Anaplastic thyroid carcinoma (ATC) is associated with a poor prognosis due to aggressive tumor growth and high treatment resistance. Hypofractionated treatment concepts may be more effective and less time consuming compared to normofractionated radiotherapy (RT). In this retrospective study, we aim to evaluate the outcome of hypofractionated regimens and perform a systematic review concerning hypofractionated RT and pooled analysis of this treatment modality. A systematic review using the MEDLINE/Pubmed and Cochrane databases was performed. Data from all eligible studies were extracted, and a pooled analysis of literature and our cohort (n = 60) was carried out to examine patient characteristics, toxicity, and outcomes of patients with ATC. As a result, median overall survival (OS) of the single center cohort was four (range 1–12) months. Survival rates at one, three, and six months were 82%, 55%, and 36%, respectively. In univariate analyses, multimodal treatment (p = 0.006) and gender (p = 0.04) were correlated with an improved OS. Six studies with a total number of 152 patients undergoing hypofractionated RT treatment were analyzed. The pooled analysis included four patient cohorts with 60 patients and showed median OS of 5.3 (range: 1–24) months. Multimodal treatment (p < 0.001) and a cumulative radiation dose ≥50 Gy in equivalent dose in 2 Gy fractions (EQD2) (p = 0.014) correlated with an improved OS. On multivariate analysis, multimodal treatment (p = 0.003, hazard ratio (HR): 0.636, 95% confidence interval (CI): 0.469–0.861) was an independent predictor for longer OS. After propensity score matching (PSM), hypofractionated RT appears to be non-inferior compared to normofractionated RT concerning OS. In conclusion, hypofractionated RT is effective with manageable toxicity. A dose escalation with ≥50 Gy (EQD2) correlated with a longer OS. Hypofractionated RT could be an integral part in multimodal treatment with a promising outcome.

Background: The present study aims to evaluate the outcomes and toxicity of elderly anaplastic thyroid cancer (ATC) patients receiving (chemo)radiotherapy, as well as to identify prognostic factors. Patients and methods: A systematic review using the MEDLINE/PubMed and Cochrane databases was performed. Individual data from all eligible studies were extracted, and a pooled analysis (n = 186) was conducted to examine patient characteristics and treatment. All consecutive ATC patients (≥65 years) treated between 2009 and 2019 at our institution were evaluated for outcomes concerning progression-free survival (PFS), overall survival (OS) probabilities and treatment-related toxicity. Results: The systematic review and pooled analysis identified age as a prognostic factor. The median OS of our patient cohort (n = 26) was three months (range = 0–125). The 6-, 12- and 24-month survival rates were 35%, 22% and 11%, respectively. In the univariate analysis, a Karnofsky performance status of >70%, the Union for International Cancer Control Tumor–Node–Metastasis classification, multimodal therapy and an EQD2 of >49 Gy were correlated with longer OS and PFS. The acute grade 3 toxicity of dysphagia, dyspnea, dermatitis, mucositis and dysphonia was found in 23%, 15%, 12%, 12% and 8% of patients. Conclusion: Age appears to be a prognostic factor in ATC. Elderly ATC patients can tolerate multimodal treatment and achieve a promising outcome. Prospective studies need to confirm our findings.

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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.

RNA replication is considered a crucial stage in the origins of life. However, both enzymatic and non-enzymatic RNA replication cycles are impeded by the 'strand separation problem' (SSP), a form of product inhibition arising from the extraordinary stability of RNA duplexes and their rapid kinetics of reannealing. Here we show that RNA trinucleotide triphosphates (triplets) can overcome the SSP by binding to and kinetically trapping dissociated RNA strands in a single-stranded form, while simultaneously serving as substrates for RNA replication by a triplet polymerase ribozyme (TPR). This enabled exponential replication of both (+) and (-) strands of double-stranded RNAs by the TPR when driven by coupled pH and freeze-thaw cycles. We demonstrate replication of a fragment of the ribozyme itself, and open-ended amplification of random RNA sequence pools over >70 cycles, with emergence of partial, distributive TPR self-replication and triplet codon drift towards a primordial genetic code.