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Original Investigation
August 6, 2020

Evaluation of Overall Survival in Patients With Anaplastic Thyroid Carcinoma, 2000-2019

Author Affiliations
  • 1Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston
  • 2Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston
  • 3Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston
  • 4Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston
  • 5Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston
JAMA Oncol. 2020;6(9):1397-1404. doi:10.1001/jamaoncol.2020.3362
Key Points

Question  Is emerging use of targeted therapy, immunotherapy, surgery, and radiation therapy associated with improved overall survival in patients with anaplastic thyroid carcinoma (ATC)?

Findings  In this single-institution cohort study of 479 patients with ATC spanning nearly 20 years, 1- and 2-year survival significantly increased from 35% and 18% in the 2000-2013 era (n = 227) to 47% and 25% in the 2014-2016 era (n = 100), and 59% and 42% in the 2017-2019 era (n = 152), respectively.

Meaning  This study suggests that ATC may be effectively treated with highly specialized molecular-based personalized therapies, and surgery when appropriate, regardless of disease stage.

Abstract

Importance  Anaplastic thyroid carcinoma (ATC) historically has a 4-month median overall survival (OS) from time of diagnosis, with disease-specific mortality approaching 100%. The association between recent major advancements in treatment and OS has yet to be evaluated.

Objective  To evaluate rates of OS in patients with ATC over the last 2 decades.

Design, Setting, and Participants  Retrospective cohort study in a single tertiary care institution. Patients with histopathological confirmation of ATC from January 2000 to October 2019 were included and divided into 3 groups according to date of presentation: 2000-2013, 2014-2016, and 2017-2019.

Main Outcomes and Measures  Overall survival compared among different treatment eras and differing therapies, including targeted therapy, immunotherapy, and surgery.

Results  Of 479 patients (246 men [51%]; median age, 65.0 [range, 21.1-92.6] years) with ATC evaluated, 52 (11%) were stage IVA, 172 (36%) stage IVB, and 255 (53%) stage IVC at presentation. The median OS of the entire cohort was 0.79 years (9.5 months), ranging from 0.01 to 16.63. The OS at 1 and 2 years was 35% (95% CI, 29%-42%) and 18% (95% CI, 13%-23%) in the 2000-2013 group (n = 227), 47% (95% CI, 36%-56%) and 25% (95% CI, 17%-34%) in the 2014-2016 group (n = 100), and 59% (95% CI, 49%-67%) and 42% (95% CI, 30%-53%) in the 2017-2019 group (n = 152), respectively (P < .001). The hazard ratio was 0.50 (95% CI, 0.38-0.67) for the 2017-2019 group compared with the 2000-2013 patients (P < .001). Factors associated with improved OS included targeted therapy (hazard ratio, 0.49; 95% CI, 0.39-0.63; P < .001), the addition of immunotherapy to targeted therapy (hazard ratio, 0.58; 95% CI, 0.36-0.94; P = .03), and surgery following neoadjuvant BRAF-directed therapy (hazard ratio, 0.29; 95% CI, 0.10-0.78; P = .02). Patients undergoing surgery following neoadjuvant BRAF-directed therapy (n = 20) had a 94% 1-year survival with a median follow-up of 1.21 years.

Conclusion and Relevance  In this large single-institution cohort study spanning nearly 20 years, changes in patient management appear to be associated with significant increase in survival. The era of untreatable ATC is progressively being replaced by molecular-based personalized therapies, with integration of multidisciplinary therapies including surgery and radiation therapy.

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    1 Comment for this article
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    Improvement of overall survival in patients with anaplastic thyroid carcinoma
    Tomoyuki Kawada, MD | Nippon Medical School
    Maniakas et al. evaluated rates of overall survival (OS) in patients with anaplastic thyroid carcinoma (ATC) over the last 2 decades (1). A total of 479 patients, including 246 men, with ATC were classified into 52 (11%) of stage IVA, 172 (36%) of stage IVB, and 255 (53%) of stage IVC. The median OS of the entire cohort was 0.79 years, ranging from 0.01 to 16.63. The OS at 1 and 2 years was 35% and 18% in the 2000-2013 group (n = 227), 47% and 25% in the 2014-2016 group (n = 100), and 59% and 42% in the 2017-2019 group (n = 152), respectively. Significant factors associated with improved OS were targeted therapy, the addition of immunotherapy to targeted therapy, and surgery following neoadjuvant BRAF-directed therapy, presenting hazard ratios (95% CI) of 0.49 (0.39-0.63, 0.58 (0.36-0.94), and 0.29 (0.10-0.78), respectively. The authors concluded that changes in patient management, molecular-based personalized therapies and integration of multidisciplinary therapies, might be associated with significant increase in survival. I want to add information regarding their study.

    Wächter et al. analyzed the changing trends of treatment concepts and associated OS over the last two decades in 42 patients with histologically confirmed ATC (2). Median OS for all tumor stages was 6 months, and 6.5 months for stage IVA/B and 4 months for stage IVC carcinoma patients. The median OS of patients with stage IVA/B carcinomas was significantly prolonged after multimodal treatment than after surgery alone. But the median OS of stage IVC patients after trimodal therapy was not significantly longer than after debulking procedures. In addition, there was no significant prolonged survival in patients with multimodal treatment by comparing data in the time period 1999-2009 and 2009 to 2019. They handled a limited number of patients, and stable estimate should be made by summing-up the data.

    Sugitani et al. previously reported prognostic factors and treatment outcomes in 677 patients with ATC, which was derived from a multicenter registry, the ATC Research Consortium of Japan (ATCCJ). The patients were treated between 1995 and 2008. ATC was classified into four types, and anaplastic transformation at a distant site showed the worst outcomes. In addition, prevalence of 6-month OS was 60% for stage IVA, 45% for IVB, and 19% for IVC, respectively. Furthermore, age ≥70 years, presence of acute symptoms, leukocytosis presenting white blood cell count ≥10,000/cubic mm, large tumor >5 cm, T4b tumor, and distant metastasis were significant risk factors for lower survival. They observed that UICC stages and prognostic factors were closely related to subsequent OS in patients with ATC. I suspect that recent OS might be improved even in this population, which should be specified by further study.


    References
    1. Maniakas A, Dadu R, Busaidy NL, et al. Evaluation of overall survival in patients with anaplastic thyroid carcinoma, 2000-2019. JAMA Oncol. 2020 Sep 1;6(9):1397-1404.
    2. Wächter S, Vorländer C, Schabram J, et al. Anaplastic thyroid carcinoma: changing trends of treatment strategies and associated overall survival. Eur Arch Otorhinolaryngol. 2020 May;277(5):1507-1514.
    3. Sugitani I, Miyauchi A, Sugino K, et al. Prognostic factors and treatment outcomes for anaplastic thyroid carcinoma: ATC Research Consortium of Japan cohort study of 677 patients. World J Surg. 2012 Jun;36(6):1247-54.
    CONFLICT OF INTEREST: None Reported
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