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Summary Background BIG 3-07/TROG 07.01 is an international, multicentre, randomised, controlled, phase 3 trial evaluating tumour bed boost and hypofractionation in patients with non-low-risk ductal carcinoma in situ following breast-conserving surgery and whole breast radiotherapy. Here, we report the effects of diagnosis and treatment on health-related quality of life (HRQOL) at 2 years. Methods The BIG 3-07/TROG 07.01 trial is ongoing at 118 hospitals in 11 countries. Women aged 18 years or older with completely excised non-low-risk ductal carcinoma in situ were randomly assigned, by use of a minimisation algorithm, to tumour bed boost or no tumour bed boost, following conventional whole breast radiotherapy or hypofractionated whole breast radiotherapy using one of three randomisation categories. Category A was a 4-arm randomisation of tumour bed boost versus no boost following conventional whole breast radiotherapy (50 Gy in 25 fractions over 5 weeks) versus hypofractionated whole breast radiotherapy (42·5 Gy in 16 fractions over 3·5 weeks). Category B was a 2-arm randomisation between tumour bed boost versus no boost following conventional whole breast radiotherapy, and category C was a 2-arm randomisation between tumour bed boost versus no boost following hypofractionated whole breast radiotherapy. Stratification factors were age at diagnosis, planned endocrine therapy, and treating centre. The primary endpoint, time to local recurrence, will be reported when participants have completed 5 years of follow-up. The HRQOL statistical analysis plan prespecified eight aspects of HRQOL, assessed by four questionnaires at baseline, end of treatment, and at 6, 12, and 24 months after radiotherapy: fatigue and physical functioning (EORTC QLQ-C30); cosmetic status, breast-specific symptoms, arm and shoulder functional status (Breast Cancer Treatment Outcome Scale); body image and sexuality (Body Image Scale); and perceived risk of invasive breast cancer (Cancer Worry Scale and a study-specific question). For each of these measures, tumour bed boost was compared with no boost, and conventional whole breast radiotherapy compared with hypofractionated whole breast radiotherapy, by use of generalised estimating equation models. Analyses were by intention to treat, with Hochberg adjustment for multiple testing. This trial is registered with ClinicalTrials.gov , NCT00470236 . Findings Between June 1, 2007, and Aug 14, 2013, 1208 women were enrolled and randomly assigned to receive no tumour bed boost (n=605) or tumour bed boost (n=603). 396 of 1208 women were assigned to category A: conventional whole breast radiotherapy with tumour bed boost (n=100) or no boost (n=98), or to hypofractionated whole breast radiotherapy with tumour bed boost (n=98) or no boost (n=100). 447 were assigned to category B: conventional whole breast radiotherapy with tumour bed boost (n=223) or no boost (n=224). 365 were assigned to category C: hypofractionated whole breast radiotherapy with tumour bed boost (n=182) or no boost (n=183). All patients were followed up at 2 years for the HRQOL analysis. 1098 (91%) of 1208 patients received their allocated treatment, and most completed their scheduled HRQOL assessments (1147 [95%] of 1208 at baseline; 988 [87%] of 1141 at 2 years). Cosmetic status was worse with tumour bed boost than with no boost across all timepoints (difference 0·10 [95% CI 0·05–0·15], global p=0·00014, Hochberg-adjusted p=0·0016); at the end of treatment, the estimated difference between tumour bed boost and no boost was 0·13 (95% CI 0·06–0·20; p=0·00021), persisting at 24 months (0·13 [0·06–0·20]; p=0·00021). Arm and shoulder function was also adversely affected by tumour bed boost across all timepoints (0·08 [95% CI 0·03–0·13], global p=0·0033, Hochberg adjusted p=0·045); the difference between tumour bed boost and no boost at the end of treatment was 0·08 (0·01 to 0·15, p=0·021), and did not persist at 24 months (0·04 [–0·03 to 0·11], p=0·29). None of the other six prespecified aspects of HRQOL differed significantly after adjustment for multiple testing. Conventional whole breast radiotherapy was associated with worse body image than hypofractionated whole breast radiotherapy at the end of treatment (difference –1·10 [95% CI –1·79 to –0·42], p=0·0016). No significant differences were reported in the other PROs between conventional whole breast radiotherapy compared with hypofractionated whole breast radiotherapy. Interpretation Tumour bed boost was associated with persistent adverse effects on cosmetic status and arm and shoulder functional status, which might inform shared decision making while local recurrence analysis is pending. Funding National Health and Medical Research Council, Susan G Komen for the Cure, Breast Cancer Now, OncoSuisse, Dutch Cancer Society.

Resume Introduction Le cas expose est un cas unique du fait de l’apparition de nodules de permeation dans le champ d’irradiation d’un cancer du sein 2 ans apres traitement chirurgical d’un melanome. Il permet egalement d’apprecier cliniquement l’efficacite du vemurafenib. Cas clinique Nous exposons le cas d’une patiente de 47 ans qui a presente un melanome type SSM, Breslow 1,02 mm, sans ulceration et d’activite mitotique faible, sous-scapulaire droit, traite par exerese chirurgicale avec des marges a 2 cm. Un mois apres, un carcinome canalaire infiltrant du sein gauche etait diagnostique. Le traitement a consiste en une tumorectomie, exerese de ganglion sentinelle et radiotherapie de 50 grays avec un boost de 15 grays. Moins de 3 mois apres la fin de la radiotherapie, la patiente a developpe de multiples metastases cutanees sur le champ d’irradiation au niveau du sein gauche. Du fait de la presence de la mutation BRAFV600E et de l’echec du traitement par dacarbazine (decitene), un traitement par vemurafenib a ete debute. Nous avons constate une regression notable de la taille des nodules de permeation sans aucune nouvelle lesion. De ce fait, une chirurgie carcinologique en marges saines avec reconstruction par lambeau pedicule de muscle grand dorsal gauche a ete l’attitude therapeutique retenue par la RCP. Les resultats anatomopathologiques ont montre une exerese complete des lesions metastatiques. Nous avons realise une symetrisation du sein controlateral afin d’ameliorer la qualite de vie de la patiente. Apres un suivi de 2 ans et demi, la patiente ne presente aucun signe de recidive local, regional ou a distance. Discussion La rapidite du developpement et la localisation des metastases cutanees dans le cas clinique presente ici nous ont amenes a reflechir sur les effets de la radiotherapie au niveau cutane. La radiotherapie entraine des complications aigues (radiodermite) et chroniques par des mecanismes cellulaires et moleculaires. De plus, un effondrement de l’immunite est retrouve apres irradiation. L’association de ces differents mecanismes pourrait expliquer l’apparition de ces metastases sur le territoire d’irradiation. L’efficacite du vemurafenib retrouve dans notre cas clinique est en accord avec ce qui est decrit dans la litterature avec des reponses souvent rapides et une augmentation de la mediane de survie. Conclusion Ce cas unique dans la litterature montre les effets de la radiotherapie sur les tissus cutanes et l’efficacite du vemurafenib. Il souligne surtout qu’une etroite collaboration entre les differents praticiens ainsi qu’une connaissance des nouvelles therapies contribuent a une meilleure prise en charge des melanomes.

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 ?

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.

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.

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.

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.

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.

Although most institutions treat all fields each day, some radiotherapists continue to adopt an alternate day schedule. The resulting daily variations of the dose per fraction in laterally located targets have been analyzed using the linear-quadratic model. Patients with breast carcinoma treated with definitive radiotherapy in 1974-1975 with one field a day were studied. An effective dose per fraction was derived, with a value higher than the average dose per fraction received by the reference point. The greater the fluctuations between the doses per fraction on successive days, the higher the effective dose per fraction. The corresponding cell survival due to alternate treatment as compared to survival with daily treatment depends on the alpha/beta ratio. For a late effect with low alpha/beta ratio, an alternate treatment may lead to almost 10-fold increase in cell kill in these lateral targets such as those responsible for subcutaneous sclerosis as compared to daily treatment of all fields with the same total dose. Taking the average effective dose per fraction in our series, the increase in cell kill was 4-fold. Acute effects would suffer less damage due to alternate treatment because of a high alpha/beta ratio. Treatment on an alternate schedule should be restricted to palliative radiotherapy.