Resected Non-small Cell Lung Cancer Research Articles

Role of Pathological Single- and Multiple-N Descriptors in Resected Non-small Cell Lung Cancer

BackgroundThe 8th edition of lung cancer N staging assignment includes the location of lymph node metastasis, but does not include single- and multiple-N descriptors. Research QuestionDo the single- and multiple-N statuses stratify the prognosis of patients with non-small cell lung cancer (NSCLC)? Study Design and MethodsUsing the National Cancer Database, we analyzed patients with pathologically staged N1–2 NSCLC. N descriptors were classified into pathological single N1 (pSingle-N1), pathological multiple N1 (pMulti-N1), pSingle-N2, and pMulti-N2. Survival analysis was performed using Kaplan–Meier method and multivariate Cox regression models. ResultsIn the general analysis cohort, 24,531, 22,256, 8,528, and 21,949 NSCLC patients had pSingle-N1, pMulti-N1, pSingle-N2, and pMulti-N2, respectively. Patients with pMulti-N1 and pMulti-N2 had a shorter survival than those with pSingle-N1 and pSingle-N2, respectively (hazard ratio [HR]: 1.22, P < 0.0001 for N1 and 1.39, P < 0.0001 for N2). After adjusting age, sex, and histology, the HR for pSingle-N2 compared with pMulti-N1 was 1.05 (P = 0.0031). Patients with pN1 were categorized by metastatic lymph node count (1, 2, 3, 4+), showing significant prognostic differences among groups (P < 0.0001). In the sensitivity analysis cohort (limited to R0 resection, lobectomy or more, survival ≥ 30 days, ≥ 10 examined lymph nodes, and without neoadjuvant therapy; n = 34,904) and the external validation cohort (n = 708) analyses supported these results. InterpretationNSCLC patients with 1 metastatic lymph node, whether in N1 or N2 stations, had better survival than those with more than 1 lymph node involved. NSCLC patients with a single skip N2 lymph node metastasis had survival similar to patients with multiple N1 lymph nodes, and the number of lymph nodes involved in N1 resections up to ≥ 4 was sequentially prognostic.

Salvage surgery and conversion surgery for patients with non-small cell lung cancer: A narrative review.

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths. With the development of screening, patient selection and treatment strategies, patients' survival outcomes and living quality significantly improved. However, some patients still have local recurrence or residual tumors after receiving definitive therapies. Salvage surgery has been regarded as an effective option for recurrent or residual NSCLC, but its effectiveness remains undetermined. Furthermore, conversion surgery is a special type of salvage surgery for tumors converted from "initially unresectable" to "potentially resectable" status due to a favorable response to systemic treatments. Although conversion surgery is a promising curative procedure for advanced NSCLC, its concept and clinical value remain unfamiliar to clinicians. In this narrative review, we provided an overview of the safety and efficacy of salvage surgery, especially salvage surgery after sublobar resection in early-stage NSCLC. More importantly, we highlighted the concept and value of conversion surgery after systemic treatment in advanced NSCLC to gain some insights into its role in the treatment of lung cancer.

A retrospective analysis of treatment patterns, overall survival, and real-world disease-free survival in early-stage non-small cell lung cancer following complete resection

BackgroundReal-world data regarding patient characteristics, adjuvant treatment patterns, and long-term survival outcomes are needed to better understand unmet needs among patients with completely resected early-stage non-small cell lung cancer (NSCLC).MethodsElectronic medical records from the U.S.-based ConcertAI Patient360™ database were analyzed in patients with stage IB-IIIA NSCLC who underwent complete resection prior to March 1, 2016. Patients were followed until death or July 1, 2021. This study evaluated adjuvant chemotherapy use, and overall survival (OS) and real-world disease-free survival (rwDFS) outcomes using the Kaplan–Meier method. The correlation between OS and rwDFS was assessed using the Kendall rank test. Among patients who did not recur 5 years following surgery, landmark analyses of OS and rwDFS were conducted to understand the subsequent survival impact of remaining disease-free for at least 5 years.ResultsData from 441 patients with completely resected stage IB-IIIA NSCLC were included. About 35% of patients received adjuvant chemotherapy post-resection. Median OS and rwDFS from resection were 83.1 months and 42.4 months, respectively. The 5-year OS and rwDFS rates were 65.7% and 42.1%, respectively. OS and rwDFS were positively correlated (Kendall rank correlation coefficient = 0.67; p < 0.0001). Among patients without recurrence within 5 years after resection, the subsequent 5-year OS and rwDFS survival rates were 52.9% and 36.6%, respectively.ConclusionsUse of adjuvant chemotherapy was low, and the overall 5-year OS rate remained low despite all patients having undergone complete resection. Patients who remained non-recurrent over time had favorable subsequent long-term survival.

A retrospective analysis of treatment patterns, overall survival, and real-world disease-free survival in early-stage non-small cell lung cancer following complete resection

BackgroundReal-world data regarding patient characteristics, adjuvant treatment patterns, and long-term survival outcomes are needed to better understand unmet needs among patients with completely resected early-stage non-small cell lung cancer (NSCLC).MethodsElectronic medical records from the U.S.-based ConcertAI Patient360™ database were analyzed in patients with stage IB-IIIA NSCLC who underwent complete resection prior to March 1, 2016. Patients were followed until death or July 1, 2021. This study evaluated adjuvant chemotherapy use, and overall survival (OS) and real-world disease-free survival (rwDFS) outcomes using the Kaplan–Meier method. The correlation between OS and rwDFS was assessed using the Kendall rank test. Among patients who did not recur 5 years following surgery, landmark analyses of OS and rwDFS were conducted to understand the subsequent survival impact of remaining disease-free for at least 5 years.ResultsData from 441 patients with completely resected stage IB-IIIA NSCLC were included. About 35% of patients received adjuvant chemotherapy post-resection. Median OS and rwDFS from resection were 83.1 months and 42.4 months, respectively. The 5-year OS and rwDFS rates were 65.7% and 42.1%, respectively. OS and rwDFS were positively correlated (Kendall rank correlation coefficient = 0.67; p < 0.0001). Among patients without recurrence within 5 years after resection, the subsequent 5-year OS and rwDFS survival rates were 52.9% and 36.6%, respectively.ConclusionsUse of adjuvant chemotherapy was low, and the overall 5-year OS rate remained low despite all patients having undergone complete resection. Patients who remained non-recurrent over time had favorable subsequent long-term survival.

Factors Associated with Postoperative Recurrence in Stage I to IIIA Non-Small Cell Lung Cancer with Epidermal Growth Factor Receptor Mutation: Analysis of Korean National Population Data.

Recent development in perioperative treatment of resectable non-small cell lung cancer (NSCLC) have changed the landscape of early lung cancer management. The ADAURA trial has demonstrated the efficacy of adjuvant osimertinib treatment in resectable NSCLC patients; however, studies are required to show which subgroup of patients are at a high risk of relapse and require adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment. This study evaluated risk factors for postoperative relapse among patients who underwent complete resection. Data were obtained from the Korean Association for Lung Cancer Registry (KALC-R), a database created using a retrospective sampling survey by the Korean Central Cancer Registry (KCCR) and the Lung Cancer Registration Committee. A total of 3,176 patients who underwent curative resection was evaluated. The mean observation time was approximately 35.4 months. Among stage I to IIIA NSCLC patients, the EGFR-mutant subgroup included 867 patients, and 75.2%, 11.2%, and 11.8% were classified as stage I, stage II, and stage III, respectively. Within the EGFR-mutant subgroup, 44 (5.1%) and 121 (14.0%) patients showed early and late recurrence, respectively. Multivariate analysis on association with postoperative relapse among the EGFR-mutant subgroup showed that age, pathologic N and TNM stages, pleural invasion status, and surgery type were independent significant factors. Among the population that underwent complete resection for early NSCLC with EGFR mutation, patients with advanced stage, pleural invasion, or limited resection are more likely to show postoperative relapse.

Comparison of radiotherapy versus surgical resection following neoadjuvant chemoimmunotherapy in potentially resectable stage III non-small-cell lung cancer: A propensity score matching analysis

BackgroundNeoadjuvant chemoimmunotherapy followed by surgery is recommended for resectable non-small-cell lung cancer (NSCLC). However, a considerable proportion of patients do not undergo surgery and opt for alternative treatments such as radiotherapy. The efficacy of radiotherapy in this context remains unclear. MethodsThis retrospective study analyzed data from patients with stage III NSCLC who received neoadjuvant chemoimmunotherapy followed by either surgery or radiotherapy. Propensity score matching (PSM) was used to balance the heterogeneity between the groups. Efficacy outcomes, safety profiles, and disease recurrence patterns were assessed. ResultsIn total, 175 patients were included; 50 underwent radiotherapy, and 125 underwent surgery. Prior to matching, radiotherapy was inferior to surgery in terms of progression-free survival (PFS; Hazard ratio [HR], 2.23; P = 0.008). Following a 1:1 PSM adjustment, each group consisted of 40 patients. The median PFS was 30.8 months in the radiotherapy group and not reached in the surgery group (HR, 1.46; P = 0.390). The 12- and 24-month PFS rates were 90.4 % and 69.0 % for the radiotherapy group compared to 94.1 % and 73.9 % for the surgery group, respectively. Subgroup analyses after PSM showed that patients with stage IIIA disease tend to benefit more from surgery than those with stage IIIB disease (HR, 3.00; P = 0.074). Grade 3–4 treatment-related adverse events (TRAEs) occurred in 62.5 % of patients in the radiotherapy group and 55.0 % in the surgery group, with no grade 5 TRAEs reported. The incidence of grade 3–4 treatment-related pneumonitis or pneumonia was 7.5 % and 2.5 % in the radiotherapy and surgery groups, respectively. ConclusionRadiotherapy may be a viable alternative to surgery in patients with resectable NSCLC who do not undergo surgical resection after initial neoadjuvant chemoimmunotherapy, offering comparable efficacy and a manageable safety profile. Larger prospective studies are needed to validate these findings and optimize the treatment strategies for this patient population.

Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Is Associated With Recurrence and Survival of Resectable Non–Small Cell Lung Cancer (NSCLC): A Retrospective Study

IntroductionCurative lung resection remains the key therapeutic strategy for early-stage non–small cell lung cancer (NSCLC). However, a proportion of patients still experience variable outcomes and eventually develop recurrence or die from their disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been identified as a deleterious factor that inhibits tumor cells apoptosis and leads to reduction of lymphocyte infiltration. However, there has been no research on the predicted role of PCSK9 as an immunohistochemical biomarker with survival in resectable NSCLC. MethodsOne hundred sixty-three patients with resectable NSCLC were retrospectively reviewed, and PCSK9 expression of resected NSCLC was analyzed by immunohistochemistry using tissue microarrays. ResultsPCSK9 was associated with recurrence (42.1% relapsed in the PCSK9lo group versus 57.9% relapsed in the PCSK9hi group, P = 0.006) and survival status (39.6% dead in PCSK9lo group versus 60.4% dead in PCSK9hi group, P = 0.004) in patients with resectable NSCLC. Moreover, resectable NSCLC patients with higher PCSK9 expression in tumor tissue experienced poorer disease-free survival (median disease-free survival: 10.5 versus 25.2 mo, hazard ratio = 1.620, 95% confidence interval: 1.124-2.334) and overall suvrival (median overall suvrival: 20.0 versus 54.1 mo, hazard ratio = 1.646, 95% confidence interval: 1.101-2.461) compared to those with lower PCSK9 expression. ConclusionsHigh PCSK9 expression of tumor was correlated with recurrence and worse survival status of resectable NSCLC in our retrospective study, which indicated that PCSK9 in NSCLC may be an immunohistochemical biomarker of poor prognosis for patients with resectable NSCLC. Further large-scale prospective studies are warranted to establish these results.

Clinical Utility of Tumor-Naïve Pre-surgical ctDNA Detection in Early-stage NSCLC

PurposeThe use of tumor-informed circulating tumor DNA (ctDNA) testing in early-stage patients before surgery is limited mainly due to restricted tissue access and extended turnaround times. This study aimed to evaluate the clinical value of a tumor-naïve, methylation-based cell-free DNA assay in a large cohort of patients with resected non-small cell lung cancer (NSCLC). MethodWe analyzed pre-surgical plasma samples from 895 patients with EGFR and ALK-wild-type, clinical stage I or II NSCLC. The ctDNA status was evaluated for its prognostic significance in relation to tumor volume, metabolic activity, histology, histological subtypes, and clinical-to-pathological TNM upstaging. ResultsPre-surgical ctDNA detection was observed in 55 out of 414 (13%) patients with clinical stage I lung adenocarcinoma (LUAD) and was associated with poor recurrence-free survival (RFS) (2-year RFS 69% versus 91%; log-rank P<0.001), approaching that of clinical stage II LUAD. Pre-surgical ctDNA detection was not prognostic in patients with clinical stage II LUAD or non-LUAD. Within LUAD, tumor volume and positron emission tomography avidity interacted to predict pre-surgical ctDNA detection. Moreover, pre-surgical ctDNA detection was predictive of the post-surgical discovery of IASLC G3 tumors (P<0.001) and pathological TNM upstaging (P<0.001). Notably, pre-surgical ctDNA detection strongly correlated with higher PD-L1 expression in tumors (positive rates 28% vs. 55%, P<0.001), identifying a subgroup likely to benefit from anti-PD-(L)-1 therapies. ConclusionThese findings support the integration of ctDNA testing into routine diagnostic workflows in early-stage NSCLC without the need of tumor tissue profiling. Furthermore, it is clinically useful in identifying high-risk patients who might benefit from innovative treatments, including neoadjuvant immune checkpoint inhibitors.

Clinical Utility of Tumor-Naïve Pre-surgical ctDNA Detection in Early-stage NSCLC

PurposeThe use of tumor-informed circulating tumor DNA (ctDNA) testing in early-stage patients before surgery is limited mainly due to restricted tissue access and extended turnaround times. This study aimed to evaluate the clinical value of a tumor-naïve, methylation-based cell-free DNA assay in a large cohort of patients with resected non-small cell lung cancer (NSCLC). MethodWe analyzed pre-surgical plasma samples from 895 patients with EGFR and ALK-wild-type, clinical stage I or II NSCLC. The ctDNA status was evaluated for its prognostic significance in relation to tumor volume, metabolic activity, histology, histological subtypes, and clinical-to-pathological TNM upstaging. ResultsPre-surgical ctDNA detection was observed in 55 out of 414 (13%) patients with clinical stage I lung adenocarcinoma (LUAD) and was associated with poor recurrence-free survival (RFS) (2-year RFS 69% versus 91%; log-rank P<0.001), approaching that of clinical stage II LUAD. Pre-surgical ctDNA detection was not prognostic in patients with clinical stage II LUAD or non-LUAD. Within LUAD, tumor volume and positron emission tomography avidity interacted to predict pre-surgical ctDNA detection. Moreover, pre-surgical ctDNA detection was predictive of the post-surgical discovery of IASLC G3 tumors (P<0.001) and pathological TNM upstaging (P<0.001). Notably, pre-surgical ctDNA detection strongly correlated with higher PD-L1 expression in tumors (positive rates 28% vs. 55%, P<0.001), identifying a subgroup likely to benefit from anti-PD-(L)-1 therapies. ConclusionThese findings support the integration of ctDNA testing into routine diagnostic workflows in early-stage NSCLC without the need of tumor tissue profiling. Furthermore, it is clinically useful in identifying high-risk patients who might benefit from innovative treatments, including neoadjuvant immune checkpoint inhibitors.

PP01.101 Estimated Cost of Adverse Events and Surgery for Resectable Non-Small Cell Lung Cancer Patients Receiving Neoadjuvant Nivolumab Plus Platinum-Doublet Chemotherapy

PP01.101 Estimated Cost of Adverse Events and Surgery for Resectable Non-Small Cell Lung Cancer Patients Receiving Neoadjuvant Nivolumab Plus Platinum-Doublet Chemotherapy

Sublobar resection for small-sized non-small cell lung cancer: a comprehensive comparison between subsegmentectomy, segmentectomy and wedge resection

ObjectivesSubsegmentectomy has been adopted for non-small cell lung cancer (NSCLC) for decades. This study aimed to compare the features between subsegmentectomy, segmentectomy and wedge resection for NSCLC. Materials and MethodsNSCLC patients who underwent subsegmentectomy, segmentectomy, or wedge resection between 2014 and 2019 were retrospectively screened. Demographic, radiomic, and perioperative characteristics between patients were compared. Further, log-rank test, univariate and multivariate Cox regression were used for prognostic evaluation. ResultsThere were 276, 670, and 494 patients undergoing subsegmentectomy, segmentectomy, and wedge resection, respectively. Patients with segmentectomy and subsegmentectomy had larger tumor sizes and greater distances to the pleura than those with wedge resection. Subsegmentectomy and segmentectomy were more likely to achieve adequate surgical margins than wedge resection (82.0% vs. 79.5% vs. 64.7%, P<0.001), which was especially true for nodules away from the pleura (80.2% vs. 81.4% vs. 55.8%, P<0.001). In addition, anatomic resection allowed for more lymph node dissection and required less preoperative localization than wedge reception. Subsegmentectomy preserved about two subsegments than segmentectomy (P<0.001). The incidence of prolonged air leakage after subsegmentectomy (3.3%) and wedge (1.8%) was similar (P=0.308). Notably, 66.8% of patients who underwent segmentectomy or subsegmentectomy were considered unsuitable for wedge. During the follow-up (55.1 months), no tumor recurrence or death occurred in patients undergoing subsegmentectomy. No significant recurrence-free survival (P=0.140) or overall survival (P=0.370) difference existed between these groups. ConclusionsSubsegmentectomy could achieve more adequate surgical margins than wedge resection and showed superiority for deep nodules. Compared to segmentectomy, subsegmentectomy could preserve more lung parenchyma.

A Locally Advanced NSCLC Patient Harboring a Rare KIF13A-RET Fusion Benefited from Pralsetinib: A Case Report

The application of adjuvant treatment has significantly enhanced the survival of patients with resectable non-small cell lung cancer (NSCLC) carrying driver gene mutations. However, adjuvant-targeted therapy remains controversial for some NSCLC patients carrying rare gene mutations such as RET, as there is currently a lack of confirmed randomized controlled trials demonstrating efficacy. In this report, we describe the case of a 58-year-old man with stage IIIA NSCLC who underwent complete lobectomy with selective lymph node dissection. Postoperative next-generation sequencing revealed that the patient harbored a rare KIF13A-RET fusion. The patient elected to receive adjuvant treatment with pralsetinib monotherapy and underwent serial circulating tumor DNA (ctDNA) monitoring after surgery. During follow-up, despite experiencing dose reduction and irregular medication adherence, the patient still achieved a satisfactory disease-free survival (DFS) of 27 months. Furthermore, ctDNA predicted tumor recurrence 4 months earlier than imaging techniques. The addition of bevacizumab to the original regimen upon recurrence continued to be beneficial. Pralsetinib demonstrated promising efficacy as adjuvant therapy, while ctDNA analysis offered a valuable tool for early detection of tumor recurrence. By leveraging targeted therapies and innovative monitoring techniques, we aim to improve outcomes and quality of life for NSCLC patients in the future.

Benefits of adjuvant chemotherapy in elderly patients with stage IB-IIIB non-small cell lung cancer: a propensity-matched analysis.

Adjuvant chemotherapy (ACT) is a well-recognized and well-established treatment for surgically resected non-small cell lung cancer (NSCLC), but its suitability for elderly patients remains controversial. Further investigation is warranted to guide ACT decisions in this demographic. We extracted data from the Surveillance, Epidemiology, and End Results (SEER) database, focusing on patients aged 70 years or older who underwent surgical resection for stage IB, II, or III NSCLC as per the 7th edition of the American Joint Committee on Cancer staging system (AJCC 7th edition). Propensity score matching (PSM), Kaplan-Meier analysis, and Cox regression were employed for statistical analyses. There were 503 participants received ACT in this study of 2,000 patients aged 70 or older with stage IB-IIIB NSCLC who underwent surgical resection without preoperative chemotherapy. Overall, ACT did not significantly correlate with extended overall survival (OS) (P=0.07) compared to non-ACT. After 2:1 PSM, the matched cohort comprised 317 non-ACT and 206 ACT recipients. Post-PSM, the ACT group exhibited improved OS (P=0.044) compared to the non-ACT group. Cox regression analysis identified gender, primary tumor site, histologic grade, N stage, and ACT as independent predictors of OS (P<0.05). Subgroup analysis indicated amplified ACT benefits in individuals aged 70-79 years, male, with N1 stage, or those without radiotherapy. ACT may confer benefits to elderly stage IB-IIIB NSCLC patients, particularly those aged 70-79 years, male, and with N1 stage.

Correlation between pre-anesthesia anxiety and emergence agitation in non-small cell lung cancer surgery patients.

Preoperative anxiety is a common emotional problem during the perioperative period and may adversely affect postoperative recovery. Emergence agitation (EA) is a common complication of general anesthesia that may increase patient discomfort and hospital stay and may be associated with the development of postoperative complications. Pre-anesthetic anxiety may be associated with the development of EA, but studies in this area are lacking. To determine the relationship between pre-anesthetic anxiety and EA after radical surgery in patients with non-small cell lung cancer (NSCLC). Eighty patients with NSCLC undergoing surgical treatment between June 2020 and June 2023 were conveniently sampled. We used the Hospital Anxiety and Depression Scale's (HADS) anxiety subscale (HADS-A) to determine patients' anxiety at four time points (T1-T4): Patients' preoperative visit, waiting period in the surgical waiting room, after entering the operating room, and before anesthesia induction, respectively. The Riker Sedation-Agitation Scale (RSAS) examined EA after surgery. Scatter plots of HADS-A and RSAS scores assessed the correlation between patients' pre-anesthesia anxiety status and EA. We performed a partial correlation analysis of HADS-A scores with RSAS scores. NSCLC patients' HADS-A scores gradually increased at the four time points: 7.33 ± 2.03 at T1, 7.99 ± 2.22 at T2, 8.05 ± 2.81 at T3, and 8.36 ± 4.17 at T4. The patients' postoperative RSAS score was 4.49 ± 1.18, and 27 patients scored ≥ 5, indicating that 33.75% patients had EA. HADS-A scores at T3 and T4 were significantly higher in patients with EA (9.67 ± 3.02 vs 7.23 ± 2.31, 12.56 ± 4.10 vs 6.23 ± 2.05, P < 0.001). Scatter plots showed the highest correlation between HADS-A and RSAS scores at T3 and T4. Partial correlation analysis showed a strong positive correlation between HADS-A and RSAS scores at T3 and T4 (r = 0.296, 0.314, P < 0.01). Agitation during anesthesia recovery in patients undergoing radical resection for NSCLC correlated with anxiety at the time of entering the operating room and before anesthesia induction.

Risk factors and prognostic analysis of right ventricular dysfunction after lung resection for NSCLC.

Lung cancer is the leading cause of cancer death, and 80-85% of all lung cancer cases are non-small cell lung cancer (NSCLC). Surgical resection is the standard treatment for early-stage NSCLC. However, lung resection, a surgical procedure, can result in complications and increased mortality. Recent studies have shown a significant correlation between complications after lung resection and right ventricular dysfunction. Transthoracic echocardiography-derived right ventricular-pulmonary artery coupling (RV-PAC) was utilized to assess right ventricular function in these patients. Multivariate logistic regression analysis was also conducted to assess risk factors independently associated with RV-PA uncoupling. The 3- and 5-year cumulative survival rates were estimated with Kaplan-Meier curves, and differences between groups were analyzed using the Mantel-Cox log-rank test. RV-PA uncoupling was defined as a TAPSE/PASP value < 0.67 mm/mm Hg according to spline analysis. The results of multivariable logistic regression analysis indicated that diabetes is an independent risk factor for right ventricular dysfunction after lung resection in patients with NSCLC. Kaplan-Meier analysis revealed a significant decrease in the survival rate of patients with RV-PA uncoupling at both the 3-year follow-up (73% vs 40%, p < 0.001) and 5-year follow-up (64% vs 37%, p < 0.001). After lung resection for NSCLC, the patient's right ventricular function predicts prognosis. Patients with right ventricular dysfunction, particularly those with diabetes mellitus, have a worse prognosis. It is crucial to actively prevent and correct risk factors to reduce the mortality rate in these patients.

Advancing neoadjuvant therapies in resectable non-small cell lung cancer: implications for novel treatment strategies and biomarker discovery.

The delivery of neoadjuvant and perioperative therapies for non-small cell lung cancer has been radically altered by significant advances and by the incorporation of targeted therapies as well as immune checkpoint inhibitors alone or alongside conventional chemotherapy. This evolution has been particularly notable in the incorporation of immunotherapy and targeted therapy into the treatment of resectable NSCLC, where recent FDA approvals of drugs such as nivolumab and pembrolizumab, in combination with platinum doublet chemotherapy, have led to considerable improvements in pathological complete response rates and the potential for enhanced long-term survival outcomes. This review emphasizes the growing importance of biomarkers in optimizing treatment selection and explores the impact of emerging studies that challenge existing treatment paradigms and investigate novel therapeutic combinations poised to redefine standard of care practices. Furthermore, the discussion extends to the unmet needs within perioperative treatment assessment and prognostication, highlighting the prospective value of biomarkers in evaluating treatment responses and prognosis.

Prognostic biomarker tumor-infiltrating lymphocytes failed to serve as a predictive biomarker for postoperative radiotherapy in completely resected pN2 non-small cell lung cancer: a retrospective analysis

BackgroundEvidence suggests that radiotherapy is a potent immunomodulator in non-small cell lung cancer (NSCLC). Conversely, it has rarely been demonstrated if immune infiltration can influence radiotherapy efficacy. Herein, we explored the effect of tumor-infiltrating lymphocytes (TILs) on the response to postoperative radiotherapy (PORT) in completely resected stage III-pN2 NSCLC.MethodsThis retrospective study included 244 patients with pathologically confirmed stage III-N2 NSCLC who underwent complete resection at our institution between 2014 and 2020. TILs were assessed with permanent full-face hematoxylin and eosin (H&E) sections and the evaluation of TILs was based on a published guideline. Patients were stratified into the TILlow or TILhigh group with a cutoff value of 50%. Kaplan-Meier method and Log‐rank test were utilized to assess disease-free survival (DFS) and overall survival (OS). Univariate and multivariate Cox regression analysis were conducted to determine prognostic indicators.ResultsAmong 244 patients, a total of 121 patients received PORT whereas 123 did not. TILs level in patients with PORT was significantly higher than that in patients without PORT (p < 0.001). High TILs level was significantly associated with an improved DFS and OS in all the entire chort (DFS, p < 0.001; OS, p = 0.001), PORT chort (DFS, p = 0.003; OS, p = 0.011) and non-PORT chort (DFS, p < 0.001; OS, p = 0.034). There were no significant survival differences between different treatment modalities in the low TILs infiltration (DFS, p = 0.244; OS, p = 0.404) and high TILs infiltration (DFS, p = 0.167; OS, p = 0.958) groups.ConclusionsTILs evaluated with H&E sections could represent a prognostic biomarker in patients with completely resected pN2 NSCLC, and high TILs infiltration was associated with favorable survival outcomes.The predictive value of TILs for PORT still need to be further explored in the future.

RWD89 Healthcare Resource Utilization and Health-Related Quality of Life in Patients With Resectable Non-Metastatic Non-Small Cell Lung Cancer Treated With Neoadjuvant Chemotherapy in China: A Real-World Survey

RWD89 Healthcare Resource Utilization and Health-Related Quality of Life in Patients With Resectable Non-Metastatic Non-Small Cell Lung Cancer Treated With Neoadjuvant Chemotherapy in China: A Real-World Survey

Response to Wu and Zhang

Response to Wu and Zhang

Osimertinib after Chemoradiotherapy in Stage III EGFR-Mutated NSCLC.

Osimertinib is a recommended treatment for advanced non-small-cell lung cancer (NSCLC) with an epidermal growth factor receptor (EGFR) mutation and as adjuvant treatment for resected EGFR-mutated NSCLC. EGFR-tyrosine kinase inhibitors have shown preliminary efficacy in unresectable stage III EGFR-mutated NSCLC. In this phase 3, double-blind, placebo-controlled trial, we randomly assigned patients with unresectable EGFR-mutated stage III NSCLC without progression during or after chemoradiotherapy to receive osimertinib or placebo until disease progression occurred (as assessed by blinded independent central review) or the regimen was discontinued. The primary end point was progression-free survival as assessed by blinded independent central review. A total of 216 patients who had undergone chemoradiotherapy were randomly assigned to receive osimertinib (143 patients) or placebo (73 patients). Osimertinib resulted in a significant progression-free survival benefit as compared with placebo: the median progression-free survival was 39.1 months with osimertinib versus 5.6 months with placebo, with a hazard ratio for disease progression or death of 0.16 (95% confidence interval [CI], 0.10 to 0.24; P<0.001). The percentage of patients who were alive and progression free at 12 months was 74% (95% CI, 65 to 80) with osimertinib and 22% (95% CI, 13 to 32) with placebo. Interim overall survival data (maturity, 20%) showed 36-month overall survival among 84% of patients with osimertinib (95% CI, 75 to 89) and 74% with placebo (95% CI, 57 to 85), with a hazard ratio for death of 0.81 (95% CI, 0.42 to 1.56; P = 0.53). The incidence of adverse events of grade 3 or higher was 35% in the osimertinib group and 12% in the placebo group; radiation pneumonitis (majority grade, 1 to 2) was reported in 48% and 38%, respectively. No new safety concerns emerged. Treatment with osimertinib resulted in significantly longer progression-free survival than placebo in patients with unresectable stage III EGFR-mutated NSCLC. (Funded by AstraZeneca; LAURA ClinicalTrials.gov number, NCT03521154.).