The efficacy profiles of concurrent chemoradiotherapy with intensity-modulated radiotherapy followed by durvalumab in patients with unresectable stage III non-small cell lung cancer: A multicenter retrospective cohort study

Yuichiro Takeda; Yusaku Kusaba; Yoko Tsukita; Yukari Uemura; Eisaku Miyauchi; Takaya Yamamoto; Hiroshi Mayahara; Akito Hata; Hidetsugu Nakayama; Satoshi Tanaka; Junji Uchida; Kazuhiro Usui; Tatsuya Toyoda; Motohiro Tamiya; Masahiro Morimoto; Yuko Oya; Takeshi Kodaira; Keiichi Jingu; Hisatoshi Sugiura

doi:10.1016/j.ctro.2022.08.010

The efficacy profiles of concurrent chemoradiotherapy with intensity-modulated radiotherapy followed by durvalumab in patients with unresectable stage III non-small cell lung cancer: A multicenter retrospective cohort study

Clin Transl Radiat Oncol. 2022 Aug 23:37:57-63. doi: 10.1016/j.ctro.2022.08.010. eCollection 2022 Nov.

Authors

Yuichiro Takeda¹, Yusaku Kusaba¹, Yoko Tsukita², Yukari Uemura³, Eisaku Miyauchi², Takaya Yamamoto⁴, Hiroshi Mayahara⁵, Akito Hata⁶, Hidetsugu Nakayama⁷, Satoshi Tanaka⁸, Junji Uchida⁸, Kazuhiro Usui⁹, Tatsuya Toyoda¹⁰, Motohiro Tamiya¹¹, Masahiro Morimoto¹², Yuko Oya¹³, Takeshi Kodaira¹⁴, Keiichi Jingu⁴, Hisatoshi Sugiura²

Affiliations

¹ Department of Respiratory Medicine, National Center for Global Health and Medicine, 1-21-1 Toyama Shinjuku-ku, Tokyo 162-8655, Japan.
² Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-Ku, Sendai 980-8574, Japan.
³ Section of Biostatistics, Department of Clinical Research Center, National Center for Global Health and Medicine, 1-21-1 Toyama Shinjuku-ku, Tokyo 162-8655, Japan.
⁴ Department of Radiation Oncology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-Ku, Sendai 980-8574, Japan.
⁵ Department of Radiation Oncology, Kobe Minimally Invasive Cancer Center, 8-5-1, Minatojimanakamachi, Chuo-ku, Kobe, Hyogo 650-0046, Japan.
⁶ Department of Respiratory Medical Oncology, Kobe Minimally Invasive Cancer Center, 8-5-1, Minatojimanakamachi, Chuo-ku, Kobe, Hyogo 650-0046, Japan.
⁷ Department of Radiation Oncology, National Center for Global Health and Medicine, 1-21-1 Toyama Shinjuku-ku, Tokyo 162-8655, Japan.
⁸ Department of Respiratory Medicine, Osaka General Medical Center, 3-1-56, Bandaihigashi, Sumiyoshi-Ku, Osaka 558-0056, Japan.
⁹ Division of Respirology, NTT Medical Center Tokyo, 5-9-22, Higashigotanda, Shinagawa, Tokyo 141-8625, Japan.
¹⁰ Department of Radiology, NTT Medical Center Tokyo, 5-9-22, Higashigotanda, Shinagawa, Tokyo 141-8625, Japan.
¹¹ Department of Thoracic Oncology, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-ku, Osaka 541-8567, Japan.
¹² Department of Radiation Oncology, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-ku, Osaka 541-8567, Japan.
¹³ Department of Thoracic Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-Ku, Nagoya 464-8681, Japan.
¹⁴ Department of Radiation Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-Ku, Nagoya 464-8681, Japan.

Abstract

Purpose: Intensity-modulated radiotherapy (IMRT) is currently used more commonly than 3-dimensional conformal radiation for definitive thoracic radiation. We examined the efficacy profiles of concurrent chemoradiotherapy (CCRT) with IMRT after durvalumab became clinically available.

Methods: We reviewed the clinical records of patients with stage III non-small cell lung cancer (NSCLC) treated with CCRT and IMRT at seven centers in Japan and investigated relapse and survival from May 2018 to December 2019. The primary endpoint of this report was progression-free survival (PFS).

Results: Among 107 patients enrolled in the study, 87 were sequentially administered durvalumab. From CCRT commencement, patients were followed up for a median period of 29.7 months. The median PFS at the end of the CCRT was 20.7 months. Among the 87 patients, 58 experienced disease relapses, of whom 36 (62.1 %) had distant metastases. Multivariate Cox regression analysis revealed that a favorable response to CCRT, a radiation dose ≥ 62 Gy, and stage IIIA NSCLC were associated with prolonged PFS (all P = 0.04). Multivariate logistic regression by landmark analysis revealed that mortality risk factors were durvalumab treatment duration ≤ 11.7 months, a lower maximum grade of immune-related adverse events, FEV₁ < 2805 mL, and radiation dose < 62 Gy (P = 0.01, 0.01, 0.03, and 0.04, respectively).

Conclusions: In patients with NSCLC receiving CCRT using IMRT, long PFS was associated with a better response to CCRT, stage IIIA NSCLC, and an increased radiation dose. The duration of durvalumab consolidation also played an essential role in the survival of patients receiving CCRT with IMRT. (250 words).

Keywords: 3D-CRT, 3-dimensional conformal radiation therapy; 95% CI, 95% confidence interval; AE, adverse event; AIC, Akaike’s information criterion; CCRT, concurrent chemoradiotherapy; Concurrent chemoradiotherapy; Durvalumab consolidation; FEV1, forced expiratory volume in 1 second; HR, hazard ratio; IMRT, intensity-modulated radiotherapy; IO, immune-oncology; Intensity-modulated radiotherapy; Landmark analysis; Multivariate analysis; NSCLC, non-small-cell lung cancer; Non-small cell lung cancer; OR, odds ratio; OS, overall survival; PFS, progression-free survival; PS, performance status; RECIST, Response Evaluation Criteria in Solid Tumors; ROC, receiver operating characteristic; irAE, immune-related adverse event.