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

Cancer is an increasing global public health burden. Lately, more emphasis has emerged on the importance of heredity in cancer, mostly driven by the introduction of germline genetic variants-directed therapeutics. It is true that 40% of cancer risk is attributed to modifiable environmental and lifestyle factors; still, 16% of cancers could be heritable, accounting for 2.9 of the 18.1 million cases diagnosed worldwide. At least two third of those will be diagnosed in countries with limited resources-low- and middle-income countries, especially where high rates of consanguine marriage and early age at diagnosis are already prevalent. Both are hallmarks of hereditary cancer. This creates a new opportunity for prevention, early detection, and recently therapeutic intervention. However, this opportunity is challenged by many obstacles along the path to addressing germline testing in patients with cancer in the clinic worldwide. Global collaboration and expertise exchange are important to bridge the knowledge gap and facilitate practical implementation. Adapting existing guidelines and prioritization according to local resources are essential to address the unique needs and overcome the unique barriers of each society.

COVID-19 and our armamentarium of strategies to combat it have evolved dramatically since the virus first emerged in late 2019. Vaccination remains the primary strategy to prevent severe illness, although the protective effect can vary in patients with hematologic malignancy. Strategies such as additional vaccine doses and now bivalent boosters can contribute to increased immune response, especially in the face of evolving viral variants. Because of these new variants, no approved monoclonal antibodies are available for pre-exposure or postexposure prophylaxis. Patients with symptomatic, mild-to-moderate COVID-19 and risk features for developing severe COVID-19, who present within 5-7 days of symptom onset, should be offered outpatient therapy with nirmatrelvir/ritonavir (NR) or in some cases with intravenous (IV) remdesivir. NR interacts with many blood cancer treatments, and reviewing drug interactions is essential. Patients with severe COVID-19 should be managed with IV remdesivir, tocilizumab (or an alternate interleukin-6 receptor blocker), or baricitinib, as indicated based on the severity of illness. Dexamethasone can be considered on an individual basis, weighing oxygen requirements and patients' underlying disease and their perceived ability to clear infection. Finally, as CD19-targeted and B-cell maturation (BCMA)-targeted chimeric antigen receptor (CAR) T-cell therapies become more heavily used for relapsed/refractory hematologic malignancies, viral infections including COVID-19 are increasingly recognized as common complications, but data on risk factors and prophylaxis in this patient population are scarce. We summarize the available evidence regarding viral infections after CAR T-cell therapy.

Antibody Drug Conjugates (ADCs) are a novel class of therapeutic that structurally comprise an antibody directed at a tumor epitope connected via a linker to a cytotoxic payload that have shown significant antitumor activity across a range of malignancies including lung cancer. In this article we review the pharmacology of ADCs, describe results of trials with ADCs directed at targets in lung cancer including Trophoblast cell-surface antigen 2(TROP2), HER3, MET, Carcinoembryonic antigen-related cell adhesion molecular 5(CECAM-5) and HER2. Trastuzumab Deruxtecan (also known as DS-8201a or T-DXd) an ADC directed at HER2 recently became the first ADC to receive FDA approval in lung cancer, on the basis of its activity in tumors with HER2 mutations, demonstrated in the Destiny-Lung01 and Lung02 trials.

Integrativety oncology (IO) is a "patient-centered, evidence-informed field of comprehensive cancer care that utilizes mind-body practices, natural products, and lifestyle modifications from different traditions alongside conventional cancer treatments." There is an urgent need to educate oncology health care providers on the fundamentals of evidence-based IO to meet the needs of people with cancer. In this chapter, we aim to provide oncology professionals with actionable guidance on the basis of the Society for Integrative Oncology (SIO)-American Society of Clinical Oncology (ASCO) guidelines on integrative medicine use during oncology visits to help alleviate symptoms and side effects in people with cancer during and after treatment.

Prior authorization (PA) is a type of utilization review that health insurers apply to control service delivery, payments, and reimbursements of health interventions. The original stated intent of PA was to ensure high-quality standards in treatment delivery while encouraging evidence-based and cost-effective therapeutic choices. However, as currently implemented in clinical practice, PA has been shown to affect the health workforce, adding administrative burden to authorize needed health interventions for patients and often requiring time-consuming peer-to-peer reviews to challenge initial denials. PA is presently required for a wide range of interventions, including supportive care medicines and other essential cancer care interventions. Patients who are denied coverage are commonly forced to receive second-choice options, including less effective or less tolerable options, or are exposed to financial toxicity because of substantial out-of-pocket expenditures, affecting patient-centric outcomes. The development of tools informed by national clinical guidelines to identify standard-of-care interventions for patients with specific cancer diagnoses and the implementation of evidence-based clinical pathways as part of quality improvement efforts of cancer centers have improved patient outcomes and may serve to establish new payment models for health insurers, thereby also reducing administrative burden and delays. The definition of a set of essential interventions and guidelines- or pathways-driven decisions could facilitate reimbursement decisions and thus reduce the need for PAs. Structural changes in how PA is applied and implemented, including a redefinition of its real need, are needed to optimize patient-centric outcomes and support high-quality care of patients with cancer.

Most thoracic cancers arise via a series of stepwise somatic alterations driven by a well-defined carcinogen (ie, tobacco or asbestos for lung cancer and mesothelioma, respectively). A small proportion can emerge on a background of pathogenic germline variants (PGVs), which have the property of heritability. In general, PGVs may be initially suspected on the basis of the presence of specific clinical features. Such gene × environment interactions significantly increase the risk of developing lung cancer (1.5- to 3.2-fold). PGVs have been discovered involving the actionable driver oncogene, epidermal growth factor receptor (EGFR), with an EGFR T790M PGV rate of 0.3%-0.9% in the nonsquamous non-small-cell lung cancer subtype. Its appearance during routine somatic DNA sequencing in those patients who have not had a previous tyrosine kinase inhibitor should raise suspicion. In patients with sporadic mesothelioma, BAP1 is the most frequently mutated tumor driver, with a PGV rate between 2.8% and 8%, associated with a favorable prognosis. BAP1 PGVs accelerate mesothelioma tumorigenesis after asbestos exposure in preclinical models and may be partly predicted by clinical criteria. At present, routine germline genetic testing for thoracic cancers is not a standard practice. Expert genetic counseling is, therefore, required for patients who carry a PGV. Ongoing studies aim to better understand the natural history of patients harboring PGVs to underpin future cancer prevention, precise counseling, and cancer management with the goal of improving the quality and length of life.

The majority of men with prostate cancer are diagnosed when they are older than 65 years; however, clinical trial participants are disproportionately younger and more fit than the real-world population treated in typical clinical practices. It is, therefore, unknown whether the optimal approach to prostate cancer treatment is the same for older men as it is for younger and/or more fit men. Short screening tools can be used to efficiently assess frailty, functional status, life expectancy, and treatment toxicity risk. These risk assessment tools allow for targeted interventions to increase a patient's reserve and improve treatment tolerance, potentially allowing more men to experience the benefit of the significant recent treatment advances in prostate cancer. Treatment plans should also take into consideration each patient's individual goals and values considered within their overall health and social context to reduce barriers to care. In this review, we will discuss evidence-based risk assessment and decision tools for older men with prostate cancer, highlight intervention strategies to improve treatment tolerance, and contextualize these tools within the current treatment landscape for prostate cancer.

Significant progress has been made in genetic and genomic testing for prostate cancer across the disease spectrum. Molecular profiling is increasingly relevant for routine clinical management, fueled in part by advancements in testing technology and integration of biomarkers into clinical trials. In metastatic prostate cancer, defects in DNA damage response genes are now established predictors of benefit to US Food and Drug Administration-approved poly (ADP-ribose) polymerase inhibitors and immune checkpoint inhibitors, and trials are actively investigating these and other targeted treatment strategies in earlier disease states. Excitingly, opportunities for molecularly informed management beyond DNA damage response genes are also maturing. Germline genetic variants (eg, BRCA2 or MSH2/6) and polygenic germline risk scores are being investigated to inform cancer screening and active surveillance in at-risk carriers. RNA expression tests have recently gained traction in localized prostate cancer, enabling patient risk stratification and tailored treatment intensification via radiotherapy and/or androgen deprivation therapy for localized or salvage treatment. Finally, emerging minimally invasive circulating tumor DNA technology promises to enhance biomarker testing in advanced disease pending additional methodological and clinical validation. Collectively, genetic and genomic tests are rapidly becoming indispensable tools for informing the optimal clinical management of prostate cancer.

Lung neuroendocrine neoplasms (NENs) encompass a spectrum of neoplasms that are subdivided into the well-differentiated neuroendocrine tumors comprising the low- and intermediate-grade typical and atypical carcinoids, respectively, and the poorly differentiated, high-grade neuroendocrine carcinomas including large-cell neuroendocrine carcinomas and small-cell lung carcinoma (SCLC). Here, we review the current morphological and molecular classifications of the NENs on the basis of the updated WHO Classification of Thoracic Tumors and discuss the emerging subclassifications on the basis of molecular profiling and the potential therapeutic implications. We focus on the efforts in subtyping SCLC, a particularly aggressive tumor with few treatment options, and the recent advances in therapy with the adoption of immune checkpoint inhibitors in the frontline setting for patients with extensive-stage SCLC. We further highlight the promising immunotherapy strategies in SCLC that are currently under investigation.

Recently, a wide spectrum of artificial intelligence (AI)-based applications in the broader categories of digital pathology, biomarker development, and treatment have been explored. In the domain of digital pathology, these have included novel analytical strategies for realizing new information derived from standard histology to guide treatment selection and biomarker development to predict treatment selection and response. In therapeutics, these have included AI-driven drug target discovery, drug design and repurposing, combination regimen optimization, modulated dosing, and beyond. Given the continued advances that are emerging, it is important to develop workflows that seamlessly combine the various segments of AI innovation to comprehensively augment the diagnostic and interventional arsenal of the clinical oncology community. To overcome challenges that remain with regard to the ideation, validation, and deployment of AI in clinical oncology, recommendations toward bringing this workflow to fruition are also provided from clinical, engineering, implementation, and health care economics considerations. Ultimately, this work proposes frameworks that can potentially integrate these domains toward the sustainable adoption of practice-changing AI by the clinical oncology community to drive improved patient outcomes.