BackgroundUntil 50% of patients with renal cancer or melanoma, develop brain metastases during the course of their disease. Stereotactic radiotherapy has become a standard of care for patients with a limited number of brain metastases. Given the radioresistant nature of melanoma and renal cancer, optimization of the fractionation of stereotactic radiotherapy is needed. The purpose of this retrospective study was to elucidate if hypofractionated stereotactic radiotherapy (HFSRT) impacts local control of brain metastases from radioresistant tumors such as melanoma and renal cancer, in comparison with radiosurgery (SRS).MethodsBetween 2012 and 2016, 193 metastases, smaller than 3 cm, from patients suffering from radioresistant primaries (melanoma and renal cancer) were treated with HFSRT or SRS. The primary outcome was local progression free survival (LPFS) at 6, 12 and 18 months. Overall survival (OS) and cerebral progression free survival (CPFS) were secondary outcomes, and were evaluated per patient. Objective response rate and radionecrosis incidence were also reported. The statistical analysis included a supplementary propensity score analysis to deal with bias induced by non-randomized data.ResultsAfter a median follow-up of 7.4 months, LPFS rates at 6, 12 and 18 months for the whole population were 83, 74 and 70%, respectively. With respect to fractionation, LPFS rates at 6, 12 and 18 months were 89, 79 and 73% for the SRS group and 80, 72 and 68% for the HFSRT group. The fractionation schedule was not statistically associated with LPFS (HR = 1.39, CI95% [0.65–2.96], p = 0.38). Time from planning MRI to first irradiation session longer than 14 days was associated with a poorer local control rate. Over this time, LPFS at 12 months was reduced from 86 to 70% (p = 0.009). Radionecrosis occurred in 7.1% for HFSRT treated metastases to 9.6% to SRS treated metastases, without any difference according to fractionation (p = 0.55). The median OS was 9.6 months. Six, 12 and 18 months CPFS rates were 54, 24 and 17%, respectively.ConclusionFractionation does not decrease LPFS. Even for small radioresistant brain metastases (< 3 cm), HFSRT, with 3 or 6 fractions, leads to an excellent local control rate of 72% at 1 year with a rate of 7.1% of radionecrosis. HFSRT is a safe and efficient alternative treatment to SRS.Electronic supplementary materialThe online version of this article (10.1186/s13014-018-1083-1) contains supplementary material, which is available to authorized users.

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Despite the progresses performed in the field of radiotherapy, toxicity to the healthy tissues remains a major limiting factor. The aim of this work was to highlight blood biomarkers whose variations could predict the occurrence of late cutaneous side effects. Two groups of nine patients treated for Merkel Cell Carcinoma (MCC) were established according to the grade of late skin toxicity after adjuvant irradiation for MCC: grade 0, 1 or 2 and grade 3 or 4 of RTOG (Radiation Therapy Oncology Group)/EORTC (European Organization for Research and Treatment of Cancer). To try to discriminate these 2 groups, biomarkers of interest were measured on the different blood compartments after ex vivo irradiation. In lymphocytes, cell cycle, apoptosis and genotoxicity were studied. Oxidative stress was evaluated by the determination of the erythrocyte antioxidant capacity (superoxide dismutase, catalase, glutathione peroxidase, reduced and oxidized glutathione) as well as degradation products (protein carbonylation, lipid peroxidation). Inflammation was assessed in the plasma by the measurement of 14 cytokines. The most radiosensitive patients presented a decrease in apoptosis, micronucleus frequency, antioxidant enzyme activities, glutathione and carbonyls; and an increase in TNF-α (Tumor Necrosis Factor α), IL-8 (Interleukin 8) and TGF-β1 (Transforming Growth Factor β1) levels. These findings have to be confirmed on a higher number of patients and before radiotherapy and could allow to predict the occurrence of late skin side effects after radiotherapy.

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BackgroundStereotactic irradiation (SBRT) is a standard of care for inoperable stage I lung cancer and brain oligometastases from lung cancer but is controversial for extracranial oligometastases. We assessed outcomes of lung cancer patients with extracranial metastases in oligometastatic, oligorecurrent, oligopersistent and oligoprogressive settings (“oligometastatic spectrum”) under strategies using SBRT +/− systemic treatments.MethodsA retrospective multicentric study of consecutive lung cancer adult patients with 1–5 extracranial metastases treated with SBRT was conducted.ResultsOf 91 patients (99 metastases, median age 63, 64.8% adenocarcinomas, 19.8% molecular alterations), 11% had oligometastases, 49.5% oligorecurrence, 19.8% oligopersistence and 19.8% oligoprogression. Of 36% of patients under systemic treatments at initiation of SBRT, systemic treatment interruption was performed in 58% of them. With median follow up of 15.3 months, crude local control at irradiated metastases was 91%, while median distant progression-free survival (dPFS) and overall survival were 6.3 and 28.4 months (2-year survival 54%). Initial nodal stage and oligometastatic spectrum were prognostic factors for dPFS; age, initial primary stage and oligometastatic spectrum were prognostic factors for survival on multivariate analysis. Patients with oncogene-addicted tumors more frequently had oligoprogressive disease. Repeat ablative irradiations were preformed in 80% of patients who had oligorelapses. Worst acute toxicities consisted of 5.5% and one late toxic death occurred.ConclusionThe oligometastatic spectrum is a strong prognosticator in patients undergoing SBRT for extracranial metastases. Median survival was over two years but dPFS was about 6 months. Continuation of systemic therapy in oligoprogressive patients should be investigated.