Phase I trial of dose-escalated stereotactic radiosurgery (SRS) boost for unfavorable locally advanced oropharyngeal cancer

Abstract

Background and purpose Patients with locally advanced oropharynx squamous cell carcinoma have suboptimal outcomes with standard chemoradiation. Here, we evaluated toxicity and oncologic outcomes of dose escalation using radiosurgical boost for patients with unfavorable oropharynx squamous cell carcinoma. Materials and methods Between 2010–2017, Thirty four patients with intermediate- or high-risk oropharynx squamous cell carcinoma were enrolled onto this prospective phase I trial. Each patient received concurrent cisplatin and fractionated radiotherapy totaling 60 Gy or 66 Gy followed by radiosurgery boost to areas of residual gross tumor: single fraction of 8 Gy or 10 Gy, or two fractions of 5 Gy each. Primary endpoint was treatment toxicity. Secondary endpoints were local, regional, and distant disease control. Results Eleven, sixteen and seven patients received radiosurgery boost with 8 Gy in 1 fraction, 10 Gy in 1 fraction, and 10 Gy in 2 fractions respectively. Acute toxicities include 4 patients with tumor necrosis causing grade 3 dysphagia, of which 3 developed grade 4 pharyngeal hemorrhage requiring surgical intervention. At 24 months after treatment, 7%, 9%, and 15% had grade 2 dysgeusia, xerostomia, and dysphagia, respectively, and two patients remained feeding tube dependent. No grade 5 toxicities occurred secondary to treatment. Local, regional, and distant control at a median follow up of 4.2 years were 85.3%, 85.3% and 88.2%, respectively. Five patients died resulting in overall survival of 85.3%. Conclusions This study is the first to report the use of radiosurgery boost dose escalation in patients with unfavorable oropharynx squamous cell carcinoma. Longer follow-up, larger cohorts, and further refinement of boost methodology are needed prior to implementation in routine clinical practice. Trial Registration: Northwell Health Protocol #09-309A (NCT02703493) (https://clinicaltrials.gov/ct2/show/NCT02703493)

Dose escalation in advanced floor of the mouth cancer: a pilot study using a combination of IMRT and stereotactic boost

“…In addition, the results suggest a potential effect of dose escalation on local control. The acute radiation toxicity in the cohort was comparable to the results reported in other published studies [ 7 , 17 , 18 , 22 ] using different radiotherapy techniques and doses. No acute CTCAE grade 4 toxicity manifested.…”

“…One patient discontinued treatment earlier due to non-compliance and a worse tolerance of radiation toxicity. In contrast, Zeno et al [ 17 ] reported an incidence of acute grade 3 dermatitis, mucositis, and dysphagia of 15%, 15%, and 40% during treatment of T2–T4 oropharyngeal, laryngeal, and hypopharyngeal cancer by a combination of EBRT and stereotactic boost. Al-Mamgani et al [ 22 ] reported acute radiation toxicity grade 3 dysphagia in 17–20% of patients treated for oropharyngeal cancer with a combination of EBRT and brachytherapy or stereotactic boost.…”

“…In technically infeasible cases, such as large tumors, patients low-performance status, and contraindications of invasive procedures, a new image-guided stereotactic radiotherapy technique is an alternative option. Recently have been published studies with stereotactic dose escalation in patients with oropharyngeal carcinomas [ 17 , 18 ]. In addition, preclinical studies suggest that the effect of stereotactic radiotherapy includes the activation of ceramide apoptosis and alteration of the tumor vasculature, which may eventually help overcome tumor radioresistance [ 19 ].…”

Treatment-Related Dysgeusia in Oral and Oropharyngeal Cancer: A Comprehensive Review

“…The subjective analysis of dysgeusia can be performed by questionnaires where patients report any daily taste changes. The severity of the taste dysfunction can be graded using several intensity scales [11,23,25,30]. Moreover, there are several H&N disease-specific QOL questionnaires, such as the University of Washington QOL Questionnaire (UW-QOL), Functional Assessment of Cancer Therapy-H&N (FACT-H&N), the European Organization for Research and Treatment of Cancer QOL Questionnaire-H&N module (EORTC-H&N35) and 14-item Oral Health Impact Profile (OHIP-14).…”

“…The mild alterations accounted for 56% and 65% of acute and tardive toxicities, respectively, whereas moderate dysgeusia was reported in 32% and 24% of acute and late toxicities, respectively. Despite a gradual return to baseline scores, moderate dysgeusia was experienced by 7% of patients at 24 months post-treatment [23]. In recent years, the use of intensity-modulated RT (IMRT) has allowed for effectively reducing radiation doses.…”