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Aim To evaluate the indications and results of preoperative radiotherapy (RT) on a series of selected patients treated at our institution with curative intent for a limb sarcoma (STS). Patients and methods From 05/1993 to 12/2011, 64 STS patients received preoperative RT. Results RT was delivered as a “limb salvage treatment” prior to surgery for the following reasons: as the preferential induction treatment in 53 patients (83%) or as a second intent (17%) after the failure of neoadjuvant systemic chemotherapy/isolated limb perfusion. Surgery was performed after RT in 54 (84%) patients and final limb salvage was performed in 98%. Musculo-cutaneous flap reconstruction was planned upfront in 44% patients, and 19% had a skin graft. Seven patients (13%) had a postoperative RT boost. Thirteen (20%) patients had grade (G) 3/4 adverse events, one after RT and 12 after surgery. At a median follow-up of 3.5 years, the 3-year actuarial overall survival (OS) and distant relapse (DR) rates were 83% and 31%, respectively. Two patients developed a local relapse and two a local progression (non-operated patients). In the multivariate analysis (MVA), histological subtype (leiomyosarcoma) and grade 3 were predictive of poorer survival. Patients with >3 month delay between the start of RT and surgery at our institution had an increased risk of DR in the MVA. Conclusion Induction RT should be personalised according to histological subtype, tumour site and risks-benefit ratio of preoperative radiotherapy and is best managed by a multidisciplinary surgical and oncology team in a specialist sarcoma centre. [ABSTRACT FROM AUTHOR]

Background: The expression levels of excision repair cross-complementation group 1 (ERCC1), replication protein A (RPA) and xeroderma pigmentosum group F (XPF) nucleotide excision repair proteins may be important in the response to platin-based therapy in lung cancer patients. It is not known whether ERCC1, RPA and XPF expression levels differ between ever smokers (ES) and never smokers (NS). [ABSTRACT FROM PUBLISHER]

Abstract: Epithelioid Hemangioendothelioma (EHE) is an uncommon angiocentric vascular tumour. We present a case of an EHE of the left femoral vein, in a young woman, diagnosed after becoming symptomatic due to metastases. Limb is a rare localisation for this primary tumour. Diagnosis may be difficult, and aetiology is yet unknown. [Copyright &y& Elsevier]

The article discusses the relevance of breast cancer molecular sub-classification to conventional diagnostic tools. It explores the characterization of molecular subclasses using conventional diagnostic tools. A comparison between the clinical performance of molecular subclasses and conventional diagnostic tools is presented. The possible clinical use of molecular subclassification is also described.

Purpose To analyse feasibility, prognostic factors and patterns of recurrence after concurrent reirradiation and bevacizumab for recurrent high-grade gliomas. Patients and methods Between 2009 and 2015, 35 patients (median 57-year-old; 21 men, 14 women) with WHO grade III ( n = 11) or grade IV ( n = 24) gliomas were included in this retrospective and consecutive single-centre study. All patients received bevacizumab (median number of treatments: 12) concomitant with reirradiation (median dose: 45 Gy, median number of fractions: 18) for recurrence with median 22 months (range: 5.6–123.7 months) from first irradiation (median dose: 60 Gy). Results The median follow-up was 9.2 months from reirradiation. The median overall survival from reirradiation was 10.5 months (95% confidence interval [95% CI]: 4.9–16.1) and the progression-free survival from reirradiation was 6.7 months (95% CI: 2.9–10.5). The median overall survival from initial diagnosis was 44.6 months (95% CI: 32–57.1). No grade 3 toxicity or above was reported. Prognostic factors significantly correlated with better overall survival in univariate analysis were: age at least 55 ( P = 0.024), initial surgery ( P = 0.003), and 2 Gy equivalent dose (EQD2) at least 50 Gy at reirradiation ( P = 0.046). Twenty-two patients bevacizumab-naïve at time of reirradiation had a significantly increased overall survival from reirradiation compared to patients treated with reirradiation after bevacizumab failure (17.7 vs. 5.4 months, P < 0.001) as well as overall survival from initial diagnosis (58.9 vs. 33.5 months, P = 0.006). This outcome was similar in patients with initial glioblastomas ( P = 0.018) or anaplastic gliomas ( P = 0.021). There was no correlation between overall survival and gross tumour volume or planning target volume, frontal localization, or number of salvage therapies before reirradiation ( P > 0.05). Conclusions Concomitant reirradiation with bevacizumab in high-grade recurrent gliomas shows encouraging results in terms of survival and toxicities. Our data suggest that reirradiation should be favoured at initiation of bevacizumab, with EQD2 at least 50 Gy. [ABSTRACT FROM AUTHOR]

These findings may potentially influence future clinical practice, with encouraging long-term survival data and better safety of masitinib with respect to sunitinib indicating a positive benefit–risk ratio. Considered in the setting of effective subsequent therapies, data show that adding masitinib to the armaterium of drugs used to treat GIST generates a clinically relevant survival benefit.Background Masitinib is a highly selective tyrosine kinase inhibitor with activity against the main oncogenic drivers of gastrointestinal stromal tumor (GIST). Masitinib was evaluated in patients with advanced GIST after imatinib failure or intolerance. Patients and methods Prospective, multicenter, randomized, open-label trial. Patients with inoperable, advanced imatinib-resistant GIST were randomized (1 : 1) to receive masitinib (12 mg/kg/day) or sunitinib (50 mg/day 4-weeks-on/2-weeks-off) until progression, intolerance, or refusal. Primary efficacy analysis was noncomparative, testing whether masitinib attained a median progression-free survival (PFS) (blind centrally reviewed RECIST) threshold of >3 months according to the lower bound of the 90% unilateral confidence interval (CI). Secondary analyses on overall survival (OS) and PFS were comparative with results presented according to a two-sided 95% CI. Results Forty-four patients were randomized to receive masitinib (n = 23) or sunitinib (n = 21). Median follow-up was 14 months. Patients receiving masitinib experienced less toxicity than those receiving sunitinib, with significantly lower occurrence of severe adverse events (52% versus 91%, respectively, P = 0.008). Median PFS (central RECIST) for the noncomparative primary analysis in the masitinib treatment arm was 3.71 months (90% CI 3.65). Secondary analyses showed that median OS was significantly longer for patients receiving masitinib followed by post-progression addition of sunitinib when compared against patients treated directly with sunitinib in second-line [hazard ratio (HR) = 0.27, 95% CI 0.09–0.85, P = 0.016]. This improvement was sustainable as evidenced by 26-month follow-up OS data (HR = 0.40, 95% CI 0.16–0.96, P = 0.033); an additional 12.4 months survival advantage being reported for the masitinib treatment arm. Risk of progression while under treatment with masitinib was in the same range as for sunitinib (HR = 1.1, 95% CI 0.6–2.2, P = 0.833). Conclusions Primary efficacy analysis ensured the masitinib treatment arm could satisfy a prespecified PFS threshold. Secondary efficacy analysis showed that masitinib followed by the standard of care generated a statistically significant survival benefit over standard of care. Encouraging median OS and safety data from this well-controlled and appropriately designed randomized trial indicate a positive benefit–risk ratio. Further development of masitinib in imatinib-resistant/intolerant patients with advanced GIST is warranted. [ABSTRACT FROM AUTHOR]

Background Pre-clinical data have suggested a therapeutic role of Hedgehog (Hh) pathway inhibitors in chondrosarcoma. Methods This phase II trial included patients with progressive advanced chondrosarcoma. They received GDC-0449 150 mg/day (days 1–28, 28-day cycle). The primary end point was the 6-month clinical benefit rate (CBR) defined as the proportion of patients with non-progressive disease at 6 months. A 6-month CBR of 40% was considered as a reasonable objective to claim drug efficacy. Results Between February 2011 and February 2012, 45 patients were included. Twenty had received prior chemotherapy. Thirty-nine were assessable for efficacy. The 6-month CBR was 25.6% (95% confidence interval 13.0–42.1). All stable patients had grade 1 or 2 conventional chondrosarcoma with documented progression within the 6 months before inclusion. All but one with available data also had overexpression of the Hh ligand. Median progression-free and overall survivals were 3.5 and 12.4 months, respectively. The most frequent adverse events were grade 1 or 2 myalgia, dysgeusia and alopecia. Conclusions GDC-0449 did not meet the primary end point of this trial. Results suggest some activity in a subset of patients with progressive grade 1 or 2 conventional chondrosarcoma. Further studies assessing its role in combination with chemotherapy are warranted. ClinicalTrials.gov Identifier NCT01267955. [ABSTRACT FROM AUTHOR]

Background We previously demonstrated that interruption of imatinib mesylate (IM) in responding patients (pts) with advanced gastrointestinal stromal tumours (GISTs) results in rapid reprogression. The impact of interruption on residual tumour, quality of response and secondary resistance has not been fully investigated. Patients and methods Within the BRF14 study, 71 non-progressing patients were randomly assigned in the interruption arms after 1, 3 or 5 years. IM was resumed in the case of progressive disease (PD). Tumour status at randomisation, relapse and after IM rechallenge, progression-free survival (PFS) and time to secondary resistance were analysed. Results At data cut-off, 51 of 71 patients had restarted IM following documented PD. Eighteen patients (35%) progressed on known lesions only, while 33 patients (65%) had new lesions, with concomitant progression of known lesions in 17 patients. Only 8 (42%) of complete remission (CR) patients and 12 (52%) of partial response (PR) patients at randomisation achieved a new CR and PR. Patients progressing rapidly after interruption had a poorer prognosis. Tumour status at randomisation influenced time to progression after rechallenge. Conclusion In advanced GIST patients interrupting IM, quality of response upon reintroduction did not reach the tumour status observed at randomisation. Rapid progression after imatinib interruption is associated with poor PFS after reintroduction. [ABSTRACT FROM PUBLISHER]

Background As most patients with retroperitoneal sarcomas (RPS) die of local recurrence, front-line aggressive surgery (FAS) has been developed, and it seems to achieve better local control. The aim of this study was to evaluate conformal postoperative radiotherapy (PORT) in patients who had enlarged surgery. Patients and methods Between 1994 and 2008, 110 patients with primary RPS mainly operated by FAS were analysed. Sixty-two patients underwent surgery and no PORT (group S), and 48 received surgery and PORT (group S + R). The median age was 52. Most patients had 3D conformal PORT (81%) with a median dose of 50 Gy. Results Comparing results at 5 years in the S and the S + R group, the cumulative rate of local failure was, respectively, 36% and 22% (NS); relapse-free survival was 47% and 60% (P = 0.02), and overall survival was, respectively, 77% and 71% (NS). Conclusion Even if patients with adjuvant PORT were at higher risk of recurrence, there was a trend for radiotherapy (RT) to decrease the local relapse rate and improve recurrence-free survival. This study confirms that adjuvant conformal RT should be evaluated in a randomized trial, the control arm being FAS. Adjuvant RT in the preoperative setting is being evaluated in an EORTC trial. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To assess the acute toxicity of intensity modulated radiotherapy as post-operative adjuvant treatment for retroperitoneal sarcoma. Patients and methods: Patients who received adjuvant intensity modulated radiotherapy from January 2009 to September 2010 were retrospectively reviewed. Results: Fourteen patients entered the study (seven primary tumours and seven relapses). All tumours were liposarcoma and had macroscopically complete resection, epiploplasty was systematically realized. Median tumour size was 21cm (range: 15–45), median planning target volume was 580cm3 (range: 329–1172) and median prescribed dose was 50.4Gy (range: 45–54). Median follow-up was 11.5 months (range: 2–21.4). Acute toxicity was mild: acute digestive toxicity grade 1–2 occurred in 12/14 patients (86%). However, there was no weight loss of more than 5% during radiotherapy and no treatment interruption was required. Two months after completion of radiotherapy, digestive toxicity grade 1 remained present in 1/14 patients (7%). One case of grade 3 toxicity occurred during follow-up (transient abdominal pain). Three relapses occurred: two were outside treaded volume and one was both in and outside treated volume. Conclusions: Intensity modulated radiotherapy in the postoperative setting of retroperitoneal sarcoma provides low acute toxicity. Longer follow-up is needed to assess late toxicity, especially for bowel, kidney and radio-induced malignancies. [Copyright &y& Elsevier]

Abstract: Background: Few data are available from clinical trials for elderly patients receiving cetuximab. Patients and methods: The clinical data of consecutive patients aged ≥70 years given cetuximab for metastatic CRC were retrospectively captured from hospital pharmacy registries in seven centers. Results: Fifty-six patients received cetuximab±with irinotecan. Median age was 76 years (70–84), 86% of patients were pretreated with fluoropyrimidines, irinotecan and oxaliplatin and 69.6% had documented resistance to irinotecan. Objective response rate was 21% (95% CI: 11–32%). The median progression-free survival was 4.4 months (95% CI: 3.0–5.7 months) and the median overall survival was 16.0 months (95% CI: 13.5–18.5 months). Skin rash occurred in 75% of the patients (11% grade 3) and diarrhea in 80% (20% grades 3–4). Conclusion: Tolerability of cetuximab was acceptable in elderly patients with pretreated metastatic CRC. Efficacy appeared similar to that observed in younger patients. [Copyright &y& Elsevier]

Objectif de l’étude Évaluer l’efficacité et la toxicité de la radiothérapie en conditions stéréotaxiques comme traitement des métastases cérébrales de différents cancers primitifs, associée ou non à une irradiation encéphalique. Matériel et méthode Trente-trois patients atteints de métastases cérébrales (dont 45,5 % de cancers primitifs pulmonaires) ont été traités par irradiation en conditions stéréotaxiques par CyberKnife ® . La dose prescrite variait de 21 (en complément d’une irradiation encéphalique prophylactique) à 33 Gy, en trois fractions. Les critères étudiés étaient le contrôle local, la survie globale, la survie sans progression, et la toxicité. Résultats Le suivi médian était de 39,9 mois. La durée médiane de survie était de 72,9 mois et la celle de survie sans progression médiane de 31,9 mois. Nous avons comparé les durées de survie selon que le cancer primitif était pulmonaire ou non. Il y avait une différence significative de survie globale (médiane de 33 mois contre 108,2 mois ; p = 0,0341) mais pas de taux de contrôle local ( p = 0,5862) ni sur la survie sans progression (médiane de 28,6 mois contre 50,3 mois ; p = 0,1756). Nous avons comparé les durées de survie en fonction de la réalisation préalable ou non d’une irradiation encéphalique de 25 Gy (en majorité pour les cancers primitifs pulmonaires). Il y avait une différence quasi significative de survie globale (médiane de 33 mois contre 163,2 mois ; p = 0,0536) en défaveur de l’irradiation panencéphalique mais non significatif en termes de survie sans progression (médiane de 29,3 mois contre 50,4 mois ; p = 0,6516). Il y avait également une tendance à la réduction de la survenue de nouvelles métastases cérébrales par la réalisation de l’irradiation prophylactique ( p = 0,06). Seuls quatre patients ont souffert d’une toxicité de grade 1, aucun de grade 2 ou plus. Conclusion La radiothérapie en conditions stéréotaxiques est une technique efficace pour le traitement des métastases cérébrales avec une excellente survie dans cette série. Les métastases de primitif pulmonaire semblent de pronostic moins favorable. L’irradiation encéphalique préalable semble impacter plutôt négativement mais non significativement la survie globale mais pourrait réduire l’apparition de nouvelles métastases. [ABSTRACT FROM AUTHOR]