O'Connell, Mary Elizabeth Ann; (1993) Treatment outcome and radioiodine dose-response in differentiated thyroid carcinoma. Doctoral thesis (M.D), UCL (University College London).

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Abstract

Radioiodine (131I) has been used to treat differentiated thyroid carcinoma for the past fifty years. The activity administered remains empirical and most clinicians prescribe a fixed activity for ablation and therapy based upon experience and likely side effects. This lack of tumour dosimetry contrasts sharply with planning for external beam radiotherapy where precise tumour-dose prescription is mandatory. Estimation of absorbed radiation dose delivered to target tissue has been largely ignored in the past partly beacuse of the difficulty in measuring that part of the target volume which is metabolically active. Where absorbed dose has been estimated there is no consensus as to what absorbed dose should be delivered in order to destroy thyroid remnants and metastatic lesions. In order to calculate the absorbed radiation dose to those tissues which concentrate radioiodine, three parameters must be determined: the initial activity in the target tissue; the effective half-life of the radioiodine and the mass of tissue. Tumour and normal thyroid absorbed doses have been determined using a dual-headed whole-body scanner with special high- resolution low-sensitivity collimators. Improved accuracy in the estimation of functioning tumour mass has been achieved using positron emission tomography with a low-cost large area multi-wire proportional chamber camera, developed by the Physics Department of the Royal Marsden Hospital in collaboration with the Rutherford Appleton Laboratories. Dosimetry studies were performed for 54 patients with differentiated thyroid carcinoma (40 papillary, 14 follicular). There were 39 females and 15 males, ages 22 to 79 years. Dose-response graphs have been constructed in order to determine the tumouricidal dose for differentiated thyroid carcinoma metastases and thus enable precise activities of radioiodine to be prescribed in order to maximise tumour kill and minimise morbidity. The clinical data demonstrate that the administration of fixed activities of radioiodine results in a very large range of radiation absorbed dose to residual normal thyroid tissue and metastases of differentiated thyroid carcinoma. Following near-total thyroidectomy and 3.0 GBq 131I, a mean absorbed dose of 349 Gy achieved complete ablation of thyroid remnants in 67[percent] of patients (73[percent] of sites). Patients who had persistent uptake in the thyroid region on subsequent radioiodine scanning had received a mean absorbed dose of only 80 Gy. Failure to ablate may be attributed to two possible factors: large residua following less than radical surgery and the presence of tumour in association with normal tissue. Radioiodine therapy appears to be most effective in destroying small volumes of tissue after optimum surgical cytoreduction. Moreover, when tumour remains in association with normal tissue, the results here indicate that a much lower concentration of radioiodine can be achieved. For these two groups of patients, higher activities of are indicated. Successful destruction of cervical node metastases has been accomplished with absorbed doses of 150 Gy following functional neck dissection. Bone metastases, which are generally associated with a poor prognosis, require doses in excess of 100 Gy for eradication but this can be achieved for solitary deposits following initial surgical debulking. Nevertheless, worthwhile palliation may still be achieved with absorbed doses lower than this. However, the clinical data suggest that absorbed doses less than 20 Gy are sub-therapeutic and that alternative therapy should be considered if less than this can be achieved with radioiodine therapy. The dose-response data explain the spectrum of clinical response to fixed activities of radioiodine. In future they will enable precise prescription of radioiodine to achieve tumouricidal doses whilst avoiding the morbidity, staff hazards and expense of ineffective therapy.

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