High-dose neoadjuvant chemoradiotherapy versus chemotherapy alone followed by surgery in potentially-resectable stage IIIA-N2 NSCLC. A multi-institutional retrospective study by the Oncologic Group for the Study of Lung Cancer (Spanish Radiation Oncology Society)

Sara Montemuiño; Núria Rodriguez de Dios; Margarita Martín; Begoña Taboada; Patricia Calvo-Crespo; María Pilar Samper-Ots; José Luis López-Guerra; M López-Mata; Josep Jové-Teixidó; Verónica Díaz-Díaz; Lourdes de Ingunza-Barón; Mauricio Murcia-Mejía; Marisa Chust; Tamara García-Cañibano; María Luz Couselo; María Mar Puertas; Elia Del Cerro; Javier Moradiellos; Sergio Amor; A Varela; I J Thuissard; David Sanz-Rosa; Felipe Couñago

doi:10.1016/j.rpor.2020.03.006

High-dose neoadjuvant chemoradiotherapy versus chemotherapy alone followed by surgery in potentially-resectable stage IIIA-N2 NSCLC. A multi-institutional retrospective study by the Oncologic Group for the Study of Lung Cancer (Spanish Radiation Oncology Society)

Rep Pract Oncol Radiother. 2020 May-Jun;25(3):447-455. doi: 10.1016/j.rpor.2020.03.006. Epub 2020 Mar 18.

Authors

Sara Montemuiño¹, Núria Rodriguez de Dios^{2

3}, Margarita Martín⁴, Begoña Taboada⁵, Patricia Calvo-Crespo⁵, María Pilar Samper-Ots⁶, José Luis López-Guerra⁷, M López-Mata⁸, Josep Jové-Teixidó⁹, Verónica Díaz-Díaz¹⁰, Lourdes de Ingunza-Barón¹⁰, Mauricio Murcia-Mejía¹¹, Marisa Chust¹², Tamara García-Cañibano¹, María Luz Couselo¹³, María Mar Puertas¹⁴, Elia Del Cerro^{15

16}, Javier Moradiellos¹⁷, Sergio Amor¹⁷, A Varela¹⁷, I J Thuissard¹⁸, David Sanz-Rosa¹⁸, Felipe Couñago^{15

16}

Affiliations

¹ Department of Radiation Oncology, Hospital Universitario de Fuenlabrada, Camino del Molino, 2, 28942, Fuenlabrada, Madrid, Spain.
² Department of Radiation Oncology, Hospital del Mar, Passeig Marítim, 25-29, 08003 Barcelona, Spain.
³ IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
⁴ Department of Radiation Oncology, Hospital Universitario Ramon y Cajal, Carretera de Colmenar Viejo Km9, Madrid, Spain.
⁵ Department of Radiation Oncology, Complexo Hospitalario Universitario Santiago de Compostela, Choupana s/n, bloque d. Santiago de Compostela, A Coruña, Spain.
⁶ Department of Radiation Oncology, Hospital Universitario Rey Juan Carlos, C/ Gladiolo s/n. Móstoles, Madrid, Spain.
⁷ Department of Radiation Oncology, Hospital Universitario Virgen del Rocio, Av. Manuel Siurot, S/N, 41013 Sevilla, Spain.
⁸ Department of Radiation Oncology, Hospital Clinico Universitario Lozano Blesa, San Juan Bosco 15, Zaragoza, Spain.
⁹ Department of Radiation Oncology, Hospital Germans Trias i Pujol, Carretera de Canyet, s/n, 08916, Badalona, Spain.
¹⁰ Department of Radiation Oncology, Hospital Universitario Puerta del Mar, Av. Ana de Viya, 21, 11009, Cadiz, Spain.
¹¹ Department of Radiation Oncology, Hospital Universitari Sant Joan de Reus, Av. del Dr. Josep Laporte, 2, 43204 Reus, Tarragona, Spain.
¹² Department of Radiation Oncology, Instituto Valenciano de Oncologia, Carrer del Professor Beltrán Báguena, 8, 46009, Valencia, Spain.
¹³ Department of Radiation Oncology, Hospital Central de la Defensa Gomez Ulla, Glorieta Ejército, 1, 28047, Madrid, Spain.
¹⁴ Department of Radiation Oncology, Hospital Universitario Miguel Servet, Paseo Isabel la Católica, 1-3, 50009, Zaragoza, Spain.
¹⁵ Department of Radiation Oncology, Hospital Universitario Quirónsalud Madrid, C/ Diego de Velázquez, 1, 28223, Pozuelo de Alarcón, Madrid, Spain.
¹⁶ Universidad Europea de Madrid, Calle Tajo, s/n, 28670 Villaviciosa de Odón, Madrid, Spain.
¹⁷ Department of Thoracic Surgery, Hospital Universitario Quirónsalud Madrid, C/ Diego de Velázquez, 1, 28223, Pozuelo de Alarcón, Madrid, Spain.
¹⁸ School of Doctoral Studies & Research, Universidad Europea, Calle Tajo, s/n, 28670 Villaviciosa de Odón, Madrid, Spain.

Abstract

Background: The optimal induction treatment in potentially-resectable stage IIIA-N2 NSCLC remains undefined.

Aim: To compare neoadjuvant high-dose chemoradiotherapy (CRT) to neoadjuvant chemotherapy (CHT) in patients with resectable, stage IIIA-N2 non-small-cell lung cancer (NSCLC).

Methods: Retrospective, multicentre study of 99 patients diagnosed with stage cT1-T3N2M0 NSCLC who underwent neoadjuvant treatment (high-dose CRT or CHT) followed by surgery between January 2005 and December 2014.

Results: 47 patients (47.5%) underwent CRT and 52 (52.5%) CHT, with a median follow-up of 41 months. Surgery consisted of lobectomy (87.2% and 82.7%, in the CRT and CHT groups, respectively) or pneumonectomy (12.8% vs. 17.3%). Nodal downstaging (to N1/N0) and Pathologic complete response (pCR; pT0pN0) rates were significantly higher in the CRT group (89.4% vs. 57.7% and 46.8% vs. 7.7%, respectively; p < 0.001)). Locoregional recurrence was significantly lower in the CRT group (8.5% vs. 13.5%; p = 0.047) but distant recurrence rates were similar in the two groups. Median PFS was 45 months (CHT) vs. "not reached" (CRT). Median OS was similar: 61 vs. 56 months (p = 0.803). No differences in grade ≥3 toxicity were observed. On the Cox regression analysis, advanced pT stage was associated with worse OS and PFS (p < 0.001) and persistent N2 disease (p = 0.002) was associated with worse PFS.

Conclusions: Compared to neoadjuvant chemotherapy alone, a higher proportion of patients treated with preoperative CRT achieved nodal downstaging and pCR with better locoregional control. However, there were no differences in survival. More studies are needed to know the optimal treatment of these patients.

Keywords: High dose radiation; N2 disease; Neoadjuvant therapy; Non-small cell lung cancer (NSCLC).