Interfractional and intrafractional errors assessed by daily cone-beam computed tomography in nasopharyngeal carcinoma treated with intensity-modulated radiation therapy: a prospective study

Heming LU 2 Hui LIN 1 Guosheng FENG 0 Jiaxin CHEN 2 Liuyang SHU 3 Qiang PANG 2 Jinjian CHENG 2 Luxing PENG 2 Danling WU 2 Chaolong LIAO 2 Ying MO 2 0 Department of Medical Oncology, People's Hospital of Guangxi Zhuang Autonomous Region , Nanning, PR China 1 Clinical Oncology Center, People's Hospital of Guangxi Zhuang Autonomous Region , Nanning, PR China 2 Department of Radiation Oncology, People's Hospital of Guangxi Zhuang Autonomous Region , Nanning, PR China 3 Department of Clinical Medicine, Guangxi Medical University , Nanning, PR China This prospective study was to assess interfractional and intrafractional errors and to estimate appropriate margins for planning target volume (PTV) by using daily cone-beam computed tomography (CBCT) guidance in nasopharyngeal carcinoma (NPC). Daily pretreatment and post-treatment CBCT scans were acquired separately after initial patient setup and after the completion of each treatment fraction in 10 patients treated with IMRT. Online corrections were made before treatment if any translational setup error was found. Interfractional and intrafractional errors were recorded in the right-left (RL), superior-inferior (SI) and anterior-posterior (AP) directions. For the translational shifts, interfractional errors >2 mm occurred in 21.7% of measurements in the RL direction, 12.7% in the SI direction and 34.1% in the AP direction, respectively. Online correction resulted in 100% of residual errors 2 mm in the RL and SI directions, and 95.5% of residual errors 2 mm in the AP direction. No residual errors >3 mm occurred in the three directions. For the rotational shifts, a significant reduction was found in the magnitudes of residual errors compared with those of interfractional errors. A margin of 4.9 mm, 4.0 mm and 6.3 mm was required in the RL, SI and AP directions, respectively, when daily CBCT scans were not performed. With daily CBCT, the margins were reduced to 1.2 mm in all directions. In conclusion, daily CBCT guidance is an effective modality to improve the accuracy of IMRT for NPC. The online correction could result in a 70-81% reduction in margin size. - In the past decade, radiation therapy (RT) techniques have evolved rapidly, aiming at delivering a higher tumoricidal dose to improve local and/or regional control, while decreasing side-effects through minimizing irradiation damage to the critical structures. However, variations in patient setup and organ motion are limiting factors to achieving this goal. In general, organ motion during RT delivery in head-and-neck cancer is not significant; setup errors, however, should not be underestimated. Guckenberger et al. [1] found that in patients with head-and-neck cancer, translational errors were 2 mm in 13.9% of all measurements for each axis separately, and rotational errors were >2 in 11.1% of all measurements. For patients with elongated target volumes and sharp dose gradients to adjacent organs at risk, both translational and rotational errors resulted in considerably decreased target coverage and highly increased doses to the organs at risk compared with the initial treatment plan. Recently, several three-dimensional (3D) imaging techniques have been introduced to assess patient setup errors on the basis of the bony anatomy and sufficient soft-tissue contrast. They include kilovoltage (KV) and megavoltage (MV) cone-beam CT (CBCT) [25], CT scanner equipped with medical accelerators [67] and tomotherapy treatment units [8]. Both KV CBCT and MV CBCT are capable of verifying patient position in 3D, their role in the future may also include dose verification and adaptive planning. With regard to the visualization of soft tissues and undesired extra dose to patients, KV CBCT appears to be superior to MV CBCT [9]. Patients with nasopharyngeal carcinoma (NPC) have critical structures adjacent to the tumor that are more likely to be involved directly with the tumor itself, or be affected by RT, compared with those with other head-and-neck cancers. Impairment of the critical structures may affect their functions, thus ultimately reducing patients quality of life. Therefore, accurate delivery of radiation doses to the targets and their surrounding normal structures is a prerequisite to maximizing tumor kill while minimizing toxicities. In our department, since May 2009 we have been treating NPC routinely using an Elekta linear accelerator (Synergy, Stockholm, Sweden) with image-guided RT (IGRT) using a mounted KV CBCT scanner. Meanwhile, a prospective study was conducted to assess the interfractional and intrafractional errors in NPC treated with intensity-modulated radiation therapy (IMRT) through daily KV CBCT imaging, and to determine the margin necessary for the clinical target volume (CTV) to planning target volume (PTV) expansion. MATERIALS AND METHODS Eligibility criteria Patients with histologically proven NPC and treated with curative intent were enrolled into this study. Inclusion criteria were as follows: age 18 years; Eastern Cooperative Oncology Group (ECOG) Performance Status 02; Stages IIVb according to the 2002 AJCC Staging System. Patients diagnosed with, or treated for other malignances, or treated with non-IMRT techniques were excluded from the study. Written informed consent was obtained for all patients. The study was approved by the Institutional Review Board (IRB) of the Peoples Hospital of Guangxi Zhuang Autonomous Region (No. 201104). Immobilization and simulation All patients were immobilized in a supine position with the head in a neutral position with a tailored thermoplastic mask covering the head, neck and shoulders. Intravenous contrast-enhanced CT using a 2-mm slice from the vertex to the manubriosternal joint was performed for planning. The CT data were imported to the CMS-XiO planning system (CMS Inc., St. Louis, MO, USA). Target delineation and treatment planning The target delineation in NPC patients has been described in detail elsewhere [10], and was in accordance with the International Commission on Radiation Units and Measurements Reports 50 and 62, as well as an Institutional Treatment Protocol. In brief, the primary gross volume (GTVnx) and the involved lymph nodes (GTVnd) included all known gross disease as determined by the imaging, clinical and endoscopic findings. CTVnx included the GTVnx plus 510-mm margin, and CTVnd included the GTVnd plus 5-mm margins. CTV1 was defined as the entire nasopharynx, parapharyngeal space, pterygopalatine fossa, posterior third of the nasal cavity and maxillary sinuses, inferior sphenoid sinus, posterior ethmoid sinus, skull base and anterior half of the clivus. CTV1 also included the ipsilateral level II for node-negative neck, or extended to the next ipsilateral level for node-positive neck, or included the full length of ipsilateral neck for node-positive in the lower neck. CTV2 was defined as the low-risk node region below the CTV1. Level V was separated by the borderline between the CTV1 and C (...truncated)