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Resume Introduction Les carcinomes in situ representent plus de 15 a 20 % des carcinomes mammaires. La radiotherapie du sein fait partie du standard therapeutique et fait suite a la chirurgie. Cependant, l’indication d’irradiation du lit tumoral reste encore controversee et heterogene selon les pratiques internationales meme s’il s’agit d’une situation clinique tres frequente. Le but de cette etude est de definir les indications d’une irradiation du lit tumoral dans le cadre des carcinomes canalaires in situ et de discuter de l’irradiation partielle acceleree du sein. Methode Les articles selectionnes ont ete publies entre 2015 et 2020 et comportaient comme terme MeSH « ductal carcinoma in situ » et « boost » pour les essais sur le complement d’irradiation, et « ductal carcinoma in situ » et « accelerated partial breast irradiation » pour les essais sur l’irradiation partielle acceleree. Resultats Le boost etait plus souvent pratique lorsque des facteurs de risque de recidive locale etaient presents, tels que un âge inferieur a 40 ou 50 ans, un mode de detection clinique, une taille tumorale de plus de 15 a 20 mm, un grade nucleaire eleve, la presence de necrose, des marges chirurgicales positive ou insuffisantes, des lesions d’hyperplasie atypique associees, et carcinome lobulaire in situ. L’irradiation partielle acceleree est une option envisageable pour les CCIS de pronostic favorable ou de pronostic intermediaire, des essais complementaires incluant plus de patientes sont necessaires. Conclusion La radiotherapie de la glande mammaire dans le cadre des CCIS a montre son efficacite en termes de controles local et locoregional de la maladie, diminuant ainsi les recidives in situ et infiltrantes. Cependant, l’indication de l’irradiation du lit operatoire reste toujours debattue et de pratique tres heterogene suivant les pays. Une autre alternative envisageable pour les patientes de pronostic favorable et presentant un lit tumoral de faible volume serait l’IPA.

Background The impact of the first coronavirus disease 2019 (COVID-19) wave on cancer patient management was measured within the nationwide network of the Unicancer comprehensive cancer centers in France. Patients and methods The number of patients diagnosed and treated within 17 of the 18 Unicancer centers was collected in 2020 and compared with that during the same periods between 2016 and 2019. Unicancer centers treat close to 20% of cancer patients in France yearly. The reduction in the number of patients attending the Unicancer centers was analyzed per regions and cancer types. The impact of delayed care on cancer-related deaths was calculated based on different hypotheses. Results A 6.8% decrease in patients managed within Unicancer in the first 7 months of 2020 versus 2019 was observed. This reduction reached 21% during April and May, and was not compensated in June and July, nor later until November 2020. This reduction was observed only for newly diagnosed patients, while the clinical activity for previously diagnosed patients increased by 4% similar to previous years. The reduction was more pronounced in women, in breast and prostate cancers, and for patients without metastasis. Using an estimated hazard ratio of 1.06 per month of delay in diagnosis and treatment of new patients, we calculated that the delays observed in the 5-month period from March to July 2020 may result in an excess mortality due to cancer of 1000-6000 patients in coming years. Conclusions In this study, the delays in cancer patient management were observed only for newly diagnosed patients, more frequently in women, for breast cancer, prostate cancer, and nonmetastatic cancers. These delays may result is an excess risk of cancer-related deaths in the coming years., Highlights • A reduction of the number of cancer patients attending cancer centers was observed in France from January to July 2020. • This reduction was observed only for newly diagnosed patients. • The reduction of new diagnosis was more pronounced in women, for breast cancer, and prostate cancer, and nonmetastatic cancer. • No compensation was observed for the last months of 2020. The magnitude of delays may be larger in centers within the same country. • An estimation of the excess cancer death resulting from these delays is presented.

Carcinomas in situ represent more than 15 to 20% of breast cancers. Radiotherapy of whole breast is part of the therapeutic standard and follows surgery. However, the indication of tumor bed irradiation is still controversial and heterogeneous according to international practice even though it is a very frequent clinical situation. The aim of this study is to define the indications of tumor bed irradiation in the context of ductal carcinomas in situ and to discuss accelerated partial irradiation of the breast.The selected papers were published between 2015 and 2020 and included as MeSH terms "ductal carcinoma in situ" and "boost" for the analysis of tumor bed irradiation, and "ductal carcinoma in situ" and "accelerated partial breast irradiation" for the analysis of accelerated partial irradiation.Boost was more often performed when risk factors for local recurrence were present, such as age less than 40 or 50 years old, clinical mode of detection, tumor size greater than 15 to 20mm, high nuclear grade, presence of necrosis, positive or insufficient surgical margins, associated atypical hyperplastic lesions, and lobular carcinoma in situ. Accelerated partial irradiation is an option for favorable or intermediate prognosis CCIS, further studies involving more patients are required.Radiotherapy of the mammary gland in the context of DCIS has shown its effectiveness in terms of local and locoregional control of the disease, thus reducing in situ and infiltrating recurrences. However, the indication of operating bed irradiation is still debated, and the practice is very heterogeneous depending on the country. Another possible alternative for patients with a favorable prognosis and a small tumor bed volume would be IPA.

In breast cancer, radiotherapy is an essential component of the treatment. However, indications of irradiation of the internal mammary chain and axillary area are debatables. Axillary recurrence in patients with invasive breast carcinoma remains an issue. Currently, the substitution of axillary lymph node dissection by sentinel node biopsy leads to revisit the role of axillary irradiation. Breast irradiation including level I, II and III might decrease the risk of axillary recurrence.A literature search was performed in PubMed and the Cochrane library to identify articles publishing data regarding dose-volume analysis of axillary levels in breast irradiation aiming to determine the potential therapeutic implications.Eleven articles were retained. A total of 375 treatment plans were analyzed. The results concerning the irradiation technique, initial dose prescribed to breast, delineated volumes and dose received at axillary levels were heterogeneous. The average dose delivered to axilla levels I-III with 3D-conformal radiotherapy using standard fields were between 24Gy and 43.5Gy, 3Gy and 32.5Gy and between 1.0Gy and 20.5Gy respectively. The average doses delivered to axilla levels I-III with 3D-conformal radiotherapy using high tangential fields were between 38Gy and 49.7Gy, 11Gy and 47.1Gy and 5Gy 38.7Gy, 32.1Gy and 5Gy (result available for only one study) respectively. Finally, the average doses delivered to axilla levels I-III with intensity modulated radiation therapy were between 14.5Gy and 42.6Gy, 3.4Gy and 35Gy and between 1.2Gy and 25.5Gy respectively.Incidental axillary dose seems insufficient to be therapeutic regardless of the irradiation technique. There are meaningful differences between intensity modulated radiation therapy and 3D-conformal radiotherapy.

Etat de la question Le traitement du cancer du sein localise fait intervenir les taxanes qui peuvent etre a l’origine d’une neuropathie peripherique precoce. La persistance de cette neurotoxicite, tres invalidante, est peu etudiee, particulierement chez les patientes âgees. Materiel et methodes Nous avons realise une etude de cohorte historique incluant toutes les patientes âgees de plus de 65 ans traitees par taxanes entre 2001 et 2016 pour un cancer du sein localise au Centre Paul Strauss. Le temps de participation etait d’au moins deux ans. Nous avons estime la persistance de la neurotoxicite deux ans apres la fin du traitement, et recherche les facteurs de risque des neuropathies de grade 2 ou 3, classees selon les « Common Terminology Criteria for Adverse Events » par une regression logistique multivariee. Resultats Parmi les 302 patientes incluses, 21 % ont presente une neuropathie persistante de grade 2 et 9 % une neuropathie de grade 3. Deux patientes sont decedees des complications d’une neuropathie de grade 3. Les facteurs de risque de neuropathie persistante etaient l’âge (p Conclusion La neuropathie persistante est un effet secondaire relativement frequent et parfois severe des taxanes. En presence de facteurs de risque, le recours a l’ancien protocole de chimiotherapie Cyclophosphamide-Methotrexate-5FU (CMF) pourrait se justifier chez les femmes âgees traitees pour un cancer du sein localise.

Objectives The incidence of skin cancers, melanoma in particular, is increasing rapidly. Consequently, specific recommendations for sun-protection measures now exist. This survey set out to assess the compliance of the general population with these guidelines. Methods The French nationwide observational survey, EDIFICE Melanoma, was conducted (28 September to 20 October 2011) through phone interviews of a representative sample of 1502 subjects aged ≥ 18 years, using the quota method. Sun-protection was defined as frequent or systematic use of clothes or sunscreen. The group of individuals who declared exposure to the sun (N = 1172) was subdivided: risk-takers (N = 442), and those who used sun protection (N = 730). Results Risk-takers were significantly more often male (62% vs. 44%, P

Patients with HER2-positive early breast cancer (EBC) preferred subcutaneous (s.c.) trastuzumab, delivered via single-use injection device (SID), over the intravenous (i.v.) formulation (Cohort 1 of the PrefHer study: NCT01401166). Here, we report patient preference, healthcare professional satisfaction, and safety data pooled from Cohort 1 and also Cohort 2, where s.c. trastuzumab was delivered via hand-held syringe.Patients were randomized to receive four adjuvant cycles of 600 mg fixed-dose s.c. trastuzumab followed by four cycles of standard i.v. trastuzumab, or vice versa. The primary endpoint was overall preference proportions for s.c. or i.v., assessed by patient interviews in the evaluable ITT population.A total of 245 patients were randomized to receive s.c. followed by i.v. and 243 received i.v. followed by s.c. (evaluable ITT populations: 235 and 232 patients, respectively). s.c. was preferred by 415/467 [88.9%; 95% confidence interval (CI) 85.7-91.6; P0.0001; two-sided test against null hypothesis of 65% s.c. preference]; 45/467 preferred i.v. (9.6%; 95% CI 7-13); 7/467 indicated no preference (1.5%; 95% CI 1-3). Clinician-reported adverse events occurred in 292/479 (61.0%) and 245/478 (51.3%) patients during the pooled s.c. and i.v. periods, respectively (P0.05; 2 × 2 χ(2)); 16 patients (3.3%) in each period experienced grade 3 events; none were grade 4/5.PrefHer revealed compelling and consistent patient preferences for s.c. over i.v. trastuzumab, regardless of SID or hand-held syringe delivery. s.c. was well tolerated and safety was consistent with previous reports, including the HannaH study (NCT00950300). No new safety signals were identified compared with the known i.v. profile in EBC. PrefHer and HannaH confirm that s.c. trastuzumab is a validated and preferred option over i.v. for improving patients' care in HER2-positive breast cancer.NCT01401166.

Resume Les criteres de jugement sont des mesures cliniques et biologiques pour l’evaluation et le developpement des therapeutiques. En cancerologie, ils peuvent etre classes en deux categories principales : les « criteres de jugement centres sur le patient » qui comprennent la survie globale (SG) et la qualite de vie relative a la sante (QdV) et les « criteres de jugement centres sur la tumeur » comme la survie sans progression. Les criteres de substitution sont des criteres de jugement principalement centres sur la tumeur dont l’objectif est de se substituer aux criteres de jugement centres sur le patient notamment la SG. Le choix des criteres de jugement dans les essais cliniques en oncologie est une problematique majeure pour apprecier le reel benefice du traitement pour le patient. La publication du guide de bonnes pratiques CONSORT conseille de reporter precisement les definitions des criteres de jugement primaires et secondaires. La SG est le critere de reference mais avec l’augmentation du nombre de traitements efficaces disponibles dans beaucoup de cancers, il est necessaire d’inclure un nombre plus important de patients et de les suivre plus longtemps ce qui augmente le cout des essais cliniques. Ainsi, les criteres de jugement dit intermediaires centres sur la tumeur qui sont evalues plus precocement et utilises comme criteres substitutifs de la survie globale sont de plus en plus utilises mais la plupart d’entre eux n’ont pas de definitions standardisees ce qui limite la comparaison des resultats de differents essais cliniques et ne sont pas valides comme criteres de substitution selon la methodologie de reference. De plus, la variabilite de leur definition peut fortement impacter les conclusions des essais en influencant l’estimation et la puissance statistique. Dans ce contexte, la QdV constitue un critere de jugement utile pour les essais assurant une evaluation du benefice du traitement tant d’un point de vue du patient que d’un point de vue de la sante publique. Les recherches en methodologie doivent se poursuivre pour developper des definitions consensuelles des criteres de jugement des essais cliniques en cancerologie et pour proposer une analyse longitudinale standardisee des donnees de QdV.

Resume Introduction L’organisation territoriale de la prise en charge du cancer est une priorite des autorites de sante. En Franche-Comte, pres de 6000 nouveaux cas de cancers sont detectes chaque annee. La necessite d’organiser les activites de chimiotherapie anti-cancereuse s’est imposee des les annees 2000. Dans cette logique, l’interet de disposer d’un systeme d’information partage sur le plan regional a ete acte. Les equipes medicales et pharmaceutiques de la region ont developpe un systeme d’information multicentrique dedie au traitement du cancer : « bonnes pratiques de la chimiotherapie ». Les objectifs du projet etaient : securiser le parcours therapeutique du patient, standardiser les pratiques tout en maintenant une prise en charge de proximite et enfin maitriser l’acces a l’innovation. Materiels et methodes Ce systeme d’information partage et securise repose sur un thesaurus regional unique de protocoles pour chaque tumeur et un dossier therapeutique regional par patient, disponibles en temps reel. La securite du processus therapeutique est assuree par une informatisation totale de la prescription medicale a l’administration infirmiere. Les referentiels nationaux sont integres dans l’outil pour accompagner les prescriptions. Un module statistique permet le suivi des indicateurs d’activite et de bon usage qui sont partages entre les professionnels de sante, les tutelles et les organismes payeurs. La gestion de la chimiovigilance est tracee dans l’outil. Resultats Le systeme d’information a ete mis en place en 2003 avec une dizaine d’acteurs. Aujourd’hui, ce systeme est utilise sur l’ensemble de la region avec 300 utilisateurs et 24 000 patients traites. Le thesaurus compte 1400 protocoles declines localement ou sur la region, dont 20 % d’essais cliniques. Aujourd’hui, 100 % des patients de la region sont integres dans BPC. Des tableaux de bord sont produits semestriellement de facon globale, par tumeur, par molecule. L’evaluation des pratiques montre un usage maitrise des therapeutiques innovantes au regard des referentiels nationaux. Discussion Les fonctionnalites de BPC optimisent et garantissent une reelle qualite et securite des soins. Son fonctionnement partage et multicentrique renforce la federation des acteurs et soutient l’organisation sanitaire de la Franche-Comte qui repose sur un institut regional federatif du cancer regroupant tous les centres autorises de la region. L’evaluation des pratiques en collaboration avec les instances regionales aide au pilotage regional de la cancerologie. Conclusions Cette experience montre l’interet des systemes d’information comme BPC dans des pathologies necessitant une gradation des soins comme la cancerologie. Sur la base d’un projet centre sur la qualite therapeutique, l’organisation globale des soins a ete grandement facilitee. La e-sante permet de combiner l’acces a l’expertise et la proximite des soins.

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

Although useful prognostic and predictive insights can be gained from patient and tumour characteristics in early-stage breast cancer, it is not always straightforward to predict the likely risk of recurrence for each individual patient following breast surgery. One of the most difficult challenges faced by clinicians is identifying patients who may benefit most from adjuvant chemotherapy, and distinguishing these cases from those where endocrine therapy may be sufficient for cure. Genomic tests such as the Oncotype DX

Summary Background The appropriate use of anticancer drugs is at major stake of steering health facilities. French health authorities have specifically elaborated evidence-based principles and guidelines on good practice for the management of anticancer drugs called “referentiels de bon usage” (RBU in French). Objectives The primary aim of the survey is to confront therapeutic practices and PGU. The secondary objective is to evaluate the impact of PGU on “outside the prescribing guidelines” therapeutic use, as compared with a similar study conducted in 2004. Patients and methods The survey was conducted from 1st July 2008 to 31st March 2009 at two reference centers in cancer research, and it included 2289 patients representing 3187 kinds of therapeutic use of an expensive anticancer drug (financed in addition to the classical system of hospital financing). Results Of all the kinds of therapeutic recourse, 79% are in accordance with PGU. The rarity of the tumor and the advanced stage of the disease are major factors of off RBU recourse. Compared with 2004, the implementation of these recommendations legitimizes 4% of additional validated therapeutic use. Therapeutic use without any scientific evidence is not frequent. Conclusion Finally, this study shows a globally controlled recourse to innovative molecules.

Resume Introduction Le bon usage des medicaments anticancereux est un enjeu majeur de pilotage des etablissements de sante. L’elaboration de referentiels de bon usage (RBU) est un dispositif specifique de notre systeme de sante. Objectif L’objectif principal de notre travail est de confronter les pratiques therapeutiques aux RBU. L’objectif secondaire est d’evaluer l’impact des RBU sur les recours « hors referentiel » en comparaison d’une etude similaire realisee en 2004. Patients et methode L’etude est realisee entre le 01/07/2008 et le 31/03/2009 sur deux centres de reference en cancerologie. Elle inclut 2289 patients representant 3187 recours a une molecule anticancereuse financee en sus de la tarification a l’activite. Resultats Sur l’ensemble des recours etudies, 79 % sont conformes aux RBU. La rarete de la tumeur et le stade avance de la maladie sont les facteurs majeurs de recours « hors referentiel ». Par rapport a 2004, la mise en place de protocoles temporaires de traitement (PTT) legitime 4 % de recours supplementaires. Les recours sans rationnel scientifique sont limites. Conclusion Au final, cette etude montre un recours globalement maitrise aux molecules innovantes.

L’essai PHARE (NCT-00381901) a ete mis en place depuis mai 2006 et continue a recruter des patientes avec un rythme soutenu. Cet essai randomise, comparant six a 12 mois de traitement chez les patientes recevant le trastuzumab en situation adjuvante est promu par l’Institut national du cancer. Plus de 450 cliniciens et une centaine d’attaches de recherche clinique sont impliques, pres de 180 etablissements de tout type, publics ou prives, y participent. Un millier de patientes est recrute annuellement; le taux de patientes recrutees represente 20 a 25 % des patientes eligibles pour ce traitement en adjuvant. Le design tres pragmatique — toute patiente eligible pour un traitement d’un an par trastuzumab en situation adjuvante peut etre incluse — accompagne d’un recueil optimal de donnees et d’un suivi clinique identique a la pratique ont largement contribue au succes de cet essai. La transparence et l’ouverture a tous les etablissements sont une autre cle de reussite. Une collaboration etroite a ete etablie avec des equipes internationales ayant des essais similaires en cours.

L’European Society for Medical Oncology (ESMO) est la premiere organisation europeenne dediee a l’oncologie medicale. Creee en 1975 dans le but de promouvoir l’oncologie medicale, elle evolue actuellement pour promouvoir une oncologie multidisciplinaire, integrant les differents acteurs medicaux de toutes specialites, ainsi que les chercheurs, les soignants et les associations de patients. La mission de l’ESMO est de procurer des soins optimaux a tous les patients. Dans cet objectif, l’ESMO propose une large variete d’activites scientifiques et d’enseignement destinees a la communaute de l’ESMO: 1) aux jeunes oncologues — pour aider et soutenir le developpement de leur carriere; 2) pour les oncologues en activite — afin de mettre a jour leurs connaissances medicale et scientifique dans le cadre de programmes accredites; 3) pour les patients — afin de les aider a acquerir une meilleure connaissance de leur maladie, comment la combattre, comment l’assumer au quotidien. Dans ce document, nous decrivons les differentes activites de l’ESMO dans le domaine de l’education et de l’enseignement.

Purpose: To describe the pathologic characteristics and prognostic factors of primary breast sarcomas (PBSs). Patients and Methods: We reviewed the clinical records and pathologic slides of 83 women with PBS treated in our institution between 1954 and 1991, with a median follow-up of 7.8 years. The majority of patients had undergone surgical treatment. Results: The main histologic type was malignant fibrohistiocytoma (n = 57). For the whole population, the 10-year overall survival (OS) and disease-free survival (DFS) rates were 62% and 50%, respectively. For Fédération Nationale des Centres de Lutte Contre le Cancer grade 1, 2, and 3 tumors, the 10-year OS and DFS rates were 82% and 61%, 62% and 51%, and 36% and 25%, respectively (P = .00007 and .004, respectively). For tumors measuring less than 5 cm, 5 to 10 cm, and more than 10 cm, the 10-year OS and DFS rates were 76% and 66%, 68% and 55%, and 28% and 15%, respectively (P = .002 and .009, respectively). In the multivariate analysis, the tumor size and histologic grade were correlated with the 10-year DFS rate (P = .04 and .01, respectively), but only the histologic grade was correlated with OS (P = .01). Angiosarcoma was the only histologic type significantly associated with a poorer outcome in the multivariate analysis. Conclusion: PBSs have the same clinical history and prognostic factors as sarcomas arising at other sites. Therefore, it is legitimate to use a similar treatment strategy for PBS as for other sarcomas.

We report on two randomized trials performed in the USA and Europe, which compared methotrexate and nolatrexed as treatment for patients with recurrent head and neck cancer. Eligibility criteria included: histologically confirmed squamous-cell carcinoma, measurable disease, adequate hematological, renal and hepatic functions, failure of a first-line chemotherapy, and informed consent. Methotrexate 40 mg/m(2) was weekly given by short infusion, and nolatrexed 725 mg/m(2) per day was administered as a five-day continuous infusion, every three weeks. A total of 139 patients (63 in the USA, 76 in Europe) were randomized based on a ratio of 2/1: 93 and 46 received nolatrexed and methotrexate, respectively. Patient characteristics included 115 males and 24 females; median age 60 years. In the nolatrexed arm, the following grade 3-4 toxicities occurred: neutropenia (29.9%) with 3.1% of febrile neutropenia, mucositis (33.3%), and vomiting (10.3%). In the MTX arm, the grade 3-4 toxicities were neutropenia (7.1%) and mucositis (6.9%). There was no difference in activity between the nolatrexed and the methotrexate treatment: 3.3% and 10.8% of objective responses, 1.9 versus 1.5 months of disease-free progression and 3.5 versus 3.7 months of overall survival, respectively. Nolatrexed has demonstrated a similar activity to methotrexate.

Le trastuzumab (Herceptin®) est un composant cle du traitement standard des patientes (pts) avec cancer du sein (CS) precoce HER2 positif [1] et est autorise en administration intraveineuse (IV). La dose de charge initiale (8 mg/kg) est administree en IV en 90 minutes, suivie par des doses d’entretien de 6 mg/kg/3 sem en 30 minutes. Une nouvelle formulation sous-cutanee (SC) de trastuzumab, avec une dose fixe de 600 mg et pour excipient une hyaluronidase recombinante humaine (rHuPH20), a ete developpee comme alternative au traitement IV. Cette formulation SC permet une administration rapide (< 5 minutes) ameliorant potentiellement la praticabilite et la compliance du traitement.

Le cancer du sein metastatique est reconnu comme etant une maladie incurable dont la prise en charge est palliative. Le but des traitements administres est alors de controler la croissance tumorale pour reduire les symptomes en induisant le moins de toxicites possible, c’est-a-dire augmenter la survie en preservant une bonne qualite de vie. Le praticien doit choisir le traitement qui permettra ďobtenir le meilleur equilibre entre ces differents objectifs. Toutefois, cette notion est a nuancer en fonction de la patiente, de sa maladie et de la ligne de traitement concernee. Si avec la succession des lignes, la preservation de la qualite de vie devient essentielle, ľefficacite du traitement doit etre un objectif prioritaire en premiere ligne. En effet, Greenberg a montre que, parmi les patientes en reponse complete apres la premiere ligne, 11% sont vivantes plus de 10 ans apres le diagnostic de metastases (1). Un deuxieme groupe de patientes, dont le site metastatique unique est accessible a une exerese chirurgicale apres un traitement systemique, pourrait egalement representer une proportion non negligeable de survivantes a long terme. En 2002, Hortobagyi s’interrogeait: «Can we cure limited metastatic breast cancer?» (2).

International audience

International audience; Introduction. The techniques used for axillary node dissection are constantly evolving. The advent of the grip Ligasure Precise raise the question of its cost-effectiveness compared with surgical clips. OBJECTIVE: To compare the effectiveness of Ligasure compared with surgical clips for simple axillary node dissection or Patey procedure in terms of duration of drainage, cost of hospitalization and complications. MATERIAL: and method. Retrospective study extending from January 1, 2003 to December 31, 2004, concerning 187 patients who underwent simple axillary dissection (100) or Patey procedure (87), with use of surgical clips or Ligasure followed by drainage. RESULTS: The use of Ligasure increased the operative cost because its price is higher than that of a clip grip with a refill. Ligasure significantly decreased the duration of drainage in the two groups but there was significantly more abundant fluid loss in the dissection group. The cost of hospitalization related to the choice of the technique of hemostasis (cost of the material + lasted of drainage X price of the day of hospitalization), was not significantly favor of Ligasure. Taking into account the choice of the hemostasis technique and the total duration of hospitalization (material cost + duration of hospitalization X price of the day of hospitalization), there is no significant difference between the two groups. CONCLUSION: This study compares grip Ligasure Precise with surgical clips for axillary dissection. The duration of drainage was significantly shorter with Ligasure Precise but its benefit in terms of fluid loss remains to be shown. The use of Ligasure does not significantly reduce the cost of hospitalization.

Epidermal Growth Factor receptor (EGFR) are a key factor for the tumoral proliferation and its tumoral over expression appears to be a powerful prognosis factor. Currently, 2 types of treatments are targeting EGFR: a monoclonal antibodies anti-EGFR and a specific inhibitors of the EGFR tyrosine kinase. The administration of these compound alone or in combination with chemotherapy gives some promising results. These targets as anti-cancer therapy had emerged to be a new perspective for oncology.

Patients suffering from locally advanced unresectable squamous cell carcinoma of the oropharynx and hypopharynx treated with radiotherapy alone have a poor prognosis. More than 70% of patients die within 5 years mainly due to local recurrences. The aim of this study was to evaluate retrospectively the Antoine Lacassagne Cancer Center's experience in a treatment by concomitant bid radiotherapy and chemotherapy. Evaluation was based on analysis of the toxicity, the response rates, the survival, and the clinical prognostic factors.From 1992 to 2000, 92 consecutive patients were treated in our single institution. All of them had stage IV, unresectable squamous cell carcinoma of the pharynx and they received continuous bid radiotherapy (two daily fractions of 1.2 Gy, 5 days a week, with a 6-h minimal interval between fractions). Total radiotherapy dose was 80.4 Gy on the oropharynx and 75.6 Gy on the hypopharynx. Two or three chemotherapy courses of cisplatin (CP)-5-fluorouracil (5FU) were given during radiotherapy at 21-day intervals (third not delivered after the end of the radiotherapy). CP dose was 100 mg/m2 (day 1) and 5-FU was given as 5-day continuous infusion (750 mg/m2/day at 1st course; 430 mg/m2/day at 2nd and 3rd courses). Special attention was paid to supportive care, particularly in terms of enteral nutrition and mucositis prevention by low-level laser energy.Acute toxicity was marked and included WHO grade III/IV mucositis (89%, 16% of them being grade IV), WHO grade III dermatitis (72%) and grade III/IV neutropenia (61%). This toxicity was significant but manageable with optimised supportive care, and never led to interruption of treatment for more than 1 week, although there were two toxic deaths. Complete global response rate at 6 months was 74%. Overall global survival at 1 and 2 years was 72% and 50% respectively, with a median follow-up of 17 months. Prognostic factors for overall survival were the Karnofsky index (71% survival at 3 years for patients with a Karnofsky index of 90-100% versus 30% for patients with a Karnofsky index of 80% versus 0% for patients with a Karnofsky index of 60-70%, p = 0.0001) and tumor location (55% at 3 years for oropharynx versus 37% for panpharynx versus 28% for hypopharynx, p = 0.009).These results confirm the efficacy of concomitant bid radiotherapy and chemotherapy in advanced unresectable tumor of the pharynx. The improvement in results will essentially depend on our capacity to restore in a good nutritional status the patients before beginning this heavy treatment.

The purpose of this study is to make a comparative analysis between acute toxicity with late toxicity. This study is based upon a French quality of life (QoL) questionnaire in a cohort of advanced head and neck (HN) cancer patients treated by concomitant twice-a-day continuous radiotherapy with no acceleration and chemotherapy with cisplatin and 5-fluorouracil.From September 1992 to November 1997, a prospective data bank of 91 patients was constituted. In November 1999, 31 patients were still alive and followed for more than 3 years. All patients had stage IV strictly unresectable squamous cell carcinoma of oropharynx or hypopharynx. A French specific HN cancer QoL questionnaire was used at the end of radiotherapy and at the last date of follow-up of each patient (during 1999). p values reflect comparison of percentages obtained at the end of treatment with percentages at long-term follow-up. Statistical analysis was performed using chi(2) test (p.05 considered as significant). Percentages obtained by the QoL questionnaire correspond to moderate-severe problems only.Twenty-nine of 31 (94%) patients participated in the QoL study. Acute treatment toxicities were severe with declines in virtually all QoL and functional domains. Globally, with an average long-term follow-up of 4.5 years (range 3-7 years after treatment), there is a statistical improvement in the following symptoms: dry mouth and sticky saliva (97% versus 55%, p.05); tasting problems (35% versus 21%, not significant); swallowing problems (77% versus 36%, p.05); and HN pain (86% versus 9%, p.05). Financial problems were not improved (21% versus 14%, not significant), and psychological problems (59% versus 5%) were statistically significant. Fourteen of 29 (48%) patients were drinking and 8 of 29 (28%) were smoking at long-term follow-up; at the diagnosis they were 86% and 90%, respectively. At long-term follow-up 22 of 29 presented good or very good QoL, and 25 of 29 said they had improved their initial QoL.The interest of twice-a-day radiotherapy with concomitant chemotherapy is to increase total radiotherapy equivalent dose without increasing late toxicity and also to improve locoregional control, survival, and long-term QoL/effectiveness ratio. Best supportive care is recommended to obtain both good QoL and cancer control in a long-term follow-up.

This review was performed to determine the efficacy of commonly used cytotoxic agents in the management of anthracycline-resistant breast cancer, using a stringent and uniform definition of drug resistance. We reviewed the reports of second- and third-line chemotherapy after anthracycline-containing regimens published over the last two decades. Only studies with sufficient information on the timing of progressive disease in relation to anthracycline therapy were considered. All assessable studies were reviewed individually, and the data obtained with taxanes in anthracycline-resistant breast cancer were also pooled to estimate the activity. The great majority of published studies on second- and third-line chemotherapy lack useful information about anthracycline resistance. Among the few studies with sufficient information about anthracycline resistance, several definitions were used. We reanalyzed those reports utilizing a uniform definition of anthracycline resistance: progression while receiving an anthracycline. Only studies using paclitaxel or docetaxel reported an activity in this anthracycline-resistant population, allowing a response rate between 6-50% and 32-57% for both agents respectively. The activity of other cytotoxic agents in anthracycline-resistant breast cancer could not be determined because a lack of accurate data using the stringent definition. Both paclitaxel and docetaxel have substantial antitumor activity in patients with clearly defined anthracycline-resistant breast cancer. The activity of other cytotoxic agents in this group of patients remains to be established.

The aim of this phase II study conducted on unresectable squamous cell carcinoma (USCC) of the oro- and hypopharynx was to associate twice-a-day (b.i.d.) continuous nonaccelerated radiotherapy with concomitant cisplatin (CP)-5-fluorouracil (5-FU) chemotherapy, both given at full dose. Feasibility, efficacy, survival, and pharmacokinetic-pharmacodynamic relationships were analyzed.Fifty-four consecutive patients with strictly USCC of oro- and/or hypopharynx received continuous b.i.d. radiotherapy (RT) (2 daily fractions of 1.2 Gy, 5 days a week, with a 6-h minimal interval between fractions). Total RT dose was 80.4 Gy on the oropharynx and 75.6 Gy on the hypopharynx. Three chemotherapy (CT) courses of CP-5-FU were given during RT at 21-day intervals (third not delivered after the end of RT). CP dose was 100 mg/m2 (day 1) and 5-FU was given as 5-day continuous infusion (day 2-day 6: 750 mg/m2/day cycle 1, 750 mg total dose/day cycle 2 and 3). Pharmacokinetics was performed for 5-FU (105 h follow-up) and CP (single sample at 16 h). Special attention was paid to supportive care.Good feasibility of RT was observed (85.2% of patients with total dose75 Gy). Five patients received 1 CT cycle, 34: 2 cycles, and 15: 3 cycles. The most frequent and severe acute toxicities were mucositis with grade 3-4 occurring in 28% at cycle 1 and 86% at cycle 2, as well as neutropenia (43% at cycle 2). Locoregional control at 6 months was observed in 66.7% of patients. No late toxicity above grade 2 RTOG was noticed. CP dose and 5-FU AUC(0-105h) were significantly linked to grade 3-4 neutropenia (cycle 2). Cumulative total platinum (Pt) concentration and Karnofsky index were the only independent predictors of locoregional control at 6 months. Finally, total RT dose and total Pt concentration were the only independent predictors of specific survival.This protocol showed good locoregional response with an acceptable toxicity profile. Pharmacokinetic survey is probably an effective approach to further reduce toxicity and improve efficacy. A multicentric randomized phase III study, now underway, should confirm these encouraging results.

To evaluate the usefulness of biologic and pharmacologic parameters for early identification of cisplatin-induced renal dysfunction.Prospective evaluation of 62 consecutively admitted patients with cancer.Cancer center.Sixty-two consecutive patients with cancer (52 men, 10 women; mean age 61.9 yrs).Patients received cisplatin as a single short intravenous infusion every 3 weeks. One hundred twenty-one cycles were analyzed. The dosage in the first cycle ranged between 61 and 105 mg/m2 (mean 84 mg/m2). All patients received a standard hydration protocol.Renal function was evaluated for each cycle before treatment (day 0) and before next cycle (day 21) based on the estimated creatinine clearance (Clcr). For each cycle, the weighted relative decrease (WD) of Clcr was calculated (WDClcr = 100 x [Clcr (day 0) - Clcr (day 21)]/[Clcr (day 0)](2). Total and ultrafilterable (UF) platinum were measured as a single-sample assay taken 16 hours after the end of cisplatin administration. The mean WDClcr was 0.07 min/100 ml (range -1.0 to +1.7 min/100 ml). The intensity of renal dysfunction evaluated by WDClcr was independent of cisplatin dosage, age, sex, body surface area, initial Clcr, and cycle number. Of interest, total and UF platinum concentrations were significantly correlated to WDClcr: the higher the platinum concentration, the greater the intensity of renal dysfunction. In stepwise regression analysis, UF platinum concentration was the only selected factor. The best prediction of UF platinum was obtained by stepwise regression including cisplatin dosage, initial Clcr, and cycle number (r=0.58, p0.0001).We consider our results to be a first step toward a clinical strategy to identify patients at risk for renal dysfunction after cisplatin treatment.