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This overview of the molecular pathology of lung cancer includes a review of the most salient molecular alterations of the genome, transcriptome, and the epigenome. The insights provided by the growing use of next-generation sequencing (NGS) in lung cancer will be discussed, and interrelated concepts such as intertumor heterogeneity, intratumor heterogeneity, tumor mutational burden, and the advent of liquid biopsy will be explored. Moreover, this work describes how the evolving field of molecular pathology refines the understanding of different histologic phenotypes of non-small-cell lung cancer (NSCLC) and the underlying biology of small-cell lung cancer. This review will provide an appreciation for how ongoing scientific findings and technologic advances in molecular pathology are crucial for development of biomarkers, therapeutic agents, clinical trials, and ultimately improved patient care.

Experimental preclinical models have been a cornerstone of lung cancer translational research. Work in these model systems has provided insights into the biology of lung cancer subtypes and their origins, contributed to our understanding of the mechanisms that underlie tumor progression, and revealed new therapeutic vulnerabilities. Initially patient-derived lung cancer cell lines were the main preclinical models available. The landscape is very different now with numerous preclinical models for research each with unique characteristics. These include genetically engineered mouse models (GEMMs), patient-derived xenografts (PDXs) and three-dimensional culture systems ("organoid" cultures). Here we review the development and applications of these models and describe their contributions to lung cancer research.

PURPOSE Cisplatin plus gemcitabine is a standard regimen for first-line treatment of advanced non–small-cell lung cancer (NSCLC). Phase II studies of pemetrexed plus platinum compounds have also shown activity in this setting. PATIENTS AND METHODS This noninferiority, phase III, randomized study compared the overall survival between treatment arms using a fixed margin method (hazard ratio [HR] < 1.176) in 1,725 chemotherapy-naive patients with stage IIIB or IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0 to 1. Patients received cisplatin 75 mg/m2 on day 1 and gemcitabine 1,250 mg/m2 on days 1 and 8 (n = 863) or cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 on day 1 (n = 862) every 3 weeks for up to six cycles. RESULTS Overall survival for cisplatin/pemetrexed was noninferior to cisplatin/gemcitabine (median survival, 10.3 v 10.3 months, respectively; HR = 0.94; 95% CI, 0.84 to 1.05). Overall survival was statistically superior for cisplatin/pemetrexed versus cisplatin/gemcitabine in patients with adenocarcinoma (n = 847; 12.6 v 10.9 months, respectively) and large-cell carcinoma histology (n = 153; 10.4 v 6.7 months, respectively). In contrast, in patients with squamous cell histology, there was a significant improvement in survival with cisplatin/gemcitabine versus cisplatin/pemetrexed (n = 473; 10.8 v 9.4 months, respectively). For cisplatin/pemetrexed, rates of grade 3 or 4 neutropenia, anemia, and thrombocytopenia ( P ≤ .001); febrile neutropenia ( P = .002); and alopecia ( P < .001) were significantly lower, whereas grade 3 or 4 nausea ( P = .004) was more common. CONCLUSION In advanced NSCLC, cisplatin/pemetrexed provides similar efficacy with better tolerability and more convenient administration than cisplatin/gemcitabine. This is the first prospective phase III study in NSCLC to show survival differences based on histologic type.

Purpose To investigate the efficacy and safety of bevacizumab plus carboplatin and paclitaxel in patients with advanced or recurrent non-small-cell lung cancer. Patients and Methods In a phase II trial, 99 patients were randomly assigned to bevacizumab 7.5 (n = 32) or 15 mg/kg (n = 35) plus carboplatin (area under the curve = 6) and paclitaxel (200 mg/m2) every 3 weeks or carboplatin and paclitaxel alone (n = 32). Primary efficacy end points were time to disease progression and best confirmed response rate. On disease progression, patients in the control arm had the option to receive single-agent bevacizumab 15 mg/kg every 3 weeks. Results Compared with the control arm, treatment with carboplatin and paclitaxel plus bevacizumab (15 mg/kg) resulted in a higher response rate (31.5% v 18.8%), longer median time to progression (7.4 v 4.2 months) and a modest increase in survival (17.7 v 14.9 months). Of the 19 control patients that crossed over to single-agent bevacizumab, five experienced stable disease, and 1-year survival was 47%. Bleeding was the most prominent adverse event and was manifested in two distinct clinical patterns; minor mucocutaneous hemorrhage and major hemoptysis. Major hemoptysis was associated with squamous cell histology, tumor necrosis and cavitation, and disease location close to major blood vessels. Conclusion Bevacizumab in combination with carboplatin and paclitaxel improved overall response and time to progression in patients with advanced or recurrent non-small-cell lung cancer. Patients with nonsquamous cell histology appear to be a subpopulation with improved outcome and acceptable safety risks.

Few cases of programmed death-ligand 1 inhibitor-induced scleroderma have been reported and their clinical features remain unpublished. Optimal management is, therefore, unknown and an autoantibody association has yet to be identified. We present the case of a female in her 60s who developed skin thickening after starting atezolizumab for metastatic non-small cell lung cancer. Skin biopsy 7 months after symptom onset showed histological changes consistent with scleroderma. Anti-PM/SCL-75 antibody was positive. Atezolizumab was discontinued and treatment was started with mycophenolate mofetil. After 5 months, she experienced mild improvement in skin thickening. Earlier identification of this complication may limit morbidity in this disease process, which otherwise has limited treatment options. In suspected cases, obtaining scleroderma-associated autoantibodies may help with earlier diagnosis.

A 70-year-old woman who had been taking oral steroids with tapering after an acute exacerbation of idiopathic pulmonary fibrosis (IPF) was diagnosed with stage IIIB squamous cell lung cancer by transbronchial lung biopsy from left hilum 6 months before admission. At the time, she had anorexia due to

The advent of immunotherapy has revolutionised the treatment of metastatic lung cancer and it has recently been established as the standard of care in the radical treatment of lung cancer. However, immune-related adverse events (IrAEs) frequently occur in patients treated with immunotherapy, and rare IrAEs continue to be identified. We report a case of immunotherapy-induced coeliac disease due to adjuvant durvalumab post-chemoradiotherapy in a patient receiving curative treatment for lung cancer. The patient had raised anti-tissue transglutaminase IgA and histological findings consistent with coeliac disease. This is the first published case report of probable immunotherapy-induced coeliac disease both with the immunotherapy drug durvalumab and in the curative lung cancer setting.

Background Salvage surgery is performed for selected patients with relapses of locally advanced lung cancer after definitive chemoradiation therapy (CRT), and seems to be effective. To date, the feasibility of such salvage surgery, particularly anatomical pulmonary resection, has not been fully evaluated. To assess the feasibility of salvage surgery after definitive CRT, we compared clinical outcomes of surgery after definitive CRT to those of surgery after induction CRT. Methods Medical records of patients who underwent surgery from January 2000 to January 2018 were reviewed. We compared patients with salvage anatomical pulmonary resection after definitive CRT to patients with surgery after induction CRT in terms of perioperative and long-term outcomes. Results Twenty-three patients underwent salvage surgery after definitive CRT for locally advanced lung cancer (salvage group) and 36 underwent surgery after induction CRT for cN2-stage III non-small cell lung cancer (induction CRT group). The surgical procedures in the salvage group were 2 segmentectomies, 13 lobectomies, 1 bi-lobectomy and 7 pneumonectomies, and those in the induction CRT group were 34 lobectomies and 2 bi-lobectomies. There was no 30-day or 90-day mortality in either group. The 5-year overall survival was 44.7% for the salvage group and 58.6% for the induction CRT group. The 5-year progression-free interval was 42.2% for the salvage group and 47.7% for the induction CRT group. Conclusions Salvage anatomical pulmonary resection after definitive CRT for locally advanced lung cancer is feasible with acceptable morbidity and prognosis in highly selected patients.

Lung cancer is the top reason for cancer-related deaths worldwide. The 5-year overall survival rate of lung cancer is approximately 20 % due to the delayed diagnosis and low response rate to regular treatments. Microbiota, both host-microbiota and alien pathogenic microbiota, have been investigated to be involved in a complicated and contradictory relationship with lung cancer initiation, treatments, and prognosis. Disorders of certain host-microbiota and pathogen infection are associated with the risk of lung cancers based on epidemiological evidence, and antibiotics (ATBs) could dramatically impair anti-cancer treatment efficacy, including chemotherapy and immunotherapy. Moreover, probiotics and microbe-mediated drugs are potential approaches to enhance regular anti-tumor treatments. Therefore, the knowledge of the complex dual effect of microbes on lung cancer is beneficial to take their essence and remove their dross. This review offers insight into the current trends and advancements in microbiota or microbial components related to lung cancer.

Small intestinal metastasis from lung cancer is a relatively rare occurrence, and often causes intestinal obstruction, gastrointestinal perforation, and/or gastrointestinal bleeding making it is an oncological emergency. Many patients have been reported to undergo emergency surgery owing to the rapid progression of the intestinal metastatic lesion; however, information regarding the changes that occur in such metastases over time remains lacking. Therefore, we analyzed 4 patients who had small intestinal metastases arising from lung cancer, who were treated during a 10-year period (January 2011 to December 2020), and whose tumor diameter changes were recorded. The average tumor volume growth rate was 1.48 (1.31-1.78) -fold, and the median observation period was 22 (4-39) days, showing a rapid increase. Histopathologically, in patients with a high degree of primary tumor atypia, rapid tumor growth caused by intratumoral hemorrhage may occur. This was considered to be one of the factors responsible for the rapid increase in tumor volume.

Purpose The illness-death model (IDM) is a comprehensive approach to evaluate the relationship between relapse and death. This study aimed to illustrate the value of the IDM for identifying risk factors and evaluating predictive probabilities for relapse and death in patients with non–small cell lung cancer (NSCLC) in comparison with the disease-free survival (DFS) model.Materials and Methods We retrospectively analyzed 612 NSCLC patients who underwent a curative operation. Using the IDM, the risk factors and predictive probabilities for relapse, death without relapse, and death after relapse were simultaneously evaluated and compared to those obtained from a DFS model.Results The IDM provided more detailed risk factors according to the patient’s disease course, including relapse, death without relapse, and death after relapse, in patients with resected lung cancer. In the IDM, history of malignancy (other than lung cancer) was related to relapse and smoking history was associated with death without relapse; both were indistinguishable in the DFS model. In addition, the IDM was able to evaluate the predictive probability and risk factors for death after relapse; this information could not be obtained from the DFS model.Conclusion Compared to the DFS model, we found that the IDM provides more comprehensive information on transitions between states and disease stages and provides deeper insights with respect to understanding the disease process among lung cancer patients.

Uniportal video-assisted thoracoscopic surgery (U-VATS) can achieve traditional clinical outcomes comparable to those of multiportal video-assisted thoracoscopic surgery (M-VATS). This study aimed to compare patient-reported outcomes between U-VATS and M-VATS for lung cancer lobectomy in the early postoperative period.This comparative analysis used data from a longitudinal prospective study (Perioperative Symptom Study of Lung Cancer [CN-PRO-Lung 1]). Symptom severity, functional status, and quality of life were compared between groups using generalized estimation equation models. Symptom severity and functional status were reported as proportion of patients with clinically meaningful severe scores on 0- to 10-point scales assessed using the MD Anderson Symptom Inventory-Lung Cancer module.Of the 174 patients included, 102 (58.6%) underwent U-VATS lobectomy and 72 (41.4%) underwent M-VATS lobectomy. After adjusting for confounders, patients in the U-VATS group reported less severe pain (P = .02), fatigue (P = .001), constipation (P = .01), coughing (P = .003), shortness of breath (P.001), and disturbed sleep (P = .007) during the 6-day postoperative hospitalization than did patients in the M-VATS group. Moreover, fewer patients reported severe impairment in walking (P = .033) or their capacity to enjoy life (P = .027) in the U-VATS group. Meanwhile, there were no significant between-group differences in the quality of life scores, operative time, chest tube duration, length of hospital stay, or early complication rate (grade II or higher) (all P.05).U-VATS may produce fewer severe symptoms and better functional status than M-VATS for lung cancer lobectomy in the early postoperative period.

BACKGROUND Measuring variation in perioperative outcomes to accurately discriminate performance between surgical providers may be limited by reliability. We aimed to evaluate reliability estimates of metrics associated with lung cancer resection. METHODS We performed a retrospective cohort study utilizing the 2015 National Cancer Database to identify patients undergoing lung cancer resection. Primary outcomes were reliability estimates for perioperative outcomes and for measures of adherence to clinical benchmarks, generated through hierarchical multi-level modeling techniques. RESULTS We identified 27,300 patients undergoing resection. Overall risk- and reliability-adjusted 30- and 90-day mortality rates were 1.7% and 3.3%, respectively; 61.0% and 41.1% of eligible patients received stage-appropriate adjuvant and neoadjuvant therapy. Video-assisted thoracoscopic surgery (VATS) was performed in 59.6% of cases with clinical stage I disease. The mean reliability of 30- and 90-day mortality was 0.11 (standard deviation (SD) 0.09) and 0.22 (SD 0.15), respectively; for performing VATS for stage I disease, 0.97 (SD 0.04). When stratified by hospital volume quartile, the mean reliability of 30-day mortality was 0.04 (SD 0.03) in the lowest and 0.20 (SD 0.10) in the highest quartile. Only 14% of hospitals met an established 0.7 reliability benchmark for 30- and 90-day mortality, but over 97% of hospitals exceeded these benchmarks for providing stage-appropriate systemic therapy and performing VATS for stage I disease. CONCLUSIONS Metrics used to compare lung cancer surgical performance between providers have varying levels of reliability. Reliability should be considered when profiling providers, which will become particularly important as lung cancer treatment under screening programs continues to expand.

Purpose: Aim was to analyze demographic and tumor characteristics, treatment, and survival of patients with lung cancer younger than 40 years of age (U40) compared to older subgroups (41–70 and >70...

Background In this study, we aimed to evaluate the R(un) category proposed by the International Association for the Study of Lung Cancer (IASLC) for non-small cell lung cancer (NSCLC). Methods We retrospectively reviewed the medical records of patients with NSCLC who underwent segmentectomy or lobectomy between 2014 and 2015 at our institution. Residual tumor (R) status was reclassified from the Union for International Cancer Control designation to the IASLC-proposed R classification [R0 and R(un)]. The underlying reasons for the R(un) reclassification were analyzed according to pathological stage, lymph node status, and resected lobe. A Cox proportional hazard model was used to evaluate the impacts of R(un) categorization on overall survival. Results Of 355 cases, 44.5% were reclassified as R(un). The most common reason for the reclassification was insufficient number of harvested lymph nodes or no station 7 lymph nodes. When stratified by tumor location, the absence of station 7 lymph nodes was especially prominent in both the right and left upper lung resections. In the multivariate Cox regression model, IASLC R classification was associated with poor overall survival in node-positive cases (hazard ratio: 2.657; P =.016). Conclusions Various factors resulted in reclassification to R(un) because the R(un) group was highly heterogeneous. Careful consideration is required to determine whether R(un) classification can be used as an indicator of lymph node dissection quality. For advanced cases, the R(un) definition may be useful in predicting poor prognosis.

The Surveillance, Epidemiology and End Results (SEER) and the National Cancer Database (NCDB) are databases for cancer analysis that may be subject to error in data reporting. This study examined the rates and impact of discordant data for non-small cell lung cancer.NCDB and SEER were queried for non-small cell lung cancer pathologic tumor, node, metastasis data (NCDB) or "derived" data (SEER). Discordancy between descriptors with stage and impact of outlier data were analyzed.Incomplete staging was noted in 71.5% of the NCDB and 10.3% of SEER patients. A total of 174 829 patients from the NCDB and 117 114 from SEER were analyzed. The NCDB had 97 cases with ≥20 positive lymph nodes recorded vs 27 in SEER (P.001). Mean and median sampled lymph nodes were skewed with inclusion of these data points (P .001). The NCDB misclassified 0.99% tumors5 cm as stage I vs 0.04% in SEER (P.001). The NCDB misstaged positive lymph nodes as pathologic N0 (0.59%) or stage 0 or stage I (0.65%). The NCDB misclassified pathologic N1 as lower than stage II (0.91%) or N2 as lower than stage III (0.36%). The NCDB misclassified stage I with documentation of pathologic N1 or N3 disease (0.24%) or stage II with evidence of N2 or N3 disease (0.50%). The NCDB misclassified pathologic M1 as pathologic stageIV in 0.9% of cases and misclassified 19.8% of stage IV as pathologic M0. SEER collaborative staging had no discordance (P.001).The NCDB and SEER are 2 powerful cancer databases. However, the cumulative discordancy rate was 4.9% for the NCDB and 0.008% for SEER, with more misstaging and outliers in the NCDB.

Background With a 5% improvement in 5-year overall survival achieved with current neoadjuvant or adjuvant chemotherapy, new treatments for resectable non-small cell lung cancer (NSCLC) are urgently needed. The use of immune checkpoint inhibitors (ICIs) is established in metastatic NSCLC and is being evaluated in resectable NSCLC. Methods Publications and conference databases and clinicaltrials.gov were searched for reports on clinical studies of neoadjuvant immunotherapy in patients with early resectable NSCLC. Results Potential advantages of neoadjuvant ICIs include the following: earlier treatment of micrometastatic disease; activation of a broader, potentially durable immune response by the whole tumor and associated lymph nodes; and pathologic assessment of neoadjuvant treatment response, which may guide adjuvant therapy. Surgical considerations include delays to surgery, potential disease progression preventing curative resection, and perioperative morbidity and mortality. Surrogate end points of efficacy (pathologic complete response, major pathologic response) and biomarkers predictive of outcome (programmed death ligand 1 expression, tumor mutational burden, and circulating tumor DNA) can accelerate clinical trial completion and early-stage treatment development; their application in neoadjuvant ICI studies in NSCLC is reviewed. Conclusions Phase 2 trials of neoadjuvant ICIs alone or in combination with chemotherapy showed encouraging safety and efficacy in patients with resectable NSCLC, thus warranting the ongoing phase 3 studies of neoadjuvant immunotherapy combined with chemotherapy. Preoperative and intraoperative unresectability after neoadjuvant ICIs appears comparable to that observed with neoadjuvant chemotherapy. To help thoracic surgeons and medical oncologists to distinguish among ICIs beyond efficacy as phase 3 data emerge, surgery-related end points for perioperative morbidity, mortality, and complexity should be defined, standardized, incorporated into trial designs, and reported.

Advances in biomarkers, targeted therapies, and immuno-oncology have transformed the clinical management of patients with advanced NSCLC. For oncogene-driven tumors, there are highly effective targeted therapies against EGFR, ALK, ROS1, BRAF, TRK, RET, and MET. In addition, investigational therapies for KRAS, NRG1, and HER2 have shown promising results and may become standard-of-care in the near future. In parallel, immune-checkpoint therapy has emerged as an indispensable treatment modality, especially for patients lacking actionable oncogenic drivers. While PD-L1 expression has shown modest predictive utility, biomarkers for immune-checkpoint inhibition in NSCLC have remained elusive and represent an area of active investigation. Given the growing importance of biomarkers, optimal utilization of small tissue biopsies and alternative genotyping methods using circulating cell-free DNA have become increasingly integrated into clinical practice. In this review, we will summarize the current landscape and emerging trends in precision medicine for patients with advanced NSCLC with a special focus on predictive biomarker testing.

Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in surgical patients. Thoracic surgery patients are at increased risk due to inherent technical and disease-specific factors. Other surgical specialties have adopted postdischarge extended VTE prophylaxis; however evidence is scarce in thoracic surgery. This study aims to identify VTE risk factors and associated mortality among surgical lung cancer patients.Using administrative databases all patients in the province of Ontario undergoing lung cancer surgery from 2007 to 2017 were identified. Logistic regression identified VTE risk factors at 90 days and 1 year postoperatively. A flexible parametric survival analysis compared mortality and survival up to 5 years after surgery between patients with and without VTE.Of 65,513 patients diagnosed with lung cancer, 12,626 (19.3%) underwent surgery. VTE incidence at 90 days and 1 year postoperatively was 1.3% and 2.7%, respectively. Open and more extensive resections carried an increased VTE risk, with pneumonectomy conferring the highest risk (odds ratio, 2.36; P.001). Stage III and IV disease carried a 3.19 and 4.97 times higher risk of VTE, respectively, compared with stage I (P.001). The hazard ratio for mortality at 1 year for patients with VTE was 2.01 (P.001). Patients suffering a VTE had reduced 5-year survival.Patients undergoing pneumonectomy and those with advanced stage have an increased VTE risk. Patients suffering a thrombotic complication have an increased risk of mortality and decreased 5-year survival. Accordingly strategies to reduce VTE risk should be considered in patients undergoing high-risk operations to reduce the mortality of VTEs.

This study aimed to investigate the oncologic outcomes of video-assisted thoracoscopic (VATS) left upper trisegmentectomy (LTS) vs left upper lobectomy (LUL) for patients presenting with stage I non-small cell lung cancer (NSCLC).A retrospective analysis identified 1543 consecutive patients presenting to Shanghai Pulmonary Hospital (Shanghai, China) with NSCLC for VATS LTS or LUL from 2013 to 2017. After propensity-score matching for patient demographics and tumor characteristics, 273 pairs were identified. Disease-free survival (DFS) and overall survival (OS) were estimated by the Kaplan-Meier method and compared using the log-rank test.The median follow-up time was 51.5 months. There were no significant differences in operative duration (2.11 ± 0.64 hours vs 2.49 ± 5.96 hours; P = .30), total blood loss (106.19 ± 170.83 mL vs 97.07 ± 149.34 mL; P = .51), and operative complications (10% vs 8%; P = .37) between the LUL and LTS groups. Patients undergoing LUL had longer postoperative hospital stays (5.55 ± 3.00 days vs 4.87 ± 2.33 days; P = .003), greater tumor margin distance (3.3 ± 1.2 cm vs 3.1 ± 0.9 cm; P.001), and greater number of lymph nodes harvested (8.0 ± 3.2 vs 6.8 ± 3.3; P.001) than patients undergoing LTS, but the margin-to-tumor ratio was not statistically different (2.5 ± 1.6 vs 2.3 ± 1.1; P = 0.11). Median DFS (49.5 months vs 54.3 months; P = .77) and OS (49.5 months vs 55.0 months; P = .88) were not significantly different between patients undergoing LTS and those undergoing LUL, and similar outcomes were noted across subgroups of patients stratified by tumor stage, pathologic type, and radiographic manifestations.VATS LTS and LUL had comparable oncologic outcomes for stage I NSCLC, regardless of tumor pathologic types and radiologic findings, as long as negative margins were confirmed.

A 42-year-old woman with chronic obstructive pulmonary disease was referred to the respiratory team due to shortness of breath on exertion and significant deterioration in pulmonary function tests. Her symptoms were progressively getting worse. This prompted a referral to the specialist team where further investigations were undertaken including a high-resolution CT scan followed by lung biopsy, which eventually revealed a diagnosis of lymphangioleiomyomatosis (LAM). Successful referral to the National LAM Centre in Nottingham provided the key therapeutic approach required to manage this rare condition. Diagnosing this rare condition was due to the multidisciplinary team approach, which involved input from the general practitioner, radiologist and respiratory consultant. The patient has been making good progress with pharmacological management.

Classic biphasic pulmonary blastoma (CBPB) is a very rare primary pulmonary malignancy with distinctive clinical and pathological features. Usually CBPB presents with either non specific symptoms or is diagnosed incidentally. Histologically CBPB is composed of a mixture of malignant epithelial and stromal cells resembling fetal lung tissue. Surgical resection is the mainstay of treatment with further chemotherapy or radiotherapy on a case-by-case basis. However, due to its rarity, no definite treatment guidelines are available. CBPB overall has a very poor prognosis with a 5-year survival rate of only 15%. Our patient presented with cough and haemoptysis. Her chest radiograph demonstrated a large right-sided lung mass. Further investigations included CT, CT-guided biopsy and PET CT which were discussed at multidisciplinary team meetings. The patient then underwent complete surgical excision. We report this rare malignancy with radiological and pathological features, comparing them with previously reported cases.

HIV status may influence survival from non-small cell lung cancer (NSCLC). Among NSCLC patients in the Bronx, NY, we assessed (1) associations of CD4 count, CD4/CD8 ratio and HIV viral load (VL) with survival and (2) prognostic factors among persons living with HIV (PLWH). We compared survival from NSCLC diagnosis (2004-2017) between HIV-negative persons (HIV-, n=2,881) and PLWH (n=88) accounting for clinical and sociodemographic factors. HIV-survival was also compared with PLWH, dichotomized by CD4 (

A 70-year-old man was referred to the pulmonary office for evaluation of a solitary lung nodule in September 2019. The patient was diagnosed with stage 1 adenocarcinoma of the rectum in November 2018 and underwent low anterior resection without any complications. No chemotherapy or radiation therapy

Purpose A fast, reliable and non-invasive method is required in differentiating brain metastases (BMs) originating from lung cancer (LC) and breast cancer (BC). The aims of this study were to assess the role of histogram analysis of apparent diffusion coefficient (ADC) maps in differentiating BMs originated from LC and BC, and then to investigate further the association of ADC histogram parameters with Ki-67 index in BMs. Methods A total of 55 patients (LC, N = 40; BC, N = 15) with BMs histopathologically confirmed were enrolled in the study. The LC group was divided into small-cell lung cancer (SCLC; N = 15) and non-small-cell lung cancer (NSCLC; N = 25) groups. ADC histogram parameters (ADCmax, ADCmean, ADCmin, ADCmedian, ADC10, ADC25, ADC75 and ADC90, skewness, kurtosis and entropy) were derived from ADC maps. Mann–Whitney U-test, independent samples t-test, receiver operating characteristic (ROC) analysis and Spearman correlation analysis were used for statistical assessment. Results ADC histogram parameters did not show significant differences between LC and BC groups ( p > 0.05). Subgroup analysis showed that various ADC histogram parameters were found to be statistically lower in the SCLC group compared to the NSCLC and BC groups ( p mean and ADC10 for differentiating SCLC BMs from NSCLC, and ADC25 for differentiating SCLC BMs from BC achieved optimal diagnostic performances. Various histogram parameters were found to be significantly correlated with Ki-67 ( p Conclusion Histogram analysis of ADC maps may reflect tumoural proliferation potential in BMs and can be useful in differentiating SCLC BMs from NSCLC and BC BMs.

BACKGROUND: Racial/ethnic minorities face stark inequalities in lung cancer incidence, treatment, survival, and mortality compared with U.S. born non-Hispanic Whites. Lung cancer screening (LCS) with low-dose computed tomography (LDCT) is effective at reducing lung cancer mortality in high-risk current and former smokers and is recommended by the U.S. Preventive Services Task Force (USPSTF). This study sought to assess primary care providers’ (PCPs’) knowledge, attitudes, beliefs, and practice related to LCS and the recent USPSTF guidelines in five high risk immigrant communities in New York City. METHODS: We surveyed 83 eligible PCPs between December 2016 and January 2018 through surveys sent by mail, email, and fax, administered by phone or in-person. The survey included questions about providers’ clinical practice, knowledge, attitudes and beliefs related to LCS and the USPSTF guidelines. Information about patient demographics, PCPs’ training background and practice type were also collected. RESULTS: Sixty-seven percent of respondents reported that they did not have established guidelines for LCS at their practice and 52% expressed that “vague” screening criteria influenced their referral processes for LCS. Barriers to LCS with LDCT included concerns that LDCT is not covered by insurance, patients’ fears of screening results, and patients’ concerns regarding radiation exposure. DISCUSSION: Targeted educational interventions for both PCPs and patients may increase access to recommended LCS, especially for populations at disproportionate risk for lung cancer.

Background: The aim was to assess the likelihood of patients with simultaneously diagnosed liver and lung metastases (SLLM) from colorectal cancer (CRC) to receive the curative treatment decided upon multidisciplinary team meeting (MDT) and to elaborate on the reasons for treatment intention failure and survival outcomes depending on final treatment strategy.Method: The study included a retrospective review of all patients discussed at the MDT at a single centre between 2010 and 2018 to identify all patients presenting with SLLM from CRC. Treatment intention, actual treatment outcome and reasons for treatment failure was documented. Descriptive and survival statistics were applied.Results: Of the 160 patients who had SLLM, resection of all metastatic sites was deemed possible in 107 patients (67%) of whom 39 patients (36%) finalized the curative treatment plan. The most common reason for noncompliance with management recommendations was disease progression or recurrence. Complete resection resulted in longer survival compared to patients who did not undergo resection of all metastatic sites with median survival of 63 and 27 months, respectively (p < 0.001).Conclusion: A low proportion of patients completed the initially intended curative resections. Simulta-neous resection of liver/lung metastases and primary tumour might increase the proportion of fulfilled hepatopulmonary resections.(c) 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Inflammation is an essential component of several respiratory diseases, such as chronic obstructive pulmonary disease (COPD), asthma and acute respiratory distress syndrome (ARDS). It is central to lung cancer, the leading cancer in terms of associated mortality that has affected millions of individuals worldwide. Inflammation and pulmonary manifestations are also the major causes of COVID-19 related deaths. Acute hyperinflammation plays an important role in the COVID-19 disease progression and severity, and development of protective immunity against the virus is greatly sought. Further, the severity of COVID-19 is greatly enhanced in lung cancer patients, probably due to the genes such as ACE2, TMPRSS2, PAI-1 and furin that are commonly involved in cancer progression as well as SAR-CoV-2 infection. The importance of inflammation in pulmonary manifestations, cancer and COVID-19 calls for a closer look at the underlying processes, particularly the associated increase in IL-6 and other cytokines, the dysregulation of immune cells and the coagulation pathway. Towards this end, several reports have identified epigenetic regulation of inflammation at different levels. Expression of several key inflammation-related cytokines, chemokines and other genes is affected by methylation and acetylation while non-coding RNAs, including microRNAs as well as long non-coding RNAs, also affect the overall inflammatory responses. Select miRNAs can regulate inflammation in COVID-19 infection, lung cancer as well as other inflammatory lung diseases, and can serve as epigenetic links that can be therapeutically targeted. Furthermore, epigenetic changes also mediate the environmental factors-induced inflammation. Therefore, a better understanding of epigenetic regulation of inflammation can potentially help develop novel strategies to prevent, diagnose and treat chronic pulmonary diseases, lung cancer and COVID-19.

Introduction Outcomes after the introduction of surgical innovations can be impaired by learning periods. The aim of this study is to compare the short-term outcomes of a recently implemented RATS approach to a standard VATS program for anatomical lung resections. Methods Retrospective review of consecutive patients undergoing pulmonary anatomical resection through a minimally invasive approach since RATS approach was applied in our department (June 01, 2018, to November 30, 2019). Propensity score matching was performed according to patients’ age, gender, ppoFEV1, cardiac comorbidity, type of malignancy, and type of resection. Outcome evaluation includes: overall morbidity, significant complications (cardiac arrhythmia, pneumonia, prolonged air leak, and reoperation), 30-day mortality, and length of hospital stay. Data were compared by two-sided chi-square or Fisher's exact test for categorical and Mann–Whitney U test for continuous variables. Results A total of 273 patients (206 VATS, 67 RATS) were included in the study. After propensity score matching, data of 132 patients were analyzed. The thirty-days mortality was nil. Overall morbidity (RATS: 22.4%, VATS: 29.2%; p = 0.369), major complications (RATS: 9% vs VATS: 9.2%; p = 0.956) and the rates of specific major complications (cardiac arrhythmia RATS: 4.5%, VATS: 4.6%, p = 1; pneumonia RATS:0%, VATS:4.6%, p = 0.117; prolonged air leak RATS: 7.5%; VATS: 4.6%, p = 0.718) and reoperation (RATS: 3%, VATS: 1.5%, p = 1) were comparable between both groups. The median length of stay was 3 days in both groups (p = 0.101). Conclusions A RATS program for anatomical lung resection can be implemented safely by experienced VATS surgeons without increasing morbidity rates.

Small cell lung cancer (SCLC) is a particular subtype of lung cancer with high mortality. Recent advances in understanding SCLC genomics and breakthroughs of immunotherapy have substantially expanded existing knowledge and treatment modalities. However, challenges associated with SCLC remain enigmatic and elusive. Most of the conventional drug discovery approaches targeting altered signaling pathways in SCLC end up in the ‘grave-yard of drug discovery’, which mandates exploring novel approaches beyond inhibiting cell signaling pathways. Epigenetic modifications have long been documented as the key contributors to the tumorigenesis of almost all types of cancer, including SCLC. The last decade witnessed an exponential increase in our understanding of epigenetic modifications for SCLC. The present review highlights the central role of epigenetic regulations in acquiring neoplastic phenotype, metastasis, aggressiveness, resistance to chemotherapy, and immunotherapeutic approaches of SCLC. Different types of epigenetic modifications (DNA/histone methylation or acetylation) that can serve as predictive biomarkers for prognostication, treatment stratification, neuroendocrine lineage determination, and development of potential SCLC therapies are also discussed. We also review the utility of epigenetic targets/epidrugs in combination with first-line chemotherapy and immunotherapy that are currently under investigation in preclinical and clinical studies. Altogether, the information presents the inclusive landscape of SCLC epigenetics and epidrugs that will help translate the knowledge of epigenetics to improve SCLC outcomes.

Background: Lung adenocarcinoma (LUAD) is a common malignancy with a poor prognosis due to the lack of predictive markers. DNA damage repair (DDR)-related genes are closely related to cancer progression and treatment. Introduction: To identify a reliable DDR-related gene signature as an independent predictor of LUAD. Methods: DDR-related genes were obtained using combined analysis of TCGA-LUAD data and literature information, followed by the identification of DDR-related prognostic genes. The DDRrelated molecular subtypes were then screened, followed by Kaplan-Meier analysis, feature gene identification, and pathway enrichment analysis of each subtype. Moreover, Cox and LASSO regression analyses were performed for the feature genes of each subtype to construct a prognostic model. The clinical utility of the prognostic model was confirmed using the validation dataset GSE72094 and nomogram analysis. Results: Eight DDR-related prognostic genes were identified from 31 DDR-related genes. Using consensus cluster analysis, three molecular subtypes were screened. Cluster2 had the best prognosis, while cluster3 had the worst. Compared to cluster2, clusters 1 and 3 consisted of more stage3 - 4, T2-T4, male, and older samples. The feature genes of clusters1, 2, and 3 were mainly enriched in the cell cycle, arachidonic acid metabolism, and ribosomes. Furthermore, a 15-feature gene signature was identified for improving the prognosis of LUAD patients. Conclusion: The 15 DDR-related feature gene signature is an independent and powerful prognostic biomarker for LUAD that may improve risk classification and provide supplementary information for a more accurate evaluation and personalized treatment.

Despite the advances in treatment using chemotherapy or targeted therapies, due to static survival rates, non-small cell lung cancer (NSCLC) is the major cause of cancer-related deaths worldwide. Epigenetic-based therapies have been developed for NSCLC by targeting DNA methyltransferases (DNMTs) and histone-modifying enzymes. However, treatment using single epigenetic agents on solid tumours has been inadequate; whereas, treatment with a combination of DNMTs inhibitors with chemotherapy and immunotherapy has shown great promise. Dietary sources of phytochemicals could also inhibit DNMTs and cancer stem cells, representing a novel and promising way to prevent and treat cancer. Herein, we will discuss the different DNMTs, DNA methylation profiling in NSCLC as well as current demethylating agents in ongoing clinical trials. Therefore, providing a concise overview of future developments in the field of epigenetic therapy in NSCLC.

Background Prolonged air leak (PAL) (>5 days) after robotic-assisted pulmonary lobectomy is a significant complication. This study aimed to determine patient- and surgeon-related factors that can predict PAL after robotic lobectomy for lung cancer. Methods This study was a retrospective review of a single-center experience of robotic-assisted lobectomy for lung cancer. Perioperative variables, including surgeon case experience, patient demographics, diffusion capacity of lung for carbon monoxide, forced expiratory volume in 1 second, body mass index, and smoking status were evaluated. Results A total of 305 robotic-assisted lobectomies performed by 4 surgeons met inclusion criteria from June 2016 to February 2019. The 30-day postoperative mortality was 1.2%. PAL developed in 27 of 305 (8.8%) patients. Surgeons’ robotic experience was grouped by 10-case increments. When adjusted for age and sex, the odds for PAL decreased by 15% for every 10 robotic lobectomies the surgeons performed (odds ratio [OR], 0.85; 95% CI, 0.74-0.99; P = .0384). Logistic regression models showed a linear transition curve at the 50th case. Female sex (OR, 2.62; 95% CI, 1.03-6.69; P = .0314) and younger age (OR, 0.61; 95% CI, 0.41-0.91; P = .0184) were statistically significant risk factors for PAL. Cumulative sum analysis similarly showed a strong association between experience and PAL. Preoperative diffusing capacity of lung for carbon monoxide, forced expiratory volume in 1 second, body mass index, and smoking status were not statistically significant predictive factors. Conclusions These results show that surgeon robotic case experience is associated with the rate of postoperative PAL: as the number of robotic lobectomies increases, the rate of PAL significantly decreases. It is imperative to emphasize that a learning curve exists for this approach that directly affects patient outcomes.

RATIONALE Future optimization of CT lung cancer screening algorithms will depend on clinical outcomes data. OBJECTIVES To report the outcomes of positive and suspicious findings in a clinical CT lung cancer screening program. METHODS We retrospectively reviewed results for patients from our institution undergoing lung cancer screening from 1/2012 through 12/2018, with follow-up through 12/2019. All exams were retrospectively re-scored using Lung-RADS® v1.1. Metrics assessed included positive, probably benign and suspicious exam rates, frequency/nature of care escalation, and lung cancer detection rates following a positive, probably benign, and suspicious exam result and overall. We calculated time required to resolve suspicious exams as malignant or benign. Results were broken down by subcategories, reason for positive/suspicious designation, and screening round. RESULTS During the study period 4301 individuals underwent a total of 10897 exams. The number of positive (13.9%), suspicious (5.5%), and significant incidental (6.4%) findings were significantly higher at baseline screening. Cancer detection and false positive rates were 2.0% and 12.3% at baseline vs 1.3% and 5.1% across subsequent screening rounds respectively. Baseline solid nodule(s) 6 to < 8 mm were the only probably benign findings resulting in lung cancer detection within 12 months. New solid nodules 6 to < 8 mm were the only Lung-RADS® 4A findings falling within the Lung-RADS® predicted cancer detection range of 5-15% (12.8%). 38.5% of Lung-RADS® 4A cancers were detected within three months. CONCLUSIONS Modification of the definition and suggested workup of positive and suspicious lung cancer screening findings appears warranted.

Retrospective performance evaluation of a computer-aided detection (CAD) system on standard posteroanterior (PA) chest radiographs (PA-CXR) in detection of pulmonary nodules, infectious consolidation, pneumothorax, pleural effusion, aortic calcification, cardiomegaly and rib fractures compared to radiologists analyzing PA-CXR including dual-energy subtraction radiography (further termed as DESR).PA-CXR/DESR images of 197 patients were included. All patients underwent chest CT (gold standard) within a short interval (mean 28 hours). All images were evaluated by three blinded readers for the presence of pulmonary nodules, infectious consolidation, pneumothorax, pleural effusion, aortic calcification, cardiomegaly, and rib fractures. Meanwhile PA-CXR were analyzed by a CAD software. CAD results were compared to the majority result of the three readers. Sensitivity and specificity were calculated. McNemar's test was applied to test for significant differences. Interobserver agreement was defined using Cohen's kappa (κ).Sensitivity of the CAD software was significantly higher (p0.05) for detection of infectious consolidation and pulmonary nodules (67.9% vs 26.8% and 54% vs 35.6%, respectively; p0.001) compared to radiologists analyzing DESR images. For the residual evaluated pathologies no statistical significant differences could be found. Overall, mean inter observer agreement between the three radiologists was moderate (k = 0.534). The best interobserver agreement could be reached for pneumothorax (k = 0.708) and pleural effusion (k = 0.699), while the worst was obtained for rib fractures (k = 0.412).The CAD system has the potential to improve the detection of infectious consolidation and pulmonary nodules on CXR images.

Purpose The role of epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR-TKIs) in the management of persistent subsolid nodules (SSNs) is unclear. This study aimed to investigate the impact of EGFR-TKIs on concurrent SSNs in patients with stage IV non–small cell lung cancer (NSCLC).Materials and Methods Patients who received an EGFR-TKI for at least 1 month for stage IV NSCLC and had concurrent SSN(s) that had existed for at least 3 months on chest computed tomography were included in this retrospective study. Size change of each nodule before and after EGFR-TKI therapies were evaluated using a cutoff value of 2 mm; increase (≥ 2 mm), decrease (≤ –2 mm), and no change (–2 mm < size change < +2 mm).Results A total of 77 SSNs, 51 pure ground-glass (66.2%) and 26 part-solid nodules (33.8%), were identified in 59 patients who received gefitinib (n=45) and erlotinib (n=14). Among 58 EGFR mutation analysis performed for primary lung cancer, 45 (77.6%) were EGFR mutant. The proportions of decrease group were 19.5% (15/77) on per-nodule basis and 25.4% (15/59) on per-patient basis. Four SSNs (5.2%) disappeared completely. On per-patient based multivariable analysis, EGFR exon 19 deletion positivity for primary lung cancer was associated with a decrease after initial EGFR-TKI therapy (adjusted odds ratio, 4.29; 95% confidence interval, 1.21 to 15.29; p=0.025).Conclusion Approximately 20% of the concurrent SSNs decreased after the initial EGFR-TKI therapy. EGFR exon 19 deletion positivity for primary lung cancer was significantly associated with the size change of concurrent SSNs.

Purpose The usefulness of rehabilitation in patients with reduced lung function before lung surgery remains unclear, and there is no adequate method for evaluating the effect of rehabilitation. We aimed to evaluate the usefulness of rehabilitation in patients with non-small cell lung cancer (NSCLC) undergoing lung cancer surgery.Materials and Methods We retrospectively analyzed the medical records of NSCLC patients at Korea University Guro Hospital between 2018 and 2020. Patients were divided into two groups depending on whether they underwent rehabilitation. Pulmonary function test (PFT) data and muscle determined using chest computed tomography (CT) images were analyzed. Because the baseline characteristics were different between the two groups, propensity score matching was performed.Results Of 325 patients, 75 (23.1%) and 250 (76.9%) were included in the rehabilitation and non-rehabilitation (control) groups, respectively. The rehabilitation group had a worse general condition at baseline. After propensity score matching, 45 patients remained in each group. Pulmonary function (forced expiratory volume in 1 second, %) (p=0.001) and the Hounsfield unit of erector spinae muscle (p=0.001) were better preserved in the rehabilitation group. Muscle loss of 3.4% and 0.6% was observed in the control and rehabilitation groups, respectively (p=0.003). In addition, the incidence of embolic events was lower in the rehabilitation group (p=0.044).Conclusion Pulmonary rehabilitation is useful in patients with NSCLC undergoing lung surgery. Pulmonary rehabilitation preserves lung function, muscle and reduces embolic events after surgery. Pulmonary rehabilitation is recommended for patients with NSCLC undergoing surgery.

Purpose Histologic change is a resistant mechanism in lung cancer. The most common histological change is the switch from adenocarcinoma (AdenoCa) to small cell carcinoma (SCC) against to tyrosine kinase inhibitor (TKI) inhibitors. However, it is not clear whether other treatment modalities are involved in the histologic changes. Materials and methods We investigated histological changes in eight cases, after various treatments, and compared the molecular profiles between primary tumors and changed tumors using exome sequencing where tissue was available. Results Three cases of AdenoCa that were changed into SCC retained the initial mutations after TKI and/or surgical treatment. After treatment with TKI and immunotherapy, an EGFR-mutant AdenoCa changed to squamous cell carcinoma (SqCa). SqCa in a patient treated with surgery was changed into combined adenoCa and SqCa. These two cases showed the same genetic variations between the two distinct non-small cell carcinomas. Only surgical treatment might induce histologic change. Three patients experienced two histologic changes, which the changed tumors returned to its original state or changed to a combined tumor after treatments. Four cases showed combined histology in first or second change. Two SqCas were changed to SCC. Conclusion The histology of non-small cell carcinoma can be changed to a single pattern or combined subtypes after various treatment modalities, and the phenotypic changes seem not fixed. Therefore, additional morphologic changes may occurred regardless of their genetic status and types of treatments. To refine the new treatment strategy, consecutive repeated biopsies in progressive disease or recurrent tumor are necessary.

Lung cancer screening with low-dose computed tomography has demonstrated at least a 20% decrease in lung cancer-specific mortality, but it has the potential harm of unnecessary invasive procedures performed because of false-positive results. This study reports the outcomes of a structured multidisciplinary lung cancer screening program in an area of endemic histoplasmosis.A retrospective review of patients undergoing lung cancer screening from December 2012 to March 2019 was conducted. Findings suggestive of lung cancer were presented to a multidisciplinary thoracic tumor board. Patients were assigned to interval imaging follow-up, additional diagnostic imaging, or referral for an invasive procedure. Invasive procedures were then compared between benign and malignant diseases.A total of 4087 scans were performed on 2129 patients; 372 (9.1%) were suspicious and were presented to a multidisciplinary thoracic tumor board. Ultimately, 108 procedures were performed: 55 bronchoscopies, 7 percutaneous biopsies, and 46 operations. A total of 25 patients (1.2%) underwent bronchoscopy resulting in benign pathologic findings, significantly associated with an indication of an endobronchial lesion (P = .01). All percutaneous biopsy specimens revealed malignancy. Five patients (0.2%) who underwent resection had benign disease. Lung cancer was diagnosed in 67 patients (3.1% of the entire cohort), 46 of whom had stage I or II disease.Lung cancer screening in a structured, multidisciplinary program successfully identifies patients with early-stage lung cancer with limited unnecessary surgical interventions. Patients with isolated endobronchial lesions should undergo short interval imaging follow-up to avoid bronchoscopy for benign disease. Future studies to minimize unnecessary procedures could incorporate biomarkers and advanced imaging analysis into risk assessment models.

The role of local surgery in patients with metastatic soft tissue sarcoma (STS) remains unknown. The study aims to assess the clinical outcomes and impact of surgical resection on survival in patients with metastatic STS and elucidate the survival differences between synchronous and metachronous metastatic groups.Among the 272 patients with STS treated between 2000 and 2018, 84 with synchronous or metachronous metastasis were included. Associations between overall survival and primary tumor resection and metastasectomy were assessed using multivariate Cox regression analyses to adjust for baseline differences between surgically and non-surgically treated patients. Propensity score matching was applied to compare synchronous and metachronous metastasis.Among the 84 patients included, 69 (82%) and 41 (49%) underwent primary tumor resection and metastasectomy, respectively. The 2- and 5-year overall survivals of all patients after first detection of metastasis were 51.1% and 24.4%, respectively. Multivariate analysis showed that size8 cm, grade3, and number of metastases4 were associated with longer overall survival. After adjusting for baseline demographic and tumor characteristics, primary tumor resection and metastasectomy still had favorable effects on survival. Tumor subtypes, grade, and number of metastases differed significantly between synchronous and metachronous groups. However, after adjusting for these valuables, both groups exhibited comparable survival.Approximately one fourth of the patients with metastatic STS survived for5 years. Our results showed that surgical resection of primary tumors or metastatic lesions had favorable impact on survival even after adjusting for patient backgrounds, with comparable survival observed between those with synchronous and metachronous metastases.

A 70-year-old man received pembrolizumab as a second-line treatment for squamous cell lung cancer of the lower right lobe. After three courses, proteinuria and hematuria were observed, which worsened after seven courses. He was diagnosed with a combination of IgA nephropathy and active interstitial nephritis. Steroid pulse therapy was started, and the dose of prednisolone was gradually reduced from 60 mg/day. Renal dysfunction as an immune-related adverse event of pembrolizumab monotherapy for non-small cell lung cancer has been reported previously. Therefore, establishing a system for the early detection and treatment that distinguishes immune-related glomerular diseases is essential.

Background: Immunotherapy drugs, known as immune checkpoint inhibitors (ICIs), work by blocking checkpoint proteins from binding with their partner proteins. The two main pathways that are specifically targeted in clinical practice are cytotoxic T-lymphocyte antigen-4 (CTLA- 4) and programmed cell death protein 1 (PD-1) that showed potent immune-modulatory effects through their function as negative regulators of T cell activation. Methods: In view of the rapid and extensive development of this research field, we conducted a comprehensive review of the literature and updated on the use of CTLA-4, PD-1, and PD-L1 targeted therapy in the treatment of several types of cancer, including melanoma, non-small-cell lung carcinoma, breast cancer, hepatocellular carcinoma, Hodgkin lymphoma, cervical cancer, and head and neck squamous cell carcinoma. Results: Based on the last updated list released on March 2019, seven ICIs are approved by the FDA, including ipilimumab, pembrolizumab, nivolumab, atezolizumab, avelumab, durvalumab, and cemiplimab. Conclusion: This review highlighted the most common adverse effects caused by ICIs which affect people in different ways.

Background Malignant tumors occurring around both the spinal column and posterior chest wall are uncommon. Surgical resection of chest wall tumors adjacent to the spinal column is still challenging due to the surrounding anatomical structures. The purpose of the present study was to evaluate the long-term outcomes of surgical management in malignant tumors involving the spinal column and posterior chest wall. Methods Between 1999 and 2007, 10 consecutive patients underwent en bloc resection combined with the posterior chest wall in the treatment of malignant tumors around the spinal column. There were 6 males and 4 females with a mean age at the surgery of 40.9 years old (range, 14–62 years old). The mean postoperative follow-up period was 159.7 months (range, 84–245 months). The clinical history, physical examination, laboratory data, radiological findings, and operative findings for each patient were retrospectively reviewed. Results All surgeries were performed via a combined anterior and posterior approach. The mean numbers of partially resected vertebrae and ribs were 3.1 and 4.1, respectively. Lower or upper lobectomy was performed in four patients, and the diaphragm was partially resected in two patients. The surgical margin was wide in seven patients and marginal in two patients. Although five patients had postoperative respiratory problem, all patients improved immediately without life-threatening complications. There were no patients with respiratory insufficiency after surgery. One patient with osteosarcoma died of lung metastases 99 months after surgery. At the final follow-up, only one patient had local recurrence, five had been continuously disease-free, and three were alive with no evidence of disease. Conclusions En bloc resection and reconstruction in selected patients with malignant tumors involving both the spinal column and posterior chest wall demonstrated good long-term results for local control and the respiratory function.

A 58-year-old man was diagnosed with stage IVB lung adenocarcinoma in the right upper lobe and underwent systemic chemotherapy. Seven months after the diagnosis, large left pleural and pericardial effusion was detected. The patient developed both chylothorax and chylopericardium following superior vena cava (SVC) obstruction with mediastinal lymphadenopathy caused by lung carcinoma. Since conservative treatment of the chyle leakage was ineffective, we administered radiotherapy to treat the SVC obstruction and mediastinal lymphadenopathy. After radiotherapy, the chylothorax and chylopericardium gradually resolved, and no further chyle leaks were identified on follow-up computed tomography. This case indicates that radiotherapy can be used to ameliorate lung cancer-related chylothorax and chylopericardium.

Background Although smokers are at an increased risk for postoperative pulmonary complications after thoracic surgery, the relationship between cessation timing and postoperative pulmonary complications has not been explored in an era of enhanced recovery protocols and active tobacco cessation programs. Because a strong preference exists among thoracic surgeons to delay surgery to continued smokers, we sought to evaluate this relationship in a modern era. Methods Patients undergoing lung resection for a diagnosis of non-small cell lung cancer from 2012 to 2017 were identified. Multivariable logistic regression was used to evaluate preoperative tobacco cessation timing to determine the impact on postoperative pulmonary complications. Results In all, 1038 ever smokers were identified. Patients were current smokers in 30 (3%) instances, and among former smokers, the preoperative cessation interval was 0 to 14 days in 10% (104), more than 14 days to 1 month in 6% (62), more than 1 month to 1 year in 18% (189), more than 1 to 5 years in 10% (107), and more than 5 years in 53% (546). Pulmonary complications occurred in 269 patients (26%). Multivariable analysis revealed that no group of recent or long-term quitters had superior outcomes in terms of pulmonary complications when evaluating various periods of abstinence in comparison with continued smokers and active quitters. Conclusions In an era of enhanced recovery protocols, minimally invasive surgery, and active tobacco cessation programs that may help patients to cut back, our data do not support the practice of delaying or denying surgery to patients who have difficulty quitting completely. Perioperative cessation counseling should be aimed at long-term benefits, including reduction of disease recurrence and secondary malignancies.

Although preoperative immunotherapy is increasingly utilized for non-small cell lung cancer, there remains a paucity of robust clinical data on its safety and long-term survival. Our objective was to evaluate the perioperative outcomes and survival associated with immunotherapy followed by surgery for patients with non-small cell lung cancer.Outcomes of patients with non-small cell lung cancer who underwent lung resection after preoperative chemotherapy with or without radiation or immunotherapy (with or without chemotherapy or chemoradiation) in the National Cancer Database (2010 to 2017) were evaluated using Kaplan-Meier analysis, multivariable logistic regression, multivariable Cox proportional hazards analysis, and propensity score-matched analysis.From 2010 to 2017, 236 patients (2.2%) received immunotherapy and 10 715 patients received preoperative chemotherapy followed by surgery. There were no significant differences between the immunotherapy and preoperative chemotherapy groups with regard to margin positivity (8.5% [n = 20] vs 7.5% [n = 715], P = .98), 30-day readmission (4.2% [n = 10] vs 4.1% [n = 440], P = .87), and 30-day mortality (0.4% [n = 1] vs 2.4% [n = 253], P = .25). The immunotherapy and preoperative chemotherapy groups had similar overall survival (5-year survival 63% [95% confidence interval, 50% to 74%] vs 51% [95% confidence interval, 50% to 52%], log rank P = .06; multivariable adjusted hazard ratio 0.98; 95% confidence interval, 0.67 to 1.41; P = .90). A propensity score matched analysis of 344 patients, well matched by preoperative characteristics, showed no significant differences in short-term outcomes and overall survival (log rank P = 1.00) between the two groups.In this national analysis, preoperative immunotherapy followed by surgery for non-small cell lung cancer was found to be safe and feasible with similar short-term outcomes and overall survival when compared with preoperative chemotherapy followed by surgery.

Background During the COVID-19 pandemic, patients with lung cancer may experience treatment delays. The objective of this study was to evaluate the impact of extended treatment delays on survival among patients with stage I typical bronchopulmonary carcinoid (BC), lepidic predominant adenocarcinoma (LPA) or invasive adenocarcinoma with a lepidic component (ADL). Methods Using National Cancer Database data (2004-2015), multivariable Cox regression analysis with penalized smoothing splines was performed to examine the association between treatment delay and all-cause mortality for stage I BC, LPA, and ADL. Propensity score–matched analyses compared the overall survival of patients who received “early” vs “delayed” surgery (ie, 0-30 vs 90-120 days after diagnosis) across the different histologic subtypes. Results During the study period, patients with stage I BC (n = 4947), LPA (n = 5340), and ADL (n = 6816) underwent surgery. Cox regression analysis of these cohorts showed a gradual steady increase in the hazard ratio the longer treatment is delayed. However, in propensity score–matched analyses that created cohorts of patients who underwent early and delayed surgery that were well-balanced in patient characteristics, no significant differences in 5-year survival were found between early and delayed surgery for stage I BC (87% [95% CI:77%-93%] vs 89% [95% CI: 80%-94%]), stage I LPA (73% [95% CI: 64%-80%] vs 77% [95% CI: 68%-83%]), and stage I ADL (71% [95% CI: 64%-76%] vs 69% [95% CI: 60%-76%]). Conclusions During the COVID-19 pandemic, for early-stage indolent lung tumors and part-solid ground glass lung nodules, a delay of surgery by 3-4 months after diagnosis can be considered.

Slow-cycling/dormant cancer cells (SCCs) have pivotal roles in driving cancer relapse and drug resistance. A mechanistic explanation for cancer cell dormancy and therapeutic strategies targeting SCCs are necessary to improve patient prognosis, but are limited because of technical challenges to obtaining SCCs. Here, by applying proliferation-sensitive dyes and chemotherapeutics to non-small cell lung cancer (NSCLC) cell lines and patient-derived xenografts, we identified a distinct SCC subpopulation that resembled SCCs in patient tumors. These SCCs displayed major dormancy-like phenotypes and high survival capacity under hostile microenvironments through transcriptional upregulation of regulator of G protein signaling 2 (RGS2). Database analysis revealed RGS2 as a biomarker of retarded proliferation and poor prognosis in NSCLC. We showed that RGS2 caused prolonged translational arrest in SCCs through persistent eukaryotic initiation factor 2 (eIF2α) phosphorylation via proteasome-mediated degradation of activating transcription factor 4 (ATF4). Translational activation through RGS2 antagonism or the use of phosphodiesterase 5 inhibitors, including sildenafil (Viagra), promoted ER stress-induced apoptosis in SCCs in vitro and in vivo under stressed conditions, such as those induced by chemotherapy. Our results suggest that a low-dose chemotherapy and translation-instigating pharmacological intervention in combination is an effective strategy to prevent tumor progression in NSCLC patients after rigorous chemotherapy.

A 46-year-old man was referred to our centre with blurring of vision in both eyes (BE) since 1 month and breathlessness for last 1 week. He was an active smoker with 13.6 pack-years of exposure. Ocular examination revealed a best-corrected visual acuity of 20/60 and 20/80 in right and left eye

The improvement seen in the diagnostic procedures and treatment of thoracic tumours means that patients have an increased chance of longer overall survival. Nevertheless, we can still find those who have had a recurrence or developed a secondary cancer in the previously treated area. These patients require retreatment including re-irradiation. We have reviewed the published data on thoracic re-irradiation, which shows that some specific healthy tissues can tolerate a significant dose of irradiation and these patients benefit from aggressive treatment; however, there is a risk of damage to normal tissue under these circumstances. We analysed the literature data on re-irradiation in the areas of vertebral bodies, spinal cord, breast, lung and oesophagus. We evaluated the doses of primary and secondary radiotherapy, the treatment techniques, as well as the local control and median or overall survival in patients treated with re-radiation. The longest OS is reported in the case of re-irradiation after second breast-conserving therapy where the 5-year OS range is 81 to 100% and is shorter in patients with loco-reginal re-irradiation where the 5-y OS range is 18 to 60%. 2-year OS in patients re-irradiated for lung cancer and oesophagus cancer range from 13 to 74% and 18 to 42%, respectively. Majority grade ≥3 toxicity after second breast-conserving therapy was fibrosis up to 35%. For loco-regional breast cancer recurrences, early toxicity occurred in up to 33% of patients resulting in mostly desquamation, while late toxicity was recorded in up to 23% of patients and were mostly ulcerations. Early grade ≥3 lung toxicity developed in up to 39% of patients and up to 20% of Grade 5 hemoptysis. The most frequently observed early toxicity grade ≥3 in oesophageal cancer was oesophagitis recorded in up to 57% of patients, followed by hematological complications which was recorded in up to 50% of patients. The most common late complications included dysphagia, recorded in up to 16.7% of patients. We have shown that thoracic re-irradiation is feasible and effective in achieving local control in some patients. Re-irradiation should be performed with maximum accuracy and care using the best available treatment methods with a highly conformal, image-guided approach. Due to tremendous technological progress in the field of radiotherapy, we can deliver radiation precisely, shorten the overall treatment time and potentially reduce treatment-related toxicities.