Contents lists available at ScienceDirect Physica Medica journal homepage: www.elsevier.com/locate/ejmp Original paper Normal tissue sparing potential of scanned proton beams with and without respiratory gating for the treatment of internal mammary nodes in breast cancer radiotherapy Alexandru Dasu a, ⁎ , Anna M. Flejmer a,b , Anneli Edvardsson c , Petra Witt Nyström a,d a The Skandion Clinic, Uppsala, Sweden b Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden c Medical Radiation Physics, Department of Clinical Sciences Lund, Lund University, Lund, Sweden d Danish Centre for Particle Therapy, Aarhus, Denmark ARTICLE INFO Keywords: Scanning proton technique Breast radiotherapy Internal mammary nodes Respiratory gating Enhanced inspiration gating ABSTRACT Proton therapy has shown potential for reducing doses to normal tissues in breast cancer radiotherapy. However data on the impact of protons when including internal mammary nodes (IMN) in the target for breast radio- therapy is comparatively scarce. This study aimed to evaluate normal tissue doses when including the IMN in regional RT with scanned proton beams, with and without respiratory gating. The study cohort was composed of ten left-sided breast patients CT-scanned during enhanced inspiration gating (EIG) and free-breathing (FB). Proton plans were designed for the target including or excluding the IMN. Targets and organs-at-risk were delineated according to RTOG guidelines. Comparison was performed between dosimetric parameters char- acterizing target coverage and OAR radiation burden. Statistical significance of differences was tested using a paired, two-tailed Student’s t-test. Inclusion of the IMN in the target volume led to a small increase of the cardiopulmonary burden. The largest differences were seen for the ipsilateral lung where the mean dose in- creased from 6.1 to 6.6 Gy (RBE) (P < 0.0001) in FB plans and from 6.9 to 7.4 Gy (RBE) (P = 0.003) in EIG plans. Target coverage parameters were very little affected by the inclusion of IMN into the treatment target. Radiotherapy with scanned proton beams has the potential of maintaining low cardiovascular burden when including the IMN into the target, irrespective of whether respiratory gating is used or not. 1. Introduction The adjuvant loco-regional radiotherapy (RT) for breast cancer (BC) has contributed to a reduction of recurrence rate and improved disease- free survival rate [1], the absolute benefit being reduced due to un- wanted doses to organs-at-risk (OAR), e.g., heart and lungs. This is also illustrated by the controversial topic on whether to include the internal mammary nodes (IMN) in the target due to the closeness to the heart and the associated risk for cardiac morbidity [2]. Drugs used in the systemic treatment settings, e.g., anthracyclines, trastuzumab, lapa- tinib, may also contribute to heart toxicity [3]. BC patients are a group of patients where the large majority is cured and additionally many become long-term survivors as the 5-years survival is well over 80% [4] and therefore radiation induced toxicity should be reduced to a minimum. Hence, much focus during the last years has been on mini- mizing the risk for normal tissue toxicity. Proton therapy has the potential of reducing unwanted radiation bath to OAR through the physical properties of protons and several dose planning studies have explored their potential for BC [5–11]. Two newly published dose planning studies compared photon and proton plans for both free breathing and respiratory gating for patients can- didates for local RT [12,13]. The studies showed that proton plans could significantly reduce doses to the heart and the left anterior des- cendent artery (LAD) even without respiratory gating. It should be noted that Ares et al. [6] showed in their dose planning study that the more complex the target the more obvious the benefit was from using protons. This may further expand the future indication for proton RT as several clinical studies have now shown that including the IMN in re- gional RT not only significantly improves disease free survival (DFS) but also indicates a better overall survival (OS) in stage I-III breast cancer [14]. However, so far there has been a shortage of data showing the impact of protons with or without respiratory gating when in- cluding the IMN. The aim of this study was to evaluate the effect on doses to normal tissue when including the IMN to the regional lymph https://doi.org/10.1016/j.ejmp.2018.06.639 Received 24 October 2017; Received in revised form 26 June 2018; Accepted 29 June 2018 ⁎ Corresponding author at: The Skandion Clinic, von Kraemers allé 26, 752 37 Uppsala, Sweden. E-mail address: alexandru.dasu@skandion.se (A. Dasu). Physica Medica 52 (2018) 81–85 Available online 03 July 2018 1120-1797/ © 2018 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved. T