The Effect of Concurrent Stereotactic Body Radiation and Anti-PD-1 Therapy for Recurrent Metastatic Sarcoma.

Patients diagnosed with metastatic sarcoma have limited options for achieving both local and distant tumor control. While SBRT can achieve local control, distant response rates remain low. There is limited evidence demonstrating the safety and efficacy for combining SBRT with concurrent PD-1 checkpoint blockade in metastatic sarcoma. In this prospective case-series, we examined five patients with metastatic sarcoma on pembrolizumab treated concurrently with SBRT from July 1, 2016-October 30, 2018. Acute and chronic toxicity were recorded using Common Terminology Criteria for Adverse Events (CTCAE, version 5.0). SBRT-treated tumor control was assessed using Response Evaluation Criteria in Solid Tumors (RECIST version 1.1). With median follow-up of 14.9 months, three patients with undifferentiated pleomorphic sarcoma, one with intimal, and one with chondroblastic osteosarcoma received SBRT with concurrent pembrolizumab to 10 sites of metastatic disease. No grade 5 toxicities were observed. There was a single incidence of transient grade 4 lymphopenia which resolved without intervention. Grade 3 toxicities included anemia, thrombocytopenia, lymphopenia and colitis. One tumor demonstrated local progression after SBRT, and all others remained stable or with response. In conclusion, combining SBRT with PD-1 inhibition appeared to be safe in this patient population. Expected high rates of treated-tumor local control after SBRT were observed. Two of five patients demonstrated either enhanced local tumor regression, or possible abscopal effect.

A Single-Institution Analysis of Thymic Carcinoma Treated with Multi-Modality Therapy.

PURPOSE: Review of our experience in treating thymic carcinoma patients using a combination of surgery, chemotherapy and radiation therapy. METHODS: An institutional review of thymic carcinoma patients treated between 2007 and 2014 was performed analyzing clinical characteristics, treatment intent, surgical margin status, and radiation treatment dose. Survival curves were generated using the Kaplan-Meier method. RESULTS: Nine individuals were treated for newly diagnosed thymic carcinoma. Three patients had unresectable disease at presentation; two of these were treated with definitive chemoradiation therapy while another received neoadjuvant chemotherapy. Seven subjects underwent surgical resection (one after neoadjuvant chemotherapy) with pathological staging ranging from IIa - IVb disease. Patients were planned for adjuvant radiotherapy followed by chemotherapy; however, one developed liver metastases prior to initiating radiotherapy and was therefore treated with palliative chemotherapy alone. A second patient was non-compliant with radiation treatments and was considered as treated with palliative chemotherapy alone. Of the seven patients who completed definitive treatment, median time to progression and overall survival has yet to be reached. Only one of these patients developed progressive disease 10 months after completing treatment and eventually succumbed to disease 41 months after completing definitive therapy. With a median follow up of 30 months, two year overall survival is 67% for all patients. CONCLUSION: Resection with an emphasis on best possible oncologic margins, followed by radiation and chemotherapy remains an effective treatment strategy for advanced stage thymic carcinoma. In patients who present with unresectable tumors, neoadjuvant chemotherapy or definitive chemoradiation therapy may also be considered as viable treatment strategies.

Induction of regulatory T-cells from memory T-cells is perturbed during acute exacerbation of multiple sclerosis.

Regulatory T-cells (Tregs) are vital for maintaining immunological self-tolerance, and the transcription factor FOXP3 is considered critical for their development and function. Peripheral Treg induction may significantly contribute to the total Treg pool in healthy adults, and this pathway may be enhanced in thymic-deficient conditions like multiple sclerosis (MS). Here, we evaluated iTreg formation from memory versus naïve CD4(+)CD25(-) T-cell precursors. We report the novel finding that memory T-cells readily expressed CD25 and FOXP3, and demonstrated significantly greater suppressive function. Additionally, the CD25(-)FOXP3(-) fraction of stimulated memory T-cells also displayed robust suppression not observed in naïve counterparts or ex vivo resting (CD25(-)) T-cells. This regulatory population was present in both healthy subjects and clinically-quiescent MS patients, but was specifically deficient during disease exacerbation. These studies indicate that iTreg development and function are precursor dependent. Furthermore, MS quiescence appears to correlate with restoration of suppressive function in memory-derived CD4(+)CD25(-)FOXP3(-) iTregs.