Concomitant Cisplatin and Hyperfractionated Radiotherapy in Locally Advanced Head and Neck Cancer: Ten-year Follow-up of a Randomized Phase III Trial (SAKK 10/94)

Purpose/Objective(s): To analyze the long-term outcome of treatment with concomitant cisplatin and hyperfractionated radiotherapy in locally advanced head and neck cancer compared with hyperfractionated radiotherapy alone.Materials/Methods: From July 1994 to July 2000 a total of 224 patients with squamous cell carcinoma of the head and neck were randomized to either hyperfractionated radiotherapy (median dose 74.4 Gy; 1.2 Gy twice daily) or the same radiotherapy combined with two cycles of concomitant cisplatin (20mg/m2 for 5 consecutive days of weeks 1 and 5). The primary endpoint was time to any treatment failure; secondary endpoints were locoregional failure, metastatic failure, overall survival, and late toxicity assessed according to RTOG criteria. The trial was registered at the National Institutes of Health (www.clinicaltrials.gov; identifier number: NCT00002654).Results: Median follow-up was 9.5 years (range, 0.1 - 15.4 years). Median time to any treatment failure was not significantly different between treatment arms (p = 0.19). Locoregional control (p\0.05), distant metastasis-free survival (p = 0.02) and cancer specific survival (p = 0.03) were significantly improved in the combined treatment arm, with no difference in late toxicity between treatment arms. However, overall survival was not significantly different (p = 0.19). Conclusions: After long-term follow-up combined treatment with cisplatin and hyperfractionated, radiotherapy maintained an improved locoregional control, distant metastasis-free survival, and cancer specific survival as compared to hyperfractionated radiotherapy alone with no difference in late toxicity.Author Disclosure: P. Ghadjar, None; M. Simcock, None; G. Studer, None; A.S. Allal, None; M. Ozsahin, None; J. Bernier, None; M. To¨ pfer, None; F. Zimmermann, None; C. Glanzmann, None; D.M. Aebersold, None.

Investigating barriers in HIV-testing oncology patients. The IBITOP study: phase I.

BACKGROUND: Since the advent of combined antiretroviral therapy (ART), the incidence of non-AIDS-defining cancers (non-ADCs) among HIV-positive patients is rising. We previously described HIV testing rates of <5% in our oncology centre, against a local HIV prevalence of 0.4% (1). We have since worked with the Service of Oncology to identify, how HIV testing can be optimized, we have conducted a study on investigating barriers in HIV-testing oncology patients (IBITOP) among treating oncologists and their patients. METHODS: After an initial two-month pilot study to examine feasibility (2), we conducted the first phase of the IBITOP study between 1st July and 31st October 2013. Patients of unknown HIV status, newly diagnosed with solid-organ non-AIDS-defining cancer, and treated at Lausanne University Hospital were invited to participate. Patients were offered HIV testing as a part of their initial oncology work-up. Oncologist testing proposals and patient acceptance were the primary endpoints. RESULTS: Of 235 patients with a new oncology diagnosis, 10 were excluded (7 with ADCs and 3 of known HIV-positive status). Mean age was 62 years; 48% were men and 71% were Swiss. Of 225 patients, 75 (33%) were offered HIV testing. Of these, 56 (75%) accepted, of whom 52 (93%) were tested. A further ten patients were tested (without documentation of being offered a test), which gave a total testing rate of 28% (62/225). Among the 19 patients who declined testing, reasons cited included self-perceived absence of HIV risk, previous testing and palliative care. Of the 140 patients not offered HIV testing and not tested, reasons were documented for 35 (25%), the most common being previous testing and follow-up elsewhere. None of the 62 patients HIV tested had a reactive test. CONCLUSIONS: In this study, one third of patients seen were offered testing and the HIV testing rate was fivefold higher than that of previously observed in this service. Most patients accepted testing when offered. As HIV-positive status impacts on the medical management of cancer patients, we recommend that HIV screening should be performed in settings, where HIV prevalence is >0.1%. Phase II of the IBITOP study is now underway to explore barriers to HIV screening among oncologists and patients following the updated national HIV testing guidelines which recommend testing in non-ADC patients undergoing chemotherapy.

Effects of a treatment gap during adjuvant chemotherapy in node-positive breast cancer: results of International Breast Cancer Study Group (IBCSG) Trials 13-93 and 14-93.

BACKGROUND: The International Breast Cancer Study Group (IBCSG) conducted two complementary randomized trials to assess whether a treatment-free gap during adjuvant chemotherapy influenced outcome. PATIENTS AND METHODS: From 1993 to 1999, IBCSG Trials 13-93 and 14-93 enrolled 2215 premenopausal and postmenopausal women with axillary node-positive, operable breast cancer. All patients received cyclophosphamide (Cytoxan, C) plus either doxorubicin (Adriamycin, A) or epirubicin (E) for four courses followed immediately (No Gap) or after a 16-week delay (Gap) by classical cyclophosphamide, methotrexate, and fluorouracil (CMF) for three courses. The median follow-up was 7.7 years. RESULTS: The Gap and No-Gap groups had similar disease-free survival (DFS) and overall survival (OS). No identified subgroup showed a statistically significant difference, but exploratory subgroup analysis noted a trend towards decreased DFS for Gap compared with No Gap for women with estrogen receptor (ER)-negative tumors not receiving tamoxifen, especially evident during the first 2 years. CONCLUSIONS: A 16-week gap between adjuvant AC/EC and CMF provided no benefit and may have increased early recurrence rates in patients with ER-negative tumors.

Epilepsy meets cancer: when, why, and what to do about it?

The lifetime risk of having epileptic seizures is profoundly increased in patients with cancer: about 20% of all patients with systemic cancer may develop brain metastases. These patients and those with primary brain tumours have a lifetime risk of epilepsy of 20-80%. Moreover, exposure to chemotherapy or radiotherapy to the brain, cancer-related metabolic disturbances, stroke, and infection can provoke seizures. The management of epilepsy in patients with cancer includes diagnosis and treatment of the underlying cerebral pathological changes, secondary prophylaxis with antiepileptic drugs, and limiting of the effect of epilepsy and its treatment on the efficacy and tolerability of anticancer treatments, cognitive function, and quality of life. Because of the concern of drug-drug interactions, the pharmacological approach to epilepsy requires a multidisciplinary approach, specifically in a setting of rapidly increasing choices of agents both to treat cancer and cancer-associated epilepsy.

Panitumumab plus radiotherapy versus chemoradiotherapy in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck (CONCERT-2): a randomised, controlled, open-label phase 2 trial.

BACKGROUND: We aimed to compare panitumumab, a fully human monoclonal antibody against EGFR, plus radiotherapy with chemoradiotherapy in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck. METHODS: In this international, open-label, randomised, controlled, phase 2 trial, we recruited patients with locally advanced squamous-cell carcinoma of the head and neck from 22 sites in eight countries worldwide. Patients aged 18 years and older with stage III, IVa, or IVb, previously untreated, measurable (≥10 mm for at least one dimension), locally advanced squamous-cell carcinoma of the head and neck (non-nasopharygeal) and an Eastern Cooperative Oncology Group performance status of 0-1 were randomly assigned (2:3) by an independent vendor to open-label chemoradiotherapy (two cycles of cisplatin 100 mg/m(2) during radiotherapy) or to radiotherapy plus panitumumab (three cycles of panitumumab 9 mg/kg every 3 weeks administered with radiotherapy) using a stratified randomisation with a block size of five. All patients received 70-72 Gy to gross tumour and 54 Gy to areas of subclinical disease with accelerated fractionation radiotherapy. The primary endpoint was local-regional control at 2 years, analysed in all randomly assigned patients who received at least one dose of their assigned protocol-specific treatment (chemotherapy, radiation, or panitumumab). The trial is closed and this is the final analysis. This study is registered with ClinicalTrials.gov, number NCT00547157. FINDINGS: Between Nov 30, 2007, and Nov 16, 2009, 152 patients were enrolled, and 151 received treatment (61 in the chemoradiotherapy group and 90 in the radiotherapy plus panitumumab group). Local-regional control at 2 years was 61% (95% CI 47-72) in the chemoradiotherapy group and 51% (40-62) in the radiotherapy plus panitumumab group. The most frequent grade 3-4 adverse events were mucosal inflammation (25 [40%] of 62 patients in the chemoradiotherapy group vs 37 [42%] of 89 patients in the radiotherapy plus panitumumab group), dysphagia (20 [32%] vs 36 [40%]), and radiation skin injury (seven [11%] vs 21 [24%]). Serious adverse events were reported in 25 (40%) of 62 patients in the chemoradiotherapy group and in 30 (34%) of 89 patients in the radiotherapy plus panitumumab group. INTERPRETATION: Panitumumab cannot replace cisplatin in the combined treatment with radiotherapy for unresected stage III-IVb squamous-cell carcinoma of the head and neck, and the role of EGFR inhibition in locally advanced squamous-cell carcinoma of the head and neck needs to be reassessed. FUNDING: Amgen.

Red meat and cancer risk in a network of case-control studies focusing on cooking practices.

BACKGROUND: Consumption of red meat has been related to increased risk of several cancers. Cooking methods could modify the magnitude of this association, as production of chemicals depends on the temperature and duration of cooking. METHODS: We analyzed data from a network of case-control studies conducted in Italy and Switzerland between 1991 and 2009. The studies included 1465 oral and pharyngeal, 198 nasopharyngeal, 851 laryngeal, 505 esophageal, 230 stomach, 1463 colon, 927 rectal, 326 pancreatic, 3034 breast, 454 endometrial, 1031 ovarian, 1294 prostate and 767 renal cancer cases. Controls included 11 656 patients admitted for acute, non-neoplastic conditions. Odds ratios (ORs) and confidence intervals (CIs) were estimated by multiple logistic regression models, adjusted for known confounding factors. RESULTS: Daily intake of red meat was significantly associated with the risk of cancer of the oral cavity and pharynx (OR for increase of 50 g/day = 1.38; 95% CI: 1.26-1.52), nasopharynx (OR = 1.29; 95% CI: 1.04-1.60), larynx (OR = 1.46; 95% CI: 1.30-1.64), esophagus (OR = 1.46; 95% CI: 1.23-1.72), colon (OR = 1.17; 95% CI: 1.08-1.26), rectum (OR = 1.22; 95% CI:1.11-1.33), pancreas (OR = 1.51; 95% CI: 1.25-1.82), breast (OR = 1.12; 95% CI: 1.04-1.19), endometrium (OR = 1.30; 95% CI: 1.10-1.55) and ovary (OR = 1.29; 95% CI: 1.16-1.43). Fried meat was associated with a higher risk of cancer of oral cavity and pharynx (OR = 2.80; 95% CI: 2.02-3.89) and esophagus (OR = 4.52; 95% CI: 2.50-8.18). Risk of prostate cancer increased for meat cooked by roasting/grilling (OR = 1.31; 95% CI: 1.12-1.54). No heterogeneity according to cooking methods emerged for other cancers. Nonetheless, significant associations with boiled/stewed meat also emerged for cancer of the nasopharynx (OR = 1.97; 95% CI: 1.30-3.00) and stomach (OR = 1.86; 95% CI: 1.20-2.87). CONCLUSIONS: Our analysis confirmed red meat consumption as a risk factor for several cancer sites, with a limited impact of cooking methods. These findings, thus, call for a limitation of its consumption in populations of Western countries.

Achievement of at least very good partial response is a simple and robust prognostic factor in patients with multiple myeloma treated with high-dose therapy: long-term analysis of the IFM 99-02 and 99-04 Trials.

PURPOSE: The prognostic impact of complete response (CR) achievement in multiple myeloma (MM) has been shown mostly in the context of autologous stem-cell transplantation. Other levels of response have been defined because, even with high-dose therapy, CR is a relatively rare event. The purpose of this study was to analyze the prognostic impact of very good partial response (VGPR) in patients treated with high-dose therapy. PATIENTS AND METHODS: All patients were included in the Intergroupe Francophone du Myelome 99-02 and 99-04 trials and treated with vincristine, doxorubicin, and dexamethasone (VAD) induction therapy followed by double autologous stem-cell transplantation (ASCT). Best post-ASCT response assessment was available for 802 patients. RESULTS: With a median follow-up of 67 months, median event-free survival (EFS) and 5-year EFS were 42 months and 34%, respectively, for 405 patients who achieved at least VGPR after ASCT versus 32 months and 26% in 288 patients who achieved only partial remission (P = .005). Five-year overall survival (OS) was significantly superior in patients achieving at least VGPR (74% v 61% P = .0017). In multivariate analysis, achievement of less than VGPR was an independent factor predicting shorter EFS and OS. Response to VAD had no impact on EFS and OS. The impact of VGPR achievement on EFS and OS was significant in patients with International Staging System stages 2 to 3 and for patients with poor-risk cytogenetics t(4;14) or del(17p). CONCLUSION: In the context of ASCT, achievement of at least VGPR is a simple prognostic factor that has importance in intermediate and high-risk MM and can be informative in more patients than CR.

Outcome and patterns of failure in testicular lymphoma: a multicenter Rare Cancer Network study.

PURPOSE: To assess the outcome and patterns of failure in patients with testicular lymphoma treated by chemotherapy (CT) and/or radiation therapy (RT). METHODS AND MATERIALS: Data from a series of 36 adult patients with Ann Arbor Stage I (n = 21), II (n = 9), III (n = 3), or IV (n = 3) primary testicular lymphoma, consecutively treated between 1980 and 1999, were collected in a retrospective multicenter study by the Rare Cancer Network. Median age was 64 years (range: 21-91 years). Full staging workup (chest X-ray, testicular ultrasound, abdominal ultrasound, and/or thoracoabdominal computer tomography, bone marrow assessment, full blood count, lactate dehydrogenase, and cerebrospinal fluid evaluation) was completed in 18 (50%) patients. All but one patient underwent orchidectomy, and spermatic cord infiltration was found in 9 patients. Most patients (n = 29) had CT, consisting in most cases of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) with (n = 17) or without intrathecal CT. External RT was delivered to scrotum alone (n = 12) or testicular, iliac, and para-aortic regions (n = 8). The median RT dose was 31 Gy (range: 20-44 Gy) in a median of 17 fractions (10-24), using a median of 1.8 Gy (range: 1.5-2.5 Gy) per fraction. The median follow-up period was 42 months (range: 6-138 months). RESULTS: After a median period of 11 months (range: 1-76 months), 14 patients presented lymphoma progression, mostly in the central nervous system (CNS) (n = 8). Among the 17 patients who received intrathecal CT, 4 had a CNS relapse (p = NS). No testicular, iliac, or para-aortic relapse was observed in patients receiving RT to these regions. The 5-year overall, lymphoma-specific, and disease-free survival was 47%, 66%, and 43%, respectively. In univariate analyses, statistically significant factors favorably influencing the outcome were early-stage and combined modality treatment. Neither RT technique nor total dose influenced the outcome. Multivariate analysis revealed that the most favorable independent factors predicting the outcome were younger age, early-stage disease, and combined modality treatment. CONCLUSIONS: In this multicenter retrospective study, CNS was found to be the principal site of relapse, and no extra-CNS lymphoma progression was observed in the irradiated volumes. More effective CNS prophylaxis, including combined modalities, should be prospectively explored in this uncommon site of extranodal lymphoma.

Levetiracetam and pregabalin for antiepileptic monotherapy in patients with primary brain tumors. A phase II randomized study.

BACKGROUND: In patients with brain tumors, the choice of antiepileptic medication is guided by tolerability and pharmacokinetic interactions. This study investigated the effectiveness of levetiracetam (LEV) and pregabalin (PGB), 2 non-enzyme-inducing agents, in this setting. METHODS: In this pragmatic, randomized, unblinded phase II trial (NCT00629889), patients with primary brain tumors and epilepsy were titrated to a monotherapy of LEV or PGB. Efficacy and tolerability were assessed using structured questionnaires. The primary composite endpoint was the need to discontinue the study drug, add-on of a further antiepileptic treatment, or occurrence of at least 2 seizures with impaired consciousness during 1 year follow-up. RESULTS: Over 40 months, 25 patients were randomized to LEV, and 27 to PGB. Most were middle-aged men, with a high-grade tumor and at least one generalized convulsion. Mean daily doses were 1125 mg (LEV) and 294 mg (PGB). Retention rates were 59% in the LEV group, and 41% in the PGB group. The composite endpoint was reached in 9 LEV and 12 PGB patients-need to discontinue: side effects, 6 LEV, 3 PGB; lack of efficacy, 1 and 2; impaired oral administration, 0 and 2; add-on of another agent: 1 LEV, 4 PGB; and seizures impairing consciousness: 1 in each. Seven LEV and 5 PGB subjects died of tumor progression. CONCLUSIONS: This study shows that LEV and PGB represent valuable monotherapy options in this setting, with very good antiepileptic efficacy and an acceptable tolerability profile, and provides important data for the design of a phase III trial.

Phase 3 randomized trial on larynx preservation comparing sequential vs alternating chemotherapy and radiotherapy.

BACKGROUND: Both induction chemotherapy followed by irradiation and concurrent chemotherapy and radiotherapy have been reported as valuable alternatives to total laryngectomy in patients with advanced larynx or hypopharynx cancer. We report results of the randomized phase 3 trial 24954 from the European Organization for Research and Treatment of Cancer. METHODS: Patients with resectable advanced squamous cell carcinoma of the larynx (tumor stage T3-T4) or hypopharynx (T2-T4), with regional lymph nodes in the neck staged as N0-N2 and with no metastasis, were randomly assigned to treatment in the sequential (or control) or the alternating (or experimental) arm. In the sequential arm, patients with a 50% or more reduction in primary tumor size after two cycles of cisplatin and 5-fluorouracil received another two cycles, followed by radiotherapy (70 Gy total). In the alternating arm, a total of four cycles of cisplatin and 5-fluorouracil (in weeks 1, 4, 7, and 10) were alternated with radiotherapy with 20 Gy during the three 2-week intervals between chemotherapy cycles (60 Gy total). All nonresponders underwent salvage surgery and postoperative radiotherapy. The Kaplan-Meier method was used to obtain time-to-event data. RESULTS: The 450 patients were randomly assigned to treatment (224 to the sequential arm and 226 to the alternating arm). Median follow-up was 6.5 years. Survival with a functional larynx was similar in sequential and alternating arms (hazard ratio of death and/or event = 0.85, 95% confidence interval = 0.68 to 1.06), as were median overall survival (4.4 and 5.1 years, respectively) and median progression-free interval (3.0 and 3.1 years, respectively). Grade 3 or 4 mucositis occurred in 64 (32%) of the 200 patients in the sequential arm who received radiotherapy and in 47 (21%) of the 220 patients in the alternating arm. Late severe edema and/or fibrosis was observed in 32 (16%) patients in the sequential arm and in 25 (11%) in the alternating arm. CONCLUSIONS: Larynx preservation, progression-free interval, and overall survival were similar in both arms, as were acute and late toxic effects.

Sagopilone (ZK-EPO, ZK 219477) for recurrent glioblastoma. A phase II multicenter trial by the European Organisation for Research and Treatment of Cancer (EORTC) Brain Tumor Group.

Background: Sagopilone (ZK 219477), a lipophylic and synthetic analog of epothilone B, that crosses the blood-brain barrier has demonstrated preclinical activity in glioma models.Patients and methods: Patients with first recurrence/progression of glioblastoma were eligible for this early phase II and pharmacokinetic study exploring single-agent sagopilone (16 mg/m(2) over 3 h every 21 days). Primary end point was a composite of either tumor response or being alive and progression free at 6 months. Overall survival, toxicity and safety and pharmacokinetics were secondary end points.Results: Thirty-eight (evaluable 37) patients were included. Treatment was well tolerated, and neuropathy occurred in 46% patients [mild (grade 1) : 32%]. No objective responses were seen. The progression-free survival (PFS) rate at 6 months was 6.7% [95% confidence interval (CI) 1.3-18.7], the median PFS was just over 6 weeks, and the median overall survival was 7.6 months (95% CI 5.3-12.3), with a 1-year survival rate of 31.6% (95% CI 17.7-46.4). Maximum plasma concentrations were reached at the end of the 3-h infusion, with rapid declines within 30 min after termination.Conclusions: No evidence of relevant clinical antitumor activity against recurrent glioblastoma could be detected. Sagopilone was well tolerated, and moderate-to-severe peripheral neuropathy was observed in despite prolonged administration.

Epithelial to mesenchymal transition in the pathogenesis of uterine malignant mixed Müllerian tumours: the role of ubiquitin proteasome system and therapeutic opportunities.

Malignant mixed Müllerian tumours (malignant mixed mesodermal tumours, MMMT) of the uterus are metaplastic carcinomas with a sarcomatous component and thus they are also called carcinosarcomas. It has now been accepted that the sarcomatous component is derived from epithelial elements that have undergone metaplasia. The process that produces this metaplasia is epithelial to mesenchymal transition (EMT), which has recently been described as a neoplasia-associated programme shared with embryonic development and enabling neoplastic cells to move and metastasise. The ubiquitin proteasome system (UPS) regulates the turnover and functions of hundreds of cellular proteins. It plays important roles in EMT by being involved in the regulation of several pathways participating in the execution of this metastasis-associated programme. In this review the specifi c role of UPS in EMT of MMMT is discussed and therapeutic opportunities from UPS manipulations are proposed.

Correlation of O6-methylguanine methyltransferase (MGMT) promoter methylation with clinical outcomes in glioblastoma and clinical strategies to modulate MGMT activity.

Resistance to alkylating agents via direct DNA repair by O(6)-methylguanine methyltransferase (MGMT) remains a significant barrier to the successful treatment of patients with malignant glioma. The relative expression of MGMT in the tumor may determine response to alkylating agents, and epigenetic silencing of the MGMT gene by promoter methylation plays an important role in regulating MGMT expression in gliomas. MGMT promoter methylation is correlated with improved progression-free and overall survival in patients treated with alkylating agents. Strategies to overcome MGMT-mediated chemoresistance are being actively investigated. These include treatment with nontoxic pseudosubstrate inhibitors of MGMT, such as O(6)-benzylguanine, or RNA interference-mediated gene silencing of MGMT. However, systemic application of MGMT inhibitors is limited by an increase in hematologic toxicity. Another strategy is to deplete MGMT activity in tumor tissue using a dose-dense temozolomide schedule. These alternative schedules are well tolerated; however, it remains unclear whether they are more effective than the standard dosing regimen or whether they effectively deplete MGMT activity in tumor tissue. Of note, not all patients with glioblastoma having MGMT promoter methylation respond to alkylating agents, and even those who respond will inevitably experience relapse. Herein we review the data supporting MGMT as a major mechanism of chemotherapy resistance in malignant gliomas and describe ongoing studies that are testing resistance-modulating strategies.

Isolated limb perfusion with tumor necrosis factor and melphalan for non-resectable soft tissue sarcomas : long-term results on efficacy and limb salvage in a selected group of patients

Rapport de synthèse : Introduction : La perfusion isolée de membre (isolated limb perfusion, ou ILP) par TNF-alpha et melphalan, utilisés en association, est une stratégie de prise en charge chirurgicale des sarcomes non opérables des extrémités. Elle a été en partie développée au CHUV dans les années 1990, sous l'impulsion du Professeur F. Lejeune, ancien Chef du Service d'oncologie médicale (CePO). Les résultats des 31 premiers patients ont été publiés en 2000 dans l'European Journal of Surgical Oncology. Les données dans la littérature manquant sur les résultats à long terme, nous avons revu tous les patients traités au CHUV depuis 1992 pour tenter des de déterminer ces résultats à long terme, en se focalisant sur l'efficacité du traitement, symbolisée par le taux de sauvetage de membres, autrement condamnés à l'amputation ou à une chirurgie mutilante. Matériel et méthode : Etude rétrospective. De 1992 à mars 2006, 51 patients ont été traités par ILP dans notre institution, certains à deux reprises (58 ILP au total). Quatre-vingt-huit pour cent présentaient un sarcome de haut grade de malignité, et 84% une tumeur localement avancée (T2b NO Mo ou plus). Résultats : Le follow-up moyen est de 38.9 mois (4-159, médiane 22 mois), on note 21 % de complications immédiates et 23% de complications tardives ou chroniques. Une réponse complète (nécrose totale ou disparition de la tumeur) a été observée dans 25% des cas, une réponse partielle (>50% de nécrose ou de diminution de taille tumorale) dans 42%, une stabilité de la maladie dans 14% et une progression tumorale dans 14%. Un traitement adjuvant a été entrepris dans 31 % des cas, une résection des résidus tumoraux a pu être effectuée chez 65% des patients. On note un taux de récidive locale de 35% (après 20,3 mois en moyenne) et un taux de récidive à distance de 45% (après 13,4 mois en moyenne). Le disease-free survival est de 14,9 mois et la survie à 5 ans de 43,5%. Le taux d'amputation s'élève à 24%. Conclusion : La perfusion isolée de membre est un traitement grevé d'un taux élevé de complications, mais il peut étre entrepris dans les sarcomes les plus sévères avec un succès significatif. Ainsi, dans notre série, une chirurgie mutilante (en général l'amputation) a pu être épargnée à 76% des patients.