Post-irradiation angiosarcoma of the breast: clinical presentation and outcome in a series of six cases.

Angiosarcoma of the breast represents 1% of all soft tissue breast tumors. With breast-conserving therapy (BCT) as standard in the last three decades, a new type of angiosarcoma has been reported: post-irradiation angiosarcoma (PIAS). A recent study based on the SEER database found an absolute risk for PIAS of seven per 100,000 person-years for BCT patients. We present a retrospective analysis of the clinical characteristics, treatment, and outcome of six cases of PIAS treated in our institution from 1995 to 2010. Mean age at diagnosis of breast cancer was 68 years (range 54-76 years). All patients underwent BCT. Adjuvant radiotherapy was given to all patients at doses of 45-50 Gy. Mean time from adjuvant radiotherapy to PIAS was 9.2 years (range 5.3-13.8 years); median follow-up from diagnosis of PIAS was 41.8 months (range 11-102 months). At diagnosis of PIAS, mean age of patients was 78 years (range 63-87 years). All patients underwent simple mastectomy, following which one patient received chemotherapy with doxorubicin and three patients received radiation therapy. Two patients developed local recurrence, one concurrent with metastatic disease. Another patient was diagnosed after 24 months with extensive small cell lung cancer and died of disease without recurrence of PIAS. Four patients are alive without evidence of recurrence. PIAS is a very rare sarcoma occurring after BCT. Careful observation after adjuvant radiotherapy is required. Standard treatment is the surgery with simple mastectomy and adjuvant radiotherapy; chemotherapy may be considered for more advanced cases.

The role of tumor-infiltrating lymphocytes (TILs) as a predictive biomarker of response to anti-PD1 therapy in patients with metastatic non-small cell lung cancer or metastatic melanoma.

Immunotherapy plays an important role in cancer treatment. Biomarkers that can predict response, including tumor-infiltrating lymphocytes (TILs), are in the spotlight of many studies. This cohort study was designed to evaluate the role of CD4+ and CD8+ TILs as predictive factors for response to anti PD-1 treatment in patients with metastatic non-small cell lung cancer (NSCLC) or metastatic melanoma. We evaluated the expression of CD4+ and CD8+ TILs in tissue samples of 56 patients with metastatic NSCLC or melanoma treated with anti-PD1 immunotherapy. The study included 30 patients with melanoma and 26 with NSCLC. An association was found between CD8+/CD4+ TILs ratio and response to anti-PD1 treatment in both cancers. Regarding melanoma patients, ratios of CD8+/CD4+ lower than 2 predicted lack of response to treatment (0%) (p = 0.006), while CD8+/CD4+ ratios higher than 2.7 had an 81.3% response rate (p = 0.0001). In addition, we found that the presence of more than 1900/mm2 of CD8+ lymphocytes in the melanoma tumor predicted a 90% response to therapy. In the metastatic NSCLC group, tumors with CD8+ lymphocyte count under 886/mm2 showed low response rates (16.7%, p = 0.046). When the CD8+ lymphocyte count was in the range of 886-1899/mm2, the response rate was high (60%, p = 0.017). In CD8+/CD4+ ratios lower than 2, the response rate was low (13.3%), and in ratios higher than 2, response rates ranged between 43 and 50% (p = 0.035). The use of CD8+/CD4+ TILs ratios in tumor biopsies may predict response to anti-PD1 treatment in metastatic melanoma and NSCLC.