Prognostic factors in radiotherapy of anaplastic thyroid carcinoma: a single center study over 31 years

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Abstract

Background

Anaplastic thyroid carcinoma has a very poor prognosis. We analyzed the effect of surgery, radiotherapy and chemotherapy on survival time and side effects in patients with ATC.

Methods

We retrospectively analyzed all patients (n = 63) with histologically confirmed ATC who presented at our clinic between 1989 and 2020. We analyzed the survival with Kaplan–Meier curves and cox proportional hazard models and acute toxicities with logistic regression models.

Results

Out of 63 patients, 62 received radiotherapy, 74% underwent surgery and 24% received combined chemotherapy. A median radiation dose of 49 Gy (range 4–66 Gy) was applied. In 32% of the cases opposing-field technique was used, in 18% 3D-conformal, in 27% a combination of opposing field and 3D-conformal technique and 21% obtained IMRT (intensity modulated radiotherapy) or VMAT (volumetric modulated arc radiotherapy). Median overall survival (OS) was 6 months. We identified five predictive factors relevant for survival: absence of distant metastases at the time of diagnosis (OS 8 months), surgery (OS 9.8 months), resection status R0 (OS 14 months), radiation dose of 50 Gy or higher (OS 13 months) and multimodal therapy (surgery, radiotherapy and chemotherapy) with a median OS of 9.7 months.

Conclusion

In spite of the dismal outcome, longer survival can be achieved in some patients with ATC using surgery and radiotherapy with a high radiation dose. Compared to our previous study, there are no significant advantages in overall survival.

Trial registration Retrospectively registered.

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Most cited references 30

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Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial

Christopher Nutting, James Morden, Kevin J. Harrington … (2011)

Summary Background Xerostomia is the most common late side-effect of radiotherapy to the head and neck. Compared with conventional radiotherapy, intensity-modulated radiotherapy (IMRT) can reduce irradiation of the parotid glands. We assessed the hypothesis that parotid-sparing IMRT reduces the incidence of severe xerostomia. Methods We undertook a randomised controlled trial between Jan 21, 2003, and Dec 7, 2007, that compared conventional radiotherapy (control) with parotid-sparing IMRT. We randomly assigned patients with histologically confirmed pharyngeal squamous-cell carcinoma (T1–4, N0–3, M0) at six UK radiotherapy centres between the two radiotherapy techniques (1:1 ratio). A dose of 60 or 65 Gy was prescribed in 30 daily fractions given Monday to Friday. Treatment was not masked. Randomisation was by computer-generated permuted blocks and was stratified by centre and tumour site. Our primary endpoint was the proportion of patients with grade 2 or worse xerostomia at 12 months, as assessed by the Late Effects of Normal Tissue (LENT SOMA) scale. Analyses were done on an intention-to-treat basis, with all patients who had assessments included. Long-term follow-up of patients is ongoing. This study is registered with the International Standard Randomised Controlled Trial register, number ISRCTN48243537. Findings 47 patients were assigned to each treatment arm. Median follow-up was 44·0 months (IQR 30·0–59·7). Six patients from each group died before 12 months and seven patients from the conventional radiotherapy and two from the IMRT group were not assessed at 12 months. At 12 months xerostomia side-effects were reported in 73 of 82 alive patients; grade 2 or worse xerostomia at 12 months was significantly lower in the IMRT group than in the conventional radiotherapy group (25 [74%; 95% CI 56–87] of 34 patients given conventional radiotherapy vs 15 [38%; 23–55] of 39 given IMRT, p=0·0027). The only recorded acute adverse event of grade 2 or worse that differed significantly between the treatment groups was fatigue, which was more prevalent in the IMRT group (18 [41%; 99% CI 23–61] of 44 patients given conventional radiotherapy vs 35 [74%; 55–89] of 47 given IMRT, p=0·0015). At 24 months, grade 2 or worse xerostomia was significantly less common with IMRT than with conventional radiotherapy (20 [83%; 95% CI 63–95] of 24 patients given conventional radiotherapy vs nine [29%; 14–48] of 31 given IMRT; p<0·0001). At 12 and 24 months, significant benefits were seen in recovery of saliva secretion with IMRT compared with conventional radiotherapy, as were clinically significant improvements in dry-mouth-specific and global quality of life scores. At 24 months, no significant differences were seen between randomised groups in non-xerostomia late toxicities, locoregional control, or overall survival. Interpretation Sparing the parotid glands with IMRT significantly reduces the incidence of xerostomia and leads to recovery of saliva secretion and improvements in associated quality of life, and thus strongly supports a role for IMRT in squamous-cell carcinoma of the head and neck. Funding Cancer Research UK (CRUK/03/005).

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2021 American Thyroid Association Guidelines for Management of Patients with Anaplastic Thyroid Cancer: American Thyroid Association Anaplastic Thyroid Cancer Guidelines Task Force

Keith Bible, Electron Kebebew, James B. Brierley … (2021)

Background: Anaplastic thyroid cancer (ATC) is a rare but highly lethal form of thyroid cancer. Since the guidelines for the management of ATC by the American Thyroid Association were first published in 2012, significant clinical and scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, and researchers on published evidence relating to the diagnosis and management of ATC. Methods: The specific clinical questions and topics addressed in these guidelines were based on prior versions of the guidelines, stakeholder input, and input of the Task Force members (authors of the guideline). Relevant literature was reviewed, including serial PubMed searches supplemented with additional articles. The American College of Physicians Guideline Grading System was used for critical appraisal of evidence and grading strength of recommendations. Results: The guidelines include the diagnosis, initial evaluation, establishment of treatment goals, approaches to locoregional disease (surgery, radiotherapy, targeted/systemic therapy, supportive care during active therapy), approaches to advanced/metastatic disease, palliative care options, surveillance and long-term monitoring, and ethical issues, including end of life. The guidelines include 31 recommendations and 16 good practice statements. Conclusions: We have developed evidence-based recommendations to inform clinical decision-making in the management of ATC. While all care must be individualized, such recommendations provide, in our opinion, optimal care paradigms for patients with ATC.

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PD-1 Blockade in Anaplastic Thyroid Carcinoma

Jaume Capdevila, Lori J Wirth, Thomas Ernst … (2020)

PURPOSE Anaplastic thyroid carcinoma is an aggressive malignancy that is almost always fatal and lacks effective systemic treatment options for patients with BRAF -wild type disease. As part of a phase I/II study in patients with advanced/metastatic solid tumors, patients with anaplastic thyroid carcinoma were treated with spartalizumab, a humanized monoclonal antibody against the programmed death-1 (PD-1) receptor. METHODS We enrolled patients with locally advanced and/or metastatic anaplastic thyroid carcinoma in a phase II cohort of the study. Patients received 400 mg spartalizumab intravenously, once every 4 weeks. The overall response rate was determined according to RECIST v1.1. RESULTS Forty-two patients were enrolled. Adverse events were consistent with those previously observed with PD-1 blockade. Most common treatment-related adverse events were diarrhea (12%), pruritus (12%), fatigue (7%), and pyrexia (7%). The overall response rate was 19%, including three patients with a complete response and five with a partial response. Most patients had baseline tumor biopsies positive for PD-L1 expression (n = 28/40 evaluable), and response rates were higher in PD-L1–positive (8/28; 29%) versus PD-L1–negative (0/12; 0%) patients. The highest rate of response was observed in the subset of patients with PD-L1 ≥ 50% (6/17; 35%). Responses were seen in both BRAF -nonmutant and BRAF -mutant patients and were durable, with a 1-year survival of 52.1% in the PD-L1–positive population. CONCLUSION To our knowledge, this is the first clinical trial to show responsiveness of anaplastic thyroid carcinoma to PD-1 blockade.

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Author and article information

Contributors

Julia Jacob: julia.jacob@student.uni-halle.de

Dirk Vordermark: dirk.vordermark@uk-halle.de

Kerstin Lorenz:

ORCID: http://orcid.org/0000-0003-0281-1950

kerstin.lorenz@uk-halle.de

Daniel Medenwald: daniel.medenwald@uk-halle.de

Journal

Journal ID (nlm-ta): Radiat Oncol

Journal ID (iso-abbrev): Radiat Oncol

Title: Radiation Oncology (London, England)

Publisher: BioMed Central (London )

ISSN (Electronic): 1748-717X

Publication date (Electronic): 19 April 2023

Publication date PMC-release: 19 April 2023

Publication date Collection: 2023

Volume: 18

Electronic Location Identifier: 71

Affiliations

[1 ]GRID grid.9018.0, ISNI 0000 0001 0679 2801, Martin Luther University Halle-Wittenberg, ; 06120 Halle, Germany

[2 ]GRID grid.9018.0, ISNI 0000 0001 0679 2801, Department of Radiation Oncology, , Martin Luther University Halle-Wittenberg, ; 06120 Halle, Germany

[3 ]GRID grid.9018.0, ISNI 0000 0001 0679 2801, Department of Visceral-, Vascular, and Endocrine Surgery, , Martin Luther University Halle-Wittenberg, ; 06120 Halle, Germany

Author information

Kerstin Lorenz http://orcid.org/0000-0003-0281-1950

Article

Publisher ID: 2249

DOI: 10.1186/s13014-023-02249-w

PMC ID: 10114488

PubMed ID: 37076888

SO-VID: 33126c01-df9f-4983-833e-bd91736c6df3

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 20 June 2022

Date accepted : 23 March 2023

Funding

Funded by: Universitätsklinikum Halle (Saale) (8960)

Open Access :

Open Access funding enabled and organized by Projekt DEAL.

Custom metadata

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: anaplastic thyroid cancer (atc),radiotherapy,prognostic factors,multimodal therapy,long-term-study

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: anaplastic thyroid cancer (atc), radiotherapy, prognostic factors, multimodal therapy, long-term-study

Prognostic factors in radiotherapy of anaplastic thyroid carcinoma: a single center study over 31 years

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Karger: Oncology

Most cited references 30

Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial

2021 American Thyroid Association Guidelines for Management of Patients with Anaplastic Thyroid Cancer: American Thyroid Association Anaplastic Thyroid Cancer Guidelines Task Force

PD-1 Blockade in Anaplastic Thyroid Carcinoma

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