Benedikt Flörsch1, Julian Taugner1, Lukas Käsmann2,3,4, Saskia Kenndoff1, Julian Guggenberger1, Amanda Tufman5, Niels Reinmuth6, Thomas Duell6, Claus Belka1,7,8, Chukwuka Eze1, Farkhad Manapov1,7,8. 1. Department of Radiation Oncology, University Hospital, LMU Munich, Marchioninistraße 15, 81377, Munich, Germany. 2. Department of Radiation Oncology, University Hospital, LMU Munich, Marchioninistraße 15, 81377, Munich, Germany. Lukas.Kaesmann@med.uni-muenchen.de. 3. Member of the German Center for Lung Research (DZL), Comprehensive Pneumology Center Munich (CPC-M), Munich, Germany. Lukas.Kaesmann@med.uni-muenchen.de. 4. German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany. Lukas.Kaesmann@med.uni-muenchen.de. 5. Division of Respiratory Medicine and Thoracic Oncology, Department of Internal Medicine V, Thoracic Oncology Centre Munich, LMU Munich, Munich, Germany. 6. Asklepios Kliniken GmbH, Asklepios Fachkliniken Munich, Gauting, Germany. 7. Member of the German Center for Lung Research (DZL), Comprehensive Pneumology Center Munich (CPC-M), Munich, Germany. 8. German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany.
Abstract
PURPOSE: To investigate the impact of treatment time and patterns in inoperable stage III non-small cell lung cancer (NSCLC) following concurrent chemoradiotherapy (cCRT) ± immune checkpoint inhibitors (ICIs). METHODS: Patients were stratified by treatment year: A (2011-2014), B (2015-2017) and C (2018-2020). Tumor- and treatment-related characteristics regarding locoregional recurrence-free survival (LRRFS), progression-free survival (PFS) and overall survival (OS) were investigated. RESULTS: One hundred and thirty-six consecutive patients were analyzed. All patients completed thoracic radiotherapy (TRT) to a total dose ≥ 60.0 Gy; 36 (26%) patients received ICI. Median PFS in subgroups A, B and C was 8.0, 8.2 and 26.3 months (p = 0.007). Median OS was 19.9 months, 23.4 months and not reached (NR), respectively. In group C, median LRRFS and PFS were 27.2 vs. NR; and 14.2 vs. 26.3 months in patients treated with and without ICI. On multivariate analysis planning target volume (PTV) ≥ 700 cc was a negative prognosticator of LRRFS (HR 2.194; p = 0.001), PFS (HR 1.522; p = 0.042) and OS (HR 2.883; p = 0.001); ICI was a predictor of LRRFS (HR 0.497; p = 0.062), PFS (HR 0.571; p = 0.071) and OS (HR 0.447; p = 0.1). In the non-ICI cohort, multivariate analyses revealed PTV ≥ 700 cc (p = 0.047) and a maximum standardized uptake value (SUVmax) ≥ 13.75 (p = 0.012) were predictors of PFS; PTV ≥ 700 cc (p = 0.017), SUVmax ≥ 13.75 (p = 0.002) and a total lung V20 ≥ 30% (V20 ≥ 30) (p < 0.05) were predictors of OS. CONCLUSIONS: Patients treated after 2018 had improved survival regardless of ICI use. Implementation of ICI resulted in further significant increase of all tested survival endpoints. PTV ≥ 700 cc and ICI were only prognosticators for LRRFS, PFS and OS in the analyzed cohort.
PURPOSE: To investigate the impact of treatment time and patterns in inoperable stage III non-small cell lung cancer (NSCLC) following concurrent chemoradiotherapy (cCRT) ± immune checkpoint inhibitors (ICIs). METHODS: Patients were stratified by treatment year: A (2011-2014), B (2015-2017) and C (2018-2020). Tumor- and treatment-related characteristics regarding locoregional recurrence-free survival (LRRFS), progression-free survival (PFS) and overall survival (OS) were investigated. RESULTS: One hundred and thirty-six consecutive patients were analyzed. All patients completed thoracic radiotherapy (TRT) to a total dose ≥ 60.0 Gy; 36 (26%) patients received ICI. Median PFS in subgroups A, B and C was 8.0, 8.2 and 26.3 months (p = 0.007). Median OS was 19.9 months, 23.4 months and not reached (NR), respectively. In group C, median LRRFS and PFS were 27.2 vs. NR; and 14.2 vs. 26.3 months in patients treated with and without ICI. On multivariate analysis planning target volume (PTV) ≥ 700 cc was a negative prognosticator of LRRFS (HR 2.194; p = 0.001), PFS (HR 1.522; p = 0.042) and OS (HR 2.883; p = 0.001); ICI was a predictor of LRRFS (HR 0.497; p = 0.062), PFS (HR 0.571; p = 0.071) and OS (HR 0.447; p = 0.1). In the non-ICI cohort, multivariate analyses revealed PTV ≥ 700 cc (p = 0.047) and a maximum standardized uptake value (SUVmax) ≥ 13.75 (p = 0.012) were predictors of PFS; PTV ≥ 700 cc (p = 0.017), SUVmax ≥ 13.75 (p = 0.002) and a total lung V20 ≥ 30% (V20 ≥ 30) (p < 0.05) were predictors of OS. CONCLUSIONS: Patients treated after 2018 had improved survival regardless of ICI use. Implementation of ICI resulted in further significant increase of all tested survival endpoints. PTV ≥ 700 cc and ICI were only prognosticators for LRRFS, PFS and OS in the analyzed cohort.
Authors: Jeffrey D Bradley; Chen Hu; Ritsuko R Komaki; Gregory A Masters; George R Blumenschein; Steven E Schild; Jeffrey A Bogart; Kenneth M Forster; Anthony M Magliocco; Vivek S Kavadi; Samir Narayan; Puneeth Iyengar; Clifford G Robinson; Raymond B Wynn; Christopher D Koprowski; Michael R Olson; Joanne Meng; Rebecca Paulus; Walter J Curran; Hak Choy Journal: J Clin Oncol Date: 2019-12-16 Impact factor: 44.544
Authors: Rina Hui; Mustafa Özgüroğlu; Augusto Villegas; Davey Daniel; David Vicente; Shuji Murakami; Takashi Yokoi; Alberto Chiappori; Ki Hyeong Lee; Maike de Wit; Byoung Chul Cho; Jhanelle E Gray; Anna Rydén; Louis Viviers; Lynne Poole; Yiduo Zhang; Phillip A Dennis; Scott J Antonia Journal: Lancet Oncol Date: 2019-10-07 Impact factor: 41.316
Authors: Jeffrey D Bradley; Rebecca Paulus; Ritsuko Komaki; Gregory Masters; George Blumenschein; Steven Schild; Jeffrey Bogart; Chen Hu; Kenneth Forster; Anthony Magliocco; Vivek Kavadi; Yolanda I Garces; Samir Narayan; Puneeth Iyengar; Cliff Robinson; Raymond B Wynn; Christopher Koprowski; Joanne Meng; Jonathan Beitler; Rakesh Gaur; Walter Curran; Hak Choy Journal: Lancet Oncol Date: 2015-01-16 Impact factor: 41.316
Authors: Scott J Antonia; Augusto Villegas; Davey Daniel; David Vicente; Shuji Murakami; Rina Hui; Takayasu Kurata; Alberto Chiappori; Ki H Lee; Maike de Wit; Byoung C Cho; Maryam Bourhaba; Xavier Quantin; Takaaki Tokito; Tarek Mekhail; David Planchard; Young-Chul Kim; Christos S Karapetis; Sandrine Hiret; Gyula Ostoros; Kaoru Kubota; Jhanelle E Gray; Luis Paz-Ares; Javier de Castro Carpeño; Corinne Faivre-Finn; Martin Reck; Johan Vansteenkiste; David R Spigel; Catherine Wadsworth; Giovanni Melillo; Maria Taboada; Phillip A Dennis; Mustafa Özgüroğlu Journal: N Engl J Med Date: 2018-09-25 Impact factor: 91.245
Authors: Greg A Durm; Salma K Jabbour; Sandra K Althouse; Ziyue Liu; Ahad A Sadiq; Robin T Zon; Shadia I Jalal; Goetz H Kloecker; Michael J Williamson; Karen L Reckamp; Robert M Langdon; Ebenezer A Kio; Ryan D Gentzler; Bamidele A Adesunloye; Wael A Harb; Radhika V Walling; Michael L Titzer; Nasser H Hanna Journal: Cancer Date: 2020-07-22 Impact factor: 6.860
Authors: Corinne Faivre-Finn; David Vicente; Takayasu Kurata; David Planchard; Luis Paz-Ares; Johan F Vansteenkiste; David R Spigel; Marina C Garassino; Martin Reck; Suresh Senan; Jarushka Naidoo; Andreas Rimner; Yi-Long Wu; Jhanelle E Gray; Mustafa Özgüroğlu; Ki H Lee; Byoung C Cho; Terufumi Kato; Maike de Wit; Michael Newton; Lu Wang; Piruntha Thiyagarajah; Scott J Antonia Journal: J Thorac Oncol Date: 2021-01-19 Impact factor: 15.609
Authors: Jhanelle E Gray; Augusto Villegas; Davey Daniel; David Vicente; Shuji Murakami; Rina Hui; Takayasu Kurata; Alberto Chiappori; Ki Hyeong Lee; Byoung Chul Cho; David Planchard; Luis Paz-Ares; Corinne Faivre-Finn; Johan F Vansteenkiste; David R Spigel; Catherine Wadsworth; Maria Taboada; Phillip A Dennis; Mustafa Özgüroğlu; Scott J Antonia Journal: J Thorac Oncol Date: 2019-10-14 Impact factor: 15.609
Authors: Ryan N Hansen; Yiduo Zhang; Brian Seal; Kellie Ryan; Candice Yong; Annie Darilay; Scott D Ramsey Journal: BMC Cancer Date: 2020-04-05 Impact factor: 4.430