Transcriptomics in cancer revealed by Positron Emission Tomography radiomics.

Metabolic images from Positron Emission Tomography (PET) are used routinely for diagnosis, follow-up or treatment planning purposes of cancer patients. In this study we aimed at determining if radiomic features extracted from 18F-Fluoro Deoxy Glucose (FDG) PET images could mirror tumor transcriptomics. In this study we analyzed 45 patients with locally advanced head and neck cancer (H&N) that underwent FDG-PET scans at the time of diagnosis and transcriptome analysis using RNAs from both cancer and healthy tissues on microarrays. Association between PET radiomics and transcriptomics was carried out with the Genomica software and a functional annotation was used to associate PET radiomics, gene expression and altered biological pathways. We identified relationships between PET radiomics and genes involved in cell-cycle, disease, DNA repair, extracellular matrix organization, immune system, metabolism or signal transduction pathways, according to the Reactome classification. Our results suggest that these FDG PET radiomic features could be used to infer tissue gene expression and cellular pathway activity in H&N cancers. These observations strengthen the value of radiomics as a promising approach to personalize treatments through targeting tumor-specific molecular processes.

Inhomogeneous tumor dose distribution provides better local control than homogeneous distribution in stereotactic radiotherapy for brain metastases.

INTRODUCTION: The aim of this study was to analyze the impact of inhomogeneous versus homogeneous dose distribution on local control (LC) and radionecrosis (RN) in patients treated with fractionated stereotactic radiotherapy (SRT) for newly-diagnosed brain metastases (BM). PATIENTS AND METHODS: From 2014 to 2017, 134 patients (median age 61 years) underwent SRT for BM (n = 114 with ≤2, n = 20 with 3-6 BM) at our institution. Treatment was delivered using volumetric modulated arc therapy on a linear accelerator. Ninety-one consecutive patients (BM = 136) were irradiated at a dose of 21-23.1 Gy in 3 fractions delivered homogeneously (99% of the dose had to cover 99% of the planning target volume (PTV)) (group 1) whereas the following 43 patients (BM = 72) received an inhomogeneous dose of 10 or 11 Gy prescribed to the isocenter with the 70% isodose line covering the PTV (group 2). Variables analyzed included dose distribution, age, gender, histology, diagnosis-specific Graded Prognostic Assessment score, number of brain metastases, presence of extracranial metastases, and tumor volumes. RESULTS: After a median follow-up of 12.4 months (range, 1.4-33.1), the 1-year LC and RN rate were 78% and 7.5% in group 1 and 93% and 0% in group 2, respectively (p = 0.005). In multivariate analysis, improved LC was significantly correlated with SRT dose distribution (p = 0.009) and tumor volume (p = 0.03). The number of metastases (p = 0.03) and SRT dose distribution (p = 0.04) were both associated with increased risk of RN. CONCLUSION: SRT delivered with inhomogeneous dose distribution resulted in better LC and a lower risk of RN compared to homogeneous distribution.

Cosmetic Outcome and Chronic Breast Toxicity After Intraoperative Radiation Therapy (IORT) as a Single Modality or as a Boost Using the Intrabeam® Device: A Prospective Study.

PURPOSE: We aim to report our results in terms of chronic toxicities and cosmetic outcomes after intraoperative radiotherapy (IORT) using kV X-rays in women treated for early breast cancer at our institution. METHODS: Patients with early breast carcinoma were recruited between April 2011 and November 2014. After breast-conserving surgery, patients were treated with IORT using the Intrabeam® device. IORT was completed by whole-breast radiotherapy (WBRT) at a dose of 46-50.4 Gy in 23-28 fractions in case of adverse pathologic criteria on the final specimen examination. Skin toxicity was graded using the Late Effects in Normal Tissues-Subjective, Objective, Management and Analytic (LENT-SOMA) scale every 6 months, and cosmetic outcomes were evaluated at 36 months by patient self-evaluation and by two radiation oncologists, on a 1-10 scale. RESULTS: Forty-one women received IORT only and 30 patients received IORT followed by WBRT (IORT + WBRT group). After a median follow-up of 38.9 months, no locoregional or distant recurrence occurred. After IORT only, 2.4% of grade 2 or higher breast fibrosis, and no other grade 2 or higher disease, was observed. In the IORT + WBRT group, grade 2 or higher fibrosis and grade 2 or higher breast retraction were observed in 43.3 and 23.3% of patients, respectively. Objective cosmetic outcomes were very good and significantly better in the IORT-only group compared with the IORT + WBRT group (8.87 vs. 6.96) (p < 0.001). CONCLUSION: IORT using the Intrabeam® is well-tolerated, with very little chronic toxicity and good cosmetic outcome. However, a high rate of grade 2 or higher chronic breast toxicity was observed when IORT had to be completed by WBRT.

ALK ambiguous-positive non-small cell lung cancers are tumors challenged by diagnostic and therapeutic issues.

Searching for ALK rearrangements using the approved fluorescent in situ hybridization (FISH) test and complementary immunohistochemistry (IHC) has become the rule to treat patients with advanced non­small cell lung cancer (NSCLC) with anti­ALK targeted therapy. The concordance between the two techniques is reported to be strong but imperfect. We report our experience with cases of ALK­rearranged lung adenocarcinomas pointing out particularly ambiguous cases. FISH and IHC data on ALK but also c­MET IHC as well as EGFR and KRAS mutation screening are considered, together with response to crizotinib treatment. We classified the 55 FISH ALK­rearranged tumors into two groups according to the FISH and IHC results: a concordant FISH+IHC+ group (31 tumors) and an ambiguous group (24 tumors). These tumors were considered as 'ambiguous' ALK­positive due to negative (21 tumors) or non­contributive (3 tumors) IHC. In addition, the percentage of FISH-positive nuclei was between 15 and 20% in 17 tumors belonging to one or the other group (now called borderline tumors). We discuss the accuracy of the different tests with intent to determine whether ambiguous and borderline tumors are real positive ALK­rearranged tumors. To conclude, ambiguous ALK­positive lung cancers are challenging tumors with diagnosis and therapeutic issues that can justify parallel FISH, IHC and molecular screening strategy.