LONG-TERM OUTCOMES FOLLOWING SUBSTANTIAL DE-ESCALATION OF ELECTIVE RADIOTHERAPY DOSE AND VOLUME IN PATIENTS TREATED WITH DEFINITIVE CHEMORADIOTHERAPY FOR HUMAN PAPILLOMAVIRUS-ASSOCIATED OROPHARYNGEAL CANCER

Purpose:

Major de-escalation of elective radiotherapy dose and volume for human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) can maintain two-year locoregional control (LRC) and survival while achieving excellent quality-of-life (QOL) profiles. We analyzed five-year follow-up to determine if these outcomes are sustained following definitive concurrent chemoradiotherapy (CCRT).

Materials and Methods:

This single-institution retrospective cohort study included consecutive patients with HPV-associated OPC starting CCRT at least five years prior to study inception. Patients underwent PET-CT and MRI staging. HPV diagnosis was confirmed by p16 immunohistochemistry and/or HPV-RNA in-situ hybridization. Elective volumes consisting of nodal levels and at-risk regions surrounding gross disease were treated to 30 Gy in 15 fractions. Cone-down volumes (gross disease without expansion) were sequentially boosted to 70 Gy in 35 fractions. Omitted nodal levels included level VII in the node-negative neck and uninvolved levels IB and V bilaterally. LRC was the primary outcome estimated using cumulative incidence functions with death as a competing risk. Overall (OS), progression-free (PFS), and distant metastasis-free survival (DMFS) were secondary outcomes estimated using Kaplan-Meier method. MD Anderson Dysphagia Index (MDADI) scores were obtained at each visit where available and compared to baseline using sign test; a clinically meaningful change (CMC) was 10 points.

Results:

From 2017-2019, 276 patients underwent CCRT; 172 (62.3%) received 300 mg/m2 high-dose cisplatin. Stage distribution included 87 (31.5%) patients with cT3-4 and 65 (23.5%) with cN2-3 disease (AJCC 8th Edition). With median follow-up of 64 months (IQR 50-74), 60-month LRC was 97.0%; OS 90.8%; PFS 85.9%, and DMFS 91.2%. No LR failure occurred after 18 months. One solitary elective nodal failure (1/267 patients [0.4%]) occurred at 6 months; this gross node, present but unidentified at diagnosis, received 30 Gy instead of the required 70 Gy. The remaining LR failures occurred in 70 Gy volumes. No failures occurred in omitted nodal levels. Two patients (0.7%) were gastrostomy-tube dependent for 12+ months. Mean (SE) MDADI composite score at baseline was 90.1 (0.86); 6 months 79.1 (1.1); 12 months 85.7 (1.3); 24 months 88.2 (1.3); 36 months 90.9 (1.7); 48 months 91.0 (1.8); and 60 months 92.2 (1.5). MDADI composite scores worsened at 6 months (p<0.001 and CMC) then stabilized (p>0.05) or numerically improved compared to baseline through 60 months.

Conclusions:

Long-term outcomes affirm the durable oncologic efficacy and QOL following substantially de-escalated elective radiotherapy. Confirmatory phase III data will help establish this systematic approach as the new standard-of-care for HPV-associated OPC treated with definitive CCRT.