Radiation Oncology/Thyroid/Medullary

Epidemiology

 * About 5% of thyroid cancers.
 * Present in 5th decade.
 * 80% are sporadic, but some can result from MEN 2 syndrome.
 * There is also a Familial (non MEN 2-related) medullary thyroid cancer syndrome

Genetics

 * Medullary thyroid CA associated w/ MEN 2 syndrome results from a mutation in RET gene.
 * MEN 2 w/ ~70% penetrance

Pathophysiology

 * Neuroendocrine tumor that derive from parafollicular C cells
 * C cells secrete can secrete calcitonin (which can therefore be used as a tumour marker)
 * Non iodine avid therefore no role for I-131 ablation after surgery

Staging
UICC/AJCC Staging
 * see Staging for details


 * Stage I - <2cm, confined to thyroid
 * Stage II - 2-4cm, confined to thyroid
 * Stage III - >4cm, N+ in level VI, or microscopic extrathyroid extension
 * Stage IV - M+, N+ outside of level VI, gross soft tissue extension

Treatment

 * Treatment includes total thyroidectomy with central neck lymph node dissection.
 * Indications for adjuvant radiation: microscopic residual dz, extensive nodal involvement, extrathyroid extension.

Adjuvant Radiation

 * University of Toronto, 1996 (1954-92) PMID 8875751 -- "Medullary thyroid cancer: analyses of survival and prognostic factors and the role of radiation therapy in local control." Thyroid. 1996 Aug;6(4):305-10.
 * 73 pts w/ medullary thyroid CA. 46 pts received xrt (median dose 40 Gy).
 * On multi-variate analysis, factors that predicted for lower CSS were extraglandular invasion and postop gross residual dz.
 * Pts w/ high risk for locoregional relapse (microscopic residual dz, extraglandular invasion, N+) benefited from RT.
 * Conclusion: external beam RT recommended if high risk


 * FFCI, 1992 (1971-89) PMID 1736326 -- "Results of postoperative radiation therapy in medullary carcinoma of the thyroid: a retrospective study by the French Federation of Cancer Institutes--the Radiotherapy Cooperative Group."  Radiother Oncol. 1992 Jan;23(1):1-5.
 * 59 pts w/ medullary thyroid CA receiving EBRT w/ curative intent. Total thyroidectomy in 55 pts.  11 pts w/ residual tumor, 44 pts w/ N+.  Mean dose 54 Gy.
 * 70% local control, with failures mostly occurring in RT field.


 * MDACC, 1988 (1943-87) PMID 2807151 -- "Medullary thyroid carcinoma: prognosis of familial versus nonfamilial disease and the role of radiotherapy." Samaan NA et al.  Horm Metab Res Suppl. 1989;21:21-5.
 * 202 pts w/ medullary thyroid CA
 * Pts w/ MEN2 had longer survival rates than sporadic medullary thyroid CA
 * When pts who were matched for age, extent of dz, and surgery were compared for effect of radiation therapy, pts who had no radiotherapy were found to live significantly longer.

Guidelines

 * ATA Guidelines - Website
 * 2009: PMID 19469690 PDF "Medullary Thyroid Cancer: Management Guidelines of the American Thyroid Association" (Kloos RT, Thyroid. 2009 Jun;19(6):565-612.)