American Society of Clinical Oncology educational book / ASCO. American Society of Clinical Oncology. Meeting最新文献

Not all melanomas are the same. They differ in presentation, mutational status, and behavior. Desmoplastic melanoma (DM) is a rare subtype of melanoma which carries a high tumor mutation burden and is found in highly sun-exposed areas. Although many cutaneous melanomas are pigmented, DM is amelanotic and frequently mistaken for more benign lesions. It is composed of spindle cells surrounded by a dense fibrinous matrix. It frequently carries NF1 mutations. It is exquisitely sensitive to single-agent PD1 blockade resulting in deep, rapid responses at all stages. These responses with single-agent pembrolizumab are durable with a 96% 3-year melanoma specific survival rate. This has influenced recommended treatments for unresectable and resectable disease. Single-agent PD1 blockade is recommended first line for unresectable disease with a reported overall response rate of 89%. The first prospective neoadjuvant study in DM demonstrated a pathologic complete response of 57% after three cycles of pembrolizumab, suggesting potential benefit to the use of neoadjuvant therapy in resectable disease. Owing to the low incidence of sentinel lymph node positivity and lack of correlation with overall survival, sentinel lymph node biopsy can be eliminated in patients with pure DM. Adjuvant radiation has been shown to result in improved local control in cases of high-risk DM, but studies have not demonstrated an impact on distant metastasis-free survival. For DM, less is more.

This article comprises three integrated sections exploring the multidimensional suffering experienced in oncology-from the perspective of both patients and health care professionals. It explores how oncology clinicians can better understand, address, and accompany the suffering of patients with advanced illness and what resources the patients themselves may appeal to when facing a terminal diagnosis. Section 1 outlines a clinical framework for attending to patient suffering when there is no cure, emphasizing psychologic formulation, attunement, and countertransference as therapeutic tools. Section 2 addresses provider overwhelm and distress in response to patient grief, with strategies grounded in neuroscience, meaning making, and emotional regulation. Section 3 considers attending to suffering in oncology in the context of spirituality and focuses in particular on when patients and providers are unable to draw support from religious belief. Together, these insights offer a narrative-driven, psychologically attuned, and spiritually inclusive approach to care.

Non-muscle-invasive bladder cancer (NMIBC) comprises 75% of newly diagnosed bladder cancer and poses significant clinical challenges because of high recurrence and progression rates. Despite the effectiveness of Bacillus Calmette-Guérin (BCG) therapy after transurethral resection of bladder tumor (TURBT), BCG fails nearly 40% of patients, requiring alternative treatments. Traditionally, radical cystectomy has been the standard for BCG-unresponsive disease, although it significantly affects quality of life. Recent advances have focused on bladder-preserving therapies that leverage immune checkpoint inhibitors, viral gene therapies, novel drug delivery systems, and targeted molecular agents. Emerging approaches such as TAR-200 and UGN-102 offer novel intravesical delivery systems that enhance therapeutic efficacy while minimizing systemic adverse effects. Viral therapies, including nadofaragene firadenovec and CG0070, deliver immune-activating and oncolytic agents directly to urothelial tumor cells. Additionally, immune checkpoint inhibitors such as pembrolizumab and durvalumab have demonstrated potential for systemic treatments in BCG-unresponsive NMIBC and may show even more promise in combinations. Ongoing trials are expected to provide crucial data on these therapies' efficacy, particularly in high-risk and intermediate-risk populations. For low-grade NMIBC, efforts are underway to de-escalate care through active surveillance and novel adjuvant therapies, reducing the need for repeated TURBT procedures. Together, these advancements highlight a promising shift toward personalized, bladder-preserving strategies that prioritize patient quality of life while addressing unmet needs in NMIBC management.

Cell-based therapies have become integral to the routine clinical management of hematologic malignancies. Tumor-infiltrating lymphocyte (TIL) therapy has demonstrated efficacy in immunogenic solid tumors, such as melanoma. However, in the GI field, evidence supporting the clinical success of cell-based therapies is still awaited. CLDN18.2, a key tight junction molecule in stomach epithelium, has emerged as a promising target for gastric cancer (GC) treatment. Because of its lineage-specific expression, significant efforts have been made to develop chimeric antigen receptor T-cell (CAR-T) therapies targeting CLDN18.2. These therapies have shown encouraging tumor shrinkage in patients with heavily pretreated GC. However, durable responses remain uncommon. CAR-T exhaustion driven by immune-suppressive cells in the tumor microenvironment, along with the heterogeneous expression of target molecules, poses significant challenges. In addition, managing on-target, off-tumor toxicities remains a critical issue in therapies targeting tissue-associated antigens. Next-generation CARs are expected to address these resistance mechanisms. Furthermore, adoptive macrophage and natural killer cell therapies hold promise for not only their efficacy but also for the ease off-the-shelf production. Advanced neoantigen prediction and identification of optimal T-cell activation targets could facilitate the clinical application of TIL and T-cell receptor-T therapies in GI cancers. Cell-based therapies might have the potential to transform the treatment landscape for GI cancers.

The growing sophistication of tumor molecular profiling has helped to slowly transition oncologic care toward a more personalized approach in different tumor types, including in bladder cancer. The National Comprehensive Cancer Network recommends that all patients with stage IVA and stage IVB urothelial carcinoma have molecular analysis that integrates at least FGFR3 testing to help facilitate the selection of future therapeutic options. Sequencing of tumor-derived tissue is the mainstay to obtain this genomic testing, but as in other cancers, there has been extensive research into the integration of liquid biopsies in longitudinal management. Liquid biopsies broadly refer to the isolation of both cellular and noncellular tumor components including proteins and nucleic acids such as mRNA and circulating free DNA within a liquid sample. Although protein-based testing and testing of circulating tumor cells are options, the bulk of promising research in bladder cancer is investigating the role of plasma-based circulating tumor DNA (ctDNA). Currently, a universal consensus on optimal preanalytic and analytic approaches has not been fully defined, and the exact role that liquid biopsies should have in screening, diagnosis, prognostication, treatment selection, and monitoring is not yet known. Still, it can be expected that ctDNA testing will be a part of appropriate management of muscle-invasive bladder cancer and metastatic bladder cancer in the near future. In this review, the goal is to provide a practical overview of the current and future role of ctDNA in bladder cancer including ongoing trials.

Data have matured to support incorporation of integrative oncology modalities into comprehensive cancer care. Clinical practice guidelines have recently been published by ASCO for diet and exercise (2022) and use of cannabinoids and cannabis (2024) and jointly by ASCO and the Society for Integrative Oncology (SIO) for application of integrative approaches in the management of pain (2022), anxiety and depression (2023), and fatigue (2024) among adults with cancer. Following the ASCO-SIO guidelines, clinicians should recommend mindfulness-based interventions (MBIs) to patients with symptoms of anxiety or depression and MBIs and exercise for management of fatigue during or after completion of cancer treatment. We will review the basis of these recommendations and evidence to support use of other mind-body approaches, exercise, nutrition, acupuncture/acupressure, and natural products in the specific contexts of GI cancers. For example, optimizing physical activity and diet is associated with improved survival after a colorectal cancer (CRC) diagnosis, in addition to conferring symptom management benefits. We will also highlight gaps in research, including that most studies enrolling patients with GI malignancies have focused on CRC. A limitation of nonpharmacologic evidence-based guidelines is that they list broad categories (eg, yoga or acupuncture) and lack implementation details. How to safely and equitably incorporate integrative approaches into conventional cancer care will be addressed. This ASCO Educational Book article aims to be both evidence-informed and practical, with attention to unique considerations for people with GI cancers.

Antibody-drug conjugates (ADCs) represent an emerging class of therapeutics across solid tumor oncology and are already positioned as a cornerstone therapy for patients with urothelial carcinoma (UC). In recent years, there has been a paradigm shift in the therapeutic landscape as frontline treatment of UC formerly relied on the use of platinum-based agents and has now evolved to include combination strategies with ADCs. These dramatic changes are due in part to our improved understanding of the molecular features of bladder tumors and the identification of tumor-associated antigens specific to UC, which may serve as druggable targets. Despite notable advances and the clinical success of ADCs in other malignancies, their full potential in UC remains largely unmet. Early clinical success of enfortumab vedotin and sacituzumab govitecan demonstrated antitumor activity; however, there are multiple challenges with these ADCs, including on-target, off-tumor toxicity and difficulty in maintaining sustained responses. Newer-generation ADC constructs, either alone or as part of combination approaches, are currently under investigation. This review examines the historical development, current landscape, and emerging trends in ADC therapy for UC, highlighting both the progress made and obstacles that continue to hinder optimal therapeutic outcomes.

Patients with hematologic malignancies (HMs) struggle with immense physical and psychological symptom burden, which negatively affect their quality of life (QOL) throughout the continuum of illness. These patients are often faced with substantial prognostic uncertainty as they navigate their illness course, which further complicates their medical decision making, especially at the end of life (EOL). Consequently, patients with HM often endure intensive medical care at the EOL, including frequent hospitalization and intensive care unit admissions, and they often die in the hospital. Our EOL health care delivery models are not well suited to meet the unique needs of patients with HMs. Although studies have established the role of specialty palliative care for improving QOL and EOL outcomes in patients with solid tumors, numerous disease-, clinician-, and system-based barriers prevail, limiting the integration of palliative care for patients with HMs. Nonetheless, multiple studies have emerged over the past decade identifying the role of palliative care integration in patients with various HMs, resulting in improvements in patient-reported QOL, symptom burden, and psychological distress, as well as EOL care. Importantly, these studies have also identified active components of specialty palliative care interventions, including strategies to promote adaptive coping especially in the face of prognostic uncertainty. Future work can leverage the knowledge gained from specialty palliative care integration to develop and test primary palliative care interventions by training clinicians caring for patients with HMs to incorporate these strategies into their clinical practice.