Radiation to the Primary Tumor in Metastatic Anaplastic Thyroid Cancer

Augustin, Teresa; Oliinyk, Dmytro; Rauch, Josefine; Koehler, Viktoria Florentine; Spitzweg, Christine; Belka, C.; Käsmann, Lukas

doi:10.21873/invivo.12279

Cited by 4 publications

(5 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this context, even though ATCs are often described as a radioresistant disease, adjuvant radiotherapy appears to increase the overall survival of patients with non-metastatic ATCs ( 158 ). Also, radiotherapy could offer a local control in advanced ATCs or for inoperable patients ( 159 ). Indeed, multimodal therapy with radiotherapy and chemotherapy (doxorubicin or cisplatin) is associated with the most extended survival and is considered a standard of care for these patients.…”

Section: The Implication In Endocrine Cancers: Thyroid Carcinoma As An Examplementioning

confidence: 99%

Hypoxia in Solid Tumors: How Low Oxygenation Impacts the “Six Rs” of Radiotherapy

et al. 2021

View full text Add to dashboard Cite

Radiotherapy is an important component of cancer treatment, with approximately 50% of all cancer patients receiving radiation therapy during their course of illness. Nevertheless, solid tumors frequently exhibit hypoxic areas, which can hinder therapies efficacy, especially radiotherapy one. Indeed, hypoxia impacts the six parameters governing the radiotherapy response, called the « six Rs of radiation biology » (for Radiosensitivity, Repair, Repopulation, Redistribution, Reoxygenation, and Reactivation of anti-tumor immune response), by inducing pleiotropic cellular adaptions, such as cell metabolism rewiring, epigenetic landscape remodeling, and cell death weakening, with significant clinical repercussions. In this review, according to the six Rs, we detail how hypoxia, and associated mechanisms and pathways, impact the radiotherapy response of solid tumors and the resulting clinical implications. We finally illustrate it in hypoxic endocrine cancers through a focus on anaplastic thyroid carcinomas.

show abstract

Section: The Implication In Endocrine Cancers: Thyroid Carcinoma As An Examplementioning

confidence: 99%

Hypoxia in Solid Tumors: How Low Oxygenation Impacts the “Six Rs” of Radiotherapy

et al. 2021

View full text Add to dashboard Cite

show abstract

“…In total, 10 studies (Takahashi et al 2019 ; Aslan et al 2014 ; Crevoisier et al 2004 ; Stavas et al 2014 ; Ito et al 2012 ; Lim et al 2012 ; So et al 2017 ; Tennvall et al 2002 ; Troch et al 2010 ; Busnardo et al 2000 ) provided individualized patient data that were eligible for a pooled analysis with our single center cohort described previously (Augustin et al 2021 ). This new cohort included 123 patients with stage IVC ATC and a median age of 71 (39–94) years (Table 2 ).…”

Section: Resultsmentioning

confidence: 99%

“…Figures 1C, 2B); however, exact dosage remains unknown due to limited SEER data. Furthermore, our previous study showed that RT in advanced ATC may also offer a durable local control and can be considered safe for patients (Augustin et al 2021 ).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Role of surgery to the primary tumor in metastatic anaplastic thyroid carcinoma: pooled analysis and SEER-based study

Oliinyk

Augustin

Rauch

et al. 2022

J Cancer Res Clin Oncol

Self Cite

View full text Add to dashboard Cite

Purpose Anaplastic thyroid carcinoma (ATC) is an orphan disease with a fatal outcome. Surgery to the primary tumor in metastatic ATC is controversial. Determination of specific surgical techniques may help facilitate local control and, hence, beneficial overall and disease-specific survival. Methods Using individualized patient data derived from our systematic review of literature and our single center study (n = 123), conducting a Surveillance, Epidemiology, and End Results register (SEER)-based study (n = 617) we evaluated surgery, its combination with systemic and local therapies in metastatic ATC. Results Pooled cohort study showed surgery (p < 0.001), RT ≥ 30 Gy (p < 0.001), ChT (p < 0.001) and multimodal treatment (p = 0.014) to result in improved OS univariately. In the multivariate analysis, surgery (1.997 [1.162–3.433], p = 0.012) and RT ≥ 30 Gy (1.877 [1.232–2.843], p = 0.012) were independent predictors for OS. In SEER-based study of patients undergoing any tumor-directed treatment (n = 445) total thyroidectomy (p = 0.031), administration of ChT (p = 0.007), RT (p < 0.001), combination of surgery and RT ± ChT (p < 0.001) and multimodal treatment (p < 0.001) correlated with an improved DSS univariately. On the multivariate analysis, debulking surgery was an independent predictor for a worse outcome (HR 0.535, 95%CI 0.332–0.862, p = 0.010), whereas RT administration correlated with a longer DSS (HR 2.316, 95%CI 1.362–3.939, p = 0.002). Among operated patients from SEER register total thyroidectomy (p = 0.031), ChT (p = 0.007), RT (p < 0.001), combination of surgery and RT ± ChT (p < 0.001) and multimodal treatment (p < 0.001) correlated with an improved DSS in the univariate analysis, whereas debulking surgery was inversely correlated with the DSS (p < 0.001). On the multivariate analysis, debulking surgery was an independent predictor for a worse DSS (HR 0.535, 95%CI 0.332–0.862, p = 0.010), whilst RT administration correlated with a longer DSS (HR 2.316, 95%CI 1.362–3.939, p = 0.002). Conclusions Surgery to the primary tumor with the aim of R0/R1 resection, but not debulking, is associated with a significant OS and DSS benefit even in systemically metastasized disease.

show abstract

“…Interestingly, the potential of radiotherapy has been already observed in ATC [ 24 ]. In particular, EBRT has shown an improvement in overall survival and a reduction in metastasis after incomplete resection of ATC [ 25 , 26 ] and in combination with chemotherapy [ 27 ]. However, its possible combination with the checkpoint PD-L1 inhibitor atezolizumab for the treatment of ATC has not been highlighted yet.…”

Section: Discussionmentioning

confidence: 99%

Anti-Proliferative Effect of Radiotherapy and Implication of Immunotherapy in Anaplastic Thyroid Cancer Cells

Wächter

Roth

Gercke

et al. 2023

Life

View full text Add to dashboard Cite

Radiotherapy and immunotherapy have shown promising efficacy for the treatment of solid malignancies. Here, we aim to clarify the potential of a combined application of radiotherapy and programmed cell death-ligand 1 (PD-L1) monoclonal antibody atezolizumab in primary anaplastic thyroid cancer (ATC) cells. The radiation caused a significant reduction in cell proliferation, measured by luminescence, and of the number of colonies. The addition of atezolizumab caused a further reduction in cell proliferation of the irradiated ATC cells. However, the combined treatment did not cause either the exposure of the phosphatidylserine or the necrosis, assessed by luminescence/fluorescence. Additionally, a reduction in both uncleaved and cleaved forms of caspases 8 and 3 proteins was detectable in radiated cells. The DNA damage evidenced the over-expression of TP53, CDKN1A and CDKN1B transcripts detected by RT-qPCR and the increase in the protein level of P-γH2AX and the DNA repair deputed kinases. PD-L1 protein level increased in ATC cells after radiation. Radiotherapy caused the reduction in cell viability and an increase of PD-L1-expression, but not apoptotic cell death in ATC cells. The further combination with the immunotherapeutic atezolizumab could increase the efficacy of radiotherapy in terms of reduction in cell proliferation. Further analysis of the involvement of alternative cell death mechanisms is necessary to clarify their cell demise mechanism of action. Their efficacy represents a promising therapy for patients affected by ATC.

show abstract

Radiation to the Primary Tumor in Metastatic Anaplastic Thyroid Cancer

Cited by 4 publications

References 23 publications

Hypoxia in Solid Tumors: How Low Oxygenation Impacts the “Six Rs” of Radiotherapy

Hypoxia in Solid Tumors: How Low Oxygenation Impacts the “Six Rs” of Radiotherapy

Role of surgery to the primary tumor in metastatic anaplastic thyroid carcinoma: pooled analysis and SEER-based study

Anti-Proliferative Effect of Radiotherapy and Implication of Immunotherapy in Anaplastic Thyroid Cancer Cells

Contact Info

Product

Resources

About