Gross Tumour Volume predicts survival in HPV related Oropharyngeal Squamous Cell Carcinoma

To investigate if tumour volume (primary, nodal and combined) predicts recurrence free (RFS) and overall survival (OS) in p16+ oropharyngeal squamous cell carcinoma.

Study design

We conducted a retrospective analysis of patients with OPSCC treated with curative radiotherapy in SLRON from 2013 - 2021. TNM 8th edition definition of stage was applied. 

Participants

Eligible participants had OPSCC and received radiotherapy as definitive, radical treatment. Diagnosis was based on clinical assessment, histological sampling and PET imaging. p16 status was available for all patients. Clinical examination and PET imaging were used to assess response to treatment. 

Treatment

Patients received 65-70Gy over 30-35 fractions, delivered using Intensity-Modulated Radiotherapy (IMRT).

Endpoints

Primary endpoints: 

1. To investigate if GTVp predict RFS & OS in p16+ OPSCC

2. To investigate if GTVn predict RFS & OS in p16+ OPSCC

3. To investigate if GTVcomb predict RFS & OS in p16+ OPSCC

Secondary endpoints:

1. To investigate if GTVp &/or GTVn predict RFS & OS in p16- OPSCC

2. To investigate if GTVp &/or GTVn predict RFS & OS in OPSCC

3. To investigate if use of concomitant chemotherapy improves outcomes in OPSCC in this cohort

4. To estimate RFS and OS 

Statistical Analysis

All analyses were performed in IBM SPSS Statistics ver 29.0, and involved descriptive statistics, survival analyses by Kaplan-Meier method, and linear regression by Cox Proportional Hazards (univariate & multivariate). OS was evaluated from date of final RT.  RFS was evaluated from date of final RT to the date of first local or distant recurrence, death, or last clinical assessment/investigation.

Baseline Characteristics

From January 2013 to April 2021, 246 patients were eligible for this review. Median age at first RT was 59.6. 187 (76%) were male.  179 (73%) had p16+ disease.  218 (88.6%) received chemotherapy. Median follow up was 25.5 months (0.5 - 96).

Disease stage & Tumour volumes

Patients with p16+ disease were diagnosed with earlier stage disease (86% stage 1 or 2), in comparison with those with p16- disease (3% stage 3 or 4; p< .001).

Treatment

Treatment was delivered using IMRT. 235 (95.5%) received 70Gy in 35 fractions and 11 (4.5%) received 65Gy in 30 fractions.  

Overall Survival

61 out of 246 patients (25%) died.  Median survival for the total population was not reached. 3, 4 and 5 year overall survival was 75% (95%CI: 69 to 81%), 69% (95%CI: 61 to 76%) and 64% (95%CI: 55 to 73%) respectively.

There was a significant difference in OS between those with P16- and P16+ (p<.001).

Median survival for the P16- population was 34.9 months (95%CI 13 to 56 months).

Median survival for the P16+ population was not reached.

Recurrence Free Survival

Median recurrence free survival for the total population was not reached.3, 4 and 5 year RFS survival was 65% (95%CI: 59 to 72%), 63% (95%CI: 56 to 70%) and 58% (95%CI: 49 to 66%) respectively.

There was a significant difference in RFS between those with P16- and P16+ (p<.001).

Median survival for the P16- population 23.6 months (95%CI 11 to 37 months).

Median survival for the P16+ population was not reached. 

Survival based on Gross Tumour Volume

For the total population (p16+ & p16-): 

• GTVp greater or less than median GTVp (dichotomized) was a statistically significant predictor of OS (p= .004)
• GTVp based on Adrian et al volume brackets <6 cm³, 6–12 cm³, 12–24 cm³, 24–48 cm³, 48–96 cm³, and>96cm³ (as suggested by Adrian et al, 2022) was a statistically significant predictor of OS (p<.001)
• GTVp greater or less than 40cm³ (as suggested by Adrian et al, 2022) was a statistically significant predictor of OS (p<.001)
• GTVcomb based on volume brackets <15cc, 15-70cc, >70cc (as suggested by Panje et al, 2017) was a statistically significant predictor of OS and RFS (p= .001 and p<.001 respectively).

When looking only at those with P16+, neither age, gender nor stage 1-2, were predictive of OS. The following variables were predictive of OS: GTVp, GTVp >18.3cc, GTV as per Adrian et al volume brackets, GTVp 15-70cc, GTVp>40cc, GTVn, GTVcomb and total dose.

We demonstrate that GTV (primary, nodal and combined) predict outcome in p16+ OPSCC. This metric is readily available to the Radiation Oncologist at tumour delineation, and therefore may aid dose de-escalation decision making, without added delay. 

Future work may investigate cautious dose de-escalation in a cohort with smaller GTVs.