Resected Non-small Cell Lung Research Articles

Video-assisted thoracic surgery is associated with faster delivery to adjuvant chemotherapy after lung resection in patients with lung cancer

BackgroundRapid recovery after surgery is especially important for patients who are scheduled for adjuvant therapy.This study aimed to investigate the effect of video-assisted thoracic surgery (VATS) on chemotherapy referral time and chemotherapy tolerance in patients who underwent lung resection for non-small cell lung cancer.MethodsThe data of 612 patients who underwent lung resection with the diagnosis of non-small cell lung cancer in our clinic between January 2014 and December 2021 were reviewed. Patients who underwent lobectomy or bilobectomy with systematic mediastinal lymph node dissection and who received at least one cycle of adjuvant chemotherapy were included in the study. The characteristics of the patients, pathological data, postoperative follow-up findings, and the time between the operation and adjuvant chemotherapy were recorded.ResultsA total of 144 patients who met the criteria were included in the study. The mean age was 61.6 ± 7.9 years. The mean visual analogue scale scores were found to be lower, and the length of hospital stay was found to be shorter in the VATS group compared to thoracotomy.The mean time (days) to initiate chemotherapy after surgery was statistically shorter in the VATS group (48.9 ± 17.6 vs 58.1 ± 27.6, p = 0.049). However, there weren't seen any statistical differences between VATS and thoracotomy groups in terms of mean cycle completed, percentage of planned regimen received, and grade ≥ 3 toxicity rates (p = 0.16, p = 0.18, and p = 0.22, respectively).ConclusionsVATS provides faster recovery compared to open surgery and shortens the time for patients to refer to adjuvant chemotherapy.

Accuracy of next-generation sequencing for molecular profiling of small specimen of lung cancer: a prospective pilot study of side-by-side comparison

BackgroundSuccessful practice of precision medicine in advanced lung cancers relies on therapeutic regimens tailored to individual molecular characteristics. The aim of this study was to investigate the accuracy of small specimens for molecular profiling using next-generation sequencing (NGS).MethodsGenetic alternations, tumor mutational burden (TMB), status of microsatellite instability (MSI), and expression of programmed death ligand 1 (PD-L1) were compared side-by-side between the concurrently obtained core needle biopsy (CNB) and resection specimens in 17 patients with resectable non-small cell lung cancers.ResultsDNA yield and library complexity were significantly lower in CNB specimens (both p < 0.01), whereas the insert size, sequencing depth, and Q30 ratio were similar between the matched specimens (all p > 0.05). The total numbers of genetic alternations detected in resection and CNB specimens were 186 and 211, respectively, with 156 alternations in common, yielding a specific concordance rate of 83.9%. The prevalence of mutations in 8 major driver genes was 100% identical between surgical and CNB specimens, though the allele frequency was lower in CNB specimens, with a median underestimation of 57%. Results of TMB were similar (p = 0.547) and MSI status was 100% matched in all paired specimens.ConclusionsPulmonary CNB specimens were suitable for NGS given the satisfactory accuracy when compared to corresponding surgical specimens. NGS results yielding from CNB specimens should be deemed reliable to provide instructive information for the treatment of advanced lung cancers.

Abstract 3070: Non-small cell lung cancer patient-derived organoids as high-throughput chemotherapy testing platforms

Abstract Background: Lung cancer is associated with phenotypic, genotypic, and transcriptomic heterogeneity among patients that poses a threat to the development of precision medicine. Despite being considered as potential drug screening platforms, patient-derived xenograft (PDX) models are limited by low rates and prolonged durations of tumor engraftment. To overcome these major limitations, patient-derived organoid (PDO) models have been developed for standard of care drug testing and the outcome of which is driven by differential transcriptome trajectories. Experimental methods: Single cell suspension from ten surgically resected patient primary non-small cell lung cancer (NSCLC) tissues (adenocarcinoma and squamous cell carcinoma) was mixed with matrigel (growth factor reduced) and cultured in organoid growth medium. Organoids were characterized for structural (Hematoxylin &amp; Eosin staining) and pathological marker (immunohistochemistry for cytokeratin (CK) 5/6, CK7, Napsin A, Thyroid transcription factor-1 (TTF-1) and p40) similarities with primary tumor. Upon passaging, organoids were seeded in triplicates, allowed to acclimate for 24h and subjected to standard of care chemotherapy testing versus vehicle control. PDOs and corresponding primary tumors were subjected to bulk RNA sequencing to understand the transcriptome driven outcome in chemotherapy sensitive versus resistant organoids. Results: Organoid growth was monitored by light microscopy. PDOs exhibited different growth kinetics indicating the inter-tumor heterogeneity. Time for PDOs to reach 100-200 μm ranged from 6 days to 14 days and exhibited structural features and pathological marker expression similar to their corresponding primary tumors reflecting respective histological subtypes - adenocarcinoma or squamous cell carcinoma. Chemotherapy testing (1 μg/ml Carboplatin plus 0.5 μg/ml Paclitaxel) showed differential responses (day 6 of treatment). Based on the scoring, PDOs were categorized as partially sensitive, very sensitive or resistant (based on organoid growth or regression in presence of chemotherapeutic drugs). Results of RNA sequencing may reveal distinct transcriptomic signatures and molecular pathways reflecting in differential chemoresponses. Conclusions and future perspectives: PDOs capitulate structural and pathological marker expression of patient primary tumors and serve as versatile, high-throughput drug testing platforms to treat NSCLC patients. Further, identification of key transcriptomic signatures and molecular pathways resulting in chemoresistance will be critical in formulating personal precision medicine to treat NSCLC patients. Citation Format: Yariswamy Manjunath, Kanve Nagaraj Suvilesh, Iuliia Innokenteva, Wesley Warren, Eric T. Kimchi, Kevin F. Staveley-O’Carroll, Guangfu Li, Jonathan B. Mitchem, Jussuf T. Kaifi. Non-small cell lung cancer patient-derived organoids as high-throughput chemotherapy testing platforms [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3070.

The role of adjuvant EGFR-TKIs for completely resected EGFR-mutant non-small cell lung cancer in an era of chemotherapy: An updated systematic review and meta-analysis.

e20501 Background: Lung cancer is the leading cause of cancer-related mortality worldwide. Previous meta-analyses explored the possible benefit of adjuvant EGFR-TKIs compared to chemotherapy for patients with completely resected non-small-cell lung cancer (NSCLC). In this meta-analysis, we present the most up-to-date efficacy and safety comparison of adjuvant tyrosine kinase inhibitors (TKIs) and adjuvant chemotherapy for those patients. Methods: We conducted a systematic review using PubMed, Scopus, and Cochrane CENTRAL databases up to January 2022. All randomized clinical trials (RCTs) comparing TKIs as a monotherapy or as a combination with chemotherapy against placebo or chemotherapy in a completely resected EGFR-mutant NSCLC adjuvant setting were included. Studies with ten or fewer patients in either arms were excluded. The primary outcomes were disease-free survival (DFS) and overall survival (OS) with a reported hazard ratio (HR), while adverse events (AEs) were the secondary outcome. Random or fixed-effects meta-analyses were performed based on heterogeneity. Results: A total of eight eligible RCTs of 1752 EGFR-mutant completely resected NSCLC patients were included in this meta-analysis. Six studies involved EGFR-TKIs as monotherapy (n = 1653) whereas two studies involved a combination of EGFR-TKIs with chemotherapy (n = 99). The DFS in the TKIs monotherapy group was significantly improved when compared to chemotherapy (HR = 0.48, 95% CI: 0.29-0.80; p = 0.005), but insignificantly when compared to placebo (HR = 0.34, 95% CI: 0.12-1.02; p = 0.06), with an overall HR of 0.42 (95% CI: 0.25-0.71; p = 0.001), while the OS difference was not of statistical significance (HR = 0.91, 95% CI: 0.70-1.17; p = 0.44). No difference in DFS was found when comparing between the Exon-19 deletion and L858R mutation types (p = 0.37). No subgroup difference in DFS was found as well between TKIs monotherapy and combination therapy when both were compared to chemotherapy (p = 0.45). Grade ≥ 3 AEs were significantly less common in the TKIs group compared to chemotherapy (OR = 0.12, 95% CI:0.06-0.24; p &lt; 0.001). Grade 3/4 rash, diarrhea, and infections were more common in the TKIs group (3.6% vs 0.0%, 2.1% vs 0.7%, and 1.7% vs 0.0%, respectively), while chemotherapy had a higher hematological involvement in terms of grade 3/4 neutropenia, leukopenia, and anemia (44.9% vs 0.2%, 25.2% vs 0.0%, and 5.8% vs 0.1%, respectively). Conclusions: The use of TKIs as adjuvant therapy in completely resected EGFR-mutant NSCLC significantly improves the DFS compared to chemotherapy, regardless of the mutation type, and with a better AEs profile as well, but does not affect the OS. Furthermore, The combination of TKIs and chemotherapy did not demonstrate a difference in DFS when compared to TKIs alone, however, prospective trials comparing both arms are needed to confirm this finding.

Multidisciplinary Management of Resectable Early-Stage Non-Small Cell Lung Cancer.

During JADPRO Live Virtual 2021, three advanced practitioners—in surgery, radiation oncology, and medical oncology—discussed their collaboration in the management of resectable early-stage non–small cell lung cancer. The presenters discussed the role of screening and early surgical resection, cancer surveillance after resection, adjuvant and neoadjuvant therapies, as well as novel therapies and their associated toxicities.

The result of adjuvant Vinorelbine plus Cisplatin in completely resected stage IB-IIIA non-small cell lung cancer at Hanoi Medical Unoversity Hospital

Background: Assess clinical, subclinical characteristics of stage IB-IIIA non - small cell lung cancer patients (NSCLC). Evaluating the result of adjuvant vinorelbine plus cisplatin in completely resected stage IB - IIIA NSCLC. Methods: Descriptive study of 70 patients completely resected stage IB - IIIA non - small cell lung cancer were received adjuvant vinorelbine plus cisplatin chemotherapy at Hanoi Medical University Hospital from 01/2016 to 6/2020. Results: The mean age of 56.94 years old, male: female ratio was 2.9:1. 23 (32.8%) patients had postoperative stage IB disease, 24 (34.3%) had stage IIA disease, 13 (18.6%) had stage IIB disease and 10 (14.3%) had stage IIIA disease. The major histological type was adenocarcinoma (78.6%). Median disease free survival was 29.10 ± 1.63 months, and 3 - year survival was 41%. Chemotherapy caused hematologic side effects in 66.67% of patients including neutropenia in 61.4% and grade 3/4 neutropenia in 28.1%. Non - hematologic toxic effects of chemotherapy were reported at low rates and almost mild (grade 1/2). Conclusions: The vinorelbine - cisplatin regimen is an effective regimen in the adjuvant treatment of non - small cell lung cancer, the study showed that the results in disease - free survival and overall survival were comparable to those of other studies in the world. The most common side effect was neutropenia, the other side effects were reported at low rate and usually mild.

Modeling the cost-effectiveness of adjuvant osimertinib in resected EGFR-mutant non-small cell lung cancer patients.

8527 Background: Adjuvant Osimertinib (Osi) was recently approved for resected EGFR-mutant non-small cell lung cancer (NSCLC) based on disease free survival (DFS) benefits from the ADAURA trial. Prior studies of adjuvant EGFR inhibitors yielding DFS benefits have lacked an overall survival (OS) benefit, leading to debate over early clinical implementation given the associated drug costs. This study aims to evaluate the cost-effectiveness (CE) of Osi in this setting. Methods: We constructed Markov models using post-resection health state transitions with digitized DFS data from the ADAURA trial to compare cost and quality-adjusted life years (QALYs) of the use of 3 years of adjuvant Osi versus placebo in the ADAURA patient population of stage IB to IIIA NSCLC patients over a 10-year time horizon. All patients entering the progressive disease (PD) state were assigned for re-treatment with Osi. Cost and utility values were derived from Medicare reimbursement data and literature (Table). A CE threshold of 3 times the GDP per capita was used. Deterministic sensitivity analyses were performed to assess the impact of a range of OS benefit, as the impact of adjuvant Osi on OS has not yet been reported. Results: The incremental cost-effectiveness ratio (ICER) for adjuvant Osi was $317,119.90 per QALY gained. Initial costs of Osi are higher in the first 3 years, but become lower than the placebo group in year 4 onward, with similar costs after year 7. Costs due to PD are higher in the placebo group through the first 6.5 years. Average pre-PD, post-PD, and total costs were $2,388, $379,047, and $502,937, respectively in the placebo group, compared to $505,775, $255,638, and $800,697, respectively in the Osi group. QALYs were higher in the Osi arm throughout. Sensitivity analysis using incremental OS gains reaches the CE threshold of $195,000 between 25-30% OS benefit of Osi over placebo. A 50% discount to the Osi annual cost yielded an ICER of $115,419. Conclusions: 3 years of adjuvant Osi is more cost-effective than placebo if one is willing to pay $317,119 more per QALY gained, with most costs accruing in the first 3 years as drug cost. This strategy became cost-effective with an OS benefit between 25-30% over placebo. Discount to Osi annual costs improves the ICER significantly. True cost-effectiveness of adjuvant Osi will require further study due to immaturity of ADAURA OS data and model limitations.[Table: see text]

Systematic Review of Neoadjuvant Immunotherapy for Patients With Non–Small Cell Lung Cancer

There is a paucity of robust clinical evidence for the role of neoadjuvant immunotherapy in patients with resectable non-small cell lung cancer. The primary aim of the study was to identify the available data on the feasibility, safety and efficacy of neoadjuvant immunotherapy. A systematic review was conducted using electronic databases. Relevant studies were identified according to predefined selection criteria. Five relevant publications on 4 completed trials were identified. In most studies, >90% of patients were able to undergo surgery within the planned timeframe after neoadjuvant immunotherapy. There was a high incidence of open thoracotomy procedures, either planned or converted from a planned minimally invasive approach. Mortality ranged from 0 to 5%, but none of the reported deaths were considered directly treatment-related. Morbidities were reported according to adverse events related to neoadjuvant systemic therapy, and postoperative surgical complications. Survival outcomes were limited due to short follow-up periods. Major pathologic response ranged from 40.5 to 56.7%, whilst complete pathologic response of the primary tumor ranged from 15 to 33%. Radiological responses were reported according to RECIST criteria and fluorodeoxyglucose-avidity. This systematic review reported safe perioperative outcomes of patients who underwent resection following neoadjuvant immunotherapy. However, there was a relatively high incidence of open thoracotomy procedures, partly due to the technical challenges associated with increased fibrosis and inflammation of tissue, as well as the more advanced stages of disease in patients enrolled in the studies. Future studies should focus on identifying predictors of pathological response.

Does the Adjuvant Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor Change the Natural History of Resected EGFR Mutation-Positive Non-Small Cell Lung Cancer? Is it for Prime Time?

Does the Adjuvant Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor Change the Natural History of Resected EGFR Mutation-Positive Non-Small Cell Lung Cancer? Is it for Prime Time?

A single-arm, phase 2 study of adjuvant chemotherapy with oral tegafur-uracil for pathologically lymphovascular invasion positive stage IA non-small cell lung cancer: LOGIK0602 study

BackgroundLymphovascular invasion (LVI), which includes vascular or lymphatic invasions, is a representative prognostic factor even in patients with resected stage IA non-small cell lung cancer (NSCLC). Because tegafur-uracil is effective on cancers with LVI, we conducted a multi-center single-arm phase II study to estimate the efficacy of adjuvant tegafur-uracil in patients with LVI-positive stage IA NSCLC.MethodsPatients with completely resected LVI-positive stage IA NSCLC were registered. LVI was diagnosed by consensus of two of three pathologists. Adjuvant chemotherapy consisted of 2 years of oral tegafur-uracil at 250 mg/m2/day. Fifty-five patients from 7 institutions were enrolled from June 2007 to September 2012.ResultsAmong the 52 eligible patients, 36 (69.2%) completed the treatment course. There were 39 male and 13 female patients. The observation period was calculated as 562 to 3107 days using the reverse Kaplan-Meier method. The 5-year overall and relapse free survival rates were 94.2 and 88.5% respectively, which were significantly better than that of any other studies conducted on patients with LVI-positive stage IA NSCLC. Notably, the overall survival rate was 15% better than that of our prior retrospective study. The retrospective analysis of stage IA NSCLC patients who had received an operation in the same period revealed that the 5-year overall survival rate of the LVI positive group was 73.6% when adjuvant chemotherapy was not applied. Among 55 safety analysis sets, 4 cases of grade 3 hepatic function disorder (9.1%) and 5 cases of grade 2 anorexia (10.9%) were most frequently observed. No grade 4 adverse effects were encountered.ConclusionA 2-year course of oral tegafur-uracil administration is feasible and might have a significant benefit in the adjuvant treatment of LVI-positive stage IA NSCLC.Trial registrationUMIN identifier: UMIN000005921; Date of enrolment of the first participant to the trial: 19 June 2007; Date of registration: 5 July 2011 (retrospectively registered).

Abstract 2028: Recent trends in use of adjuvant chemotherapy in elderly stage II-III non-small cell lung cancer

Abstract Background: Although randomized trials demonstrated survival benefit of adjuvant chemotherapy, previous reports have suggested that its use in elderly populations for early stage non-small cell lung cancer (NSCLC) was infrequent. Oncologists often hesitate to offer adjuvant chemotherapy in resected early stage non-small cell lung cancer for elderly population. The status of adjuvant chemotherapy in this population is unknown for recent decades. Materials and Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database which represents about 28% of the US population, we examined the incidence of chemotherapy in resected stage II-III NSCLC between 2004 and 2015. Staging was determined according to the American Joint Committee on Cancer (AJCC) 6th version. Cases were grouped by age (20-69, 70-79, and 80+). Trends in use of chemotherapy by age group was assessed by univariate and multivariate analyses. Results: A total of 35,009 were selected as surgically resected stage II-III NSCLC. Use of chemotherapy was 66.9%, 48.2%, 25.0% in age 20-69, 70-79, 80+, respectively. Multivariate analysis demonstrated that younger age (20-69) and recent year (2010-2015) of diagnosis were associated with increased use of chemotherapy. Chemotherapy use increased from 2004 to 2015 by 11.0%, 18.3%, and 11.3% in age 20-69, 70-79, 80+, respectively. In the age 70-79 group, increased use of chemotherapy was greater in stage II (24.3%) than stage III (14.1%). Five-year overall survival in age 70-79 group mildly increased by 7.6% from 2004 to 2011. Conclusion: This study suggests that use of adjuvant chemotherapy in elderly population increased primarily in age 70-79. Few patients in age 80+ receive adjuvant chemotherapy even in recent years. This study not only informs oncologists of current status but also suggests further research on very elderly populations. Citation Format: Takefumi Komiya, Emily Powell, Achuta Kumar Guddati. Recent trends in use of adjuvant chemotherapy in elderly stage II-III non-small cell lung cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2028.

Supraclavicular Recurrence in Completely Resected (y)pN2 Non-Small Cell Lung Cancer: Implications for Postoperative Radiotherapy

Background: The clinical value and delineation of clinical target volume (CTV) of postoperative radiotherapy (PORT) in completely resected (y)pN2 non-small cell lung cancer (NSCLC) remain controversial. Investigations specifically focusing on the cumulative incidence and prognostic significance of initial disease recurrence at the supraclavicular region (SCR) in this disease population are seldom reported.Methods: Consecutive patients with curatively resected (y)pN2 NSCLC who received adjuvant chemotherapy from January 2013 to December 2018 at our cancer center were retrospectively examined. Disease recurrence at the surgical margin, ipsilateral hilum, and/or mediastinum was defined as loco-regional recurrence (LRR). Disease recurrence beyond LRR and SCR, was defined as distant metastasis (DM). Overall survival (OS1 and OS2) were calculated from surgery and disease recurrence to death of any cause, in the entire cohort and in patients with recurrent disease, respectively.Results: Among the 311 patients enrolled, PORT without elective supraclavicular nodal irradiation (ESRT) was performed in 94 patients and neoadjuvant chemotherapy was administered in 31 patients. With a median follow-up of 26 months, 203 patients developed recurrent disease, including 27 SCRs, among which 16 were without DM and 22 involved the ipsilateral supraclavicular region. The 1, 3, and 5-year cumulative incidence of SCR were 6.53, 13.0, and 24.7%, respectively. Chosen DM as a competing event, cN2, ypN2, not receiving lobectomy, and negative expression of CK7 were significantly associated with SCR using the univariate competing risk analysis, while ypN2 was identified as the only independent risk factor of SCR (p = 0.012). PORT significantly reduced LRR (p = 0.031) and prolonged OS1 (p = 0.018), but didn't impact SCR (p = 0.254). Pattern of failure analyses indicated that the majority of LRRs developed within the actuarial or virtual CTV of PORT, and 15 of the 22 ipsilateral SCRs could be covered by the virtual CTV of proposed ESRT. In terms of OS2, patients who developed SCR but without DM had intermediate prognosis, compared with those who had DM (p = 0.009) and those who had only LRR (p = 0.048).Conclusions: SCR is not uncommon and has important prognostic significance in completely resected (y)pN2 NSCLC. The clinical value of PORT and ESRT in such patients need to be further investigated.

Peripheral blood T-cell receptor immune repertoire characterization of resectable stage IIIA non-small cell lung cancer patients receiving neo-adjuvant chemo-immunotherapy treatment from NADIM study.

9041 Background: Characterization of the peripheral blood T-cell receptor (TCR) repertoire has become a novel approach to predict the clinical benefit to anti-PD1/PDL1 therapy. However, there is lack of knowledge about the clinical relevance of TCR repertoire in terms of pathological response and clinical outcomes (PFS and OS) in chemo-immunotherapy. To answer this question we have analysed samples from the NADIM study (NCT03081689), in which resectable stage IIIA NSCLC patients were treated with neoadjuvant chemo-immunotherapy with Nivolumab. Methods: Using ION Torrent-based next-generation sequencing we have analysed TCR repertoire of peripheral blood from 30 patients receiving chemo-immunotherapy. Using 25ng of total RNA from PBMCs, clonal convergence, evenness and diversity were calculated at diagnosis (pre-treatment) and after 3 cycles of Nivolumab plus carboplatin (post-treatment). Regarding pathological responses, patients were classified in 3 groups: complete response (pCR) (0% viable tumour at the resection specimen), mayor response (pMR) ( &lt; 10% viable tumour) and incomplete response (pIR) ( &gt; 10% of viable tumour). At data analysis, PFS and OS median follow-up times were longer than 20 months. Results: No statistically significant differences in TCR repertoire in terms of evenness (p = 0,373), diversity (p = 0,691) or convergence (p = 0,054) between pre- and post-neoadjuvant treatment were observed. Similarly, no significant differences were observed in these metrics between pathological response groups. However, a detailed analysis of the clones showed that the percentage of frequent clones (greater than 0.1%) that increase after neoadjuvant therapy does show differences between the different pathological response groups (pIR vs pMR), being elevated in patients who presented responses greater than 90% (p = 0.0385). Regarding the clinical benefit, having this parameter higher than the median (43,90% in this cohort) is associated with a higher PFS (p = 0.0490) and OS (p = 0.078) using KM Log-rank test. Conclusions: Evenness, Diversity and Convergence derived from immune repertoire analysis do not appear to be clinically useful in the context of neoadjuvant chemo-immunotherapy in lung cancer. However, the detailed analysis of the clones seems promising. The increase of the most frequent clones after treatment seems to be associated to different clinical variables such as pathological response and PFS in these patients. Clinical trial information: NCT03081689.

Association of postoperative radiotherapy with survival in patients with completely resected pathologic N2 non-small cell lung cancer treated with chemotherapy.

e21008 Background: The current staging system for completely resected pathological N2 non-small-cell lung cancer (NSCLC) treated with chemotherapy is not suitable for predicting those patients most likely to benefit or not from post-operative radiotherapy (PORT). This study aimed to construct a survival prediction model that will enable individualized predictions of the net survival of PORT. Methods: A total of 3094 cases between 2002 and 2014 were extracted from the Surveillance, Epidemiology, and End Results databases. Patient characteristics were included as covariates, and their association for overall survival (OS) with and witout PORT was assessed. Externally validate data of 602 patients were included from China. Results: A total of 3696 patients were included for analysis. Age, gender, examined lymph node, positive lymph node, tumor size, extent of surgery, and visceral pleural invasion were significantly associated with OS, with P &lt; .05. The calibration curve for OS showed great agreement between prediction by survival prediction model and actual observation.In the training cohort, the C-index for OS was 0.619 (95% CI, 0.598-0.641) in the PORT group and 0.627 (95% CI, 0.605-0.648) in the non-PORT group. In the externally validation cohort, the C-index for OS was 0.599 (95% CI, 0.485- 0.713) in the PORT group and 0.595 (95% CI, 0.544-0.646) in non-PORT group. The two survival prediction models were developed based on clinical variables to estimate an individual's net survival gain or not attributable to PORT. We found that PORT could improve OS (HR, 0.861; P = 0.044) for patients with a positive PORT net survival benefit. Conclusions: We established a practical survival prediction model that can be used to make individualized predictions about the expected survival of PORT or without PORT in patients with completely resected pathological N2 NSCLC, treated with chemotherapy.

Randomized phase II study of canakinumab (CAN) or pembrolizumab (PEM) as monotherapy or in combination as neoadjuvant therapy in patients (Pts) with surgically resected (Stage IB-IIIA) non-small cell lung cancer (NSCLC): CANOPY-N.

TPS9626 Background: Complete surgical resection is the standard treatment (tx) for pts with stage I-IIIA NSCLC. 5-year survival rates range from 19-50%, with most pts dying from distant recurrence. Neoadjuvant or adjuvant chemotherapy improves overall survival (OS) by only 5% in pts with NSCLC, and new tx options are needed. Preliminary data with PD-1 or PD-L1 inhibitors as neoadjuvant therapy has shown major pathologic responses (MPR) or pathologic complete responses (pCR) in pts with early stage NSCLC. CANTOS study demonstrated reduced incidence of NSCLC and decreased lung cancer-related mortality with CAN (IL-1β inhibitor) versus placebo, in a dose-dependent manner for pts with atherosclerosis. In pre-clinical NSCLC humanized models, tx with CAN±anti PD-1 inhibitor could lead to anti-tumor activity. Combination of CAN and PEM is expected to enhance the efficacy of PD-1 inhibition by inhibiting dysregulated inflammation in tumor microenvironment. Based on available evidence, CANOPY-N study was designed to evaluate effect of CAN and PEM as monotherapy or in combination as neoadjuvant tx for pts with resectable NSCLC. Methods: CANOPY-N (NCT03968419) is a phase II, randomized, open-label study evaluating effect of CAN or PEM monotherapy or in combination as neoadjuvant tx in resectable NSCLC pts. Histologically confirmed stage IB-IIIA, tx-naive, ECOG PS 0-1 NSCLC pts eligible for surgery and with a planned surgical resection in approximately 4-6 weeks (after 1st dose of study tx), are eligible to participate. An archival (if obtained up to 6 months before 1st day of tx) or new biopsy is required. Approximately 110 pts will be randomized in 2:2:1 ratio (stratified by histology [squamous/non-squamous]) to one of the tx arms to receive a total of 2 doses (200 mg Q3w) of CAN alone (n = 44) or in combination with PEM (n = 44) or PEM (n = 22) with safety follow-up up to 130 days from last study drug dose. Primary endpoint is to determine MPR rate (≤10% of residual viable tumor cells at time of surgery), secondary endpoints include determination of ORR, MPR rate based on local review, surgical feasibility rates, anti-drug antibodies incidence and PK parameters. Clinical trial information: NCT03968419 .

Toripalimab Combined With Double Platinum Based Chemotherapy for Potentially Resectable Non-driver Gene Mutation Non-small Cell Lung Cancer

Toripalimab Combined With Double Platinum Based Chemotherapy for Potentially Resectable Non-driver Gene Mutation Non-small Cell Lung Cancer

Haematological biomarkers of pathological response on neo-adjuvant chemo-immunotherapy treatment for resectable stage IIIA non-small cell lung cancer (NSCLC) patients.

e20026 Background: PD1/PDL1 treatments have become the main therapy in advanced stages of NSCLC due to its significant increase in overall survival (OS), but recently, combination with chemotherapy in locally advanced stages is showing promising results. Many studies have described the neutrophil-to-lymphocyte ratio (NLR) and platelets-to-lymphocyte ratio (PLR) as indicator of systemic inflammation, that could be use as biomarker of response to immunotherapy. In our study, we described the effect of neoadjuvant chemo-immunotherapy in Complete Blood Count (CBC) parameters and evaluated their relationship with pathological responses. Methods: Immune cell populations of 46 resectable stage IIIA NSCLC patients treated with neo-adjuvant chemo-immunotherapy from NADIM clinical trial were analysed. Samples were extracted before initiating the neo-adjuvant treatment with nivolumab plus carboplatin and at the third cycle before patients underwent surgery. We classified patients in 3 subgroups of pathological response assessed in the resection specimen: complete response (pCR), mayor response (&lt; 10% viable tumour) and incomplete response (&gt; 10% viable tumour). Wilcoxon and Mann-Whitney U statistic test were used to evaluated differences between pre and post treatment and between pathological responses groups respectively. Results: From 46 patients, 5 patients did not undergo surgery, so they were excluded from the analysis. Absolute numbers (x103cells/µl) of CBC were significantly reduced after neo-adjuvant treatment in patients, leucocytes (8.80 vs 6.64), Eosinophil (0.22 vs 0.15), Monocytes (0.72 vs 0.62), Neutrophils (5.53 vs 3.53), Haemoglobin (35.82 vs 29.68), Platelets (292.44 vs 227.22), NLR (2.73 vs 1.71) and PLR (143.34 vs 115.85) except Lymphocytes (2.22 vs 2.25) and Basophils (0.06 vs 0.05). Moreover, when the analysis was done by subgroups of pathological responses, PLR variation was significantly different between pCR and incomplete response (-21.33 vs -76.98) whereas NLR and the rest of the immune populations were no different between subgroups. Conclusions: In our study, NLR is not associated to chemo-immune neo-adjuvant treatment response. Nevertheless, in our cohort a higher decrease on PLR post neo-adjuvant treatment is associated to an incomplete pathological response.

What are the benefits and harms of adjuvant chemotherapy in people with resected early-stage non-small cell lung cancer?

What are the benefits and harms of adjuvant chemotherapy in people with resected early-stage non-small cell lung cancer?

Tumor CD47 expression and a high M2/M1 ratio of tumor-associated macrophages as an adverse prognostic factor in resected stage Ⅲa non-small cell lung cancer.

e20531Background: Immunotherapy is one of the most promising advances in the field of oncology. However, limited information exists regarding characterization of the tumor associated macrophages (T...

Histological type predicts mediastinal metastasis and surgical outcome in resected cN1 non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) patients at cN1 have unfavorable outcomes. It has been reported that a substantial proportion of cN1 patients have occult mediastinal disease, and treatment guidelines suggest invasive preoperative mediastinal evaluation. However, the population that would most benefit from invasive staging has not been defined. The aims of this study are to identify factors predicting mediastinal metastasis and outcomes in cN1 NSCLC patients to select appropriate candidates for invasive mediastinal evaluation. We retrospectively studied 164 patients with radiologically diagnosed cN1 NSCLC. Clinicopathological factors including radiological nodal findings were reviewed. Factors predicting the pN2 status, disease-free survival (DFS), and overall survival (OS) were investigated. Among 164 patients with cN1 disease, pN2 was diagnosed in 43 (26.4%). This pN2 subgroup included a higher proportion of cases with adenocarcinoma (AD) histology than the pN0/1 subgroup (60.5 vs. 38.8%, p=0.012). Logistic regression analyses revealed AD as an independent predictor of the pN2 status, while radiological nodal findings were unrelated. Cox regression analyses identified lower preoperative serum CEA, non-AD, and pN0/1 status as favorable factors of DFS and adjuvant therapy to be associated with OS. Five-year DFS was much lower in the pN2 subgroup than the pN0/1 subgroup of AD patients (p<0.001), while DFS was independent of pN status in non-AD patients. Adenocarcinoma is predictive of pN2 and poor prognosis in radiologically diagnosed cN1 NSCLC. Accurate mediastinal staging may be more beneficial for prognoses and optimal treatment planning in NSCLC patients with AD histology.