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01-08-2021 | NSCLC | Original Article

The surgical perspective in neoadjuvant immunotherapy for resectable non-small cell lung cancer

Authors: Long Jiang, Jia Huang, Shanshan Jiang, Wenwen Rong, Yaofeng Shen, Chongwu Li, Yu Tian, Junwei Ning, Xiaoke Chen, Yunhai Yang, Zhengping Ding, Ziming Li, Qingquan Luo

Published in: Cancer Immunology, Immunotherapy | Issue 8/2021

Abstract

Background

The recent novel conception of neoadjuvant immunotherapy has generated interest among surgeons worldwide, especially the lack of experience involving surgical treatment for the neoadjuvant immunotherapy population.

Methods

Patients with non-small cell lung cancer (NSCLC), who underwent neoadjuvant immunotherapy or chemo-immunotherapy, were retrospectively collected between September 2018 and April 2020. Demographic data, pathological and clinical features, therapeutic regimens and outcome data of all individuals were collected by retrospective chart review. Operative details, information of neoadjuvant therapy, were also abstracted.

Results

In total, 31 patients were included in the final analysis. The patients’ median age was 61 years. In total, 29 of the patients were males, while 2 were females. Patients received a median of 3 doses before resection. The median duration from final treatment to surgery was 34 days. After neoadjuvant treatment, post-treatment computed tomography scan showed that 24 patients had partial response. In total, 12 of 31 patients had a major pathological response, 15 pathological downstaging. Three patients had no residual viable tumor. A positive surgical margin was identified in 7 cases. One or more postoperative complications occurred in 18 of all 31 patients. In total, 26 patients underwent next-generation sequencing before surgery in total. Among them, 2 patients were detected STK11 mutations, none of whom had a major pathological response by final pathological examination.

Conclusions

Pulmonary resection after neoadjuvant immunotherapy or chemo-immunotherapy for resectable NSCLC appears to be safe with low operative mortality and morbidity rate in the current population.

Siegel RL, Miller KD, Jemal A (2020) Cancer statistics, 2020. CA Cancer J Clin. 70:7–30. https://doi.org/10.3322/caac.21590CrossRef

Bagcchi S (2017) Lung cancer survival only increases by a small amount despite recent treatment advances. Lancet Respir Med. 5:169. https://doi.org/10.1016/S2213-2600(17)30041-3CrossRefPubMed

Herbst RS, Morgensztern D, Boshoff C (2018) The biology and management of non-small cell lung cancer. Nature. 553:446–54. https://doi.org/10.1038/nature25183CrossRefPubMed

Hirsch FR, Scagliotti GV, Mulshine JL, Kwon R, Curran WJ Jr, Wu YL, Paz-Ares L (2017) Lung cancer: current therapies and new targeted treatments. Lancet. 389:299–311. https://doi.org/10.1016/S0140-6736(16)30958-8CrossRefPubMed

Garon EB, Hellmann MD, Rizvi NA et al (2019) Five-year overall survival for patients with advanced nonsmall-cell lung cancer treated with pembrolizumab: results from the phase I KEYNOTE-001 Study. J Clin Oncol. 37:2518–27. https://doi.org/10.1200/JCO.19.00934CrossRefPubMedPubMedCentral

Gandhi L, Rodriguez-Abreu D, Gadgeel S et al (2018) Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med. 378:2078–92. https://doi.org/10.1056/NEJMoa1801005CrossRefPubMed

DeBerardinis RJ (2020) Tumor microenvironment, metabolism, and immunotherapy. N Engl J Med. 382:869–71. https://doi.org/10.1056/NEJMcibr1914890CrossRefPubMed

Lin JJ, Shaw AT (2017) Raising the bar on first-line immunotherapy in lung cancer. Lancet Oncol. 18:2–3. https://doi.org/10.1016/S1470-2045(16)30594-0CrossRefPubMed

Ettinger DS, Wood DE, Aggarwal C et al (2019) NCCN guidelines Insights: non-small cell lung cancer, version 1.2020. J Natl Compr Canc Netw. 17:1464–72. https://doi.org/10.6004/jnccn.2019.0059CrossRefPubMed

10.

Forde PM, Chaft JE, Smith KN et al (2018) Neoadjuvant PD-1 blockade in resectable lung cancer. N Engl J Med. 378:1976–86. https://doi.org/10.1056/NEJMoa1716078CrossRefPubMedPubMedCentral

11.

Bott MJ, Yang SC, Park BJ et al (2019) Initial results of pulmonary resection after neoadjuvant nivolumab in patients with resectable non-small cell lung cancer. J Thorac Cardiovasc Surg. 158:269–76. https://doi.org/10.1016/j.jtcvs.2018.11.124CrossRefPubMed

12.

Provencio M, Nadal E, Insa A et al (2018) OA01.05 phase II study of neo-adjuvant chemo/immunotherapy for resectable stages IIIA non-small cell lung cancer- Nadim study-SLCG. J Thoracic Oncol. 13:320. https://doi.org/10.1016/j.jtho.2018.08.236CrossRef

13.

Altorki N, Borczuk A, Saxena A et al (2019) P2.04. J Thoracic Oncol. 14:746. https://doi.org/10.1016/j.jtho.2019.08.1597CrossRef

14.

Shu CA, Gainor JF, Awad MM et al (2020) Neoadjuvant atezolizumab and chemotherapy in patients with resectable non-small-cell lung cancer: an open-label, multicentre, single-arm, phase 2 trial. Lancet Oncol. 21:786–95. https://doi.org/10.1016/S1470-2045(20)30140-6CrossRefPubMed

15.

Cascone T, William WN, Weissferdt A et al (2019) Neoadjuvant nivolumab (N) or nivolumab plus ipilimumab (NI) for resectable non-small cell lung cancer (NSCLC): clinical and correlative results from the NEOSTAR study. J Clin Oncol 37:8504. https://doi.org/10.1200/JCO.2019.37.15_suppl.8504CrossRef

16.

Kwiatkowski DJ, Rusch VW, Chaft JE et al (2019) Neoadjuvant atezolizumab in resectable non-small cell lung cancer (NSCLC): Interim analysis and biomarker data from a multicenter study (LCMC3). J Clin Oncol 37:8503. https://doi.org/10.1200/JCO.2019.37.15_suppl.8503CrossRef

17.

Provencio M, Nadal E, Insa A et al (2019) Neoadjuvant chemo-immunotherapy for the treatment of stage IIIA resectable non-small-cell lung cancer (NSCLC): A phase II multicenter exploratory study—final data of patients who underwent surgical assessment. J Clin Oncol 37:8509. https://doi.org/10.1200/JCO.2019.37.15_suppl.8509CrossRef

18.

Broderick SR (2020) Adjuvant and neoadjuvant immunotherapy in non-small cell lung cancer. Thorac Surg Clin. 30:215–20. https://doi.org/10.1016/j.thorsurg.2020.01.001CrossRefPubMed

19.

Broderick SR, Bott MJ (2019) Neoadjuvant immunotherapy in patients with resectable non-small cell lung cancer. J Thorac Cardiovasc Surg. 158:1471–4. https://doi.org/10.1016/j.jtcvs.2019.06.114CrossRefPubMed

20.

Goldstraw P, Chansky K, Crowley J et al (2016) The IASLC Lung cancer staging project: proposals for revision of the TNM stage groupings in the forthcoming (eighth) edition of the TNM classification for lung cancer. J Thorac Oncol. 11:39–51. https://doi.org/10.1016/j.jtho.2015.09.009CrossRefPubMed

21.

Fernandez FG, Falcoz PE, Kozower BD, Salati M, Wright CD, Brunelli A (2015) The society of thoracic surgeons and the European Society of Thoracic Surgeons general thoracic surgery databases: joint standardization of variable definitions and terminology. Ann Thorac Surg. 99:368–76. https://doi.org/10.1016/j.athoracsur.2014.05.104CrossRefPubMed

22.

Hellmann MD, Chaft JE, William WN Jr et al (2014) Pathological response after neoadjuvant chemotherapy in resectable non-small-cell lung cancers: proposal for the use of major pathological response as a surrogate endpoint. Lancet Oncol. 15:e42-50. https://doi.org/10.1016/S1470-2045(13)70334-6CrossRefPubMedPubMedCentral

23.

Popovic A, Jaffee EM, Zaidi N (2018) Emerging strategies for combination checkpoint modulators in cancer immunotherapy. J Clin Invest. 128:3209–18. https://doi.org/10.1172/JCI120775CrossRefPubMedPubMedCentral

24.

Havel JJ, Chowell D, Chan TA (2019) The evolving landscape of biomarkers for checkpoint inhibitor immunotherapy. Nat Rev Cancer. 19:133–50. https://doi.org/10.1038/s41568-019-0116-xCrossRefPubMedPubMedCentral

25.

Ribas A, Wolchok JD (2018) Cancer immunotherapy using checkpoint blockade. Science. 359:1350–5. https://doi.org/10.1126/science.aar4060CrossRefPubMedPubMedCentral

26.

Non-small Cell Lung Cancer Collaborative Group (1995) Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials. Non-small Cell Lung Cancer Collaborative Group BMJ 311:899–909

27.

Gilligan D, Nicolson M, Smith I et al (2007) Preoperative chemotherapy in patients with resectable non-small cell lung cancer: results of the MRC LU22/NVALT 2/EORTC 08012 multicentre randomised trial and update of systematic review. Lancet. 369:1929–37. https://doi.org/10.1016/S0140-6736(07)60714-4CrossRefPubMed

28.

Hellmann MD, Nathanson T, Rizvi H et al (2018) Genomic features of response to combination immunotherapy in patients with advanced non-small-cell lung cancer. Cancer Cell. 33(843–52):e4. https://doi.org/10.1016/j.ccell.2018.03.018CrossRef

29.

Eichhorn F, Klotz LV, Bischoff H, Thomas M, Lasitschka F, Winter H, Hoffmann H, Eichhorn ME (2019) Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable nodal positive stage II/IIIa non-small-cell lung cancer (NSCLC): the NEOMUN trial. BMC Cancer. 19:413. https://doi.org/10.1186/s12885-019-5624-2CrossRefPubMedPubMedCentral

30.

Gao S, Li N, Gao S et al (2020) Neoadjuvant PD-1 inhibitor (Sintilimab) in NSCLC. J Thorac Oncol. 15:816–26. https://doi.org/10.1016/j.jtho.2020.01.017CrossRefPubMed

31.

Kennedy LB, Salama AKS (2020) A review of cancer immunotherapy toxicity. CA Cancer J Clin. 70:86–104. https://doi.org/10.3322/caac.21596CrossRefPubMed

32.

Yang CJ, McSherry F, Mayne NR et al (2018) Surgical outcomes after neoadjuvant chemotherapy and ipilimumab for non-small cell lung cancer. Ann Thorac Surg. 105:924–9. https://doi.org/10.1016/j.athoracsur.2017.09.030CrossRefPubMed

33.

Thorsteinsson H, Alexandersson A, Oskarsdottir GN, Skuladottir R, Isaksson HJ, Jonsson S, Gudbjartsson T (2012) Resection rate and outcome of pulmonary resections for non-small-cell lung cancer: a nationwide study from Iceland. J Thorac Oncol. 7:1164–9. https://doi.org/10.1097/JTO.0b013e318252d022CrossRefPubMed

34.

Dy GK, Bogner PN, Tan W et al (2014) Phase II study of perioperative chemotherapy with cisplatin and pemetrexed in non-small-cell lung cancer. J Thorac Oncol. 9:222–30. https://doi.org/10.1097/JTO.0000000000000062CrossRefPubMed

35.

Pan A, Liu L, Wang C et al (2020) Association of public health interventions with the epidemiology of the COVID-19 outbreak in Wuhan. JAMA, China. https://doi.org/10.1001/jama.2020.6130CrossRef

36.

Chen S, Yang J, Yang W, Wang C, Barnighausen T (2020) COVID-19 control in China during mass population movements at New Year. Lancet. 395:764–6. https://doi.org/10.1016/S0140-6736(20)30421-9CrossRefPubMedPubMedCentral

Title: The surgical perspective in neoadjuvant immunotherapy for resectable non-small cell lung cancer
Authors: Long Jiang
Jia Huang
Shanshan Jiang
Wenwen Rong
Yaofeng Shen
Chongwu Li
Yu Tian
Junwei Ning
Xiaoke Chen
Yunhai Yang
Zhengping Ding
Ziming Li
Qingquan Luo
Publication date: 01-08-2021
Publisher: Springer Berlin Heidelberg
Keywords: NSCLC
NSCLC
Cytostatic Therapy
Published in: Cancer Immunology, Immunotherapy / Issue 8/2021
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-021-02847-1

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