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Routine Electronic Monitoring of Health-Related Quality of Life (HRQoL) (REMOQOL) in clinical care with real-time feedback to physicians could help to enhance patient-centered care. We evaluated the feasibility of REMOQOL in the French context in the QOLIBRY study. The primary objective was to assess the patients’ compliance with REMOQOL. The QOLIBRY study was a single-center, prospective study conducted in the University Hospital of Besancon (France). Eligible patients were those treated with systemic therapies for breast, lung or colorectal cancer at any stage. Patients were invited to complete the EORTC QLQ-C30 questionnaire and cancer-site-specific modules before each visit on tablets and/or computers in the hospital or at home. During the consultation, physicians had real-time access to visual summaries of HRQoL scores. Compliance was assessed as adequate if at least 66% of HRQoL assessments were completed during the 4 months of follow-up. Between March 2016 and October 2018, 177 patients were included in the QOLIBRY study. Median age was 64 years (IQR 54–71). The proportion of patients with an adequate compliance rate was 95.5% (n = 63) in the breast cancer cohort, 98.2% (n = 55) in the colorectal cancer cohort, and 90.9% (n = 50) in the lung cancer cohort. The physicians checked the HRQoL results in 73.1% of visits and prescribed supportive care and adapted patient management in 8.3% and 5.2% of visits, respectively. The results of QOLIBRY study suggest that REMOQOL is feasible in the French context. However, information about HRQoL monitoring, training of the physicians in the use of the software, and recommendations for using HRQoL results to guide care are essential and must be improved.

Monoclonal antibodies targeted against the immune checkpoint molecules CTLA-4 and PD-1 have recently obtained approval for the treatment of metastatic melanoma and advanced/refractory non small-cell lung cancers and metastatic renal cancer. Besides their efficacy profile, these immune targeted agents also generate immune-related adverse events that may be life threatening if not anticipated and managed appropriately. This new family of dysimmune toxicities remains largely unknown to the broad oncology community. We propose here some practical guidelines for the oncologist to help in the clinical care of patients under immune checkpoint molecules.

International audience; Objectives: Several studies have reported that patients operated on for non-small cell lung cancer (NSCLC) are at high risk of second primary lung cancer (SPLC). However, widely varying estimates of this risk have been reported, with very few studies taking into account that these patients are at particularly high competing risk of death, due to recurrence of the initial disease and to comorbidities. Risk factor evaluation over time has significant repercussions on the post-surgery surveillance strategy offered for NSCLC. This study primarily sought to measure the risk of SPLC in a long-term follow-up series, using statistical methods considering competing risks of death.Materials and methods: The cumulative SPLC risk was estimated using the cumulative incidence of patients with completely resected Stage I-III NSCLC diagnosed between 2002 and 2015 based on the Doubs and Belfort cancer registry (France). A proportional sub-distribution hazard model (sdRH) was used to investigate factors associated with SPLC risk in the presence of competing risks.Results: Among the 522 patients, adenocarcinoma and Stage I or II disease accounted for 52.3% and 75.7% of patients, respectively. Overall, 84 patients developed SPLC (16.1%). The cumulative risk of SPLC was 20.2% at 10 years post-surgery (95% confidence interval [CI]: 15.3-23.2), and 25.2% (CI: 19.4-31.3) at 14 years post-surgery. On multivariate analysis, the SPLC risk was significantly higher in patients with postoperative thoracic radiotherapy (sdRH 2.79; 95% CI: 1.41-5.52; p = 0.003).Conclusion: This study using appropriate statistical methods to consider competing risks showed that after complete NSCLC resection, the cumulative incidence function of SPLC was high, with patients receiving postoperative thoracic radiotherapy at higher risk. These data support the need for life-long follow-up of patients who undergo NSCLC surgery, with the objective of screening for SPLC.

Introduction La cohorte TELOCAP a permis d’evaluer l’influence de divers parametres immunologiques dans le cancer bronchique non a petites cellules (CBNPC). Nous presentons ici l’influence de la lymphopenie T CD4 + sanguine dans cette cohorte. Methodes Ont ete inclus les patients diagnostiques d’un CBNPC, de stade clinique I a IV, traites au CHU de Besancon et a l’hopital europeen Georges-Pompidou [1] . La lymphopenie T CD4 + la lymphopenie T CD8 + dans le sang circulant, etaient respectivement definies comme un nombre absolu de lymphocytes (ALC) [2] . Le critere principal de jugement etait la survie globale. Resultats Au total, 186 patients ont ete inclus de 2010 a 2014. Les analyses univariees ont montre que la lymphopenie T CD4 + etait correlee a une plus faible survie globale (HR 1,616 [IC95 % = 1,107 ; 2,358] p = 0,0127). En revanche, aucune association n’a ete trouvee avec la lymphopenie T CD8+. En analyse multivariee, le statut de performance ≥ 2 (HR : 2,191 [IC95 % = 1,413 ; 3,396] p = 0,0005), le stade metastatique (HR : 2,558 [IC95 % = 1,722 ; 3,802] p . Conclusion Dans la presente etude, nous avons identifie la lymphopenie T CD4 + comme un facteur pronostique independant, pejoratif, pour la survie globale dans le CPNPC chez les patients atteints de CBNPC localise.

3044 Background: Increasing evidence highlights the crucial roles played by CD4+ Th1 cells in cancer immunity and immunotherapy (Spitzer et al., Cell 2017, Borst et al., Nat rev Immunol 2018). Here, we investigate the relevance of circulating CD4 Th1 response against shared tumor-associated antigens (TAA) in cancer patients treated by anti-PD-1 immunotherapy. Methods: A total of 46 advanced cancer patients (pts) including 32 pts with non-small cell lung cancer (NSCLC), 14 pts with melanoma, were enrolled (ITHER trial NCT02840058). Patients were treated with anti-PD-1 therapy as standard of care (26 pts with nivolumab and 20 pts with pembrolizumab). Peripheral blood mononuclear cells were collected before and after treatment at 1 and 3 months. The presence of circulating TAA-specific Th1 response was measured by IFNy ELISPOT assay using a mixture of 15mer peptides derived from telomerase (TERT) (Laheurte et al., Oncoimmunology 2016 and Br J C 2019). Results: At the baseline, the anti-TERT Th1 response was observed in 37% of pts. After anti-PD-1 therapy, de novo induction and/or amplification of pre-existing anti-TERT Th1 response was found in 26 % of pts (12/46). Whereas, a decrease of this response was documented in 15% of pts (7/46).The presence of anti-TERT Th1 response in peripheral blood during anti-PD-1 treatment was associated with a prolonged progression free-survival (PFS) as compared to the immune non responder pts (14.4 vs 2.6 months respectively, p = 0.006, HR 0.39 [0.2;0.76]). Similar observation was made for the overall survival (OS) (22.3 vs 12.3 months respectively, p = 0.04 HR 0.45 [0.21;0.96]). Notably, de novo reinvigoration of peripheral anti-TERT Th1 response after anti-PD-1 therapy was associated with a better clinical outcome as compared to the group of pts with decreased immune response after treatment (Median OS not reached vs 5.8 months). In contrast, no association with anti-PD-1 response was observed neither with circulating anti-NY-ESO-1 or with anti-viral Th1 response, concurrently measured in these patients. Conclusions: The reinvigoration of circulating CD4 Th1 against telomerase in patients treated by anti-PD-1 is associated with a better clinical outcome. These results underline the potential interest of monitoring circulating antitumor CD4 Th1 response for immune checkpoint inhibitors management.

Resume Les metastases osseuses concernent 40 % des patients atteints de cancer bronchopulmonaire dont le pronostic est aggrave par les complications et le handicap fonctionnel qu'elles engendrent. Le diagnostic, l’evaluation sous traitement systemique, les complications et la prise en charge therapeutique ne sont pas tres differents de ceux des autres cancers mais comportent quelques particularites propres au site pulmonaire primitif. Les methodes therapeutiques, plus souvent palliatives ou preventives des complications que curatrices, font appel a la chirurgie, a la radiotherapie, aux techniques de radiologie interventionnelle et aux inhibiteurs de la resorption osseuse. Ces traitements peuvent etre diversement associes entre eux et repetes au cours de l'evolution. Des scores pronostiques peuvent aider a en poser les indications. L’evaluation de leur efficacite est essentiellement basee sur l’etude des evenements osseux et de la survie. La chimiotherapie et les traitements antalgiques medicamenteux ne sont pas abordes.

Despite the critical roles played by IFN-γ+ CD4 Th1 response in tumor immunity, the translation of their potential in clinic remains challenging. Here, we evaluate the clinical significance of circulating anti-tumor CD4 Th1 response in non-small cell lung cancer (NSCLC) patients. 170 naïve-treatment patients were enrolled in this immune monitoring study. The antitumor adaptive Th1 response was assessed by IFN-γ ELISPOT assay in blood lymphocytes using a mixture of eight highly promiscuous and Th1-polarized HLA class II-restricted epitopes from telomerase (TERT). The presence of anti-TERT Th1 response was detected in 59/170 patients (35%). We found an opposite link between anti-TERT Th1 and hyper exhausted T cells co-expressing PD-1+ and TIM-3+ in NSCLC patients. In contrast to hyper exhausted CD8 T cells, the presence of anti-TERT Th1 response was associated with a low rate of hyper exhausted CD4 T cells. We showed that NSCLC stage dissemination is associated with a decrease of anti-TERT Th1 response but an increase of circulating hyper exhausted PD-1+/TIM-3+ CD4 T cells. Notably, anti-telomerase Th1 response and hyper exhausted CD4 T-cells displayed opposite prognosis value in NSCLC. While high level of anti-TERT Th1 cells play a protective role, hyper-exhausted PD-1+TIM-3+ CD4 T cells negatively affect patients’ survival. By using these two circulating immune factors, we stratified patients in distinct prognostic group. Patients with anti-TERT Th1high/CD4 PD-1 TIM-3low immune profile had better overall survival than anti-TERT Th1low/CD4 PD-1 TIM-3high group (median OS : not reached versus 4 months respectively p Citation Format: Caroline Laheurte, Magalie Dosset, Dewi Vernerey, Elodie Lauret Marie Joseph, Laura Boullerot, Vincent Kaulec, Marion Jacquin, Laurie Cuche, Guillaume Eberst, Pascale Jacoulet, Virginie Westeel, Olivier Adotevi. Adaptive CD4 Th1 response against telomerase in blood counteracts T-cell exhaustion in non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 575.

Points essentiels Les traitements perioperatoires des carcinomes bronchiques non a petites cellules (CBNPC) ont pour objectif de reduire le risque de recidive apres chirurgie, par la destruction precoce des eventuelles micrometastases. Les donnees de la litterature permettent d’en preciser les indications et modalites, qui doivent toutefois etre discutees au cas par cas en reunion de concertation pluridisciplinaire. Les CBNPC de stades II et III relevent d’une chimiotherapie perioperatoire a base d’un sel de platine. La chimiotherapie adjuvante, qui a le niveau de preuves le plus eleve, est le standard. Elle apporte un benefice de survie a cinq ans de l’ordre de 5 %. La chimiotherapie postoperatoire doit etre debutee dans les deux mois qui suivent la chirurgie. La chimiotherapie preoperatoire est une option. L’interet de la chimiotherapie postoperatoire a ete demontre avec un niveau de preuve superieur a celui de la chimiotherapie preoperatoire. La radiotherapie mediastinale postoperatoire doit etre discutee en cas de CBNPC classe pN2. Les etudes en cours cherchent a etablir la place des therapies ciblees dans le cadre perioperatoire, et evaluent prospectivement des strategies perioperatoires basees sur des analyses de biomarqueurs.

BACKGROUND: Combining bevacizumab with platinum-based chemotherapy significantly improves survival for patients with advanced non-squamous non-small cell lung cancer. The objective of this study was to assess the proportion of patients who could receive this combined therapy. METHODS: This was a retrospective single centre analysis of patients treated between 2007 and 2008. Exclusion criteria for bevacizumab included: squamous cell carcinoma, contraindication to platinum-based chemotherapy, uncontrolled hypertension, haemoptysis superior to 2.5 mL, recent surgery, and/or tomodensitometric criteria after independent review by two radiologists (contact with a proximal vessel, tracheobronchial involvement, cavitation). Cardiovascular diseases and central tumour location were not systematically considered as contraindications. RESULTS: Among 194 patients analysed, 21 (10.8%) to 35 (18%) patients were eligible for bevacizumab, whether or not cardiovascular diseases and central tumour location were considered as contraindications. The kappa coefficient was 0.49. CONCLUSION: Even though the proportion of patients who can receive chemotherapy plus bevacizumab may vary according to the eligibility criteria chosen and the interpretation of the CT scan, it is unlikely to exceed 25% of patients in daily practice.

Resume Les metastases osseuses sont une localisation secondaire frequente du cancer du poumon auxquelles pneumologues et oncologues doivent faire face. Les biphosphonates et la radiotherapie conventionnelle sont la base de leur prise en charge. De nouvelles modalites therapeutiques semblent egalement avoir leur place dans l’arsenal therapeutique.

Introduction Le diagnostic de cancer s’accompagne pour environ 30 % des patients de l’utilisation de plantes medicinales. Le probleme principal pose par le recours a ces plantes ou herbes aux proprietes medicinales supposees est leurs interactions pharmacologiques avec d’autres medicaments, en particulier les agents anti-neoplasiques oraux. Observation Nous rapportons le cas d’une patiente atteinte d’un cancer pulmonaire non a petites cellules et traitee depuis plus de 5 ans par erlotinib, avec tres bonnes tolerance et efficacite. Elle a brutalement developpe une eruption cutanee severe caracteristique d’un effet indesirable de l’erlotinib, mais resistante aux anti-fongiques topiques et aux dermocorticoides. L’interrogatoire precis de la patiente nous apprenait finalement l’introduction recente et quotidienne de the a l’hibiscus fourni par son pharmacien. Les lesions se sont rapidement ameliorees apres arret du breuvage et traitements topiques ( Fig. 1 et 2 ). Discussion Le the a l’hibiscus (Hibiscus sabdariffa) est une boisson populaire tres consommee a travers le monde, et appreciee pour ses qualites anti-oxydantes, anti-inflammatoires et anti-tumorales demontrees in vitro. Ses proprietes d’inhibition enzymatique effectives sur 9 isochromes du cytochrome P450 sont par contre moins connues. De facon similaire au pamplemousse, l’inhibition du metabolisme de l’erlotinib suite a la consommation de the a l’hibiscus explique son accumulation tissulaire et la toxicite cutanee engendree. A l’oppose, le millepertuis et le tabac sont des inducteurs du cytochrome P450 et diminuent la biodisponibilite de l’erlotinib. Conclusion Il est important pour les patients, medecins, infirmiers et pharmaciens de connaitre et de rechercher ces interactions entre agents anti-neoplasiques oraux et plantes medicinales, afin de prevenir leurs effets indesirables severes.

Cumulative evidence supports that CD4(+) Th1 cells play a key role in antitumor immunity. We previously reported the presence of spontaneous HLA-DR-restricted CD4(+) Th1 responses against telomerase reverse transcriptase (TERT) in various cancers by using promiscuous HLA-DR epitopes. Here, we described novel highly immunogenic HLA-DP4-binding epitopes from TERT named TERT541-555, TERT573-587, TERT613-627 and TERT911-925 and addressed the question about the immunoprevalence and magnitude of the naturally occurring antitumor CD4(+) T cell responses restricted by HLA-DP4 or HLA-DR, the two most common HLA class II. Direct comparative study of spontaneous anti-TERT CD4(+) T cell responses in a cohort of 87 lung cancer patients showed that HLA-DP4 and HLA-DR sustained specific Th1 responses in 10.1% and 25.2% of cancer patients respectively (p = 0.01). The magnitude of the HLA-DR-restricted responses was two to three times significantly higher than HLA-DP one (p = 0.005). Similar results were found in other cancers such as melanoma, breast cancer, renal cell carcinoma and colon cancer. Thus, our results describe for the first time in a large cohort of cancer patients a high immunoprevalence of HLA-DR-restricted spontaneous anti-TERT Th1 immunity compared to HLA-DP restriction. These results provide a new tool for comprehensive monitoring of antitumor CD4(+) Th1 response in various cancers.

Resume La chimiotherapie est souvent le seul traitement possible pour les mesotheliomes localement avances ou metastatiques. Ce travail permet de rappeler quelles sont les drogues potentiellement efficaces et les etudes recemment publiees dans le domaine de la chimiotherapie ou des therapeutiques ciblees. Si le patient ne peut etre inclus dans un essai therapeutique, la premiere ligne de choix est, en l’absence de contre-indication, l’association cisplatine-pemetrexed, le pemetrexed ayant obtenu une autorisation de mise sur le marche (AMM) en Septembre 2004. Parmi les alternatives sont passes en revue les taxanes, les anthracyclines liposomiques, les inhibiteurs de la topo-isomerase, les derives du cisplatine, les vinca-alcaloides, les anti-metabolites. Si les 3 premiers semblent avoir un interet tres limite voire inexistant, les vinca-alcaloides (vinorelbine, vinflunine) et surtout les antimetabolites (gemcitabine, raltitrexed, pemetrexed) sont tres prometteurs. Les etudes associant un anti-metabolite et un sel de platine sont les plus nombreuses, reunissant pres de 200 patients pour la gemcitabine ; elles montrent des resultats assez homogenes avec environ 50 % de survivants a un an. Quelques essais de chimiotherapie de deuxieme ligne sont egalement rapportes, encore preliminaires. Enfin, les therapeutiques ciblees telles que les anti-EGFR, anti-VEGF et anti-PDGF sont a l’etude, n’ayant pas demontre pour l’instant d’activite majeure.

Resume Les metastases osseuses sont la cause la plus frequente de douleur chez les patients atteints de cancer. Leur prise en charge sur le plan antalgique est un challenge therapeutique. La composante douloureuse ne repond pas toujours aux antalgiques majeurs, a la chimiotherapie et a la radiotherapie. Quand ces traitements sont depasses, la vertebroplastie, la cimentoplastie, la radiofrequence par voie percutanee et la radiotherapie metabolique sont des methodes elegantes et efficaces venant en complement des traitement classiques.

Resume But. – Le but de cette etude est d'evaluer l'efficacite et la tolerance du traitement de la rhizarthrose primitive du pouce par une prothese trapezometacarpienne contrainte modulaire non scellee ARPE. Materiel d'etude clinique. – Les patients ayant beneficie de ce traitement sont porteurs d'une rhizarthrose primitive evoluee aux stades 1 et 2 de COMTET, leur activite manuelle est reduite. Le recueil des donnees est retrospectif. Ainsi 37 protheses ont ete posees selon la meme technique par le meme operateur chez 29 patients, 28 femmes et un homme, huit patientes ont ete operes des deux cotes (21 droits, 16 gauches). L'âge moyen est de 67 ans. Un patient est decede et trois patientes ont ete perdues de vue. Le recul maximal est de sept ans. Resultats. – Le taux de satisfaction subjective est tres eleve. L'efficacite sur la douleur est constante. La mobilite est amelioree en particulier par l'obtention d'une retropulsion. L'analyse des radiographies et en particulier de l'index scaphotrapezien met en evidence un allongement de la colonne du pouce apres l'intervention qui diminue ensuite ce qui correspond a un glissement longitudinal de la prothese dans le tissu spongieux. Les complications tardives sont au nombre de quatre et de type mecanique (3 luxations et une absence de scellement) : trois cas ont necessite l'ablation de la prothese suivie d'une interposition tendineuse–ligamentoplastie. Conclusions. – La prothese non scellee ARPE apporte des resultats satisfaisants dans le traitement de l'arthrose trapezometacarpienne primitive isolee chez des patients a activite manuelle reduite et faiblement osteoporotiques.

Brain metastases are a frequent feature of the course of non-small cell lung carcinoma (NSCLC). The potential usefulness of prophylactic cranial irradiation (PCI) has led to the search for target groups likely to derive benefit. This multivariate analysis looked for factors predictive of brain metastases in a group of stages I-III NSCLC patients under care of the thoracic oncology unit of Besancon University Hospital from 1977 to 2001. All the patients had the same follow-up. They were divided into two groups: BM+ when they had a brain metastasis as the first site of progression, whether solitary or not, and BM(-) otherwise. Variables analysed were age, gender, performance status (0-1 versus 2-3), weight-loss stage T-status, N-status, pathological type, type of treatment, administration of chemotherapy, use of cisplatin and response to treatment. Three hundred and five patients were eligible and there were 77 patients (25.25%) in the BM+ group. Median time to onset of brain metastases was 12 months (1-163 months) and median survival from the diagnosis of brain metastases was 6 months (1-65 months). Factors predictive of brain progression were age < or =62 years (RR: 2.5, 95% CI: 1.33-4.76 and P = 0.004), T4 tumour status (RR: 3.75, 95% CI: 1.72-8.21 and P = 0.0009), N2-3 (RR: 2.61, 95% CI: 1.32-5.15 and P = 0.0057), and adenocarcinoma (RR: 3.39, 95% CI: 1.78-6.46 and P = 0.0002). No aspect of treatment plays a role in the frequency of this type of metastasis. These factors predictive of brain progression could serve as a basis for the selection of patients with the aim of sitting of studies on prophylactic cranial irradiation in NSCLC.

Context The 'Standards, Options and Recommendations' (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French cancer centres and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. Objectives To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for the management of stage I and II non small cell lung carcinoma treated by radiotherapy alone. Methods Data were identified by searching Medline and personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to independent reviewers, and to the medical committees of the 20 French cancer centres. Results The main recommendations for the management of stage I and II non small cell lung carcinoma treated by radiotherapy alone are: 1) The curative external irradiation with a continual course is an alternative to surgery only in the case of medically inoperable tumors or because the patient refuses surgery; 2) The external irradiation of the primary tumor only without the mediastinum could be proposed in peripheral stage IA. In proximal stage IA and IB, external irradiation should be carried out only as part of prospective randomised controlled trials comparing a localised irradiation of the primary tumor with a large irradiation of the mediastinum and the primary tumor. The treated volume must include the macroscopic tumoral volume with or without the microscopic tumoral volume and with a security margin from 1.5 to 2 cm; 3) There is a benefit to delivering a total dose in the primary tumor higher than 60 Gy in so far as the proposed irradiation, taking into account the respiratory function, does not increase the likelihood of severe adverse events due to radiation; and 4) The change in fractionation, the radiochemotherapy combination, the endobronchial brachytherapy with high dose rate alone or with external irradiation could be proposed only as part of prospective controlled trials for tumors classified as stage IB or II.

Contexte. - La Federation nationale des centres de lutte contre le cancer (FNCLCC) et les Centres regionaux de lutte contre le cancer (CRLCC), en collaboration avec des partenaires des secteurs public (CHU, CHG), prive et certaines societes savantes ont entrepris depuis 1993 d'elaborer des recommandations pour la pratique clinique en cancerologie: les « Standards, Options et Recommandations » (SOR). L'objectif de l'operation SOR est d'ameliorer la qualite et l'efficience des soins aux patients atteints de cancer en fournissant aux praticiens une aide a la decision facilement utilisable. La methodologie d'elaboration des SOR repose sur une revue et une analyse critique des donnees de la litterature scientifique par un groupe d'experts pluridisciplinaire, permettant de definir, sur la base du niveau de preuve scientifique et du jugement argumente des experts, des « Standards », des « Options » et des « Recommandations ». Avant publication, les SOR sont revus par des experts independants. Objectifs. - Definir, sur la base d'une revue de la litterature et de l'accord d'experts, des Standards, Options et Recommandations pour la prise en charge des patients atteints de cancer broncho-pulmonaire primitif de stade I ou Il traites par irradiation exclusive. Methodes. - Un groupe de travail multidisciplinaire mis en place par la Federation nationale des centres de lutte contre le cancer (FNCLCC) a revu les donnees scientifiques disponibles concernant la prise en charge des patients atteints de cancer broncho-pulmonaire primitif non a petites cellules de stade I et Il traites par irradiation exclusive. Apres selection des articles, synthese des resultats et redaction des SOR, le document a ete soumis pour relecture et approbation a des relecteurs. Resultats.- Les principales recommandations sont: 1) l'irradiation externe exclusive continue a visee curative, avec un fractionnement conventionnel, n'est une alternative a la chirurgie d'exerese qu'en cas de contre-indications a un acte chirurgical liees au terrain medical ou de refus du malade de tout acte chirurgical; 2) l'irradiation externe du volume tumoral primitif seul, sans le mediastin, peut etre proposee dans les formes classees stade IA, de topographie peripherique. Dans les formes classees stade IA proximal et IB, elle ne peut se concevoir que dans le cadre d'un essai therapeutique prospectif randomise et controle comparant une irradiation localisee au volume tumoral et une irradiation large mediastino-tumorale. Le volume traite doit inclure le volume tumoral macroscopique avec ou sans le volume tumoral microscopique, avec une marge de securite de 1,5 a 2 cm; 3) il y a un benefice a delivrer une dose totale dans le volume tumoral superieure a 60 Gy dans la mesure ou la technique d'irradiation proposee tenant compte de la fonction respiratoire du malade, n'augmente pas la probabilite de risque de complications severes radio-induites; 4) les modifications du fractionnement, l'association radiochimiotherapie concomitante, la curietherapie endoluminale a haut debit de dose seule ou en association a une irradiation externe, ne peuvent etre proposees que dans le cadre d'essais prospectifs controles pour des formes classees de stade IB ou II.

A dose escalation study of paclitaxel in combination with vinorelbine was conducted in 21 patients with previously untreated stage IIIb or IV non-small cell lung cancer (NSCLC). All three patients treated with the initial dose of paclitaxel 135 mg/m2 administered as a 1-h intravenous infusion and vinorelbine 25 mg/m2 experienced dose-limiting toxicity (febrile neutropenia). After modification of the dosing schedule, the MTD of paclitaxel was found to be 115 mg/m2 when combined with vinorelbine 20 mg/m2 on day 1, followed by vinorelbine 20 mg/m2 on day 5. Partial responses were achieved in 24% of patients, with a median duration of response of 126 days (range from 84 to 484 days) and a 1-year survival rate of 42%. In conclusion, haematologic toxicity (febrile neutropenia/neutropenia) severely restricts the dosing schedule of combined paclitaxel and vinorelbine, and possibly limits anti-tumour efficacy.

This study reports the results of 120 patients with inoperable non-small cell lung cancer treated with Navelbine at a dose of 25-30 mg/m2/week in a single-drug chemotherapy regimen. Surgery was contraindicated due to staging or to concomitant morbidity. Twenty patients achieved survival greater than or equal to 18 months, and one patient obtained exceptional survival of more than 120 months. The mean dose intensity of Navelbine in long-term survivors was 21.61 mg/m2/week. Objective response to Navelbine was found by multivariate analysis to be a prognostic factor for survival beyond 18 months. Weight loss of more than 5 kg of corporal weight was an unfavorable prognostic factor in patients with metastatic disease.

Thirty-one previously untreated patients with limited stage small-cell lung cancer (LSCLC) were included in a prospective study, to investigate the feasability and the efficacy of a combined modality treatment using concurrent hyperfractionated chest irradiation and cisplatin (P) plus etoposide (E) chemotherapy. All patients received intravenously P=75 mg/m 2 at day 1, plus E=120 mg/m 2 days 1–3, at 3-week intervals for six cycles. Irradiated patients received 45 Gy in two daily fractions, 5 days a week, from week 4 to week 6. During week 5, prophylactic cranial irradiation was initiated, in one daily fraction of 2.5 Gy for a total dose of 25 Gy. Twenty-nine patients were evaluable for response. Twenty-two (76%) achieved a complete response, five (17%) had a partial response. Five patients are currently alive. The overall response rate was 93% (CI 95% (83.7–100)). The median survival time was 14 months and the 2-year survival rate was 25%. Main toxicities were grade 3–4 esophagitis in half of the patients and myelosuppression. The results are not as optimistic as other studies using a similar regimen.

The authors present a case of isolated fracture of the trapezoid bone. The diagnosis was made late and needed modern diagnostic tools such as CT scanning. Diagnostic and treatment strategies for isolated fractures of the trapezoid bone are reviewed according to the literature.

Summary Background The aim of this study was to analyze SCLC patients beyond 30 months, particularly their outcome, their way of life, and factors which could influence relapses, second-primary cancers and death. Patients and methods Between January 1986 and May 1995, 263 SCLC patients who survived longer than 30 months were included from 52 French institutions. The analysis was performed on the 155 cases confirmed by a pathologic review. Results Physical, mental and psychological states were considered as normal at 30 months in respectively 70.3%, 87.7% and 67.7% of patients, not influenced by prophylactic cranial irradiation, number of chemotherapy cycles, CCNU or cisplatin. Therapeutic sequelae were neurological impairment (13%), pulmonary fibrosis (18%) and cardiac disorders (11%) at 30 months. Return to work was possible for 40% of patients in the first two years following diagnosis. Among 43 relapsing patients, 33 benefited from a second-line treatment. Their median survival was 12 months since retreatment, and seven patients have survived again longer than 30 months. Age > 60 at the time of diagnosis was found as an independent factor increasing the risk of relapse beyond 30 months (OR = 2.46, IC 95% (1.16–5.26), P = 0.01). The risk of relapse became less than 10% beyond five years. Twenty patients (13%) developed a second primary cancer in a mean time of 58.6 months. The risk of second primary cancer was increased by a number of chemotherapy cycles > 6 (OR = 3.25, IC 95% (1.08–9.8) P = 0.02) and by an age > 60 (OR = 2.92, IC 95% (1.07–7.97), P = 0.03). Five- and 10-year survival rates were respectively 68% and 44%. In these patients having reached a 30-month survival, three independent factors were predictive of a survival longer than five years: age ≤60 at the time of diagnosis (OR = 2.85, IC 95% (1.23–6.6), P = 0.01), chest radiotherapy (OR = 3.1, IC 95% (1.28–7.69), P – 0.006) and absence of relapse (OR = 4.5, IC 95% (1.75–12.5), P – 0.002). This study suggests that: 1) therapeutic sequelae are rather mild, allowing return to work in 40% of patients; 2) relapsing 30-month survivors can benefit from second-line treatment; 3) SCLC cure can be achieved with a 10-year follow-up.

Thirty-one patients with previously untreated advanced non-small cell lung cancer were included in a Phase I study to determine the optimal dose of Carboplatin (CBDCA) which preserves the best Navelbine (NVB) dose-intensity. NVB was administered at a 30-mg/m 2 fixed-dose on days 1–8/q 3 weeks, whereas CBDCA doses were planned to be escalated from 275 to 400 mg/m 2 on day 1/q 3 weeks for six successive groups of patients. The toxicity limiting dose of CBDCA in the combination was 350 mg/m 2 on day 1/q 3 weeks because of repetitive Grade IV neutropenia, and the optimal dose of CBDCA was 325 mg/m 2 on day 1/q 3 weeks, offering a 86.4% NVB and a 92.6% CBDCA relative dose-intensity for the first 9 weeks. Responses were observed at each step. This study demonstrates the feasibility and the efficacy of the NVB-CBDCA combination. It suggests that dose-intensity calculation can be helpful to determine the recommended dose for Phase II studies of new drug combinations.

Resume L'association d'un double syndrome canalaire — cubital au coude et median au canal carpien — en rapport avec un tophus goutteux est rare. Nous rapportons le cas d'un homme de 71 ans goutteux connu et traite, vu pour des dysesthesies des doigts et une perte de la force musculaire de la main droite. L'examen trouve deux masses au niveau du coude, l'une dans la gouttiere epitrochleo-olecrânienne, l'autre dans la bourse olecrânienne associees a une paralysie cubitale et un syndrome du canal carpien. Le traitement a ete chirurgical : neurolyse du cubital au coude et du median au canal carpien avec section du ligament annulaire anterieur du carpe. Avec un recul de 30 mois, les dysesthesies ont disparu mais l'amyotrophie des intrinseques cubitaux reste inchangee. La litterature est revue. Si le syndrome du canal carpien dans la goutte est connu (28 cas), il est en rapport avec une tenosynovite uratique. Le syndrome du cubital au coude n'a ete decrit qu'une fois (Akizuki, 1984). L'association de deux syndromes canalaires n'a pas ete retrouvee.

Summary Purpose The purpose of the study was to assess the possible benefit of the combination vinorelbine (NVB)-cisplatin (DDP) in comparison with NVB alone in advanced non- small cell lung cancer (NSCLC), not treated previously. It also involved confirmation of the efficacy of vinorelbine as monotherapy. Patients and methods In this phase 111 trial, 231 eligible patients were stratified by centre and randomized to receive either NVB alone, 30 mg/m2/week or the combination of NVB 30 mg/m2/week and DDP 80 mg/m2/3 weeks. Patients were to be treated for a minimum of 6 weeks, with the first response assessment performed 9 weeks after the beginning of treatment. Results The two groups differed in terms of objective response rates (16% and 43%, respectively, p = 0.0001) and median time to progression (10 weeks and 20 weeks, p = 0.0001). However, the difference was not significant for median survival time (32 weeks, 33 weeks, p = 0.48). The addition of DDP resulted in an increase in toxicity, in particular renal, hematologic, neurologic and emetic. This toxicity led to treatment discontinuation in 8% and 21% of patients, respectively. Respectively 3% and 13% of patients stopped treatment early during objective response (toxicity or refusal). Conclusions The NVB-DDP combination increased objective response rates and time to progression in comparison with NVB alone, but did not influence the survival of patients. The activity of NVB in the treatment of advanced NSCLC was confirmed.

La strategie therapeutique des cancers doit reposer sur l’usage de referentiels et faire l’objet d’une discussion au cours d’une reunion de concertation pluridisciplinaire pour deboucher sur la presentation au patient de son programme personnalise de soins. La decision therapeutique prend en compte plusieurs parametres, parmi lesquels l’extension de la maladie, le type histologique, l’etat general du patient, son âge, ses comorbidites et le contexte socio-psychologique. Nous n’aborderons pas dans ce chapitre le traitement des patients dont l’etat general est altere et des sujets âges qui fait l’objet d’autres chapitres.

The authors present a case of isolated fracture of the trapezoid bone. The diagnosis was made late and needed modern diagnostic tools such as CT scanning. Diagnostic and treatment strategies for isolated fractures of the trapezoid bone are reviewed according to the literature.

International audience; BACKGROUND: The interest of first- and second-line treatments in non-small cell lung cancer (NSCLC) has been demonstrated by successive randomized trials. Improvements in lung cancer care have routinely allowed a significant proportion of patients to be considered for third-line treatment. METHODS: A retrospective analysis was performed, including all consecutive patients with advanced NSCLC, who received at least three lines of systemic antineoplastic treatment at our institution. RESULTS: From a population of 613 patients treated with first-line treatment, a total of 173 patients received third-line treatment (cytotoxic chemotherapy in 131 patients; epidermal growth factor (EGFR) tyrosine kinase inhibitors in 42 patients). Only 13 patients (8%) received less than 75% of the theoretical dose intensity; 22 patients (13%) presented with severe toxicities. Symptom relief and performance status (PS) improvement were observed in 121 (92% of the 131 patients with symptoms) and 90 patients (52%), respectively. Using multivariate analysis, survival after third-line treatment was significantly increased in patients younger than 70 years-old (hazard ratio [HR] = 0.73, 95% confidence interval [CI]: 0.53-0.99, p = 0.047), who smoked less than 10 pack-years (HR = 0.82, 95% CI: 0.57-0.93, p = 0.036), with no cancer-related symptoms (HR = 0.75, 95% CI: 0.61-0.92, p = 0.007), a weight loss inferior to 5 kg since the beginning of second-line (HR = 0.63, 95% CI: 0.52-0.75, p = 0.013), a PS 0 to 1 (HR = 0.81, 95% CI: 0.76-0.86, p = 0.008), and no extrathoracic tumor spread at initiation of third-line treatment (HR = 0.67, 95% CI: 0.47-0.94, p = 0.042). Disease control after both first- and second-line treatments was the strongest predictor of prolonged survival after third-line treatment (HR = 0.47, 95% CI: 0.33-0.67, p = 0.001). CONCLUSIONS: Patients with advanced NSCLC may benefit from third-line treatment. The best candidates can be identified using standard prognostic factors, such as PS, and disease control after first- and second-line treatments.

Navelbine (vinorelbine, NVB) is the first semisynthetic 5'-nor-vinca-alkaloid selected for clinical trial. NVB has been shown to have a good level of activity against different experimental solid tumors in animals, with low neurotoxicity. In the phase II study, 78 patients with an inoperable non-small-cell lung cancer (NSCLC) were treated with NVB at a weekly dose of 30 mg/m2. No patient had previously received chemotherapy. Twenty-three of the 78 eligible patients showed a partial response (29.4% with a 95% confidence limits: 19.5-39.5). Eight patients were not evaluable and the percentage of partial response were 32.8% in the evaluable patients group. The median response duration was 34 weeks, and the median survival time for the overall population reached 33 weeks. Grade 3-4 leukopenia was seen in 12.5% of cycles. No thrombocytopenia occurred. At the dosage schedule used, NVB seems a very promising agent in the treatment of NSCLC.

The aortic valve area was serially evaluated in 45 patients, mean age 78 years, suffering from severe aortic stenosis who underwent percutaneous aortic valvuloplasty. The aortic valve area was calculated from haemodynamic data prior to and immediately after the procedure using the mean gradient. Serial determinations of the aortic valve area were also obtained 1 day before, 1 day after and 2 months after valvuloplasty from the thermodilution cardiac output and Doppler echocardiography mean left ventricle-to-aorta gradient. The mean gradient significantly decreased from 75±24 to 42±16mmHg (P>0.01) when measured from haemodynamic data and from 63±20 to 41±13 mmHg (P>001) when estimated from Doppler-derived data. It rose to 48±15 mmHg at 2 months (NS). The aortic valve area increased significantly from 0–48±0–13 to 0–67±0–29 cm2 (P>0.01) when calculated from haemodynamic data, and from 0–53±0–18 to 0–74±0–23 cm2 (P 0.01) but poorly afterwards (r=0.57, P>0.01). The aortic valve area was not influenced by valvuloplasty in eight patients. At 2 months, restenosis was apparent in eight patients out of 32 that were re-evaluated. Three patients died within 5 days of the procedure. After an average 12 months 'follow-up, eight more patients died. Symptoms were not influenced or recurred in 17 patients, while 17 others remained improved by at least one NYHA functional class. Seven patients were operated on, and there was one operative death. The calculated aortic valve area was significantly greater at the end of the procedure in the patients with persistent improvement compared with those with a poor result (0–83±0–29 cm2 vs 065±0–14 cm2, P < 0–05). In conclusion, in this study one third of the patients submitted to percutaneous aortic valvuloplasty had no objective improvement in calculated valve area or early restenosis after 2 months. Functional improvement was observed in one third of the patients. Immediate re-estimation of the aortic valve area from haemodynamic data at the end of the procedure may not reflect the actual effect of valvuloplasty on the aortic orifice

International audience; In this phase II study, gemcitabine and vinorelbine were combined at suboptimal doses for weekly administration in advanced non-small cell lung cancer (NSCLC). The primary objectives were to determine objective response rate (ORR) and time to progression (TTP). Secondary endpoints were safety and overall survival. Chemonaive patients with histologically or cytologically confirmed stage IIIB or IV NSCLC received vinorelbine (25 mg/m2) immediately followed by gemcitabine (800 mg/m2) once each week (on day 1) for 6 months without rest. From May 1998 to May 1999, 40 patients were enrolled (85% males; 70% stage IV) with a median age of 65.5. A total of 478 doses were administered, with a median of 9 per patient (range 2-72). The ORR was 27.5% (95% CI, 15.1-44.1%). The median TTP was 3.5 months (95% CI, 2.9-4.4 months). At a median follow-up of 6.5 months, the median survival was 11.6 months, and survival rates at 1 and 2 year(s) were 47.5% and 15.8%, respectively. The most common grade 3/4 hematologic toxicity was neutropenia, in 70% of patients, with febrile neutropenia in 28%. The most common grade 3/4 non-hematologic toxicity was transaminase elevation, in 22.5% of patients, which was transient and reversible. The other most prominent toxicities were, unexpectedly, pulmonary and cardiac toxicities. Based on these results, weekly, long-term administration of gemcitabine-vinorelbine appears to be an active regimen in NSCLC that warrants further investigation.

We report five patients with enchondromas of long bones in the hand. They were successfully treated by curettage and implantation of a biodegradable bone substitute (calcium phosphate). Bone regained normal X-ray appearance by 9 months. The full range of motion and normal function of the hand were restored. There were no complications and no recurrence at follow-up visits 28 months after operation. There are several advantages to this technique. The operative procedure may be performed under local anaesthesia on an out-patient basis and the operative time is shortened. Complications of a cancellous bone donor site are avoided, as are the potential infectious complications of allogenic bone implantation.

Invasion of bone by a metastatic lesion is the most common cause of pain in cancer patients. Pain management in these patients is an important and difficult task. The pain is not always properly controlled by high doses of specific medication, radiation therapy or chemotherapy. When these therapies do not provide adequate pain relief, percutaneous vertebroplasty, cementoplasty, radiofrequency ablation and internal radiotherapy appear to be elegant and efficient complementary alternative pain control methods.

Chemotherapy is often the only treatment possible for locally advanced or metastatic mesothelioma. This paper recalls which drugs might have therapeutic benefits in this condition and reviews recent studies of chemotherapy or targeted therapy. If the patient cannot be enrolled in a therapeutic trial the first line therapy in the absence of contraindications is a combination of cisplatin and pemetrexed, the latter having received a licence for this indication in September 2004. Among the alternatives reviewed are taxanes, liposomal anthracyclines, topoisomerase inhibitors, cisplatin derivatives, vinca alkaloids, and antimetabolites. Although the first three have show little or no benefit the vinca alkaloids (vinorelbine, vinflunine) and particularly the antimetabolites (gemcitabine, raltitrexed, pemetrexed) are very promising. Recent studies have looked most frequently at combinations of an anti-metabolite and a platinum salt, with data available from nearly 200 patients treated with gemcitabine. These studies have had fairly homogeneous results showing a one year survival of about 50%. Some preliminary data from studies of second line chemotherapy is also available. Finally studies of targeted therapies such as anti-EGFR, anti VEGF and anti PDGF are underway but have not as yet demonstrated major therapeutic benefit.