Prospective In Silico Study of the Feasibility and Dosimetric Advantages of MRI-Guided Dose Adaptation for Human Papillomavirus Positive Oropharyngeal Cancer Patients Compared With Standard IMRT

Abstract

We aim to determine the feasibility and dosimetric benefits of a novel MRI-guided IMRT dose-adaption strategy for human papillomavirus positive (HPV+) oropharyngeal carcinoma (OPC). Patients with locally advanced HPV+ OPC were consented. Pretreatment and biweekly in-treatment serial MRIs were acquired using RT immobilization setup. The initial gross tumor volume (GTVinitial) was manually segmented using MRI then propagated to the registered simulation CT. CTVinitial was defined as GTVinitial+6-8mm to incorporate high-risk subclinical disease. For each patient, two IMRT plans were created (i.e. standard and adaptive). The prescription dose for the standard plans was 2.12 Gy for 33 fractions to the PTVinitial (CTVinitial+3mm). For adaptive plan, a new GTVadaptive was segmented on serial MRIs in case of a detectable tumor shrinkage, then a new CTVadaptive was generated. The prescription dose to PTVadaptive (CTVadaptive+3mm) was 2.12 Gy/fx to allow for maximum dose to the residual disease. Prescription dose for any previously involved volumes was 1.52 Gy/fx to ensure a floor dose of 50.16 Gy to any region ever deemed to have been directly involved with tumor. All elective nodal volumes were encompassed in CTVelective, and prescribed 1.52 Gy/fx for a total of 50.16 Gy. Organs at risk (OARs) were auto-segmented using a validated atlas-based autosegmentation software. Dosimetric parameters of OARs were recorded for standard vs adaptive plans then the normal tissue complication probability (NTCP) for toxicity endpoints were calculated using literature-derived multivariate logistic regression models. Five patients were included, 3 men and 2 women. Median age was 58 years. Three tumors originated at the tonsillar fossa and two at the base of tongue. The average dose to 95% of PTVinitial volume was 70.6 Gy (SD, 0.5) for standard plans vs 59.5 Gy (SD, 2.0) for adaptive plans. Results showed the majority of OARs had decrease in dosimetric parameters using adaptive compared with standard plans particularly for swallowing-related structures, as illustrated in table 1. The average reduction of the probability of developing dysphagia≥ grade 2 and feeding tube persistence at 6-month was 11% and 4%, respectively. The probability of developing hypothyroidism at 2-year post-treatment was also reduced by average 5% while the probability of xerostomia at 1-year was only reduced by average 1% for adaptive plans compared with standard IMRT. This in silico results showed the suggested adaptive approach is technically feasible, safe, and advantageous in reducing dose to OARs specially swallowing musculature, thus reducing the NTCP of dysphagia≥ grade 2 and feeding tube persistence at 6-month post-treatment.Abstract 3666; Table 1OARMean dose Standard (Gy)Mean dose Adaptive (Gy)Supraglottis5346SPC6358MPC5248IPC3532Mylogeiohyoid3833Genioglossus5247Oral cavity4238Soft palate5549Ipsilat. parotid3027Contralat. parotid1716Brain Stem118Thyroid gland3633 Open table in a new tab