Anaplastic Thyroid Carcinoma

Anaplastic Thyroid Carcinoma

Case presentation

73M w CAD (MI x1, no interventions), T2DM (not on insulin), hx smoking (0.3 ppd x 45y, quit 10y ago), p/w 50lb weight loss, dysphagia, ~4mo enlarging neck mass, found to have AKI and large neck mass on imaging.

TImeline

• 2022-04 intermittent sinus issues began, multiple courses of abx, voice hoarse
• 2022-07-12 PCP visit: noted 36lb weight loss since January. Dysphagia at times. Left face hurts when he lies down. Nontender thryomegaly present on exam. TSH 7.14
• 2022-07-13 US thyroid: left lobe heterogenous and 6.8x5.6x4.4 (R lobe 3.4x1.3x1.4)
• 2022-08-14 presented to VUMC

Case presentation

Timeline

• 2022-08-15 FNA: ATC vs PDTC, but need more tissue for confirmation and ancillary testing
• 2022-08-19 Core bx:
  • Gross: Sections show an infiltrative malignant neoplasm composed primarily of plump, epithelioid and spindle cells with pleomorphic nuclei, mitotic activity, and background acute and chronic inflammation. In this tumor component, there is no appreciable nesting, squamous, glandular, or other differentiation. There is, however, a focus of a more well-differentiated neoplasm in nests, cords, and small follicles, a few with colloid, which is morphologically consistent with a follicular neoplasm.
  • IHC: +PAX-8 (nested foci and spindled component strong and extensive) and TTF-1 (nested foci strong and extensive and spindled component more focal). The nested foci are strongly and extensively positive for cytokeratins AE1/AE3 and 8/18 while the spindled component is negative for both cytokeratins.
• 2022-08-21 BRAF PCR: + for c.1799T>A (p. V600E)

Case presentation

Tumor board

• Surgery: not a surgical candidate (mostly tumor factors)
• RT: planned
• Med onc: let's talk

And then...

• PEG placed
• many discussions w primary, med onc, family
• home w hospice
• died at home 3mo later
  • ~11mo from first sx (weight loss)
  • ~6mo from notable thyroid mass
  • ~4mo from tissue dx

Questions

• What is ATC?
• Why is it so gnarly?
• What is the prognosis?
• What are the key details of workup that change management?
  • What kind of imaging should we get?
  • Do we need to ask for anything special from pathology?
• How was it managed classically?
• How is it managed in the modern era?
  • What is the role of surgery?
  • What is the role of RT?
  • What is the role of systemic (chemo/immuno/small molecule) therapy?

Epidemiology

• some geographies have higher percent prevalence, up to 10%
• differences in percent prevalence appear to be largely driven by general healthcare disparities
• percent prevalence has fallen rapidly since the 1960s (25-35%)
  • iodine
  • fixing earlier-stage thyroid cancers

Epidemiology

• median OS: 3-6mo, median 1y survival: 20% (historically)
• accounts for up to 50% of deaths due to thyroid cancer
  • general thyroid cancer 2009 incidence: 37,200
  • general thyroid cancer 2009 death rate: 1,630
  • ATC incidence: 2%
  • ATC yearly death rate: near 100%
  • 37000 * 0.02 = 740

Epidemiology

• male:female 1.5:2
• typically >60yo
• 30% have long-standing goiter, then rapid progression
• IVa - localized - 10%
• IVb - locally advanced - 35%
• IVc - metastatic - 55% (lung, bone, liver, brain)
• Differentiated thyroid cancer (DTC) component or hx of DTC in 58-90% of cases

Overview (WHO Criteria changed in 2022)

Staging (AJCC 8th Edition)

All ATC is considered stage IV.

Advanced T stages are defined by extrathyroidal invasion.

Management

Management continued - targets

• 70% PD-L1 ≥70%
• 73% TPS ≥5%
• 10-15% dMMR
• 20-45% BRAF (dabrafenib-trametinib¹, vemurafenib, cobimetinib)
• 2-3% ALK (crizotinib, brigatinib, ceritinib)
• 2-3% NTRK (larotrectinib, entrectinib)
• 2-3% RET (selpercatinib, praseltinib)
• mKI - lenvatinib

Management continued - chemo +/- RT

• modest overall benefit, but can be started quickly
• typically taxane+platinum or doxorubicin+taxane/platinum
• most prefer regimens with weekly dosing given rapid doubling time
  • e.g. carbo AUC2 + paclitaxel 50-100mg/m2
  • there's no real data for this, very institution and provider specific
• involve RT early for consideration of chemo+RT

Ongoing trials (as of early 2023)

Key points

• ATC is universally fatal, but early targeted and multidisciplinary intervention can improve outcomes, including extending survival to years in some cases
• Call pathology, get BRAF IHC and/or PCR as fast as possible
• Even if the mgmt appears to be primarily surgical, involve H&N med onc specialist up front
• TKI+IO is an attractive option, but it can be difficult to get IO approved quickly enough to make a difference
  • TKI can typically get approved quickly
• resection can be beneficial even in the metastatic setting, neoadjuvant therapies can increase the feasibility