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Living guidelines are developed for selected topic areas with rapidly evolving evidence that drives frequent change in recommended clinical practice. Living guidelines are updated on a regular schedule by a standing expert panel that systematically reviews the health literature on a continuous basis, as described in the ASCO Guidelines Methodology Manual . ASCO Living Guidelines follow the ASCO Conflict of Interest Policy Implementation for Clinical Practice Guidelines . Living Guidelines and updates are not intended to substitute for independent professional judgment of the treating clinician and do not account for individual variation among patients. See appendix for disclaimers and other important information (Appendix 1 and 2). Updates are published regularly and can be found at https://ascopubs.org/nsclc-da-living-guideline .

People living with cancer should have access to clear and comprehensible treatment information to empower informed decision-making. With the increasing adoption of open access publishing and plain-language summaries, clinical trial findings in journals are becoming more accessible. However, this will only help patients if they are equipped with the relevant knowledge and understanding to make sense of these findings. This podcast highlights the need to support this aspect of health literacy by bringing together the perspectives of a patient, a patient advocate and a medical oncologist. It is accompanied by two visual, plain-language guides designed to help general audiences understand the key efficacy end points that are commonly used in trials of solid tumor treatments.

Introduction: In the dynamic landscape of metastatic NSCLC (mNSCLC) management, marked by several frontline options and the integration of next generation sequencing (NGS) for informed decision-making, barriers persist despite advancements. This includes challenges in clinical trial recruitment. To gain global insights into clinicians' practices, we conducted a survey on their testing and management approaches for patients with mNSCLC., Methods: The survey, conducted from July 12 to August 20, 2023, utilized multiple-choice questions and qualitative research questions, employing the Likert Scale for comprehensive insights., Results: A total of 127 individuals responded, with 72% affiliated with academic health systems, and 55% practicing in the USA. Regarding testing practices, 93% consistently ordered NGS for non-squamous histology, while 54% did so for squamous cell histology. Concurrent tissue and liquid biopsies were routinely ordered by 28%, while 39% reported ordering both testing platforms concurrently for select cases only. Respondents cited logistical barriers, such as insufficient tissue and lack of infrastructure, as the most common hindrance to molecular testing (76%), followed by reimbursement challenges (56%) and concerns about delayed turnaround time (50%). While most respondents were confident in interpreting NGS results, 22% lacked confidence. Concerning treatment decisions, 72% preferred awaiting molecular testing results before initiating systemic therapy. Less than 50% routinely referred patients for clinical trials in the frontline setting for mNSCLC. For patients with disease expressing high PD-L1 levels, most oncologists preferred pembrolizumab monotherapy. For disease with low PD-L1 expression, a platinum doublet chemotherapy regimen combined with pembrolizumab was favored. In disease cases with negative PD-L1 expression, a platinum doublet chemotherapy regimen with pembrolizumab was preferred. Key factors influencing oncologists' preferred immune checkpoint inhibitor (ICI) included experience with one ICI over another, preferred status per national guidelines, availability of trial data with a significant follow-up period, and consideration of drug cost., Conclusion: Although this study demonstrates an improved awareness and adoption of ordering NGS for the management of mNSCLC, it underscores the persistence of various barriers that must be addressed to improve upon the quality of care for patients diagnosed with mNSCLC., Competing Interests: Disclosure AS: None. HJW: Howard Jack West reports a relationship with Summit Therapeutics plc that includes: employment. Howard Jack West reports a relationship with AbbVie Inc that includes: consulting or advisory. Howard Jack West reports a relationship with Amgen Inc that includes: consulting or advisory. Howard Jack West reports a relationship with Genetech Biotech Co Ltd that includes: consulting or advisory. Howard Jack West reports a relationship with Gilead Sciences Inc that includes: consulting or advisory. Howard Jack West reports a relationship with Merck & Co Inc that includes: consulting or advisory. Howard Jack West reports a relationship with Mirati Therapeutics Inc that includes: consulting or advisory. Howard Jack West reports a relationship with Regeneron Pharmaceuticals Inc that includes: consulting or advisory. Howard Jack West reports a relationship with AstraZeneca Pharmaceuticals LP that includes: speaking and lecture fees. Howard Jack West reports a relationship with Merck & Co Inc that includes: speaking and lecture fees. EKS: Eric K. Singhi reports a relationship with AstraZeneca Pharmaceuticals LP that includes: consulting or advisory. Eric K. Singhi reports a relationship with Novocure that includes: consulting or advisory. Eric K. Singhi reports a relationship with Amgen Inc that includes: consulting or advisory. Eric K. Singhi reports a relationship with Janssen Pharmaceuticals Inc that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Like many other aspects of hematology-oncology training, medical education experienced rapid changes throughout the COVID-19 pandemic that continue until today. We discuss some of the most transformative areas within medical education, including, but not limited to, educational philosophy; use of virtual resources; inter-institutional connections, shifts in clinical training; changes in recruitment practice; and attention to equity and diversity. Moreover, we add our own experiences to complement the limited literature addressing these topics. We conclude by highlighting some of the benefits of this unprecedented transformation in democratizing medical education that we hope endure beyond the pandemic.

Immunotherapy is an effective and generally well-tolerated treatment strategy for older adult patients (aged ≥70 years) with advanced non-small cell lung cancer (NSCLC). Unfortunately, most patients who receive immunotherapy eventually exhibit disease progression during treatment. The present study reports on a subset of older adult patients with advanced NSCLC who could effectively continue immunotherapy beyond radiographic disease progression due to perceived clinical benefit. Local consolidative radiotherapy may be used in select older adult patients to prolong the duration of immunotherapy they receive, with a particular consideration of their preexisting co-morbidities, performance status and tolerance of potential toxicities associated with combined modality therapy. However, prospective research is needed to determine which patients benefit most from the addition of local consolidative radiotherapy, including whether type of disease progression (i.e., sites of progression, pattern of progression) and/or extent of consolidation offered (i.e., complete or incomplete) impact clinical outcomes. Further research is also warranted to determine which patients would most benefit from the continuation of immunotherapy beyond documented radiographic disease progression., Competing Interests: MW is an employee of Medscape, LLC, New York, NY. JVH has served on the scientific advisory boards for AstraZeneca, EMD Serono, Boehringer-Ingelheim, Catalyst, Genentech, GlaxoSmithKline, Hengrui Therapeutics, Eli Lilly, Spectrum, Sanofi, Takeda, Mirati Therapeutics, BMS, BrightPath Biotherapeutics, Janssen Global Services, Nexus Health Systems, Pneuma Respiratory, Kairos Venture Investments, Roche, Leads Biolabs, RefleXion, and Chugai Pharmaceuticals. He receives research support from AstraZeneca, Bristol-Myers Squibb, Spectrum, and Takeda and royalties and licensing fees from Spectrum outside of the submitted work. MA received research funding (to institution) from Genentech, Nektar Therapeutics, Merck, GlaxoSmithKline, Novartis, Jounce Therapeutics, Bristol Myers Squibb, Eli Lilly, Adaptimmune, Shattuck Lab, and Gilead and receives consultant and advisor fees from GlaxoSmithKline, Shattuck Lab, Bristol Myers Squibb, and AstraZeneca. He receives speaker fees from AstraZeneca, Nektar Therapeutics, and SITC and acknowledges participation in safety review committees for Nanobiotix-MDA alliance and Hengenix outside of the submitted work. The remaining authors declare no conflict of interest., (Copyright © 2023, Spandidos Publications.)

The therapeutic landscape of lung cancer treatment is changing rapidly, and new data was presented at the recently concluded American Society of Clinical Oncology 2022 (ASCO22) meeting. We highlight studies of clinical relevance that represent significant updates in the current management of non-small cell lung cancer (SCLC) and small cell lung cancer (NSCLC). We summarize the updates in early-stage NSCLC, mutated and non-mutated advanced NSCLC as well as small cell lung cancer (SCLC), and discuss these advances in the context of the current clinical standard of care.

Introduction: As a result of the approval of several immune checkpoint inhibitors (ICIs) for the treatment of non-small cell lung cancer (NSCLC), many older adults are being treated with ICIs. Older adults are underrepresented in most pharmaceutical clinical trials. Therapy outcomes in this population with ICIs is particularly important since, age related factors may have an influence on the immune system., Methods: We utilized the MD Anderson Cancer Center Gemini Team's Lung Cancer Database to retrospectively study patients ≥70 years of age with advanced NSCLC treated with anti-PD-(L)1 monotherapy to look at the clinical outcomes., Results: 179 patients met the inclusion criteria for this retrospective analysis. There were 106 men and 73 women. The median age of the cohort was 74.9 years, and overall survival was 20.6 months. 27.6% of all patients had an objective response to therapy. In 33 patients who had radiological progression, treatment continued beyond progression due to clinical benefit. In this group, 6 patients had subsequent improvement in radiologic assessment. Age groups were not significantly associated with differences in clinical outcomes., Conclusions: This study suggests that anti-PD-(L)1 monotherapy is effective and well tolerated among older adults with advanced NSCLC. While pseudoprogression is rare, treatment beyond progression may provide clinical benefit in a subset of patients and warrants further investigation., (Copyright © 2022 Elsevier Inc. All rights reserved.)

In response to the COVID-19 social distancing guidelines, residency and fellowship programs transitioned to virtual instruction to deliver didactics and continue with medical education. The efficacy of such a fully online learning environment, however, remains unknown. To investigate its impact on medical education, this study surveyed hematology/oncology fellows at The University of Texas MD Anderson Cancer Center on their attitudes regarding the online-based lecture program. Fellows were emailed a 19-question survey with questions on demographics, ease of technical access to the online platform, level of comfort with participation, knowledge acquisition, wellness, and COVID-19-specific coverage. A free-text question soliciting ways to improve upon online learning was also included. The response rate was 71% (30/42). Most respondents reported easy/very easy accessibility to the online environment. Seventy-seven percent of the participants did not experience a technical issue. Seventy percent felt comfortable/very comfortable with participating in the conference. Thirty-seven percent felt comfortable/very comfortable with actively offering an answer to questions during the interactive board review session. Eighty-seven percent would have been more willing to offer an answer during the board review session if an anonymous poll format was utilized. Sixty-three percent felt they learned the same amount as they typically do during an in-person session. Thirty-three percent reported they were less focused as compared with an in-person session. One hundred percent of the participants had their questions answered, either at all times (87%) or sometimes (13%). Sixty percent experienced a change in social interactions as compared with an in-person session. Fifty-four percent reported that it was easy/very to balance online attendance despite personal/family commitments. One hundred percent appreciated the flexibility of the online learning environment. Ninety percent felt safer at home attending these lectures compared with receiving these lectures in-person during the COVID-19 pandemic. Overall, most fellows felt comfortable with the transition to a fully online learning environment. Strategies to encourage active participation, enhance social interaction, and provide additional flexibility are still needed.

The addition of PD-L1 targeting consolidation therapy to previously standard of care concurrent chemoradiation for locally advanced, unresectable non-small cell lung cancer resulted in dramatic improvements in clinical outcomes. However, in contrast to patients with metastatic disease, the application of immunotherapies is not currently guided by molecular characteristics of patient tumors. Furthermore, despite increasing awareness of predictive and/or prognostic genomic alterations in patients with locally advanced disease, the utility of targeted therapies, such as those aimed at alterations in EGFR or ALK , remains unclear in this subset of patients. As a result, patients with unresectable, locally advanced non-small cell lung cancer are treated uniformly according to histology, regardless of other molecular features despite the potential for treatment-associated risks without a clear benefit. Here, we first discuss the advantages of utilizing molecular biomarkers to guide treatment of non-small cell lung cancer based on treatment outcomes in the metastatic setting. Next, we review preclinical and retrospective clinical data that supports potential further personalization of these treatment strategies in earlier stages of disease. Finally, we discuss some of the ongoing clinical trials attempting to address these hypotheses prospectively., Competing Interests: Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr-20-330). The series “New era of treatment for unresectable locally advanced non-small cell lung cancer” was commissioned by the editorial office without any funding or sponsorship. CG reports grants from AstraZeneca. The other author has no other conflicts of interest to declare., (2020 Translational Lung Cancer Research. All rights reserved.)

Background: Early palliative care (PC) improves quality of life and prolongs survival for patients with metastatic non-small cell lung cancer (NSCLC). Despite these benefits, patient- and provider-specific barriers lead to underutilization of PC. To investigate these barriers, this 2 part study surveyed United States oncologists and patients with NSCLC., Patients and Methods: Oncologists in the International Association for the Study of Lung Cancer membership directory were surveyed on referral practice and attitudes regarding the role of PC for patients with NSCLC. Patients with advanced NSCLC at the Vanderbilt Ingram Cancer Center were surveyed separately regarding their understanding of PC and factors influencing them to seek referral., Results: Of 279 oncologists, 93 responded. Eighty-three percent believe definitive evidence exists supporting early PC; however, in practice, oncologists only refer an average of 19% of patients at diagnosis. Reasons for not referring included lack of symptoms (56%), belief that oncologists can manage PC independently (46%), not wanting to burden patients with appointments (41%), concern that referral may not be well received (38%), and long wait times (20%). Of 100 patients with NSCLC, 64% were unfamiliar with PC. Six percent had seen a PC provider. Ninety-eight percent of patients would accept referral if recommended by their oncologist. Patients desired referral for uncontrolled pain (95%), weak support system (86%), other cancer-related symptoms (85%), goals of care discussion (76%), and depression/anxiety (76%)., Conclusion: Although most oncologists acknowledge benefits of early PC for patients with metastatic NSCLC, a minority of patients are referred. Few patients with NSCLC are familiar with PC, but most are interested in referral., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Personalized therapy based on actionable molecular markers has completely transformed the therapeutic landscape in advanced non-small cell lung cancer (NSCLC). In less than 15 years, multiple molecular targets, led by EGFR and anaplastic lymphoma kinase (ALK), have been identified, and myriad oral tyrosine kinase inhibitors (TKIs) are now available to target these oncogenic drivers, with the expectation that the majority of patients will respond to treatment and that progression-free survival (PFS) will exceed 10 to 30 months, far better than we observed historically with chemotherapy alone. As a result, prognosis has improved dramatically in this subset of patients. Osimertinib has largely displaced first- and second-generation EGFR TKIs, including gefitinib, erlotinib, and afatinib, in the management of EGFR-mutated NSCLC. PFS now exceeds 18 months, and central nervous system penetrance is enhanced. Dacomitinib has the distinction of being the first EGFR TKI to demonstrate a survival advantage compared with older TKIs. Recent data suggest therapeutic additivity, if not synergy, for the concurrent use of chemotherapy, as well as monoclonal antibodies targeting angiogenesis, with EGFR TKIs. Alectinib and brigatinib, very specific ALK inhibitors, have proven superior to the erstwhile standard crizotinib in treatment-naive ALK+ NSCLC; PFS now routinely exceeds 2 to 3 years. In addition, these newer agents have far superior central nervous system penetration. As a result, many patients with ALK+ advanced NSCLC with brain metastases, even some who are symptomatic, can defer or indefinitely avoid brain irradiation. Mechanisms of resistance in ALK are complicated, with multiple new agents being developed in this arena. Although many patients with molecular targets can reasonably expect to live 5 years or more, the emergence of molecular resistance is virtually inevitable. In this regard, systemic platinum-based chemotherapy is the final common therapeutic pathway for virtually all patients with oncogenic drivers. Standard regimens include pemetrexed and carboplatin, as well as the E4599 regimen, combination solvent-based paclitaxel, carboplatin, and bevacizumab. Checkpoint inhibitors, as single agents, have not yielded much benefit, even in those with high levels of PD-L1 expression. However, in a subanalysis of patients with ALK and EGFR mutations enrolled in IMpower150, the addition of atezolizumab to the E4599 regimen led to a major overall survival benefit (hazard ratio < 0.40). In the absence of systemic chemotherapy, combining checkpoint inhibitors with TKIs in this setting remains investigational; several studies have demonstrated untoward pulmonary and hepatic toxicity.

Despite significant advancements in the treatment of anaplastic lymphoma kinase (ALK) positive non-small-cell lung cancer (NSCLC) since the advent of crizotinib, the development of acquired resistance and poor CNS efficacy have necessitated the search for novel and more robust therapies. Ensartinib (X-396) is a novel second-generation ALK-tyrosine kinase inhibitor (TKI) that holds much clinical promise. Preclinical data have demonstrated increased potency of the drug as compared with crizotinib and other second-generation ALK-TKI therapies such as alectinib and ceritinib. This review highlights the first- and second-generation ALK inhibitors approved for the treatment of ALK-positive NSCLC and discusses the clinical trial protocol for the eXalt3 trial (NCT02767804) comparing the efficacy and safety of ensartinib to crizotinib in patients diagnosed with ALK-positive NSCLC who are naive to prior ALK-TKI treatment.

Soft tissue sarcomas represent a group of heterogeneous mesenchymal tumors that occur rarely in adults. While a variety of histological subtypes exist, some of the most common are leiomyosarcoma and liposarcoma. For eligible patients, standard first-line treatment of metastatic disease has typically comprised anthracycline-containing regimens. While traditional cytotoxic chemotherapy has been the mainstay of treatment in metastatic soft tissue sarcoma, emerging targeted and novel therapies are creating new frontiers of treatment for a variety of histological subtypes. Olaratumab (Lartruvo, Eli Lilly) in combination with doxorubicin represents a new potential first-line treatment option. Second-line therapy is often histology-driven, and novel treatment options include trabectedin (Yondelis, Janssen) and eribulin (Halaven, Eisai). This review discusses the diagnosis, role of chemotherapy in unresectable and metastatic disease, and role of emerging therapies in the treatment of metastatic soft tissue sarcoma., Competing Interests: Disclosures: The authors report no commercial or financial interests in regard to this article.

The neuropeptide galanin has been implicated in the regulation of appetitive and consummatory behaviors. Prior studies have shown that direct injection of galanin into the hypothalamus results in increased release of dopamine (DA) in the nucleus accumbens (NAcc), and parallel increases in food and alcohol consumption. These studies are consistent with a role of hypothalamic galanin in regulating reward system reactivity. In humans, a common functional haplotype (GAL5.1) within a remote enhancer region upstream of the galanin gene (GAL) affects promoter activity and galanin expression in hypothalamic neurons in vitro. Given the effects of hypothalamic galanin on NAcc DA release and the effects of the GAL5.1 haplotype on GAL expression, we examined the impact of this functional genetic variation on human reward-related ventral striatum (VS) reactivity. Using an imaging genetics strategy in Caucasian individuals (N = 138, 72 women) participating in the ongoing Duke Neurogenetics Study, we report a significant gender-by-genotype interaction (right hemisphere: F1,134  = 8.08, P = 0.005; left hemisphere: F1,134  = 5.39, P = 0.022), such that homozygosity for the GG haplotype, which predicts greater GAL expression, is associated with relatively increased VS reactivity in women (n = 50, right hemisphere: P = 0.015; left hemisphere: P = 0.060), but not in men (N = 49, P-values > 0.10). Furthermore, these differences in VS reactivity correlated positively with differences in alcohol use, such that VS reactivity mediated a gender-specific association between GAL5.1 haplotype and problem drinking. Our current results support those in animal models implicating galanin signaling in neural pathways associated with appetitive and consummatory behaviors of relevance for understanding risk for substance use and abuse., (© 2013 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.)