progeny were determined at various dose values. 60Co gamma-rays were used as reference radiation.RBE values evaluated at the survival level given by 2 Gy of gamma-rays increased with increasing depth from close to 1.0 at the proximal to about 1.2 at the distal part of the peak. Within the declining edge it reached the value of about 1.4 at 27.2 and about 2 at 27.8 mm. For the progeny of irradiated cells, the RBE value ranged from 1.0 to 1.1 within the spread-out Bragg peak and then increased up to a value of 2.0 at the last position. The dose-effect curves for the progeny always had a larger shoulder than for the irradiated progenitors, their alpha parameters being lower by a factor of about 4 and their beta parameters always being higher. The alpha/beta ratio was about 50 Gy for the progenitors and about 6 Gy for their progeny. The incidence of delayed effects increased with dose and with the depth within the beam.RBE values for the inactivation of cells irradiated in the spread-out Bragg peak are compatible with the value currently assumed in clinical applications. In the distal declining edge of the beam, the RBE values increased significantly to an extent that may be of concern when the region of the treatment volume is close to sensitive tissues. The yield of delayed reproductive cell death was significant at each position along the beam line.

Despite the fact that fast neutron irradiation of glioblastoma has shown on autopsies an ability to sterilize tumors, no therapeutic windows have been found for these particles due to their toxicity toward normal brain. Therefore, the Boron Neutron Capture Enhancement (BNCE) of fast neutron beam has been suggested. This paper addresses the problem of fast neutron beam collimation, which induces a dramatic decrease of the thermal neutron flux in the depth of the tissues when smaller irradiation fields are used. Thermoluminescent dosimeter TLD-600 and TLD-700 were used to determine the thermal neutron flux within a Plexiglas phantom irradiated under the Nice Biomedical Cyclotron p(60)+Be(32) fast neutron beam. A BNCE of 4.6% in physical dose was determined for a 10×10 cm2 field, and of 10.4% for a 20×20 cm2 one. A Dose Modification Factor of 1.19 was calculated for CAL 58 glioblastoma cells irradiated thanks to the larger field. In order to increase the thermal flux in depth while shaping the beam, heavy material collimation was studied with Monte Carlo simulations using coupled FLUKA and MCNP-4A codes. The use of 20 cm width lead blocks allowed a 2 fold thermal neutron flux increase in the depth of the phantom, while shielding the fast neutron beam with a fast neutron dose transmission of 23%. Using the DMF of 1.19, a BNCE of 40% was calculated in the beam axis. This enhancement might be sufficient to open, at least theoretically, a therapeutic window.

Objectifs Les carcinomes palpebraux peuvent etre traites par irradiation ou chirurgie. L’irradiation peut etre delivree par electrons, iridium 192 ou photons de 50 kV. Les avantages de la radiotherapie de contact par photons de 50 kV sont la precision, le faible volume de traitement, la bonne protection des organes a risque, la simplicite et l’efficacite. Patients et methodes Entre juin 2010 et juin 2014, 38 patients ont recu une radiotherapie, par deux appareils (RT50 Philips ou PAPILLON50) delivrant un faisceau de photons de 50 kV, trois pour deux localisations synchrones. Ils etaient âges de 48 a 94 ans, 79 ans en moyenne. La tumeur etait situee sur la paupiere superieure pour 12 %, le canthus externe pour 7 %, la paupiere inferieure pour 22 %, le canthus interne pour 59 %. Il s’agissait d’un carcinome basocellulaire pour 76 %, un carcinome epidermoide pour 15 %, un melanome pour 6 %, un adenocarcinome sebace pour 3 %, de stade T1 pour 95 % et T2 pour 5 %. La radiotherapie etait exclusive et radicale pour 30 %, adjuvante pour 70 %, apres une resection R0 pour 38 % et R1 pour 62 %. Un tiers (34 %) des traitements a ete effectue pour des lesions en rechute de traitements anterieurs. Deux schemas principaux ont ete utilises : 42 Gy en six fractions de 7 Gy (traitements radicaux) et 35 Gy en 5 cinq fractions de 7 Gy. Resultats Le suivi median etait de 14 mois (2 a 45). Deux tumeurs (5 %) ont rechute, a 6 et 15 mois, et ont pu beneficier d’une chirurgie de rattrapage. Le taux de survie sans recidive etait de 89 %. La toxicite aigue etait a type d’erytheme de grade 1 pour 39 %, grade 2 pour 39 %, conjonctivite de grade 1 ou 2 pour 22 %, larmoiement de grade 1 pour 22 %, depilation ciliaire transitoire pour 100 %. La toxicite tardive etait a type de larmoiement de grade 1 pour 35 %, xerose oculaire de grade 1 pour 5 %, depilation ciliaire persistante pour 15 %, depigmentation pour 38 %. Une baisse d’acuite visuelle a ete constatee chez 5 % des patients, dont deux atteints anterieurement d’un glaucome ou d’une cataracte de l’œil traite. Conclusion La radiotherapie de contact de 50 kV des carcinomes palpebraux est efficace et bien supportee dans cette population selectionnee.

La reponse des cellules tumorales humaines a l'irradiation in vitro par des particules de TEL eleve depend de plusieurs facteurs. Pour les particules chargees, la radiosensibilite augmente avec le TEL jusqu'a des valeurs de TEL voisines de 200 KeV/μm, puis diminue pour des valeurs de TEL superieures. En clinique, l'augmentation du TEL moyen de la particule chargee en profondeur est responsable d'une efficacite biologique relative (EBR) croissante. La probabilite de mortalite de la cellule par une particule traversant le noyau est proche de 1 pour les particules de TEL tres eleve comme l'Ar de 7 MeV par nucleon (TEL = 1500 KeV/μm); elle n'est que de 0,02 pour les ions d'O de 400 MeV (TEL = 20 KeV/μm). L'EBR est plus elevee pour les petites doses, la relation EBR/dose etant plus marquee dans les cellules ayant un rapport α/β plus faible apres exposition aux photons, selon le modele lineaire-quadratique. Les particules moins efficaces que les photons en terme de mortalite cellulaire moyenne induisent des degâts individuels importants, reveles par la production de micronoyaux (MN) multiples. Concernant le lien entre l'EBR et la radiosensibilite intrinseque, les donnees recentes utilisant a la fois la technique des colonies et la methode des MN, montrent que l'EBR est d'autant plus elevee que les cellules sont radioresistantes aux photons.

Les tumeurs cerebrales de haut grade gardent un pronostic effroyable bien qu'elles ne metastasent pas. L'utilisation de neutrons rapides a permis des sterilisations, mais elle s'est heurtee a la grande radiosensibilite des tissus cerebraux sains. Une perspective nouvelle est representee par l'utilisation des captures de neutrons sur le Bore-10 ( 10 B), c'est-a-dire par la creation selectivement a l'interieur des cellules tumorales de reactions nucleaires avec emission de particules a en surdosage dans un faisceau de neutrons rapides. L'utilisation de ces reactions pourrait permettre une amelioration de l'index therapeutique des neutrons rapides, sous reserve que des teneurs superieures a 100 μg/g de 10 B puissent etre obtenues dans les cellules tumorales.

In an effort to clarify the relationship between sensitivity of human tumour cells to low-LET and to fast neutron irradiation, 10 human tumour cell lines were exposed to cobalt gamma-rays and to 60 MeV (p -Be+) neutron beam. The data were pooled with results of 31 human tumour cell lines previously published. The analysis of date using the linear-quadratic model indicated that not only alpha values increased after neutron irradiation, but so did beta values too, although to a lesser extent. The mean inactivation dose (MID) was derived for each cell line from the linear-quadratic parameters after low-LET and high-LET exposure. MID values following neutron irradiation were closely correlated to those after gamma-ray irradiation. In these 41 cell lines, the extreme values of RBE derived by the ratio of MID varied by a factor of 3 among the cell lines. RBE was positively correlated to photon MID, meaning that intrinsically radiation resistant tumour cells have a higher neutron RBE, on average. Similar findings were observed if alpha ratios were used instead of MID ratios. In addition, the RBE/dose variations were more marked in cells with the higher RBE. Taken together, these data suggest that, although considerable variations exist among human tumour cell lines, intrinsically radioresistant cells are relatively more sensitized when exposed to high LET beams than radioresponsive tumours. An 'intrinsic gain factor' may thus be expected in irradiating radiation resistant tumours with fast neutrons, in addition to the hypoxic or kinetic gain factors. Because the quadratic component is still present after neutron irradiation, we suggest using MID ratio as a reference RBE when comparing survival curves of cells exposed to radiations of different qualities.

Dose-response relationships of most tumours and normal tissues after neutron irradiation are characterized by relatively high alpha/beta ratios. Late reacting tissues are not as protected by low doses per fraction as they are after low linear energy transfer (LET) irradiation. Using the linear-quadratic (LQ) model with the time factor (when needed), we have calculated the therapeutic ratio (TR) as the ratio of the effect on a tumour (or an acutely responding tissue) over that on late reacting tissue. Hypothetical cases are given as well as a case derived from LQ parameters obtained experimentally in animals. It is shown that X-ray fractionation schemes that lead to a high TR will lead to a low neutron TR. For epithelial tumours, a neutron gain factor, GF (ratio of TR) is possible if neutron fractionation is compared to hypofractionated X-irradiation. Neutron treatment over conventional overall times of rapidly proliferating tumours carries a low TR and offers no GF. Neutron therapy for tumours with low alpha/beta ratios offer a potential advantage compared to tumours with high alpha/beta ratios.

Summary The proton therapy facility of the Centre Antoine-Lacassagne in Nice began treatment of ocular tumors in June 1991. Up to October 1995, a total number of 600 patients were treated. An overview of the cases treated during the first 4 years of activity is given and the main problems encountered in the field, possibly interacting with the accuracy and reliability of the dose distribution, are listed.

Little is known about the action of charged particles of very high linear energy transfer (LET) on human cells and, in particular, the relationship between DNA damage and reproductive death. The aim of this study was to measure the biological efficiency of a low-energy argon beam (E = 7.1 MeV/nucleon, LET = 1590 keV/micron) produced at GSI, Darmstadt, on a human melanoma cell line (CAL4) established in our Institute. Two different methods were used: the micronucleus (MN) test and the colony-forming assay. The MN test, using the cytochalasin-block method, is a measure of genotoxic damage. MN are scored in binucleate cells (BNC) and are formed from acentric fragments or whole chromosomes that have not been incorporated into daughter nuclei at mitosis. The colony-forming assay quantifies reproductive death. Parallel experiments were run with cobalt gamma-rays for comparison. After Co irradiation, the MN-free BNC dose-response curve coincided with that of the loss of colony-forming ability, suggesting the potential of the former as a predictive test of cell killing. After Ar irradiation, there was a dissociation between the two effects, especially at high doses: cell death was greater than the frequency of BNC with MN. The inactivation cross-section was 74 microns2; it was 39 microns2 for MN yield. Therefore, the relative biological effectiveness (RBE) was higher for cell killing than for MN yield (0.8 and 0.5, respectively at a Co dose of 3 Gy). The total MN count in BNC followed the same pattern of response as the fraction of BNC with MN.(ABSTRACT TRUNCATED AT 250 WORDS)

Dans le cancer du sein, de nombreux facteurs pronostiques et predictifs sont accessibles, ces facteurs permettent d’evaluer l’evolution de la maladie mais aussi d’affiner le choix d’une prise en charge therapeutique. Le statut d’envahissement ganglionnaire (positif ou atients) est un des plus importants parametres pronostiques independants [1]. Les patientes montrant un envahissement ganglionnaire negatif presentent une maladie a bas ou moyen risque alors que les malades montrant au moins un ganglion envahi sont d’emblee considerees a moyen ou haut risque [2]. Le statut ganglionnaire doit etre considere comme un facteur pronostique » pur « et non comme un facteur predictif permettant de predire la reponse au traitement

Radiation therapy with positively charged particles implies that the Bragg peak be spread out to deliver a homogeneous dose to the tumour. The spread-out Bragg peak (SOBP) has a higher linear energy transfer (LET) than the entrance beam. In addition, there is an LET gradient from proximal to distal SOBP. The aim of this study is to find out whether these small LET variations lead to differences in radiation response. Human melanoma cells (CAL4) were exposed to 65 MeV proton beams produced by the cyclotron Medicyc at five different positions: 2 mm depth corresponding to the entrance, 15, 20, 25 and 26.8 mm depth corresponding to four different positions in the half-modulated SOBP. Survival curves were generated using the in vitro colony method and fitted with the linear-quadratic model. Survival differences were observed at high doses; they were statistically significant at a dose of 8 Gy. With respect to the entrance position (2 mm), the relative biological effectiveness (RBE) at 1% survival was 1.09, 1.12, 1.19 and 1.27 at 15, 20, 25 and 26.8 mm in the SOBP, respectively. Whereas RBE values in the SOBP greater than 1.0 relative to the entrance beam represent a small biological advantage to be added to the well-known physical advantage of high energy proton beams; the RBE gradient along the SOBP would imply that the distal end of the tumour would receive a higher biologically equivalent dose than the proximal end, despite a homogeneous physical dose, especially at the high doses per fraction given in ocular melanomas. Although the increase in effectiveness with depth is mild, it should be kept in mind during eye treatment planning, in case a critical target is present at the extreme end of the SOBP.

Le modele lineaire-quadratique, base sur un concept biologique, a acquis une certaine popularite ces dernieres annees, principalement en raison de son rapprochement avec les observations cliniques. Son usage est recommande pour les equivalences de dose en radiotherapie dans le cas de changement de fractionnement. Dans cette synthese, nous indiquons les diverses utilisations de ce modele en radiotherapie quotidienne. Initialement prevu pour les reactions tardives, il s'est enrichi par la suite en incorporant d'autres facteurs comme l'etalement, l'intervalle entre les seances et le debit de dose. Ces ameliorations l'ont rendu utile pour les equivalences concernant les reactions precoces et pour le controle tumoral, en cas de modification du schema standard en radiotherapie externe, ainsi qu'en curietherapie

Bien que la reponse des cellules tumorales humaines a des irradiations de faible transfert d'energie lineique (TEL) soit bien documentee, il existe peu de donnees dans la litterature concernant la reponse de ces lignees apres irradiation par des particules de TEL eleve. Nous avons expose trois lignees tumorales humaines: CAL 1 (melanome), CAL 51 (cancer du sein) et CHP 100 (neuroblastome) a des particules de Ne 11 MeV (400 KeV/μm), Ar 14 MeV (900 KeV/μm), Ar 7 MeV (1500 KeV/μm), Kr 13 MeV (4000 KeV/υm) et Au 11 MeV (9000 KeV/μm), produits par l'accelerateur Unilac de GSI, Darmstadt. Des courbes de survie ont ete produites par la methode des colonies in vitro et la reponse comparee a celle apres irradiation au Cobalt

Purpose: Young age is known to be an independent factor for developing local recurrence (LR) in breast cancer patients. It has also been shown that the occurrence of LR negatively affects patient outcome, especially if LR occurs within 3 years after treatment of the primary tumour. The question whether the impact of LR on patient outcome differs according to the patient’s age has not been addressed before. The purpose of the present study is to investigate cancer-specific survival (CSS) as well as overall survival after LR in young patients (Patients and Methods: Between 1974 and 2003, 2,130 breast cancer patients were treated with conservative surgery and axillary dissection. All of them received post-operative radiotherapy. Adjuvant chemo- and/or hormonal therapy was given according to the prognostic factors and the treatment policy at the time of diagnosis. Only biopsy-confirmed ipsilateral LRs were taken into account. Early LRs were those observed within 36 months after surgery, and late LRs were those which occurred thereafter. The median follow-up was 100 months. Survival analysis was conducted with the Kaplan-Meier method. Results: The median age was 59 years. There were 472 patients aged Conclusion: Although young patients experience more LR than older ones, once LR occurs, young patients have a better outcome than the others. Possible hypotheses are: (1) more aggressive treatment in young patients after LR; (2) the treatment is better sustained in young patients; (3) biological differences in the characteristics of LR.

Purpose To assess early clinical results and evaluate patient satisfaction in case of second conservative treatment (2nd CT) combining lumpectomy plus high-dose rate (HDR) interstitial brachytherapy for patients (pts) presenting with ipsilateral breast cancer recurrence (IBCR). Methods and Materials From June 2005 to July 2009, 42 pts presenting with an IBCR underwent a second lumpectomy with intraoperative implantation of plastic tubes in the tumor bed. After performing the dose distribution analysis on the postimplant CT scan, a total dose of 34 Gy in 10 fractions over 5 consecutive days was delivered. Toxicity evaluation was based on the Common Terminology Criteria for Adverse Events v3.0 criteria. Applying a visual analogic scale (VAS) analysis, patient satisfaction regarding cosmetic result and 2nd CT possibility was performed after the end of brachytherapy. Results Median followup was 21 months (range, 6–50 months) and median age at the time of local recurrence was 65 years (range, 30–85 years). Median delay between primary and recurrence was 11 years (range, 1–35 years). Median recurrence tumor size was 12 mm (range, 2–30 mm). Median number of plastic tubes and planes were nine (range, 5–12) and two (range, 1–3), respectively. Median clinical target volume was 68 cc (range, 31.2–146 cc). Second local control rate was 97%. Twenty-two pts (60%) developed complications. Cutaneous and subcutaneous fibrosis was the most frequent side effect. Median VAS satisfaction score regarding cosmetic result was 7 of 10 (range, 4–9), whereas median VAS satisfaction score for 2nd CT was 10 of 10 (range, 8–10). Conclusion A 2nd CT for IBCR using high-dose rate brachytherapy seems feasible with encouraging results in terms of second local control with an acceptable toxicity. Patient satisfaction regarding the possibility of second breast preservation should be considered.

Acute skin toxicity is frequent during radiation therapy and can lead to temporary arrest of the treatment. Chronic toxicity can occur and conduct to cosmetic problems. Alopecia is the most frequent toxicity concerning hair and is most of the time reversible. Several factors linked to patients influence skin toxicity, such as undernutrition, old age, obesity, smoking, skin diseases, autoimmune diseases, failure of DNA reparation. Skin, hair and nail toxicities depend also on radiation schedule. Acute toxicity is greater when dose per fraction increases. Chronic and acute toxicities are more often when total dose increases. Under 45 Gy, the risk of severe skin toxicity is low, and begins above 50 Gy. Skin toxicity depends also on the duration of radiotherapy and split course schedules are associated with less toxicities. Irradiation surface seems to influence skin toxicity but interaction is more complex. Reirradiation is often feasible in case of cancer recurrence but with a risk of grade 3-4 toxicity above all in head and neck cancer. The benefit/risk ratio has to be always precisely evaluated. Permanent alopecia is correlated with the follicle dose. Modern techniques of radiation therapy allow to spare skin.

Currently, radical mastectomy represents the gold standard for ipsilateral breast cancer recurrence. However, we already showed that a second conservative treatment was feasible combining lumpectomy plus low-dose rate interstitial brachytherapy. In this study, we reported the preliminary results of a second conservative treatment using a high-dose rate brachytherapy.From June 2005 to July 2009, 42 patients presenting with an ipsilateral breast cancer recurrence underwent a second conservative treatment. Plastic tubes were implanted intra-operatively at the time of the lumpectomy. After a post-implant CT scan, a total dose of 34 Gy in 10 fractions over 5 consecutive days was delivered through an ambulatory procedure. The toxicity evaluation used the Common Terminology Criteria for Adverse Events v3.0.The median follow-up was 21 months (6-50 months), median age at the time of the local recurrence was 65 years (30-85 years). The median delay between the primary and the recurrence was 11 years (1-35 years). The location of the recurrence was in the tumor bed for 22 patients (52.4%), in the same quadrant for 14 patients (33.3%) and unknown for six patients (14.3%). The median tumor size of the recurrence was 12 mm (2-30 mm). The median number of plastic tubes and plans were nine (5-12) and two (1-3) respectively. The median CTV was 68 cm(3) (31.2-146 cm(3)). The rate of second local control was 97%. Twenty-two patients (60%) experienced complications. The most frequent side effect consisted in cutaneous and sub-cutaneous fibrosis (72% of all the observed complications).A second conservative treatment for ipsilateral breast cancer recurrence using high-dose rate brachytherapy appears feasible leading to encouraging results in terms of second local control with an acceptable toxicity. Considering that a non-inferiority randomized trial comparing mastectomy versus second conservative treatment could be difficult to perform, what proof level will be necessary to achieve in order to change the medical procedures?

Background: Treatment of metastatic breast cancer (MBC) remains palliative. Patients with MBC represent a heterogeneous group whose prognosis and outcome may be dependent on host factors. The purpose of the present study was dual: first, to draw up a list of factors easily available in everyday clinical practice requiring no sophisticated or costly methods and second, to provide results from a large cohort of women who underwent diagnostic and treatment at a single institution. Patients and methods: From 1975 to 2005, a total of 1038 women with MBC during their follow-up were included in this retrospective analysis. Patients were subsequently assigned to five groups according to the period of metastatic diagnosis. Results: It is shown that age at initial diagnosis, hormonal receptor status and site of metastasis are the most relevant prognostic factors for predicting survival from the time of metastastic occurrence. It is also shown that a metastasis-free interval is an easily and immediately available multifactorial prognostic index reflecting the multiparametric variability of the disease. Conclusion: These fundamental observations may assist physicians in evaluating the survival potential of patients and in directing them toward the appropriate therapeutic decision.