Anaplastic Thyroid Cancer: Current Concepts

Abstract

Anaplastic thyroid cancer (ATC) is a rare and aggressive malignancy with an extremely poor prognosis compared to other types of thyroid cancer. Survival rates for ATC are dependent on the extent of disease at diagnosis, and many patients present with locally advanced or metastatic disease. Strong evidence suggests that ATC develops from pre-existing differentiated thyroid cancer (DTC) through a post-malignant cancer progression or anaplastic transformation. Current treatments are multimodal and offer little hope for a cure. Unfortunately, ATC has remained a highly lethal malignancy. ATCs possess genetic and molecular derangements that could be targeted by novel therapies in the future.

Commentary

Janice L. Pasieka

Anaplastic thyroid cancer (ATC) is a rare but highly lethal form of thyroid cancer. All ATCs are considered stage IV tumours, according to the current American Joint Committee on Cancer (AJCC) staging system. Galindo and Wiseman have provided strong evidence to suggest that an ATC develops from pre-existing well-differentiated thyroid cancer. The current treatment regimes are multimodal and include surgery, radiation and systemic therapy. This chapter covers presentation, the molecular and genetic characterization of these tumours, and the treatment option currently utilized. Although to date treatment of ATC remains largely ineffective, the authors outline the potential benefit of surgery, radiation, chemotherapy, and the newer targeted molecular therapies that have shown promise as therapeutic options.

Recently, guidelines for the management of ATC were published by the American Thyroid Association (ATA) [1]. This is the first time the ATA has put together guidelines for the management of ATC. This chapter nevertheless serves as a great resource for the clinician caring for patients with this rare tumour. To summarize, the ATA guidelines, patients with stages IVa and IVb (potentially resectable disease) should be treated with a multimodality approach, including surgery, external beam radiation and systemic therapy. The role of surgery in this disease ultimately depends on the disease characteristics. Ten per cent of patients with ATC present with intra-thyroidal disease alone. The recommendation from the ATA is for a total thyroidectomy with therapeutic lymph node dissection in these patients. When extrathyroidal is encountered, en bloc resection should be considered if grossly negative margins can be achieved. This is then followed by radiation and chemotherapy. Where surgery is not amenable as a first-line option, radiation and chemotherapy may downstage the disease, allowing for surgery to aid with locoregional control.

Unresectable ATC patients may respond initially to systemic therapy in combination with external beam radiation as such, patients with stage IVc disease (distant metastatic disease) should be considered for clinical trial or palliative care.

Systemic therapy, both targeted and with cytotoxic agents, has not shown clear benefits in improving survival or quality of life. Consequently, the need for the development of novel systemic therapeutic options is critical. As such, all patients with ATC should be considered for a therapeutic trial. The largest prospective study conducted in ATC was recently published [2]. The addition of fosbretabulin (CA4P), a novel tubulin-blinding compound, in combination with thyroid surgery, suggested an improvement in patient survival [2]. This FACT1 trial was a randomized controlled phase II/III trial assessed in the safety and efficacy of carboplatin/paclitaxel—with or without CA4P. Unfortunately, the study was terminated after enrolling only 80 patients because of the low accrual rate of the subjects needed for the trial. This study illustrated the difficulty in enrolling patients with rare tumours across 40 centres in 11 different countries. However, it did provide insight into the need for multimodality therapy and the role surgery plays in this disease.

References

1. Smallridge RC, Ain KB, Asa SL, et al. American Thyroid Association guidelines for the management of patients with anaplastic thyroid cancer. Thyroid. 2012;22:1104–39.

2. Sosa JA, Balkissoon J, Lu SP, et al. Thyroidectomy followed by fosbretabulin (CA4P) combination regimen appears to suggest improvement in patients survival in anaplastic thyroid cancer. Surgery. 2012;152:1078–87.