Concurrent chemoradiotherapy using proton beams can reduce cardiopulmonary morbidity in esophageal cancer patients: a systematic review

Tetsuo Nonaka; Shohei Kawashiro; Hitoshi Ishikawa; Yoshinori Ito; Kenji Nemoto; Ryu Ishihara; Takashi Oyama; Tsuneo Oyama; Ken Kato; Hiroyuki Kato; Hirofumi Kawakubo; Hiroshi Kawachi; Shiko Kuribayashi; Koji Kono; Takashi Kojima; Hiroya Takeuchi; Takahiro Tsushima; Yasushi Toh; Eisuke Booka; Tomoki Makino; Satoru Matsuda; Hisahiro Matsubara; Masayuki Mano; Keiko Minashi; Tatsuya Miyazaki; Manabu Muto; Taiki Yamaji; Tomoki Yamatsuji; Masahiro Yoshida; Yuko Kitagawa; Esophageal Cancer Practice Guidelines Preparation Committee

doi:10.1007/s10388-023-01015-x

Concurrent chemoradiotherapy using proton beams can reduce cardiopulmonary morbidity in esophageal cancer patients: a systematic review

Esophagus. 2023 Oct;20(4):605-616. doi: 10.1007/s10388-023-01015-x. Epub 2023 Jun 17.

Authors

Tetsuo Nonaka¹, Shohei Kawashiro², Hitoshi Ishikawa³, Yoshinori Ito⁴, Kenji Nemoto², Ryu Ishihara⁵, Takashi Oyama⁶, Tsuneo Oyama⁷, Ken Kato⁸, Hiroyuki Kato⁹, Hirofumi Kawakubo¹⁰, Hiroshi Kawachi¹¹, Shiko Kuribayashi¹², Koji Kono¹³, Takashi Kojima¹⁴, Hiroya Takeuchi¹⁵, Takahiro Tsushima¹⁶, Yasushi Toh¹⁷, Eisuke Booka¹⁵, Tomoki Makino¹⁸, Satoru Matsuda¹⁰, Hisahiro Matsubara¹⁹, Masayuki Mano²⁰, Keiko Minashi²¹, Tatsuya Miyazaki²², Manabu Muto²³, Taiki Yamaji²⁴, Tomoki Yamatsuji²⁵, Masahiro Yoshida²⁶, Yuko Kitagawa¹⁰; Esophageal Cancer Practice Guidelines Preparation Committee

Affiliations

¹ Department of Radiation Oncology, Japanese Red Cross Medical Center, Tokyo, Japan.
² Department of Radiation Oncology, Faculty of Medicine, Yamagata University, Yamagata, Japan.
³ QST Hospital, National Institutes for Quantum Science and Technology, 4-9-1 Anagawa, Inage, Chiba, 263-8555, Japan. ishikawa.hitoshi@qst.go.jp.
⁴ Department of Radiation Oncology, Showa University School of Medicine, Tokyo, Japan.
⁵ Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan.
⁶ Department of Hepato‑Biliary‑Pancreatic and Gastrointestinal Surgery, International University of Health and Welfare School of Medicine, Chiba, Japan.
⁷ Department of Endoscopy, Saku Central Hospital Advanced Care Center, Nagano, Japan.
⁸ Department of Head and Neck, Esophageal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
⁹ Kiryu Kosei General Hospital, Kiryu, Japan.
¹⁰ Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
¹¹ Department of Pathology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
¹² Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, Maebashi, Japan.
¹³ Department of Gastrointestinal Tract Surgery, Fukushima Medical University, Fukushima, Japan.
¹⁴ Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan.
¹⁵ Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
¹⁶ Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
¹⁷ National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.
¹⁸ Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
¹⁹ Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
²⁰ Department of Central Laboratory and Surgical Pathology, National Hospital Organization Osaka National Hospital, Osaka, Japan.
²¹ Clinical Trial Promotion Department, Chiba Cancer Center, Chiba, Japan.
²² Department of Surgery, Japanese Red Cross Maebashi Hospital, Maebashi, Japan.
²³ Department of Clinical Oncology, Kyoto University Hospital, Kyoto, Japan.
²⁴ Division of Epidemiology, National Cancer Center Institute for Cancer Control, National Cancer Center, Tokyo, Japan.
²⁵ Department of General Surgery, Kawasaki Medical School, Okayama, Japan.
²⁶ Department of Hepato‑Biliary‑Pancreatic and Gastrointestinal Surgery, School of Medicine, International University of Health and Welfare, Ichikawa, Japan.

PMID: 37328706
DOI: 10.1007/s10388-023-01015-x

Abstract

This systematic review was performed to investigate the superiority of proton beam therapy (PBT) to photon-based radiotherapy (RT) in treating esophageal cancer patients, especially those with poor cardiopulmonary function. The MEDLINE (PubMed) and ICHUSHI (Japana Centra Revuo Medicina) databases were searched from January 2000 to August 2020 for studies evaluating one end point at least as follows; overall survival, progression-free survival, grade ≥ 3 cardiopulmonary toxicities, dose-volume histograms, or lymphopenia or absolute lymphocyte counts (ALCs) in esophageal cancer patients treated with PBT or photon-based RT. Of 286 selected studies, 23 including 1 randomized control study, 2 propensity matched analyses, and 20 cohort studies were eligible for qualitative review. Overall survival and progression-free survival were better after PBT than after photon-based RT, but the difference was significant in only one of seven studies. The rate of grade 3 cardiopulmonary toxicities was lower after PBT (0-13%) than after photon-based RT (7.1-30.3%). Dose-volume histograms revealed better results for PBT than photon-based RT. Three of four reports evaluating the ALC demonstrated a significantly higher ALC after PBT than after photon-based RT. Our review found that PBT resulted in a favorable trend in the survival rate and had an excellent dose distribution, contributing to reduced cardiopulmonary toxicities and a maintained number of lymphocytes. These results warrant novel prospective trials to validate the clinical evidence.

Keywords: Cardiopulmonary morbidities; Esophageal cancer; Proton beam therapy.

Publication types

Systematic Review
Review

MeSH terms

Chemoradiotherapy / adverse effects
Chemoradiotherapy / methods
Esophageal Neoplasms* / therapy
Humans
Prospective Studies
Proton Therapy* / adverse effects
Protons

Substances

Protons