Dosimetric comparison of intensity-modulated proton therapy versus intensity-modulated radiation therapy in unilateral treatment of patients with head and neck cancer

Summary: There is currently no consensus on the role of proton therapy in head and neck cancers, pending multiple prospective studies. We conduct a dosimetric comparison of their treatment IMRT plans with simulated intensity-modulated proton therapy (IMPT) treatment plans, examining target coverage and dose to critical OARs involved in acute and late toxicities. In this single-institution retrospective review, patients with primary tumors from all head and neck sites treated with unilateral IMRT, who experienced worsened dysphagia symptoms post-radiation, were included in the study. Deterioration in dysphagia symptoms was defined using the MD Anderson Dysphagia Inventory (MDADI) composite score (range 20-100, higher scores reflect better function) as a ≥10 point decrease between pre- and post-radiation or < 60 point MDADI score post-radiation. Xerostomia Questionnaire scores (XQ, range 0-100, higher scores reflect worse function) were also prospectively collected for these patients. A total of 23 patients were included in the study. For dosimetric comparison between treated IMRT plans and simulated IMPT plans, we reported maximum dose for serial critical structures and mean dose for other organs at risk (OARs). Target coverage (V95%) was reported for both high-dose and low-dose clinical target volumes (CTV). Statistical analysis was performed using Wilcoxon signed-rank tests. We employed a Bonferroni correction for multiple comparisons, with an adjusted significance level of 0.003. Median MDADI scores decreased from 81 pre-radiation therapy (RT) to 56 post-RT (p< 0.001). XQ scores reflected a similar worsening of xerostomia symptoms post-RT. Both IMRT and IMPT plans provided appropriate target coverage of the high-dose CTV (median V95 99.91% for both) and low-dose CTV (median V95 99.71% and 99.90%, respectively). IMPT plans allowed for reduction in dose to critical OARs, including the spinal cord (6.4Gy vs 37.3Gy IMRT, p< 0.001) and brainstem (5.6Gy vs 33.0Gy IMRT, p< 0.001). Furthermore, mean dose to the oral cavity and contralateral pharyngeal constrictors were significantly reduced in IMPT plans (19.7Gy vs 33.6Gy IMRT oral cavity, p< 0.001; 20.4Gy vs 26.2Gy IMRT contralateral pharyngeal constrictor, p< 0.001). Examining dose to the major salivary glands confirmed the dosimetric advantage of IMPT. Mean dose to the contralateral parotid was 7.6Gy and 0.04Gy for IMRT and IMPT, respectively, and mean dose to the contralateral submandibular gland was 15.4Gy and 1.4Gy for IMRT and IMPT. IMPT spares dose to OARs compared to IMRT plans in head and neck cancers treated with unilateral radiation. We hypothesize that IMPT can prevent acute and long-term toxicity for these patients, particularly dysphagia and xerostomia. Stephanie Zhao (she/her/hers), BA (Presenting Author) - Washington University School of Medicine; Kevin Chen, MD (Co-Author) - Department of Radiation Oncology, Washington University School of Medicine; Michael Watts, MS (Co-Author) - Department of Radiation Oncology, Washington University School of Medicine; Kenneth Walker, MS (Co-Author) - Department of Radiation Oncology, Washington University School of Medicine; Jessica Hillard, MS (Co-Author) - Department of Radiation Oncology, Washington University School of Medicine; Anthony J. Apicelli, MD, PhD (Co-Author) - Department of Radiation Oncology, Washington University School of Medicine; Nikhil Rammohan, MD, PhD (Co-Author) - Department of Radiation Oncology, Washington University School of Medicine