Palbociclib in Patients With Soft Tissue Sarcoma With CDK4 Amplifications: Results From the Targeted Agent and Profiling Utilization Registry Study.

PURPOSE: Targeted Agent and Profiling Utilization Registry (TAPUR) is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations known to be drug targets. Results of a cohort of patients with soft tissue sarcoma with cyclin-dependent kinase 4 (CDK4) amplification treated with palbociclib are reported. METHODS: Eligible patients had measurable disease, Eastern Cooperative Oncology Group performance status 0 to 2, adequate organ function, and no standard treatment options. The primary end point was disease control (DC), defined as objective response (OR) or stable disease (SD) of at least 16+ weeks duration (SD16+) according to RECIST v1.1. The DC rate was estimated with a 90% CI. Secondary end points included OR, progression-free survival (PFS), overall survival (OS), duration of response, duration of SD, and safety. RESULTS: Forty-two patients with CDK4 amplification were enrolled. One patient was not evaluable for efficacy. One patient with partial response and 18 with SD16+ were observed for DC and OR rates of 46% (90% CI, 36 to 100) and 2% (95% CI, <1 to 13), respectively. Median PFS was 16 weeks (95% CI, 9 to 28) and median OS was 69 weeks (95% CI, 31 to 111) for evaluable patients. Twenty patients had at least one grade 3 to 4 adverse event (AE) at least possibly related to palbociclib, including alanine aminotransferase increase, anemia, fatigue, hypophosphatemia, leukopenia, neutropenia, and thrombocytopenia. No serious AEs were reported. CONCLUSION: Palbociclib met prespecified criteria to declare a signal of antitumor activity in patients with sarcoma and CDK4 amplification.

Ectopic production of beta-hCG in anal cancer: A case report.

Key Clinical Message: Beta-hCG-producing anal cancer, though rare, poses significant diagnostic challenges and may resist standard therapies. Recognizing the potential for hormone production in anal cancer is important, as it underscores the need for more specialized diagnostic techniques and tailored treatments. Abstract: This case report describes the second reported case of ectopic production of beta-hCG in anal cancer. A 53-year-old female presented with a new anal lesion. Biopsy showed a poorly differentiated squamous cell cancer (SCC) with undifferentiated sarcomatoid features, stage IIIA (cT2cN1cM0). Before starting concurrent chemotherapy and radiation, the patient had a positive urine pregnancy test. The beta-human chorionic gonadotropin (beta-hCG) production was attributed to the tumor, and upon completion of treatment, beta-hCG normalized. Six weeks from treatment completion, recurrence was noted along with a positive beta-hCG urine test. This case aims to highlight beta-hCG as an ectopic hormone that can indicate the presence of squamous cell anal cancer and discuss the potential implications it may have on management.

Cocaine-induced microangiopathic hemolytic anemia mimicking idiopathic thrombotic thrombocytopenic purpura: a case report and review of the literature.

Our understanding of the pathogenesis of idiopathic thrombotic thrombocytopenic purpura (TTP) has increased, but remains incomplete, particularly with respect to cases of suspected TTP that are either unresponsive to therapeutic plasma exchange (TPE) or have normal ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type 1 motif 13) activity. A 53-year-old woman presented with severe anemia (hemoglobin 1.8 g/dL) and clinical and laboratory findings consistent with TTP in conjunction with acute cocaine use. The patient was treated with TPE until the pre-treatment ADAMTS13 activity was reported as normal without evidence of an inhibitor. TPE was stopped and the patient continued to improve without treatment. This patient's microangiopathic hemolytic anemia (MAHA) appeared to be secondary to cocaine use. The proposed pathogenesis is likely a combination of cocaine-induced vasoconstriction, vascular damage, platelet activation, and procoagulation. This is the fifth published report of cocaine-induced MAHA and to our knowledge the first with ADAMTS13 testing.

Immature platelet fraction can help adjust therapy in refractory thrombotic microangiopathic hemolytic anemia cases.

Hemolytic uremic syndrome and thrombotic thrombocytopenic purpura share presentations, therapies and diagnostic evaluation of activity of the metalloprotease ADAMTS13. Here, we report a patient with the clinical presentation of thrombotic microangiopathic thrombocytopenia, normal ADAMTS13, prolonged regimen of therapeutic plasma exchanges (TPEs), bone marrow biopsy showing adequate tri-lineage hematopoiesis, and low immature platelet fraction (%-IPF) (<1.0%). Low %-IPF suggested platelet hypoproduction; high steroid therapy, in conjunction with TPEs, resulted in the recovery of platelet count. Further investigation is needed to determine if %-IPF can guide therapy in cases of microangiopathic hemolytic anemias refractory to therapy.