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Summary Context The administration of immune checkpoints inhibitors (ICIs) within hospitalization at home (HaH) organizations is an interesting alternative to conventional care. Three surveys were carried out to describe the different organizational models of French HaHs and criteria used by physicians in patient selection. Methods Three surveys were conducted between April 1 and August 31, 2020. The first one was addressed to all French HaHs, and the two others to public HaHs and oncologists treating patients with solid cancer in the Auvergne-Rhone-Alpes region. Results Overall, 54 French HaHs and 23 oncologists participated to the study. The health professionals involved in the patients’ care were very heterogeneous, although in 92% of cases, the treatment prescription was made by the oncologist. HaH physicians were more involved in clinical assessment the day before treatment (19% vs. 0%), treatment validation (56% vs. 15%), and treatment prescription (19% vs. 0%), while nurses were better equipped (emergency kit available in 81% versus 50% of cases) when HaHs did carry out ICIs compared to when they did not. Most oncologists agreed that age, neuropsychiatric disorders, home environment, as well as treatment duration and good tolerance should be considered in patient selection. ECOG PS status and treatment response were less consensually considered. Conclusion These results highlight the variability in French HaH organizations and patient selection criteria for employing ICIs at home. This study resulted in recommendations for administrating ICIs in HaH settings, which will likely be instrumental in further promoting this activity across France.

International audience; Introduction: Immune-checkpoint inhibitors have been approved for first and second line treatments of metastatic non-small cell lung cancer based on the results of several phase III trials. Patients with organ transplantation were excluded from these studies because checkpoint inhibitors could activate allo-reactive T cells leading to acute graft rejection.Case report: A 71-year-old Caucasian-male was diagnosed with stage IV pulmonary adenocarcinoma with multiple metastases, without molecular alteration and negative PD-L1 status. He had a left kidney transplant, and his immunosuppressive regimen consisted of sirolimus and mycophenolate mofetil. After failure of two therapeutic lines (carboplatin-paclitaxel and erlotinib) a multidisciplinary oncology meeting with the nephrologist started third line treatment with nivolumab 3mg/kg every 15 days, with no modification of the immunosuppressive treatment. The patient received a total of 14 injections of nivolumab with stable disease but treatment was discontinued due to acute rejection of the transplanted kidney 6 months later, without need for dialysis. The patient died of a chylothorax related to progression of the tumour 12 months after initiation of nivolumab.Conclusion: Immune checkpoint inhibitors are a potential treatment for solid organ transplant patients despite the risk of graft rejection.

Resume Deux nouvelles classes therapeutiques ont permis d’enrichir l’arsenal therapeutique des cancers broncho-pulmonaires (CBP) ces dernieres annees: l’immunotherapie et les therapies ciblees. Elles ont ameliore significativement la survie des patients pouvant en beneficier. De nouvelles questions se posent concernant leur admission en reanimation. La question de l’admission en reanimation peut se poser au diagnostic, avant l’initiation de ces nouveaux traitements, ou en cours de traitement, notamment pour gerer certains effets secondaires graves. Une collaboration etroite entre oncologues et intensivistes-reanimateurs est indispensable pour une prise en charge optimale de ces patients. Dans cette revue, nous decrirons donc l’impact de ces nouveaux traitements anti-tumoraux sur la decision d’admission et la prise en charge en reanimation des patients atteints d’un CBP.

Le cancer bronchopulmonaire (CBP) est la première cause de mortalité par cancer en France et dans le monde, mais son pronostic tend à s’améliorer depuis une dizaine d’années grâce à de nouvelles classes de traitements : l’immunothérapie et les thérapies ciblées. L’immunothérapie stimule le système immunitaire afin d’engendrer une réponse antitumorale. Ces molécules peuvent être prescrites chez la plupart des patients avec un CBP non à petites cellules (CBNPC) métastatique et entraînent parfois des réponses tumorales majeures et durables pouvant dépasser les 24 mois. Toutefois, cette efficacité concerne entre 20 et 50 % des patients selon la ligne de traitement. Les thérapies ciblées sont des traitements oraux visant les cellules tumorales porteuses d’anomalies génétiques spécifiques (addictions oncogéniques) et intéressent moins de 15 % des patients avec CBNPC, majoritairement les non-fumeurs. Les deux principales sont les mutations du gène de l’epithelial growth factor receptor (EGFR) et les réarrangements d’anaplastic lymphoma kinase (ALK). Ces anomalies peuvent être diagnostiquées en quelques jours, parfois sur un prélèvement sanguin (biopsie liquide pour détecter les mutations EGFR). Les thérapies ciblées améliorent la survie globale des patients dont la médiane dépasse les 30 mois. Toutefois, ces deux classes de traitement entraînent des toxicités spécifiques, fréquentes mais souvent bénignes. Les hospitalisations en réanimation des patients porteurs de CBNPC sont croissantes. L’amélioration du pronostic de ces patients est à prendre en compte lors de la discussion d’admission en réanimation sans conduire à des prises en charge déraisonnables.

Introduction L’utilisation de l’immunotherapie en premiere ligne de traitement des CBNPC de stade avance necessite de redefinir les lignes ulterieures. La combinaison paclitaxel-bevacizumab avait montre son efficacite dans l’essai ULTIMATE en seconde et troisieme ligne. AVATAX est une etude francaise evaluant cette combinaison en vie reelle. Methodes Il s’agit d’une etude retrospective multicentrique. L’objectif principal etait d’evaluer la tolerance et l’efficacite de l’association paclitaxel-bevacizumab pour les CBNPC non epidermoides en seconde ligne et plus, avec un interet plus particulier pour le sous-groupe des patients traites juste apres progression sous inhibiteurs des points de controle immunitaire (ICI). Resultats Entre janvier 2010 et fevrier 2020, 314 patients ont debute la combinaison : 55 % d’hommes, avec âge median au diagnostic de 60 ans, 27 % avaient un statut PS ≥ 2, 45 % avec des metastases cerebrales (tableau 1). Une majorite de patients etaient traites en deuxieme (20 %) et en troisieme (39 %) ligne et 28 % avaient recu un ICI a la ligne precedente. Le nombre de cures median a ete de 4 [interquartiles (IQ) [3–6]. Le taux de reponse objective etait de 40 % et le taux de controle de la maladie de 77 %. Les medianes de survie sans progression (SSP) et de survie globale (SG) etaient de 5,7 mois [IQ,3,2–9,6] et 10,8 mois [IQ,5,3–19,6] respectivement. Les effets secondaires tous grades confondus ont concerne 82 % des patients : 53 % d’asthenie et 39 % de neurotoxicite. La combinaison est devenue une monotherapie pour 25 % des patients en raison de toxicite. La SSP mediane des patients traites juste apres ICI etait significativement superieure par rapport a celle des patients non prealablement traites par ICI : 7,0 mois [IQ,4,2–11,0] vs 5,2 mois [IQ,2,9–8,8] p (log-rank) = 0,01. En revanche, il n’y avait pas de difference significative en termes de SG mediane entre ces 2 groupes. En analyse multivariee ( Tableau 1 ), les facteurs associes a une meilleure SSP etaient un traitement par ICI la ligne precedente et l’indice de performance. Seul l’indice de performance etait associe a la SG. Conclusion Ces donnees confirment en vie reelle les resultats d’efficacite et de tolerance de l’essai ULTIMATE. La combinaison paclitaxel-bevacizumab est particulierement efficace apres progression sous ICI.

Background End-of-life (EOL) communication is crucial, particularly for cancer patients. While advanced care planning is still uncommon, we sought to investigate its impact on care intensity in case of organ failure in lung cancer patients. Methods We prospectively included consecutive lung cancer patients hospitalised at the Grenoble University Hospital, France, between January 1, 2014 and March 31, 2016. Patients could be admitted several times and benefited from advanced care planning based on three care intensities: intensive care, maximal medical care, and exclusive palliative care. Patients’ wishes were addressed. Results Data of 739 hospitalisations concerning 482 patients were studied. During the three first admissions, 173 (25%) patients developed organ failure, with intensive care proposed to 56 (32%), maximal medical care to 104 (60%), and exclusive palliative care to 13 (8%). Median time to organ failure was 9 days [IQR 25%–75%: 3–13]. All patients benefited from care intensity that was either equal to or lower than the care proposed. Specific wishes were recorded for 158 (91%) patients, with a discussion about EOL conditions held in 116 (73%). Conclusions In case of organ failure, advanced care planning helps provide reasonable care intensity. The role of the patient's wishes as to the proposed care must be further investigated. Clinical Trial Registration The study was registered at www.ClinicalTrials.gov with the identifier NCT02852629 .

Immune-checkpoint inhibitors have been approved for first and second line treatments of metastatic non-small cell lung cancer based on the results of several phase III trials. Patients with organ transplantation were excluded from these studies because checkpoint inhibitors could activate allo-reactive T cells leading to acute graft rejection.A 71-year-old Caucasian-male was diagnosed with stage IV pulmonary adenocarcinoma with multiple metastases, without molecular alteration and negative PD-L1 status. He had a left kidney transplant, and his immunosuppressive regimen consisted of sirolimus and mycophenolate mofetil. After failure of two therapeutic lines (carboplatin-paclitaxel and erlotinib) a multidisciplinary oncology meeting with the nephrologist started third line treatment with nivolumab 3mg/kg every 15 days, with no modification of the immunosuppressive treatment. The patient received a total of 14 injections of nivolumab with stable disease but treatment was discontinued due to acute rejection of the transplanted kidney 6 months later, without need for dialysis. The patient died of a chylothorax related to progression of the tumour 12 months after initiation of nivolumab.Immune checkpoint inhibitors are a potential treatment for solid organ transplant patients despite the risk of graft rejection.

e21086 Background: With the growing role of immunotherapy (ICI) as first-line setting for advanced NSCLC, strategies must be redefined after failure. The combination paclitaxel-bevacizumab showed in the ULTIMATE trial a significant superiority versus docetaxel as second or third-line treatment. Limited restropective studies has demonstrated unexpected efficacy of chemotherapy after prior progression on ICI. This combination could be use as salvage treatment following ICI. Methods: This multi-centric retrospective study identifies patients treated with the combination paclitaxel-bevacizumab in metastatic non-squamous NSCLC as second-line therapy or beyond. Main objectives were to describe safety and efficacy of this combination, with a special attention to the sub-group treated just after ICI. Results: From January 2010 to February 2020, 314 patients started the paclitaxel-bevacizumab combination : 55% male, with a median age of 60 years, 27% with a performance status ≥2, 45% with brain metastases. A majority of patients were treated in second (20%) and third-line (39%), and 28% were treated just after ICI failure (88/314). Objective response rate (ORR) was 40% and disease control rate was 77 %. Median progression-free survival (PFS) and overall survival (OS) were 5,7 months [IQ,3,2–9,6] and 10,8 months [IQ,5,3–19,6] respectively. All grades adverse events concerned 82% of patients, including 53% asthenia and 39% neurotoxicity, and 25% of patients continued a monotherapy alone due to toxicity. Median PFS for patients treated after ICI failure (ICI+) was significantly superior compare to those not previously treated with ICI (ICI-) : 7,0 months [IQ,4,2–11,0] vs 5,2 months [IQ,2,9–8,8] p (log-rank) = 0,01. There was not statistically significant difference in term of OS between this two groups. In multivariate analysis, factors associated with superior PFS were previous ICI treatment (ICI+) and performance status. Conclusions: This study confirms an acceptable toxicity profile associated with interesting efficacy of the combination paclitaxel-bevacizumab as second-line treatment or beyond for non–squamous NSCLC patients, particularly after progression with ICI.

9091 Background: To determine real-world outcomes with first line pembrolizumab monotherapy, for aNSCLC with PD-L1 TPS ≥50%. Methods: Bispective, national and multicentric study including consecutively aNSCLC patients who initiated first-line pembrolizumab monotherapy from May 5, 2017 (marketing authorization of pembrolizumab monotherapy in France) to Nov 22, 2019 (marketing authorization of pembrolizumab-chemotherapy for non-squamous aNSCLC). Data were collected on medical charts. Responses were locally assessed according to RECIST v1.1; overall survival (OS) and real-world progression-free survival (rwPFS) were assessed by Kaplan-Meier method. Results: 845 patients (pts) were included by 33 centres: 67.8% were men, PS 0/1/≥2: 25.5%/46.9%/27.6%, active/former/nonsmokers: 39.1%/51.7%/6.4%, adenocarcinoma: 70.8%; stage IV at diagnosis: 91.6%; median number of metastatic sites at baseline: 2±1 (brain (20.8%), liver (13.9%) and bone (35%)); KRAS mutated: 27.7%, PDL1 TPS > 75%: 53.7% At the cut off date (31 December 2020), on the 783/845 (92.7%) evaluable pts, CR, PR, disease stabilization and progression were reported on 4.7%, 42.6%, 24.1% and 28.6% of cases, respectively; 588 (69.6%) pts had discontinued pembrolizumab, 390 (66.4%) had a first disease progression; 320/390 (82.1%) received a second line treatment, mainly platinum-based chemotherapy (90.6%). With a median follow up of 25,8 [95%CI: 24,8-26,7] months, median rwPFS and median OS were 8,2 [95%CI: 6,9-9,5] and 22,6 [95%CI: 18,5-27,4] months, respectively; 6, 12, 18-months survival rates were 76,8%, 64,8% and 54,3%. 835 adverse events were reported in 48% of the patients, grade ≥3 in 13.8% of cases, mainly asthenia, colitis, pneumonitis. For evaluable patients receiving a platinum-based doublet in second line (266/290, 89%), CR, PR, disease stabilization and progression were reported on 1.9%, 41%, 35.3% and 21.8% of cases, respectively. Uni and multivariate analysis of factors related to OS will be presented at the congress. Conclusions: Despite a less stringent selection of patients, pembrolizumab as a single agent achieves similar tumor shrinkage, rwPFS and OS than those of pivotal clinical trials.

The use of complementary and alternative medicine at least once during or after cancer treatment has increased over the past years from an estimated 25% in the 1970s and 1980s to more than 32% in the 1990s and to 49% after 2000. The risk of herb-drug interaction is therefore increasingly recognized as a public health problem. To the best of our knowledge, we report here the first case of interaction between ginger and anticancer drug, with serious consequences for the patient. There is an urgent need regarding complementary and alternative medicine: Both clinicians and patients should be aware of the potential interactions between herbs and prescribed drugs.

Objectives The aim of the present study was firstly to assess in a clinical setting the yields of an amplicon-based parallel RNA sequencing (RNA-seq) assay for ALK fusion transcript variants detection in comparison with immunohistochemistry (IHC) and fluorescent in-situ hybridization (FISH) in a selected population of ALK-positive and ALK-negative non-small cell lung cancer (NSCLC) cases, and secondly to evaluate the impact of the ALK variant on crizotinib efficacy. Materials and methods The cohort used for the assessment of the RNA-seq assay comprised 53 samples initially diagnosed as being ALK-positive based on the results obtained by IHC and/or FISH, and 23 ALK-negative samples. A distinction was made between ‘truly’ IHC/FISH positive or ‘truly’ IHC/FISH negative samples, and those for which the IHC and/or FISH were equivocal (IHC) or borderline-positive (FISH). Results On the overall population, RNA-seq sensitivity (Se) and specificity (Spe) were of 80% and 100%, respectively when IHC and FISH were combined. For the 31 ‘truly positive’ samples, Se and Spe of 100% were reached. An ALK status could be assigned by RNA-seq in 10/10 of the equivocal and/or borderline-positive IHC/FISH cases, 2/7 IHC/FISH discordant cases. When crizotinib efficacy was evaluated according to the type of ALK variant, better clinical outcomes were observed in crizotinib-treated patients with EML4-ALK v1/v2/others variants compared to v3a/b variants. Conclusion RNA-seq detects ALK rearrangements with a high sensitivity and specificity using only 10 ng of RNA. It appears to be a promising rescue technique for non-clear-cut IHC/FISH cases and also offers a unique opportunity to identify ALK fusion variants and evaluate their predictive value for ALK inhibitors efficacy.

Background We describe a case of pemetrexed toxicities related to reabsorption by an ileal neobladder, which caused prolonged hematotoxicity and nephrotoxicity. Case presentation A 59-year-old white man was diagnosed with metastatic wild-type adenocarcinoma of the upper lobe of his right lung. After a first cycle of cisplatin and pemetrexed, he had unusually prolonged aplasia and acute kidney injury. The prolonged aplasia was caused by pemetrexed reabsorption by the ileal mucosa of the neobladder as pemetrexed was eliminated renally in an active form and is partly lipophilic. Conclusions Pemetrexed may be reabsorbed by the ileal mucosa of the neobladder because of its hydrophobic structure and renal excretion in its active form. Acute urinary retention may maintain this phenomenon. Published data excluded a potential role for cisplatin in this toxicity; furthermore, we could not assess pemetrexed concentrations in the blood or urine as these assay techniques are not validated. Thus, care is needed when giving chemotherapy to patients with a neobladder.

Background Nivolumab, a monoclonal antibody targeting the programmed death-1 receptor, is indicated in locally advanced or metastatic non-small cell lung cancer, with progression after platinum-based chemotherapy. Up-to-now, few data are available concerning brain activity of this treatment and concomitant use of corticosteroids. Case presentation A 64-year-old caucasian man with a pulmonary adenocarcinoma associated with brain metastases received four courses of nivolumab in concomitance with a high dose of corticosteroids for his neurologic symptoms. He experienced a partial response in his brain and chest with an improvement in his general condition. Nivolumab was effective in shrinking symptomatic brain metastases, and metastases at other sites, in a patient with non-small cell lung cancer and first-line chemotherapy failure. The effect of nivolumab was obtained despite concomitant high-dose corticosteroid therapy. Combined nivolumab and high-dose corticosteroid therapy did not induce unexpected adverse events. Conclusion Nivolumab and concomitant high-dose corticosteroid therapy was found to be efficient and well tolerated.

Introduction La communication sur les souhaits de fin de vie est cruciale, en particulier pour les patients atteints de cancer. Les discussions concernant la conduite a tenir en cas d’aggravation des patients avec une maladie avancee sont peu frequentes et rarement documentees. Notre objectif est d’etudier l’impact d’une reflexion anticipee sur la prise en charge en cas d’aggravation aigue de patients presentant un cancer bronchopulmonaire. Methodes Cette etude prospective a inclus les patients hospitalises en oncologie thoracique au CHU de Grenoble entre le 28/01/2014 et le 31/03/2016. Lors de chaque admission, une fiche tracant les conduites a tenir en cas d’aggravation etait remplie par ecrit. Nous avons defini 3 niveaux d’intensite de soins proposes : soins intensifs, soins medicaux maximaux, soins palliatifs exclusifs. Les souhaits des patients etaient rapportes. Resultats Les donnees de 739 hospitalisations (482 patients) ont ete etudiees. Lors des 3 premieres admissions, 173 (25 %) patients ont presente une defaillance d’organes ( Tableau 1 ). Parmi eux, 56 (32 %) etaient proposes en soins intensifs, 104 (60 %) en soins medicaux maximaux, et 13 (8 %) en soins palliatifs exclusifs. La duree moyenne entre l’admission et la defaillance d’organes etait de 9 jours [IQ 25 %–75 %, 3–13]. Aucun soin d’intensite superieure a celle proposee n’a ete realise. Les souhaits des patients ont ete rapportes pour 158 (91 %) d’entre eux, avec une discussion sur les conditions de fin de vie dans 116 (73 %) cas. Conclusion En cas de defaillance d’organe, la reflexion anticipee sur la conduite a tenir permet de mettre en place une intensite de soins raisonnable. La majorite des patients ayant presente une defaillance d’organes ont eu une discussion sur les conditions de fin de vie pendant l’hospitalisation. La place du souhait du patient dans la proposition de soins devrait etre investiguee plus en detail.

Introduction Le cancer bronchique non a petites cellules de stade III (CBNPC) represente une population heterogene avec differentes strategies de traitement, souvent en association (chirurgie, radiotherapie et chimiotherapie). L’objectif de ce travail est de comparer les survies des patients selon la strategie therapeutique proposee en reunion de concertation pluridisciplinaire (RCP) et finalement realisee. Methodes A partir de la base de donnees de la RCP d’oncologie thoracique du CHU Grenoble Alpes, les patients atteints d’un CBNPC de stade III pris en charge entre 2010 et 2017 ont ete inclus. Les strategies de traitement proposees et celles qui ont ete reellement mises en œuvre ont ete decrites, en particulier en cas de recours a la chirurgie ou a la radiotherapie. Les caracteristiques des patients et leurs survies en fonction de ces traitements ont ete etudiees. Resultats Sur les 411 patients etudies, 249 avaient un CBNPC de stade IIIA et 162 un stade IIIB. Un tiers (n = 141) des patients a beneficie d’une chirurgie premiere avec une survie mediane de 761 jours [311–1180]. Les survies medianes des patients traites par radiochimiotherapie concomitante ou sequentielle (n = 72, 17 %) et ceux planifies pour une chimiotherapie neoadjuvante avant chirurgie (n = 60, 15 %) etaient similaires : 496 jours [IQ 25 %–75 %, 363–1089] et 482 jours [IQ 25 %–75 %, 257–720]. Parmi les 60 patients prevus pour une chimiotherapie neoadjuvante, 37 (62 %) ont effectivement beneficie de la chirurgie. Pour 23 (38 %) patients l’indication de chirurgie n’a finalement pas ete retenue ; 13 d’entre eux ont pu beneficier d’une irradiation thoracique. La survie de ces derniers est similaire a celle des patients ayant pu etre operes ( Tableau 1 ). Conclusion Dans notre cohorte, les survies des patients traites par radiochimiotherapie concomitante ou sequentielle et celle de ceux operes apres chimiotherapie neoadjuvante sont similaires. Le durvalumab en adjuvant a demontre une amelioration de la survie apres radiochimiotherapie concomitante. Proposer d’emblee une radiochimiotherapie concomitante avec le durvalumab en adjuvant aux patients non eligibles pour une chirurgie d’emblee pourrait ameliorer leur survie. Des etudes de vraie vie dans les annees a venir seront utiles.

Background ULTIMATE, a phase III trial, showed a significant superiority regarding progression free survival (PFS) of the combination paclitaxel-bevacizumab versus docetaxel as second or third line treatment for advanced non-small cell lung cancer (NSCLC). With the increase use of immunotherapy in first-line setting, second line strategies must be redefined. Paclitaxel-bevacizumab combination could be an option. Methods The main objectives were to describe safety and efficacy of this combination in metastatic non-squamous NSCLC as second-line therapy or beyond with a special attention paid to the sub-group treated just after immune checkpoint inhibitors. It was a multicentric retrospective study. Results This analysis included from 1st September 2010 to 1st april 2018, 76 patients: 42 (55%) male, 18 (24%) and 36 (47%) treated in second and third line respectively, and 22 (29%) in fourth line or more. Overall response rate (ORR) was 37% (28/76) and disease control rate 74 % (56/76). Median PFS and OS were 5,7 [95%CI: 4,1-6,9] months and 11,2 [95%CI: 8-not reached] months respectively. In second and third line, ORR was respectively 39% and 42%, PFS 4 months [95%CI: 2,5-7,7] and 6 months [95%CI: 4-7], OS 9,4 months [95%CI: 2,7-not reached] and was not reached in third line at 12 months. Grade 3–4 adverse events included asthenia 5% (4/76), neurotoxicity 3% (2/76), bleeding events 4% (3/76), and hematological toxicity 1% (1/76). In the subset of patients treated in third-line or beyond, immediately after immunotherapy (33/76), we note with interest that ORR was 42% (14/33), median PFS was 6,2 [95% CI: 4,6-7,7] months, and median overall survival was not reached at 12 months. Conclusion This study shows an acceptable toxicity profile associated with encouraging efficacy of the combination paclitaxel-bevacizumab as second-line treatment or beyond for non –squamous NSCLC patients. Moreover, these results seems to be very promising preliminary findings for patients treated just after immunotherapy. AVATAX is ongoing and should collect data from about 200 patients. Legal entity responsible for the study Chantal Decroisette. Funding Has not received any funding. Disclosure C. Chouaid: Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: AZ; Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: BI; Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer and Amgen; Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Takeda; Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Sanofi Aventis; Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: GSK. G. Rousseau-Bussac: Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self): roche; Travel / Accommodation / Expenses: Bristol-Myers-Squibb, Travel / Accommodation / Expenses: Takeda; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: MSD; Travel / Accommodation / Expenses: Mundipharma; Travel / Accommodation / Expenses: Lilly; Travel / Accommodation / Expenses: Janssen-Cilag; Travel / Accommodation / Expenses: Boehringer Ingelheim. J. Pinsolle: Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Takeda; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pierre Fabre. R. Descourt: Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Boehringer Ingelheim; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Takeda. M. Geier: Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb. C. Decroisette: Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Takeda; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Boehringer Ingelheim; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb. All other authors have declared no conflicts of interest.

Background ULTIMATE, a phase III trial, showed a significant superiority in terms of progression free survival (PFS) and less toxicity of the combination paclitaxel-bevacizumab versus docetaxel as second or third-line treatment. With the growing role of immunotherapy as first-line setting for advanced non-small cell lung cancer (NSCLC), there is a need to redefine strategies to failure. The use of the paclitaxel-bevacizumab combination could be an option. Methods This retrospective study identified patients treated with paclitaxel and bevacizumab according to the ULTIMATE study in 3 centers in France. Main objectives were to describe safety and efficacy of this combination in metastatic non-squamous NSCLC as second-line therapy or beyond, with a particular interest for the sub-group of patients treated just after immune checkpoint inhibitors. Results From 1st September 2010 to 1st avril 2018, 76 patients started the paclitaxel-bevacizumab combination : 42 (55%) male, 18 (24%) and 36 (47%) treated in second and third-line respectively, and 22 (29%) in fourth-line or more. Objective response rate (ORR) was 37% (28/76) and disease control rate 74 % (56/76). Median PFS and OS were 5,7 [95%CI: 4,1-6,9] months and 11,2 [95%CI: 8-not reached] months respectively. For patients treated in second and third-line, ORR was respectively 39% and 42%, PFS 4 months [95%CI: 2,5-7,7] and 6 months [95%CI: 4-7], OS 9,4 months [95%CI: 2,7-not reached] and was not reached in third-line at 12 months. Grade 3–4 adverse events included asthenia 5% (4/76), neurotoxicity 3% (2/76), bleeding events 4% (3/76), and hematological toxicity 1% (1/76). Interestingly, in the subgroup of patients treated with immunotherapy just before paclitaxel-bevacizumab (33/76), ORR was 42% (14/33), median PFS was 6,2 [95% CI: 4,6-7,7] months, and median overall survival was not reached at 12 months. Conclusions This results exhibited an acceptable toxicity profile and an encouraging efficacy as second-line treatment or beyond for non-squamous NSCLC patients. For patient treated just after immunotherapy the results are very promising. Legal entity responsible for the study Dr Chantal Decroisette CH Annecy Genevois France. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Introduction Differents variants de fusion ont ete decrits dans les rearrangements du gene ALK au sein des cancers pulmonaires non a petites cellules (CPNPC) et influeraient sur la sensibilite cellulaire au traitement par crizotinib. Le but de cette etude etait de tester et d’ameliorer l’efficacite du sequencage massif parallele (NGS) a partir d’ARN base sur des PCR multiplexes (RNA-seq) dans la detection du rearrangement et des variants de fusion ALK par rapport a l’immunohistochimie (IHC) et l’hybridation in situ en fluorescence (FISH) dans des echantillons de CPNPC. Le second objectif etait de mettre en evidence un lien entre la nature du variant de fusion ALK et la reponse au crizotinib. Methodes Cinquante-trois echantillons fixes au formol et inclus en paraffine ALK-positifs en FISH et/ou en IHC et 23 echantillons ALK-negatifs ont ete testes par RNA-seq. Dans un 2e temps, un protocole associant le RNA-seq a une PCR ancree multiplexe a ete evalue sur 10 echantillons en echec apres RNA-seq. Resultats Un resultat concluant par RNA-seq a ete obtenu dans 75 % des echantillons. Parmi les 33 cas ALK-positifs en RNA-seq, un transcrit de fusion a ete identifie parmi 27 echantillons. Comparees a l’association IHC/FISH, la sensibilite et la specificite du RNA-seq etaient respectivement de 80 et 100 %. Dans les cas ALK-positifs en IHC et en FISH, le RNA-seq a detecte un rearrangement ALK dans 100 % des cas analysables. Le RNA-seq a rendu un resultat concluant dans tous les cas equivoques et/ou borderlines en FISH et IHC. Concernant les cas discordants en IHC et FISH, le RNA-seq a ete mis en echec pour 5 des 7 echantillons. Sur les 10 echantillons consideres en echec apres RNA-seq testes, l’ajout d’une PCR ancree multiplexe dans le protocole de RNA-seq a permis de detecter 3 transcrits de fusion dont un variant CLIP1(12)-ALK(20) jamais decrit auparavant. Au sein des patients traites par crizotinib, la survie sans progression mediane etait plus allongee pour ceux presentant un variant 1 ou 2 d’EML4-ALK par rapport a ceux arborant un variant 3a/b (314 contre 192 jours, respectivement ; p = 0,1743). Conclusion Le RNA-seq est efficace pour le diagnostic des rearrangements ALK dans les CPNPC et pourrait etre integre a l’algorithme diagnostique de cette anomalie. De plus, il autorise l’identification des transcrits de fusion ALK qui pourraient constituer un marqueur pronostique chez ces patients.

Introduction La mediane de survie globale des patients atteints d’un carcinome bronchique a petites cellules (CBPC) tous stades confondus est de moins d’un an. Ces dernieres annees, avec le developpement de nouvelles molecules et l’optimisation des soins de confort, il se peut que le pronostic de ces patients se soit ameliore. L’objectif de ce travail est d’evaluer l’evolution de la survie de patients atteints d’un CBPC sur les 20 dernieres annees. Methodes Tous les patients avec un CBPC presentes en reunion de concertation pluridisciplinaire d’oncologie thoracique au CHU Grenoble-Alpes entre 1997 et 2017 ont ete inclus. Leurs caracteristiques, la reponse a la chimiotherapie et la survie ont ete comparees entre 1997–2009 (periode 1) et 2010–2017 (periode 2). Resultats Parmi les 529 patients inclus, 498 ont recu une 1re ligne de chimiotherapie et 279 patients une 2e ligne. La plupart de ces patients (n = 290, 58 %) avait une maladie avancee au diagnostic. Le taux de reponse a la 1re ligne de chimiotherapie chez les patients metastatiques etait de 72 % pour la periode 1 et de 69 % pour la periode 2 ; pour la 2e ligne de traitement le taux de reponse etait respectivement de 39 % et 29 %. La mediane de survie globale depuis l’initiation de la chimiotherapie etait de 13,2 mois [interquartiles (IQ) 25 %–75 %, 7,4–24,4] pour la periode 1 et de 11,2 mois [IQ 25 %–75 %, 7,1–21,2] pour la periode 2. La mortalite dans ces deux periodes ne differait pas de facon significative, meme apres ajustement sur les facteurs pronostiques (hazard ratio (HR) = 0,82, [Intervalle de confiance (IC) a 95 %, 0,66–1,00]). Les facteurs independamment associes au deces de ces patients etaient la presence de comorbidites cardiovasculaires (HR = 1,28 [IC 95 %, 1,05–1,55]), hepatiques (HR = 1,31 [IC 95 %, 1,03–1,65]), un performance status (PS) eleve (ECOG-PS 3–4 vs ECOG-PS 0–1 (HR = 2,45 [IC 95 %, 1,83–3,30]), ainsi qu’une maladie d’emblee metastatique (HR = 2,69 [IC 95 %, 2,18–3,33]). Conclusion Depuis 1997, il n’y a eu aucune amelioration ni de la reponse a la chimiotherapie ni de la survie des patients atteints d’un CBPC. Il existe un reel besoin de nouvelles therapeutiques pour augmenter la survie de ces patients.

e20572Background: Small cell lung cancers (SCLC) represent 10 to 15% of lung cancers, with a median survival at any stage of one year. In the last two decades, there was no dramatic breakthrough in...

The aim of the study was to assess the results of curative treatment of patients with squamous cell carcinoma of the tongue and to evaluate survival and predictive factors of recurrence.A series of 309 patients with squamous cell carcinoma of the tongue treated with curative intent was studied from January 1988 to December 1999. The percentage of oral tongue cancer was 82.2 and the percentage of cancer of base of the tongue was 17.8. Most patients underwent surgical procedure alone or combined with radiotherapy (92%). We performed 252 neck dissections. Bilateral dissections were performed for cancer of the apex linguae, cancer of the base of the tongue, for patients with N2c neck disease and whenever the primary tumor site crossed the median line. Twenty-five patients (8%) were treated with radiation therapy alone. Mean follow-up was 55 months. The functional results were assessed within a minimum of 10 months postoperative follow-up.In 45.2%, there was histological evidence of node invasion with 53.5% of extracapsular node spread in the neck specimens. Extracapsular node spread did not influence survival or recurrences. Occult cervical metastasis in an elective neck dissection in clinically negative necks was found in about 20% of patients with 47% of extracapsular node spread (41% for cancer of mobile tongue and 80% for those of base of the tongue). About 23% of patients with cancer of base of the tongue staged N0 had histological node invasion in controlateral neck nodes. The postoperative mortality rate was 0.9%. The rate of complications was 17%. The cancer recurred in 41.7% of all cases. Twelve percent of all patients had second primary cancers of the upper aerodigestive tract. The overall survival and non-recurrence rates at 2 and 5 years were higher in cancer of oral tongue than in cancer of base of the tongue. Survival rates were better when neck nodes were clinically or histologically negatives and in early-stage carcinomas. Non-recurrence rates were better when nodes were clinically or histologically negatives and when margins of exeresis were not involved. The functional results were better in oral tongue cancer than in base of the tongue cancer.Prognosis (survival and non-recurrence rates and functional results) of squamous cell carcinomas of oral tongue was better than prognosis of those of base of tongue. We recommend an aggressive surgical procedure even in patients with neck classed N0 (with reservations for T1 lesions with small depth of invasion): an ipsilateral supraomohyoid neck dissection for cancer of oral tongue and a bilateral supraomohyoid neck dissection for cancer of base of the tongue, cancer of oral tongue which crosses the median line of the oral cavity and cancer of the apex linguae. Postoperative radiotherapy must be performed when margins are positives and/or when nodes are involved with or without extracapsular spread.

The principle of mandibular reconstruction by dynamic bridging plates in association with a bone graft is based on the double bridge reconstruction method. However, the plate can be used alone. Our aim was to report the long-term results of this treatment for mandibular lateral defects in fragile patients. From 1993 to 1999, 38 consecutive patients had primary reconstructions with bridging plate for lateral mandibular defects. Their mean age was 58.4 years (26-86) and the mean follow-up was 50 months (6-89). Excluding removal of plates for local recurrences, the overall success rate was 78%. Plates were removed after a mean of 20.4 months (1-66). No plates fractured. Dynamic bridging plates allow an immediate and efficient reconstruction with reduced operating time and compare favourably with conventional plates. They can also be used as a stand-by for patients who are to have a delayed free flap reconstruction.

To present 8 new cases of primary intraosseous carcinoma of the jaws and to review the literature for an analysis of treatment modalities and patient outcomes.A MEDLINE search from 1970 to 1999. The articles chosen and the study of the references of every one that produced additional articles provided database information for 28 patients. Eight new patients from our institutions were added.Our criteria of inclusion included the absence of ulceration of the oral mucosa, a negative result in the search for a distant primary tumor, and convincing histological documentation.The variables of the analysis included age, sex, site of the tumor, condition of the oral mucosa, tumor size, neck status, treatment modalities, recurrences, and survival.Twenty-eight patients were identified in the literature, for a total of 36 patients. There were 28 males (78%) and 8 females (22%) ranging in age from 4 to 76 years (mean, 54 years). The tumor site was the mandible in 33 patients (92%) and the maxilla in 3 (8%). Of the 34 patients treated, 19 (56%) had recurrences. Overall 2- and 4-year survival was 60.5% and 39.9%, respectively. Patients who underwent radical surgery and postoperative radiotherapy (n = 11) had a 2- and 3-year survival probability of 61.3% and 40.9%, respectively, whereas in the remaining patients (n = 25), the rates were 59.7% and 31.3%, respectively (P =.60).Strict diagnostic criteria must be applied. The prognosis associated with primary intraosseous carcinoma of the jaws is poor and suggests the need for aggressive treatment.

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 systematic review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery.To develop clinical practice guidelines according to the definitions of Standards, Options and Recommendations for the management of squamous carcinoma of the oropharynx.Data have been identified by literature search using Medline (1991-1998) and the expert groups personal reference lists. Once the guidelines were defined, the document was submitted for review to national and international independent reviewers and to the medical committees of the 20 French Cancer Centres.The main recommendations for squamous cell carcinoma of the oropharynx management are that: 1) diagnosis and initial assessment should be based on appropriate clinical and radiological findings; 2) the therapeutic strategy is based on surgery, radiotherapy, bradytherapy and chemotherapy; 3) in limited tumours, the recommended strategy involved the use of one of these modality; 4) a multimodality approach is recommended for the treatment of extended resectable tumours. Following results of recent meta-analyses, use of neo-adjuvant chemotherapy is not recommended. The same studies have shown that association of chemotherapy and radiotherapy either in sequence or in combination significantly improve survival of extended curable tumours. These associations are recommended within the framework of clinical trials; 5) follow-up of squamous carcinoma of the oropharynx should involve physical examination of the upper aerodigestive tract and the lymph nodes areas every three months during the first year, every six months during the second year and then every year. An annual chest x-ray is recommended. Other investigations should be performed as indicated by symptoms and clinical manifestations.

Our large experience of shotgun injuries to the face emphasizes the need for a reappraisal of primary treatment for this poorly documented topic. The medical records of 165 patients, treated at our institution between january 1st, 1982 and december, 31st 1996 for such an injury, were reviewed. Almost all cases were exclusively self-inflicted lesions. The guns were mainly twelve-gauge and occasionally 16 or 20-gauge. Close range wounds in an heterogeneous area--soft-tissue, mandible, muscles of the tongue and floor of the mouth, oral and nasal cavities, maxilla and paranasal sinuses--caused massive damage. A topographic classification based on the soft-tissue and bone loss is reported. After initial management (including securing the airway and control of bleeding), conservative debridement of all devitalized tissues and stabilization of the fractures were performed. As soon as possible, bone and soft tissue reconstruction was undertaken using local or distant flaps. However, immediate definitive reconstructive procedures were scarcely [corrected] used and only in particular cases. We believe that a carefully planned reconstruction schedule is required to achieve satisfactory appearance and function.

Fibrous dysplasia accounts for approximately 2% of bone tumors. The ribs, proximal femurs and cranio-facial bones represent the majority of bone lesions. Surgery is the mainstay of treatment but the technique is controversial: conservative surgery or removal of dysplastic lesions followed by implantation of autogenous bone graft. The aim of this study was to assess the indications of each method. The medical records of 25 patients with fibrous dysplasia of the cranio-facial bones treated between January 1, 1980 and December 31, 1994 at the Department of Maxillofacial Surgery, Centre Hospitalier Universitaire de Bordeaux, France, were reviewed. Fourteen (56%) patients were women and 11 (44%) men. The median age at the time of diagnosis was 23 years (ranging from 8 to 56 years). The mean follow-up was 8 years. Two patients were unavailable for follow-up after treatment. The primary sites of the tumors were the mandible (n = 19 [76%]), maxilla (n = 1 [4%]) and skull (n = 5 [20%]). For mandibular lesions, the primary treatment always included a correction of deformations and asymmetry, which was the only treatment in 14 cases. Two patients required subsequent surgery to reduce further bone enlargement (1 and 2 years later in the first case and 11 years later in the second) without further problems. In 3 cases a segmental mandibulectomy followed by implantation of autogenous bone graft was required, and no further recurrence was observed. Therefore, the success rate of conservative surgery was 74% initially, and up to 86% after subsequent surgery. Skull lesions, although often very extensive, were remarkably stable and asymptomatic. They were successfully treated 4 times by conservative surgery, mainly for cosmetic reasons. One patient, with an ethmoidal tumor producing a mass effect along the course of the optic nerve, underwent a combined cranio-facial resection. As for the only maxillary tumor, three curettages were performed throughout an 11-year period and there was no evidence of further recurrence 4 years after the last intervention. In all cases, conservative surgery may be recommended as primary treatment of fibrous of the craniofacial bones, providing essential structures like the optic nerve are not at risk. Cosmetic results and local control proved excellent, and a further removal of the tumor remained feasible in the event of a recurrence. Success or failure did not correlate with tumor size, which justifies the use of this technique.

Tumors of the salivary glands are exceptional, representing approximately 2% of head and neck tumors. The parotid gland is most often involved, at a frequency reaching 80%. Histology examination generally shows a pleomorphous adenoma. The choice of a surgical technique best adapted to curative treatment depends on the type of tumor and is widely debated. Our management strategy is based on simultaneous histology examination and superficial parotidectomy. Several pre and intra-operative factors determine the need for resection. We verified our strategy with a retrospective study.

Radical neck dissection was the golden standard of treatment for cervical nodes in head and neck tumors. From the seventies, the preservation of the spinal accessory nerve has become increasingly popular in order to improve the functional result of the neck dissections. The aim of this study was to assess the degree of functional disability associated with each type of neck dissection and the value of anatomical references for dissection of the spinal accessory nerve. One hundred twenty seven patients were evaluated 1 month and 1 year after radical, functional or supraomohyoid neck dissection with a questionnaire and a physical examination. Anatomical measurements of the spinal accessory nerve were performed in 20 patients. We found considerable or severe shoulder dysfunction in 7%, 34% and 51% respectively of patients in whom supraomohyoid, functional and radical neck dissections were performed. Furthermore 49% of patients having undergone a radical neck dissection had little or no symptoms. Sacrifice of the spinal accessory nerve in radical neck dissection may lead to shoulder dysfunction. A functional disability may also be associated, although in a less extent, with any neck dissection in which the spinal accessory nerve is dissected and placed in traction. There is a large variation in the degree of functional disability and pain in patients with similar neck dissections. The course of the spinal accessory nerve in the neck makes it particularly vulnerable to injury during the dissection near the sternocleidomastoid muscle and in the posterior cervical triangle.

Marginal mandibulectomies are now widely performed in the anterior aspect of the mandible providing that the preoperative clinical and radiologic evaluation shows no bone invasion. These marginal resections can be extended to the posterior area. Molar, retromolar and ascending ramus resections can be performed. This removes the upper bone segment preserving the dental canal whenever possible. From 1990, 14 patients were treated with this technique for carcinoma of the retromolar triangle (9 cases) and oropharynx (5 cases). 11 different flaps were used to cover the soft tissue defect and 3 direct sutures were performed. Eleven patients underwent postoperative radiotherapy with a mean dose of 58 Gray. Median follow-up was 32 months. Functional and cosmetic results were very satisfactory due to preservation of mandibular continuity. We found no osteomyelitis, postoperative fracture or radionecrosis. This technique avoids a segmental resection in some well-defined cases and the disability produced as a result of this treatment. There is therefore, no need for complex reconstruction and the operating time is shortened in fragile patients.

Carcinoma of the oral cavity in patients less than thirty years of age is quite uncommon. Moreover, the usual tobacco and alcohol exposure is not found in these patients. We reviewed retrospectively the medical files of 7 patients with squamous cell carcinoma of the oral cavity treated between 1980 and 1993. Six patients were male. Mean age was 26 years. The primary site was staged T1 in 2 patients, T2 in 3 patients, T3 in 1 patient and T4 in 1 patient. The results of treatment suggest that there is no difference in control rate between this group and older patients. It is difficult to draw conclusions from most of published reports because studies often include patients up to fourty years of age and tumors of various anatomic sites. Young age and alcohol and tobacco exposure do not appear significant factors of prognosis.

The aim of the study was to assess the results of segmental mandibular resections and the validity of mandibular reconstructions. The medical records of 95 patients treated between January 1, 1987 and December 31, 1992 were reviewed. There were 82 (86%) carcinomas, 9 ameloblastomas and 4 sarcomas. Among the 82 patients treated for carcinoma, the overall 2- and 5-year survival rates were 70% and 33% respectively. The functional results evaluated one year after surgery showed no significant difference according to the reconstruction procedure: myocutaneous flap, osteomyocutaneous flap, titanium mandibular reconstruction plate or microsurgical transfer. The most important factor in functional rehabilitation is the amount of soft tissue resected. In head and neck oncology, aggressive surgical reconstruction of the mandible must only be used in patients with good general status and fair survival probability.

Described since 1976, the lateral trapezius flap is not very used in cervico facial reconstructive surgery because of its dissection which is considered as difficult and because of the variability of its vascular pedicle. This latter problem can be removed by the systematic use of preoperative arteriography. We present our retrospective experience of 89 flaps (70 cases of tumors and 19 cases of balistic pathology. We can conclude that the lateral trapezius flap owns specific indications: cutaneous and mucous defects of lips and cheeks, defects of pharyngeal area, defects of floor of the mouth considering of its thin thickness, mandibular defects where it takes place between reconstructive plates and revascularized bone transplants especially for the symphysis area.

The medical records of 31 patients with histologically proven primary carcinoma of the parotid gland seen between January 1980 and December 1992 were reviewed. The efficiency of combined treatment both on locoregional control and overall survival was assessed. Twenty nine patients underwent extensive surgery and postoperative radiotherapy, two patients underwent extensive surgery alone. Locoregional control of disease at the end of treatment was achieved in 29 patients (94%). Eleven patients had recurrences. For the complete series the overall two and five-year survival rates were 73% and 46% respectively. Even in case of locoregional control with combined treatment, overall survival rates are low because of distant metastases.

The aim of this study was to assess the use of titanium mandibular reconstruction plates after cancer surgery. The medical records of 36 patients were reviewed. The mean follow-up was 22 months. All patients had primary reconstruction of the mandible with Leibinger titanium plates. Thirty patients underwent postoperative radiotherapy with the plate in the field. The mean dose was 60 Grays over 6 weeks and the overdosage into tissues was reduced to 5%. Thirty patients (83%) had retained the plate at 6 months and no sign of osteomyelitis was found in any patient. Quality of speech and deglutition were satisfactory in 63% and 94% of the patients respectively; sixty-six p. cent of them found their cosmetic appearance good or excellent. The overall success rate of the technique was 74%. This technique did not excessively prolong operating time unlike microvascular transfer. Plates are an effective method of primary reconstruction in patients with advanced cancer and uncertain long-term survival. Tolerance of plates after radiotherapy is outstanding. Speech, deglutition and facial contour are immediately restored and further bone reconstruction is feasible.

A series of 200 patients bitten on the face by a dog between January 1979 and December 1990 was reviewed. The aim of the study was to assess our attitude of delayed sutures and to determine the origin of the dogs, their behaviour, and the circumstances of the bites. In this series, 146/200 patients (73%) were less than 15 years old and 85/200 (43%) less than 5 years old; most adults bitten had a job at risk. The rate of infectious complications was 2.5%. There were 70% (105/150) dogs from an identifiable breed (25% (38/150) pedigree) and 30% (45/150) mongrels. In 70% of the cases the victim did not know or hardly knew the dog. The study of our series and others previously published clearly demonstrates that a dog bite must never be sutured directly. By calculating the incidence of dog bite for each particular breed in France, we conclude that, with very few exceptions, no breed is more aggressive than another. Reducing the rate of dog bites implies better knowledge of dogs and respect for some common sense rules, both on the part of children and dog owners.

Mandibular reconstruction plates are now used after cancer surgery in particular patients. This study assesses the irradiation of Titanium mandibular reconstruction plates in terms of both dosimetry and mid-term tolerance. Twenty patients with mandibular plates underwent radiotherapy (mean dose 60 Gy). The radiation dose on the patient itself was calculated with 3-dimensional treatment planning. A clinical and radiological evaluation of tolerance was made 6 months after the end of the treatment: intraoral and cutaneous healing and possible osteomyelitis. Mid-term tolerance was very satisfactory with only two failures at 6 months. When using parallel opposing fields, the overdosage into tissues was reduced to approximately 5 p. cent; and radiotherapy has probably no effect on titanium plate tolerance.

The study of adenoid cystic carcinoma of the salivary glands is limited by the paucity of series described and the lack of prospective reports. The medical records of 21 patients with histologically proven adenoid cystic carcinoma seen between January 1975 and December 1991 were reviewed. The efficiency of postoperative radiotherapy both on locoregional control and overall survival was assessed. Seventeen patients underwent extensive surgery and postoperative radiotherapy. Three patients had recurrences in the surgery and postoperative radiotherapy group. Two patients who underwent surgery alone presented tumor recurrences. For the complex series the overall five and ten-year survival rates were 83% and 67% respectively. For the 17 patients in the surgery and postoperative radiotherapy group, five and ten-year survival rates were 87% and 77% respectively. These results show postoperative radiotherapy to be effective in decreasing the recurrence rate which is largely reported elsewhere.