Rituximab-Associated Liver Toxicity Without Known Viral Reactivation.

Rituximab is a targeted immunotherapeutic agent that has demonstrated efficacy in treating CD20+ B-cell neoplasms as well as other lymphoproliferative and autoimmune disorders. A major adverse effect of rituximab is hepatocellular injury attributed to hepatitis B viral reactivation, necessitating viral titers before treatment. In this case report, we illustrate the rare presentation of a patient with marginal zone B-cell lymphoma who experienced symptomatic liver injury with a peak 15-fold aminotransferase elevation following his first dose of rituximab, without evidence of viral reactivation.

A Rare Case of Duodenal Adenocarcinoma With Brain Metastasis.

Small bowel malignancies are relatively rare, accounting for only 3% of all gastrointestinal cancers. Duodenum is the most common location among small bowel cancers, followed by Jejunum and then Ileum. Duodenal adenocarcinoma produces vague symptoms, leading to late presentation and a poor prognosis compared to similarly staged colon cancer. It is rare to have brain metastasis in duodenal adenocarcinoma, and not many case reports have been reported. Only approximately 6% of patients with gastrointestinal malignancy have brain metastasis. Here, we present a case of a 64-year-old female patient diagnosed initially with stage IV duodenal adenocarcinoma presenting with duodenal mass, abdominal lymphadenopathy, and liver metastasis. She had excellent systemic control for over two years with systemic chemotherapy, with a close to complete response on follow-up imaging. She presented with a 2 cm left frontal mass biopsy consistent with duodenal adenocarcinoma metastasis. She underwent resection of the left frontal tumor and gamma knife to the resection cavity. She continues to have good systemic control of disease. This case highlights the rare possibility of brain metastasis with duodenal adenocarcinoma, especially in patients who have good systemic control with chemotherapy.

Radiomic biomarkers from chest computed tomography are assistive in immunotherapy response prediction for non-small cell lung cancer.

Background: Immunotherapies, such as programmed death 1/programmed death ligand 1 (PD-1/PD-L1) antibodies have been shown to improve overall and progression-free survival (PFS) in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). However, not all patients derive a meaningful clinical benefit. Additionally, patients receiving anti-PD-1/PD-L1 therapy can experience immune-related adverse events (irAEs). Clinically significant irAEs may require temporary pause or discontinuation of treatment. Having a tool to identify patients who may not benefit and/or are at risk for developing severe irAEs from immunotherapy will aid in an informed decision-making process for the patients and their physicians. Methods: Computed tomography (CT) scans and clinical data were retrospectively collected for this study to develop three prediction models using (I) radiomic features, (II) clinical features, and (III) radiomic and clinical features combined. Each subject had 6 clinical features and 849 radiomic features extracted. Selected features were run through an artificial neural network (NN) trained on 70% of the cohort, maintaining the case and control ratio. The NN was assessed by calculating the area-under-the-receiver-operating-characteristic curve (AUC-ROC), area-under-the-precision-recall curve (AUC-PR), sensitivity, and specificity. Results: A cohort of 132 subjects, of which 43 (33%) had a PFS ≤90 days and 89 (67%) of which had a PFS >90 days was used to develop the prediction models. The radiomic model was able to predict progression-free survival with a training AUC-ROC of 87% and testing AUC-ROC, sensitivity, and specificity of 83%, 75%, and 81%, respectively. In this cohort, the clinical and radiomic combined features did add a slight increase in the specificity (85%) but with a decrease in sensitivity (75%) and AUC-ROC (81%). Conclusions: Whole lung segmentation and feature extraction can identify those that would see a benefit from anti-PD-1/PD-L1 therapy.

Pharmacological ascorbate improves the response to platinum-based chemotherapy in advanced stage non-small cell lung cancer.

PURPOSE: Platinum-based chemotherapy with or without immunotherapy is the mainstay of treatment for advanced stage non-small cell lung cancer (NSCLC) lacking a molecular driver alteration. Pre-clinical studies have reported that pharmacological ascorbate (P-AscH-) enhances NSCLC response to platinum-based therapy. We conducted a phase II clinical trial combining P-AscH- with carboplatin-paclitaxel chemotherapy. EXPERIMENTAL DESIGN: Chemotherapy naïve advanced stage NSCLC patients received 75 g ascorbate twice per week intravenously with carboplatin and paclitaxel every three weeks for four cycles. The primary endpoint was to improve tumor response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 compared to the historical control of 20%. The trial was conducted as an optimal Simon's two-stage design. Blood samples were collected for exploratory analyses. RESULTS: The study enrolled 38 patients and met its primary endpoint with an objective response rate of 34.2% (p = 0.03). All were confirmed partial responses (cPR). The disease control rate was 84.2% (stable disease + cPR). Median progression-free and overall survival were 5.7 months and 12.8 months, respectively. Treatment-related adverse events (TRAE) included one grade 5 (neutropenic fever) and five grade 4 events (cytopenias). Cytokine and chemokine data suggest that the combination elicits an immune response. Immunophenotyping of peripheral blood mononuclear cells demonstrated an increase in effector CD8 T-cells in patients with a progression-free survival (PFS) ≥ 6 months. CONCLUSIONS: The addition of P-AscH- to platinum-based chemotherapy improved tumor response in advanced stage NSCLC. P-AscH- appears to alter the host immune response and needs further investigation as a potential adjuvant to immunotherapy.

Non-Conventional Treatments for Conventional Chondrosarcoma.

Chondrosarcomas are the most common malignant tumors of the cartilage, are seen predominantly in adults, and have varied clinical behavior. The majority of them affect the medullary canal of long bones and pelvic bones. The prognosis of chondrosarcoma is closely related to histological grading; however, the grading is subject to interobserver variability. Conventional chondrosarcomas are overall considered to be chemotherapy- and radiation-resistant, resulting in limited treatment options. The majority of advanced conventional chondrosarcomas are treated with chemotherapy without any survival benefit. Recent studies have evaluated molecular genetic findings which have improved the understanding of chondrosarcoma biology. Newer therapeutic targets are desperately needed. In this review article, we explore ongoing clinical trials evaluating novel ways of treating advanced conventional chondrosarcoma.

Linagliptin-associated bullous pemphigoid treated with rituximab.

Dipeptidyl peptidase 4 (DPP-4) inhibitors are increasingly used these days in management of diabetes. There has been reported in a few case reports of increasing association between DPP-4 inhibitor use and bullous pemphigoid (BP). We report a case of association between linagliptin use and BP and subsequent treatment with rituximab.

Isolated brachiocephalic artery dissection presenting as acute stroke.

Isolated brachiocephalic artery dissection is an extremely rare condition. Its presentation as an acute stroke can pose a significant diagnostic challenge in patients because of its rarity. We present a case of isolated spontaneous brachiocephalic artery dissection presenting as acute cerebrovascular accident. This case also illustrates the treatment dilemma brachiocephalic artery dissection can present, whether to choose antithrombotic/anticoagulation therapy and/or surgery, and also the dilemma in blood pressure management.