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Short-Term E Cacy Comparison Between Helical Tomotherapy and Intensity-Modulated Radiotherapy in Patients with Locally Advanced

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Short-Term E Cacy Comparison Between Helical Tomotherapy and Intensity-Modulated Radiotherapy in Patients with Locally Advanced Short-term ecacy comparison between helical tomotherapy and intensity-modulated radiotherapy in patients with locally advanced nasopharyngeal carcinoma Zhen Cui ( [email protected] ) Aliated Hospital of Bengbu Medical College Jia Liu Aliated Hospital of Bengbu Medical College Qiaoyu Sun Aliated hospital of Bengbu medical college Chaoge Wang Aliated Hospital of Bengbu Medical College Meifang Fang Aliated Hospital of Bengbu Medical College Zelai He Aliated Hospital of Bengbu Medical College Duojie Li Aliated Hospital of Bengbu Medical College Hao Jiang Aliated Hospital of Bengbu Medical College Research article Keywords: Nasopharyngeal carcinoma, helical tomotherapy, intensity-modulated radiotherapy, Dosimetry analysis, Adverse events Posted Date: April 9th, 2020 DOI: https://doi.org/10.21203/rs.3.rs-21288/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 1/14 Abstract Background: To evaluate short-term safety and ecacy of helical tomotherapy (HT) versus intensity- modulated radiotherapy (IMRT) in patients with nasopharyngeal carcinoma (NPC). Methods: Retrospective analysis of locally advanced nasopharyngeal carcinoma treated with radiotherapy and concurrent platinum based neoadjuvant chemotherapy (cisplatin 80 mg/m2 every 3 weeks for 1 cycle) in our hospital from February 2017 to October 2019, including 70 patients in HT group and 70 in IMRT group. The target area of the tumor was delineated by magnetic resonance (MRI) imaging. The prescription doses delivered to the gross tumor volume (pGTVnx) and positive lymph nodes (pGTVnd), the high risk planning target volume (PTV1), and the low risk planning target volume (PTV2), were 69.96 Gy, 66-70 Gy, 60 Gy and 50-54 Gy, in 33 fractions, respectively. Acute reactions were evaluated according to the RTOG/EORTC criteria, whereas the therapeutic ecacy was assessed according to RECTST version 1.1 criteria in a 3-months period. Results: The CI of PGTVnx, PGTVnd, PTV1 and PTV2, and HI of PGTVnx, PTV1 and PTV2 in HT group was signicantly better than those in IMRT group. The OAR Dmax and Dmean in HT group were better than those in IMRT group with a signicant difference (all p <0.05). Patients in the HT group were signicantly better than those in the IMRT group in the protection of acute parotid gland injury and hearing damage (p <0.05), but not other acute adverse reaction. No signicant difference was found on the short-term ecacy illustrated by ORR between HT group and IMRT group (x2 = 0.119; p = 0.730). Conclusions: Compared with IMRT, HT has better radiophysical-related dosimetric advantages in radiotherapy for locally advanced nasopharyngeal carcinoma. Despite similar on short-term effects, HT has lower incidence of adverse reactions than IMRT. Background Nasopharyngeal carcinoma is one of the most common cancer type located in head and neck. In 2018, 130,000 people were diagnosed with nasopharyngeal carcinoma worldwide, and its incidence was as high as 9.8/100,000 in China, of which 70% of patients were locally advanced nasopharyngeal cancer [1, 2]. Due to the special anatomical structure of the nasopharynx and the radiation sensitivity property possessed in biological characteristics of nasopharyngeal carcinoma, radiotherapy is considered as the preferred treatment choice for nasopharyngeal carcinoma [3]. For locally advanced nasopharyngeal carcinoma, concurrent chemoradiotherapy is the standard treatment in clinical practice [4]. In recent years, with the rapid development of radiotherapy modality and radiotherapy technology, the 5-year overall survival of nasopharyngeal carcinoma radiotherapy has exceeded 80% [5]. However, adverse reactions resulted from radiotherapy (such as dry mouth etc) remain the main factors affecting the quality of life of patients with radiotherapy. Effectively reduction of the side effects generated by radiotherapy in the treatment nasopharyngeal carcinoma is one of the major concerns in clinical practice. Page 2/14 Helical tomotherapy (HT) is one of the most advanced intensity-modulated radiotherapy (IMRT) technologies used in current clinical practice. As a newly emerging IMRT technology, HT integrates IMRT, Image-Guided Intensity Modulated Radiotherapy (IGRT), and Dose-Guided Intensity Modulated Radiotherapy (DGRT) via combining 360°spiral tomography scan with straight accelerator in tumor radiotherapy, thereby realizing real dynamic intensity modulation. Regarding few study, small sample size and inconsistent results on the ecacy of HT in nasopharyngeal carcinoma radiotherapy in China and worldwide [6–8], elucidation of the role of HT in nasopharyngeal carcinoma treatment via a large sample study is required. Here, we performed a retrospective study to evaluate the advantages of HT radiotherapy for locally advanced nasopharyngeal carcinoma via comparison of the differences in target conformation index, homogeneity index, acute adverse reactions, and short-term ecacy between the patients treated with HT and conventional IMRT. Methods 1.1 Patient inclusion From February 2017 to September 2019, 140 cases of stage IIIa-IVb locally advanced NPC treated in our department were collected. Inclusion criteria: (1) NPC with conrmed pathological diagnosis; (2) complete clinical data; (3) stage IIIa-IVb according to 8th edition of American Joint Committee on Cancer (AJCC) staging classications; (4) The Karnofsky Performance Scale (KPS) ≥70 points; (5) no contraindication to radiotherapy and chemotherapy; (6) with written form of informed consent. The study was approved by the Ethical committee of the First Aliated Hospital of Bengbu Medical College. Patients were divided into HT group and IMRT group according to radiotherapy methods, with 70 cases in each group. No signicant difference was found on general information between the two groups (all p >0.05) (Table 1). 1.2 CT scan for simulation and immobilization The patient was placed in supine position and was xed with a head-neck-shoulder thermoplastic mask before subjection to a Spiral computed tomography (CT) simulator. The scanning range was 5 cm length from head to subclavian, and the layer thickness is 3 mm. 1.3 Target area and organs at risk (OAR) delineation Target area was delineated according to the International Commission on Radiation Units & Measurements (ICRU) Reports 50 & 62. The primary nasopharyngeal tumor was dened as GTVnx and metastatic lymph nodes as GTVnd. CTV1 was dened as the high-risk areas of microscopic extension encompassing the entire nasopharynx, parapharyngeal space, retropharyngeal lymph node area, skull base, clivus, sphenoid sinus, pterygopalatine fossa, nasal cavity and 5 mm anterior to the posterior wall Page 3/14 of the maxillary sinus, part of the oropharyngeal and superior neck lymph drainage area, including gross tumor (GTVnx) and regional metastatic nodes (GTVnd). CTV2 was dened as the low-risk region of inferior neck lymph drainage area below CTV1. PTV1 and PTV2 was respectively generated by 3 mm expansion outside of CTV1 and CTV2, and at least 3-mm distant away from the skin for protection purpose. OARs included brain stem, spinal cord, lens, optic nerves, optic chiasm, parotid glands, temporomandibular joints (TMJs), inner ear, parotid gland, oral cavity, spinal cord and other non-specied tissues. A re-delineation of the target area and OAR were processed when the larger volume of primary or metastatic lymph nodes were observed. The Pinnacle 9.8 system was used for the target area and OAR delineation. IMRT plans and HT plans were respectively formulated on Pinnacle 9.8 system and TomoTherapy Hi-Art Planning Station by the same medical physicist. 1.4 Planning techniques 1.4.1 IMRT plan IMRT plan were optimized by Dose Volume Optimize Version 11.0.31, and treatment dose was initially calculated using the Eclipse TPS algorithm. After interactively optimization by inverse planning software, the nal dose was calculated using the Anisotropic Analytical Algorithm version 11.031 dose algorithm with a grid size of 2.5 mm. 1.4.2 HT plan HT plan were optimized by TomoTherapy Hi-Art Software Version 2.07 (Accurray, Madison, WI, USA), and 3 major parameters were set as follows: 2.5 cm for eld width, 0.287 for a pitch and 2.1-2.6 for modulation factor. Dose calculation was performed by a collapsed cone convolution model with a grid size of 1.95 mm. 1.5 Dose prescription The prescribed dose was 69.96Gy/33F for PGTVnx, 66-70Gy/33F for PGTVnd, 60Gy/33F for PTV1, and 54Gy/33F for PTV2 respectively. Moreover, an at least 98% of the target area coverage, and >110% and > 93%of the prescribed dose was respectively cover <20% and <3% of planning target volume (PTV). OAR and target doses were restrained according to the protocol of Radiation Therapy Oncology Group (RTOG)-0615 as follows: parotid gland V30 <50%, temporal lobe <60Gy, brain stem <54Gy, spinal cord <45Gy, optic nerve and optic chiasm <54Gy, TMJ <60Gy, lens <5Gy, inner ear <50Gy. Page 4/14 1.6 Chemotherapy In both HT and IMRT treatment groups, cisplatin-based concurrent chemotherapy was given during radiotherapy. The dose of cisplatin was 80 mg / m2 every 3 weeks for 1 cycle. During chemotherapy, symptomatic treatment was applied for anti-vomiting and the gastrointestinal mucosa protection. 1.7 Dosimetric comparisons 1.7.1 Conformity index (CI) CI: measurement of how conformed the dose distribution is along target volume of PTV1 and PTV2. Formula: CI = (TVPV × TVPV)/(VPTV × VTV), whereas the denitions of TVPV , TVPV,VPTV and VTV were as follows: VPTV: volume
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