Dose-Escalation of Radiotherapy Dose in Oropharyngeal Squamous Cell Cancers

Abstract

The incidence of oropharyngeal squamous cell cancer (OPSCC) has increased greatly in recent years, while a considerable portion of intermediate and high risk HPV- patients with a significant smoking history continue to relapse despite radical radiotherapy. This current study investigates whether increasing the delivered radiotherapy dose to the gross tumour volume (GTV) to 84 Gy is feasible while maintaining optimal PTV coverage along with acceptable organs at risk (OARs) doses. Ten representative patients (HPV-, smokers) with high risk, locally advanced OPSCC, were re-planned retrospectively using a commercially available treatment planning system, RapidPlan® (RP) and multi-criteria optimisation (MCO). All plans consisted of two VMAT fields with two full rotational arcs at 6 MV and 600 MU/min. At our centre, OPSCCs are typically prescribed 65 Gy in 30# to the high risk planning target volume (PTV_65) while the low risk PTV_54 is treated to 54 Gy in 30#. The original clinical plans were re-optimised with a locally published RP model and MCO to achieve an escalated dose to the GTV [84 Gy in 30# (78 Gy {EQD2Gy})] while achieving comparable PTV coverage and OAR sparing consistent with our centre’s specified dose constraints. Comparisons were made between the 1) clinically reviewed plans and four additional groups consisting of the clinical plans re-optimised with 2) RP, 3) RP + MCO, 4) Escalated + RP and 5) Escalated + RP + MCO. Finally, plan deliverability for all plans was assessed using MapCheck, modulation factor (MF) and MLC average leaf pair opening (ALPO). Dose escalated (Group 5) plans offered significantly superior PTV_65 and GTV coverage (p<0.05) at particular dose metrics compared to the original (Group 1) plans (D95%, D2%). We found no significant difference between these groups for PTV_54 coverage for D95% (p=0.87) and D2% (p=0.09). Also, escalating the GTV dose did not significantly increase the OARs pertinent to this study; mean laryngeal (p=0.51), contralateral- (p=0.14) and ipslateral- (p=0.11) parotid doses between these groups. On average, the overall hotspot increased from 108.6% to 128.4% for Group 5 resulting in sharper dose gradients around the target volumes affording equivalent OAR sparing. We found that Group 5 and Group 1 plans were clinically comparable in terms of plan deliverability with pre-treatment QA MapCheck results recorded at 3%/3mm. Also, the MF and ALPO for group 5 (0.48; 3.5) compared to group 1 (0.49; 3.1) further proved comparable plan deliverability. This planning feasibility study exploring RP combined with MCO has, rather promisingly, enabled the dose to the GTV to be escalated without significantly increasing pertinent OARs. As evidence showing that recurrences most often occur in the GTV is growing, dose escalation has the potential to treat high risk patients more effectively in the first instance and is likely to be safe due to comparable OAR doses currently administered.