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.

Smoking Cessation, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology.

Although the harmful effects of smoking after a cancer diagnosis have been clearly demonstrated, many patients continue to smoke cigarettes during treatment and beyond. The NCCN Guidelines for Smoking Cessation emphasize the importance of smoking cessation in all patients with cancer and seek to establish evidence-based recommendations tailored to the unique needs and concerns of patients with cancer. The recommendations contained herein describe interventions for cessation of all combustible tobacco products (eg, cigarettes, cigars, hookah), including smokeless tobacco products. However, recommendations are based on studies of cigarette smoking. The NCCN Smoking Cessation Panel recommends that treatment plans for all patients with cancer who smoke include the following 3 tenets that should be done concurrently: (1) evidence-based motivational strategies and behavior therapy (counseling), which can be brief; (2) evidence-based pharmacotherapy; and (3) close follow-up with retreatment as needed.

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.

Phase 1 trial of dasatinib combined with afatinib for epidermal growth factor receptor- (EGFR-) mutated lung cancer with acquired tyrosine kinase inhibitor (TKI) resistance.

BACKGROUND: Bypass activation of Src family kinases can confer resistance to EGFR tyrosine kinase inhibitors (TKIs) based on preclinical models. We prospectively assessed the safety and clinical activity of dasatinib and afatinib in combination for patients with resistant EGFR-mutant lung cancer. METHODS: An open-label, dose-escalation phase 1/2 trial (NCT01999985) with 2-stage expansion was conducted with 25 lung cancer patients. Dose expansion required activating EGFR mutations and progression following prior EGFR TKI. RESULTS: Patients were 72% Caucasian and received median of 2 prior lines of therapy. Maximum-tolerated dose was 30 mg afatinib with 100 mg dasatinib. New or increased pleural effusions were observed in 56% of patients. No radiologic responses were observed, although several EGFR-mutant TKI-resistant patients (26%) had prolonged stable disease over 6 months. The combination reduced the EGFR mutation and T790M variant allele frequency in cell-free DNA (p < .05). Nonetheless, the threshold for futility was met, based on 6-month progression-free survival. For EGFR TKI-resistant patients, median progression-free survival was 3.7 months (95% confidence interval (CI), 2.3-5.0) and overall survival was 14.7 months (95% CI, 8.5-20.9). CONCLUSIONS: The combination had a manageable toxicity profile and in vivo T790M modulation, but no objective clinical responses were observed.

Randomized-controlled phase II trial of salvage chemotherapy after immunization with a TP53-transfected dendritic cell-based vaccine (Ad.p53-DC) in patients with recurrent small cell lung cancer.

Small cell lung cancer TP53 mutations lead to expression of tumor antigens that elicits specific cytotoxic T-cell immune responses. In this phase II study, dendritic cells transfected with wild-type TP53 (vaccine) were administered to patients with extensive-stage small cell lung cancer after chemotherapy. Patients were randomized 1:1:1 to arm A (observation), arm B (vaccine alone), or arm C (vaccine plus all-trans-retinoic acid). Vaccine was administered every 2 weeks (3 times), and all patients were to receive paclitaxel at progression. Our primary endpoint was overall response rate (ORR) to paclitaxel. The study was not designed to detect overall response rate differences between arms. Of 69 patients enrolled (performance status 0/1, median age 62 years), 55 were treated in stage 1 (18 in arm A, 20 in arm B, and 17 in arm C) and 14 in stage 2 (arm C only), per 2-stage Simon Minimax design. The vaccine was safe, with mostly grade 1/2 toxicities, although 1 arm-B patient experienced grade 3 fatigue and 8 arm-C patients experienced grade 3 toxicities. Positive immune responses were obtained in 20% of arm B (95% confidence interval [CI], 5.3-48.6) and 43.3% of arm C (95% CI 23.9-65.1). The ORRs to the second-line chemotherapy (including paclitaxel) were 15.4% (95% CI 2.7-46.3), 16.7% (95% CI 2.9-49.1), and 23.8% (95% CI 9.1-47.5) for arms A, B, and C, with no survival differences between arms. Although our vaccine failed to improve ORRs to the second-line chemotherapy, its safety profile and therapeutic immune potential remain. Combinations with the other immunotherapeutic agents are reasonable options.

Loneliness as a mediator of the relationship of social cognitive variables with depressive symptoms and quality of life in lung cancer patients beginning treatment.

OBJECTIVE: Loneliness, or the discrepancy between perceived and desired level of social connectedness, is an understudied but important psychosocial factor in cancer patients. The current study investigated the relationship between loneliness, depressive symptoms, quality of life, and social cognitive variables (eg, stigma, social constraint, and cancer-related negative social expectations), and explored loneliness as a mediator of the relationship between social cognitive variables and depressive symptoms and quality of life in lung cancer patients beginning treatment. METHODS: Patients within 3 months of beginning treatment for lung cancer completed measures of loneliness, depressive symptoms, quality of life, and social cognitive variables. Correlational, chi-square, and hierarchical regression analyses evaluated relationships among variables. Bias-corrected bootstrapping methods estimated the indirect effect and 95% confidence interval for mediation models. RESULTS: Participants (n = 105, M = 65.5 years, 55% female) endorsed low to moderate levels of loneliness. Greater loneliness was associated with greater depressive symptoms and worse quality of life (P's < .001), and loneliness explained unique variance in depressive symptoms (F = 10.18, P < .001, ΔR2  = .06, Total R2  = .35) and quality of life (F = 19.55, P < .001, ΔR2  = .05, Total R2  = .52) after controlling for significant covariates. Greater stigma, social constraint, and cancer-related negative social expectations were associated with greater loneliness and depressive symptoms and worse quality of life (P's < .001). Loneliness partially mediated the relationship of social cognitive variables with depressive symptoms and quality of life. CONCLUSIONS: Beyond its direct impact on clinically relevant outcomes, the experience of loneliness may be a mechanism by which social cognitive factors influence depressive symptoms and quality of life in lung cancer patients.

A phase I/randomized phase II study of GM.CD40L vaccine in combination with CCL21 in patients with advanced lung adenocarcinoma.

The GM.CD40L vaccine, which recruits and activates dendritic cells, migrates to lymph nodes, activating T cells and leading to systemic tumor cell killing. When combined with the CCL21 chemokine, which recruits T cells and enhances T-cell responses, additive effects have been demonstrated in non-small cell lung cancer mouse models. Here, we compared GM.CD40L versus GM.CD40L plus CCL21 (GM.CD40L.CCL21) in lung adenocarcinoma patients with ≥ 1 line of treatment. In this phase I/II randomized trial (NCT01433172), patients received intradermal vaccines every 14 days (3 doses) and then monthly (3 doses). A two-stage minimax design was used. During phase I, no dose-limiting toxicities were shown in three patients who received GM.CD40L.CCL21. During phase II, of evaluable patients, 5/33 patients (15.2%) randomized for GM.DCD40L (p = .023) and 3/32 patients (9.4%) randomized for GM.DCD40L.CCL21 (p = .20) showed 6-month progression-free survival. Median overall survival was 9.3 versus 9.5 months with GM.DCD40L versus GM.DCD40L.CCL21 (95% CI 0.70-2.25; p = .44). For GM.CD40L versus GM.CD40L.CCL21, the most common treatment-related adverse events (TRAEs) were grade 1/2 injection site reaction (51.4% versus 61.1%) and grade 1/2 fatigue (35.1% versus 47.2%). Grade 1 immune-mediated TRAEs were isolated to skin. No patients showed evidence of pseudo-progression or immune-related TRAEs of grade 1 or greater of pneumonitis, endocrinopathy, or colitis, and none discontinued treatment due to toxicity. Although we found no significant associations between vaccine immunogenicity and outcomes, in limited biopsies, one patient treated with GMCD40L.CCL21 displayed abundant tumor-infiltrating lymphocytes. This possible effectiveness warrants further investigation of GM.CD40L in combination approaches.

Smoking Cessation, Version 1.2016, NCCN Clinical Practice Guidelines in Oncology.

Cigarette smoking has been implicated in causing many cancers and cancer deaths. There is mounting evidence indicating that smoking negatively impacts cancer treatment efficacy and overall survival. The NCCN Guidelines for Smoking Cessation have been created to emphasize the importance of smoking cessation and establish an evidence-based standard of care in all patients with cancer. These guidelines provide recommendations to address smoking in patients and outlines behavioral and pharmacologic interventions for smoking cessation throughout the continuum of oncology care.

Repeat cytoreductive surgery and heated intraperitoneal chemotherapy may offer survival benefit for intraperitoneal mesothelioma: a single institution experience.

INTRODUCTION: Cytoreduction with heated intraperitoneal chemotherapy (HIPEC) has demonstrated improved overall survival (OS) in malignant peritoneal mesothelioma (MPM). The role of repeated HIPEC for MPM is less clear. METHODS: An institutional review board-approved database of MPM patients was analyzed for clinical factors and outcomes. RESULTS: From June 2004 to March 2012, 29 patients underwent surgical treatment for mesothelioma. HIPEC was aborted in 3 and completed in 26; 8 underwent additional repeat HIPEC. The majority was male (62 %), median age 66 years. There was no significant difference in surgery duration, blood loss, or hospital-stay-duration between initial and repeat HIPEC. Cisplatin was the chemotherapy used. Complications occurred in 17 (65 %) initial and 6 (50 %) repeat HIPEC, with wound complications being most common. Reoperation was less common (4 % initial and 25 % repeat), and perioperative death was rare (4 % initial, 0 % repeat). Fourteen (54 %) initial and seven (58 %) repeat HIPEC patients received adjuvant chemotherapy. Median time from HIPEC to initiation of chemotherapy was not different between initial and repeat HIPEC (8.8 and 4.6 months, respectively, p = 0.68). Median treatment-free time (time from initial to repeat HIPEC or chemotherapy) also was not different between initial and repeat HIPEC (8.8 and 6.3 months, respectively, p = 0.92). Median OS for the cohort was 41.2 months. Patients who underwent repeat HIPEC had improved median OS (80 months) versus single HIPEC (27.2 months; p = 0.007). A lower peritoneal carcinoma index and complete cytoreduction were associated positively with OS. CONCLUSIONS: Cytoreduction and HIPEC for MPM are associated with longer OS. Patients who are candidates for repeat HIPEC may derive an even greater OS advantage.

Current clinical application of genomic and proteomic profiling in non-small-cell lung cancer.

BACKGROUND: Genomic or proteomic profiling of cancer can be broadly defined as a systematic grouping of cancer based on its genetic or protein makeup. In the management of non-small-cell lung cancer (NSCLC), genomic and proteomic profiling applications have become useful in early disease detection, diagnosis, treatment, and prognostication. METHODS: We reviewed the recent literature on the applications of genomic and proteomic profiling in NSCLC. Important applications were summarized into those already adopted as standard care and those still under investigation. RESULTS: For genomic profiling, testing for EGFR mutation and ALK rearrangement has become routine for adenocarcinoma. Multiplex assay and malignancy-risk gene signature are both important applications in development. A test to predict outcome after treatment with an epidermal growth factor rector/tyrosine kinase inhibitor and a screening blood test for lung cancer are being investigated for use in proteomic profiling. CONCLUSIONS: Genomic profiling is routine in patients with NSCLC, and proteomic profiling shows promise. Additional genomic and proteomic profiling applications may also prove to be useful contributions in the care of these patients.

Timeliness of EGFR/ALK Inhibitor Treatment and Survival in Lung Cancer: A Population-Based Analysis.

BACKGROUND: ALK or EGFR inhibitor is an ideal frontline treatment for patients with advanced non-small cell lung cancer (NSCLC) harboring targetable alteration in ALK or EGFR. However, in the real-world setting, frontline treatment may be delayed or not ideal. For such patients, the benefit of initiating ALK or EGFR inhibitor at a later timepoint remains uninvestigated. METHODS: We utilized a nationwide electronic health record-derived, deidentified database collected from diverse oncology practices across the United States to investigate the timeliness of preferred targeted therapy (PTT). Individualized data obtained from patients with stage IV NSCLC at diagnosis treated with PTT from 2018 to 2023 were analyzed. RESULTS: Data from 3250 patients were analyzed: 2640 patients (81%) with EGFR mutation and 610 patients (19%) with ALK rearrangement. The median time to PTT was 7 weeks from diagnosis with 26.4% of patients started PTT within 1 month. Landmark analyses using timepoints ranging from 1 to 12 months after diagnosis showed that at all timepoints, patients who had started on PTT had a significantly better survival than those who had not. In a multivariable analysis, time to PTT ≤ 1 month from diagnosis was an independent predictor of survival: HR 0.74 (95% CI: 0.62-0.89), P = .002. Time to PTT was significantly associated with age, smoking status and genomic class. CONCLUSIONS: In this population-based analysis, an initiation of PTT occurring as late as at least 1 year from diagnosis still resulted in a significant survival benefit, though the magnitude of benefit appeared decreased as time passed.

Surgery and Stereotactic Radiotherapy for Stage I Small-Cell Lung Carcinoma: A 25-Year Experience.

OBJECTIVES: Small-cell lung carcinoma (SCLC) is usually a wide-spread, highly-lethal malignancy but occasionally presents as localized, limited stage cancer amenable to local treatment. We reviewed our experience using surgery or stereotactic body radiotherapy (SBRT) to assess safety, survival rates and treatment toxicity in clinical stage I SCLC patients. MATERIALS AND METHODS: Electronic medical records of patients with clinical stage I lymph node-negative SCLC who underwent surgical resection or SBRT between 1996 and 2021 were retrospectively reviewed. A multivariable Cox Proportional Hazards model was constructed. RESULTS: Of 96 patients meeting inclusion criteria, 77 underwent resection and 19 underwent SBRT. Surgical patients were younger (mean 68.4 ± 9.2 years surgery versus 74.3 ± 6.6 years SBRT, P = .005) and had better pulmonary function (81.5 ± 19.6 FEV1% of predicted surgery versus 44.0 ± 20.9% SBRT, P < .001). SBRT patients had significantly more comorbidities. For both cohorts, 59 tumors were pure SCLC and 37 were mixed SCLC/NSCLC histology. Median survivals were 21 months versus 31 months for SBRT and surgery patients respectively (P = .07). There were no treatment-related mortalities. Mean length of hospital stay for surgical patients was 5.4 ± 5.7 days. Survival was longer in lymph node-negative surgery patients (median 48 months node-negative versus 19 months node-positive, P = .04). For node-negative-surgery patients, the estimated 2- and 5-year survival rates are 60% and 48%. CONCLUSIONS: Our single-institutional experience over 25 years demonstrates that local treatment with surgery or SBRT for clinical stage I SCLC is safe and effective, with survivals lower than similar stage non-small-cell carcinoma patients. However, our results compare favorably with prior small-cell surgical series and far better than reported results of chemoradiotherapy for similar stage patients, thereby validating current recommendations for employing surgery or SBRT for stage I SCLC.

Amivantamab for Metastatic Lung Cancer With Paraneoplastic Disseminated Intravascular Coagulation: A Case Report.

Advanced cancers may be accompanied by paraneoplastic disseminated intravascular coagulation (DIC), resulting in thromboembolism or thrombocytopenia. Thrombocytopenia can limit the feasibility of myelosuppressive chemotherapy. Therefore, an alternative treatment option is needed. This report described a patient with metastatic pulmonary adenocarcinoma with EGFR exon 20 insertion and paraneoplastic DIC. Frontline chemotherapy failed to control the disease and worsened thrombocytopenia. However, treatment with amivantamab resulted in a rapid resolution of DIC and produced a partial tumor response. Based on our experience, for patients with EGFR exon 20 insertions with paraneoplastic DIC, amivantamab could be considered a preferred frontline treatment.

Fatal Tracheoesophageal Puncture Leakage Associated With Lenvatinib.

Tracheoesophageal puncture (TEP) is a voice restorative option adopted by many head and neck cancer patients following laryngectomy. Though generally safe, TEP may develop leakage. Lenvatinib is a tyrosine kinase inhibitor (TKI) with anti-tumoral activity against head and neck malignancies.TKIs, including lenvatinib, have been associated with organ perforation or fistula formation. There remains a paucity of literature on the association between lenvatinib and TEP leakage. In this report, we described a patient with adenoid cystic carcinoma of the larynx who had a TEP. After approximately two weeks of treatment with lenvatinib, the patient developed a leakage of TEP. Despite several interventions, the patient died three months afterward due to a retropharyngeal abscess secondary to Fusobacterium nucleatum. To our knowledge, this is the first report of fatal lenvatinib-associated TEP leakage. Clinicians should be cognizant of a potentially rapid development of this complication when prescribing TKI for patients with TEP.

Association Between ALK Rearrangement and Ultra-Late Recurrence in Lung Cancer: Case Report and Pooled Analysis.

Ultra-late recurrence, defined as recurrence occurring 10 years or longer after curative treatment, is uncommon for non-small cell lung cancer (NSCLC). To date, factors associated with ultra-late recurrence remain unknown. We report a case with ultra-late recurrence and reviewed the literature published during 2010-2023. This is a case of a 66-year-old woman, with a significant smoking history and a previous history of lung adenocarcinoma, who underwent surgery for a brain metastasis detected on imaging. The pathology confirmed lung adenocarcinoma with an epidermal growth factor receptor (EGFR) exon 20 insertion, a finding consistent with the initial lung surgery a decade ago. With receiving intrathecal topotecan, the patient has maintained stable disease 10 months post-surgery. Given the rarity of ultra-late recurrence of NSCLC, we also conducted a pooled analysis with the outcome of interest being a time to recurrence. Data from this case report was analyzed along with previously published 26 cases of ultra-late recurrence. Multivariable analysis indicated that the only factor significantly predicting time to recurrence was anaplastic lymphoma kinase (ALK) rearrangement.

Iatrogenic Rupture of Saline Breast Implant Following Robotic-Assisted Lung Surgery.

Breast implants are prevalent in the United States. Patients with breast implants may be susceptible to iatrogenic implant rupture during cardiothoracic surgery. To our knowledge, however, this complication has never been described following robot-assisted thoracic surgery (RATS). We described a patient who developed a rupture of a saline breast implant after undergoing a robot-assisted left lower lobectomy. We hypothesized that a tear to the breast implant may have occurred either during the extraction of one of the surgical ports or during the forceful extraction of the resected specimen. This case highlights another potential complication of minimally invasive thoracic surgery. For patients with breast implants undergoing thoracic RATS, extra care should be made to the site of port placement and the avoidance of excessive force during surgery.