Acquired von Willebrand syndrome in a patient with monoclonal gammopathy of unknown significance: A case report.

Monoclonal gammopathy of uncertain significance associated acquired von Willebrand syndrome is a serious bleeding condition driven by immunological clearance of von Willebrand factor and has limited treatment options. We present a patient who achieved durable remission through eradication of the monoclonal paraprotein with clonal directed therapy with bortezomib.

Case report: Uridine triacetate in the management of delayed onset 5-fluorouracil toxicity: A case report and review of literature.

5-fluorouracil (5FU) and capecitabine are fluoropyrimidine anti-neoplastic drugs commonly used in the treatment of different types of cancer. Hereditary dihydropyrimdine deaminase (DPD), thymidylate synthase mutations and drug overdose may lead to life-threatening toxicities. Uridine triacetate (UTA) is an emergency treatment for overdoses and early onset, severe or life-threatening toxicities from fluoropyrimidines. It is approved for use in adults and children within 96 h of last fluoropyrimidine administration. We present the case of a 64-year-old male treated with 5-FU and oxaliplatin as adjuvant systemic therapy for stage IIIA rectal cancer who developed delayed central nervous system toxicity 18 days after initiating chemotherapy. He had rapidly worsening encephalopathy and ataxia. Laboratory workups, MRI brain and EEG were negative. He was started on UTA with concerns of 5-FU toxicity due to the life-threatening nature of his condition even beyond the recommended 96-h time cut-off. He had rapid improvement in clinical status and resolution of encephalopathy. DPD deficiency testing later resulted as heterozygous for IVS14+1G>A allele indicating enzyme deficiency. This report demonstrates the importance of identifying delayed side effects with fluoropyrimidine therapy and potential treatment for reversing these effects. We also did an extensive literature review and obtained reports from the uridine triacetate clinical trials on patients receiving UTA after the 96-h cut-off. Based on our experience and previous published reports, a patient developing life-threatening delayed 5-FU toxicity should also be considered for UTA on a case-by-case basis.

Clinical Benefit of Comprehensive Genomic Profiling for Advanced Cancers in India.

PURPOSE: Comprehensive genomic profiling (CGP) assay is increasingly used in low-middle-income countries to detect clinically relevant genomic alterations despite its clinical benefits not being well known. Here, we describe the proportion of patients with advanced cancer in India who received targeted therapy for an actionable genetic alteration identified on CGP assays. METHODS: This was a multicenter, retrospective cohort study in adult patients with advanced nonhematologic malignancies who underwent a CGP test. If patients received a targeted therapy for ≥ 6 months, they were considered to have obtained a clinical benefit from the medication, whereas those continuing for ≥ 12 months were considered to have attained an exceptional response. Descriptive statistics were used to describe the proportion of patients with subsequent targeted therapy. RESULTS: During 2019-2020, 12 medical oncologists provided CGP reports for 297 patients; 221 met the inclusion criteria. Patients received a median of two lines (range: 0-5) of prior systemic therapy. On the basis of the CGP assay, 21 patients (10%) received targeted therapy. Among them, 33% was for human epidermal growth factor receptor 2 (HER2) amplification (nonbreast cancer) and 19% for HER2 or epidermal growth factor receptor exon 20 insertion mutation (lung cancer). After excluding patients with HER2 or epidermal growth factor receptor exon 20 insertions, 8% of 217 patients received targeted therapy. In the overall cohort of 221 patients, clinical benefit was seen in nine patients (4%), of whom two were exceptional responders (1%). CONCLUSION: We observed that in a low-middle-income country setting, 10% of patients received targeted therapy on the basis of CGP assay. Only 4% of patients who underwent CGP testing obtained a clinical benefit.

Current Strategies for Extensive Stage Small Cell Lung Cancer Beyond First-line Therapy.

Extensive stage small cell lung cancer carries extremely poor prognosis and adding immune checkpoint inhibitor to platinum etoposide combination in first line only improved outcomes modestly. Once disease recurs, treatment response is only transient in nature. Various strategies that are being explored include dual checkpoint blockade, BiTE and CAR-T cell approaches. Immune checkpoint inhibitors are being combined with PARP inhibitors. Other approaches currently being investigated include liposomal irinotecan and combining known active agents for SCLC in relapsed setting such as newly approved lurbinectedin with doxorubicin, paclitaxel, irinotecan or topotecan with ATR inhibitor (Berzosertib). Temozolomide has also been tested in combination with a Parp inhibitor. New antibody or small molecule drug conjugates are being actively investigated, so is a biomarker based approach. Better understanding of small cell lung cancer disease biology via high through-put genomic, proteomic and methylation profiling offer glimpse of hope in our efforts to contain this deadly disease. A table of representative molecular targets under investigation is provided in the end.

Biliary tract large cell neuroendocrine carcinoma: current evidence.

BACKGROUND: Primary neuroendocrine carcinomas of the gallbladder and biliary tract are rare, with pure large cell neuroendocrine carcinomas (LCNEC) being exceedingly rare and with a particularly poor prognosis. METHODS: We performed a review of published data on biliary tract large cell neuroendocrine carcinomas in PubMed. RESULTS: Preliminary search revealed over 2000 results but we found only 12 cases of pure large cell neuroendocrine carcinomas of biliary tract noted in literature to date. Because it commonly presents with non-specific symptoms of abdominal pain and jaundice, diagnosis is made after resection with histo-pathological and immunohistochemical analysis. These cancers are particularly aggressive with high recurrence rates, most often presenting with metastasis to regional lymph nodes and/or the liver resulting in a poor prognosis. Overall, complete surgical excision with systemic chemotherapy is the treatment mainstay. If the cancer is unresectable due to multiple metastases, medical management with systemic chemotherapy is the primary treatment modality. CONCLUSION: The prognosis of hepatobiliary LCNEC remains poor with median survival of only 11 months from initial diagnosis. Studies focusing on high grade neuroendocrine carcinoma are needed to enhance our understanding of biology and therapeutics in this rare but aggressive cancer.