Alpelisib and Immunotherapy: A Promising Combination for Recurrent and Metastatic Squamous Cell Carcinoma of the Head and Neck.

BACKGROUND: Recurrent squamous cell carcinoma (SCC) of the head and neck (SCCHN) remains a formidable clinical challenge despite available treatments. The phosphatidylinositol 3-kinase (PI3K) pathway has been identified as a potential therapeutic target, and alpelisib, a selective PI3Kα inhibitor, has demonstrated efficacy in certain malignancies. Combining this targeted therapy with immunotherapy has been suggested in previous studies as a promising strategy to bolster the immune response against cancer. CASES: A 69-year-old woman with locoregional recurrence of PIK3CA-mutated SCC of the left maxilla and cervical nodal metastases. Several chemotherapeutic regimens, including cisplatin, docetaxel, 5FU, chemoradiotherapy, and mono-immunotherapy, resulted in disease progression. Alpelisib combined with pembrolizumab led to a sustained response for 9 months. A 58-year-old man with recurrent metastatic PIK3CA-mutated SCC of the oropharynx, involving the left lung, hilar, and mediastinal lymph nodes. Despite prior palliative radiation and platinum-based chemotherapy with pembrolizumab and cetuximab, treatment with alpelisib and nivolumab resulted in a partial response. Severe hyperglycemia and rash led to treatment discontinuation. CONCLUSION: Our findings highlight the potential of this innovative therapeutic combination, suggesting a need for further investigations in this setting.

Advancing head and neck cancer management: Unveiling the diagnostic and therapeutic potentials of molecular profiling.

BACKGROUND: Head and neck cancers (HNC) present diagnostic challenges due to multifocal disease manifestations, posing difficulties in distinguishing between metastatic disease and second primary malignancies (SPM). This complexity underscores the need for advanced diagnostic approaches. Emerging technologies, such as next-generation sequencing (NGS) and molecular classifier assays, show promise in providing precise insights into the diverse etiologies of HNC. METHOD: In this article, we employed NGS and molecular classifier assays to delve into three distinct clinical cases. The objective was to showcase the instrumental role of these technologies in facilitating accurate diagnoses and differentiating between metastatic disease and SPM in HNC cases. RESULTS: The results of this series highlight the effectiveness of NGS and molecular classifier assays in enhancing diagnostic accuracy for HNC and contributing to the precise differentiation of disease etiologies. The utilization of these advanced technologies proved instrumental in avoiding unnecessary interventions and paved the way for more targeted and effective treatment strategies. CONCLUSION: Our findings underscore the necessity of incorporating advanced molecular testing technologies into the diagnostic and therapeutic approaches for HNC, thereby championing a more nuanced and effective approach to managing these complex cases.

Does High-Dose Thromboprophylaxis Improve Outcomes in COVID-19 Patients? A Meta-analysis of Comparative Studies.

Background Thromboembolism remains a detrimental complication of novel coronavirus disease (COVID-19) despite the use of prophylactic doses of anticoagulation Objectives This study aimed to compare different thromboprophylaxis strategies in COVID-19 patients Methods We conducted a systematic database search until June 30, 2022. Eligible studies were randomized (RCTs) and nonrandomized studies that compared prophylactic to intermediate or therapeutic doses of anticoagulation in adult patients with COVID-19, admitted to general wards or intensive care unit (ICU). Primary outcomes were mortality, thromboembolism, and bleeding events. Data are analyzed separately in RCTs and non-RCTs and in ICU and non-ICU patients. Results. We identified 682 studies and included 53 eligible studies. Therapeutic anticoagulation showed no mortality benefit over prophylactic anticoagulation in four RCTs (odds ratio [OR] = 0.67, 95% confidence interval [CI], 0.18-2.54). Therapeutic anticoagulation didn't improve mortality in ICU or non-ICU patients. Risk of thromboembolism was significantly lower among non-ICU patients who received enhanced (therapeutic/intermediate) anticoagulation (OR = 0.21, 95% CI, 0.06-0.74). Two additional RCTs (Multiplatform Trial and HEP-COVID), not included in quantitative meta-analysis, analyzed non-ICU patients, and reported a similar benefit with therapeutic-dose anticoagulation. Therapeutic anticoagulation was associated with a significantly higher risk of bleeding events among non-randomized studies (OR = 3.45, 95% CI, 2.32-5.13). Among RCTs, although patients who received therapeutic-dose anticoagulation had higher numbers of bleeding events, these differences were not statistically significant. Studies comparing prophylactic and intermediate-dose anticoagulation showed no differences in primary outcomes. Conclusion There is a lack of mortality benefit with therapeutic-dose over prophylactic-dose anticoagulation in ICU and non-ICU COVID-19 patients. Therapeutic anticoagulation significantly decreased risk of thromboembolism risk in some of the available RCTs, especially among non-ICU patients. This potential benefit, however, may be counter balanced by higher risk of bleeding. Individualized assessment of patient's bleeding risk will ultimately impact the true clinical benefit of anticoagulation in each patient. Finally, we found no mortality or morbidity benefit with intermediate-dose anticoagulation.

Life-Threatening Fungal Infection in Richter Transformation of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Case Report and Brief Review of Literature.

Chronic lymphocytic leukemia/small lymphocytic lymphoma is an indolent B cell lymphoproliferative malignancy typically affecting the elderly. Clinical outcomes of this condition have steadily improved as a result of advances in therapy. However, an increase in survival is accompanied by increased incidence of Richter transformation into an aggressive lymphoma. We present one such case and delve into its risk factors and associated complications. Exposure to increased lines of treatment appears to be a contributing factor in transformation, such that those with fewer than two lines of treatment are considered to have a lower risk of transformation. Fever, rapid lymph node involvement and drastic increases in lactate dehydrogenase, as seen in our patient, are concerning for transformation and treatment options include chemotherapy versus novel agent therapy. However, patients receiving therapy are at risk for adverse outcomes such as invasive infections, particularly in those receiving consolidation chemotherapy. Fungal infections such as Aspergillus and Candida are gaining prominence in the setting of neutropenia which adversely impact survival, but are underreported. Efforts to improve outcomes may include consideration of growth factor therapy in neutropenic patients and continuing to be vigilant for early signs of infection.

Optic Nerve Infiltration in Systemic Lymphoma in an HIV Patient.

Different mechanisms have been proposed in lymphomatous involvement of the optic nerve. They include isolated optic nerve lymphoma, optic nerve lymphoma associated with primary central nervous system (CNS) lymphoma, or with systemic lymphoma. We present one case of non-Hodgkin lymphoma of the optic nerve in a Human Immunodeficiency Virus (HIV) patient and discuss the mechanism of metastasis, classification of optic nerve involvement with clinical and radiologic features as well as treatment options. Despite the uncommon nature of optic nerve infiltration by lymphoma, prompt evaluation should be considered in patients with a history of lymphoma and visual symptoms as delays in treatment can result in permanent vision loss. The recommended initial workup includes neuroimaging and cerebrospinal fluid evaluation. Treatment options are not standardized but include intravenous and intrathecal chemotherapy, corticosteroids, and radiation.