Subtype of SCLC Is an Intrinsic and Persistent Feature Through Systemic Treatment.

Introduction: SCLC is an aggressive malignancy with poor outcome. Most patients have disease recurrence despite treatments with multiple modalities. Subtyping of SCLC has been proposed recently, and novel agents targeting specific subtypes are actively being investigated. In this study, we evaluated the plasticity of subtypes in paired pre- and post-treatment samples. The aim was to understand possible subtype evolution after chemotherapy resistance that could lead to alternate targeted therapy strategies. Methods: A total of 68 samples from 32 patients with sufficient paired specimens were identified from 1998 to 2022. ASCL1, NEUROD1, and POU2F3 immunohistochemistry studies were performed on all cases, and subtyping by predominant expression was determined. Subtype comparison in each patient was performed, and expression analysis was performed on the basis of subtypes. Results: Of 32 cases, 28 (88%) had the same subtype in pre- and first post-treatment specimens. Protein expression level of subtype-specific transcription factor remained stable after chemotherapy. Two of five (40%) NEUROD1-predominant SCLC switched to ASCL1-predominant phenotype after treatment. One case had a pitfall of scoring ASCL1 on specimen with marked crushing artifacts. One case revealed the challenge of proper subtyping for samples with borderline POU2F3 expression. Conclusions: Subtype of SCLC generally remains the same after acquiring chemotherapy resistance. Plasticity was observed with rare cases switching from NEUROD1-predominant to ASC1-predominant SCLC. Resubtyping is unnecessary for the consideration of novel subtype-specific targeted agents, except cases with NEUROD1-predominant subtype.

Dosimetric predictors of pneumonitis in locally advanced non-small cell lung cancer patients treated with chemoradiation followed by durvalumab.

OBJECTIVES: The incidence and predictors of pneumonitis for patients with unresectable, locally advanced non-small cell lung cancer (NSCLC) in the era of consolidation durvalumab have yet to be fully elucidated. In this large single institution analysis, we report the incidence of and factors associated with grade 2 + pneumonitis in NSCLC patients treated with the PACIFIC regimen. MATERIALS AND METHODS: We identified all patients treated at our institution with definitive CRT followed by durvalumab from 2018 to 2021. Clinical documentation and imaging studies were reviewed to determine grade 2 + pneumonitis events, which required the following: 1) pulmonary symptoms warranting prolonged steroid taper, oxygen dependence, and/or hospital admission and 2) radiographic findings consistent with pneumonitis. RESULTS: One-hundred ninety patients were included. The majority received 60 Gray (Gy) in 30 fractions with concurrent carboplatin and paclitaxel. Median number of durvalumab cycles received was 12 (IQR: 4-22). At a median follow-up of 14.8 months, 50 (26.3%) patients experienced grade 2 + pneumonitis with a 1-year cumulative incidence of 27.8% (95% CI: 21.9-35.4). Seventeen (8.9%) patients experienced grade 3 + pneumonitis and 4 grade 5 (2.1%). Dosimetric predictors of pneumonitis included ipsilateral and total lung volume receiving 5 Gy or greater (V5Gy), V10Gy, V20Gy, V40Gy, and mean dose and contralateral V40Gy. Heart V5Gy, V10Gy, and mean dose were also significant variables. Overall survival estimates at 1 and 3 years were 87.4% (95% CI: 82.4-92.8) and 60.3% (95% CI: 47.9-74.4), respectively. CONCLUSION: We report a risk of pneumonitis higher than that seen on RTOG 0617 and comparable to the PACIFIC study. Multiple lung and heart dosimetric factors were predictive of pneumonitis.

Challenges in the Use of Targeted Therapies in Non-Small Cell Lung Cancer.

Precision oncology has fundamentally changed how we diagnose and treat cancer. In recent years, there has been a significant change in the management of patients with oncogene-addicted advanced-stage NSCLC. Increasing amounts of identifiable oncogene drivers have led to the development of molecularly targeted drugs. Undoubtedly, the future of thoracic oncology is shifting toward increased molecular testing and the use of targeted therapies. For the most part, these novel drugs have proven to be safe and effective. As with all great innovations, targeted therapies pose unique challenges. Drug toxicities, resistance, access, and costs are some of the expected obstacles that will need to be addressed. This review highlights some of the major challenges in the use of targeted therapies in NSCLC and provides guidance for the future strategies.

Bleeding assessment in female patients with the Hermansky-Pudlak syndrome-A case series.

INTRODUCTION: The Hermansky-Pudlak syndrome (HPS) is an autosomal recessive rare disorder characterized by oculocutaneous albinism, bleeding diathesis, chronic granulomatous colitis and/or pulmonary fibrosis. HPS is the most common single-gene disorder in Puerto Rico with a prevalence of 1:1,800 in the Northwest of the island. Risk of menorrhagia and post-partum hemorrhage (PPH) in cases of women with HPS have been described in the medical literature, but data regarding comprehensive description of bleeding diathesis remains lacking. For this reason, we aim to identify bleeding events using the International Society on Thrombosis and Hemostasis Bleeding Assessment Tool (ISTH-BAT), a standardized quantitative tool that translates the range of severity of bleeding symptoms into a cumulative bleeding score (BS). OBJECTIVE: To use the ISTH-BAT in HPS in order to describe bleeding symptoms and allow for comparison with other inherited bleeding disorders. METHODS: Puerto Rican females and adult participants with HPS based on genetic linkage were enrolled. The ISTH-BAT was administered and results were identified using descriptive statistical analysis. RESULTS: Questionnaire answers of twelve women with HPS-1 and HPS-3 were evaluated. Participants' mean BS was HPS-1 (11.4) and HPS-3 (8.0) Participants with HPS-1 and HPS-3 reported abnormal bleeding events that presented during dental extractions, menorrhagia, surgical interventions, gastrointestinal, oral cavity and post-partum. Patients with history of pulmonary fibrosis (PF) showed a higher mean bleeding score than those who had no history of PF. CONCLUSIONS: Female patients with HPS type 1 and 3 experienced abnormal bleeding events according to the ISTH-BAT bleeding score. Bleeding medications were inconsistently used and varied independently from healthcare professionals. The benefits of this study were to understand the history of bleeding complications in patients with HPS type 1 and 3 using an international validated system. The results of this study will help design strategies to improve the care we provide to this population.

The Zika Virus: An Association to Guillain-Barré Syndrome in the United States - A Case Report.

Case of a 37 year-old Puerto Rican male with no past medical history who was admitted to the hospital after developing paresthesia in the upper and lower extremities with associated skin rash, weakness, and dysautonomia. After rigorous analysis of the clinical patterns, neurologic manifestations, laboratory workups, CSF analysis, and nerve conduction studies we conclude the existence of a strong relationship between the Zika virus and the Guillain-Barré syndrome. The patient recovered promptly and his response to treatment was excellent.