International Association For The Study Of Lung Cancer Research Articles

Prognostic impact of the newly revised IASLC proposed grading system for invasive lung adenocarcinoma: a systematic review and meta-analysis.

This study aimed to evaluate the prognostic value of the newly revised International Association for the Study of Lung Cancer (IASLC) grading system (2020) on the 5-year overall survival (OS) and recurrence-free survival (RFS) in patients with lung adenocarcinoma (LADC). Clinical studies that investigated the prognostic value of revised IASLC staging system in patients with LADC were retrieved from the PubMed, Web of Science, ScienceDirect, and Cochrane Library databases. This study was conducted in accordance to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and checklists. Based on inclusion and exclusion criteria, we included 12 studies for analysis. The grade of LADC was assessed by revised IASLC system, which included three grades. Compared to Grade 3 LADC, grade 1 (total [95% CI]: 1.38 [1.19, 1.60]) and grade 2 (total [95% CI]: 1.29 [1.15, 1.44]) LADC had higher 5-year OS rates. Similarly, Grade 1 (total [95% CI]: 1.76 [1.42, 2.18]) and Grade 2 (total [95% CI]: 1.51 [1.28, 1.77]) had higher 5-year RFS rates Grade 3 LADC. However, 5-year OS and RFS had no significant difference between Grade 1 and Grade 2 patients. This systematic review and meta-analysis provides evidence that the newly revised IASLC grading system is significantly associated with the prognosis of patients with LADC, where Grade 3 indicated unfavorable prognosis.

Combination of grade and spread through air spaces (STAS) predicts recurrence in early stage lung adenocarcinoma: a retrospective cohort study.

Adenocarcinomas, a common subtype of lung cancer, exhibit diverse histological patterns. In 2020, The International Association for the Study of Lung Cancer (IASLC) introduced a grading system emphasizing high-grade components, which has shown prognostic value. Spread through air spaces (STAS) is recognized as a prognostic feature increasing the risk of recurrence in lung cancer. This study evaluates the combination of STAS status and the IASLC-grading system in surgically resected Stage I lung adenocarcinomas. This study is a retrospective analysis of 123 patients with Stage I lung adenocarcinoma who underwent lobectomy between 2011 and 2019. Histological patterns were assessed according to the IASLC criteria, and STAS status was documented. Patients were categorized based on their IASLC Grade and STAS status. Statistical analyses included Kaplan-Meier survival estimates, Cox proportional hazards models, and comparisons using Chi-square and t-tests. The cohort comprised 43 females and 80 males with a mean age of 61.8 ± 7.6years. STAS positivity was noted in 52.8% of patients. STAS positivity correlated significantly with Grade 3 tumors (p < 0.001). The 5-year recurrence-free survival was significantly lower in STAS-positive patients (70.7% vs. 88.7%, p = 0.026). Patients with Grade 3 and STAS positivity had significantly lower recurrence-free survival compared to other groups (p = 0.002). Grade 3 and STAS positivity were independent predictors of poor recurrence-free survival in multivariate analysis. IASLC Grade 3 tumors and STAS positivity are independent prognostic factors for poor recurrence-free survival in Stage I lung adenocarcinomas. Adjuvant treatment strategies should be considered for patients with these characteristics to improve outcomes.

Impact on Prognosis of Stage I Non-Small Cell Lung Cancer Secondary to Delays in Diagnostic Workup.

Background Diagnostic workup of small pulmonary nodules often requires follow-up CT scans to confirm nodule growth before invasive diagnostics or treatment. Purpose To confirm prior results from the International Early Lung Cancer Action Program (I-ELCAP) on quantifying decreases in lung cancer prognosis by using two large databases, the National Lung Screening Trial (NLST) and International Association for the Study of Lung Cancer (IASLC). Materials and Methods In this retrospective study, a model was developed to predict cure rates based on size of solid nodules using the NLST (August 2002 to summer 2007) and IASLC (January 2011 to December 2019) databases, focusing on stage I non-small cell lung cancer (NSCLC). Kaplan-Meier methods were used to calculate 10-year lung cancer-specific survival and 5-year overall survival rates for different tumor sizes. Tumor diameter increases after 90-, 180-, and 365-day delays were estimated using volume doubling times (VDTs) of 60, 120, and 240 days corresponding to fast, moderate, and slow tumor growth. Initial and delayed lung cancer cure rates were assessed across nine scenarios of time delays and tumor growth rates and compared with the previous results of the I-ELCAP database. Results Using regression models based on 166 NLST and 22 590 IASLC patients with NSCLC, 10-year lung cancer-specific survival and 5-year overall survival, respectively, for tumors 4.0-20.0 mm in diameter were estimated. For a 20.0-mm tumor with a 60-day VDT in the NLST database, the lung cancer-specific survival decreased from 83.4% to 76.5%, 66.8%, and 32.3% after 90, 180, and 365 days, respectively. The IASLC database showed similar decreases in 5-year overall survival, from 81.2% to 73.4%, 62.4%, and 23.3% after 90, 180, and 365 days, respectively. Comparison across NLST, IASLC, and I-ELCAP databases revealed minor variations in lung cancer cure rates between 79.9% and 83.4%, with reductions of 6.9%-8.3% after a 180-day delay with a 120-day VDT. Conclusion The NLST and IASLC databases confirmed prior estimates from the I-ELCAP database for the decrease in lung cancer prognosis due to diagnostic delays. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Park and Lee in this issue.

Evolution of overall survival (OS) after curative-intent lung cancer surgery in a population-based Mississippi Delta cohort.

278 Background: Surgical resection is the most important curative modality for patients with lung cancer, with long-term OS influenced by both surgical quality and cancer biology. We compared surgical care and outcomes over 4 eras in the population-based Mid-South Quality of Surgical Resection (MS-QSR) cohort, an ongoing regional surgical and pathologic quality improvement (QI) dissemination and implementation project. Methods: We implemented a surgical lymph node collection kit and a novel pathology gross dissection method across 12 hospitals encompassing &gt;95% of lung cancer resections in 5 contiguous Dartmouth Hospital Referral Regions. We analyzed the MS-QSR cohort at 5-year intervals characterized by stepped-wedge implementation of specific QI interventions: Era 1 (2004-2008; baseline, no QI), Era 2 (2009-2013; quality feedback, surgical QI pilot), Era 3 (2014-2018; surgical QI implementation), and Era 4 (2019-2023; combined surgical QI and pathology QI implementation). We used standard statistical methods to compare surgical quality; Kaplan-Meier plot, log-rank test, and Cox proportional hazards model with Era 1 as reference to compare OS across eras. Results: Of 7240 resections, 14%, 31%, 29%, and 26% were performed in Eras 1-4, respectively (Table). Attainment of the stringent International Association for the Study of Lung Cancer (IASLC) definition of complete resection increased from 0% in Era 1 to 32% in Era 4; attainment of the American College of Surgeons Operative Standard 5.8 (ACS_OS 5.8), the current US definition of surgical quality, improved from 4% in Era 1 to 67% in Era 4; 120-day mortality rate decreased from 10% to 4% (p&lt;0.0001 for all comparisons). With median follow-up of 4.7, 5.5, 5.6, and 2 years for Eras 1-4, 3-year OS rates were 60%, 64%, 70%, and 79%; 5-year OS rates were 48%, 52%, 58%, and 70%, respectively (p&lt;0.0001). The Hazard Ratio (HR) for mortality decreased from 0.91 (95% CI: 0.8-0.99) in Era 2 to 0.49 (95% CI: 0.43-0.56) in Era 4. Conclusions: Surgical quality and OS sequentially improved in this diverse, high-risk population-based Mississippi Delta surgical resection cohort. We are evaluating the full range of factors associated with this striking OS improvement. Ongoing work is exploring biologic correlates to this improvement. Variable Era 1 N= 988 Era 2 N=2235 Era 3 N=2107 Era 4 N=1910 Median age (Q1, Q3) 68 (62, 74) 68 (62, 74) 68 (61, 74) 68 (61, 74) Male sex (%) 514 (52%) 1234 (55%) 1082 (51%) 977 (51%) Black race 221 (22%) 416 (19%) 450 (21%) 451 (24%) Attained ACS_OS 5.8 40 (4%) 533 (24%) 1050 (50%) 1272 (67%) IASLC complete resectionUncertain completeness 0 (0%)930 (94%) 194 (9%)1932 (86%) 435 (21%)1594 (76%) 606 (32%)1227 (64%) 120-day mortality 100 (10%) 197 (9%) 139 (7%) 72 (4%) 5-year OS 48 (45-51) 52 (50-55) 58 (56-60) 70 (66-74) HR (95% CI) Reference 0.91 (0.83-0.99) 0.75 (0.69-0.83) 0.49 (0.43-0.56)

Safety and Efficacy of Salvage Surgery after Treatment With Immune-Checkpoint Adjuvant Inhibitors for Advanced Non-Small Cell Lung Cancer: A Multicentric Study.

In advanced non-small cell lung cancer (NSCLC), immune-checkpoint inhibitors (ICIs) can achieve significant clinical responses. This raises the question of whether to consider salvage surgery as a curative treatment option. Few case series reported encouraging results in terms of pathological response. However, intraoperative risk and postoperative morbidity have been highlighted. This study aims to assess the safety and feasibility of surgery after ICIs administration and to evaluate its effectiveness on the final pathological examination. We retrospectively identified stages III-IVA NSCLC consecutive patients who underwent surgery with radical intent after ICIs at three National Centers (2016-2022). Before treatment, all patients were considered unresectable by a multidisciplinary discussion. After surgery, pathological response was evaluated according to the International Association for the Study of Lung Cancer (IASLC) recommendation. Thirty-one patients were included; pretreatment clinical stage was: IIIA in 4 patients (10%), IIIB in 13 (42%), IIIC in 3 (13%), and IVA in 11 (35%). Median treatment duration was four cycles. Only anatomical resections were performed, with lobectomy that represent the main type of resection (22 patients, 74%). A minimally invasive approach was performed in 10 patients (32%), with a conversion rate of 0%. Postoperative complications were observed in eight patients (25%). Complete pathologic response (CPR) and major pathologic response (MPR) were 48% and 16%, respectively. Two and 3-years survival were 88%. Based on our experience, salvage surgery of advanced NSCLC treated with ICIs confirm his feasibility and safety in responder patients. Moreover, it is associated with low morbidity, high CPR rate, and satisfying medium-term survival.

Evaluation of the novel International Association for the Study of Lung Cancer grading system in adenocarcinoma with spread through air space.

The International Association for the Study of Lung Cancer (IASLC) pathology panel has proposed a new grading system for invasive lung adenocarcinoma (LADC). This study aims to validate this novel grading system for invasive LADC using propensity score matching (PSM), with a specific focus on patients exhibiting spread through air space (STAS). We retrospectively analyzed the clinicopathologic features of a large cohort of 910 non-mucinous LADCs with STAS from 2017 to 2020 and classified them according to the novel grading system. We applied PSM to adjust for potential confounders between the grading groups. Kaplan-Meier and Cox proportional hazards models were adopted for prognostic evaluation. The results showed that the IASLC grading system (grades 2 and 3) stratified well in terms of recurrence-free survival (RFS) and overall survival (OS) (P=0.02 and P=0.02, respectively) after matching, with Grade 3 being an independent predictor of RFS [hazard ratio (HR), 1.533; P=0.02] and OS (HR, 2.765; P=0.02) in multivariable models. The concordance index (C-index) and area under the curve (AUC) of the IASLC system were 0.719 and 0.754 for recurrence and 0.844 and 0.891 for death, respectively. In addition, anaplastic lymphoma kinase (ALK) fusion and tumor protein p53 (TP53) mutations were detected more frequently in grade 3 tumors, while epidermal growth factor receptor (EGFR) mutations were more prevalent in grade 2 tumors. The IASLC grade did not predict the benefit of adjuvant chemotherapy (ACT). This study suggests that the new IASLC grading system is a valuable prognostic tool for patients with STAS-positive LADC.

Peritumoral radiomics increases the efficiency of classification of pure ground-glass lung nodules: a multicenter study

PurposeWe aimed to evaluate the efficiency of computed tomography (CT) radiomic features extracted from gross tumor volume (GTV) and peritumoral volumes (PTV) of 5, 10, and 15 mm to identify the tumor grades corresponding to the new histological grading system proposed in 2020 by the Pathology Committee of the International Association for the Study of Lung Cancer (IASLC).MethodsA total of 151 lung adenocarcinomas manifesting as pure ground-glass lung nodules (pGGNs) were included in this randomized multicenter retrospective study. Four radiomic models were constructed from GTV and GTV + 5/10/15-mm PTV, respectively, and compared. The diagnostic performance of the different models was evaluated using receiver operating characteristic curve analysisResultsThe pGGNs were classified into grade 1 (117), 2 (34), and 3 (0), according to the IASLC grading system. In all four radiomic models, pGGNs of grade 2 had significantly higher radiomic scores than those of grade 1 (P < 0.05). The AUC of the GTV and GTV + 5/10/15-mm PTV were 0.869, 0.910, 0.951, and 0.872 in the training cohort and 0.700, 0.715, 0.745, and 0.724 in the validation cohort, respectively.ConclusionsThe radiomic features we extracted from the GTV and PTV of pGGNs could effectively be used to differentiate grade-1 and grade-2 tumors. In particular, the radiomic features from the PTV increased the efficiency of the diagnostic model, with GTV + 10 mm PTV exhibiting the highest efficacy.

IASLC grading system predicts distant metastases for resected lung adenocarcinoma

AimsThe International Association for the Study of Lung Cancer (IASLC) has proposed a new histological grading system for invasive lung adenocarcinoma (LUAD). However, the efficacy of this grading system in...

Are there features that can predict the unresectability of pleural mesothelioma?

The current clinical staging of pleural mesothelioma (PM) is often discordant with the pathologic staging. This study aimed to identify clinical and radiological features that could help predict unresectability in PM. Twenty-two descriptive radiologic features were retrospectively evaluated on preoperative computed tomography (CT) and/or positron emission tomography/CT (PET/CT) performed in patients with presumably resectable PM who underwent surgery. Measurements of maximum and sum pleural thickness at three levels of the thorax (upper, middle, and lower) were taken and stratified based on the cutpoints provided by the International Association for the Study of Lung Cancer (IASLC). Clinical and radiological features, including clinical-stage, were compared between resectable and unresectable tumors by univariate analysis and logistic regression modeling. Of 133 patients, 69/133 (52%) had resectable and 64/133 (48%) had unresectable PM. Asbestos exposure (p = 0.005), neoadjuvant treatment (p = 0.001), clinical T-stage (p < 0.0001), all pleural thickness measurements (p < 0.05), pleural thickness pattern (p < 0.0001) and degree (p = 0.033), lung invasion (p = 0.004), extrapleural space obliteration (p < 0.0001), extension to subphrenic space (p = 0.0004), and two combination variables representing extensive diaphragmatic contact and/or chest wall involvement (p = 0.002) and mediastinal invasion (p < 0.0001) were significant predictors at univariate analysis. At multivariable analysis, all models achieved a strong diagnostic performance (area under the curve (AUC) > 0.8). The two best-performing models were one that included the upper-level maximum pleural thickness, extrapleural space obliteration, and mediastinal infiltration (AUC = 0.876), and another that integrated clinical variables and radiological assessment through the clinical T-stage (AUC = 0.879). Selected clinical and radiologic features, including pleural thickness measurements, appear to be strong predictors of unresectability in PM. A more accurate prediction of unresectability in the preoperative assessment of patients with pleural mesothelioma may avoid unnecessary surgery and prompt initiation of nonsurgical treatments. About half of pleural mesothelioma patients are reported to receive an incorrect disease stagepreoperatively. Eleven features identified as predictors of unresectability were included in strongly performing predictive models. More accurate preoperative staging will help clinicians and patients choose the most appropriate treatments.

Recurrence Dynamics of Pathological N2 Non-small Cell Lung Cancer Based on IASLC Residual Tumor Descriptor.

This study investigated the recurrence patterns and timing in patients with pathologic N2 (pN2) non-small cell lung cancer (NSCLC) according to the residual tumor (R) descriptor proposed by the International Association for the Study of Lung Cancer (IASLC). From 2004 to 2021, patients with pN2 NSCLC who underwent anatomical resection were analyzed according to the IASLC R criteria using medical records from a single center. Survival analysis was performed using Cox proportional hazards models. Recurrence patterns between complete (R0) and uncertain resections (R[un]) were compared. In total, 1,373 patients were enrolled in this study: 576 (42.0%) in R0, 286 (20.8%) in R(un), and 511 (37.2%) in R1/R2 according to the IASLC R criteria. The most common reason for R(un) classification was positivity for the highest lymph node (88.8%). In multivariable analysis, the hazard ratios for recurrence in R(un) and R1/R2 compared to R0 were 1.18 (95% confidence interval [CI], 0.96-1.46) and 1.58 (1.31-1.90), respectively. The hazard rate curves displayed similar patterns among groups, peaking at approximately 12 months after surgery. There was a significant difference in distant recurrence patterns between R0 and R(un). Further analysis after stratification with the IASLC N2 descriptor showed significant differences in distant recurrence patterns between R0 and R(un) in patients pN2a1 and pN2a2 disease, but not in those with pN2b disease. The IASLC R criteria has prognostic relevance in patients with pN2 NSCLC. R(un) is a highly heterogeneous group, and the involvement of the highest mediastinal lymph node can affect distant recurrence patterns.

Brief Report: Precision Language and Deletion of the “S” Word

IntroductionIn 2021, the International Association for the Study of Lung Cancer (IASLC) published the IASLC Language Guide as guidance on preferred language and phrasing in oral and written communications, including presentations at conferences. This study analyzed presentations from the 2022 IASLC World Conference on Lung Cancer (WCLC) one year after implementation of the Language Guide to identify adoption rates of non-stigmatizing language and to determine correlations with presenter characteristics. MethodsWe downloaded 522 slide presentations from the IASLC WCLC 2022 conference attendee portal. We searched each presentation, including images, for discussion of tobacco use and the use of the term “smoker,” which is an indicator of stigmatizing language. We conducted internet searches to gather presenters’ stated home continent, sex, specialty, and professional degree. ResultsOf 177 presentations that discussed smoking status, 77 presenters used non-stigmatizing language, whereas 100 presenters used the stigmatizing term “smoker.” Male MDs and female PhDs and non-medicine subspecialties and advocates were more likely to use non-stigmatizing language. ConclusionsEncouragingly, only after one year post-release of the Language Guide, more than one-third of the presenters at the WCLC used non-stigmatizing language. This finding represents a step toward improving respectful and inclusive language surrounding smoking within the thoracic oncology community.

Precision medicine preceptorship in breast and lung cancer for Latin American oncologists.

9040 Background: Cancer is the second leading cause of death in Latin America. Integrating genomic discoveries into patient care could improve morbidity and mortality; however economic barriers to capacity development and access to therapeutics remain. In response to an RFP for a preceptorship for oncologists from Latin America, Emory’s Winship Cancer Institute (WCI) developed a 2-week immersion involving didactics, clinical exposures, and research meetings to increase knowledge and competence of breast and lung cancer genomics. Methods: Interviews with Latin American medical oncologists, Latin America Lung Cancer Association (LALCA) leadership, and literature review were conducted to understand areas of unmet need in oncology training. A gap in knowledge and practice of genomic management of breast and lung cancer was identified and informed development of didactic and clinical exposures. The WCI website, International Association for the Study of Lung Cancer (IASLC) and LALCA publicized the program. Medical oncologists within 6 years of final oncology training applied. Participants completed a baseline needs assessment, pre-program survey to assess goals and confidence in skills, and post-program interview to evaluate the program and reassess confidence in skills. Instruments were developed with WCI’s Intervention, Development, Dissemination and Implementation Shared Resource. WCI faculty were interviewed for feedback. Results: WCI hosted 12 Latin American oncologists over 3 two-week preceptorships between 2020-23, coinciding with local scientific meetings. All participants reported the program was a valuable use of time, valuable for career development and rated the program as excellent/very good. 92% reported the program met their goals and felt engaged all/most of the time. 75% rated attendance at breast and lung cancer clinics, didactics, research meetings, tumor boards as very/extremely valuable. Two-thirds intended to make changes (apply knowledge, improve communication, work with other providers like nurses, aid students in research, improve flow of activity when seeing patients, incorporate clinical research into daily practice, and add immunotherapy) in their practice at home institutions. Phase 1 and surgical oncology clinics were deemed least helpful. Themes emerged from faculty interviews: be strategic about the number of learners in clinic, characterize learner preferences and prior training/experience, articulate the preceptorship’s long-term goals, and include time to team-build. Conclusions: Participants gained exposure to the latest molecular diagnostics and systemic treatments, appreciation for optimal team-based cancer care, and how clinical research drives development of novel biomarkers and therapeutics. Future goals include expanding program access to oncologists from other low- and middle-income countries and promoting post-program collaborations.

Integrating IASLC grading and radiomics for predicting postoperative outcomes in stage IA invasive lung adenocarcinoma.

The International Association for the Study of Lung Cancer (IASLC) Pathology Committee introduced a histologic grading system for invasive lung adenocarcinoma (LUAD) in 2020. The IASLC grading system, hinging on the evaluation of predominant and high-grade histologic patterns, has proven to be practical and prognostic for invasive LUAD. However, there are still limitations in evaluating the prognosis of stage IA LUAD. Radiomics may serve as a valuable complement. To establish a model that integrates IASLC grading and radiomics, aimed at predicting the prognosis of stage IA LUAD. We conducted a retrospective analysis of 628 patients diagnosed with stage IA LUAD who underwent surgical resection between January 2015 and December 2018 at our institution. The patients were randomly divided into the training set (n=439) and testing set (n=189) at a ratio of 7:3. Overall survival (OS) and disease-free survival (DFS) were taken as the end points. Radiomics features were obtained by PyRadiomics. Feature selection was performed using the least absolute shrinkage and selection operator (LASSO). The prediction models for OS and DFS were developed using multivariate Cox regression analysis, and the models were visualized through nomogram plots. The model's performance was evaluated using area under the curves (AUC), concordance index (C-index), calibration curves, and survival decision curve analysis (DCA). In total, nine radiomics features were selected for the OS prediction model, and 15 radiomics features were selected for the DFS prediction model. Patients with high radiomics scores were associated with a worse prognosis (p<0.001). We built separate prediction models using radiomics or IASLC alone, as well as a combined prediction model. In the prediction of OS, we observed that the combined model (C-index: 0.812±0.024, 3 years AUC: 0.692, 5 years AUC: 0.792) achieved superior predictive performance than the radiomics (C-index: 0.743±0.038, 3 years AUC: 0.633, 5 years AUC: 0.768) and IASLC grading (C-index: 0.765±0.042, 3 years AUC: 0.658, 5 years AUC: 0.743) models alone. Similar results were obtained in the models for DFS. The combination of radiomics and IASLC pathological grading proves to be an effective approach for predicting the prognosis of stage IA LUAD. This has substantial clinical relevance in guiding treatment decisions for early-stage LUAD.

Novel Insights Into the International Association for the Study of Lung Cancer Grading System for Lung Adenocarcinoma

The new grading system for lung adenocarcinoma proposed by the International Association for the Study of Lung Cancer (IASLC) defines prognostic subgroups on the basis of histologic patterns observed on surgical specimens. This study sought to provide novel insights into the IASLC grading system, with particular focus on recurrence-specific survival (RSS) and lung cancer–specific survival among patients with stage I adenocarcinoma. Under the IASLC grading system, tumors were classified as grade 1 (lepidic predominant with <20% high-grade patterns [micropapillary, solid, and complex glandular]), grade 2 (acinar or papillary predominant with <20% high-grade patterns), or grade 3 (≥20% high-grade patterns). Kaplan-Meier survival estimates, pathologic features, and genomic profiles were investigated for patients whose disease was reclassified into a higher grade under the IASLC grading system on the basis of the hypothesis that they would strongly resemble patients with predominant high-grade tumors. Overall, 423 (29%) of 1443 patients with grade 1 or 2 tumors classified based on the predominant pattern–based grading system had their tumors upgraded to grade 3 based on the IASLC grading system. The RSS curves for patients with upgraded tumors were significantly different from those for patients with grade 1 or 2 tumors (log-rank P < .001) but not from those for patients with predominant high-grade patterns (P = .3). Patients with upgraded tumors had a similar incidence of visceral pleural invasion and spread of tumor through air spaces as patients with predominant high-grade patterns. In multivariable models, the IASLC grading system remained significantly associated with RSS and lung cancer–specific survival after adjustment for aggressive pathologic features such as visceral pleural invasion and spread of tumor through air spaces. The IASLC grading system outperforms the predominant pattern–based grading system and appropriately reclassifies tumors into higher grades with worse prognosis, even after other pathologic features of aggressiveness are considered.

Reproducibility of Assessment of Lepidic (Noninvasive) Patterns in Lung Adenocarcinoma With Cytokeratin Immunostain Compared With Hematoxylin and Eosin and the Proposed New International Association for the Study of Lung Cancer (IASLC) Algorithm

IntroductionLepidic growth is considered noninvasive in lung nonmucinous adenocarcinoma, whereas other patterns are invasive. Considerable interobserver variability in assessing “invasion” has been reported. We assessed the utility of cytokeratin 7 (CK7) stain and recently proposed International Association for the Study of Lung Cancer criteria to improve assessment of noninvasion in lung adenocarcinoma. MethodsFour pathologists (two staff, two trainees) assessed 158 hematoxylin and eosin (HE)- and CK7-stained slides of 108 pT1N0-2 nonmucinous lung adenocarcinoma cases. Scoring took place in four rounds. First, sections were independently scored for percentage of noninvasive or probable noninvasive and invasive or probable invasive patterns. Second, after a consensus scoring algorithm for CK7 was formulated, the slides were rescored. Subsequent third-round scoring was conducted only on HE slides using the 2023 International Association for the Study of Lung Cancer proposed criteria, and fourth-round scoring on both HE and CK7 slides simultaneously. Intraclass correlation coefficient (ICC) was calculated for each round. Recurrence-free survival was assessed using Cox proportional hazards regression methods. ResultsIn the first two rounds, interobserver concordance was consistently higher with CK7 (ICC range = 0.44–0.6) than HE (range = 0.24–0.49) scores. The IASLC proposed algorithm improved ICC of HE scores to 0.60 (95% confidence interval: 0.52–0.67), and round 4 HE and CK7 combined improved ICC to 0.75 (95% confidence interval: 0.70–0.80). Continuous measures of averaged noninvasive and probable noninvasive scores on HE were associated with improved recurrence-free survival (hazard ratio: 0.83–0.86). ConclusionsCK7 staining consistently increased interobserver concordance in assessment of invasive versus noninvasive patterns than HE. Combining CK7 with the 2023 IASLC criteria for morphologic features of invasion may further improve the interobservers’ concordance for the recognition of lepidic growth in nonmucinous lung adenocarcinoma.

Tumor Location Is an Independent Prognostic Factor in Completely Resected Pathological Stage I Non-Small Cell Lung Cancer: A Multicenter Retrospective Study.

Previous studies suggested that the location of the primary tumor in non-small cell lung cancer (NSCLC) is associated with clinical features and prognosis, but results are conflicting. The purpose of this study was to explore tumor location as an independent risk factor of survival for patients with completely resected pathological stage I NSCLC. This was a multicenter retrospective study conducted in Taiwan. Included patients were diagnosed with stage I NSCLC and had undergone primary tumor resection. Variables including tumor location, pathological stage, histological differentiation, and International Association for the Study of Lung Cancer (IASLC) grade were evaluated for predictive ability for disease-free survival (DFS) and overall survival (OS). A total of 208 patients were included, with 123 (59.1%) patients having a primary tumor in the upper and middle lobes. The median duration of follow-up for survivors was 60.5 months. Compared to patients with IASLC Grade 3 disease, patients with Grade 1 disease had significantly longer DFS. Tumor location and IASLC grade were independent predictors for OS in multivariate analysis. Specifically, patients with NSCLC in the lower lobe and patients who are histologically classified as IASLC Grade 3 may have poorer prognosis and require greater attention to improve outcomes.

The Grading System for Lung Adenocarcinoma: Brief Review of its Prognostic Performance and Future Directions.

Histologic grading of tumors is associated with prognosis in many organs. In the lung, the most recent grading system proposed by International association for the Study of Lung Cancer (IASLC) and adopted by the World Health Organization (WHO) incorporates the predominant histologic pattern, as well as the presence of high-grade architectural patterns (solid, micropapillary, and complex glandular pattern) in proportions >20% of the tumor surface. This system has shown improved prognostic ability when compared with the prior grading system based on the predominant pattern alone, across different patient populations. Interobserver agreement is moderate to excellent, depending on the study. IASLC/WHO grading system has been shown to correlate with molecular alterations and PD-L1 expression in tumor cells. Recent studies interrogating gene expression has shown correlation with tumor grade and molecular alterations in the tumor microenvironment that can further stratify risk of recurrence. The use of machine learning algorithms to grade nonmucinous adenocarcinoma under this system has shown accuracy comparable to that of expert pulmonary pathologists. Future directions include evaluation of tumor grade in the context of adjuvant and neoadjuvant therapies, as well as the development of better prognostic indicators for mucinous adenocarcinoma.

Abstract 3782: IASLC grading system predict distant metastases for resected lung adenocarcinoma

Abstract The International Association for the Study of Lung Cancer (IASLC) proposed a new histological grading system for invasive lung adenocarcinoma (LUAD). However, whether this new grading system is able to predict distant metastases in LUAD patients has not been evaluated. This study investigated the feasibility of using this grading system to predict the occurrence of brain and bone metastases in patients with resectable LUAD which identifies patients who have a high probability of developing distant metastases after surgery. We collected clinical information and pathological reports of 179 early stage LUAD patients who underwent resection during 2008 to 2015 from Wake Forest Comprehensive Cancer Center. All patients were followed up for 5 years and both bone and brain metastasis-free survival were calculated. Tumor grading of all samples was evaluated by both IASLC grading and predominant pattern-based grading systems. The ability of predicting distant metastases using IASLC grading and tumor stage were examined by receiver operating characteristic curves (ROC). 28 out of 179 patients developed distant metastases in five years with a median overall survival of 60 months for metastasis-free patients and 38.9 for patients with distant metastasis. Compared to predominant pattern-based grading system, IASLC grading system showed a stronger correlation with distant metastasis incidence. Complex gland pattern is enriched in patients who developed bone and brain metastases compared to metastasis-free patients. IASLC grading system also showed a superior prediction power of distant metastasis compared to tumor stage with area under curve (AUC) of 0.69 for brain metastasis and 0.71 for bone metastasis. IASLC grading system is capable of predicting the incidence of distant metastasis among early-stage invasive LUAD patients. Citation Format: Yuezhu Wang, Margaret R. Smith, Yin Liu, Mary E. Green, Omer A. Hassan, Alexandra M. Balmaceda, Tammy Sexton, Wencheng Li, Fei Xing. IASLC grading system predict distant metastases for resected lung adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3782.

The International Association for the Study of Lung Cancer (IASLC) Staging Project for Lung Cancer: Recommendation to Introduce Spread Through Air Spaces as a Histologic Descriptor in the Ninth Edition of the TNM Classification of Lung Cancer. Analysis of 4061 Pathologic Stage I NSCLC

IntroductionSpread through air spaces (STAS) consists of lung cancer tumor cells that are identified beyond the edge of the main tumor in the surrounding alveolar parenchyma. It has been reported by meta-analyses to be an independent prognostic factor in the major histologic types of lung cancer, but its role in lung cancer staging is not established. MethodsTo assess the clinical importance of STAS in lung cancer staging, we evaluated 4061 surgically resected pathologic stage I R0 NSCLC collected from around the world in the International Association for the Study of Lung Cancer database. We focused on whether STAS could be a useful additional histologic descriptor to supplement the existing ones of visceral pleural invasion (VPI) and lymphovascular invasion (LVI). ResultsSTAS was found in 930 of 4061 of the pathologic stage I NSCLC (22.9%). Patients with tumors exhibiting STAS had a significantly worse recurrence-free and overall survival in both univariate and multivariable analyses involving cohorts consisting of all NSCLC, specific histologic types (adenocarcinoma and other NSCLC), and extent of resection (lobar and sublobar). Interestingly, STAS was independent of VPI in all of these analyses. ConclusionsThese data support our recommendation to include STAS as a histologic descriptor for the Ninth Edition of the TNM Classification of Lung Cancer. Hopefully, gathering these data in the coming years will facilitate a thorough analysis to better understand the relative impact of STAS, LVI, and VPI on lung cancer staging for the Tenth Edition TNM Stage Classification.

Prognostic impact of the IASLC grading system of lung adenocarcinoma: a systematic review and meta-analysis.

Tumour grading is an essential part of the pathologic assessment that promotes patient management. The International Association for the Study of Lung Cancer (IASLC) proposed a grading system for non-mucinous lung adenocarcinoma in 2020. We aimed to validate the prognostic impact of this novel grading system on overall survival (OS) and recurrence-free survival (RFS) based on literature data. The review protocol was registered in PROSPERO (CRD42023396059). We aimed to identify randomized or non-randomized controlled trials published after 2020 comparing different IASLC grade categories in Medline, Embase, and CENTRAL. Hazard ratios (HRs) with 95% confidence intervals (CIs) of OS and RFS were pooled and the Quality In Prognosis Studies (QUIPS) tool was used to assess the risk of bias in the included studies. Ten articles were eligible for this review. Regarding OS estimates, grade 1 lung adenocarcinomas were better than grade 3 both in univariate and multivariate analyses (HROSuni = 0.19, 95% CI: 0.05-0.66, p = 0.009; HROSmulti = 0.21, 95% CI: 0.12-0.38, p < 0.001). Regarding RFS estimates, grade 3 adenocarcinomas had a worse prognosis than grade 1 in multivariate analysis (HRRFSmulti: 0.22, 95% CI: 0.14-0.35, p < 0.001). The literature data and the result of our meta-analysis demonstrate the prognostic relevance of the IASLC grading system. This supports the inclusion of this prognostic parameter in daily routine worldwide.