Objectives Percutaneous radiofrequency ablation (RFA) is stated as a treatment option for renal cell carcinoma (RCC) smaller than 4 cm (T1a). Microwave ablation (MWA) is a newer technique and is... Show moreObjectives Percutaneous radiofrequency ablation (RFA) is stated as a treatment option for renal cell carcinoma (RCC) smaller than 4 cm (T1a). Microwave ablation (MWA) is a newer technique and is still considered experimental in some guidelines. The objective of this study was to compare the safety and efficacy of RFA and MWA for the treatment of RCC. Methods Patients with T1a RCC treated by RFA or MWA in two referral centers were retrospectively analyzed. Patient records were evaluated to generate mRENAL nephrometry scores. Local tumor progression (LTP) was considered when new (recurrence) or residual tumor enhancement within/adjacent to the ablation zone was objectified. Differences in LTP-free interval (residual + recurrence) between ablation techniques were assessed with Cox proportional hazards models and propensity score (PS) methods. Results In 164 patients, 87 RFAs and 101 MWAs were performed for 188 RCCs. The primary efficacy rate was 92% (80/87) for RFA and 91% (92/101) for MWA. Sixteen patients had residual disease (RFA (n = 7), MWA (n = 9)) and 9 patients developed recurrence (RFA (n = 7), MWA (n = 2)). LTP-free interval was significantly worse for higher mRENAL nephrometry scores. No difference in LTP-free interval was found between RFA and MWA in a model with inverse probability weighting using PS (HR = 0.99, 95% CI 0.35-2.81, p = 0.98) and in a PS-matched dataset with 110 observations (HR = 0.82, 95% CI 0.16-4.31, p = 0.82). Twenty-eight (14.9%) complications (Clavien-Dindo grade I-IVa) occurred (RFA n = 14, MWA n = 14). Conclusion Primary efficacy for ablation of RCC is high for both RFA and MWA. No differences in efficacy and safety were observed between RFA and MWA. Show less
Background Therapeutic regimens designed to augment the immunological response of a patient with breast cancer (BC) to tumor tissue are critically informed by tumor mutational burden and the... Show moreBackground Therapeutic regimens designed to augment the immunological response of a patient with breast cancer (BC) to tumor tissue are critically informed by tumor mutational burden and the antigenicity of expressed neoepitopes. Herein we describe a neoepitope and cognate neoepitope-reactive T-cell identification and validation program that supports the development of next-generation immunotherapies. Methods Using GPS Cancer, NantOmics research, and The Cancer Genome Atlas databases, we developed a novel bioinformatic-based approach which assesses mutational load, neoepitope expression, human leukocyte antigen (HLA)-binding prediction, and in vitro confirmation of T-cell recognition to preferentially identify targetable neoepitopes. This program was validated by application to a BC cell line and confirmed using tumor biopsies from two patients with BC enrolled in the Tumor-Infiltrating Lymphocytes and Genomics (TILGen) study. Results The antigenicity and HLA-A2 restriction of the BC cell line predicted neoepitopes were determined by reactivity of T cells from HLA-A2-expressing healthy donors. For the TILGen subjects, tumor-infiltrating lymphocytes (TILs) recognized the predicted neoepitopes both as peptides and on retroviral expression in HLA-matched Epstein-Barr virus-lymphoblastoid cell line and BC cell line MCF-7 cells; PCR clonotyping revealed the presence of T cells in the periphery with T-cell receptors for the predicted neoepitopes. These high-avidity immune responses were polyclonal, mutation-specific and restricted to either HLA class I or II. Interestingly, we observed the persistence and expansion of polyclonal T-cell responses following neoadjuvant chemotherapy. Conclusions We demonstrate our neoepitope prediction program allows for the successful identification of neoepitopes targeted by TILs in patients with BC, providing a means to identify tumor-specific immunogenic targets for individualized treatment, including vaccines or adoptively transferred cellular therapies. Show less
Pexidartinib is an orally administered small molecule tyrosine kinase inhibitor. Phase III ENLIVEN study results provided clinical evidence for US FDA approval for treatment of adult patients with... Show morePexidartinib is an orally administered small molecule tyrosine kinase inhibitor. Phase III ENLIVEN study results provided clinical evidence for US FDA approval for treatment of adult patients with symptomatic tenosynovial giant cell tumor associated with severe morbidity or functional limitations and not amenable to improvement with surgery. Recommended dosage is 400 mg orally twice daily on an empty stomach. Long-term follow-up in pooled analyses showed increased response rates compared with those observed in ENLIVEN. Patients on pexidartinib also experience meaningful improvements in range of motion. Side effects associated with pexidartinib are generally manageable; however, there is a risk of potentially life-threatening mixed or cholestatic hepatotoxicity and pexidartinib has a Risk Evaluation and Mitigation Strategy (REMS) program to ensure appropriate monitoring. Show less
Kooiman, J.; Exter, P.L. den; Cannegieter, S.C.; Cessie, S. le; Toro, J. del; Sahuquillo, J.C.; ... ; Huisman, M.V. 2013
Aims: To describe the characteristics and outcomes of cancer patients receiving Whole Brain Radiotherapy (WBRT) and delineate poor outcome groups after WBRT.Materials and methods: From 1991 to 2007... Show moreAims: To describe the characteristics and outcomes of cancer patients receiving Whole Brain Radiotherapy (WBRT) and delineate poor outcome groups after WBRT.Materials and methods: From 1991 to 2007, 3459 patients receiving WBRT for brain metastases at three centres (in Australia and the Netherlands) were retrospectively reviewed. The effect of clinicodemographic factors, including age, gender, primary cancer, time to WBRT from primary cancer diagnosis and WBRT timing relative to other radiotherapy courses on overall survival, survival from WBRT commencement (WBRT-SV) and death within 6 weeks were analysed.Results: WBRT was the first radiotherapy course in 2161/3459 (63%) and the last in 2932/3459 (85%). The most common primary cancer sites with brain metastases were lung (n = 1800; 52%), breast (n = 568; 16%), melanoma (n = 350; 10%) and colorectal (n = 209; 6%). The median time to WBRT from primary cancer diagnosis was 34 weeks, overall survival 1.42 years (0.04-28.70) and WBRT-SV 0.33 years (0-8.60). Older age, male gender and a shorter time from the primary cancer diagnosis to WBRT predicted worse overall survival and WBRT-SV. Seventeen per cent survived less than 6 weeks. Older patients with a shorter time from the primary cancer diagnosis to WBRT and a lower WBRT episode number were more likely to die less than 6 weeks after WBRT.Conclusions: Cancer patients with brain metastases have poor overall outcomes. High mortality within 6 weeks of starting WBRT suggests patient selection remains challenging. (C) 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. Show less
