AREST Study


AREST- Study

AdjuvantRadiotherapy in Early Stage Oral Cancers (AREST)

CTRI Reg No: CTRI/2017/07/009114

Aim

The aim of this study is to assess the benefit of post-operative adjuvant radiotherapy in patients with an early Oral squamous cell carcinoma (OSCC).

Hypothesis

Post-operative adjuvant radiotherapy would significantly reduce the risk of loco-regional recurrence in patients with pathologically proven early stage oral cancers with depth of invasion >/=5mm.

Objectives

Primary objective:

  • To determine the impact of post-operative adjuvant radiotherapy on loco-regional recurrence free survival in patients with early-stage oral cancer with depth of invasion >/=5 mm.

Secondary objectives:

  • To compare disease-free survival and overall survival between the two groups.
  • To assess and compare the quality of life between the two groups.
  • To assess the acute and long-term radiation toxicity.

Study Design

Phase III Open Label Prospective Randomized Controlled Trial using stratified randomization. Patients will be randomized to one of the two arms.

  • Arm I: Observation – observed as per the standard protocol followed at TMH.
  • Arm II: Adjuvant Radiotherapy - Patients belonging to study arm will receive Adjuvant radiotherapy 60Gy, 30 fractions for 30 days over 6 weeks as routinely prescribed according to TMC recommendations and timely implementing it within or by 6 weeks of surgery.

Patients will be stratified on the following factors:

  • Presence of PNI/Lympho-Vascular Emboli (LVE)
  • Histological grade (well-differentiated/moderately differentiated vs poorly differentiated)
  • Tongue/Floor of Mouth vs Buccal Mucosa

Study Population

Treatment naïve pathologically proven post-operative early stage squamous cell carcinoma of oral Cavity.

Intervention

Intervention in the study group will be in the form of post-operative adjuvant radiotherapy starting within 6-weeks of primary surgery.

Endpoints

Primary endpoint will be to determine loco regional recurrence free survival for Adjuvant radiotherapy in tumor thickness ≥ 4 mm.

Secondary end point

  • Overall survival
  • Disease free survival
  • Quality of life
  • Radiation induced toxicity
  • Performance status assessment

Summary of statistical methods

A two-sided log rank test with an overall sample size of 392 subjects (196 in the control group and 196 in the treatment group) achieves 80.0% power at a 0.050 significance level to detect a hazard ratio of 00.6256 when the proportion surviving in the control group is 70% and considering 10% lost to follow-up for both arms. The study lasts for 7 time periods (years) of which subject accrual (entry) occurs in the first 4 time years. The accrual pattern across time periods is uniform (all periods equal).