Does the Incorporation of Chemotherapy to Adjuvant Radiation Skew the Influence of Treatment Package Time in High-risk Oral Cavity Carcinoma? A Multi-institutional Collaborative Study
Ghanem A, Woody N, Shymick M, Geiger J, Tsai CJ, Dunlap N, Liu H, Burkey B, Lamarre E, Caudell J, Porceddu S, Lee N, Adelstein D, Koyfman S, and Siddiqui F. Does the Incorporation of Chemotherapy to Adjuvant Radiation Skew the Influence of Treatment Package Time in High-risk Oral Cavity Carcinoma? A Multi-institutional Collaborative Study. International Journal of Radiation Oncology Biology Physics 2020; 108(2):E5.
International Journal of Radiation Oncology Biology Physics
Background: Treatment package time (TPT) defined as days elapsing from surgery to the end of adjuvant radiation therapy (RT) is known to impact outcomes in head and neck cancer patients receiving adjuvant RT alone.
Objectives: We sought to explore the influence of adding concomitant chemotherapy to adjuvant RT (CRT) on the effect of TPT in high risk oral cavity squamous cell carcinoma (OCSCC).
Methods: We queried our multi-institutional oral cavity collaborative database with 1282 cases to identify OCSCC diagnosed between 2005-2015 that received adjuvant CRT after surgery. All included cases had at least a high-risk feature (extracapsular nodal extension (ECE) and/or positive final surgical margin (PM)) and were treated within 180 days beyond surgery. TPT was calculated in days between surgery date and the last RT fraction and was stratified in 10 days increments (10D-INC). Kaplan-Meier curves, log-rank p-values and uni/multi-variate analyses (MVA) were used to investigate the interaction between TPT in 10D-INC and Overall (OS), locoregional failure free (LRFS) and distant metastases free (DMFS) survival.
Results: We identified 187 cases treated with CRT who met out inclusion criteria after excluding cases with inadequate RT and those with unknown treatment dates. Median age was 58 years (24-87), males were 66% and ever smokers were 69% with median smoking pack years of 30. ECE and PM were detected in 32% and 85% respectively; and oral tongue then floor of mouth constituted 49% and 18% of the study cohort. Median RT dose delivered was 66 Gy and median cisplatin dose received was 200 mg/m2 per patient. For the entire cohort median TPT was 98 days (63-162) divided between time to start RT of 51 days (29-109) and median total RT duration of 45 days (33-97). Two- and 5-years OS were significantly better for TPT≤90 days (28%) than TPT>90 days of 71% vs. 65% (2-years) and 62% vs. 45% (5-years); p=0.05 respectively. However, there was no difference for LRFS or DMFS (p>0.05). Clinico-pathological features, smoking index as well as RT and cisplatin doses were non-different between TPT≤90 vs. >90 days; nevertheless, more extensive lymph node (LN) dissection (p=0.039) and unplanned reoperation (p=0.037) were associated with TPT>90 days. On MVA, TPT in 10D-INC was independently detrimental for OS (HR:1.14; CI [1-1.28]; p=0.043) in addition to perineural invasion, age and positive LN (p<0.05 for all).
Conclusions: TPT was associated with worsened OS in one of the largest multi-institutional cohorts treated with modern modalities with no influence on LRFS or DMFS for high-risk OCSCC managed with adjuvant CRT. The addition of concurrent chemotherapy to adjuvant RT is suggested to negate the established impact of TPT on oncologic outcomes. Worse OS with prolonged TPT seemed to be driven by peri-operative complications and poor performance status.