A review of treatments targeting DNA-repair gene defects in metastatic castration resistant prostate cancer.

Prostate cancer is the most common cancer in men. About 6% of those diagnosed will develop metastatic disease. Unfortunately, metastatic prostate cancer is fatal. Prostate cancer can be castration sensitive or castration resistant. Many treatments have been shown to improve progression free survival and overall survival in metastatic castration resistant prostate cancer (mCRPC). In recent years, studies have been exploring targeting mutations in the DNA Damage Repair (DDR) response that may amplify oncogenes. In this paper, we aim to discuss DDR, new approved targeted therapies, and the most recent clinical trials in the setting of metastatic CRPC.

Pericardial Relapse of Acute Lymphoblastic Leukemia (ALL).

Acute lymphoblastic leukemia (ALL) is a neoplasm of the B cell or T cell. Diagnosis is made by peripheral blood smear and bone marrow biopsy. Those with relapse/measurable residual disease (MRD) present with fever, weakness, fatigue, and easy bruising due to bone marrow infiltration (Kantarjian et al., 2017). A 59-year-old male with history of relapsed acute lymphoblastic leukemia and allogeneic stem cell transplant presented to the Emergency Department (ED) multiple times with shortness of breath. 2D Echo revealed recurrent pericardial effusion. His MRD was discovered in the pericardium. He underwent the creation of a pericardial window with cytology and culture which confirmed B cell lymphoblastic leukemia/lymphoma, consistent with relapsed disease. We present a case of a patient with B-ALL and MRD who presented with symptoms of shortness of breath. His MRD was discovered not in the bone marrow, but in the pericardium.

Timing of steroid initiation and response rates to immune checkpoint inhibitors in metastatic cancer.

BACKGROUND: Corticosteroids (CS) are the mainstay of immune-related adverse effect (irAE) management, as well as for other indications in cancer treatment. Previous studies evaluating whether CS affect immune checkpoint inhibitor (CPI) efficacy compared patients receiving CS versus no CS. However, there is a paucity of clinical data evaluating the timing of concomitant CS and CPI efficacy. METHODS: We retrospectively collected data from patients who received CS during CPI treatment at a single institution. Patients were in two cohorts based on timing of initiation of CS (≥2 months vs <2 months after initiating CPI). Patient characteristics, irAEs, cancer type, treatment type, treatment response/progression per RECIST V.1.1, and survival data were collected. Kaplan-Meier and Cox proportional hazard regression methods estimated HRs for the primary endpoint of progression-free survival (PFS) along with overall survival (OS). RESULTS: We identified 247 patients with metastatic cancer who received CS concurrently with CPIs. The median time on CS was 1.8 months. After adjusting for treatment type, tumor type, brain metastases, and irAEs, those treated with CS ≥2 months after starting CPI had a statistically significant longer PFS (HR=0.30, p<0.001), and OS (HR 0.34, p<0.0001) than those who received CS <2 months after starting CPI. Objective response rate (ORR) for patients on CS ≥2 months was 39.8%, versus ORR for patients <2 months was 14.7% (p value =<0.001) CONCLUSION: Our results suggest that early use of CS during CPI treatment significantly hinders CPI efficacy. This data needs to be validated prospectively. Future studies should focus on the immune mechanisms by which CSs affect T-cell function early in the CPI treatment course.

Utilization of Nivolumab in Adenoid Cystic Carcinoma After Progression on Platinum-Based Chemotherapy.

INTRODUCTION: Adenoid cystic carcinoma (ACC) is a rare malignant neoplasm within the secretory glands of the head and neck. Clinical findings include a lump on the palate, tongue, or bottom of the mouth. Because symptoms can be mild, patients go for long periods of time without investigation. ACC is diagnosed using histology. Treatment is by surgical resection because there is no effective chemotherapy. Radiation can be effective adjuvant therapy, and proton therapy and stereotactic irradiation can be used for those who are ineligible for surgery. Immunotherapy has clinical activity for those with metastatic head and neck cancers who progress on proton therapy. This case reviews the use of immunotherapy in a patient with ACC. CASE PRESENTATION: A man in his 20s presented with a 6-month history of nasal congestion, epistaxis, and sinus tenderness. Noncontrast computed tomography of the sinuses revealed a mass of the lateral wall of the nasal cavity, lateral wall of the maxillary sinus, and pterygoid plates. Positron emission tomography confirmed metastatic disease in the right iliac crest and right cervical lymph node; biopsy of the nasopharynx confirmed ACC. The patient received proton therapy and intensity-modulated radiotherapy and completed 2 Phase 1 trails but continued to have progressive disease. The patient started nivolumab and died 12 weeks later. CONCLUSION: The patient recently received proton therapy, intensity-modulated radiotherapy, and completed 2 Phase 1 trials but continued to have progressive disease.

COVID-19 and Cold Agglutinin Hemolytic Anemia.

Novel coronavirus disease 2019 (COVID-19) has spread throughout the world and has infected close to 4 million people. It commonly presents with fever, cough, and fatigue. Due to the high inflammatory response, it is suggested that the coagulation cascade is enhanced causing thrombotic events for many patients. We describe a patient with clinical features of cerebrovascular accident, as well as documented blood clots in bilateral upper extremities. Labs revealed the presence of cold agglutinin hemolytic anemia. The association between cold agglutinin autoimmune hemolytic anemia and thrombotic events in COVID-19 patients has not been well investigated. The patient unfortunately passed away within 48 hours after admission. This case stresses the importance of considering a full workup to diagnose autoimmune hemolytic anemia (AIHA) in COVID-19 patients with thromboses and possible implications for management.