Does a short course of prophylactic prednisolone prevent short-term and medium term side effects of radioactive iodine in patients with differentiated thyroid cancer?

Study Setting: Apeksha Hospital (National Institute of Cancer), Maharagam, Sri Lanka.

After obtaining informed written consent from patients who accept the invitation, they will be randomized to either intervention arm or placebo arm based on a computer based random number generator. Randomization will be stratified by the total dose of radioactive iodine 50-100, >100 and <200, and >200 milliCuries. Recruitment will be allocated to each group in a ratio of 1:1:1. Patients who withdraw their consent to participate prior to response evaluation will be replaced. Participants will be given an information sheet and will be explained in detail about the study, and informed written consent will be taken prior to recruitment. The basic demographic information such as age, sex, ethnicity and medical history including the details related to thyroid cancer (such as type, grade, stage, lymph node involvement), comorbidities and the current treatment will be collected using the clinic notes and interviewer administered questionnaire. The contact details will also be collected for the purpose of follow up. A general physical examination will be performed for a baseline assessment prior to administration of radioactive iodine (RAI). Basic haematological parameters including full blood count and renal functions will be performed before RAI treatment. A baseline quality of life scores which include Euro-Qol (EQ-5D-5L)and Functional Assessment of Cancer Therapy-Head and Neck (FACT H&N) will be measured. Patients will be stratified based on the dose of the RAI into three strata (50-100, >100 and <200, and >200 milliCuries) based on the American Thyroid Association Guidelines 2015. Then from each group, patients will be randomised to two arms, the experimental arm and the placebo arm.

Experimental arm: Prophylactic oral (prednisolone 0.5mg/kg and omeprazole 20mg) single dose 6 hours before RAI therapy and followed by oral (prednisolone 0.5mg/kg and omeprazole 20mg) daily for 3 days

Control/ placebo arm: Oral (Placebo + omeprazole 20mg) single dose 6 hours before RAI therapy and followed by oral (Placebo + omeprazole 20mg) daily for 3 days. Starch tablets of similar shape, size and colour would be used as placebo.

All patients will be given a diary and asked to keep a log of any new symptoms after RAI therapy. Patients in both groups will be instructed to have sugar-free hard candy or gum in their mouths at all times when awake for a period of one week. Proton pump inhibitors are routinely given in our setting to minimise dyspeptic symptoms which is reported to occur in around 50% and thus will be given to both arms. This will also be helpful to minimise the gastrointestinal adverse effects of glucocorticoids. At least a fluid input of 2,400 mL will be maintained during the first week after therapy. If patient develops adverse effects of RAI, symptomatic management would be given and the given treatment will be documented. After completion of the study patients will subjected to standard routine follow up for thyroid cancer.

a) Patients with histologically proven differentiated papillary and follicular thyroid cancer following total thyroidectomy and are eligible for RAI therapy, referred to the National Institute of Cancer, Sri Lanka will be invited to participate in this study. b) Without any history of radiotherapy c) Age >18 years d) An ECOG performance status score of 0-1 e) Patients must have normal marrow function as defined below: leukocytes >3,000/mcL absolute neutrophil count >1,500/mcL platelets >100,000/mcL f) In females of the reproductive age group, exclusion of pregnancy before commencing RAI and avoiding future pregnancy for 6 months using contraceptives is mandatory. Therefore, such patients who are capable of child bearing on adequate contraception will be included in this study. g) Available for follow up and management in the study centre for at least 6 months h) Informed, voluntary, written consent i) Patients must sufficiently understand English, Sinhala or Tamil to fill in the quality of life and patient reported outcome measures.

a). Those with absolute and relative contraindications for glucocorticoids such as uncontrolled diabetes mellitus, gastric and duodenal ulcers, immunosuppression, ongoing or active infections, chronic infective diseases b). History of previous RAI therapy c). Previous major head and neck surgery d). Patients with severe debilitating diseases that can affect the quality of life. e). Patients with previous history of salivary gland diseases such as sialadenitis, duct obstruction, calculi, and ophthalmological diseases such as xerophthalmia and conjunctivitis f) Uncontrolled concurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations (within 12 months before study) that would limit compliance with study requirements. g) Pregnant women and breast feeding mothers are excluded as RAI therapy is contraindicated in such patients. h) Diagnosed HIV-positive patients on combination antiretroviral therapy are ineligible as glucocorticoids may further suppress the immunity and increase the chances of opportunistic infection i) Prior diagnosis of cancer that was: • More than 5 years prior to current diagnosis with subsequent evidence of disease recurrence or clinical expectation of recurrence is greater than 10% • Within 5 years of current diagnosis with the exception of successfully treated basal cell or squamous cell skin carcinoma or carcinoma in situ of the cervix