Prospective Trial of Neutrophil/Lymphocyte Ratio and Other Blood Counts as Biomarkers of Survival among Patients with High-Grade Soft Tissue Sarcomas Treated with Pegylated Liposomal Doxorubicin and Ifosfamide

Several studies have reported an association between levels of circulating blood cells, in particular the neutrophil to lymphocyte ratio (absolute neutrophil count (ANC)/absolute lymphocyte count (ALC)) and outcomes in patients with cancer. In the current study, the association between lymphocyte, neutrophil, monocyte, and platelet counts and survival was examined in a prospective trial of preoperative pegylated-liposomal doxorubicin and ifosfamide for high-grade soft-tissue sarcomas. A statistically significant association between overall survival, but not progression free-survival, was observed with the ANC/ALC ratio at a cutoff value of ≥2 and a statistically significant trend using a cutoff of ≥5. Our results suggest that a balance between the lymphocyte count and the number of circulating myeloid cells that can suppress lymphocyte function may be predictive of survival in patients with soft-tissue sarcomas. Future research should therefore examine the role of lymphocyte-myeloid cell balance in sarcoma biology

Gene Expression and Mutational Profile in BAP-1 Inactivated Melanocytic Lesions of Progressive Malignancy from a Patient with Multiple Lesions

BAP-1 (BRCA1-associated protein 1) inactivated melanocytic lesions are a group of familial or sporadic lesions with unique histology and molecular features. They are of great clinical interest, at least in part due to the potential for malignant transformation and association with a familial cancer predisposition syndrome. Here, we describe a patient with multiple spatially and temporally distinct melanocytic lesions with loss of BAP1 expression by immunohistochemistry. RNA sequencing was performed on three independent lesions spanning the morphologic spectrum: a benign nevus, an atypical tumor, and a melanoma arising from a pre-existing BAP1-inactivated nevus. The three lesions demonstrated largely distinct gene expression and mutational profiles. Gene expression analysis revealed that genes involved in receptor protein kinase pathways were progressively upregulated from nevus to melanoma. Moreover, a clear enrichment of genes regulated in response to UV radiation was found in the melanoma from this patient, as well as upregulation of MAPK pathway-related genes and several transcription factors related to melanomagenesis

Near complete response to Pembrolizumab in microsatellite-stable metastatic sebaceous carcinoma

Abstract Background Sebaceous carcinoma is an aggressive adnexal skin tumor with a predilection for the eyelids and sebaceous glands of the head and neck. Case presentation A 73 year-old man presented with confusion and was found to have widely disseminated sebaceous carcinoma with metastases to brain, lungs, liver, bowel, lymph nodes, and bone. Following initial treatment of the brain metastases with surgery he received post-operative radiosurgery. He then began systemic immunotherapy with pembrolizumab. After 6 months, he developed a near complete response to therapy by irRECIST and RECIST v.1.1. The response was associated with circulating CD8+ T cells with central memory (CM) and effector memory (EM) phenotype and mature CD16 + CD57+ NK cells. During treatment the patient developed adrenal insufficiency requiring high-dose systemic corticosteroids and later adrenal replacement therapy. After 12-months of follow-up he showed imaging evidence of progression in liver, mediastinum, and abdominal lymph nodes. Given persistent, strong PD-L1 expression he resumed pembrolizumab therapy and showed radiographic evidence of an ongoing response to therapy. Conclusions This is the first report describing objective clinical and radiographic responses following immunotherapy for widely metastatic sebaceous carcinoma. The dramatic therapeutic response to pembrolizumab was associated with peripheral blood circulating memory T cells and mature Natural Killer cells after 6 months (24 weeks) of therapy. This report supports prospective clinical trials of anti-PD1 checkpoint blockade for metastatic sebaceous carcinoma

Additional file 1 of Near complete response to Pembrolizumab in microsatellite-stable metastatic sebaceous carcinoma

: Figure S1. Coronal and axial contrast enhanced CT-images were obtained at 13 months and shows mediastinal and liver recurrence. Repeat imaging at 15 months shows increased size of the mediastinal lesion (top row), and decreased size of the hepatic lesion (bottom row), suggesting mixed immune related responses and pseudoprogression. (DOCX 600 kb

SALVO: Single Arm Trial of Ipilimumab and Nivolumab as Adjuvant Therapy for Resected Mucosal Melanoma.

BACKGROUND: Mucosal melanoma is a rare, aggressive form of melanoma with extremely high recurrence rates despite definitive surgical resection with curative intent. Currently there is no consensus on adjuvant therapy. Data on checkpoint inhibitors (CPI) for adjuvant therapy is lacking. METHODS: We performed a single arm, multicenter clinical trial using flip dose ipilimumab (1mg/kg q3w x4 cycles), and nivolumab (3 mg/kg q3w x4 cycles), then Nivolumab 480 mg q4w x 11 cycles to complete a year of adjuvant therapy. Participants must have had R0/R1 resectionregistration, no prior systemic therapy (adjuvant radiation allowed), ECOG 0/1, no uncontrolled autoimmune disease or other invasive cancer. Patients were recruited through the Midwest Melanoma Partnership/Hoosier Oncology Network. RESULTS: From Sept 2017 to August 2021 35 patients enrolled. Of these, 29 (83%) had R0 resections, and 7 (20%) received adjuvant radiation. Median age was 67 years, 21 (60.0%) female. Relapse-free survival rates at 1 and 2 years were 50% (95% CI 31-66%) and 37% (95% CI 19-55%), respectively. Overall survival rates at 1 and 2 years were 87% (95% CI 68-95%) and 68% (95% CI 46-83%), respectively. Median RFS was 14.3 m (95% CI 5.7-25.8). Most common grade 3 toxicities were diarrhea (14%), hypertension (14%), and hyponatremia (11%), with no grade 4/5 toxicities. CONCLUSIONS: Flip dose ipilimumab and nivolumab after resection of mucosal melanoma is associated with outcomes improved over that of surgical resection alone. Long term follow up, subgroup analyses and correlative studies are ongoing