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.

Evidence 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. This 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. Among 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. TILs 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.

Li J ，Li L ，Wang J ，Liu N ，Liu H ，Xu F ，Li M ，Yuan S ... -  《RESPIRATORY RESEARCH》

Prognostic value of tumor-infiltrating lymphocytes for patients with completely resected stage IIIA(N2) non-small cell lung cancer.

Feng W ，Li Y ，Shen L ，Cai XW ，Zhu ZF ，Chang JH ，Xiang JQ ，Zhang YW ，Chen HQ ，Fu XL ... -  《Oncotarget》

Evaluation of tumor-infiltrating lymphocytes using routine H&E slides predicts patient survival in resected non-small cell lung cancer.

The presence of tumor-infiltrating lymphocytes (TILs) positively impacts the outcome of non-small cell lung cancer (NSCLC) patients. Most previous studies have assessed TILs using different immunohistochemical assays. The purpose of this study was to develop and validate a histopathological scoring model for the assessment of TILs in whole-tissue hematoxylin and eosin (H&E)-stained section slides of NSCLC patients and to evaluate the model in an immunoscore setting. Therefore, TIL was evaluated manually on H&E slides from 537 surgical specimens of primary resected stage I-III NSCLC patients. Using stromal TIL score as a stepwise discrete variable, increasing survival was seen with rising TIL level: disease-specific survival (DSS; P = .008), overall survival (P = .036) and disease-free survival (P = .006). Subgroup analysis revealed that high stromal TILs level was associated with superior DSS (P = .047) in patients with squamous cell carcinoma, but not in patients with adenocarcinoma. Multivariable analysis confirmed that high TIL levels independently predict improved prognosis for all endpoints in the overall cohort. In conclusion, high stromal TIL level is an independent favorable prognostic factor in stage I-III NSCLC patients. The comprehensive histological evaluation conducted in this study may be helpful in streamlining TIL quantification for routine clinical use in a future NSCLC immunoscore setting.

Rakaee M ，Kilvaer TK ，Dalen SM ，Richardsen E ，Paulsen EE ，Hald SM ，Al-Saad S ，Andersen S ，Donnem T ，Bremnes RM ，Busund LT ... -  《-》

The Prognostic Role of PORT and EGFR Mutation Status in Completely Resected Stage IIIA/N2 Non-Small Cell Lung Cancer Patients with Postoperative Chemotherapy.

Background: The treatment choice for completely resected stage IIIA/N2 non-small cell lung cancer (NSCLC) patients is still controversial now. Our study aims to identify potential prognostic factors in stage IIIA/N2 NSCLC patients with complete surgical resection and postoperative chemotherapy. Methods: In this study, we screened the stage IIIA/N2 NSCLC patients diagnosed in the Affiliated Cancer Hospital of Zhengzhou University from 2015 to 2019. Completely resected patients with postoperative chemotherapy (PCT) were enrolled. The univariate and multivariate COX proportional hazards regression analyses were used to identify the prognostic factors. The Kaplan-Meier survival curve was used to compare the disease-free survival (DFS) and overall survival (OS) in the subgroup analyses. Results: 180 patients were collected, including 142 patients with PCT treatment alone and 38 patients with postoperative radiotherapy (PORT) treatment. The median DFS was 17.8 months (95% CI: 16.5-19.1 months) and the median OS was 50.6 months (47.4-53.9 months) in all the patients. The median DFS of the PORT group was significantly longer than the PCT group (38.7 vs 16.7 months, p < 0.001). Epidermal growth factor receptor (EGFR) mutation-positive patients had a worse DFS compared with EGFR mutation-negative patients (16.8 vs 18.0 months, p = 0.032). Possible prognostic factors were evaluated through univariate COX regression analysis. The further multivariate COX regression analysis showed that patients with PORT (HR: 0.318, 95% CI: 0.185-0.547, p < 0.001), EGFR mutation-negative (HR: 0.678, 95% CI: 0.492-0.990, p = 0.044), T1 (HR: 0.661, 95% CI: 0.472-0.925, p = 0.016), and lobectomy (HR: 0.423, 95% CI: 0.191-0.935, p = 0.034), had better DFS. The only independent prognostic factor of OS was the type of surgery (p = 0.013). Conclusion: PORT might improve the DFS of stage IIIA/N2 NSCLC patients with complete surgical resection and PCT, but it cannot increase OS. Besides, EGFR mutation status, T stage, and type of surgery are possible independent prognostic factors for DFS, and type of surgery is associated with OS. These factors remain to be clarified in further studies.

Yang H ，Wang K ，Li S ，Li Y ，Yuan L ... -  《-》

Prognostic factors for resected non-small cell lung cancer with pN2 status: implications for use of postoperative radiotherapy.

Moretti L ，Yu DS ，Chen H ，Carbone DP ，Johnson DH ，Keedy VL ，Putnam JB Jr ，Sandler AB ，Shyr Y ，Lu B ... -  《-》