Dosimetric comparison between proton beam therapy and photon radiation therapy for locally advanced esophageal squamous cell carcinoma

Hirano et al. Radiation Oncology (2018) 13:23 https://doi.org/10.1186/s13014-018-0966-5 RESEARCH Open Access Dosimetric comparison between proton beam therapy and photon radiation therapy for locally advanced esophageal squamous cell carcinoma Yasuhiro Hirano1, Masakatsu Onozawa1, Hidehiro Hojo1, Atsushi Motegi1, Sadatomo Zenda1, Kenji Hotta1, Shunsuke Moriya1, Hidenobu Tachibana1, Naoki Nakamura1, Takashi Kojima2 and Tetsuo Akimoto1* Abstract Background: The purpose of this study was to perform a dosimetric comparison between proton beam therapy (PBT) and photon radiation therapy in patients with locally advanced esophageal squamous cell carcinoma (ESCC) who were treated with PBT in our institution. In addition, we evaluated the correlation between toxicities and dosimetric parameters, especially the doses to normal lung or heart tissue, to clarify the clinical advantage of PBT over photon radiation therapy. Methods: A total of 37 consecutive patients with Stage III thoracic ESCC who had received PBT with or without concurrent chemotherapy between October 2012 and December 2015 were evaluated in this study. The dose distributions of PBT were compared with those of dummy 3-dimensional conformal radiation therapy (3DCRT) and Intensity Modulated Radiation Therapy (IMRT), focusing especially on the doses to organs at risk, such as normal lung and heart tissue. Results: Of the 37 patients, the data from 27 patients were analyzed. Among these 27 patients, four patients (15%) developed grade 2 pericardial effusion as a late toxicity. None of the patients developed grade 3 or worse acute or late pulmonary and cardiac toxicities. When the dosimetric parameters between PBT and planned 3DCRT were compared, all the PBT domestic variables for the lung dose except for lung V10 GyE and V15 GyE were significantly lower than those for the dummy 3DCRT plans, and the PBT domestic variables for the heart dose were also significantly lower than those for the dummy 3DCRT plans. When the PBT and IMRT plans were compared, all the PBT domestic variables for the doses to the lung and heart were significantly lower than those for the dummy IMRT plans. Regarding the correlation between the grades of toxicities and the dosimetric parameters, no significant correlation was seen between the occurrence of grade 2 pericardial effusion and the dose to the heart. Conclusions: When the dosimetric parameters of the dose distributions for the treatment of patients with locally advanced stage III ESCC were compared between PBT and 3DCRT or IMRT, PBT enabled a significant reduction in the dose to the lung and heart, compared with 3DCRT or IMRT. Keywords: Proton beam therapy, IMRT, 3DCRT, Locally advanced esophageal cancer, In silico dose distribution * Correspondence: 1 Division of Radiation Oncology and Particle Therapy, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, Chiba 277-8577, Japan Full list of author information is available at the end of the article © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Hirano et al. Radiation Oncology (2018) 13:23 Background One standard treatment option for stage II-III esophageal squamous cell carcinoma (ESCC) is neoadjuvant chemotherapy followed by surgical resection, and the 5-year overall survival rate is reported to be 36.8%–61% [1–3]. Chemoradiotherapy (CRT) is also a curative-intent non-surgical treatment option for resectable ESCC, especially for patients who refuse surgical resection or are unsuited for surgical resection. The results of the Japan Clinical Oncology Group (JCOG) 9906, a Phase II study that evaluated CRT for the patients with stage II-III ESCC, showed an initial complete response rate of 62.2% and a 5-year survival rate of 36.8% [4]. However, 4 (5.3%) related deaths occurred because of late toxicities including pneumonitis (n = 2), pericarditis (n = 1), and pleural effusion (n = 1). Long-term cardiopulmonary toxicities sometimes caused life-threatening events or death in patients who have received CRT, and the main causes for the development of cardiopulmonary toxicities are excessive radiation doses to normal lung and heart tissue, in addition to the combination of chemotherapy with radiation therapy. Therefore, it is important to reduce the incidence and severity of late toxicities, since this would lead to an improved quality of life (QOL) for patients who are able to achieve disease control. Particle therapy including proton beam therapy (PBT) has a unique physical characteristic, called the Bragg peak, and can deliver a high dose to the tumor while sparing the surrounding normal tissues. An in silico dose distribution comparison between photon radiation therapy and PBT for esophageal cancer shows that proton beam therapy has clear therapeutic advantages, especially a dose reduction to at-risk organs, over conventional external radiotherapy [5]. Based on these backgrounds, we have been applying PBT with concurrent chemotherapy for the treatment of patients with ESCC since 2012. The purpose of the present study was to perform a dosimetric comparison between PBT and photon radiation therapy in patients who were treated with PBT for locally advanced esophageal ESCC in our institution. We also evaluated the correlation between the grade and/or incidence of toxicities and dosimetric parameters, especially the doses to normal lung or heart tissue, to clarify the clinical advantages of PBT over photon radiation therapy. Methods Patients Approval for this study was obtained from the National Cancer Center Institutional Review Board. Consecutive patients with thoracic ESCC who received PBT with or without concurrent chemotherapy between October 2012 and December 2015 were enrolled as candidates for this study. Among these, we selected 37 consecutive patients with Stage III thoracic ESCC for dosimetric Page 2 of 9 comparison between PBT and photon radiation therapy because the rationale for the coverage of the radiation field, including the elective nodal region, differs according to disease stage, and this might have resulted in differences in the doses to risk organs, such as the lung and heart. Pretreatment evaluation Clinical staging was based on the American Joint Committee on Cancer staging, 7th edition. The staging evaluations included a barium swallow test, an endoscopy examination of the esophagus and stomach, and a computed tomography examination of the neck (...truncated)