Phase II randomized Controlled trial of postoperative Intensity modulated Radiotherapy (IMRT) in locally Advanced Thyroid Cancers.

Title:    Phase IIRandomised Controlled Trial of Postoperative Intensity Modulated Radiotherapy(IMRT) in Locally Advanced Thyroid Cancers

Background and rationale: Locally advanced thyroid cancers (AJCC - T4a, N1), are known to havehigh rates of loco-regional recurrences after conventional treatment withsurgery and radioactive iodine therapy. Most patients with recurrences areamenable to salvage surgeries; however these surgeries have very highmorbidity. A few retrospective studies have shown that the addition ofradiotherapy (RT) after surgery and radioiodine treatment has decreased theloco-regional recurrence rate in locally advanced thyroid cancers (LATC).However, all these studies are retrospective and heterogenous with no clearindications or protocols for radiotherapy  Recommendation41 of ATA guidelines states that, “The use of external beam irradiation totreat the primary tumor should be considered in patients over age 45 withgrossly visible extrathyroidal extension at the time of surgery and a highlikelihood of microscopic residual disease, and for those patients with grossresidual tumor in whom further surgery or RAI would likely be ineffective.â€5Thus the use of adjuvant RT in advanced differentiated thyroid cancer may beconsidered as standard of care.

However there are certain caveats to this:

1. The level of recommendation is B (‘thestrength of the evidence is limited by the number, quality, or consistency ofthe individual studies’).

2. All the previous studies have been retrospective,with heterogenous patient population, no clearly defined inclusion criteria andend points.

3. There is no data regarding toxicity ofadjuvant RT in any of these studies in these studies as most have beenretrospective in nature.

Aims,Objectives and hypotheses:

Primaryaim:

• To assess the impact of adjuvant RT on loco-regional control  in patients with locally advanced thyroid cancers who have undergone surgery with radioiodine therapy

Secondaryaim:

• To assess toxicity (early and late at 2 years) of adjuvant RT in these patients

Study Methodology

All patients who are willing toparticipate on the trial and have signed the informed consent form will be randomized toeither receive adjuvant external beam RT or no treatment. All patients(irrespective of randomization), will proceed toreceive radio-active iodine scanning and therapy as is standard for patientswith locally advanced differentiated thyroid cancers. This will be performedbetween 4-6 weeks after thyroidectomy providing adequate period for thyroidhormone withdrawal, to allow TSH to risebeyond 30microIU/ml. Adjuvant radiotherapy will be administered afterradioiodine therapy, within 8-10 weeks of the surgery. Patientsin both arms of the trial will be followed up for 5 years.

Sample size for the study has been calculatedconsidering a 23% decrease in loco-regional recurrence with addition ofadjuvant RT, as obtained from a previous study.

Eightpatients (5%) have been added to account for lost to follow up. The totalsample size is 72 with 36 in each arm

Alpha-80%

Beta-0.05