Chemotherapy and Immune Checkpoint Inhibitors in a Case of SMARCA4-dUT: A Case Report and Review of Literature.

SMARCA4-deficient undifferentiated tumors (SMARCA4-dUT) are infrequently occurring aggressive neoplasms found predominantly in young male smokers. These tumors are distinguished by the loss of expression of Brahma-related gene 1 (BRG1) due to a deactivating mutation of SMARCA4. Immunophenotype can be variable but characteristically lack the expression of BRG1. SMARCA4-dUT has a poor prognosis and generally progresses or recurs. The median survival is around 6 months. Here, we report a case of a 36-year-old male smoker who presents with multiple right-sided lung masses. The patient was found to have a loss of SMARAC4 and SMARCA2 along with the absence of markers of vascular, melanocytic, lymphoid, keratin, or myogenic origin. Tumor size was reduced significantly after 3 cycles of carboplatin and 1 cycle of pembrolizumab. From reviewing the literature and the clinical course in our case, we suggest combination chemotherapy plus immune checkpoint inhibitor (ICI) therapy to be the first choice of therapy for treating SMARCA4-dUT of lungs. Further research and studies are needed to evaluate the response to ICI therapy alone or combination therapy (chemotherapy plus ICI).

A Hematological Menace: Multiple Venous Thrombosis Complicated by Acquired Factor VIII Deficiency.

BACKGROUND: Acquired hemophilia A (AHA) classically presents with spontaneous bleeding of mucosal sites, GI tract, and subcutaneous tissues, often leading to large hematomas and ecchymosis. Among documented cases, 50% are idiopathic and few have been associated with trauma or surgery. We present a case of life-threatening bleeding caused by AHA, following trauma and complicated by multiple venous thrombi. CASE REPORT: A 21-year-old man presented with multiple injuries secondary to trauma leading to extensive life-saving surgery. Two weeks post-operatively, he developed multiple deep venous thrombi and was started on anticoagulation. Twenty-four days post-operatively, he started bleeding from multiple mucosal sites and developed an abdominal hematoma. Anticoagulation was stopped, with administration of fresh frozen plasma and vitamin K. Diagnosis of AHA was made based on low factor VIII level and presence of factor VIII inhibitors after an appropriate battery of tests ruled out other possible diagnoses. He was started on steroids and recombinant factor VIIa, leading to immediate improvement. Once stable, Rituximab infusions resulted in decreasing factor VIII inhibitor levels, with gradual normalization of PTT. CONCLUSIONS: AHA remains a diagnostic challenge because of its rarity, leading to delay in diagnosis and causing significant morbidity and mortality. Elevated PTT relative to PT/INR is a strong clue which should be followed by mixing studies. Very few cases have been associated with surgery or trauma and relatively few large, controlled trials have compared different treatment modalities for AHA. Growing evidence supports anti-CD20 (Rituximab) as an effective treatment option, as in this case.

Phase II trial of erlotinib and capecitabine for patients with previously untreated metastatic colorectal cancer.

BACKGROUND: This Simon 2-stage phase II trial was designed to document antitumor activity of capecitabine in combination with erlotinib in patients with previously untreated metastatic colorectal cancer (CRC). PATIENTS AND METHODS: Time to tumor progression, objective response rate, and time to treatment failure were to be assessed. Secondary objectives included determination of toxicity. This trial was closed prematurely because of slower-than-expected accrual. Thirteen patients were enrolled, and all are off protocol treatment at the time of this report. RESULTS: Notably, 4 subjects discontinued therapy because of adverse events. Of 10 evaluable patients, 1 attained a complete response, 1 attained a partial response, 3 had stable disease, and 5 had progressive disease. Median time to disease progression was 21 weeks, with a range of 8-85 weeks. Overall survival ranged from 12 weeks to 182 weeks, with a median of 76 weeks. CONCLUSION: The toxicities and challenge to complete accrual observed in this trial are consistent with the experience of others attempting to develop erlotinib as part of combination treatment for advanced CRC.