Hypofractionated Radiotherapy for Anaplastic Thyroid Cancer: Systematic Review and Pooled Analysis

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.

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Clinical Outcome and Toxicity in the Treatment of Anaplastic Thyroid Cancer in Elderly Patients

Journal of Clinical Medicine ◽

10.3390/jcm9103231 ◽

2020 ◽

Vol 9 (10) ◽

pp. 3231

Author(s):

Teresa Augustin ◽

Dmytro Oliinyk ◽

Viktoria Florentine Koehler ◽

Josefine Rauch ◽

Claus Belka ◽

...

Keyword(s):

Systematic Review ◽

Thyroid Cancer ◽

Prognostic Factor ◽

Karnofsky Performance Status ◽

Performance Status ◽

Univariate Analysis ◽

Survival Rates ◽

Progression Free Survival ◽

Anaplastic Thyroid Cancer ◽

Pooled Analysis

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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Systematic review and pooled analysis of survival rates, success, and outcomes of osseointegrated implants in a variety of composite free flaps

Head & Neck ◽

10.1002/hed.26238 ◽

2020 ◽

Vol 42 (9) ◽

pp. 2669-2686 ◽

Cited By ~ 1

Author(s):

Darius Khadembaschi ◽

Gary I. Brierly ◽

Mark D. Chatfield ◽

Nicholas Beech ◽

Martin D. Batstone

Keyword(s):

Systematic Review ◽

Survival Rates ◽

Free Flaps ◽

Pooled Analysis ◽

Osseointegrated Implants

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Valproic acid, a histone deacetylase inhibitor, enhances sensitivity to doxorubicin in anaplastic thyroid cancer cells

Journal of Endocrinology ◽

10.1677/joe.1.06970 ◽

2006 ◽

Vol 191 (2) ◽

pp. 465-472 ◽

Cited By ~ 73

Author(s):

Maria G Catalano ◽

Nicoletta Fortunati ◽

Mariateresa Pugliese ◽

Roberta Poli ◽

Ornella Bosco ◽

...

Keyword(s):

Valproic Acid ◽

Thyroid Cancer ◽

Histone Deacetylase ◽

Topoisomerase Ii ◽

Human Cancer ◽

Combined Therapy ◽

Survival Rates ◽

Hdac Inhibitors ◽

Anaplastic Thyroid Cancer ◽

Anaplastic Thyroid Carcinoma

Multimodality treatments (i.e. surgery, chemotherapy, and radiotherapy) are recommended for anaplastic thyroid carcinoma (ATC), an extremely lethal human cancer, but to date there is little evidence that such approaches improve survival rates. It is thus necessary to seek new therapeutic tools. Histone deacetylase (HDAC) inhibitors are a promising class of anti-neoplastic agents that induce differentiation and apoptosis. Moreover, they may enhance the cytotoxicity of drugs targeting DNA through acetylation of histones. Using two ATC cell lines (CAL-62 and ARO), we show here that valproic acid (VPA), a clinically available HDAC inhibitor, enhances the activity of doxorubicin, whose anti-tumor properties involve binding to DNA and inhibiting topoisomerase II. A meager 0.7 mM VPA, which corresponds to serum concentrations in patients treated for epilepsy, is able to increase the cytotoxicity of doxorubicin about threefold in CAL-62 cells and twofold in ARO cells. The sensitizing effect, which is through histone acetylation, involves increased apoptosis, which is also shown by the increased caspase 3 activation and the enhancement of doxorubicin-induced G2 cell cycle arrest. These results might offer a rationale for clinical studies of a new combined therapy in an effort to improve the outcome of patients with anaplastic thyroid cancer.

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Long-Term Drug Survival of TNF Inhibitor Therapy in RA Patients: A Systematic Review of European National Drug Registers

International Journal of Rheumatology ◽

10.1155/2013/764518 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 18

Author(s):

Anamika Arora ◽

Anadi Mahajan ◽

Dean Spurden ◽

Helen Boyd ◽

Duncan Porter

Keyword(s):

Systematic Review ◽

English Language ◽

Survival Rates ◽

Pooled Analysis ◽

Tnf Inhibitors ◽

Drug Discontinuation ◽

Tnf Inhibitor ◽

Drug Survival ◽

Lower Drug ◽

Underlying Mechanisms

Objective. The present systematic review of RA registry data was undertaken to analyse the time on treatment of licensed TNF inhibitors in patients with RA in Europe.Methods. English language European registry studies comparing TNF inhibitors were searched using MEDLINE, Embase, Cochrane, and WHO: ICTRP up to 16 April 2012 and proceedings of three selected conferences held between 2010 and 2012. Pooled analysis was performed to determine drug survival rates for each TNF inhibitor.Results. Sixteen studies met the inclusion criteria, of which 11 studies assessed biologic-naive patients and five studies included a mixed population of biologic-naive and biologic pretreated patients. The overall effectiveness of TNF inhibitors diminished with time, leading to decreased drug survival rates. Pooled drug survival rates after 60 months follow-up were 37% (infliximab), 48% (adalimumab), and 52% (etanercept). Further, in an observational study, when TNF inhibitors were used in combination with methotrexate, a longer drug survival was observed compared to TNF inhibitors alone.Conclusion. The findings of this systematic review indicated numerically lower drug discontinuation rates with etanercept than adalimumab, whereas infliximab had the highest rate. Further research is needed to understand the underlying mechanisms of treatment discontinuation with TNF inhibitors.

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A Systematic Review of Phase II Targeted Therapy Clinical Trials in Anaplastic Thyroid Cancer

Cancers ◽

10.3390/cancers11070943 ◽

2019 ◽

Vol 11 (7) ◽

pp. 943 ◽

Cited By ~ 13

Author(s):

Josip Ljubas ◽

Therese Ovesen ◽

Maria Rusan

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Targeted Therapy ◽

Phase Ii ◽

Anaplastic Thyroid Cancer ◽

Anaplastic Thyroid Carcinoma ◽

Braf V600e ◽

Novel Treatments ◽

Molecular Alterations ◽

Molecular Landscape

Anaplastic thyroid carcinoma (ATC) is a rare, but devastating disease. Despite multimodal approaches combining surgery, chemotherapy and radiation therapy, ATC is associated with a dire prognosis, with a median overall survival of only three to ten months. Novel treatments are thus urgently needed. Recent efforts towards the characterization of the molecular landscape of ATC have led to the identification of pro-oncogenic targetable alterations, lending promise for novel targeted therapeutic approaches. This systematic review summarizes the results of phase II clinical trials of targeted therapy in ATC, providing an overview of efficacy and safety profiles. The majority of trials to date have consisted of small single-arm studies and have presented modest results. However, only a minority of trials have selected or stratified patients by molecular alterations. In the setting of BRAF V600E mutated ATC, dabrafenib/trametinib combination therapy and vemurafenib monotherapy have both demonstrated efficacy. Everolimus has furthermore shown promising results in patients with PI3K/mTOR/AKT pathway alterations. These studies underscore the importance of molecular profiling of tumors for appropriate patient selection and determination of genomic correlates of response. Clinical trials are underway testing additional targeted therapies as monotherapy, or as a part of multimodal treatment, and in combination with immunotherapy.

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