Deep abscopal response to radiotherapy and anti-PD-1 in an oligometastatic melanoma patient with unfavorable pretreatment immune signature

Radiotherapy can elicit abscopal effects in non-irradiated metastases, particularly under immune checkpoint blockade (ICB). We report on two elderly patients with oligometastatic melanoma treated with anti-PD-1 and stereotactic body radiation therapy (SBRT). Before treatment, patient 1 showed strong tumor infiltration with exhausted CD8+ T cells and high expression of T cell-attracting chemokines. This patient rapidly mounted a complete response, now ongoing for more than 4.5 years. Patient 2 exhibited low CD8+ T cell infiltration and high expression of immunosuppressive arginase. After the first SBRT, his non-irradiated metastases did not regress and new metastases occurred although neoepitope-specific and differentiation antigen-specific CD8+ T cells were detected in the blood. A second SBRT after 10 months on anti-PD-1 induced a radiologic complete response correlating with an increase in activated PD-1-expressing CD8 T cells. Apart from a new lung lesion, which was also irradiated, this deep abscopal response lasted for more than 2.5 years. However, thereafter, his disease progressed and the activated PD-1-expressing CD8 T cells dropped. Our data suggest that oligometastatic patients, where a large proportion of the tumor mass can be irradiated, are good candidates to improve ICB responses by RT, even in the case of an unfavorable pretreatment immune signature, after progression on anti-PD-1, and despite advanced age. Besides repeated irradiation, T cell epitope-based immunotherapies (e.g., vaccination) may prolong antitumor responses even in patients with unfavorable pretreatment immune signature

Intraoperative radiotherapy boost as part of breast-conservation therapy for breast cancer: a single-institution retrospective analysis

Background!#!There are currently no data from randomized controlled trials on the use of intraoperative radiotherapy (IORT) as a tumor bed boost as part of a breast-conservation approach for breast cancer. This study retrospectively reviewed the safety and efficacy of IORT as a boost treatment at a tertiary cancer center.!##!Methods!#!From 2015 to 2019, patients underwent breast-conserving surgery with axillary lymph node staging and a single dose of 20 Gy IORT with 50-kV photons, followed by whole-breast irradiation (WBI) and adjuvant systemic therapy (if applicable). Patients were followed for assessment of acute and late toxicities (using the Common Terminology Criteria for Adverse Events version 5.0) at 3-6-month intervals. Outcomes included ipsilateral (IBTR) and contralateral breast progression-free survival (CBE), distant metastasis-free survival (DMFS), and overall survival (OS).!##!Results!#!Median follow-up for the 214 patients was 28 (range 2-59) months. Most patients had T1 disease (n = 124) and were clinically node negative. Only few patients had high-grade and/or triple-negative disease. The vast majority of patients underwent sentinel node biopsy, and 32 (15%) required re-resection for initially positive margins. Finally, all tumor bed margins were clear. Nine (4.2%) and 48 (22.4%) patients underwent neoadjuvant and adjuvant chemotherapy, respectively. WBI was predominantly performed as conventionally fractionated WBI (n = 187, 87.4%), and the median time from BCS to WBI was 54.5 days. IORT was delivered with a single dose of 20 Gy. The median WBI dose was 50 Gy (range 29.4-50.4 Gy). No patients experienced grade 4 events; acute grade 3 toxicities were limited to 17 (8%) cases of radiation dermatitis. Postoperative toxicities were mild. After WBI only one case of late grade ≥ 2 events was reported. There were two recurrences in the tumor bed and one contralateral breast event.!##!Conclusion!#!This investigation provides additional preliminary data supporting the using of IORT in the boost setting and corroborates the existing literature. These encouraging results should be prospectively validated by the eventual publication of randomized studies such as TARGIT‑B

Additional file 4: of Identification of a blood-borne miRNA signature of synovial sarcoma

Illustration of the miRNA-expression levels of the two active synovial sarcoma patients who received chemotherapy (Patient 2 and 3 of the screening cohort of active synovial sarcoma patients as depicted in Additional file 3 ) marked with a triangle, patients receiving anticoagulation (Patient 3 of the screening cohort of active synovial sarcoma patients and Patient 1 of the independent cohort of active synovial sarcoma patients as depicted in Additional file 3 ) marked in green and patients receiving radiotherapy/presenting localized disease (Patient 1 of the screening cohort of active synovial sarcoma patients as depicted in Additional file 3 ) marked in red. A, C, E, G, I, K and M include the screening cohort of active synovial sarcoma patients, B, D, F, H, J, L and N depict the independent cohort (IC) of synovial sarcoma patients. (JPEG 5044 kb

Additional file 5: of Identification of a blood-borne miRNA signature of synovial sarcoma

Comparison of whole blood miRNA expression levels of patients with active synovial sarcoma and miRNA expression levels of corresponding synovial sarcoma tissue. MiRNA-expression of patients with synovial sarcoma expressing SS18-SSX2 are marked in purple. A. miR-99a-5p. B. miR-146b-5p. C. miR-148b-3p. D. miR-195-5p. E. miR-223-3p. F. miR-500b-3p. G. miR-505-3p. (JPEG 2837 kb

Additional file 3: of Identification of a blood-borne miRNA signature of synovial sarcoma

Disease and therapy status of sarcoma patients. M0 = localized disease. M1 = metastatic disease. Current chemotherapy/radiotherapy involves treatment within the last 6 weeks. (PPTX 67 kb

Additional file 1: of Identification of a blood-borne miRNA signature of synovial sarcoma

Demographic patient data and blood count of patients with active sarcoma and control groups. Demographic patient data (age, BMI) and blood count (hemoglobin level, platelet count and leukocyte count) of patients with active synovial sarcoma compared to healthy donors, patients with synovial sarcoma in remission and patients with active leiomyosarcoma, MPNST, Ewing sarcoma and liposarcoma. Data are presented as mean value ± standard error of mean (SEM). p- values were determined using a Student’s t-test for independent samples. Hb = Hemoglobin. BMI = Body Mass Index. (PPTX 68 kb

Additional file 2: of Identification of a blood-borne miRNA signature of synovial sarcoma

Demographic patient data and blood count of patients with active sarcoma (Individual Cohort (IC)) and control groups. Demographic patient data (age, BMI) and blood count (hemoglobin level, platelet count and leukocyte count) of patients with active synovial sarcoma (Individual Cohort (IC)) compared to healthy donors and patients with synovial sarcoma in remission. Data are presented as mean value ± standard error of mean (SEM). p- values were determined using a Student’s t-test for independent samples. Hb = Hemoglobin. BMI = Body Mass Index. IC = Independent Cohort. (PPTX 66 kb