Prognostic factors in neoadjuvant immunotherapy for non-small cell lung cancer：pathologic lymph node metastasis and primary tumor response

doi:10.3969/j.issn.1006-7795.2024.04.014

Abstract

Abstract: Objective To investigate the prognostic impact of pathologic lymph node metastasis and primary tumor response after neoadjuvant immunotherapy in patients with non-small cell lung cancer (NSCLC). Methods Clinicopathological data of 40 NSCLC patients who underwent surgical resection after neoadjuvant immunotherapy were retrospectively analyzed. The relationships of pathologic nodal stage (N1/N2) and primary tumor response ［pathological complete response (pCR)/major pathological response (MPR)/non-objective response (non-OR)］with progression-free survival (PFS) were evaluated, and a prognostic risk stratification model was established. Results Pathologic nodal stage and primary tumor response were not significantly associated with PFS when considered separately. However, their interaction had a significant impact on prognosis： for N1 patients, the ones with pCR/MPR had better PFS than those with non-OR (P =0.038); for N2 patients, primary tumor response was not significantly associated with PFS. Based on the interaction, patients were stratified into low-risk (N1+pCR/MPR) and high-risk (N1+non-OR/N2) groups, with significant differences in PFS (P =0.003). Conclusions The interaction between pathologic lymph node metastasis and primary tumor response is a key prognostic factor in NSCLC after neoadjuvant immunotherapy. The prognostic risk stratification model based on their interaction may help guide individualized treatment decisions, but prospective validation is needed.

Key words: non-small cell lung cancer, neoadjuvant immunotherapy, pathologic lymph node metastasis, primary tumor response, prognosis

CLC Number:

R734.2

Xu Yuan, Liang Naixin, Liu Hongsheng. Prognostic factors in neoadjuvant immunotherapy for non-small cell lung cancer：pathologic lymph node metastasis and primary tumor response[J]. Journal of Capital Medical University, doi: 10.3969/j.issn.1006-7795.2024.04.014.

References

［1］ Siegel R L, Miller K D, Statistics J A C, et al. Cancer statistics, 2020［J］. CA Cancer J Clin, 2020, 70(1): 7-30.
［2］ Blumenthal G M, Bunn P A J, Chaft J E, et al. Current status and future perspectives on neoadjuvant therapy in lung cancer［J］. J Thorac Oncol, 2018, 13(12): 1818-1831.
［3］ Forde P M, Chaft J E, Smith K N, et al. Neoadjuvant PD-1 blockade in resectable lung cancer［J］. N Engl J Med, 2018, 378(21): 1976-1986.
［4］ Cascone T, William W N J, Weissferdt A, et al. Neoadjuvant nivolumab or nivolumab plus ipilimumab in operable non-small cell lung cancer: the phase 2 randomized NEOSTAR trial［J］. Nat Med, 2021, 27(3): 504-514.
［5］ Hellmann M D, Chaft J E, William W N J, et al. Pathological response after neoadjuvant chemotherapy in resectable non-small-cell lung cancers: proposal for the use of major pathological response as a surrogate endpoint［J］. Lancet Oncol, 2014, 15(1): e42-e50.
［6］ Qu Y, Emoto K, Eguchi T K H, et al. Pathologic assessment after neoadjuvant chemotherapy for NSCLC: importance and implications of distinguishing adenocarcinoma from squamous cell carcinoma［J］. J Thorac Oncol, 2019, 14(3): 482-493.
［7］ Ren S J, Wang C G, Shen J F, et al. Neoadjuvant immunotherapy with resectable non-small cell lung cancer: recent advances and future challenges［J］. J Thorac Dis, 2020, 12(4): 1615-1620.
［8］ Zhang J J, Ji Z C, Caushi J X, et al. Compartmental analysis of t-cell clonal dynamics as a function of pathologic response to neoadjuvant PD-1 blockade in resectable Non-Small cell lung cancer［J］. Clin Cancer Res, 2020, 26(6): 1327-1337.
［9］ Bott M J, Yang S C, Park B J, et al. Initial results of pulmonary resection after neoadjuvant nivolumab in patients with resectable non-small cell lung cancer［J］. J Thorac Cardiovasc Surg, 2019, 158(1): 269-276.
［10］ Detterbeck F C, Boffa D J, Kim A W, et al. The eighth edition lung cancer stage classification［J］. Chest, 2017, 151(1): 193-203.
［11］ Zhu J W, Li R, Tiselius E, et al. Immunotherapy (excluding checkpoint inhibitors) for stage I to Ⅲ non-small cell lung cancer treated with surgery or radiotherapy with curative intent［J］. Cochrane Database Syst Rev, 2017, 12(12): CD011300.
［12］ Bott M J, Cools-Lartigue J, Tan K S, et al. Safety and feasibility of lung resection after immunotherapy for metastatic or unresectable tumors［J］. Ann Thorac Surg, 2018, 106(1): 178-183.
［13］ Garon E B, Hellmann M D, Costa E C, et al. Five-year overall survival for patients with advanced non-small-cell lung cancer treated with pembrolizumab: results from the phase I KEYNOTE-001 study［J］. J Clin Oncol, 2019, 37(28): 2518-2527.
［14］ Cottrell T R, Thompson E D, Forde P M, et al. Pathologic features of response to neoadjuvant anti-PD-1 in resected non-small-cell lung carcinoma: a proposal for quantitative immune-related pathologic response criteria (irPRC)［J］. Ann Oncol, 2018, 29(8): 1853-1860.
［15］ Stein J E, Lipson E J, Cottrell T R, et al. Pan-tumor pathologic scoring of response to PD-(L)1 blockade［J］. Clin Cancer Res, 2020, 26(3): 545-551.

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