Non-Small Cell Lung Cancer, Version 4.2024, NCCN Clinical Practice Guidelines in Oncology

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.

NCCN Guidelines® Insights: 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.

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.

NCCN Guidelines® Insights: Non-Small Cell Lung Cancer, Version 2.2023.

The NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) provide recommendations for management of disease in patients with NSCLC. These NCCN Guidelines Insights focus on neoadjuvant and adjuvant (also known as perioperative) systemic therapy options for eligible patients with resectable NSCLC.

Non-Small Cell Lung Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology.

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) provide recommended management for patients with NSCLC, including diagnosis, primary treatment, surveillance for relapse, and subsequent treatment. Patients with metastatic lung cancer who are eligible for targeted therapies or immunotherapies are now surviving longer. This selection from the NCCN Guidelines for NSCLC focuses on targeted therapies for patients with metastatic NSCLC and actionable mutations.

Postoperative Trapped Lung After Orthotopic Liver Transplantation is a Predictor of Increased Mortality.

Pleural effusions are a common complication of orthotopic liver transplantation (OLT), and chronic post-OLT pleural effusions have been associated with worse outcomes. Furthermore, "trapped lung" (TL), defined as a restrictive fibrous visceral pleural peel preventing lung re-expansion, may have prognostic significance. We performed a retrospective analysis of adult OLT recipients over a 9-year period at UCLA Medical Center. Post-OLT patients with persistent pleural effusions, defined by the presence of pleural fluid requiring drainage one to 12 months after OLT, were included for analysis. Outcomes for patients with and without TL were compared using univariate and multivariate analysis. Of the 1722 patients who underwent OLT, 117 (7%) patients met our criteria for persistent postoperative pleural effusion, and the incidence of TL was 21.4% (25/117). Compared to patients without TL, those with TL required more surgical pleural procedures (OR 59.8, 95%CI 19.7-181.4, p < 0.001), spent more days in the hospital (IRR 1.56, 95%CI 1.09-2.23, p = 0.015), and had a higher risk of mortality (HR 2.47, 95%CI 1.59-3.82, p < 0.001) following transplant. In sum, we found that post-OLT TL was associated with higher morbidity, mortality, and healthcare utilization. Future prospective investigation is warranted to further clarify the risk factors for developing postoperative pleural effusions and TL.

NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 2.2021.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines regarding targeted therapies, immunotherapies, and their respective biomarkers.

Society of Interventional Radiology Quality Improvement Standards on Percutaneous Ablation of Non-Small Cell Lung Cancer and Metastatic Disease to the Lungs.

PURPOSE: To provide guidance on quality improvement thresholds for outcomes and complications of image-guided thermal ablation for the treatment of early stage non-small cell lung cancer, recurrent lung cancer, and metastatic disease. MATERIALS AND METHODS: A multidisciplinary writing group conducted a comprehensive literature search to identify studies on the topic of interest. Data were extracted from relevant studies and thresholds were derived from a calculation of 2 standard deviations from the weighted mean of each outcome. A modified Delphi technique was used to achieve consensus agreement on the thresholds. RESULTS: Data from 29 studies, including systematic reviews and meta-analyses, retrospective cohort studies, and single-arm trials were extracted for calculation of the thresholds. The expert writing group agreed on thresholds for local control, overall survival and adverse events associated with image-guided thermal ablation. CONCLUSION: SIR recommends utilizing the indicator thresholds to review and assess the efficacy of ongoing quality improvement programs. When performance falls above or below specific thresholds, consideration of a review of policies and procedures to assess for potential causes, and to implement changes in practices, may be warranted.

Society of Interventional Radiology Multidisciplinary Position Statement on Percutaneous Ablation of Non-small Cell Lung Cancer and Metastatic Disease to the Lungs: Endorsed by the Canadian Association for Interventional Radiology, the Cardiovascular and Interventional Radiological Society of Europe, and the Society of Interventional Oncology.

PURPOSE: To state the Society of Interventional Radiology's position on the use of image-guided thermal ablation for the treatment of early stage non-small cell lung cancer, recurrent lung cancer, and metastatic disease to the lung. MATERIALS AND METHODS: A multidisciplinary writing group, with expertise in treating lung cancer, conducted a comprehensive literature search to identify studies on the topic of interest. Recommendations were drafted and graded according to the updated SIR evidence grading system. A modified Delphi technique was used to achieve consensus agreement on the recommendation statements. RESULTS: A total of 63 studies, including existing systematic reviews and meta-analysis, retrospective cohort studies, and single-arm trials were identified. The expert writing group developed and agreed on 7 recommendations on the use of image-guided thermal ablation in the lung. CONCLUSION: SIR considers image-guided thermal ablation to be an acceptable treatment option for patients with inoperable Stage I NSCLC, those with recurrent NSCLC, as well as patients with metastatic lung disease.

Recurrent ventricular tachycardia after cardiac sympathetic denervation: Prolonged cycle length with improved hemodynamic tolerance and ablation outcomes.

INTRODUCTION: Cardiac sympathetic denervation (CSD) is utilized for the management of ventricular tachycardia (VT) in structural heart disease when refractory to radiofrequency ablation (RFA) or when patient/VT characteristics are not conducive to RFA. METHODS: We studied consecutive patients who underwent CSD at our institution from 2009 to 2018 with VT requiring repeat RFA post-CSD. Patient demographics, VT/procedural characteristics, and outcomes were assessed. RESULTS: Ninety-six patients had CSD, 16 patients underwent RFA for VT post-CSD. There were 15 male and 1 female patients with mean age of 54.2 ± 13.2 years. Fourteen patients had nonischemic cardiomyopathy. A mean of 2.0 ± 0.8 RFAs for VT was unsuccessful before the patient undergoing CSD. The median time between CSD and RFA was 104 days (interquartile range [IQR] = 15-241). The clinical VT cycle length was significantly increased after CSD both spontaneously on ECG and/or ICD interrogation (355 ± 73 ms pre-CSD vs. 422 ± 94 ms post-CSD, p = .001) and intraprocedurally (406 ± 86 ms pre-CSD vs. 457 ± 88 ms post-CSD, p = .03). Two patients had polymorphic and 14 had monomorphic VT (MMVT) pre-CSD, and all patients had MMVT post-CSD. The proportion of mappable, hemodynamically stable VTs increased from 35% during pre-CSD RFA to 58% during post-CSD RFA (p = .038). At median follow-up of 413 days (IQR = 43-1840) after RFA, eight patients had no further VT. CONCLUSION: RFA for recurrent MMVT post-CSD is a reasonable treatment option with intermediate-term clinical success in 50% of patients. Clinical VT cycle length was significantly increased after CSD with associated improvement in mappable, hemodynamically tolerated VT during RFA.

Short-Term Readmissions After Open, Thoracoscopic, and Robotic Lobectomy for Lung Cancer Based on the Nationwide Readmissions Database.

BACKGROUND: Readmission after surgery is an established surrogate indicator of quality of care. We aimed to compare short-term readmission rates and patient outcomes between open, video-assisted thoracoscopic (VATS), and robotic lobectomies in the Nationwide Readmissions Database (NRD). METHODS: Adults who underwent open, VATS, or robotic lobectomy for lung cancer from 2010 to 2014 were evaluated. Propensity-matched analysis was used to assess differences in readmission characteristics, GDP-adjusted cost, and mortality. RESULTS: Of the 129,539 lobectomies for lung cancer, 74,493 (57.5%) were open, 48,185 (37.2%) VATS, and 6861 (5.3%) robotic. Open surgery was associated with significantly higher readmission rate (10.5 vs 9.3%, p < 0.001), mortality (2 vs 1.2%, p < 0.001), index hospitalization cost [$21,846 (16,158-31,034) vs $20,779 (15,619-27,920), p < 0.001], and length of stay [6 (5-9) vs 4 (3-7) days, p < 0.001] compared to minimally invasive surgery. The robotic approach had similar mortality, readmission rate, and length of stay compared to VATS, but higher index cost [$23,870 (18,372-31,300) vs $20,279 (15,275-27,375), p < 0.001] and incidence of pulmonary complication (35.9 vs 31.6%, p < 0.001). The robotic approach was associated with greater direct discharges to home. CONCLUSIONS: Analysis of the NRD revealed significantly reduced readmission rates, better clinical outcomes, and lower cost in the minimally invasive approach compared to open surgery. Although VATS and robotic surgery had similar readmission and mortality rates, VATS is associated with significantly reduced risk of short-term complications and lower cost.

Quality of patient-reported outcome reporting across cancer randomized controlled trials according to the CONSORT patient-reported outcome extension: A pooled analysis of 557 trials.

BACKGROUND: The main objectives of this study were to identify the number of randomized controlled trials (RCTs) including a patient-reported outcome (PRO) endpoint across a wide range of cancer specialties and to evaluate the completeness of PRO reporting according to the Consolidated Standards of Reporting Trials (CONSORT) PRO extension. METHODS: RCTs with a PRO endpoint that had been performed across several cancer specialties and published between 2004 and 2013 were considered. Studies were evaluated on the basis of previously defined criteria, including the CONSORT PRO extension and the Cochrane Collaboration's tool for assessing the risk of bias of RCTs. Analyses were also conducted by the type of PRO endpoint (primary vs secondary) and by the cancer disease site. RESULTS: A total of 56,696 potentially eligible records were scrutinized, and 557 RCTs with a PRO evaluation, enrolling 254,677 patients overall, were identified. PROs were most frequently used in RCTs of breast (n = 123), lung (n = 85), and colorectal cancer (n = 66). Overall, PROs were secondary endpoints in 421 RCTs (76%). Four of 6 evaluated CONSORT PRO items were documented in less than 50% of the RCTs. The level of reporting was higher in RCTs with a PRO as a primary endpoint. The presence of a supplementary report was the only statistically significant factor associated with greater completeness of reporting for both RCTs with PROs as primary endpoints (ß = .19, P = .001) and RCTs with PROs as secondary endpoints (ß = .30, P < .001). CONCLUSIONS: Implementation of the CONSORT PRO extension is equally important across all cancer specialties. Its use can also contribute to revealing the robust PRO design of some studies, which might be obscured by poor outcome reporting.

Glucose Deprivation Promotes Pseudohypoxia and Dedifferentiation in Lung Adenocarcinoma.

Increased utilization of glucose is a hallmark of cancer. Sodium-glucose transporter 2 (SGLT2) is a critical player in glucose uptake in early-stage and well-differentiated lung adenocarcinoma (LUAD). SGLT2 inhibitors, which are FDA approved for diabetes, heart failure, and kidney disease, have been shown to significantly delay LUAD development and prolong survival in murine models and in retrospective studies in diabetic patients, suggesting that they may be repurposed for lung cancer. Despite the antitumor effects of SGLT2 inhibition, tumors eventually escape treatment. Here, we studied the mechanisms of resistance to glucose metabolism-targeting treatments. Glucose restriction in LUAD and other tumors induced cancer cell dedifferentiation, leading to a more aggressive phenotype. Glucose deprivation caused a reduction in alpha-ketoglutarate (αKG), leading to attenuated activity of αKG-dependent histone demethylases and histone hypermethylation. The dedifferentiated phenotype depended on unbalanced EZH2 activity that suppressed prolyl-hydroxylase PHD3 and increased expression of hypoxia-inducible factor 1α (HIF1α), triggering epithelial-to-mesenchymal transition. Finally, a HIF1α-dependent transcriptional signature of genes upregulated by low glucose correlated with prognosis in human LUAD. Overall, this study furthers current knowledge of the relationship between glucose metabolism and cell differentiation in cancer, characterizing the epigenetic adaptation of cancer cells to glucose deprivation and identifying targets to prevent the development of resistance to therapies targeting glucose metabolism. SIGNIFICANCE: Epigenetic adaptation allows cancer cells to overcome the tumor-suppressive effects of glucose restriction by inducing dedifferentiation and an aggressive phenotype, which could help design better metabolic treatments.

The 2023 American Association for Thoracic Surgery (AATS) Expert Consensus Document: Management of subsolid lung nodules.

OBJECTIVE: Lung cancers that present as radiographic subsolid nodules represent a subtype with distinct biological behavior and outcomes. The objective of this document is to review the existing literature and report consensus among a group of multidisciplinary experts, providing specific recommendations for the clinical management of subsolid nodules. METHODS: The American Association for Thoracic Surgery Clinical Practice Standards Committee assembled an international, multidisciplinary expert panel composed of radiologists, pulmonologists, and thoracic surgeons with established expertise in the management of subsolid nodules. A focused literature review was performed with the assistance of a medical librarian. Expert consensus statements were developed with class of recommendation and level of evidence for each of 4 main topics: (1) definitions of subsolid nodules (radiology and pathology), (2) surveillance and diagnosis, (3) surgical interventions, and (4) management of multiple subsolid nodules. Using a modified Delphi method, the statements were evaluated and refined by the entire panel. RESULTS: Consensus was reached on 17 recommendations. These consensus statements reflect updated insights on subsolid nodule management based on the latest literature and current clinical experience, focusing on the correlation between radiologic findings and pathological classifications, individualized subsolid nodule surveillance and surgical strategies, and multimodality therapies for multiple subsolid lung nodules. CONCLUSIONS: Despite the complex nature of the decision-making process in the management of subsolid nodules, consensus on several key recommendations was achieved by this American Association for Thoracic Surgery expert panel. These recommendations, based on evidence and a modified Delphi method, provide guidance for thoracic surgeons and other medical professionals who care for patients with subsolid nodules.

The majority of patients with resectable incidental lung cancers are ineligible for lung cancer screening.

Objective: The study objective was to determine what proportion of asymptomatic patients had resectable lung cancer detected through lung cancer screening versus incidentally. Methods: We performed a retrospective study of patients who underwent resection for lung cancer between January 2015 and December 2020. We then assessed whether asymptomatic patients with incidentally found lung cancers were eligible for lung cancer screening using the National Comprehensive Cancer Network, United States Preventive Services Task Force, Centers for Medicare & Medicaid Services, American College of Chest Physicians, American Cancer Society, and American Society of Clinical Oncology guidelines. Results: Of 539 patients who underwent resection for primary lung cancer, 437 (81%) were asymptomatic and 355 (66%) of these patients had lung cancer found discovered incidentally. Of the 355 patients with incidentally detected lung cancer, 10 were excluded for insufficient data. Of the remaining 345 patients, 110 (32%) would have been eligible for screening using National Comprehensive Cancer Network guidelines, 65 (19%) using 2021 United States Preventive Services Task Force guidelines, 53 (15%) using 2013 United States Preventive Services Task Force guidelines, 64 (19%) using 2022 Centers for Medicare & Medicaid Services guidelines, 52 (15%) using 2015 Centers for Medicare & Medicaid Services/American College of Chest Physicians guidelines, and 45 (13%) using American Cancer Society/American Society of Clinical Oncology guidelines. Of the 280 patients who were screen ineligible by 2021 United States Preventive Services Task Force criteria, 143 patients (51%) never smoked, 112 patients (40%) quit smoking more than 15 years ago, 89 patients (32%) did not smoke at least 20 pack-years, and 44 patients (16%) were ineligible due to age. Conclusions: The majority of asymptomatic patients with resectable lung cancers had lung cancer identified incidentally and not through lung cancer screening. Most of these patients were not eligible for screening under current guidelines. This study suggests a need for improved lung cancer screening implementation and further investigation in the identification and assessment of risk factors for lung cancer.

Glucose deprivation promotes pseudo-hypoxia and de-differentiation in lung adenocarcinoma.

Increased utilization of glucose is a hallmark of cancer. Several studies are investigating the efficacy of glucose restriction by glucose transporter blockade or glycolysis inhibition. However, the adaptations of cancer cells to glucose restriction are unknown. Here, we report the discovery that glucose restriction in lung adenocarcinoma (LUAD) induces cancer cell de-differentiation, leading to a more aggressive phenotype. Glucose deprivation causes a reduction in alpha-ketoglutarate (αKG), leading to attenuated activity of αKG-dependent histone demethylases and histone hypermethylation. We further show that this de-differentiated phenotype depends on unbalanced EZH2 activity, causing inhibition of prolyl-hydroxylase PHD3 and increased expression of hypoxia inducible factor 1α (HIF1α), triggering epithelial to mesenchymal transition. Finally, we identified an HIF1α-dependent transcriptional signature with prognostic significance in human LUAD. Our studies further current knowledge of the relationship between glucose metabolism and cell differentiation in cancer, characterizing the epigenetic adaptation of cancer cells to glucose deprivation and identifying novel targets to prevent the development of resistance to therapies targeting glucose metabolism.

Single-Cell Characterization of Pulmonary Nodules Implicates Suppression of Immunosurveillance across Early Stages of Lung Adenocarcinoma.

A greater understanding of molecular, cellular, and immunological changes during the early stages of lung adenocarcinoma development could improve diagnostic and therapeutic approaches in patients with pulmonary nodules at risk for lung cancer. To elucidate the immunopathogenesis of early lung tumorigenesis, we evaluated surgically resected pulmonary nodules representing the spectrum of early lung adenocarcinoma as well as associated normal lung tissues using single-cell RNA sequencing and validated the results by flow cytometry and multiplex immunofluorescence (MIF). Single-cell transcriptomics revealed a significant decrease in gene expression associated with cytolytic activities of tumor-infiltrating natural killer and natural killer T cells. This was accompanied by a reduction in effector T cells and an increase of CD4+ regulatory T cells (Treg) in subsolid nodules. An independent set of resected pulmonary nodules consisting of both adenocarcinomas and associated premalignant lesions corroborated the early increment of Tregs in premalignant lesions compared with the associated normal lung tissues by MIF. Gene expression analysis indicated that cancer-associated alveolar type 2 cells and fibroblasts may contribute to the deregulation of the extracellular matrix, potentially affecting immune infiltration in subsolid nodules through ligand-receptor interactions. These findings suggest that there is a suppression of immune surveillance across the spectrum of early-stage lung adenocarcinoma. SIGNIFICANCE: Analysis of a spectrum of subsolid pulmonary nodules by single-cell RNA sequencing provides insights into the immune regulation and cell-cell interactions in the tumor microenvironment during early lung tumor development.

The landscape of drug sensitivity and resistance in sarcoma.

Sarcomas are a family of rare malignancies composed of over 100 distinct histological subtypes. The rarity of sarcoma poses significant challenges in conducting clinical trials to identify effective therapies, to the point that many rarer subtypes of sarcoma do not have standard-of-care treatment. Even for established regimens, there can be substantial heterogeneity in responses. Overall, novel, personalized approaches for identifying effective treatments are needed to improve patient out-comes. Patient-derived tumor organoids (PDTOs) are clinically relevant models representative of the physiological behavior of tumors across an array of malignancies. Here, we use PDTOs as a tool to better understand the biology of individual tumors and characterize the landscape of drug resistance and sensitivity in sarcoma. We collected n=194 specimens from n=126 sarcoma patients, spanning 24 distinct subtypes. We characterized PDTOs established from over 120 biopsy, resection, and metastasectomy samples. We leveraged our organoid high-throughput drug screening pipeline to test the efficacy of chemotherapeutics, targeted agents, and combination therapies, with results available within a week from tissue collection. Sarcoma PDTOs showed patient-specific growth characteristics and subtype-specific histopathology. Organoid sensitivity correlated with diagnostic subtype, patient age at diagnosis, lesion type, prior treatment history, and disease trajectory for a subset of the compounds screened. We found 90 biological pathways that were implicated in response to treatment of bone and soft tissue sarcoma organoids. By comparing functional responses of organoids and genetic features of the tumors, we show how PDTO drug screening can provide an orthogonal set of information to facilitate optimal drug selection, avoid ineffective therapies, and mirror patient outcomes in sarcoma. In aggregate, we were able to identify at least one effective FDA-approved or NCCN-recommended regimen for 59% of the specimens tested, providing an estimate of the proportion of immediately actionable information identified through our pipeline. Highlights: Standardized organoid culture preserve unique sarcoma histopathological featuresDrug screening on patient-derived sarcoma organoids provides sensitivity information that correlates with clinical features and yields actionable information for treatment guidanceHigh-throughput screenings provide orthogonal information to genetic sequencingSarcoma organoid response to treatment correlates with patient response to therapyLarge scale, functional precision medicine programs for rare cancers are feasible within a single institution.

Surgical Issues for Operable Early-Stage Non-Small-Cell Lung Cancer.

Surgical care for early stage non-small-cell lung cancer continuously evolves with new procedures, techniques and care pathways. The most obvious recent change was the transition to minimally invasive procedures, but numerous other aspects of care have also been refined to improve safety and tolerability. These care advancements are essential as we move into an era with increased early detection as a result of screening and greater indications for the use of adjuvant and neoadjuvant strategies.

National Use and Short-term Outcomes of Video and Robot-Assisted Thoracoscopic Thymectomies.

BACKGROUND: Transsternal open thymectomy has long been the most widely used approach for thymectomy, but recent decades have seen the introduction of minimally invasive surgery (MIS), such as video-assisted thoracoscopic surgery (VATS) and robot-assisted thoracoscopic surgery (RATS) thymectomy. This retrospective cohort study provides a national comparison of trends, outcomes, and resource utilization of open, VATS, and RATS thymectomy. METHODS: Admissions for thymectomies from 2008 to 2014 were identified in the National Inpatient Sample. Patients were identified as undergoing open, VATS, or RATS thymectomy. Propensity score-matched analyses were used to compare overall complication rates, length of stay (LOS), and cost of VATS and RATS thymectomies. RESULTS: An estimated 23,087 patients underwent thymectomy during the study period: open in 16,025 (69%) and MIS in 7217 (31%). Of the MIS cohort, 4119 (18%) underwent VATS and 3097 (13%) underwent RATS. Performance of RATS and VATS thymectomy increased while that of open thymectomy declined. Baseline characteristics between VATS and RATS were similar, except more women underwent VATS thymectomy. No differences in LOS or overall complication rates were appreciable in this study. VATS was associated with the lowest cost of the 3 approaches. CONCLUSIONS: Our findings demonstrate the increasing adoption of MIS and declining use of the open surgical approach for thymectomy. There are no differences in overall complication rates between RATS and VATS thymectomy, but RATS is associated with greater cost and lower cardiac complication rates.