Radiation Oncology/Thyroid/Anaplastic

Epidemiology

• 2% of thyroid cancers
• 13-39% thyroid cancer deaths
• F>M 3:1
• Mean age of diagnosis is 65

Pathophysiology

• Thought to be a de-differentiation of a previously differentiated thyroid cancer.
• 20% have history of differentiated thyroid CA
• 20-30% have concurrent papillary thyroid CA
• loss of p53 thought to be a major step in de-differentiation.

Histologic Subtypes

Histologic subtype has not been found to affect prognosis.

• Spindle Cell
• Giant Cell
• Squamoid

Staging

All anaplastic thyroid CA is considered stage IV.

see Staging for details.

Treatment

• Monotherapy (surgery, chemo, xrt) have not shown to benefit overall survival.
• Current treatment of choice is multi-modality. Upfront resection is preferred if tumor confined to thyroid.
• Hyperfractionated xrt with adriamycin treatment of choice for locally advanced non-metastatic. Consider consolidative surgery if good response to chemoxrt.
• Dose of 60 Gy in 40 fx over 4 wks.

Treatment Prognostic Factors

• SEER Database Analysis, 2005 PMID 15739211 "Anaplastic thyroid carcinoma. Treatment outcome and prognostic factors," (Kebebew E, Cancer. 2005; 103(7):1330-5.)
  • 516 pts from SEER cancer registry tx'd for anaplastic thyroid CA from 1973-2000.
  • Overall cause-specific mortality at 6 mo's was 68.4% and at 12 mo's was 80.7%.
  • On multi-variate analysis age<60 and intrathyroid tumor (w/o mets) were independent predictors of lower cause-specific mortality.
  • Conclusion: given the majority of data for ATC derived from small single institution series which are subject to selection bias, this analysis identifies prognostic factors that may be used to triage more aggressive treatments to patients who may benefit.

Combined Modality Approach

• SEER Database Analysis, 2008 (1983-2002) PMID 18838882 — "Surgery and radiotherapy improves survival in patients with anaplastic thyroid carcinoma: analysis of the surveillance, epidemiology, and end results 1983-2002." (Chen J, Am J Clin Oncol. 2008 Oct;31(5):460-4.)
  • 261 pts who had surgery performed or recommended
  • Median survival 4 months. On multivariate analysis, distant disease, tumor size > 7 cm, and treatment with surgery (+/- RT) were significant related to survival. The addition of RT to surgery resulted in improved survival for pts with disease extending into adjacent tissue but not for those with disease limited to the capsule or with distant metastatic disease
  • Conclusion: surgery and radiotherapy improves survival.

• Princess Margaret, 2001 PMID 11413523 "Completely resected anaplastic thyroid carcinoma combined with adjuvant chemotherapy and irradiation is associated with prolonged survival," (Haigh PI, Cancer. 2001; 91(12):2335-42.)
  • 33 pts w/ anaplastic thyroid cancer retrospectively reviewed to determine prognostic factors. 64% w/ metastatic dz. 92% received adjuvant therapy.
  • Pts w/ curative resection w/ longer median survival.
  • Conclusion: Complete resection or maximum tumor debulking followed by adjuvant chemo/xrt resulted in some long term survivals.

• Mayo Clinic, 2001 PMID 11742333 "Anaplastic thyroid carcinoma: a 50-year experience at a single institution," (McIver B, Surgery. 2001; 130(6):1028-34.)
  • 134 cases b/w 1949-99, mean age 67, 46% w/ mets at time of dx
  • 72% underwent surgery, 30% w/ complete resection
  • Neither surgery, chemo, nor radiation improved survival significantly. Combined modality approach was the only approach that led to long-term survivors.

Altered Fractionation of Radiotherapy

• Princess Margaret, 2006 PMID 16967442 "Clinical outcome of anaplastic thyroid carcinoma treated with radiotherapy of once- and twice-daily fractionation regimens," (Wang Y, Cancer. 2006; 107(8):1786-92)
  • 47 pts w/ anaplastic thyroid CA tx'd b/w 1983-2004. Pts tx'd palliatively or w/ curative intent w/ goal to assess local control, survival, toxicity of once vs twice daily regimens.
  • 94% 6 mo local PFS if xrt w/ radical intent, 64% if palliative intent. Median OS 3.3 mo's longer if BID fractionation (13.6 vs 10.3 mo's)
  • Conclusion: twice daily fractionation appears to lead to better outcome.

• Royal Marsden Pure Accelerated XRT, 1999 PMID 10225555 "Phase II evaluation of high dose accelerated radiotherapy for anaplastic thyroid carcinoma," (Mitchell G, Radiother Oncol. 1999; 50(1):33-8.)
  • 17 pts w/ anaplastic thyroid CA tx'd w/ BID xrt to 60.8 Gy (1.8 Gy in AM, 2 Gy in PM)
  • 3 pts w/ CR, 7 pts w/ partial response; toxicity from esophagitis/dysphagia high (40% grade 4 pharyngo-esophagitis, dysphagia)
  • Conclusions of the authors were that toxicities of pure acceleration were unacceptably high in spite of improved local control rate.

• Sweden, 1994 PMID 8055459 "Combined doxorubicin, hyperfractionated radiotherapy, and surgery in anaplastic thyroid carcinoma. Report on two protocols. The Swedish Anaplastic Thyroid Cancer Group," (Tennvall J, Cancer. 1994; 74(4):1348-54. )
  • 33 pts w/ anaplastic thyroid CA tx'd w/ hyperfractionated xrt (30 Gy preop, 46 Gy postop), doxorubicin, surgery
  • 48% local control, 24% death from local failure, 4 pts survived 2 yrs