{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:24:41Z","timestamp":1760149481288,"version":"build-2065373602"},"reference-count":32,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T00:00:00Z","timestamp":1692230400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Introduction: Predictive biomarkers associated with pathological response, progression precluding surgery, and\/or recurrence after surgery are needed for patients with resectable non-small cell lung carcinoma (NSCLC) treated by neoadjuvant treatment. We evaluated the clinical impact of the pretreatment tumor growth rate (TGR0) and radiological response for patients with resectable NSCLC treated with neoadjuvant therapies. Methods: Consecutive patients with resectable stage IB (\u22654 cm) to IIIA NSCLC treated by neoadjuvant platinum-doublet chemotherapy with or without nivolumab at our tertiary center were retrospectively analyzed. TGR0 and RECIST objective responses were determined. Multivariable analyses identified independent predictors of event-free survival (EFS), overall survival (OS), and major pathological response (MPR). Results: Between November 2017 and December 2022, 32 patients (mean [SD] age, 63.8 [8.0] years) were included. At a median follow-up of 54.8 months (95% CI, 42.3\u201360.4 months), eleven patients (34%) experienced progression or recurrence, and twelve deaths (38%) were recorded. The TGR0 cutoff of 30%\/month remained the only independent factor associated with EFS (HR = 0.04; 95% CI, 0.01\u20130.3; p = 0.003) and OS (HR = 0.2; 95% CI, 0.03\u20130.7; p = 0.01). The TGR0 cut-off had a mean time-dependent AUC of 0.83 (95% CI, 0.64\u20130.95) and 0.80 (95% CI, 0.62\u20130.97) for predicting EFS and OS, respectively. Fifteen of 26 resection cases (58%) showed MPR including nine with pathological complete responses (35%). Only the objective response of the primary tumor was associated with MPR (OR = 27.5; 95% CI, 2.6\u2013289.1; p = 0.006). Conclusions: Assessment of TGR0 can identify patients who should benefit from neoadjuvant treatment. A tumor objective response might be a predictor of MPR after neoadjuvant treatment, which will help to adapt surgical management.<\/jats:p>","DOI":"10.3390\/cancers15164158","type":"journal-article","created":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T10:42:29Z","timestamp":1692268949000},"page":"4158","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Pretreatment Tumor Growth Rate and Radiological Response as Predictive Markers of Pathological Response and Survival in Patients with Resectable Lung Cancer Treated by Neoadjuvant Treatment"],"prefix":"10.3390","volume":"15","author":[{"given":"Toulsie","family":"Ramtohul","sequence":"first","affiliation":[{"name":"Department of Radiology, Institut Curie Paris, PSL Research University, 75005 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L\u00e9a","family":"Challier","sequence":"additional","affiliation":[{"name":"Department of Radiology, Institut Curie Paris, PSL Research University, 75005 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8378-8432","authenticated-orcid":false,"given":"Vincent","family":"Servois","sequence":"additional","affiliation":[{"name":"Department of Radiology, Institut Curie Paris, PSL Research University, 75005 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolas","family":"Girard","sequence":"additional","affiliation":[{"name":"Institut du Thorax Curie Montsouris, Institut Curie, 75005 Paris, France"},{"name":"Paris Saclay Campus, Versailles Saint Quentin University, 78000 Versailles, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/S0140-6736(21)00312-3","article-title":"Lung Cancer","volume":"398","author":"Thai","year":"2021","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1056\/NEJMoa1911793","article-title":"Reduced Lung-Cancer Mortality with Volume CT Screening in a Randomized Trial","volume":"382","author":"Scholten","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"publisher","first-page":"1162","DOI":"10.1093\/annonc\/mdz117","article-title":"Prolonged Lung Cancer Screening Reduced 10-Year Mortality in the MILD Trial: New Confirmation of Lung Cancer Screening Efficacy","volume":"30","author":"Pastorino","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_4","doi-asserted-by":"publisher","first-page":"e2137508","DOI":"10.1001\/jamanetworkopen.2021.37508","article-title":"Association of Stage Shift and Population Mortality Among Patients with Non\u2013Small Cell Lung Cancer","volume":"4","author":"Flores","year":"2021","journal-title":"JAMA Netw. Open"},{"key":"ref_5","doi-asserted-by":"publisher","first-page":"S898","DOI":"10.21037\/jtd.2018.01.172","article-title":"Surgical Treatment for Early Stage Non-Small Cell Lung Cancer","volume":"10","author":"Raman","year":"2018","journal-title":"J. Thorac. Dis."},{"key":"ref_6","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1159\/000458533","article-title":"Recurrence and Risk Factors for Relapse in Patients with Non-Small Cell Lung Cancer Treated by Surgery with Curative Intent","volume":"92","author":"Cruz","year":"2017","journal-title":"Oncology"},{"key":"ref_7","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.suronc.2013.04.002","article-title":"Local Recurrence Following Lung Cancer Surgery: Incidence, Risk Factors, and Outcomes","volume":"22","author":"Fedor","year":"2013","journal-title":"Surg. Oncol."},{"key":"ref_8","doi-asserted-by":"publisher","first-page":"5218","DOI":"10.1002\/cncr.24625","article-title":"Local Recurrence after Surgery for Early Stage Lung Cancer: An 11-Year Experience with 975 Patients","volume":"115","author":"Kelsey","year":"2009","journal-title":"Cancer"},{"key":"ref_9","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.lungcan.2008.05.002","article-title":"Magnitude of Benefit of Adjuvant Chemotherapy for Non-Small Cell Lung Cancer: Meta-Analysis of Randomized Clinical Trials","volume":"63","author":"Bria","year":"2009","journal-title":"Lung Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"NSCLC Meta-Analyses Collaborative Group (2010). Adjuvant Chemotherapy, with or without Postoperative Radiotherapy, in Operable Non-Small-Cell Lung Cancer: Two Meta-Analyses of Individual Patient Data. Lancet, 375, 1267\u20131277.","DOI":"10.1016\/S0140-6736(10)60059-1"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"NSCLC Meta-Analysis Collaborative Group (2014). Preoperative Chemotherapy for Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis of Individual Participant Data. Lancet, 383, 1561\u20131571.","DOI":"10.1016\/S0140-6736(13)62159-5"},{"key":"ref_12","doi-asserted-by":"publisher","first-page":"1973","DOI":"10.1056\/NEJMoa2202170","article-title":"Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer","volume":"386","author":"Forde","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"publisher","first-page":"2924","DOI":"10.1200\/JCO.21.02660","article-title":"Overall Survival and Biomarker Analysis of Neoadjuvant Nivolumab Plus Chemotherapy in Operable Stage IIIA Non\u2013Small-Cell Lung Cancer (NADIM Phase II Trial)","volume":"40","author":"Provencio","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_14","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1158\/1078-0432.CCR-13-2098","article-title":"Tumor Growth Rate Is an Early Indicator of Antitumor Drug Activity in Phase I Clinical Trials","volume":"20","author":"Fernandez","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_15","doi-asserted-by":"publisher","first-page":"6692","DOI":"10.1158\/1078-0432.CCR-19-0963","article-title":"Tumor Growth Rate as a Validated Early Radiological Biomarker Able to Reflect Treatment-Induced Changes in Neuroendocrine Tumors: The GREPONET-2 Study","volume":"25","author":"Lamarca","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_16","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1038\/s41416-022-01793-8","article-title":"Tumor Growth Rate Improves Tumor Assessment and First-Line Systemic Treatment Decision-Making for Immunotherapy in Patients with Liver Metastatic Uveal Melanoma","volume":"127","author":"Ramtohul","year":"2022","journal-title":"Br. J. Cancer"},{"key":"ref_17","doi-asserted-by":"publisher","first-page":"95","DOI":"10.21037\/atm.2019.02.14","article-title":"Clinical Significance of Pretreatment Tumor Growth Rate for Locally Advanced Non-Small Cell Lung Cancer","volume":"7","author":"Osorio","year":"2019","journal-title":"Ann. Transl. Med."},{"key":"ref_18","doi-asserted-by":"publisher","first-page":"1920","DOI":"10.1158\/1078-0432.CCR-16-1741","article-title":"Hyperprogressive Disease Is a New Pattern of Progression in Cancer Patients Treated by Anti-PD-1\/PD-L1","volume":"23","author":"Champiat","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_19","doi-asserted-by":"publisher","first-page":"1281","DOI":"10.1016\/j.jtho.2020.05.020","article-title":"Neoadjuvant Immunotherapy for NSCLC: Current Concepts and Future Approaches","volume":"15","author":"Uprety","year":"2020","journal-title":"J. Thorac. Oncol."},{"key":"ref_20","doi-asserted-by":"publisher","first-page":"621329","DOI":"10.3389\/fonc.2020.621329","article-title":"Pre-Treatment Tumor Growth Rate Predicts Clinical Outcomes of Patients With Advanced Non-Small Cell Lung Cancer Undergoing Anti-PD-1\/PD-L1 Therapy","volume":"10","author":"He","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_21","doi-asserted-by":"publisher","first-page":"e002350","DOI":"10.1136\/jitc-2021-002350","article-title":"Pretreatment Metastatic Growth Rate Determines Clinical Outcome of Advanced Melanoma Patients Treated with Anti-PD-1 Antibodies: A Multicenter Cohort Study","volume":"9","author":"Wagner","year":"2021","journal-title":"J. Immunother. Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Matsumura, S., Kato, T., Kujime, Y., Kitakaze, H., Nakano, K., Hongo, S., Yoshioka, I., Okumi, M., Nonomura, N., and Takada, S. (2023). Pre-Treatment Metastatic Growth Rate Is Associated with Clinical Outcome in Patients with Metastatic Renal Cell Carcinoma Treated with Nivolumab. BMC Urol., 23.","DOI":"10.1186\/s12894-023-01248-z"},{"key":"ref_23","doi-asserted-by":"publisher","first-page":"100673","DOI":"10.1016\/j.eclinm.2020.100673","article-title":"Predicting Hyperprogressive Disease in Patients with Advanced Hepatocellular Carcinoma Treated with Anti-Programmed Cell Death 1 Therapy","volume":"31","author":"Zhang","year":"2021","journal-title":"EClinicalMedicine"},{"key":"ref_24","doi-asserted-by":"publisher","first-page":"763790","DOI":"10.3389\/fonc.2021.763790","article-title":"Circulating Tumor DNA and Minimal Residual Disease (MRD) in Solid Tumors: Current Horizons and Future Perspectives","volume":"11","author":"Peng","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_25","doi-asserted-by":"publisher","first-page":"1482","DOI":"10.1093\/annonc\/mdw168","article-title":"Targeting the Tumor Microenvironment: Removing Obstruction to Anticancer Immune Responses and Immunotherapy","volume":"27","author":"Pitt","year":"2016","journal-title":"Ann. Oncol."},{"key":"ref_26","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/s41568-018-0081-9","article-title":"The Lung Microenvironment: An Important Regulator of Tumour Growth and Metastasis","volume":"19","author":"Altorki","year":"2019","journal-title":"Nat. Rev. Cancer"},{"key":"ref_27","doi-asserted-by":"publisher","first-page":"2872","DOI":"10.1200\/JCO.21.00276","article-title":"SAKK 16\/14: Durvalumab in Addition to Neoadjuvant Chemotherapy in Patients with Stage IIIA(N2) Non\u2013Small-Cell Lung Cancer\u2014A Multicenter Single-Arm Phase II Trial","volume":"39","author":"Rothschild","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_28","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1056\/NEJMoa2215530","article-title":"Perioperative Nivolumab and Chemotherapy in Stage III Non-Small-Cell Lung Cancer","volume":"389","author":"Provencio","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_29","doi-asserted-by":"publisher","first-page":"e42","DOI":"10.1016\/S1470-2045(13)70334-6","article-title":"Pathological Response after Neoadjuvant Chemotherapy in Resectable Non-Small-Cell Lung Cancers: Proposal for the Use of Major Pathological Response as a Surrogate Endpoint","volume":"15","author":"Hellmann","year":"2014","journal-title":"Lancet Oncol."},{"key":"ref_30","doi-asserted-by":"publisher","first-page":"100384","DOI":"10.1016\/j.jtocrr.2022.100384","article-title":"Association of Pathologic Complete Response and Long-Term Survival Outcomes Among Patients Treated with Neoadjuvant Chemotherapy or Chemoradiotherapy for NSCLC: A Meta-Analysis","volume":"3","author":"Rosner","year":"2022","journal-title":"JTO Clin. Res. Rep."},{"key":"ref_31","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.1016\/j.jtho.2021.03.029","article-title":"Evaluation of Pathologic Response in Lymph Nodes of Patients with Lung Cancer Receiving Neoadjuvant Chemotherapy","volume":"16","author":"Pataer","year":"2021","journal-title":"J. Thorac. Oncol."},{"key":"ref_32","doi-asserted-by":"publisher","first-page":"563","DOI":"10.21037\/tlcr-20-509","article-title":"Surgery after Neoadjuvant Immunotherapy in Patients with Resectable Non-Small Cell Lung Cancer","volume":"10","author":"Huynh","year":"2021","journal-title":"Transl. Lung Cancer Res."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/16\/4158\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:36:15Z","timestamp":1760128575000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/16\/4158"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,17]]},"references-count":32,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["cancers15164158"],"URL":"https:\/\/doi.org\/10.3390\/cancers15164158","relation":{},"ISSN":["2072-6694"],"issn-type":[{"type":"electronic","value":"2072-6694"}],"subject":[],"published":{"date-parts":[[2023,8,17]]}}}