Search

To evaluate the safety and feasibility of implantation and retrieval of a novel implantable microdevice (IMD) in NSCLC patients undergoing operative resection.Adjuvant therapy has limited impact on post-surgical outcomes in NSCLC due to the inability to predict optimal treatment regimens.An IMD measuring 6.5 mm by 0.7 mm, containing micro-reservoirs allowing for high-throughput localized drug delivery, was developed and loaded with 12 chemotherapeutic agents. Five patients with peripheral lung lesions larger than 1.0 cm were enrolled in this phase 1 clinical study. IMDs were inserted into tumors intraoperatively under direct vision, removed with the resected specimen, and retrieved in pathology. Surrounding tissues were sectioned, stained, and analyzed for tissue drug response to the IMD-delivered microdoses of these agents by a variety of pharmacodynamic markers.A total of 14 IMDs were implanted intraoperatively with 13 (93%) successfully retrieved. After technique refinement, IMDs were reliably inserted and retrieved in open, VATS, and robotic cases. No severe adverse reactions were observed. The one retained IMD has remained in place without movement or any adverse effects. Analysis of patient blood revealed no detection of chemotherapeutic agents. We observed differential sensitivities of patient tumors to the drugs on the IMD.A multi-drug IMD can be safely inserted and retrieved into lung tumors during a variety of surgical approaches. Future studies will encompass pre-operative placement to better examine specific tumor responsiveness to therapeutic agents, allowing clinicians to tailor treatment regimens to the microenvironment of each patient.

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.

Interstitial lung disease (ILD) including idiopathic pulmonary fibrosis increases the risk of developing lung cancer. Diagnosing and staging lung cancer in patients with ILD is challenging and requires careful interpretation of computed tomography (CT) and fluorodeoxyglucose PET/CT to distinguish nodules from areas of fibrosis. Minimally invasive tissue sampling is preferred but may be technically challenging given tumor location, coexistent fibrosis, and pneumothorax risk. Current treatment options include surgery, radiation therapy, percutaneous thermal ablation, and systemic therapy; however, ILD increases the risks associated with each treatment option, especially acute ILD exacerbation.

BH3 mimetic drugs, which inhibit prosurvival BCL2 family proteins, have limited single-agent activity in solid tumor models. The potential of BH3 mimetics for these cancers may depend on their ability to potentiate the apoptotic response to chemotherapy and targeted therapies. Using a novel class of potent and selective MCL1 inhibitors, we demonstrate that concurrent MEK + MCL1 inhibition induces apoptosis and tumor regression in KRAS-mutant non–small cell lung cancer (NSCLC) models, which respond poorly to MEK inhibition alone. Susceptibility to BH3 mimetics that target either MCL1 or BCL-xL was determined by the differential binding of proapoptotic BCL2 proteins to MCL1 or BCL-xL, respectively. The efficacy of dual MEK + MCL1 blockade was augmented by prior transient exposure to BCL-xL inhibitors, which promotes the binding of proapoptotic BCL2 proteins to MCL1. This suggests a novel strategy for integrating BH3 mimetics that target different BCL2 family proteins for KRAS-mutant NSCLC.Significance:Defining the molecular basis for MCL1 versus BCL-xL dependency will be essential for effective prioritization of BH3 mimetic combination therapies in the clinic. We discover a novel strategy for integrating BCL-xL and MCL1 inhibitors to drive and subsequently exploit apoptotic dependencies of KRAS-mutant NSCLCs treated with MEK inhibitors.See related commentary by Leber et al., p. 1511.This article is highlighted in the In This Issue feature, p. 1494

Supplementary Figure 1-5, Supplementary Tables 1-3

Supplemental Appendix 7: Paired pre- and post- treatment SNaPshot molecular profiling available for 11 patients.

Supplementary Legends, Table

Purpose:We performed a NCI-sponsored, prospective study of neoadjuvant FOLFIRINOX followed by chemoradiation with carboplatin/paclitaxel followed by surgery in patients with locally advanced gastric or gastroesophageal cancer.Patients and Methods:The primary objective was to determine completion rate of neoadjuvant FOLFIRINOX × 8 followed by chemoradiation. Secondary endpoints were toxicity and pathologic complete response (pCR) rate. Exploratory analysis was performed of circulating tumor DNA (ctDNA) to treatment response.Results:From October 2017 to June 2018, 25 patients were enrolled. All patients started FOLFIRINOX, 92% completed all eight planned cycles, and 88% completed chemoradiation. Twenty (80%) patients underwent surgical resection, and 7 had a pCR (35% in resected cohort, 28% intention to treat). Tumor-specific mutations were identified in 21 (84%) patients, of whom 4 and 17 patients had undetectable and detectable ctDNA at baseline, respectively. Presence of detectable post-chemoradiation ctDNA (P = 0.004) and/or postoperative ctDNA (P = 0.045) were associated with disease recurrence.Conclusions:Here we show neoadjuvant FOLFIRINOX followed by chemoradiation for locally advanced gastroesophageal cancer is feasible and yields a high rate of pCR. ctDNA appears to be a promising predictor of postoperative recurrence.See related commentary by Catenacci, p. 6281

Supplementary figures

Purpose:To evaluate the prognostic value of posttreatment fibrosis in human PDAC patients, and to compare a type I collagen targeted MRI probe, CM-101, to the standard contrast agent, Gd-DOTA, for their abilities to identify FOLFIRINOX-induced fibrosis in a murine model of PDAC.Experimental Design:Ninety-three chemoradiation-treated human PDAC samples were stained for fibrosis and outcomes evaluated. For imaging, C57BL/6 and FVB mice were orthotopically implanted with PDAC cells and FOLFIRINOX was administered. Mice were imaged with Gd-DOTA and CM-101.Results:In humans, post-chemoradiation PDAC tumor fibrosis was associated with longer overall survival (OS) and disease-free survival (DFS) on multivariable analysis (OS P = 0.028, DFS P = 0.047). CPA increased the prognostic accuracy of a multivariable logistic regression model comprised of previously established PDAC risk factors [AUC CPA (−) = 0.76, AUC CPA (+) = 0.82]. In multiple murine orthotopic PDAC models, FOLFIRINOX therapy reduced tumor weight (P < 0.05) and increased tumor fibrosis by collagen staining (P < 0.05). CM-101 MR signal was significantly increased in fibrotic tumor regions. CM-101 signal retention was also increased in the more fibrotic FOLFIRINOX-treated tumors compared with untreated controls (P = 0.027), consistent with selective probe binding to collagen. No treatment-related differences were observed with Gd-DOTA imaging.Conclusions:In humans, post-chemoradiation tumor fibrosis is associated with OS and DFS. In mice, our MR findings indicate that translation of collagen molecular MRI with CM-101 to humans might provide a novel imaging technique to monitor fibrotic response to therapy to assist with prognostication and disease management.

Pulmonary function can predict all-cause mortality, and chronic obstructive pulmonary disease (COPD) is associated with worse overall survival (OS) in non-small cell lung cancer (NSCLC) patients. Though pre-operative lung function is predictive of in-hospital mortality following lung cancer surgery, its predictive utility for long-term survival is unclear. The prognostic role of commonly used spirometry tests in survival of lung cancer also remains uncertain. This study evaluates the role of spirometry at lung cancer diagnosis in predicting OS of NSCLC patients. This was a retrospective study using data from the Boston Lung Cancer Study on newly diagnosed NSCLC patients with spirometry tests performed before cancer therapy (n = 2805). Spirometric test values, after being categorized using quartiles, were analyzed for association with OS using univariate and risk-adjusted multiple regression models. Further, we analyzed OS by the status of COPD determined by spirometry, and, among those with COPD, by its stage defined by the Global Initiative for Chronic Obstructive Lung Disease criteria. Both univariate and multiple regression models demonstrated that lower quartiles of actual and percent predicted forced expiratory volume in 1 second and forced vital capacity at lung cancer diagnosis were significantly associated with worse OS. Spirometry-determined COPD, and more advanced stage of COPD at lung cancer diagnosis were associated with worse lung cancer OS. The findings provide evidence that a good pulmonary function at diagnosis may help improve OS in NSCLC patients.

BACKGROUND Airway release (AR) maneuvers performed during airway resection to reduce anastomotic tension have not been thoroughly studied. METHODS This study retrospectively analyzed consecutive resections for postintubation stenosis (PITS) and primary tracheal neoplasms (PTNs) at Massachusetts General Hospital (Boston, MA). Anastomotic complications were defined as stenosis, separation, necrosis, granulation tissue, and air leak. Logistic regression modeling was used to identify factors associated with AR and adverse outcome. RESULTS From 1993 to 2019, 545 patients with PITS (375; 68.8%) and PTNs (170; 31.2%) underwent laryngotracheal, tracheal, or carinal (resections and reconstructions; 5.7% (31 of 545) were reoperations. AR was performed in 11% (60 of 545): in 3.8% of laryngotracheal resections (6 of 157; all laryngeal), in 9.8% of tracheal resections (34 of 347; laryngeal, 12, and hilar, 22), and in 49% of carinal resections (20 of 41; laryngeal, 1, and hilar, 19). Mean resected length was 3.5 cm (range, 1to- 6.3 cm) with AR and 3.0 cm (range, 0.8 to 6.5 cm) without AR (P < .01). Operative mortality was 0.7% (4 of 545); all 4 anastomoses were intact until death. Anastomotic complications were present in 5% of patients who underwent AR (3 of 60) and in 9.3% (45 of 485) of patients who did not. AR was associated with resection length of 4 cm or longer (odds ratio [OR], 6.15; 95% confidence interval [CI], 1.37 to 27.65), PTNs (OR, 7.81; 95% CI, 3.31 to 18.40), younger age (OR, 0.96; 95% CI, 0.94 to 0.98), and lung resection (OR, 6.09; 95% CI, 1.33 to 27.90). Anastomotic complications in patients with tracheal anastomoses were associated with preexisting tracheostomy (OR, 2.68; 95% CI, 1.50 to 4.80), but not release. CONCLUSIONS Tracheal reconstruction succeeds, even when anastomotic tension requires AR. Because intraoperative assessment may underestimate tension, lowering the threshold for AR seems prudent, particularly in patients with diabetes.

We sought to determine the rate and risk factors of recurrent spontaneous pneumothorax in a diverse population.Cohort study using the California Public Discharge Data file (1995-2010). We identified patients with first-time spontaneous pneumothorax. The primary outcome was recurrent pneumothorax. Associations with clinical, patient, and hospital characteristics were assessed using Cox regression analysis.Among 14,609 patients with a first-time episode of spontaneous pneumothorax, 26.2% developed a recurrence. Risk factors included age35 (Hazard Ratio [HR] 1.24 95%-Confidence Interval [CI] 1.14-1.36), Asian race (HR 1.24, CI 1.13-1.37), and tube thoracostomy (HR 1.2, CI 1.15-1.31). Mechancial pleurodesis (HR 0.37 CI 0.31-0.45) was superior to chemical pleurodesis (HR 0.71 CI 0.58-0.86) in reducing recurrence risk.The risk of recurrent pneumothorax is greatest in patients age35, Asians, and those requiring a tube thoracostomy. The risks of operative intervention should be balanced against patient risk for recurrence.

Background: Body mass index (BMI) change after a lung cancer diagnosis has been associated with non–small cell lung cancer (NSCLC) survival. This study aimed to quantify the association based on a large-scale observational study. Methods: Included in the study were 7,547 patients with NSCLC with prospectively collected BMI data from Massachusetts General Hospital and Brigham and Women's Hospital/Dana-Farber Cancer Institute. Cox proportional hazards regression with time-dependent covariates was used to estimate effect of time-varying postdiagnosis BMI change rate (% per month) on overall survival (OS), stratified by clinical subgroups. Spline analysis was conducted to quantify the nonlinear association. A Mendelian Randomization (MR) analysis with a total of 3,495 patients further validated the association. Results: There was a J-shape association between postdiagnosis BMI change and OS among patients with NSCLC. Specifically, a moderate BMI decrease [0.5–2.0; HR = 2.45; 95% confidence interval (CI), 2.25–2.67] and large BMI decrease (≥2.0; HR = 4.65; 95% CI, 4.15–5.20) were strongly associated with worse OS, whereas moderate weight gain (0.5–2.0) reduced the risk for mortality (HR = 0.78; 95% CI, 0.68–0.89) and large weight gain (≥2.0) slightly increased the risk of mortality without reaching statistical significance (HR = 1.10; 95% CI, 0.86–1.42). MR analyses supported the potential causal roles of postdiagnosis BMI change in survival. Conclusions: This study indicates that BMI change after diagnosis was associated with mortality risk. Impact: Our findings, which reinforce the importance of postdiagnosis BMI surveillance, suggest that weight loss or large weight gain may be unwarranted.

Purpose: We performed a NCI-sponsored, prospective study of neoadjuvant FOLFIRINOX followed by chemoradiation with carboplatin/paclitaxel followed by surgery in patients with locally advanced gastric or gastroesophageal cancer. Patients and Methods: The primary objective was to determine completion rate of neoadjuvant FOLFIRINOX × 8 followed by chemoradiation. Secondary endpoints were toxicity and pathologic complete response (pCR) rate. Exploratory analysis was performed of circulating tumor DNA (ctDNA) to treatment response. Results: From October 2017 to June 2018, 25 patients were enrolled. All patients started FOLFIRINOX, 92% completed all eight planned cycles, and 88% completed chemoradiation. Twenty (80%) patients underwent surgical resection, and 7 had a pCR (35% in resected cohort, 28% intention to treat). Tumor-specific mutations were identified in 21 (84%) patients, of whom 4 and 17 patients had undetectable and detectable ctDNA at baseline, respectively. Presence of detectable post-chemoradiation ctDNA (P = 0.004) and/or postoperative ctDNA (P = 0.045) were associated with disease recurrence. Conclusions: Here we show neoadjuvant FOLFIRINOX followed by chemoradiation for locally advanced gastroesophageal cancer is feasible and yields a high rate of pCR. ctDNA appears to be a promising predictor of postoperative recurrence. See related commentary by Catenacci, p. 6281

PURPOSE For patients with surgically resected disease, multiple studies suggest a benefit of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in delaying cancer recurrence. The necessary duration of therapy for benefit is unknown. MATERIALS AND METHODS This randomized phase II study enrolled patients with completely resected stage IA-IIIB EGFR-mutant non–small-cell lung cancer (American Joint Committee on Cancer 7th edition) after stage-appropriate standard-of-care adjuvant therapy. Patients were randomly assigned 1:1 to 3 months or 2 years of adjuvant afatinib starting at 30 mg by mouth daily. Computed tomography imaging was performed every 6 months for 3 years and then annually. The primary study end point for this planned 92-patient trial was recurrence rate at 2 years from randomization. A 20% improvement (from 70% with 3 months to 90% with 2 years) was targeted. RESULTS Forty-six patients enrolled and 45 were treated. The assigned course of afatinib treatment was completed by 96% (22/23) of patients in the 3-month group and only 41% (9/22) in the 2-year group. The 2-year recurrence-free survival (RFS) rates were 70% in the 3-month group and 81% in the 2-year group ( P = .55). The median RFS was 42.8 months in the 3-month group and 58.6 months in the 2-year group. Side effects were consistent with those previously described for afatinib. CONCLUSION Recurrences at 2 years were 11% less common with 2 years versus 3 months of adjuvant afatinib. This difference did not meet the 20% primary study target, likely because of underaccrual and early drug discontinuation on the 2-year group. With the availability of osimertinib with better efficacy and tolerability than earlier-generation agents, the optimal duration of adjuvant EGFR TKI therapy remains an important question.

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.

Introduction: Interleukin 12 (IL-12) is an important bridge between the innate and adaptive immune systems. It is mainly produced by macrophages and can bind to its receptor (IL12R) on T cells. It affects several aspects of T cell activation, including IFN-γ and perforin production. Tumor-infiltrating CD8+ T cells perform important anti-tumoral actions, which need to be overcome to allow cancer cell growth. This work studied IL-12 administration as an HCC preventive strategy in cirrhotic mice. We investigated whether IL-12 can boost the recruitment of macrophages to the liver, increase their antigen-presenting ability, and activate cytolytic T cells to inhibit HCC development in cirrhotic livers. Method: 8 weeks old mice were fed a choline-deficient High fat diet (CDAHFD) for 16 weeks to create NAFLD-induced HCC. A subset of CDAHFD mice was injected intravenously with IL-12 (0.5mg/gr) weekly from 12 to 16 weeks. Mice were euthanized after 16 weeks, and liver and serum were collected for further analysis. Results: After tissue collection, we observed that 50% of untreated animals developed HCC lesions, while IL-12-treated mice did not have any HCC. After treatment with IL12, qPCR and western blot on total liver tissue showed up-regulation in the IL12 receptor and activation of the IL-12 pathway, evidenced by the increase in Stat4 expression and phosphorylation. Additionally, we detected an increase in IFN-γ expression by qPCR in IL-12-treated mice. Histological analysis showed a significant decrease in fat and collagen deposition in IL-12-treated livers compared to untreated livers. IL-12-treated mice had lower serum aminotransferase enzymes (AST & ALT), indicating improved liver function. Immunostaining and flow cytometry of F4/80 (macrophage marker) showed an increase in the number of macrophages in the livers treated with IL-12. Flow cytometry data showed that the majority of macrophages present in the IL-12 livers were CCR2+, a marker for recruited macrophages. Notably, IL-12-treated macrophages expressed more MHCII (antigen presentation marker) and less B7H4 (inhibitory marker). In addition, we observed a significant increase in the number of cytolytic T cells (CD8+) in the IL-12 treated livers, which had higher expression of the T cell activation marker (CD25) and elevated levels of perforin and IFN-γ that are nessacery for their cytotoxic activity. Conclusion: There is a lack of substantial evidence to describe the underlying mechanisms supporting the idea of cirrhosis regression and HCC prevention. Our study shows that the exogenous administration of IL-12 causes an increase in migrating profibrolysis macrophages to the liver and elevates cytolytic T-cell activity. IL-12 immunotherapy can trigger cirrhosis regression and prevent HCC development. Citation Format: Mozhdeh Sojoodi, Stephen C. Barrett, Derek J. Erstad, Veronica Clavijo Jordan, Eric M. Gale, Shadi Salloum, Yongtao Wang, Michael Lanuti, Lawrence Zukerberg, Peter Caravan, Georg M. Lauer, Kenneth K. Tanabe. IL-12 immunotherapy prevents hepatocellular carcinoma in a murine NAFLD induced cirrhosis model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB278.

The aim of this study was to report outcomes following percutaneous microwave and cryoablation of lung metastases from adenoid cystic carcinoma (ACC) of the head and neck. This bi-institutional retrospective cohort study included 10 patients (6 females, median age 59 years [range 28–81]) who underwent 32 percutaneous ablation sessions (21 cryoablation, 11 microwave) of 60 lung metastases (median 3.5 tumors per patient [range 1–16]) from 2007 to 2019. Median tumor diameter was 16 mm [range 7–40], significantly larger for cryoablation (22 mm, p = 0.002). A median of two tumors were treated per session [range 1–7]. Technical success, local control, complications, and overall survival were assessed. Primary technical success was achieved for 55/60 tumors (91.7%). Median follow-up was 40.6 months (clinical) and 32.5 months (imaging, per tumor). Local control at 1, 2, and 3 years was 94.7%, 80.8%, and 76.4%, respectively, and did not differ between ablation modalities. Five of fifteen recurrent tumors underwent repeat ablation, and secondary technical success was achieved in four (80%). Assisted local tumor control at 1, 2, and 3 years was 96.2%, 89.8%, and 84.9%, respectively. Complications occurred following 24/32 sessions (75.0%) and 57.2% Common Terminology Criteria for Adverse Events (CTCAE) lower than grade 3. Of 13 pneumothoraces, 7 required chest tube placements. Hemoptysis occurred after 7/21 cryoablation sessions, and bronchopleural fistula developed more frequently with microwave (p = 0.037). Median length of hospital stay was 1 day [range 0–10], and median overall survival was 81.5 months (IQR 40.4–93.1). Percutaneous computed tomography-guided microwave and cryoablation can treat lung metastases from ACC of the head and neck. Complications are common but manageable, with full recovery expected.

BACKGROUND. Lung cancer (LC) associated with cystic airspaces is an uncommon presentation that is underrecognized on imaging. Additionally, understanding of its underlying pathology and risk factors is limited, which can contribute to delays in diagnosis. OBJECTIVE. The purpose of this analysis was to systematically review, analyze, and synthesize the medical literature to determine the imaging features of LC associated with cystic airspaces. EVIDENCE ACQUISITION. In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we included published research reporting the clinical, pathologic, and imaging features of LC associated with cystic airspaces. We then performed a pooled analysis of continuous and categoric data with respect to patient clinical characteristics, tumor pathologic features, underlying driver mutation, CT features, and evolution of these features over time. EVIDENCE SYNTHESIS. The analysis included eight original observational studies with a combined total of 341 patients with LC associated with cystic airspaces (weighted mean age, 61.8 years; range, 30-87 years; 135 women and 206 men). Most patients were current or previous smokers (127/192 [66.1%]). The most common histologic finding was adenocarcinoma (289/328 [88.1%]) followed by squamous cell carcinoma (30/328 [9.1%]). The most common driver mutations were EGFR (46/122 [37.7%]) and KRAS (21/122 [17.2%]). The cysts in LC associated with cystic airspaces commonly had nonuniform (104/114 [91.2%]) and thick (83/222 [37.4%]) walls, irregular margins (53/142 [37.3%]), and were unilocular (173/272 [63.6%]). Most cysts had a nodular component (210/328 [64.0%]). Over time, most cysts showed development or enlargement of the nodular component (61/89 [68.5%]), approximately half showed wall thickening (43/89 [48.3%]), and a minority evolved into completely solid lesions (11/89 [12.4%]). The size of the cystic component increased in 36 of 89 patients (40.4%), decreased in 28 (31.5%), and remained stable in 24 (27.0%). CONCLUSION. LC associated with cystic airspaces occurs most commonly as adeno-carcinoma and is seen in both smokers and nonsmokers. The cysts associated with LC show wall thickening and mural nodularity, which may evolve over time. LC associated with cystic airspaces can be indolent, and long-term surveillance with imaging should be considered if cysts are not resected. CLINICAL IMPACT. Familiarity with the imaging features and temporal evolution of LC associated with cystic airspaces can minimize delays in LC diagnosis. Future management guidelines should include protocols for follow-up and management of cystic lung lesions identified during diagnostic and LC screening CT.

Many studies have reported that estrogen (E2) promotes lung cancer by binding to nuclear estrogen receptors (ER), and altering ER related nuclear protein expressions. With the GEO database analysis, Human centromere protein F (CENPF) is highly expressed in lung adenocarcinoma (LUAD), and the co-expression of CENPF and ERβ was found in the nucleus of LUAD cells through immunofluorescence. We identified the nuclear protein CENPF and explored its relationship with the ER pathway. CENPF and ERβ2/5 were related with T stage and poor prognosis (P

This study aims to evaluate whether postoperative radiotherapy using newer techniques (intensity-modulated radiotherapy [IMRT]) is associated with improved survival for patients with stage IIIA-N2 non-small cell lung cancer (NSCLC) who underwent complete resection.The overall survival of patients with stage IIIA-N2 NSCLC who received postoperative IMRT versus no postoperative IMRT following induction chemotherapy and lobectomy in the National Cancer Database from 2010-2018 was assessed via Kaplan-Meier analysis, Cox proportional hazards analysis and propensity score-matched analysis. Additional survival analyses were also conducted in patients with completely resected stage IIIA-pN2 NSCLC who had upfront lobectomy (without induction therapy) followed by adjuvant chemotherapy alone or adjuvant chemotherapy with postoperative IMRT. Only patients receiving IMRT, which is a newer, more conformal radiotherapy technique, were included. Patients with positive surgical margins were excluded.A total of 3203 patients with stage IIA-N2 NSCLC who underwent lobectomy were included. Five hundred eighty-eight (18.4%) patients underwent induction chemotherapy followed by lobectomy, and 2615 (82%) underwent lobectomy followed by chemotherapy. In unadjusted, multivariable-adjusted, and propensity score--matched analyses, there were no significant differences in overall survival between the patients who also received postoperative IMRT versus those who did not.In this national analysis, the use of postoperative IMRT was not associated with improved survival in patients with completely resected stage IIIA-N2 NSCLC with or without induction chemotherapy.

BACKGROUND: Vaping, including the use of electronic cigarettes (e-cigarettes), has become increasingly prevalent, yet the associated long-term health risks are largely unknown. Given the prevalence of use, particularly among adolescents early in their lifespan, it is vital to understand the potential chronic pathologic sequelae of vaping. METHODS: We present the cases of four patients with chronic lung disease associated with e-cigarette use characterized by clinical evaluation, with pulmonary function tests (PFTs), chest high-resolution computed tomography (HRCT), endobronchial optical coherence tomography (EB-OCT) imaging, and histopathologic assessment. RESULTS: Each patient presented with shortness of breath and chest pain in association with a 3- to 8-year history of e-cigarette use, with mild progressive airway obstruction on PFTs and/or chest HRCT findings demonstrating evidence of air trapping and bronchial wall thickening. EB-OCT imaging performed in two patients showed small airway–centered fibrosis with bronchiolar narrowing and lumen irregularities. The predominant histopathologic feature on surgical lung biopsy was small airway–centered fibrosis, including constrictive bronchiolitis and MUC5AC overexpression in all patients. Patients who ceased vaping had a partial, but not complete, reversal of disease over 1 to 4 years. CONCLUSIONS: After thorough evaluation for other potential etiologies, vaping was considered to be the most likely common causal etiology for all patients due to the temporal association of symptomatic chronic lung disease with e-cigarette use and partial improvement in symptoms after e-cigarette cessation. In this series, we associate the histopathologic pattern of small airway–centered fibrosis, including constrictive bronchiolitis, with vaping, potentially defining a clinical and pathologic entity associated with e-cigarette use. (Funded in part by the National Institutes of Health.)

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.

Pulmonary fibrosis (PF) is the pathologic accumulation of extracellular matrix components in lung tissue that result in scarring following chronic lung injury. PF is typically diagnosed by high resolution computed tomography (HRCT) and/or invasive biopsy. However, HRCT cannot distinguish old injury from active fibrogenesis. We previously demonstrated that allysine residues on oxidized collagen represent an abundant target during lung fibrogenesis, and that magnetic resonance imaging (MRI) with a small-molecule, gadolinium-containing probe, Gd-Hyd, could specifically detect and stage fibrogenesis in a mouse model. In this work, we present an improved probe, Gd-CHyd, featuring an N,N-dialkyl hydrazine which has an order of magnitude both greater reactivity and affinity for aldehydes. In a paired study in mice with bleomycin induced lung injury we show that the improved reactivity and affinity of Gd-CHyd results in significantly higher lung-to-liver contrast, e.g. 77% higher at 45 min post injection, and slower lung clearance than Gd-Hyd. Gd-CHyd enhanced MRI is >60-fold higher in bleomycin injured mouse lungs compared to uninjured mice. Collectively, our data indicate that enhancing hydrazine reactivity and affinity towards allysine is an effective strategy to significantly improve molecular MRI probes for lung fibrogenesis.