Retrospective Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Nov 24, 2021; 12(11): 1047-1063
Published online Nov 24, 2021. doi: 10.5306/wjco.v12.i11.1047
Pathological response to neoadjuvant therapy with chemotherapy vs chemoradiotherapy in stage III NSCLC-contribution of IASLC recommendations
Diego Muñoz-Guglielmetti, David Sanchez-Lorente, Roxana Reyes, Daniel Martinez, Carmen Lucena, Marc Boada, Pilar Paredes, Marta Parera-Roig, Ivan Vollmer, Joel Mases, Roberto Martin-Deleon, Sergi Castillo, Mariana Benegas, Silvia Muñoz, Maria Mayoral, Carla Cases, Meritxell Mollà, Francesc Casas
Diego Muñoz-Guglielmetti, Joel Mases, Carla Cases, Radiation Oncology Department, Hospital Clínic de Barcelona, Barcelona 08036, Cataluña, Spain
David Sanchez-Lorente, Marc Boada, Thoracic Surgery Department, Thoracic Unit, Hospital Clínic de Barcelona, Barcelona 08036, Cataluña, Spain
Roxana Reyes, Medical Oncology Department, Thoracic Unit, Hospital Clínic de Barcelona, Barcelona 08036, Cataluña, Spain
Daniel Martinez, Pathology Department, Thoracic Unit, Hospital Clínic de Barcelona, Barcelona 08036, Cataluña, Spain
Carmen Lucena, Pneumology Department, Thoracic Unit, Hospital Clínic de Barcelona, Barcelona 08036, Cataluña, Spain
Pilar Paredes, Nuclear Medicine Department, Faculty of Medicine of University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona 08036, Cataluña, Spain
Marta Parera-Roig, Medical Oncology Department, Hospital Comarcal de Vic, Vic 08500, Cataluña, Spain
Ivan Vollmer, Mariana Benegas, Radiology Department, Thoracic Unit, Hospital Clínic de Barcelona, Barcelona 08036, Cataluña, Spain
Roberto Martin-Deleon, Pneumology Department, Hospital Universitario Reina Sofia, Córdoba 14004, Andalucía, Spain
Sergi Castillo, Medical Oncology Department, Hospital de Mollet, Mollet 08100, Cataluña, Spain
Silvia Muñoz, Medical Oncology Department, Hospital General de Granollers, Granollers 08402, Cataluña, Spain
Maria Mayoral, Nuclear Medicine Department, Thoracic Unit, Hospital Clínic de Barcelona, Barcelona 08036, Cataluña, Spain
Meritxell Mollà, Francesc Casas, Radiation Oncology Department, Thoracic Unit, Hospital Clínic de Barcelona, Barcelona 08036, Cataluña, Spain
Author contributions: Muñoz Guglielmetti D, Sanchez-Lorente D, Reyes R, Martinez D, Lucena C, Boada M, Paredes P, Parera-Roig M, Vollmer I, Mases J, Martin-Deleon R, Castillo S, Benegas M, Muñoz S, Mayoral M, Cases C, Mollà M and Casas F collaborated in the preparation of this manuscript; Statistical analyses and the final review were performed by Muñoz Guglielmetti D.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of the Hospital Clínic de Barcelona.
Conflict-of-interest statement: We have no conflict of interest or financial relationships to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Diego Muñoz-Guglielmetti, MD, Doctor, Radiation Oncology, Hospital Clínic de Barcelona, Carrer de Villarroel 170, Barcelona 08036, Cataluña, Spain. dimunoz@clinic.cat
Received: March 26, 2021
Peer-review started: March 26, 2021
First decision: June 16, 2021
Revised: June 22, 2021
Accepted: October 25, 2021
Article in press: October 25, 2021
Published online: November 24, 2021
Processing time: 237 Days and 17.6 Hours
Abstract
BACKGROUND

Neoadjuvant treatment (NT) with chemotherapy (Ch) is a standard option for resectable stage III (N2) NSCLC. Several studies have suggested benefits with the addition of radiotherapy (RT) to NT Ch. The International Association for the Study of Lung Cancer (IASLC) published recommendations for the pathological response (PHR) of NSCLC resection specimens after NT.

AIM

To contribute to the IASLC recommendations showing our results of PHR to NT Ch vs NT chemoradiotherapy (ChRT).

METHODS

We analyzed 67 consecutive patients with resectable stage III NSCLC with positive mediastinal nodes treated with surgery after NT Ch or NT ChRT between 2013 and 2020. After NT, all patients were evaluated for radiological response (RR) according to Response Evaluation Criteria in Solid Tumours criteria and evaluated for surgery by a specialized group of thoracic surgeons. All histological samples were examined by the same two pathologists. PHR was evaluated by the percentage of viable cells in the tumor and the resected lymph nodes.

RESULTS

Forty patients underwent NT ChRT and 27 NT Ch. Fifty-six (83.6%) patients underwent surgery (35 ChRT and 21 Ch). The median time from ChRT to surgery was 6 wk (3-19) and 8 wk (3-21) for Ch patients. We observed significant differences in RR, with disease progression in 2.5% and 14.8% of patients with ChRT and Ch, respectively, and partial response in 62.5% ChRT vs 29.6% Ch (P = 0.025). In PHR we observed ≤ 10% viable cells in the tumor in 19 (54.4%) and 2 cases (9.5%), and in the resected lymph nodes (RLN) 30 (85.7%) and 7 (33.3%) in ChRT and Ch, respectively (P = 0.001). Downstaging was greater in the ChRT compared to the Ch group (80% vs 33.3%; P = 0.002). In the univariate analysis, NT ChRT had a significant impact on partial RR [odds ratio (OR) 12.5; 95% confidence interval (CI): 1.21 - 128.61; P = 0.034], a decreased risk of persistence of cancer cells in the tumor and RLN and an 87.5% increased probability for achieving downstaging (OR 8; 95%CI: 2.34-27.32; P = 0.001).

CONCLUSION

We found significant benefits in RR and PHR by adding RT to Ch as NT. A longer follow-up is necessary to assess the impact on clinical outcomes.

Keywords: Non-small cell lung cancer; Chemotherapy; Chemoradiotherapy; Neoadjuvant treatment; Resectable stage III; Pathological response

Core Tip: Preoperative chemotherapy (Ch) has become a standard treatment option, especially in resectable stage III (primarily N2) non-small cell lung cancer (NSCLC). Phase II and phase III studies have raised the question as to whether preoperative Ch plus radiotherapy provides any additional benefits to preoperative Ch. The objective of our retrospective study was to contribute (with an experienced team of medical oncologists, radiation oncologists, thoracic surgeons, and pathologists) to the International Association for the Study of Lung Cancer recommendations in relation to differences in the pathological evaluation of tumors and mediastinal and hilar nodes in resectable stage III NSCLC, comparing neoadjuvant Ch vs chemoradiotherapy.