[Management of non-small cell lung cancer patients harboring activating mutations and CNS progression]. / Caractéristiques et prise en charge de l'évolutivité cérébro-méningée des cancers bronchiques dans un contexte de mutation activatrice.

The central nervous system (CNS), through carcinomatous meningitis or solid brain metastases, is the most common site of recurrence in non-small cell lung cancers (NSCLC) with activating mutations. Our retrospective study describes the population of patients with CNS metastases of NSCLC harboring activating mutation with targeted therapy (EGFR, ALK, BRAF, HER2) in 4 French regional reference hospitals. 60 patients were analyzed. The proposed treatments were heterogeneous and included combinations of chemotherapy, targeted therapy and radiotherapy±associated with topical treatments. Median overall survival following CNS metastasis in these patients was 15.8 months for meningitis carcinoma and 26 months for brain metastases. In patients with brain metastases, the addition of targeted therapy treatment allows a significant improvement in median progression free survival from 5.9 months to 10.6 months (HR 0.48 CI95 [0.24 to 0.97] P=0.035). These patients seem therefore benefit from systemic therapy and particularly targeted therapy with better survival than usual.

Subventricular zone involvement at recurrence is a strong predictive factor of outcome following high grade glioma reirradiation.

We aimed to assess the efficacy of stereotactic irradiation for patients with recurrent high-grade glioma (HGG) and identify predictive factors of progression-free survival (PFS) and overall survival (OS) following reirradiation. We identified 32 patients with recurrent brain HGG who had been treated with either single-dose (stereotactic radiosurgery) or fractionated stereotactic radiotherapy between April 2008 and October 2015. Median follow up was 21.4 months (range 12.9-23.2) and median PFS was and 3.3 months (95% CI [2.3-4.7]), respectively. OS was 90.40% (95% CI [73.09-96.80]) at 6 months and 79.55% (95% CI [59.9-90.29]) at 12 months. Univariate analysis showed that biological effective dose at isocenter ≤ 76 Gy was a poor prognostic factor for both OS (83.33 vs. 100% at 6 months, p = 0.032) and median PFS (2.7 vs. 4.7 months, p = 0.025), as was gross tumor volume (GTV) above 1 cm3 for OS (86.15 vs. 94.12% at 6 months, p = 0.043). Contact with the subventricular zone (SVZ) was also a poor prognostic factor for median PFS (2.3 vs. 4.7 months, p = 0.002). Multivariate analysis showed that SVZ contact remained a poor prognostic factor for PFS (hazard ratio = 3.44, 95% CI [1.21-9.82], p = 0.021). Results suggest that reirradiation is a safe and effective treatment option for recurrent HGG in patients with a good Karnosfsky Performance Scale score, a long progression-free interval since first radiation and limited GTV, and that contact to SVZ is a strong prognostic factor for PFS.

[Acute toxicity of breast cancer irradiation with modulated intensity by tomotherapy®]. / Toxicité aiguë de la tomothérapie des cancers mammaires.

PURPOSE: Helical radiation intensity modulated by tomotherapy improves dose distribution to complex and large volumes. The aim of the study was to assess acute toxicity of this technique during breast cancer irradiation after conserving surgery or mastectomy. PATIENTS AND METHODS: Cutaneous toxicities, lung and oesophageal side effects, and breast lymphedema were retrospectively collected according to the Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) in 292 patients treated for a breast cancer by tomotherapy between May 2010 and December 2014. After conservative surgery, the dose administered to breast volume and the tumour bed was respectively 52.2Gy and 63.8Gy in 29 fractions. After mastectomy, the dose was 50Gy in 25 fractions. Univariate and multivariate analyses were performed to highlight risk factors for dermatitis and breast oedema. RESULTS: The rate of dermatitis grade 2 and 3 were 22.9% and 1.7% respectively. In univariate analysis, factors associated with acute radiation dermatitis were breast volume (P=0.002), body mass index (BMI) (P<0.0001), the use of chest compression mask (net) (P=0.005) and the localization of the irradiation (P <0.0001). In multivariate analysis, BMI greater than 25kg/m2 (odds ratio [OR]: 3.61, 95% confidence interval [CI]: [1.93-6.74], P<0.0001), the use of a chest mask (OR 2.01, 95% CI [1.06-3.79] P=0.0328) and irradiation after conservative treatment increase the risk of acute radiation dermatitis (mastectomy: OR 0.64, 95% CI [0.04-0.43]; mastectomy with immediate reconstruction with prosthesis: OR 0.13 95% CI [0.10-0.38] P=0.0003). The incidence of breast oedema grade 2 or above was 19.5%, in univariate analysis, there was a correlation with BMI (P=0.003) and smoking (P=0.009). In multivariate analysis, smoking and BMI greater than 25kg/m2 increased the risk of breast oedema (OR 2.47, respectively [95% CI 1.22-5.01] P=0.012 and OR 2.37 [95% CI 1.22-4.59] P=0.01). The rate of radiation pneumonitis of grade 2 or above was 1.4%. Among the patients, 19.9% had esophagitis grade 1 or 2. CONCLUSION: The helical irradiation intensity modulation tomotherapy is a well-tolerated treatment for breast cancer that reduces the high radiation doses to organs at risk.

[Postoperative external beam radiotherapy for medullary thyroid carcinoma with high risk of locoregional relapse]. / Radiothérapie postopératoire des carcinomes médullaires de la thyroïde à haut risque de rechute locorégionale.

PURPOSE: To assess the outcome of locally advanced medullary thyroid carcinoma treated with surgery and adjuvant external beam radiotherapy. PATIENTS AND METHODS: Twenty-nine consecutive patients with non-metastatic medullary thyroid carcinoma treated in our institution between January 1995 and December 2012 were retrospectively evaluated. All underwent curative-intended optimal surgery, followed by external beam radiotherapy because of high risk of locoregional relapse. Twelve patients were stage III, 16 IVa and 1 IVb. Positive surgical margins were present in 11 cases (10 R1 and 1 R2). Median and average preradiotherapy serum calcitonin were 141pg/mL and 699pg/mL, respectively. Fourteen patients received 3D-conformal radiotherapy and 15 received intensity-modulated radiotherapy. Median prescribed dose was 63Gy to the high-risk volumes and 54Gy to the low-risk volumes. Treatment was delivered in 30 fractions. The median gap between surgery and radiotherapy was 1.9months. Median follow-up was 76.4months. RESULTS: Kaplan-Meier estimates of 5-year locoregional relapse-free survival and overall survival were 79 and 96 %, respectively. Among the five locoregional relapses, two were related to a macroscopic metastatic cervical lymph node that was unfortunately not removed during the lymphadenectomy. Eight of ten patients with microscopic positive margins (R1) were controlled regarding the thyroidectomy bed. Eight patients had normal serum calcitonin after external beam radiotherapy, of whom only one developed a locoregional relapse during follow-up. Regarding the 21 patients with persistent positive serum calcitonin after treatment, only ten developed a macroscopic locoregional or distant relapse. One grade III and no grade IV acute morbidity were reported. Fifteen patients reported grade II chronic morbidity and no grade III/IV. CONCLUSION: Maximal surgery followed by adjuvant external beam radiotherapy as a treatment for locally advanced medullary thyroid carcinoma provides a high rate of long-term locoregional control and overall survival with limited toxicity. Postoperative external beam radiotherapy should be considered when patients present features indicating a high risk of locoregional relapse.

Identification of a candidate biomarker from perfusion MRI to anticipate glioblastoma progression after chemoradiation.

OBJECTIVE: To identify relevant relative cerebral blood volume biomarkers from T2* dynamic-susceptibility contrast magnetic resonance imaging to anticipate glioblastoma progression after chemoradiation. METHODS: Twenty-five patients from a prospective study with glioblastoma, primarily treated by chemoradiation, were included. According to the last follow-up MRI confirmed status, patients were divided into: relapse group (n = 13) and control group (n = 12). The time of last MR acquisition was tend; MR acquisitions performed at tend-2M, tend-4M and tend-6M (respectively 2, 4 and 6 months before tend) were analyzed to extract relevant variations among eleven perfusion biomarkers (B). These variations were assessed through R(B), as the absolute value of the ratio between ∆B from tend-4M to tend-2M and ∆B from tend-6M to tend-4M. The optimal cut-off for R(B) was determined using receiver-operating-characteristic curve analysis. RESULTS: The fraction of hypoperfused tumor volume (F_hPg) was a relevant biomarker. A ratio R(F_hPg) ≥ 0.61 would have been able to anticipate relapse at the next follow-up with a sensitivity/specificity/accuracy of 92.3 %/63.6 %/79.2 %. High R(F_hPg) (≥0.61) was associated with more relapse at tend compared to low R(F_hPg) (75 % vs 12.5 %, p = 0.008). CONCLUSION: Iterative analysis of F_hPg from consecutive examinations could provide surrogate markers to predict progression at the next follow-up. KEY POINTS: • Related rCBV biomarkers from DSC were assessed to anticipate GBM progression. • Biomarkers were assessed through their patterns of variation during the follow-up. • The fraction of hypoperfused tumour volume (F_hP g ) seemed to be a relevant biomarker. • An innovative ratio R(F_hP g ) could be an early surrogate marker of relapse. • A significant time gain could be achieved in the management of GBM patients.

Efficacy of trabectedin in malignant solitary fibrous tumors: a retrospective analysis from the French Sarcoma Group.

BACKGROUND: Advanced malignant solitary fibrous tumors (SFTs) are rare soft-tissue sarcomas with a poor prognosis. Several treatment options have been reported, but with uncertain rates of efficacy. Our aim is to describe the activity of trabectedin in a retrospective, multi-center French series of patients with SFTs. METHODS: Patients were mainly identified through the French RetrospectYon database and were treated between January 2008 and May 2013. Trabectedin was administered at an initial dose of 1.5 mg/m(2), q3 weeks. The best tumor response was assessed according to the Response Evaluation Criteria In Solid Tumors 1.1. The Kaplan-Meier method was used to estimate median progression-free survival (PFS) and overall survival (OS). The growth-modulation index (GMI) was defined as the ratio between the time to progression with trabectedin (TTPn) and the TTP with the immediately prior line of treatment (TTPn-1). RESULTS: Eleven patients treated with trabectedin for advanced SFT were identified. Trabectedin had been used as second-line treatment in 8 patients (72.7 %) and as at least third-line therapy in a further 3 (27.3 %). The best RECIST response was a partial response (PR) in one patient (9.1 %) and stable disease (SD) in eight patients (72.7 %). Disease-control rate (DCR = PR + SD) was 81.8 %. After a median follow-up of 29.2 months, the median PFS was 11.6 months (95 % CI = 2.0; 15.2 months) and the median OS was 22.3 months (95 % CI = 9.1 months; not reached). The median GMI was 1.49 (range: 0.11-4.12). CONCLUSION: Trabectedin is a very promising treatment for advanced SFTs. Further investigations are needed.