Stage I-IIIA Non-small Cell Lung Research Articles

Assessment of surgery delay-associated risk in resectable stage I-IIIA non-small cell lung cancer.

Assessment of surgery delay-associated risk in resectable stage I-IIIA non-small cell lung cancer.

NGS-based Tissue-Blood TMB Comparison and Blood-TMB Monitoring in Stage-III Non-Small Cell Lung Cancer Treated with Concurrent Chemoradiotherapy

In this study, we analyzed the blood-based TMB (b-TMB) and its dynamic changes in patients with locally advanced non-small cell lung cancer (LA-NSCLC) who received concurrent chemoradiotherapy. Baseline tissue and blood TMB from 15 patients showed a strong positive correlation (Pearson correlation = 0.937), and nearly all mutations were markedly reduced in the later course of treatment, indicating a treatment-related response. This study suggests that in patients with LA-NSCLC, b-TMB is a reliable biomarker, and its dynamic monitoring can help distinguish patients who might benefit most from the consolidated immunotherapy.

302 Health Care System Factors Associated with Receipt of Treatment and with Treatment Intent in Stage Iii Non-Small Cell Lung Cancer: A Population-Based Study in Ontario

302 Health Care System Factors Associated with Receipt of Treatment and with Treatment Intent in Stage Iii Non-Small Cell Lung Cancer: A Population-Based Study in Ontario

Correlation analysis of MRD positivity in patients with completely resected stage I-IIIA non-small cell lung cancer: a cohort study.

The primary objective of this study is to thoroughly investigate the intricate correlation between postoperative molecular residual disease (MRD) status in individuals diagnosed with stage I-IIIA non-small cell lung cancer (NSCLC) and clinicopathological features, gene mutations, the tumour immune microenvironment and treatment effects. The retrospective collection and analysis were carried out on the clinical data of ninety individuals diagnosed with stage I-IIIA NSCLC who underwent radical resection of lung cancer at our medical facility between January 2021 and March 2022. The comprehensive investigation encompassed an evaluation of multiple aspects including the MRD status, demographic information, clinicopathological characteristics, results from genetic testing, the tumor immune microenvironment, and treatment effects. No significant associations were observed between postoperative MRD status and variables such as gender, age, smoking history, pathological type, and gene mutations. However, a statistically significant correlation was found between MRD positivity and T (tumor diameter > 3cm) as well as N (lymph node metastasis) stages (p values of 0.004 and 0.003, respectively). It was observed that higher proportions of micropapillary and solid pathological subtypes within lung adenocarcinoma were associated with increased rates of MRD-positivity after surgery (p = 0.007;0.005). MRD positivity demonstrated a correlation with the presence of vascular invasion (p = 0.0002). For the expression of programmed cell death ligand 1 (PD-L1), tumour positive score (TPS) ≥ 1% and combined positive score (CPS) ≥ 5 were correlated with postoperative MRD status (p value distribution was 0.0391 and 0.0153). In terms of ctDNA elimination, among patients identified as having postoperative MRD and lacking gene mutations, postoperative adjuvant targeted therapy demonstrated superiority over chemotherapy (p = 0.027). Postoperative ctDNA-MRD status in NSCLC patients exhibits correlations with the size of the primary tumor, lymph node metastasis, pathological subtype of lung adenocarcinoma, presence of vascular invasion, as well as TPS and CPS values for PD-L1 expression; in postoperative patients with MRD, the effectiveness of adjuvant EGFR-TKI targeted therapy exceeds that of chemotherapy, as evidenced by the elimination of ctDNA.

Benefit of post-operative radiation therapy for incompletely resected stage I-IIIA non-small cell lung cancer: An analysis of the National Cancer Database.

8558 Background: The presence of micro-residual (R1) or macro-residual (R2) disease in non-small cell lung cancer (NSCLC) is associated with a higher risk of recurrence. The benefits of post-operative radiation therapy (PORT) in incompletely resected NSCLC is not clear. The purpose of this study is to compare median overall survival (mOS) of treatment modalities in the post-operative setting for resected stage I-IIIA NSCLC with residual disease (R1/R2) and to determine if PORT provides benefit in this patient population using the National Cancer Database (NCDB). Methods: From the NCDB dataset for the years of 2006-2016, we extracted patients diagnosed with stage I-IIIA NSCLC and who had incomplete resection with residual disease (R1/R2). Kaplan-Meier analysis was performed to differentiate the effect of different post-operative treatment modalities, concurrent chemo-radiotherapy (CCRT), sequential chemo-radiotherapy (SCRT) and chemotherapy (CT) alone on mOS. Subsequently, univariate Cox regression was used to identify statistically significant variables, then multivariate Cox regression was performed to establish variables that contributed to the survival. Lastly, multinomial logistic regression was utilized to establish association of the independent factors. SAS version 9.4 was used to analyze the data. Results: Among the 2701 patients who met inclusion criteria, the average age was 64.1, 64.8 and 65.9 year old for CCRT, SCRT and CT, respectively. Male's constituted 53.6% and white's were 88.1%, and patient's were distributed equally across clinical stages. The majority of patients received SCRT (51.7%) followed by CT alone (39%), and CCRT (9.2%). There were no statistically significant differences in mOS between the different treatment modalities (p=0.220). Patients with R2 were 177% more likely to receive CCRT than CT compared to R1 (OR 2.77, CI 1.86-4.13 and p<0.001). Male's were 28% more likely to receive SCRT than CT compared to females (OR 1.28, CI 1.08-1.52 and p=0.0041). Nodal involvement was associated with decreased mOS with N2/N3 having 37% lower mOS compared to N0 (HR=1.37, CI 1.19-1.57 and p<0.0001). Patients who had R2 disease had a 38% lower mOS compared to those R1 (HR 1.38%, CI 1.19-1.62, p<0.0001). Conclusions: Despite the risk of unfavorable outcomes for patients with residual disease after surgery for NSCLC, the addition of radiotherapy, either concurrently or sequentially, to CT did not offer statistically significant mOS benefit compared to CT alone. Given the known toxicities of radiation, and the lack of impact on survival, the benefit of post-operative radiation is questionable among patients with residual disease after resection.

The accuracy of clinical staging of stage I-IIIA non-small cell lung cancer by using thoracic computed tomography

Purpose: To assess the accuracy of clinical staging of stage I-IIIA non-small cell lung cancer (NSCLC) by using thoracic computed tomography (CT). Patients and Methods: Medical records of patients with NSCLC operated in two years 2018-2019 at Surgery Department No 2, HCMC Oncology Hospital were studied retrospectively. Results: Thoracic CT diagnosed tumor stage with an accuracy of 79% but failed to detect T3-4 disease in 8% of cases. Of nodal disease, thoracic CT had a diagnostic accuracy of 58% but misclassified N2 disease in 18% of cases. Agreement was poor between clinical and pathologic stage (Kappa coefficient= 0.186). Only 48% of patients was diagnosed accurately, and clinically understaged patients (45%) were more frequent than clinically overstaged one. Thoracic CT had a low sensitivity of only 19% in detecting stage IIIA disease, with 13 stage IIIA patients (21%) were missed diagnosis. Conclusion: Thoracic CT is not an ideal means for clinical staging of stage I-IIIA non-small cell lung cancer. To prevent the worsened outcomes associated with inaccurate staging, physicians should rely on established staging guidelines. Key words: non-small cell lung cancer, clinical staging, thoracic computed tomography

Survival prediction for stage I-IIIA non-small cell lung cancer using deep learning

Background and purposeThe aim of this study was to develop and evaluate a prediction model for 2-year overall survival (OS) in stage I-IIIA non-small cell lung cancer (NSCLC) patients who received definitive radiotherapy by considering clinical variables and image features from pre-treatment CT-scans. Materials and methodsNSCLC patients who received stereotactic radiotherapy were prospectively collected at the UMCG and split into a training and a hold out test set including 189 and 81 patients, respectively. External validation was performed on 228 NSCLC patients who were treated with radiation or concurrent chemoradiation at the Maastro clinic (Lung1 dataset). A hybrid model that integrated both image and clinical features was implemented using deep learning. Image features were learned from cubic patches containing lung tumours extracted from pre-treatment CT scans. Relevant clinical variables were selected by univariable and multivariable analyses. ResultsMultivariable analysis showed that age and clinical stage were significant prognostic clinical factors for 2-year OS. Using these two clinical variables in combination with image features from pre-treatment CT scans, the hybrid model achieved a median AUC of 0.76 [95 % CI: 0.65–0.86] and 0.64 [95 % CI: 0.58–0.70] on the complete UMCG and Maastro test sets, respectively. The Kaplan-Meier survival curves showed significant separation between low and high mortality risk groups on these two test sets (log-rank test: p-value < 0.001, p-value = 0.012, respectively) ConclusionWe demonstrated that a hybrid model could achieve reasonable performance by utilizing both clinical and image features for 2-year OS prediction. Such a model has the potential to identify patients with high mortality risk and guide clinical decision making.

The prognostic value of decrease in prognostic nutritional index in stage III non-small cell lung cancer patients during curative thoracic radiotherapy.

Curative thoracic radiotherapy (CTRT) with concurrent chemotherapy has been considered as standard treatment approach for stage-III non-small cell lung cancer (NSCLC). The hematological and esophageal toxicities that have been encountered during CTRT would affect the immunonutritional status of the patients. The aim of this study is to evaluate the prognostic value of the change in pre- and post-treatment prognostic nutritional index (PNI) in stage-III NSCLC patients. Eighty seven consecutive stage III NSCLC patients' data were collected. Pre-radiotherapy (RT) and post-RT PNI values were calculated and the impact of prognostic value of PNI change on overall survival (OS) was evaluated by univariate and multivariate Cox regression analyses. A cutoff value of PNI change was obtained by receiver operator characteristic (ROC) curve analysis. The cutoff value was found to be a 22% decrease in PNI by ROC curve analysis in terms of effect on OS. The median OS of low and high PNI decrease groups were 22.5 and 16.5 months respectively (P = 0,001). In univariate and multivariate analyses PNI decrease of ≥ 22% was found to be an independent poor prognostic factor for OS (P = 0.012) and hazard ratio (95% confidence interval)= 2.05 (1.16-3.62). The PNI change would be a convenient parameter to assess the immunonutritional status of the patient at the end of CTRT. A decrease of more than 22% of PNI value may predict poor prognosis.

Systematic review and meta-analysis of the prognostic impact of lymph node micrometastasis and isolated tumour cells in patients with stage I-IIIA non-small cell lung cancer.

Lymph node micrometastases could be one of the reasons for the high recurrence rate after complete surgical resection in stage I-IIIA non-small cell lung cancer (NSCLC). The standard evaluation of a single haematoxylin and eosin (H&E) slide of a paraffin-embedded section of a lymph node is insufficient for the detection of micrometastases, and there is a need for additionalhistopathological evaluation. The association of lymphnode micrometastases with survival remains asyet unresolved. The aim of this systematic review and meta-analysis is to investigate if lymph node micrometastases and isolated tumour cells in patients with stage I-IIIA NSCLC, detected with multiple sectioning and/or immunohistochemistry (IHC) and/or reverse transcriptase polymerase chain reaction (RT-PCR), are associated with overall survival (OS) and disease-free survival (DFS) after surgical resection. We performed a meta-analysis of time-to-event outcomes based on 15 articles using ancillary techniques to detect micrometastases. We extracted the OS and DFS every 3-6 months after surgery, for patients with and without occult lymph node micrometastasis, from the survival curves published in each article. These data were used to reconstruct OS and DFS for 'micrometastasis' and 'no micrometastasis' groups. Based on all included studies that used IHC, serial sectioning, or RT-PCR, we found a 5-year OS of 55% (micrometastasis) vs. 75% (no micrometastasis), and a 5-year DFS of 53% (micrometastasis) vs. 75% (no micrometastasis). Patients with stage I-IIIA NSCLC with lymph node micrometastases detected by ancillary histopathological and molecular techniques have a significantly poorer OS and DFS compared to patients without lymph node micrometastases.

Real-life long-term outcomes of upfront surgery in patients with resectable stage I-IIIA non-small cell lung cancer.

BackgroundTreatment of early-stage non-small cell lung cancer (NSCLC) is rapidly evolving. When introducing novelties, real-life data on effectiveness of currently used treatment strategies are needed. The present study evaluated outcomes of stage I–IIIA NSCLC patients treated with upfront radical surgery in everyday clinical practice, between 2010–2017.Patients and methodsData of 539 consecutive patients were retrieved from a prospective hospital-based registry. All diagnostic, treatment and follow-up procedures were performed at the same thoracic oncology centre according to the valid guidelines. The primary outcome was overall survival (OS) analysed by clinical(c) and pathological(p) TNM (tumour, node, metastases) stage. The impact of clinicopathological characteristics on OS was evaluated using univariable (UVA) and multivariable regression analysis (MVA).ResultsWith a median follow-up of 53.9 months, median OS and 5-year OS rate in the overall population were 90.4 months and 64.4%. Five-year OS rates by pTNM stage I, II and IIIA were 70.2%, 60.21%, and 49.9%, respectively. Both cTNM and pTNM stages were associated with OS; but only pTNM retained its independent prognostic value (p = 0.003) in MVA. Agreement between cTNM and pTNM was 69.0%. Next to pTNM, age (p = 0.001) and gender (p = 0.004) retained their independent prognostic value for OS.ConclusionsThe study showed favourable outcomes of resectable stage I–IIIA NSCLC treated with upfront surgery in real-life. Relatively low agreement between cTNM and pTNM stages and independent prognostic value of only pTNM, observed in real-life data, suggest that surgery remains the most accurate provider of the anatomical stage of disease and important upfront therapy.

A validated nomogram integrating baseline peripheral T-lymphocyte subsets and NK cells for predicting survival in stage I-IIIA non-small cell lung cancer after resection.

BackgroundAccurately predicting the risk of recurrence in stage I–IIIA non-small cell lung cancer (NSCLC) after resection is critical in the treatment process. This study aimed to establish a novel nomogram to identify patients with a risk of disease progression in stage I–IIIA lung cancer based on clinical characteristics, peripheral T-lymphocyte subsets, and CD16+56 natural killer (NK) cells.MethodsA total of 306 NSCLC patients from Shanghai Municipal Hospital of Traditional Chinese Medicine between 2010 and 2020 who met the inclusion and exclusion criteria between January 2011 and December 2020 were retrospectively reviewed. Patients were randomly assigned to the training cohort (206 patients) and the validation cohort (100 patients). A nomogram model was developed based on the results of multivariate Cox regression in the training cohort. The optimal cut-off values were determined by X-tile software. The bootstrap method was used to validate the nomogram. Receiver operating characteristics curves (ROC) and the area under the ROC curve (AUC) were used to compare prognostic factors. The concordance index (C-index) was calculated to determine the accuracy of the nomogram in predicting disease-free survival (DFS).ResultsGender, drinking history, TNM stage, and CD4+T/CD8+T were independent factors for DFS and were integrated into the model, while CD16+56 NK cells were not proven to be significant independent factors for DFS. The calibration curves for probability of 3- and 5-year DFS showed excellent agreement between predicted and actual survival. The C-index for the nomogram to predict DFS was 0.839 in the training cohort. The nomogram showed an excellent predictive performance in the training cohort (3-/5-year AUC: 0.860/0.847) and in the validation cohort (3-/5-year AUC: 0.726/0.748).ConclusionsWe developed a prognostic model which provided individual prediction of DFS for stage I–IIIA NSCLC patients after resection. This practical prognostic tool may help oncologists in clinical treatment planning.

Abstract LBA035: Canakinumab or Pembrolizumab as Monotherapy or in Combination as Neoadjuvant Therapy in Patients With Resectable Non-Small Cell Lung Cancer: CANOPY-N Trial

Abstract Background: Complete surgical resection is the standard treatment for patients with stage I-IIIA non-small cell lung cancer (NSCLC). Five-year survival rates in this population range from 19% to 50%, with most patients dying from distant recurrence. As neoadjuvant/adjuvant chemotherapy yields a modest 5% absolute overall survival benefit for these patients with NSCLC, new treatment options are needed. Preliminary data with PD-1 or PD-L1 inhibitors as neoadjuvant therapy have shown major pathologic responses (MPRs) or pathologic complete responses in patients with resectable NSCLC. In the CANTOS study, reduced incidence of NSCLC and decreased lung cancer–related mortality were observed in a dose-dependent manner in patients with atherosclerosis who received canakinumab (interleukin 1β inhibitor) versus those who received placebo. In preclinical NSCLC humanized models, treatment with canakinumab ± anti–PD-1 inhibitor has shown promising activity, and a synergistic effect was observed with this combination, which may enhance the efficacy of PD-1 inhibition by modulating pro-tumor inflammation in the tumor microenvironment. In this context, the CANOPY-N study was designed to evaluate the effect of canakinumab or pembrolizumab as monotherapy or in combination as neoadjuvant treatment for patients with resectable NSCLC. Methods: CANOPY-N (NCT03968419) is a Phase II, randomized, open-label study evaluating the effect of canakinumab or pembrolizumab as monotherapy or in combination as neoadjuvant treatment in patients with resectable NSCLC. Patients with histologically confirmed stage IB-IIIA NSCLC (excluding N2 and T4 tumors), no prior systemic therapy, Eastern Cooperative Oncology Group performance status 0 or 1, and eligibility for surgery with a planned resection in approximately 4-6 weeks after first dose of study treatment are eligible to participate. An archival (if obtained up to 6 months before first day of treatment) or new biopsy is required. Approximately 110 patients will be randomized in a 2:2:1 ratio (stratified by histology [squamous/nonsquamous]) to receive a total of 2 doses (200 mg every 3 weeks) of canakinumab alone (n=44) or in combination with pembrolizumab (n=44) or pembrolizumab alone (n=22), with safety follow-up up to 130 days from last study-drug dose. The primary endpoint is MPR rate (≤10% of residual viable tumor cells at time of surgery), and secondary endpoints include overall response rate per RECIST 1.1, MPR rate based on local assessment, surgical feasibility rates, safety, incidence of antidrug antibodies, pharmacokinetic parameters, and assessment of the relationship between blood- or tissue-based biomarkers and MPR. As of May 27, 2021, there are 44 active study locations. Citation Format: Jay M. Lee, Jean-Louis Pujol, Pilar Garrido, Edward S. Kim, Masahiro Tsuboi, Rafael Caparica Bitton, Jiawei Duan, Cecile Blin, Alexander Savchenko, Tony Mok. Canakinumab or Pembrolizumab as Monotherapy or in Combination as Neoadjuvant Therapy in Patients With Resectable Non-Small Cell Lung Cancer: CANOPY-N Trial [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr LBA035.

OA08.03 The 5-year Survival Rate of Postoperative Non-small Cell Lung Cancer Patients with Two Different Follow-up Patterns

Recent studies suggest that different follow-up patterns may influence the survival of cancer patients. This study aimed to compare the 5-year survival rates between the two post-operation follow-up patterns of the patients with stage I-IIIA non-small cell lung cancer (NSCLC). This is a China multicenter, retrospective, observational study. Clinical stage I-IIIA NSCLC (adjusted by AJCC 8th edition) patients who underwent surgical resection and received follow-up within 6 months after initial diagnosis through LinkDoc telephone follow-up system were included from July 2014 to July 2020. Patients who died within 3 months after the surgery were excluded. All enrolled patients are grouped into proactive follow-up (AF) group or passive follow-up (PF) group according to patients’ behavior during follow-up. In the AF group, patients proactively reached out for medical advice at least once aside from routine follow-up. In the PF group, patients underwent routine follow-up (every 3 months for the first 2 years and every 6 months for the following years). The Kaplan-Meier and Cox proportional hazards regression model were used. A total of 11,958 stage I-IIIA NSCLC patients were included from 9 hospitals with a wide geographical representation. No significant difference for the demographic and clinical characteristics were found between the AF group (N=3825) and the PF group (N=8133). In both groups, most patients were male, non-squamous histological type, stage I and the Eastern Cooperative Oncology Group Performance Status (ECOG-PS)≤2. In the AF group and PF group, median call duration were 3.77 and 3.58 minutes; the 5-year survival rate were 81.8% and 74.2% (Figure.1), respectively. Compared with the PF group, the AF group had better 5-year survival rate [hazard ratio (HR)=0.60, 95% confidence interval (CI), 0.53-0.67, P<0.001]. Further, in subgroups of clinical stages, the AF group all presented significantly better 5-year survival rate than the PF group (stage I subgroup, HR=0.59, 95%CI, 0.46-0.75, P <0.001; stage II subgroup, HR=0.64, 95%CI, 0.51-0.79, P <0.001; stage IIIA subgroup, HR=0.54, 95%CI, 0.46-0.64, P <0.001). Multivariate analysis showed that follow-up pattern, age, gender and operation mode were independent prognostic factors of stage I-IIIA NSCLC, and the results were consistent in all subgroups stratified by clinical stages. This real-world study indicated that proactive follow-up through telephone follow-up system leads to better overall survival for resected stage I-IIIA NSCLC patients.

ES12.01 Defining Operability

ES12.01 Defining Operability

Effect of intraoperative blood loss on postoperative pulmonary complications in patients undergoing video-assisted thoracoscopic surgery.

Background We aimed to investigate the impact of intraoperative blood loss on postoperative pulmonary complications in patients who underwent video-assisted thoracoscopic lobectomy for nonsmall cell lung cancer. Methods Data of a total of 409 patients (227 males, 182 females; median age: 62 years; range, 20 to 86 years) who underwent lung resection for Stage I-IIIa non-small cell lung cancer in our clinic between July 2017 and April 2018 were retrospectively analyzed. The receiver operating characteristic analysis was used to confirm the threshold value of intraoperative blood loss for the prediction of postoperative pulmonary complications. Propensity score matching was performed to compare between high-intraoperative blood loss and low-intraoperative blood loss groups. A post-matching conditional logistic regression was conducted to determine the independent risk factors for postoperative pulmonary complications. Results Of the patients, 86 (21.03%) developed postoperative pulmonary complications. In the propensity score matching analysis, intraoperative blood loss was shown to be a predictive factor of postoperative pulmonary complications (3.992; 95% confidence interval [CI]: 1.54-10.35; p=0.004). The rate of postoperative pulmonary complications in high-intraoperative blood loss group was significantly higher than that the low-intraoperative blood loss group (37.5% vs. 13.9%, respectively; p=0.003). The postoperative length of stay and duration of postoperative antibiotic use were significantly prolonged in the high-intraoperative blood loss group. Conclusion Intraoperative blood loss serves as a significant risk factor for postoperative pulmonary complications after lung resection for non-small cell lung cancer. Surgeons should strive to reduce intraoperative blood loss for better surgical outcomes.

Abstract CT237: Canakinumab or pembrolizumab as monotherapy or in combination as neoadjuvant therapy in patients with surgically resected non-small cell lung cancer: CANOPY-N trial

Abstract Background: Complete surgical resection is the standard treatment for patients with stage I-IIIA non-small cell lung cancer (NSCLC). Five-year survival rates range from 19% to 50%, with most patients dying from distant recurrence. Neoadjuvant or adjuvant chemotherapy improves overall survival (OS) by only 5% in patients with NSCLC, and new treatment options are needed. Preliminary data for PD1 or PD-L1 inhibitors as neoadjuvant therapy have shown major pathologic responses (MPRs) or pathologic complete responses (pCRs) in patients with early-stage NSCLC. The CANTOS study demonstrated reduced incidence of NSCLC and decreased lung cancer-related mortality with canakinumab (interleukin 1β inhibitor) versus placebo, in a dose-dependent manner for patients with atherosclerosis. In preclinical NSCLC humanized models, treatment with canakinumab ± anti-PD-1 inhibitor could lead to antitumor activity. Combination of canakinumab and pembrolizumab is expected to enhance the efficacy of PD-1 inhibition by inhibiting dysregulated inflammation in the tumor microenvironment. Based on available evidence, the CANOPY-N study was designed to evaluate the effect of canakinumab and pembrolizumab as monotherapy or in combination as neoadjuvant treatment for patients with resectable NSCLC. Methods: CANOPY-N (NCT03968419) is a Phase II, randomized, open-label study evaluating the effect of canakinumab and pembrolizumab as monotherapy or in combination as neoadjuvant treatment in patients with resectable NSCLC. Patients with histologically confirmed stage IB-IIIA NSCLC (excluding N2 and T4 tumors), no prior systemic therapy, Eastern Cooperative Oncology Group performance status 0 or 1, and eligibility for surgery and with a planned surgical resection in approximately 4-6 weeks (after first dose of study treatment) are eligible to participate. An archival (if obtained up to 6 months before first day of treatment) or new biopsy is required. Approximately 110 patients will be randomized in a 2:2:1 ratio (stratified by histology [squamous/nonsquamous]) to one of the treatment arms to receive a total of 2 doses (200 mg every 3 weeks) of canakinumab alone (n=44) or in combination with pembrolizumab (n=44) or pembrolizumab alone (n=22), with safety follow-up up to 130 days from last study drug dose. The primary endpoint is MPR rate (≤10% of residual viable tumor cells at time of surgery), and secondary endpoints include determination of overall response rate, MPR rate based on local review, surgical feasibility rates, incidence of antidrug antibodies, and pharmacokinetic parameters. As of October 19, 2020, there are 36 active study locations. Citation Format: Jay M. Lee, Tony Mok, Pilar Garrido, Edward S. Kim, Çağatay Arslan, Masahiro Tsuboi, Tuochuan Dong, Cecile Blin, Vanessa Rodrik-Outmezguine, Bijoyesh Mookerjee, Vanessa Passos, Jean-Louis Pujol. Canakinumab or pembrolizumab as monotherapy or in combination as neoadjuvant therapy in patients with surgically resected non-small cell lung cancer: CANOPY-N trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT237.

Evaluation of different treatment strategies between right-sided and left-sided pneumonectomy for stage I-IIIA non-small cell lung cancer patients.

BackgroundThis study aimed to assess the different survival outcomes of stage I–IIIA non-small cell lung cancer (NSCLC) patients who received right-sided and left-sided pneumonectomy, and to further develop the most appropriate treatment strategies.MethodsWe accessed data from the Surveillance, Epidemiology, and End Results database from the United States for the present study. An innovative propensity score matching analysis was used to minimize the variance between groups.ResultsFor 2,683 patients who received pneumonectomy, cancer-specific survival [hazard ratio (HR) =0.863, 95% confidence interval (CI): 0.771 to 0.965, P=0.010] and overall survival (OS; HR =0.875, 95% CI: 0.793 to 0.967, P=0.008) were significantly superior in left-sided pneumonectomy patients compared with right-sided pneumonectomy patients. Cancer-specific survival (HR =0.847, 95% CI: 0.745 to 0.963, P=0.011) and OS (HR =0.858, 95% CI: 0.768 to 0.959, P=0.007) were also significantly longer with left-sided compared to right-sided pneumonectomy after matching analysis of 2,050 patients. Adjuvant therapy could significantly prolong cancer-specific survival (67 versus 51 months, HR =1.314, 95% CI: 1.093 to 1.579, P=0.004) and OS (46 versus 30 months, HR =1.458, 95% CI: 1.239 to 1.715, P<0.001) among left-sided pneumonectomy patients after the matching procedure, while adjuvant therapy did not increase cancer-specific survival for right-sided pneumonectomy patients (46 versus 42 months, HR =1.112, 95% CI: 0.933 to 1.325, P=0.236). Subgroup analysis showed that adjuvant chemotherapy could significantly improve cancer-specific survival and OS for all pneumonectomy patients. However, radiotherapy was associated with worse survival for patients with right-sided pneumonectomy.ConclusionsPneumonectomy side can be deemed as an important factor when physicians determine the most optimal treatment strategies.

Long-term outcomes following neoadjuvant or adjuvant chemoradiotherapy for stage I-IIIA non-small cell lung cancer: a propensity-matched analysis.

BackgroundThis study aimed to evaluate the long-term survival outcomes of patients undergoing neoadjuvant chemoradiotherapy or adjuvant chemoradiotherapy for T1-4N0-1M0 disease.MethodsPatients with pT1-4N0-1M0 between 2010 and 2015 who received pre- or postoperative (R0 resection) chemoradiotherapy were identified. The exclusion criteria included N2 or M1 disease, immunotherapy, and targeted therapy. The staging was recalculated according to the new 8th edition TNM classification. Survival and predictors were assessed using Kaplan-Meier and multivariate Cox proportional-hazards model. Propensity-score matching with a ratio of 2:1 was performed to reduce bias in various clinicopathological factors.ResultsOf the 1,769 patients who met the inclusion criteria, 407 and 814 were included in the neoadjuvant and adjuvant chemoradiotherapy group, respectively, after propensity-score matching. The 5-year overall survival (OS) and cancer-specific survival (CSS) were 38.1% and 40.0% for neoadjuvant chemoradiotherapy and 26.3% and 26.5% for adjuvant chemoradiotherapy, respectively [P<0.0001, hazard ratio (HR): 0.7418, 95% confidence interval (CI): 0.6434–0.8553; P<0.0001, HR: 0.7444, 95% CI: 0.6454–0.8587)]. When stratified by stage, stage IIA (P=0.4166, HR: 0.8575, 95% CI: 0.5917–1.243) and IIIA (P=0.0740, HR: 0.7687, 95% CI: 0.5748–1.028) did not show improved 5-year OS in patients receiving neoadjuvant chemoradiotherapy. When stratified by age, similar trends were observed for patients aged more than 75 years. The multivariable analysis showed a significant association of neoadjuvant chemoradiotherapy with better survival.ConclusionsNeoadjuvant chemoradiotherapy might improve the long-term survival of patients with stage I–IIIA non-small cell lung cancer (NSCLC). For patients aged more than 75 years, neoadjuvant chemoradiotherapy was not associated with an improvement in survival.

Lung cancer chemotherapy and radiotherapy toxicity in patients with HIV.

e13616 Background: Lung cancer is the leading cause of cancer death for people living with HIV (PWH), and this group experiences lung cancer outcome disparities for unclear reasons. To better understand these disparities, we explored potential differences in adverse events since the start of chemotherapy, or radiation therapy (RT), among PWH with stage I-IIIA non-small cell lung cancer (NSCLC). Methods: Our matched case-cohort study used data from SEER-Medicare data on stage I-IIIA NSCLC diagnosed between 2000 and 2013. We identified 809 early stage NSCLC patients with HIV; 40 were treated with chemotherapy and 60 with RT. For each therapy type, a PWH case was matched, by age, sex, and cancer stage to 10 controls with no evidence of HIV infection. Outcome Measures: Acute severe chemotherapy or RT toxicity ascertained by a relevant inpatient diagnosis within 6 months of chemotherapy initiation or chronic toxicities from outpatient diagnostic codes within 24 months. We also evaluated overall (all-cause) and lung cancer-specific survival. Results: Among hematologic toxicities, PWH treated with chemotherapy were more than twice as likely to develop severe anemia [odds ratio [OR] = 2.3 (95% confidence interval [95% CI]: 1.2-4.6)]; but not neutropenia or thrombocytopenia (both p &gt; 0.06). Among patients receiving chemotherapy, HIV was not associated with any other severe acute toxicities including fever, infection, nausea, renal dysfunction, and septicemia. For chronic complications, PWH had increased risk of neuropathy (OR 4.2; 95% CI: 1.3-13.6). Overall, HIV was associated with an increased count of chemotherapy complications seen per patient [p = 0.02]. PWH receiving chemotherapy had worse all-cause mortality (hazard ratio (HR) = 1.7; 95% CI: 1.2-2.4) and higher lung cancer-specific mortality (HR 1.8; 95% CI: 1.2-2.7) compared to uninfected persons after adjusting for treatment with surgery. In contrast, HIV was not significantly associated with severe RT complications (esophagitis, pneumonitis or hemoptysis), although all-cause mortality (HR 1.5; 95% CI: 1.1-2.0) and lung-cancer specific mortality (HR 1.5; 95% CI: 1.1-2.0) were higher among PWH receiving RT after adjusting for treatment with surgery. Conclusions: Antiretroviral-era PWH with early stage lung cancer experienced more frequent complications after chemotherapy but not radiotherapy compared to matched uninfected persons. These toxicities may have led to treatment alterations potentially contributing to outcome disparities seen in this high-risk group.

A Potent Multi-Omics Signature for Predicting Recurrence in Patients with Non-Small Cell Lung Cancer after Surgery

Background: study has integrated multiple levels of biological datasets to predict outcome in lung cancer patients. We aimed to develop and validate a prognostic model integrating copy number variation (CNV), DNA methylation, mRNA, and miRNA expression data to predict recurrence in patients with stage I-IIIA non-small cell lung cancer (NSCLC) after surgery. Methods: 509 NSCLC patients with the clinical and four types omics data collected from The Cancer Genome Atlas database were assigned into the discovery (n=237) and validation (n=272) cohorts according to resource of cases. We adopted principal component analysis to reduce the dimension of multi-omics data, and built a multi-omics signature for resected NSCLC using the LASSO Cox regression model. We assessed the predictive ability of the signature with the Harrell's concordance index (C-index). Findings: We built a multi-omics signature (MOSLC) based on 5 CNVs, 14 DNA methylations, 2 miRNAs, and 27 miRNAs. Using this signature, patients were classified into high- or low-risk groups with significant differences in recurrence-free survival in the discovery (hazard ratio [HR] 5.81, 95%CI 3.74-9.03; P<.001), and validation (HR: 2.73, 95%CI 1.78-4.18; P<.001) cohorts. Additionally, the MOSLC showed better predictive performance than the tumor-node-metastasis stage in the discovery (C-index: 0.753 vs. 0.636, P = .002) and validation (0.707 vs. 0.641, P =.098) cohorts. Interpretation: MOSLC is a reliable tool in predicting recurrence for patients with NSCLC, individualizing treatment and follow-up schedule. Funding Statement: This work was supported by grants from the National Natural Science Foundation of China (No. 81672872 and No. 81472386). The collection of cancer data used in this study was supported by The Cancer Genome Atlas pilot project established by the National Cancer Institute. Declaration of Interests: The authors stated: No potential conflicts of interest were disclosed. Ethics Approval Statement: Missing.