Comprehensive analysis of predictive factors for efficacy in concurrent chemo-radiotherapy for locally advanced non-small cell lung cancer, utilizing individual patient data from the Japan lung cancer society integrated clinical trial database: Is there room for further improvement?

person Yuichi Ozawa Hamamatsu Medical Center, Hamamatsu-Shi, Japan info_outline Yuichi Ozawa, Kouji Yamamoto, Shunichi Sugawara, Seiji Niho, Yuichiro Ohe, Hiroaki Okamoto, Katsuyuki Hotta, Norihiko Ikeda, Nobuyuki Yamamoto

Authors person Yuichi Ozawa Hamamatsu Medical Center, Hamamatsu-Shi, Japan info_outline Yuichi Ozawa, Kouji Yamamoto, Shunichi Sugawara, Seiji Niho, Yuichiro Ohe, Hiroaki Okamoto, Katsuyuki Hotta, Norihiko Ikeda, Nobuyuki Yamamoto Organizations Hamamatsu Medical Center, Hamamatsu-Shi, Japan, Department of Biostatistics, Yokohama City University School of Medicine, Yokohama, Japan, Department of Pulmonary Medicine, Sendai Kousei Hospital, Sendai, Japan, Department of Thoracic Oncology, National Cancer Center Hospital East, Mibu, Japan, National Cancer Center Hospital, Tokyo, Japan, Yokohama Municipal Citizen's Hospital, Yokohama, Japan, Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan, Department of Surgery, Tokyo Medical University, Tokyo, Japan, Wakayama Medical University, Wakayama, Japan Abstract Disclosures Research Funding No funding sources reported Background: The standard treatment for unresectable, locally advanced NSCLC is concurrent chemoradiotherapy followed by durvalumab. While the effectiveness of chemoradiotherapy is pivotal, the exploration into predictive factors of the efficacy is notably limited. Methods: The Japanese Lung Cancer Society (JLCS) integrated eight randomized Phase II/III trials (JCOG9812, JCOG0301, NJLCG0601, OLCSG0007, SPECTRA, TORG1018, WJOG5008L, WJTOG0105) concerning chemoradiotherapy for locally advanced NSCLC, constructing the JLCS Integrated Clinical Trial Database (JIDB), with individual data of 1288 patients. This study analyzed 1162 patients who underwent concurrent chemoradiotherapy, focusing on factors impacting PFS. A logistic regression with the least absolute shrinkage and selection operator (LASSO) analyses for 3-yr PFS were performed, and the five most related factors were further evaluated using the Kaplan-Meier method and log-rank tests. The impact of pneumonitis and esophagitis on PFS was also explored. Results: Age [median (Q1;Q3)]; 64 (57;71), male/female; 961/201, Ad/Sq/Oth; 580/446/134, PS 0/1/2; 562/578/5, stage IIIA/IIIB; 468/694, T factor 4/3/2/1/0; 436/158/341/156/3, N factor 3/2/1/0; 300/692/44/62, PS 0/1/2; 562/578/5, primary site; upper, middle/lower lobe; 599/161, BMI; 21.8 (19.7;24.0), weight loss (≥5% within 6m) yes/no; 135/644, LDH (IU/l); 203 (175;276), CRP (mg/dl); 0.70 (0.20;2.60), irradiated dose (Gy); 60 (60;60), combined regimen; platinum/taxane 303, CDDP/mitomycin/vindesine; 254, CDDP/5-FU-based; 196, CDDP/vinorelbine 87, CDDP/pemetrexed 50, others 272. The median PFS in all patients was 9.72m (95% CI; 9.33 – 10.38), with 3-yr, 5-yr, and 10-yr PFS rates of 19.7, 14.3, 10.1%. LASSO logistic regression identified Sq, lower lobe primary, age, pack-years, and weight loss as the top negative influencers. The PFS curve was significantly shorter in patients with lower lobe primary (median of 8.15 vs. 9.46m, p = 0.023) and weight loss (median of 7.29 vs. 9.72m, p < 0.0001). Pneumonitis occurred in 50.9% (grade≥3 in 6.7%) and esophagitis in 41.9% (grade≥3 in 3.9%). Grade≥2 pneumonitis shortened PFS (8.2 vs. 10.2m, p = 0.00015), while, unexpectedly, grade≥1 esophagitis was associated with longer PFS (12.9 vs. 8.6m, p < 0.0001). Conclusions: The efficacy of concurrent chemoradiotherapy varies significantly based on the primary site. Weight loss is a significant predictor of efficacy, as is in metastatic disease. The impact of pneumonitis and esophagitis suggest that modifying lung and esophageal irradiation might enhance treatment efficacy. Further research in this area is still certainly warranted.