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Journal of Thoracic Oncology : Official... Nov 2023The standard of care (SoC) for medically operable patients with early-stage (stages I-IIIB) NSCLC is surgery combined with (neo)adjuvant systemic therapy for patients... (Review)
Review
The standard of care (SoC) for medically operable patients with early-stage (stages I-IIIB) NSCLC is surgery combined with (neo)adjuvant systemic therapy for patients with stages II to IIIB disease and some stage IB or, rarely, chemoradiation (stage III disease with mediastinal lymph node metastases). Despite these treatments, metastatic recurrence is common and associated with poor survival, highlighting the need for systemic therapies that are more effective than the current SoC. After the success of targeted therapy (TT) in patients with advanced NSCLC harboring oncogenic drivers, these agents are being investigated for the perioperative (neoadjuvant and adjuvant) treatment of patients with early-stage NSCLC. Adjuvant osimertinib is the only TT approved for use in the early-stage setting, and there are no approved neoadjuvant TTs. We discuss the importance of comprehensive biomarker testing at diagnosis to identify individuals who may benefit from neoadjuvant targeted treatments and review emerging data from neoadjuvant TT trials. We also address the potential challenges for establishing neoadjuvant TTs as SoC in the early-stage setting, including the identification and validation of early response markers to guide care and accelerate drug development, and discuss safety considerations in the perioperative setting. Initial data indicate that neoadjuvant TTs are effective and well tolerated in patients with EGFR- or ALK-positive early-stage NSCLC. Data from ongoing trials will determine whether neoadjuvant targeted agents will become a new SoC for individuals with oncogene-addicted resectable NSCLC.
Topics: Humans; Lung Neoplasms; Neoadjuvant Therapy; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents; Combined Modality Therapy
PubMed: 37451404
DOI: 10.1016/j.jtho.2023.07.006 -
Cureus Jul 2023Superior vena cava syndrome (SVCS) is a medical emergency that encompasses an array of signs and symptoms due to obstruction of blood flow through the superior vena cava... (Review)
Review
Superior vena cava syndrome (SVCS) is a medical emergency that encompasses an array of signs and symptoms due to obstruction of blood flow through the superior vena cava (SVC). It poses a significant healthcare burden due to its associated morbidity and mortality. Its impact on the healthcare system continues to grow due to the increasing incidence of the condition. This incidence trend has been attributed to the growing use of catheters, pacemakers, and defibrillators, although it is a rare complication of these devices. The most common cause of SVCS remains malignancies accounting for up to 60% of the cases. Understanding the pathophysiology of SVCS requires understanding the anatomy, the SVC drains blood from the right and left brachiocephalic veins, which drain the head and the upper extremities accounting for about one-third of the venous blood to the heart. The most common presenting symptoms of SVCS are swelling of the face and hand, chest pain, respiratory symptoms (dyspnea, stridor, cough, hoarseness, and dysphagia), and neurologic manifestations (headaches, confusion, or visual/auditory disturbances). Symptoms generally worsen in a supine position. Diagnosis typically requires imaging, and SVCS can be graded based on classification schemas depending on the severity of symptoms and the location, understanding, and degree of obstruction. Over the past decades, the management modalities of SVCS have evolved to meet the increasing burden of the condition. Here, we present an umbrella review providing an overall assessment of the available information on SVCS, including the various management options, their indications, and a comparison of the advantages and disadvantages of these modalities.
PubMed: 37605686
DOI: 10.7759/cureus.42227 -
Blood Jul 2023Previous analyses of the phase 2 KEYNOTE-170 (NCT02576990) study demonstrated effective antitumor activity and acceptable safety of pembrolizumab 200 mg given every 3... (Clinical Trial)
Clinical Trial
Previous analyses of the phase 2 KEYNOTE-170 (NCT02576990) study demonstrated effective antitumor activity and acceptable safety of pembrolizumab 200 mg given every 3 weeks for up to 35 cycles (∼2 years) in patients with relapsed/refractory (R/R) primary mediastinal B-cell lymphoma (PMBCL) whose disease progressed after or who were ineligible for autologous stem cell transplantation. The end points included objective response rate (ORR), progression-free survival (PFS), and duration of response (DOR) according to the investigator per 2007 Response Criteria; overall survival (OS); and safety. In this final analysis, median duration of follow-up was 48.7 months (range, 41.2-56.2). The ORR was 41.5% (complete response, 20.8%; partial response, 20.8%). The median DOR was not reached; no patients who achieved a complete response progressed at the data cutoff. The median PFS was 4.3 months; the 4-year PFS rate was 33.0%. The median OS was 22.3 months; the 4-year OS rate was 45.3%. At the data cutoff, 30 patients (56.6%) had any-grade treatment-related adverse events (AEs); the most common were neutropenia, asthenia, and hypothyroidism. Grade 3/4 treatment-related AEs occurred in 22.6% of the patients; no grade 5 AEs occurred. After 4 years of follow-up, pembrolizumab continued to provide durable responses, with promising trends for long-term survival and acceptable safety in R/R PMBCL.
Topics: Adult; Humans; Antibodies, Monoclonal, Humanized; Hematopoietic Stem Cell Transplantation; Lymphoma, Large B-Cell, Diffuse; Mediastinal Neoplasms; Thymus Neoplasms; Transplantation, Autologous
PubMed: 37130017
DOI: 10.1182/blood.2022019340