Journal of Immunotherapy and Precision Oncology最新文献

Clear cell renal cell carcinoma (RCC) is commonly associated with alterations in the VHL tumor suppressor gene, resulting in upregulation of hypoxia-inducible factor pathways. Immune checkpoint inhibitors and vascular endothelial growth factor inhibitors are the mainstays of systemic treatment for metastatic RCC; however, most patients encounter disease progression after the initial response. The phase 3 clinical trial LITESPARK-005-belzutifan (HIF-2α inhibitor) demonstrated improvement in progression-free survival compared with everolimus in heavily pretreated patients unselected for somatic/germline VHL alterations (an objective response rate of 23% and a median time on therapy of 7.6 months in the belzutifan cohort), resulting in U.S. FDA approval for patients with advanced RCC. Herein, we present two cases of refractory metastatic RCC (including one with brain metastases) with somatic VHL mutations who received belzutifan after discussion in the institutional Molecular Tumor Board. Both patients had an excellent clinical response (partial remissions ongoing at >12 and >20 months). Future studies should assess the merits of biomarker selection for belzutifan treatment.

Introduction: Galectin-3 plays critical roles in the adhesion, proliferation, and differentiation of tumor cells. Recent data have suggested that galectin-3 plays a role in the development of hepatocellular carcinoma (HCC); however, its prognostic value has not been validated. The aim of our study was to evaluate the clinical and prognostic value of galectin-3 in patients with HCC.

Methods: We prospectively enrolled and collected clinicopathologic data and serum samples from 767 patients with HCC between 2001 and 2014 at The University of Texas MD Anderson Cancer Center. Two hundred patients without HCC were also enrolled and had data collected. The Kaplan-Meier method was used to estimate overall survival (OS) distributions.

Results: The median OS in this cohort was 14.2 months (95% CI, 12-16.1). At the time of analysis, the 1-year OS rate was 45% (95% CI, 0.4-0.51) among patients with high galectin-3 levels and 59% (95% CI, 0.54-0.63) among patients with low galectin-3 levels. OS was significantly inferior in patients with high galectin-3 levels than in patients with lower galectin-3 levels (median OS: 10.12 vs. 16.49 months; p = 0.0022). Additionally, the multivariate model showed a significant association between high galectin-3 level and poor OS (hazard ratio [HR] = 1.249; 95% CI, 1.005-1.554). Comparison between low ( n = 464 patients) and high ( n = 302 patients) galectin-3 levels showed that mean serum galectin-3 levels were significantly higher in patients with HCC who had hepatitis C virus (HCV) infection ( p = 0.0001), higher Child-Pugh score (CPS) ( p = 0.0009), and higher Cancer of the Liver Italian Program (CLIP) score ( p = 0.0015).

Conclusion: Our study shows that serum galectin-3 level is a valid prognostic biomarker candidate.

Leukemic masses are a known complication in patients with hematologic malignancies. Here we present a case regarding a patient with recently diagnosed B-acute lymphoblastic leukemia (B-ALL) who presented with multiple sites of extramedullary involvement including an anterior mediastinal mass. This mass persisted despite multiple rounds of multiagent cytotoxic therapy. In this report, we summarize the literature regarding mediastinal masses in the setting of B-ALL and illustrate that such masses in patients with leukemias may have surprising etiology, separate from the primary disease.

The tumor microenvironment (TME) encompasses the complex and diverse surroundings in which tumors arise. Emerging insights highlight the TME's critical role in tumor development, progression, metastasis, and treatment response. Consequently, the TME has attracted significant research and clinical interest, leading to the identification of numerous novel therapeutic targets. Advances in molecular technologies now enable detailed genomic and transcriptional analysis of cancer cells and the TME and the integration of microenvironmental data to the tumor genomic landscape. This comprehensive review discusses current progress in targeting the TME for drug development, addressing associated challenges, strategies for modulating the pro-tumor microenvironment, and the discovery of new targets.

Non-small cell lung cancer (NSCLC) is a heterogeneous disease with diverse molecular alterations. Two of the most common genetic abnormalities found in advanced NSCLC are mutations in the epidermal growth factor receptor (EGFR) and rearrangements in the ROS proto-oncogene 1 (ROS-1). Although these two alterations are typically mutually exclusive, there have been reports of their co-occurrence in a small subset of NSCLC patients. The discovery of this comutation has recently become apparent due to the increased use of more sensitive whole genome sequencing. We share our experience with two cases of coexisting EGFR and ROS-1 alterations. The first case is a 60-year-old man diagnosed with advanced adenocarcinoma of the lung with metastasis to bone and left adrenal gland. The second case is a 49-year-old woman diagnosed with stage IV lung adenocarcinoma with metastasis to the contralateral lung and diffuse abdominal lymphadenopathy. The first case was treated with osimertinib, and currently has had a stable disease on this medication for more than 3 years. The second case had a short interval of stable disease on osimertinib; then she developed progressive disease with poor response to anti-ROS-1 therapy. We believe patients with advanced NSCLC may have a higher incidence of coalterations, especially in the areas of the world with higher EGFR mutations and in the era of higher usage of whole genome sequencing. The presence of comutations will allow for a good long-term response to anti-EGFR therapy. This highlights the importance of the use of next-generation sequencing whenever possible and considers variant allele frequency as a factor in directing the therapy. There are many other unanswered questions, such as the best treatment sequencing or even the combined targeted therapy approach. This case series may add some information to the current literature.

Immune checkpoint inhibitors (ICIs) have substantially advanced the treatment of patients with malignant melanoma. However, improving therapeutic efficacy requires identifying drug combinations that elicit durable responses without inducing intolerable toxicity. Within that context, selinexor emerges as a possible combination option that has been shown in preclinical studies to enhance the efficacy of ICI therapy. Methods: In this phase 1b study, we investigated selinexor in combination with pembrolizumab in 25 patients with advanced non-uveal melanoma. Patients received selinexor at a dosage of 60 mg taken orally twice weekly, and pembrolizumab intravenously at a dosage of 200 mg every 3 weeks. Results: Despite the high incidence of adverse events (96%), most treatment-related toxicities were manageable with supportive care and dose reductions. The most common adverse events of any grade were nausea (n = 20; 80%), decreased white blood cell count (n = 15; 60%), vomiting (n = 14; 56%), anemia (n = 12; 48%), fatigue (n = 12; 48%), and decreased platelet count (n = 12; 48%). The 10 patients with treatment-naïve evaluable disease had an objective response rate (ORR) of 70% (n = 7, including three patients with complete response), which was significantly higher than that of the 14 patients with prior anti-programmed cell death protein 1 (anti-PD-1) therapy, whose ORR was 7% (n = 1; p = 0.002). Stable disease was observed in two patients (20%) with treatment-naïve disease and seven patients (50%) with prior anti-PD-1 therapy. Conclusion: Selinexor combined with pembrolizumab showed promising antitumor activity in patients with treatment-naïve metastatic melanoma. The toxicity profile of the combination was consistent with that reported for individual agents, with no additional safety concerns.

A 62-year-old man presented with a slowly growing, painless lesion on his face. This eventually led to a progressive left-eye vision lesion, and the patient was subsequently diagnosed with advanced basal cell carcinoma (BCC). Of note, BCC involving cranial nerves is extremely rare, making this case unique and important to highlight. Standard treatment options for BCC involve surgery, radiation, or platinum-based chemotherapy. However, targeted therapies such as sonidegib and vismodegib - sonic hedgehog pathway inhibitors - have emerged that have been approved for treating BCC, as have anti-PD1 immunotherapies, such as cemiplimab, with their success likely based on the high tumor mutational burden seen in some of these tumors. Epidermal growth factor receptor (EGFR) inhibitors also serve a role in treating this condition as well. Molecular studies on metastatic/advanced BCC and other rare malignancies may inform treatment therapeutic decisions.