Hepatocellular Carcinoma: Advances in Systemic Therapy.

Hepatocellular carcinoma (HCC) is a prevalent primary liver cancer, representing over 90% of cases globally and ranking as the third leading cause of cancer-related death. This article reviews the evolving landscape of systemic therapies for advanced HCC, emphasizing recent advancements and their impact on patient outcomes. The advent of molecular targeted therapies has transformed HCC management, with sorafenib being the first FDA-approved molecular targeted therapy, setting a standard for a decade. However, recent breakthroughs involve the combination of atezolizumab and bevacizumab, demonstrating superior outcomes over sorafenib, leading to FDA approval in 2020. Another notable combination is tremelimumab and durvalumab, showing efficacy in a multinational phase III trial. Beyond these combinations, this article explores the role of other first-line treatments and subsequent therapies after progression. The evolving landscape of systemic therapies for HCC reflects a paradigm shift, with immunotherapy combinations emerging as key players alongside targeted therapies. This article highlights the complexity of treatment decisions, considering individual patient characteristics and disease etiology, and underscores the ongoing quest to optimize both systemic and local-regional therapies for improved long-term outcomes in HCC patients.

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.

Unilateral Ptosis in an Older Adult; a Rare Presentation of Primary Extranodal Hodgkin's Lymphoma.

Hodgkin lymphoma (HL) is a neoplasm arising from B cells characterized by the presence of Reed-Steenberg cells. Primary extranodal presentation is rare and accounts for less than 1% of all HL cases. In addition, the orbit is an uncommon site of extranodal HL, with only 9 cases reported in the literature. We present a case of an 84-year-old male who presented with right eye ptosis. He was diagnosed with stage IIE Orbital HL and treated with combined modalities of radiation and chemotherapy. He continues to be in complete remission after 1 year of therapy. Hodgkin's disease has an excellent prognosis, and recent data show it is curable in at least 80% of the patients. Extranodal involvement represents systemic dissemination of Hodgkin's disease in most cases and is usually considered an advanced-stage disease with a poor prognosis. In rare circumstances, extranodal involvement can be the primary manifestation. Unfortunately, there are only a few case reports and case series regarding this topic. We attempt to add another case to the literature emphasizing the prognosis and outcome of primary extranodal HL.

Management of Relapsed Hairy Cell Leukemia: A Systematic Review of Novel Agents and Targeted Therapies.

BACKGROUND: Hairy cell leukemia (HCL) responds well to purine analogs with an overall median relapse free survival of 11-16 years. Most patients can be retreated with the same or a different purine analog however a subset of patients will become resistant or develop cumulative toxicities. Novel agents such as Vemurafenib (BRAF kinase inhibitor), Bendamustine/Rituximab (BR), Moxetumomab pasudotox (anti CD-22 recombinant immunotoxin) and Ibrutinib have emerging roles in patients with relapsed HCL. METHODS: Five databases (PubMed, Embase, Cochrane Library, Web of Science and ClinicalTrials.gov) were searched using the following search terms: "hairy cell leukemia" or "leukemia, hairy cell" AND "relapse" or "recurrence". We included only prospective clinical trials with outcome data. RESULTS: Vemurafenib monotherapy was evaluated in two separate arms of a phase 2 trial. In the US arm (n=24), the ORR was 100% (CR 42%; PR 58%). In the Italian arm (n=26), the ORR was 96% (CR 35%; PR 62%). In a phase 2 study (n=25), the combination of vemurafenib and rituximab showed CR of 100%. The combination of BR achieved an ORR of 100% whereas CR was 50% and 67% at a bendamustine dose of 70mg/m2 (n=6) and 90 mg/m2 (n=6) respectively. In a phase 3 trial, moxetumomab pasudotox (n=80) had an ORR of 75% (CR 41%). Single agent Ibrutinib (n=37) had an ORR of 54%. Therapies were generally well tolerated. CONCLUSION: Novel agents have good efficacy in HCL in patients with multiple relapses.

Atezolizumab-Induced Bell's Palsy in a Patient With Small Cell Lung Cancer.

Immune checkpoint inhibitors are rapidly becoming popular therapeutic options for patients suffering from a number of malignancies. Atezolizumab is a programmed cell death ligand-1 inhibitor, and binding to this ligand decreases the ability of tumor cells to evade the immune system, resulting in self-tolerance. While inhibition of these molecules leads to increased T-cell destruction of tumor cells, it also may lead to autoimmune destruction of healthy cells. Neurotoxicity is a rare complication of immune checkpoint inhibitor therapy, and facial palsy as a complication of atezolizumab therapy has only been reported in one additional study. We present the case of a 68-year-old female with a history of small cell carcinoma of the lung presenting with sudden-onset facial palsy and numbness of the distal extremities in the setting of receiving atezolizumab immunotherapy. Our patient was managed with temporary cessation of her immunotherapy, oral prednisone, and supportive measures. Within 4 weeks, the patient had complete resolution of her facial palsy and was able to resume immunotherapy without further complication. Clinicians should be aware of this rare adverse effect in order to enact early management including temporary cessation of therapy to prevent morbidity in patients undergoing immunotherapy.

Presentation Patterns, Diagnostic Markers, Management Strategies, and Outcomes of IgD Multiple Myeloma: A Systematic Review of Literature.

Immunoglobulin (Ig) D multiple myeloma (MM) is a rare subtype of MM comprising 2% of all the cases. Malignant plasma cell invasion leads to signs and symptoms similar to other subtypes of MM. The synthesis rate of IgD is lower in IgD MM patients, making it very difficult to diagnose compared to other subtypes. As there is no available diagnostic test with 100% accuracy, the diagnosis of IgD MM is based on multiple factors. Recent advances in the treatment have resulted in a better overall survival for IgD MM patients. The aim of this systematic review was to summarize the data on presentation patterns, diagnosis modalities, management strategies, and outcomes in patients with IgD MM.