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RATIONALE: Occult lymph node metastasis (OLNM) is frequently found in patients with resectable non-small cell lung cancer (NSCLC), despite using diagnostic methods recommended by guidelines. OBJECTIVES: To evaluate the risk of OLNM in NSCLC patients using the radiologic characteristics of the primary tumor on computed tomography (CT). METHODS: We retrospectively reviewed clinicopathologic features of 2042 clinical T1-4N0 NSCLC patients undergoing curative intent pulmonary resection. Unique radiological features (i.e., air-bronchogram throughout the whole tumor, heterogeneous ground-glass opacity (GGO), mainly cystic appearance, endobronchial location), percentage of solid portion, and shape of tumor margin were analyzed via a stepwise approach. We used multivariable logistic regression to assess the relationship between OLNM and tumor characteristics. RESULTS: Compared with the other unique features, endobronchial tumors were associated with the highest risk of OLNM (OR = 3.9, 95% confidence interval (CI) = 2.29-6.62), and heterogeneous GGO and mainly cystic tumors were associated with a low risk of OLNM. For tumors without unique features, the percentage of the solid portion was measured, and solid tumors were associated with OLNM (OR = 2.49, 95% CI = 1.86-3.35). Among part-solid tumors with solid proportion > 50%, spiculated margin, and peri-tumoral GGO were associated with OLNM. CONCLUSIONS: The risk of OLNM could be assessed using radiologic characteristics on CT. This could allow us to adequately select optimal candidates for invasive nodal staging procedures (INSPs) and complete systematic lymph node dissection. CLINICAL RELEVANCE STATEMENT: These data may be helpful for clinicians to select appropriate candidates for INSPs and complete surgical systematic lymph node dissection in NSCLC patients. KEY POINTS: Lymph node metastasis status plays a key role in both prognostication and treatment planning. Solid tumors, particularly endobronchial tumors, were associated with occult lymph node metastasis (OLNM). The risk of OLNM can be assessed using radiologic characteristics acquired from CT images.
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Purpose: To develop an MRI-based radiomics model to predict high-risk pathologic features for lung adenocarcinoma: micropapillary and solid pattern (MPsol), spread through air space (STAS), and poorly differentiated patterns. Materials and Methods: As a prospective study, we screened clinical N0 lung cancer patients who were surgical candidates and had undergone both 18F-fluorodeoxyglucose (FDG) positron emission tomography-CT (PET/CT) and chest CT from August 2018 to January 2020. We recruited patients meeting our proposed imaging criteria indicating high-risk, that is, poorer prognosis of lung adenocarcinoma, using CT and FDG PET/CT. If possible, these patients underwent an MRI examination from which we extracted 77 radiomics features from T1-contrast-enhanced and T2-weighted images. Additionally, patient demographics, SUVmax (maximum standardized uptake value) on FDG PET/CT, and the mean ADC value on DWI, were considered together to build prediction models for high-risk pathologic features. Results: Among 616 patients, 72 patients met the imaging criteria for high-risk lung cancer and underwent lung MRI. The MR-eligible group showed a higher prevalence of nodal upstaging (29.2% vs. 4.2%, p<0.001), vascular invasion (6.5% vs. 2.1%, p=0.011), high-grade pathologic features (p<0.001), worse 4-year disease free survival (p<0.001) compared with non-MR-eligible group. The prediction power for MR-based radiomics model predicting high-risk pathologic features was good, with mean area under the receiver operating curve (AUC) value measuring 0.751-0.886 in test sets. Adding clinical variables increased the predictive performance for MPsol and the poorly differentiated pattern using the 2021 grading system (AUC 0.860 and 0.907, respectively). Conclusion: Our imaging criteria can effectively screen high-risk lung cancer patients and predict high-risk pathologic features by our MR-based prediction model using radiomics.
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Purpose: Optimal treatment for stage IIIA/N2 non-small cell lung cancer (NSCLC) is controversial. We aimed to assess the efficacy and safety of adjuvant pembrolizumab for stage IIIA/N2 NSCLC completely resected after neoadjuvant concurrent chemoradiation therapy (CCRT). Materials and Methods: In this open-label, single-center, single-arm phase 2 trial, patients with stage IIIA/N2 NSCLC received adjuvant pembrolizumab for up to two years after complete resection following neoadjuvant CCRT. The primary endpoint was disease-free survival (DFS). Secondary endpoints included overall survival (OS) and safety. As an exploratory biomarker analysis, we evaluated the proliferative response of blood CD39+PD-1+CD8+ T cells using fold changes in the percentage of proliferating Ki-67+ cells from days 1 to 7 of cycle 1 (Ki-67D7/D1). Results: Between October 2017 and October 2018, 37 patients were enrolled. Twelve (32%) and three (8%) patients harbored EGFR and ALK alterations, respectively. Of 34 patients with programmed cell death ligand 1 assessment, 21 (62%), 9 (26%), and 4 (12%) had a tumor proportion score of <1%, 1-50%, and ≥50%, respectively. The median follow-up was 71 months. The median DFS was 22.4 months in the overall population, with a five-year DFS rate of 29%. The OS rate was 86% at two years and 76% at five years. Patients with tumor recurrence within six months had a significantly lower Ki-67D7/D1 among CD39+PD-1+CD8+ T cells than those without (p=0.036). No new safety signals were identified. Conclusion: Adjuvant pembrolizumab may offer durable disease control in a subset of stage IIIA/N2 NSCLC patients after neoadjuvant CCRT and surgery.
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Background: Major pulmonary resection after neoadjuvant concurrent chemoradiation therapy (nCCRT) is associated with a substantial risk of postoperative complications. This study investigated postoperative complications and associated risk factors to facilitate the selection of suitable surgical candidates following nCCRT in stage IIIA-N2 non-small cell lung cancer (NSCLC). Methods: We conducted a retrospective analysis of patients diagnosed with clinical stage IIIA-N2 NSCLC who underwent surgical resection following nCCRT between 1997 and 2013. Perioperative characteristics and clinical factors associated with morbidity and mortality were analyzed using univariable and multivariable logistic regression. Results: A total of 574 patients underwent major lung resection after induction CCRT. Thirty-day and 90-day postoperative mortality occurred in 8 patients (1.4%) and 41 patients (7.1%), respectively. Acute respiratory distress syndrome (n=6, 4.5%) was the primary cause of in-hospital mortality. Morbidity occurred in 199 patients (34.7%). Multivariable analysis identified significant predictors of morbidity, including patient age exceeding 70 years (odds ratio [OR], 1.8; p=0.04), low body mass index (OR, 2.6; p=0.02), and pneumonectomy (OR, 1.8; p=0.03). Patient age over 70 years (OR, 1.8; p=0.02) and pneumonectomy (OR, 3.26; p<0.01) were independent predictors of mortality in the multivariable analysis. Conclusion: In conclusion, the surgical outcomes following nCCRT are less favorable for individuals aged over 70 years or those undergoing pneumonectomy. Special attention is warranted for these patients due to their heightened risks of respiratory complications. In high-risk patients, such as elderly patients with decreased lung function, alternative treatment options like definitive CCRT should be considered instead of surgical resection.
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BACKGROUND: Recent studies have reported the predictive and prognostic value of novel transcriptional factor-based molecular subtypes in small-cell lung cancer (SCLC). We conducted an in-depth analysis pairing multi-omics data with immunohistochemistry (IHC) to elucidate the underlying characteristics associated with differences in clinical outcomes between subtypes. METHODS: IHC (n = 252), target exome sequencing (n = 422), and whole transcriptome sequencing (WTS, n = 189) data generated from 427 patients (86.4% males, 13.6% females) with SCLC were comprehensively analysed. The differences in the mutation profile, gene expression profile, and inflammed signatures were analysed according to the IHC-based molecular subtype. FINDINGS: IHC-based molecular subtyping, comprised of 90 limited-disease (35.7%) and 162 extensive-disease (64.3%), revealed a high incidence of ASCL1 subtype (IHC-A, 56.3%) followed by ASCL1/NEUROD1 co-expressed (IHC-AN, 17.9%), NEUROD1 (IHC-N, 12.3%), POU2F3 (IHC-P, 9.1%), triple-negative (IHC-TN, 4.4%) subtypes. IHC-based subtype showing high concordance with WTS-based subtyping and non-negative matrix factorization (NMF) clusterization method. IHC-AN subtype resembled IHC-A (rather than IHC-N) in terms of both gene expression profiles and clinical outcomes. Favourable median overall survival was observed in IHC-A (15.2 months) compared to IHC-N (8.0 months, adjusted HR 2.3, 95% CI 1.4-3.9, p = 0.002) and IHC-P (8.3 months, adjusted HR 1.7, 95% CI 0.9-3.2, p = 0.076). Inflamed tumours made up 25% of cases (including 53% of IHC-P, 26% of IHC-A, 17% of IHC-AN, but only 11% of IHC-N). Consistent with recent findings, inflamed tumours were more likely to benefit from first-line immunotherapy treatment than non-inflamed phenotype (p = 0.002). INTERPRETATION: This study provides fundamental data, including the incidence and basic demographics of molecular subtypes of SCLC using both IHC and WTS from a comparably large, real-world Asian/non-Western patient cohort, showing high concordance with the previous NMF-based SCLC model. In addition, we revealed underlying biological pathway activities, immunogenicity, and treatment outcomes based on molecular subtype, possibly related to the difference in clinical outcomes, including immunotherapy response. FUNDING: This work was supported by AstraZeneca, Future Medicine 2030 Project of the Samsung Medical Center [grant number SMX1240011], the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) [grant number 2020R1C1C1010626] and the 7th AstraZeneca-KHIDI (Korea Health Industry Development Institute) oncology research program.
Subject(s)
Lung Neoplasms , Small Cell Lung Carcinoma , Male , Female , Humans , Transcription Factors/genetics , Lung Neoplasms/genetics , Lung Neoplasms/therapy , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Small Cell Lung Carcinoma/genetics , Small Cell Lung Carcinoma/therapy , PrognosisABSTRACT
Limited information is available regarding the association between preoperative lung function and postoperative pulmonary complications (PPCs) in patients with esophageal cancer who undergo esophagectomy. This is a retrospective cohort study. Patients were classified into low and high lung function groups by the cutoff of the lowest fifth quintile of forced expiratory volume in 1 s (FEV1) %predicted (%pred) and diffusing capacity of the carbon monoxide (DLco) %pred. The PPCs compromised of atelectasis requiring bronchoscopic intervention, pneumonia, and acute lung injury/acute respiratory distress syndrome. Modified multivariable-adjusted Poisson regression model using robust error variances and inverse probability treatment weighting (IPTW) were used to assess the relative risk (RR) for the PPCs. A joint effect model considered FEV1%pred and DLco %pred together for the estimation of RR for the PPCs. Of 810 patients with esophageal cancer who underwent esophagectomy, 159 (19.6%) developed PPCs. The adjusted RR for PPCs in the low FEV1 group relative to high FEV1 group was 1.48 (95% confidence interval [CI] = 1.09-2.00) and 1.98 (95% CI = 1.46-2.68) in the low DLco group relative to the high DLco group. A joint effect model showed adjusted RR of PPCs was highest in patients with low DLco and low FEV1 followed by low DLco and high FEV1, high DLco and low FEV1, and high DLco and high FEV1 (Reference). Results were consistent with the IPTW. Reduced preoperative lung function (FEV1 and DLco) is associated with post-esophagectomy PPCs. The risk was further strengthened when both values decreased together.
Subject(s)
Esophageal Neoplasms , Respiratory Distress Syndrome , Humans , Esophagectomy/adverse effects , Retrospective Studies , Lung/surgery , Forced Expiratory Volume , Respiratory Distress Syndrome/etiology , Esophageal Neoplasms/complications , Postoperative Complications/etiologyABSTRACT
Background: Contralateral pulmonary resection after pneumonectomy presents considerable challenges, and few reports in the literature have described this procedure. Methods: We retrospectively reviewed the medical records of all patients who underwent contralateral lung resection following pneumonectomy for any reason at our institution between November 1994 and December 2020. Results: Thirteen patients (9 men and 4 women) were included in this study. The median age was 57 years (range, 35-77 years), and the median preoperative forced expiratory volume in 1 second was 1.64 L (range, 1.17-2.12 L). Contralateral pulmonary resection was performed at a median interval of 44 months after pneumonectomy (range, 6-564 months). Surgical procedures varied among the patients: 10 underwent single wedge resection, 2 were treated with double wedge resection, and 1 underwent lobectomy. Diagnoses at the time of contralateral lung resection included lung cancer in 7 patients, lung metastasis from other cancers in 3 patients, and tuberculosis in 3 patients. Complications were observed in 4 patients (36%), including acute kidney injury, pneumothorax following chest tube removal, pneumonia, and prolonged air leak. No cases of operative mortality were noted. Conclusion: In carefully selected patients, contralateral pulmonary resection after pneumonectomy can be accomplished with acceptable operative morbidity and mortality.
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Background: Lung cancer diagnostic guidelines advocate for invasive mediastinal nodal staging (IMNS), but the survival benefits of this approach in patients with non-small cell lung cancer (NSCLC) without radiologic evidence of lymph node metastasis (rN0) remain uncertain. We aimed to investigate the impact of IMNS in patients with rN0 NSCLC by comparing the long-term survival between patients who underwent IMNS and those who did not (non-IMNS). Methods: In this retrospective cohort study, we included patients with NSCLC but without radiologic evidence of lymph node metastasis from the Registry for Thoracic Cancer Surgery and the clinical data warehouse at the Samsung Medical Centre, Republic of Korea between January 2, 2008 and December 31, 2016. We compared the 5-year overall survival (OS) rate as the primary outcome after propensity score matching between the IMNS and non-IMNS groups. The age, sex, performance statue, tumor size, centrality, solidity, lung function, FDG uptake in PET-CT, and histological examination of the tumor before surgery were matched. Findings: A total of 4545 patients (887 in the IMNS group and 3658 in the non-IMNS group) who received curative treatment for NSCLC were included in this study. By the mediastinal node dissection, the overall incidence of unforeseen mediastinal node metastasis (N2) was 7.2% (317/4378 patients). Despite the IMNS, 67% of pathological N2 was missed (61/91 patients with unforeseen N2). Based on propensity score matching, 866 patients each for the IMNS and non-IMNS groups were assigned. There was no significant difference in 5-year OS and recurrence-free survival (RFS) between two groups: 5-year OS was 73.9% (95% confidence interval, CI: 71%-77%) for IMNS and 71.7% (95% CI: 68.6%-74.9%; p = 0.23), for non-IMNS (hazard ratio, HR 0.90, 95% CI: 0.77-1.07), while 5-year RFS was 64.7% (95% CI: 61.5%-68.2%) and 67.5% (95% CI: 64.3%-70.9%; p = 0.35 (HR 1.08, 95% CI: 0.92-1.27), respectively. Moreover, the timing and locations of recurrence were similar in both groups. Interpretation: IMNS might not be required before surgery for patients with NSCLC without LN suspicious of metastasis. Further randomised trials are required to validate the findings of the present study. Funding: None.
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AIMS: Programmed death-ligand 1 (PD-L1) expression is a predictive biomarker for adjuvant immunotherapy and has been linked to poor differentiation in lung adenocarcinoma. However, its prevalence and prognostic role in the context of the novel histologic grade has not been evaluated. METHODS: We analysed a cohort of 1233 patients with resected lung adenocarcinoma where PD-L1 immunohistochemistry (22C3 assay) was reflexively tested. Tumour PD-L1 expression was correlated with the new standardized International Association for the Study of Lung Cancer (IASLC) histologic grading system (G1, G2, and G3). Clinicopathologic features including patient outcome were analysed. RESULTS: PD-L1 was positive (≥1%) in 7.0%, 23.5%, and 63.0% of G1, G2, and G3 tumours, respectively. PD-L1 positivity was significantly associated with male sex, smoking, and less sublobar resection among patients with G2 tumours, but this association was less pronounced in those with G3 tumours. PD-L1 was an independent risk factor for recurrence (adjusted hazard ratio [HR] = 3.25, 95% confidence intervals [CI] = 1.93-5.48, P < 0.001) and death (adjusted HR = 2.69, 95% CI = 1.13-6.40, P = 0.026) in the G2 group, but not in the G3 group (adjusted HR for recurrence = 0.94, 95% CI = 0.64-1.40, P = 0.778). CONCLUSION: PD-L1 expression differs substantially across IASLC grades and identifies aggressive tumours within the G2 subgroup. This knowledge may be used for both prognostication and designing future studies on adjuvant immunotherapy.
Subject(s)
Adenocarcinoma of Lung , Adenocarcinoma , B7-H1 Antigen , Lung Neoplasms , Humans , Male , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/surgery , B7-H1 Antigen/genetics , B7-H1 Antigen/metabolism , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Prevalence , Prognosis , Retrospective StudiesABSTRACT
Background: This retrospective study aimed to determine the treatment patterns and the surgical and oncologic outcomes after completion lobectomy (CL) in patients with locoregionally recurrent stage I non-small cell lung cancer (NSCLC) who previously underwent sublobar resection. Methods: Data from 36 patients who initially underwent sublobar resection for clinical, pathological stage IA NSCLC and experienced locoregional recurrence between 2008 and 2016 were analyzed. Results: Thirty-six (3.6%) of 1,003 patients who underwent sublobar resection for NSCLC experienced locoregional recurrence. The patients' median age was 66.5 (range, 44-77) years at the initial operation, and 28 (77.8%) patients were men. Six (16.7%) patients underwent segmentectomy and 30 (83.3%) underwent wedge resection as the initial operation. The median follow-up from the initial operation was 56 (range, 9-150) months. Ten (27.8%) patients underwent CL, 22 (61.1%) underwent non-surgical treatments (chemotherapy, radiation, concurrent chemoradiation therapy), and 4 (11.1%) did not receive treatment or were lost to follow-up after recurrence. Patients who underwent CL experienced no significant complications or deaths. The median follow-up time after CL was 64.5 (range, 19-93) months. The 5-year overall survival (OS) and post-recurrence survival (PRS) were higher in the surgical group than in the non-surgical (p<0.001) and no-treatment groups (p<0.001). Conclusion: CL is a technically demanding but safe procedure for locoregionally recurrent stage I NSCLC after sublobar resection. Patients who underwent CL had better OS and PRS than patients who underwent non-surgical treatments or no treatments; however, a larger cohort study and long-term surveillance are necessary.
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PURPOSE: Recently, we developed allele-discriminating priming system (ADPS) technology. This method increases the sensitivity of conventional quantitative polymerase chain reaction up to 100 folds, with limit of detection, 0.01%, with reinforced specificity. This prospective study aimed to develop and validate the accuracy of ADPS epidermal growth factor receptor (EGFR) Mutation Test Kit using clinical specimens. MATERIALS AND METHODS: In total 189 formalin-fixed paraffin-embedded tumor tissues resected from patients with non-small cell lung cancer were used to perform a comparative evaluation of the ADPS EGFR Mutation Test Kit versus the cobas EGFR Mutation Test v2, which is the current gold standard. When the two methods had inconsistent results, next-generation sequencing-based CancerSCAN was utilized as a referee. RESULTS: The overall agreement of the two methods was 97.4% (93.9%-99.1%); the positive percent agreement, 95.0% (88.7%-98.4%); and the negative percent agreement, 100.0% (95.9%-100.0%). EGFR mutations were detected at a frequency of 50.3% using the ADPS EGFR Mutation Test Kit and 52.9% using the cobas EGFR Mutation Test v2. There were 10 discrepant mutation calls between the two methods. CancerSCAN reproduced eight ADPS results. In two cases, mutant allele fraction was ultra-low at 0.02% and 0.06%, which are significantly below the limit of detection of the cobas assay and CancerSCAN. Based on the EGFR genotyping by ADPS, the treatment options could be switched in five patients. CONCLUSION: The highly sensitive and specific ADPS EGFR Mutation Test Kit would be useful in detecting the patients who have lung cancer with EGFR mutation, and can benefit from the EGFR targeted therapy.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/surgery , Carcinoma, Non-Small-Cell Lung/diagnosis , Lung Neoplasms/genetics , Lung Neoplasms/surgery , Lung Neoplasms/diagnosis , Alleles , Prospective Studies , ErbB Receptors/genetics , MutationABSTRACT
BACKGROUND: The prevalence of lymph node (LN) metastasis in small-sized lung cancer varies depending on the tumor size and proportion of ground-glass opacity. We investigated occult LN metastasis and prognosis in patients with small-sized non-small cell lung cancer (NSCLC), mainly focusing on the pure-solid tumor. METHODS: We retrospectively reviewed patients with ≤2-cm clinical N0 NSCLC who underwent lung resection with curative intent from 2003 to 2017. Among them we analyzed patients who also underwent adequate complete systematic LN dissection. Pathologic results and disease-free survival of the radiologically mixed ground-glass nodule (mGGN) and pure-solid nodule (PSN) groups were analyzed. RESULTS: Of 1329 patients analyzed, 591 had mGGNs and PSNs. As tumor size increased, patients in the mGGN group showed no difference in LN metastasis: ≤1 cm, 2.27%; 1.0 to 1.5 cm, 2.19%; and 1.5 to 2.0 cm, 2.18% (P = .999). However the PSN group showed a significant difference in LN metastasis as the tumor size increased: ≤1 cm, 2.67%; 1.0 to 1.5 cm, 12.46%; and 1.5 to 2.0 cm, 21.31% (P < .001). In the multivariate analysis tumor size was a significant predictor of nodal metastasis in the PSN group but not in the mGGN group. In terms of 5-year disease-free survival, the mGGN group showed a better prognosis than the PSN group (94.4% vs 71.2%, P < .001). CONCLUSIONS: We need to conduct a thorough LN dissection during surgery for small-sized NSCLC, especially for pure-solid tumors ≥ 1 cm.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/surgery , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/pathology , Retrospective Studies , Lymph Nodes/pathology , Lymph Node Excision/methods , Prognosis , Lymphatic Metastasis/pathology , Neoplasm StagingABSTRACT
INTRODUCTION: Accurate diagnostic criteria for tumor invasion are essential for precise pathologic tumor (pT) staging. Recently, the International Association for the Study of Lung Cancer (IASLC) Pathology Committee suggested a new set of criteria for assessing tumor invasion, but the clinical usefulness of the proposed criteria has not been evaluated. METHODS: The study included 1295 patients with resected part-solid lung adenocarcinoma from January 2017 to December 2019 at the Samsung Medical Center, Seoul, Korea. The revised pT stage was determined by the extent of the newly measured invasive component using the IASLC criteria. The primary outcome was to compare the performance of the revised pT stage with the original pT stage in predicting recurrence-free survival and proof of invasion status (i.e., recurrence or lymph node metastasis). The secondary outcome was the correlation with radiologic surrogates of tumor invasiveness (consolidation-to-tumor ratio and maximum standardized uptake value) and pathologic risk factors. RESULTS: The re-evaluation resulted in a 22% downstaging and 2.5% upstaging of pT, which improved the correlation with radiologic (consolidation-to-tumor ratio and maximum standardized uptake value) and pathologic risk factors. The revised pT staging allowed for more accurate discrimination of recurrence-free survival than the original pT staging (c-index = 0.794 versus 0.717). Moreover, the revised pT staging significantly improved the prediction of recurrence or lymph node metastasis (area under the curve = 0.818 versus 0.741, p < 0.001). CONCLUSIONS: To our knowledge, this is the first study evaluating the clinical significance of the IASLC-proposed criteria for invasion. The proposed IASLC criteria offered better alignment with clinicopathologic risk factors and improved prognostication. Further studies are warranted to assess the impact of the IASLC criteria on treatment decisions and patient outcomes.
Subject(s)
Adenocarcinoma of Lung , Adenocarcinoma , Lung Neoplasms , Humans , Lymphatic Metastasis , Clinical Relevance , Adenocarcinoma of Lung/surgery , Adenocarcinoma of Lung/pathology , Adenocarcinoma/surgery , Neoplasm Staging , Neoplasm Invasiveness/pathology , Retrospective Studies , PrognosisABSTRACT
BACKGROUND: Invasive mucinous adenocarcinoma (IMA) is distinct from non-mucinous adenocarcinoma, but studies on recurrent IMA are scarce. Thus, this study aimed to evaluate the recurrence patterns of IMA and the role of pulmonary local therapy (LT) in resectable pulmonary recurrence of IMA. METHODS: The study reviewed 403 patients with surgically resected IMA between 1998 and 2018. The recurrence patterns were categorized as solitary pulmonary recurrence (SPR), multiple pulmonary recurrence (MPR), and extra-pulmonary recurrence (EPR). The clinicopathologic characteristics, overall survival (OS), and post-recurrence survival (PRS) were analyzed according to the recurrence pattern and LT administration. RESULTS: Recurrences were found in 91 (22.6%) patients, including 18 patients with SPR, 37 patients with MPR, and 36 patients with EPR. Compared with the MPR and EPR groups, the SPR group had a longer disease-free interval (32.5 vs. 9.6 vs. 10.1 months, respectively; p < 0.01) and a better OS (5-year OS: 88.5%, 41.5%, and 22.9%, respectively; p < 0.01). In case of resectable pulmonary recurrence, pulmonary LT was administered to 15 patients with SPR and 3 patients with MPR. These patients showed a better 5-year PRS than the other patients with pulmonary recurrence (86.3% vs. 30.4%; p < 0.01). Notably, long-term survival was observed for one patient with MPR undergoing LT and two patients with SPR undergoing a second LT for a second pulmonary recurrence. CONCLUSIONS: In this series, the patients with recurrent IMA showed different prognoses according to the recurrence pattern. The patients with pulmonary recurrence of IMA undergoing LT showed a favorable prognosis, suggesting the potential role of LT for resectable pulmonary recurrence of IMA.
Subject(s)
Adenocarcinoma, Mucinous , Adenocarcinoma , Lung Neoplasms , Humans , Lung Neoplasms/surgery , Neoplasm Recurrence, Local/surgery , Adenocarcinoma, Mucinous/surgery , Lung/pathology , Adenocarcinoma/pathology , Prognosis , Retrospective StudiesABSTRACT
Despite the recognition of various molecular subtypes in small cell lung cancer (SCLC), most information has been derived from tissue microarrays or biopsy samples. Using whole sections of curatively resected SCLCs, we aimed to elucidate the clinicopathologic relevance and prognostic significance of the molecular subtypes. Whole-section immunohistochemistry was conducted for 73 resected SCLC samples using antibodies representative of molecular subtypes: ASCL1 (SCLC-A), NEUROD1 (SCLC-N), POU2F3 (SCLC-P), and YAP1. Furthermore, multiplexed immunofluorescence was performed to evaluate the spatial relationship of YAP1 expression with other markers. The molecular subtype was correlated with clinical and histomorphologic features, and its prognostic role was explored in this cohort and validated in a previously published surgical cohort. Overall, the molecular subtypes were SCLC-A (54.8%), SCLC-N (31.5%), SCLC-P (6.8%), and SCLC-TN (triple negative, 6.8%). We found significant enrichment of SCLC-N (48.0%; P = .004) among combined SCLCs. Although a distinct subtype with high YAP1 expression was not found, YAP1 expression was reciprocal with ASCL1/NEUROD1 at the cellular level within tumors and was increased in areas with non-small cell-like morphology. Furthermore, the YAP1-positive SCLCs showed significantly increased recurrence at mediastinal lymph nodes (P = .047) and are an independent poor prognostic factor after surgery (adjusted hazard ratio, 2.87; 95% CI, 1.20-6.86; P = .017). The poor prognostic impact of YAP1 was also validated in the external surgical cohort. Our whole-section analysis in resected SCLCs reveals the highly heterogeneous nature of the molecular subtype and its clinicopathologic relevance. Although YAP1 is not a subtype delineator, YAP1 relates to the phenotypic plasticity of SCLC and may serve as a poor prognostic factor in resected SCLC.
Subject(s)
Lung Neoplasms , Small Cell Lung Carcinoma , Humans , Small Cell Lung Carcinoma/genetics , Lung Neoplasms/genetics , Prognosis , Proportional Hazards Models , Immunohistochemistry , Gene Expression Regulation, NeoplasticABSTRACT
OBJECTIVES: The aim of the study was to evaluate the clinical outcomes of patients with lung cancer in whom left ventricular ejection fraction (LVEF) was reduced. METHODS: A total of 9814 patients with lung cancer who underwent pulmonary resection from 2010 to 2018 were included for the study. Fifty-six (0.57%) patients had LVEFs ≤45% and we performed propensity score matching (1:3) to compare postoperative clinical outcomes and survival in 56 patients (reduced LVEF group) with those in 168 patients with normal LVEFs (nonreduced LVEF group). RESULTS: The data of the reduced LVEF group and nonreduced group were matched and compared. The 30- (1.8%) and 90-day (7.1%) mortality rates were higher in the reduced LVEF group than those (0% for both 30- and 90-day mortality rates) in the nonreduced LVEF group (P < 0.001). The estimated rates of overall survival at 5-year point were similar in the nonreduced LVEF group (66.0%) and in the reduced LVEF group (60.1%). The estimated rates of overall survival at 5-year point were almost the same between in the nonreduced and reduced LVEF groups for clinical stage 1 lung cancer (76.8% vs 76.4%, respectively), but for stages 2 and 3, they were significantly better in the nonreduced LVEF group than in the reduced LVEF group (53.8% vs.39.8%, respectively). CONCLUSIONS: Lung cancer surgery for selected patients with reduced LVEFs can yield favourable long-term outcomes despite the relatively high early mortality rate. A careful patient selection and meticulous postoperative care could further improve clinical outcome with reduced LVEF.
Subject(s)
Heart Failure , Neoplasms , Ventricular Dysfunction, Left , Humans , Ventricular Function, Left , Stroke Volume , Retrospective StudiesABSTRACT
PURPOSE: Guidelines recommend that non-small cell lung cancer (NSCLC) patients with suspected hilar lymph node (LN) metastases should undergo invasive mediastinal LN staging prior to surgical treatment via endosonography. We evaluated the diagnostic performance of endosonography for detecting occult mediastinal metastases (OMM) and determined the factors associated with OMM in NSCLC patients with radiological N1. Materials and Methods: Patients with confirmed primary NSCLC with radiological N1 who underwent endosonography for nodal staging assessment from January 2013 to December 2019 were retrospectively analyzed. RESULTS: The prevalence of OMM was found to be 83/279 (29.7%) and only 38.6% (32/83) were diagnosed via endosonography. However, five of them were confirmed as N3 by endosonography. The overall diagnostic sensitivity, negative predictive value, accuracy, and area under the curve of endosonography were 38.6%, 79.4%, 81.7%, and 0.69, respectively. In multivariable analysis, central tumor (adjusted odds ratio [aOR], 2.05; 95% confidence interval [CI], 1.15 to 3.68; p=0.016), solid tumor (aOR, 10.24; 95% CI, 1.32 to 79.49; p=0.026), and adenocarcinoma (aOR, 3.01; 95% CI, 1.63 to 5.55; p < 0.001) were related to OMM in radiological N1 NSCLC patients. CONCLUSION: Although the sensitivity of endosonography for detecting OMM was only 40%, the prevalence of OMM was not low (30%) and some cases even turned out to be N3 diseases. Clinicians should be aware that OMM may be more likely in patients with central, solid, and adenocarcinomatous tumor when performing nodal staging in radiological N1 NSCLC via endosonography.