Non-Small Cell Lung Cancer, Version 4.2024.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) provide recommendations for the treatment of patients with NSCLC, including diagnosis, primary disease management, surveillance for relapse, and subsequent treatment. The panel has updated the list of recommended targeted therapies based on recent FDA approvals and clinical data. This selection from the NCCN Guidelines for NSCLC focuses on treatment recommendations for advanced or metastatic NSCLC with actionable molecular biomarkers.

Thermal Characterization and Preclinical Feasibility Verification of an Accessible, Carbon Dioxide-Based Cryotherapy System.

To investigate the potential of an affordable cryotherapy device for the accessible treatment of breast cancer, the performance of a novel carbon dioxide-based device was evaluated through both benchtop testing and an in vivo canine model. This novel device was quantitatively compared to a commercial device that utilizes argon gas as the cryogen. The thermal behavior of each device was characterized through calorimetry and by measuring the temperature profiles of iceballs generated in tissue phantoms. A 45 min treatment in a tissue phantom from the carbon dioxide device produced a 1.67 ± 0.06 cm diameter lethal isotherm that was equivalent to a 7 min treatment from the commercial argon-based device, which produced a 1.53 ± 0.15 cm diameter lethal isotherm. An in vivo treatment was performed with the carbon dioxide-based device in one spontaneously occurring canine mammary mass with two standard 10 min freezes. Following cryotherapy, this mass was surgically resected and analyzed for necrosis margins via histopathology. The histopathology margin of necrosis from the in vivo treatment with the carbon dioxide device at 14 days post-cryoablation was 1.57 cm. While carbon dioxide gas has historically been considered an impractical cryogen due to its low working pressure and high boiling point, this study shows that carbon dioxide-based cryotherapy may be equivalent to conventional argon-based cryotherapy in size of the ablation zone in a standard treatment time. The feasibility of the carbon dioxide device demonstrated in this study is an important step towards bringing accessible breast cancer treatment to women in low-resource settings.

Uveal melanoma immunogenomics predict immunotherapy resistance and susceptibility.

Immune checkpoint inhibition has shown success in treating metastatic cutaneous melanoma but has limited efficacy against metastatic uveal melanoma, a rare variant arising from the immune privileged eye. To better understand this resistance, we comprehensively profile 100 human uveal melanoma metastases using clinicogenomics, transcriptomics, and tumor infiltrating lymphocyte potency assessment. We find that over half of these metastases harbor tumor infiltrating lymphocytes with potent autologous tumor specificity, despite low mutational burden and resistance to prior immunotherapies. However, we observe strikingly low intratumoral T cell receptor clonality within the tumor microenvironment even after prior immunotherapies. To harness these quiescent tumor infiltrating lymphocytes, we develop a transcriptomic biomarker to enable in vivo identification and ex vivo liberation to counter their growth suppression. Finally, we demonstrate that adoptive transfer of these transcriptomically selected tumor infiltrating lymphocytes can promote tumor immunity in patients with metastatic uveal melanoma when other immunotherapies are incapable.

Mesothelioma: Pleural, Version 1.2024.

Mesothelioma is a rare cancer that originates from the mesothelial surfaces of the pleura and other sites, and is estimated to occur in approximately 3,500 people in the United States annually. Pleural mesothelioma is the most common type and represents approximately 85% of these cases. The NCCN Guidelines for Mesothelioma: Pleural provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with pleural mesothelioma. These NCCN Guidelines Insights highlight significant updates to the NCCN Guidelines for Mesothelioma: Pleural, including revised guidance on disease classification and systemic therapy options.

The Efficacy and Safety of Treating Acquired MET Resistance Through Combinations of Parent and MET Tyrosine Kinase Inhibitors in Patients With Metastatic Oncogene-Driven NSCLC.

Introduction: Acquired MET gene amplification, MET exon 14 skip mutations, or MET fusions can emerge as resistance mechanisms to tyrosine kinase inhibitors (TKIs) in patients with lung cancer. The efficacy and safety of combining MET TKIs (such as crizotinib, capmatinib, or tepotinib) with parent TKIs to target acquired MET resistance are not well characterized. Methods: Multi-institutional retrospective chart review identified 83 patients with metastatic oncogene-driven NSCLC that were separated into the following two pairwise matched cohorts: (1) MET cohort (n = 41)-patients with acquired MET resistance continuing their parent TKI with a MET TKI added or (2) Chemotherapy cohort (n = 42)-patients without any actionable resistance continuing their parent TKI with a platinum-pemetrexed added. Clinicopathologic features, radiographic response (by means of Response Evaluation Criteria in Solid Tumors version 1.1), survival outcomes, adverse events (AEs) (by means of Common Terminology Criteria for Adverse Events version 5.0), and genomic data were collected. Survival outcomes were assessed using Kaplan-Meier methods. Multivariate modeling adjusted for lines of therapy, brain metastases, TP53 mutations, and oligometastatic disease. Results: Within the MET cohort, median age was 56 years (range: 36-83 y). Most patients were never smokers (28 of 41, 68.3%). Baseline brain metastases were common (21 of 41, 51%). The most common oncogenes in the MET cohort were EGFR (30 of 41, 73.2%), ALK (seven of 41, 17.1%), and ROS1 (two of 41, 4.9%). Co-occurring TP53 mutations (32 of 41, 78%) were frequent. Acquired MET alterations included MET gene amplification (37 of 41, 90%), MET exon 14 mutations (two of 41, 5%), and MET gene fusions (two of 41, 5%). After multivariate adjustment, the objective response rate (ORR) was higher in the MET cohort versus the chemotherapy cohort (ORR: 69.2% versus 20%, p < 0.001). Within the MET cohort, MET gene copy number (≥10 versus 6-10) did not affect radiographic response (54.5% versus 68.4%, p = 0.698). There was no difference in ORR on the basis of MET TKI used (F [2, 36] = 0.021, p = 0.978). There was no difference in progression-free survival (5 versus 6 mo; hazard ratio = 0.64; 95% confidence interval: 0.34-1.23, p = 0.18) or overall survival (13 versus 11 mo; hazard ratio = 0.75; 95% confidence interval: 0.42-1.35, p = 0.34) between the MET and chemotherapy cohorts. In the MET cohort, dose reductions for MET TKI-related toxicities were common (17 of 41, 41.4%) but less frequent for parent TKIs (two of 41, 5%). Grade 3 AEs were not significant between crizotinib, capmatinib, and tepotinib (p = 0.3). The discontinuation rate of MET TKIs was 17% with no significant differences between MET TKIs (p = 0.315). Among pre- and post-treatment biopsies (n = 17) in the MET cohort, the most common next-generation sequencing findings were loss of MET gene amplification (15 of 17, 88.2%), MET on-target mutations (seven of 17, 41.2%), new Ras-Raf-MAPK alterations (three of 17, 17.6%), and EGFR gene amplification (two of 17, 11.7%). Conclusions: The efficacy and safety of combining MET TKIs (crizotinib, capmatinib, or tepotinib) with parent TKIs for acquired MET resistance are efficacious. Radiographic response and AEs did not differ significantly on the basis of the underlying MET TKI used. Loss of MET gene amplification, development of MET on-target mutations, Ras-Raf-MAPK alterations, and EGFR gene amplification were molecular patterns found on progression with dual parent and MET TKI combinations.

Patient perspectives of weight stigma across the cancer continuum: A scoping review.

BACKGROUND: Weight stigma has been defined as the social devaluation and denigration of individuals because of their weight. The purpose of this scoping systematic review was to assess and understand patient experiences with weight stigma in the cancer care setting. METHODS: We conducted a systematic scoping review of studies examining shame, prejudice, bias, and stigma in relation to weight and cancer-related care using five databases: PubMed, CINAHL Plus Full Text (ProQuest), Cochrane Library, PsycINFO (EBSCO), and Scopus. Articles were uploaded into Covidence for de-duplication and screening. Included studies were peer reviewed, reported adult patient experiences in cancer-related care, and were published in English between October 2012 and February 2023. Study characteristics and key findings were abstracted and qualitatively synthesized. RESULTS: Publications meeting inclusion criteria yielded five studies (n = 113 participants). Most focused on the experiences of women (n = 4) and cancers which predominantly impact women (i.e., breast, cervical, endometrial; n = 4). All stages of the cancer continuum were included with studies examining screening (n = 2), treatment (n = 1), and post-treatment survivorship (n = 2). Weight discrimination was discussed in four studies and weight-biased stereotypes were discussed in three studies. Experiences of weight bias internalization were reported in four studies. One study described an instance of implicit weight bias. CONCLUSIONS: Limited studies examine patient experiences of weight stigma in cancer care; however, current evidence suggests that patients do experience weight stigma in cancer-related care. This review highlights critical gaps and a need for more research on the prevalence and impact of weight stigma in cancer screening and care.

Impact of Intermittent Fasting and/or Caloric Restriction on Aging-Related Outcomes in Adults: A Scoping Review of Randomized Controlled Trials.

Intermittent fasting (IF) and caloric restriction (CR) are dietary strategies to prevent and attenuate obesity associated with conditions and aging-related outcomes. This scoping review examined the cardiometabolic, cancer, and neurocognitive outcome differences between IF and CR interventions among adults. We applied a systematic approach to scope published randomized controlled trials (databases: PubMed, CINAHL Plus, PsychInfo, Scopus, and Google Scholar) from inception through August 2023. The initial search provided 389 unique articles which were critically appraised. Thirty articles met the eligibility criteria for inclusion: 12 were IF, 10 were CR, and 8 were combined IF and CR interventions. IF and CR were associated with weight loss; however, IF studies tended to report greater adherence compared with CR. Overall, IF and CR were equivalently effective across cardiometabolic, cancer, and neurocognitive outcomes. Our findings suggest that IF has health benefits in a variety of conditions and may be better accepted and tolerated than CR, but more comparative research is required.

Therapeutic efficacy of an alpha-particle emitter labeled anti-GD2 humanized antibody against osteosarcoma-a proof of concept study.

PURPOSE: Current treatments for osteosarcoma (OS) have a poor prognosis, particularly for patients with metastasis and recurrence, underscoring an urgent need for new targeted therapies to improve survival. Targeted alpha-particle therapy selectively delivers cytotoxic payloads to tumors with radiolabeled molecules that recognize tumor-associated antigens. We have recently demonstrated the potential of an FDA approved, humanized anti-GD2 antibody, hu3F8, as a targeted delivery vector for radiopharmaceutical imaging of OS. The current study aims to advance this system for alpha-particle therapy of OS. METHODS: The hu3F8 antibody was radiolabeled with actinium-225, and the safety and therapeutic efficacy of the [225Ac]Ac-DOTA-hu3F8 were evaluated in both orthotopic murine xenografts of OS and spontaneously occurring OS in canines. RESULTS: Significant antitumor activity was proven in both cases, leading to improved overall survival. In the murine xenograft's case, tumor growth was delayed by 16-18 days compared to the untreated cohort as demonstrated by bioluminescence imaging. The results were further validated with magnetic resonance imaging at 33 days after treatment, and microcomputed tomography and planar microradiography post-mortem. Histological evaluations revealed radiation-induced renal toxicity, manifested as epithelial cell karyomegaly and suggestive polyploidy in the kidneys, suggesting rapid recovery of renal function after radiation damage. Treatment of the two canine patients delayed the progression of metastatic spread, with an overall survival time of 211 and 437 days and survival beyond documented metastasis of 111 and 84 days, respectively. CONCLUSION: This study highlights the potential of hu3F8-based alpha-particle therapy as a promising treatment strategy for OS.

Prospective Clinical Prognostication of Endometrial Carcinomas Based on Next-Generation Sequencing and Immunohistochemistry-Real-World Implementation and Results at a Tertiary Care Center.

Based on findings from The Cancer Genome Atlas and the Proactive Molecular Risk Classifier for Endometrial Cancer algorithm, endometrial carcinoma can now be stratified into 4 prognostically distinct subgroups based on molecular alterations and immunohistochemical (IHC) aberrations. In this study, we describe the de novo adoption and clinical reporting of prognostic subgroup classification based on next-generation sequencing (NGS) and IHC analyses of all endometrial carcinoma resections at a single institution, framed by the Exploration, Preparation, Implementation, and Sustainment model. Results from the first 13 months show 188 tumors underwent analysis by a combination of IHC and a medium-sized (56 analyzed genes) NGS-based assay. All cases were assigned as either POLE (POLE-mutated) (5.3%), mismatch repair deficient (27.7%), no specific molecular profile (45.7%), or p53 abnormal (21.3%) inclusive of multiple-classifier cases. NGS-based analysis revealed additional distinctions among the subgroups, including reduced levels of PI3K pathway activation in the p53 abnormal subgroup, an increased rate of CTNNB1 activating mutation in the no specific molecular profile subgroup, and lower TP53 mutation variant allele frequencies in POLE and mismatch repair deficient subgroups compared with the p53 abnormal subgroup. Overall, we describe the testing protocol, reporting, and results of a combination of NGS and IHC to prospectively prognosticate endometrial carcinomas at a single tertiary care center.

The association between endometrial polyps, chronic endometritis, and IVF outcomes.

OBJECTIVE: Endometrial polyps (EPs) are one of the most common pathologies detected during the examination of the uterine cavity of infertile women. We aimed to demonstrate the relationship between EPs, chronic endometritis (CE) and in vitro fertilization (IVF) outcomes. PATIENTS AND METHODS: This retrospective study was performed on 394 hysteroscopically examined infertility cases. We performed polyp resections (PR) and extensive biopsies of the endometrium to demonstrate the association with clinical pregnancy (CP) by IVF. We performed statistical analysis to compare these associations. RESULTS: The incidence of CE was twice as high in the presence of EPs as in the absence of EPs. The associations between EPs and PR were found to be significant for positive CP outcomes. A significant difference in IVF outcome was found between the group with EPs and the group without EPs. All these associations were statistically significant (p < 0.05). CONCLUSIONS: We found a frequent association between EPs and CE. The pregnancy rate obtained after IVF was negatively affected by the presence of EPs. Treatment of these pathologies improved IVF outcomes.

Mesothelioma: Peritoneal, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology.

Mesothelioma is a rare cancer originating in mesothelial surfaces of the peritoneum, pleura, and other sites. These NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) focus on peritoneal mesothelioma (PeM). The NCCN Guidelines for PeM provide recommendations for workup, diagnosis, and treatment of primary as well as previously treated PeM. The diagnosis of PeM may be delayed because PeM mimics other diseases and conditions and because the disease is so rare. The pathology section was recently updated to include new information about markers used to identify mesothelioma, which is difficult to diagnose. The term "malignant" is no longer used to classify mesotheliomas, because all mesotheliomas are now defined as malignant.

Well-being predictors of body composition and associated behavioral risk factors in midlife/older women participating in a meditative movement intervention: an exploratory analysis.

Introduction: Greater than 40% of women are obese, a key risk factor for cardiometabolic, neurocognitive disease, mood disorders, and certain cancers. Obesity and unfavorable body composition can compromise physical and psychological health and well-being. Preliminary evidence demonstrates Meditative Movement (i.e., Tai Chi Easy) improves health outcomes and body composition among midlife/older women. This single-group pilot study explored relationships between well-being predictors related to body composition and associated behavioral risk factors in midlife/older women pre-to-post Tai Chi Easy intervention. Methods: Eligible women 45-75 years old, participated in once-weekly 30-minute Tai Chi Easy classes over 8-weeks. Pre/post-intervention data included self-report surveys and on-site body composition. Multivariate linear regression models were fitted with putative predictor variables having correlations p-values of 0.20 or less with sleep quality and eating behaviors. Results: Participants (N = 36) (M age = 53.7) were White (80.4%) and attended ≥ 4 years of college (70.6%). Analyses resulted in one independent variable per model as a predictor of the dependent variables of sleep quality and emotional eating. Results indicated: (1) stress explained 13.4% sleep quality variance (F (2, 20) = 2.71, p = 0.09) and (2) self-compassion explained 42.1% emotional eating variance (F (2, 31) = 12.54, p < .01). Conclusion: Findings suggest stress and self-compassion partially explain variance in the dependent variables of sleep quality and emotional eating, both associated behavioral risk factors of body composition. Additional research may guide interventions to test efficacy and examine mediators to improve well-being predictors, body composition, and associated behavioral risk factors among midlife/older women.

The Genomics Organization for Academic Laboratories (GOAL): A vision for a genomics future for academic pathology.

Innovative and self-sustaining clinical genomics laboratories specializing in cutting-edge oncology testing are critical to the success of academic pathology departments and resident and fellow education in molecular pathology. However, the pressures and challenges facing these laboratories are numerous, including the complexities of validating comprehensive cancer next-generation sequencing (NGS) panels, competition from commercial laboratories, and the reimbursement and regulatory hurdles inherent in high-complexity testing. Cross-institutional collaborations, including shared assay content and interpretative frameworks, are a valuable element to academic laboratory success. To address these and other needs, the Genomics Organization for Academic Laboratories (GOAL) was conceived in 2018, incorporated in 2020 and has grown to include 29 participating institutions in 2022. Here, we describe the mission of GOAL, its structure, and the outcomes and projects undertaken in its first years.

The impact of a meditative movement practice intervention on short- and long-term changes in physical activity among breast cancer survivors.

PURPOSE: Tai Chi Easy (TCE) is a low-impact, meditative movement practice that is feasible for breast cancer survivors, even in the face of post-treatment symptoms, and may even serve as a gateway into developing an active lifestyle and improving overall physical activity (PA). In the context of a randomized controlled trial testing effects of an 8-week TCE intervention on breast cancer survivors' symptoms, we examined the short- (8-week) and long-term (9-month) impact on total PA compared to an educational control group. METHODS: Participants were recruited from two hospital systems, local community organizations, and different media platforms. Eligible participants were predominant non-Hispanic White (82%), college educated (92%), and middle- to high-income (65%), and most commonly reported stage 1 (40%) or 2 breast cancer (38%). After baseline assessments, participants were randomized to the 8-week TCE intervention (N=51) or education control (N=53). Weekly intervention TCE classes were led by a trained instructor. Weekly educational control classes focused on a series of readings and group discussions. Total PA and steps were objectively measured via accelerometry, and the international physical activity questionnaire was used to measure self-reported total PA. RESULTS: Multilevel mixed-effects linear regression models revealed no significant short- or long-term changes in objectively measured total PA or steps in either group; however, participants in the intervention reported short- and long-term changes in self-reported total PA. CONCLUSIONS: TCE is an appropriate PA strategy for survivors that may lead to modest improvements in PA; however, more research is needed to examine the long-term impact on PA as well as other physical and psychological outcomes (i.e., flexibility, mobility, stress). IMPLICATIONS FOR CANCER SURVIVORS: Low-impact, low-intensity activities like meditative movement practices are needed to assist survivors in overcoming post-treatment physical and psychological limitations to initiate a more active lifestyle.

Current clinical practices and challenges in molecular testing: a GOAL Consortium Hematopathology Working Group report.

While molecular testing of hematologic malignancies is now standard of care, there is variability in practice and testing capabilities between different academic laboratories, with common questions arising on how to best meet clinical expectations. A survey was sent to hematopathology subgroup members of the Genomics Organization for Academic Laboratories consortium to assess current and future practice and potentially establish a reference for peer institutions. Responses were received from 18 academic tertiary-care laboratories regarding next-generation sequencing (NGS) panel design, sequencing protocols and metrics, assay characteristics, laboratory operations, case reimbursement, and development plans. Differences in NGS panel size, use, and gene content were reported. Gene content for myeloid processes was reported to be generally excellent, while genes for lymphoid processes were less well covered. The turnaround time (TAT) for acute cases, including acute myeloid leukemia, was reported to range from 2 to 7 calendar days to 15 to 21 calendar days, with different approaches to achieving rapid TAT described. To help guide NGS panel design and standardize gene content, consensus gene lists based on current and future NGS panels in development were generated. Most survey respondents expected molecular testing at academic laboratories to continue to be viable in the future, with rapid TAT for acute cases likely to remain an important factor. Molecular testing reimbursement was reported to be a major concern. The results of this survey and subsequent discussions improve the shared understanding of differences in testing practices for hematologic malignancies between institutions and will help provide a more consistent level of patient care.

Intermittent fasting interventions to leverage metabolic and circadian mechanisms for cancer treatment and supportive care outcomes.

Intermittent fasting entails restricting food intake during specific times of day, days of the week, religious practice, or surrounding clinically important events. Herein, the metabolic and circadian rhythm mechanisms underlying the proposed benefits of intermittent fasting for the cancer population are described. We summarize epidemiological, preclinical, and clinical studies in cancer published between January 2020 and August 2022 and propose avenues for future research. An outstanding concern regarding the use of intermittent fasting among cancer patients is that fasting often results in caloric restriction, which can put patients already prone to malnutrition, cachexia, or sarcopenia at risk. Although clinical trials do not yet provide sufficient data to support the general use of intermittent fasting in clinical practice, this summary may be useful for patients, caregivers, and clinicians who are exploring intermittent fasting as part of their cancer journey for clinical outcomes and symptom management.

Key takeaways for knowledge expansion of early-career scientists conducting Transdisciplinary Research in Energetics and Cancer (TREC): a report from the TREC Training Workshop 2022.

The overall goal of the annual Transdisciplinary Research in Energetics and Cancer (TREC) Training Workshop is to provide transdisciplinary training for scientists in energetics and cancer and clinical care. The 2022 Workshop included 27 early-to-mid career investigators (trainees) pursuing diverse TREC research areas in basic, clinical, and population sciences. The 2022 trainees participated in a gallery walk, an interactive qualitative program evaluation method, to summarize key takeaways related to program objectives. Writing groups were formed and collaborated on this summary of the 5 key takeaways from the TREC Workshop. The 2022 TREC Workshop provided a targeted and unique networking opportunity that facilitated meaningful collaborative work addressing research and clinical needs in energetics and cancer. This report summarizes the 2022 TREC Workshop's key takeaways and future directions for innovative transdisciplinary energetics and cancer research.