Surgery combined with adjuvant radiation and chemotherapy prolonged overall survival in stage IVC anaplastic thyroid cancer: a SEER-based analysis.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is a rare but aggressive malignancy, which accounts for only 1-2% of all thyroid cancers. The median overall survival (OS) time for all stages patients is at about 5 months. The benefit of surgery combined with adjuvant radiation and chemotherapy in stage IVC anaplastic thyroid cancer is still controversial. The aim of this study is to investigating surgery combined with adjuvant radiation and chemotherapy and survival outcomes in stage IVC ATC patients. METHOD: Anaplastic thyroid carcinoma patients from the Surveillance, Epidemiology, and End Results database from 2004 to 2016 were used to conduct a cross-sectional study in the analysis. The endpoint of this study was overall survival. RESULTS: The median OS of the overall population was 2.0 months. Multivariate analysis showed that age (<67 vs. ≥67 years old, P = 0.017, HR = 1.355, 95% CI: 1.057-1.738), tumor size (<7 cm vs. ≥7 cm, P = 0.001, HR = 1.579, 95% CI: 1.202-2.073), Surgery (thyroidectomy vs. non-surgery, P < 0.001, HR = 0.554, 95% CI: 0.401-0.766), radiation therapy (P < 0.001, HR = 0.571, 95% CI: 0.445-0.733) and chemotherapy (P = 0.003, HR = 0.684, 95% CI: 0.531-0.881) were independent prognostic factor for worse OS in stage IVC ATC patients. Surgery combined with adjuvant radiation and chemotherapy exhibited the better overall survival time for 4 months. CONCLUSIONS: Surgery combined with adjuvant radiation and chemotherapy can improve overall survival in stage IVC ATC patients. We recommend surgical approach with fully evaluation combined with radiation therapy and chemotherapy for selected stage IVC ATC patients.

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

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.

Impact of radiotherapy on survival in resected or unresectable anaplastic thyroid carcinomas, a Rare Cancer Network study.

PURPOSE: Anaplastic thyroid carcinomas (ATC) are a heterogenous group of tumors of overall dismal prognosis. We designed models to identify relevant prognostic factors of survival of irradiated ATC patients including radiotherapy modalities (field size, dose). MATERIAL AND METHODS: Between 2000 and 2017, 166 ATC patients' treatments were divided into surgery and postoperative radiotherapy (poRT) or definitive radiotherapy (RT). Multiple imputation approach was used for missing data. Prognostic factors were identified using Lasso-penalized Cox modelling and predicted risk scores were built. RESULTS: Patients undergoing RT (n=70) had more adverse patient and disease characteristics than those undergoing poRT (n=96). Corresponding median survival rates were 5.4 and 12.1 months, respectively. PoRT patients undergoing poRT more likely received extended-field radiotherapy with prophylactic nodal irradiation, but rather received platinum- vs. adriamycin-based chemoradiotherapy. Radiotherapy was conventionally fractionated, delivered >60Gy in 51.9% and 61.7% and used extended fields in 88.5% and 71.2% of patients with poRT or RT. Radiotherapy interruption rates for toxicity were similar in the two groups. The best poRT-group model identified age>45yo, PS≥1, pathologic tumor stage≥pT4b,>N1 and R2 resection as poor prognostic factors. The best RT-group model (C-index of 0.72) identified PS≥3,>N1 and extended-field radiotherapy with prophylactic nodal irradiation (as opposed to tumour-bed irradiation only) as poor prognostic factors. CONCLUSION: In patients undergoing poRT, radiotherapy parameters had little influence over their survival irrespective of patient, disease characteristics, and quality of resection. In patients undergoing RT, extended-field radiotherapy improved survival in addition to PS and nodal stage.

Evaluating the therapeutic efficacy of radiolabeled BSA@CuS nanoparticle-induced radio-photothermal therapy against anaplastic thyroid cancer.

Bovine serum albumin (BSA) has been employed as a mild biological template in nanoscale particles. Copper sulfide (CuS) has been used for photothermal therapy (PTT) in several studies. In this study, we aimed to synthesize the 131 I-labeled BSA-modified CuS nanoparticles (131 I-BSA@CuS), with attributes of both radiotherapy and PTT, as a therapeutic agent against anaplastic thyroid carcinoma (ATC). BSA@CuS nanoparticles were prepared using the solvothermal reaction and then labeled with Na131 I by the chloramine-T method. The products were characterized and their cytotoxicity was investigated in vitro and in vivo. The therapeutic efficacy of 131 I-BSA@CuS was evaluated in ARO cell (an ATC cell line) subcutaneous tumors. The nanoparticles showed good biocompatibility and low toxicity in vitro and in vivo. BSA@CuS rapidly and effectively converted the light energy from an 808 nm laser into thermal energy with a conversion efficiency of 28.07%. SPECT/CT imaging demonstrated that the accumulation of radioactivity peaked within 24 hr and resided in the tumors for 5 days post intratumoral injection. In vivo assays indicated that, compared to monotherapy, the synthesized nanoparticles employing both PTT and radiotherapy possess better therapeutic efficacy against tumors. The synthesized nanomaterial showed uniform dispersion, good stability and aqueous solubility, excellent photothermal properties, and long-term retention in ATC. Hence, combined radiotherapy and PTT can significantly inhibit tumor growth compared to monotherapy, and can be applied in clinical settings.

Indications of external beams radiation for thyroid cancer.

PURPOSE OF REVIEW: The use of external beam radiation therapy (EBRT) for the treatment of the different histologic subtypes of thyroid cancer is a matter of debate. This article provides an up-to-date review on the current evidence concerning the benefits of EBRT in thyroid cancer in specific indications. RECENT FINDINGS: Based on retrospective studies, adjuvant EBRT lessens the risk of locoregional recurrence in locally advanced differentiated thyroid cancer (DTC) and medullary thyroid cancer (MTC) with high-risk features. The effect of EBRT on overall survival remains uncertain. EBRT should also be part of the multimodality treatment in anaplastic thyroid cancer (ATC), as it improves survival rates in incompletely resected ATC. SUMMARY: The role of EBRT in thyroid cancer remains unclear. To date, no randomized control studies are available. Retrospective data showed improved outcomes in patients with high-risk features for locoregional recurrence.

Radiotherapy Plus Chemotherapy Leads to Prolonged Survival in Patients With Anaplastic Thyroid Cancer Compared With Radiotherapy Alone Regardless of Surgical Resection and Distant Metastasis: A Retrospective Population Study.

Background: Whether anaplastic thyroid cancer (ATC) patients benefit more from radiotherapy plus chemotherapy (RCT) than from radiotherapy alone (RT) was controversial. We aimed to investigate the effectiveness of RCT versus RT on ATC overall and within subgroups by surgical resection and distant metastasis in a large real-world cohort. Methods: Patients with ATC diagnosed between 2004 and 2015 were identified from the Surveillance, Epidemiology, and End Results Program database. Inverse probability weighting (IPW) was performed to balance variables between the two groups. Multivariate Cox proportional hazard model and Fine-Gray compete-risk model were carried out to investigate prognostic factors relating to overall survival (OS) and cancer-specific survival (CSS). Subgroup analysis was carried out, and a forest plot was graphed. Results: Of the 491 ATC patients, 321 (65.4%) were in the RCT group and 170 (34.6%) were in the RT group. The median OS was 4 months [interquartile range (IQR) 2-7] and 2 months (IQR 1-4) for patients in the RCT and RT groups, respectively. As indicated by the inverse probability weighting multivariate regression, RCT was associated with significantly improved OS (adjusted HR = 0.69, 95% CI = 0.56-0.85, p < 0.001) and CSS (adjusted subdistribution HR = 0.77, 95% CI = 0.61-0.96, p = 0.018). The prominent effect of RCT versus RT alone remains significant within each subgroup stratified by surgical resection and distant metastasis. Older age, single marital status, surgical resection, distant metastasis, and tumor extension were significant prognostic factors of survival. Conclusions: RCT contributes to prolonged OS and CSS compared with RT alone in ATC patients, regardless of surgical resection and distant metastasis. RCT should be preferentially applied to ATC patients.

Multimodal treatments and outcomes for anaplastic thyroid cancer before and after tyrosine kinase inhibitor therapy: a real-world experience.

BACKGROUND: Anaplastic thyroid cancer (ATC) has dismal prognosis and there is no effective treatment. We aimed to evaluate the efficacy of tyrosine kinase inhibitor (TKI) therapy in real-world clinic and to suggest the most effective treatment modality according to the combination of treatments. METHODS: This retrospective study evaluated clinical outcomes and cause of death with multimodal treatments in patients with ATC at Samsung Medical Center. RESULTS: A total of 120 patients received anti-cancer treatment for ATC. Seventy-seven (64.2%) patients underwent surgery, 64 (53.3%) received radiotherapy, 29 (24.2%) received cytotoxic chemotherapy, and 19 (15.8%) received TKI therapy. In the TKI therapy group, eight achieved partial response (three with lenvatinib and five with dabrafenib plus trametinib), and two patients with lenvatinib showed stable disease. Median progression-free survival (PFS) of the TKI therapy group was 2.7 months (range: 0.1-12.7) and their median overall survival (OS) was 12.4 months (range: 1.7-47.7). Patients who received surgery or radiotherapy for local control showed superior OS than those who did not. In a multivariate analysis, surgery, TKI therapy, younger age, and no distant metastasis were associated with favorable OS. The combination of surgery, radiotherapy, and TKI therapy (median OS: 34.3 months, 6-month survival rates: 77.8%) was the most effective. Compared to the era without TKI therapy, distant metastasis has recently become the major cause of death in ATC over airway problems. CONCLUSIONS: Multimodality treatment including TKI therapy demonstrated prolonged survival with dabrafenib plus trametinib as the most effective therapeutic option demonstrated for BRAF mutant ATC patients.

Tunicamycin as a Novel Redifferentiation Agent in Radioiodine Therapy for Anaplastic Thyroid Cancer.

The silencing of thyroid-related genes presents difficulties in radioiodine therapy for anaplastic thyroid cancers (ATCs). Tunicamycin (TM), an N-linked glycosylation inhibitor, is an anticancer drug. Herein, we investigated TM-induced restoration of responsiveness to radioiodine therapy in radioiodine refractory ATCs. 125I uptake increased in TM-treated ATC cell lines, including BHT101 and CAL62, which was inhibited by KClO4, a sodium-iodide symporter (NIS) inhibitor. TM upregulated the mRNA expression of iodide-handling genes and the protein expression of NIS. TM blocked pERK1/2 phosphorylation in both cell lines, but AKT (protein kinase B) phosphorylation was only observed in CAL62 cells. The downregulation of glucose transporter 1 protein was confirmed in TM-treated cells, with a significant reduction in 18F-fluorodeoxyglucose (FDG) uptake. A significant reduction in colony-forming ability and marked tumor growth inhibition were observed in the combination group. TM was revealed to possess a novel function as a redifferentiation inducer in ATC as it induces the restoration of iodide-handling gene expression and radioiodine avidity, thereby facilitating effective radioiodine therapy.

Synergistic Anticancer Activity of N-Hydroxy-7-(2-Naphthylthio) Heptanomide, Sorafenib, and Radiation Therapy in Patient-Derived Anaplastic Thyroid Cancer Models.

Anaplastic thyroid cancer (ATC) is an undifferentiated and advanced form of thyroid cancer, accompanied with a high ratio of epigenetic adjustment, which occurs more than genetic mutations. In this study, we aimed to evaluate the synergistic anticancer effect (in vitro and in vivo) of the new combination of N-hydroxy-7-(2-naphthylthio) heptanomide (HNHA) and sorafenib with radiation therapy in pre-clinical models of ATC. The ATC cell lines, YUMC-A1 and YUMC-A2, were isolated from the current patients who were treated with HNHA and sorafenib, either as monotherapy or combination therapy. Synergistic anticancer effect of the combination therapy on the intracellular signaling pathways and cell cycle was assessed via flow cytometry and immunoblot analysis. To examine tumor shrinkage activity in vivo, an ATC cell line-derived mouse xenograft model was used. Results showed that the combination therapy of HNHA and sorafenib with radiation promoted tumor suppression via caspase cleavage and cell cycle arrest in patient-derived ATC. In addition, the combination therapy of HNHA and sorafenib with radiation was more effective against ATC than therapy with HNHA or sorafenib with radiation. Thus, the combination of HNHA and sorafenib with radiation may be used as a novel curative approach for the treatment of ATC.

REGγ ablation impedes dedifferentiation of anaplastic thyroid carcinoma and accentuates radio-therapeutic response by regulating the Smad7-TGF-ß pathway.

Anaplastic thyroid cancer (ATC) is the most aggressive human thyroid malignancy, characterized by dedifferentiation and resistance to radioiodine therapy. The underlying mechanisms regulating ATC dedifferentiation are largely unknown. Here, we show that REGγ, a noncanonical proteasome activator highly expressed in ATC, is an important regulator of differentiation in ATC cells. Ablation of REGγ significantly restored expression of thyroid-specific genes, enhanced iodine uptake, and improved the efficacy of 131I therapy in ATC xenograft models. Mechanistically, REGγ directly binds to the TGF-ß signaling antagonist Smad7 and promotes its degradation, leading to the activation of the TGF-ß signal pathway. With gain- and loss-of-function studies, we demonstrate that Smad7 is an important mediator for the REGγ function in ATC cell dedifferentiation, which is supported by expression profiles in human ATC tissues. It seems that REGγ impinges on repression of thyroid-specific genes and promotion of tumor malignancy in ATC cells by activating the TGF-ß signal pathway via degradation of Smad7. Thus, REGγ may serve as a novel therapeutic target for allowing radioiodine therapy in anaplastic thyroid cancer patients with poor prognosis.

MEK Inhibition Induces Therapeutic Iodine Uptake in a Murine Model of Anaplastic Thyroid Cancer.

Anaplastic thyroid carcinoma (ATC) is refractory to radioiodine therapy in part because of impaired iodine metabolism. We targeted the mitogen-activated protein kinase and phosphatidylinositol 3-kinase (PI3'K) pathways with the intent to induce radioiodine uptake for radioiodine treatment of ATC. Methods: Human ATC cells were used to evaluate the ability of pharmacologic inhibition of the mitogen-activated protein kinase and PI3'K pathways to induce radioiodine uptake. Thyrocyte-specific double-mutant BRAFV600E PIK3CAH1047R mice were treated with a MEK inhibitor followed by radioiodine treatment, and tumor burden was monitored by ultrasound imaging. Results: ATC cell lines showed an increase in sodium-iodine symporter transcription when treated with a MEK or BRAFV600E inhibitor alone and in combination with PI3'K inhibitor. This translated into a dose-dependent elevation of iodine uptake after treatment with a MEK inhibitor alone and in combination with a PI3'K inhibitor. In vivo, MEK inhibition but not BRAF or PI3'K inhibition upregulated sodium-iodine symporter transcription. This translated into a stable reduction of tumor burden when mice were treated with a MEK inhibitor before radioiodine administration. Conclusion: This study confirms the ability of MEK inhibition to induce iodine uptake in in vitro and in vivo models of ATC. The approach of using a MEK inhibitor before radioiodine treatment could readily be translated into clinical practice and provide a much-needed therapeutic option for patients with ATC.

Hypofractionated Radiotherapy Is Superior to Conventional Fractionation in an Orthotopic Model of Anaplastic Thyroid Cancer.

BACKGROUND: Anaplastic thyroid cancer (ATC) is an aggressive and highly lethal disease with poor outcomes and resistance to therapy. Despite multimodality treatment, including radiation therapy and chemotherapy, response rates remain <15%, with a median time to progression of less than three months. Recent advances in radiotherapy (RT) delivery and gene-expression profiling may help guide patient selection for personalized therapy. The purpose of this study was to characterize the response to radiation in a panel of ATC cell lines and to test alternative RT fractionation schedules for overcoming radioresistance. MATERIALS AND METHODS: The cellular response to radiation was characterized based on clonogenic assays. Radiation response was correlated with microarray gene-expression data. Hypofractionated and conventional RT was tested in an orthotopic ATC tumor model, and tumor growth was assayed locally and distantly with in vivo and ex vivo bioluminescence imaging. RESULTS: A spectrum of radiosensitivities was observed in ATC cell lines. Radioresistant cell lines had higher levels of CXCR4 compared to radiosensitive cell lines. Compared to conventionally fractionated RT, hypofractionated RT resulted in significantly improved tumor growth delay, decreased regional and distant metastases, and improved overall survival. CONCLUSIONS: The findings demonstrate the heterogeneity of response to radiation in ATC tumors and the superiority of hypofractionated RT in improving local control, metastatic spread, and survival in preclinical models. These data support the design of clinical trials targeting radioresistant pathways in combination with hypofractionated RT.

Wild-Type P53 Induces Sodium/Iodide Symporter Expression Allowing Radioiodide Therapy in Anaplastic Thyroid Cancer.

AIMS: Anaplastic thyroid cancer(ATC) is one of the most aggressive solid tumors. Mutations in the p53 gene are common in anaplastic thyroid cancer, but the effects of p53 mutations are yet to be elucidated. Here, we investigated the role of p53 in ATC. METHODS: p53 mutation was detect by immunohistochemistry in ATC tissues. Expression of NIS were measured using immunohistochemistry, qRT-PCR, western blot, immunofluorescence in ATC tissues and cell line 8505c. Luciferase reporter assay was performed to examine the effect of wild-type p53 on NIS. Radioiodide uptake assay and flow cytometry analysis were used to detect the role of wild-type p53 on radioiodide uptake.and cell apoptosis in ATC cell line. RESULTS: We showed that the p53 mutation can be detected in ATC tissues. Furthermore, we demonstrated that wild-type p53 transactivated the NIS promoter. In 8505c cells transfected with wild-type p53, treatment with radioiodine resulted in increased radioiodine uptake and increased apoptotic cell death compared with 8505c cells harboring the p53 mutation. CONCLUSION: In summary, transfection with wild-type p53 can increase the therapeutic effect of radioiodine by regulating the expression of the NIS.

[Clinical characteristics and prognosis of anaplastic thyroid carcinoma].

Objective: To investigate the clinical characteristics, treatment outcomes and prognostic factors in patients with anaplastic thyroid cancer. Methods: Clinical data of 56 patients with anaplastic thyroid cancer at Zhejiang Cancer Hospital from January 2006 to June 2016 were retrospectively reviewed and followed up. Results: Of the 56 patients, there were 24 male and 32 female. The median age was 65 years old. At diagnosis, 10 patients have different degrees of breathing difficulty; 8 patients have varying degrees of dysphagia, and 12 patients have hoarseness. Distant metastases were found in 23 patients at presentation. Patient staging was performed in accordance with the tumor-node-metastasis system as follows: stage ⅣA (n=19), stage ⅣB (n=14) and stage ⅣC (n=23). The median survival time of 56 patients was 4.5 months.The overall 1-year survival rate was 5.4%. Univariate analysis showed that radiotherapy and multimodality therapy were prognostic factors for 1-year overall survival (both of P<0.05). The overall 1-year survival rate of the patients who received precision radiotherapy was 16.7%, which was higher than who received the other radiation therapy (4.0%, P=0.040). Furthermore, the overall 1-year survival rate of the patients who received surgery combined with radiotherapy was 12.5%, which was higher than who received the other treatments(4.2%, P=0.040). Multivariate analysis indicated that radiotherapy was independently associated with improved survival (P=0.020). Conclusions: Patients with anaplastic thyroid cancer should receive multimodality therapies combining surgery with radiotherapy. Radiotherapy is independently associated with improved overall survival. Notably, the precision radiotherapy that based on image guidance has a significantly beneficial impact on the prognosis of patients.

Radiotherapy in anaplastic thyroid carcinoma: An Australian experience.

INTRODUCTION: Anaplastic thyroid cancer is a rare and fatal malignancy, associated with significant local tumour and often treatment related morbidity. We report our experience in treating this cancer over a 20-year period. METHODS: A retrospective review of prospectively collected data from a single Australian Institution (Alfred Health Radiation Oncology) was carried out on patients referred with anaplastic thyroid carcinoma between 1992 and 2013. RESULTS: Thirty patients (17 females and 13 males) were identified with a median age at presentation of 72 years. At presentation, six (20%), 14 (47%) and 10 (33%) patients had stage IVA, IVB and IVC disease respectively. Thirteen patients underwent radical surgical resection with five having microscopic residual (R1) and eight having macroscopic residual (R2) disease. Twenty-eight patients were offered radiotherapy with 27 proceeding with treatment. Of those who received radiotherapy, three, six and 18 were treated with adjuvant, definitive and palliative intent respectively. Six patients had concomitant chemotherapy of which three received trimodality therapy. Only one patient experienced a grade 3 toxicity (oesophagitis). Median survival was 5.3 months and at last follow-up or time of death, 19 of 27 (70.4%) maintained loco-regional control. All patients who had R1 surgical resections and radiotherapy had loco-regional control. Seven of nine (77.8%) and 12 of 18 (66.7%) achieved loco-regional control after receiving definitive or palliative radiotherapy, respectively. CONCLUSIONS: Our study suggests that radiotherapy with or without surgery or chemotherapy is well-tolerated and results in durable loco-regional control in a high proportion of patients with anaplastic thyroid carcinoma.

Spanish consensus for the management of patients with anaplastic cell thyroid carcinoma

Anaplastic thyroid cancer (ATC) is the most aggressive solid tumor and almost uniformly lethal in humans. The Boards of the Thyroid Cancer Group of the Spanish Society of Endocrinology and Nutrition and the Grupo Español de Enfermedades Huérfanas e Infrecuentes of the Spanish Society of Oncology requested that an independent task force draft a more comprehensive consensus statement regarding ATC. All relevant literature was reviewed, including serial PubMed searches together with additional articles. This is the first, comprehensive Spanish consensus statement for ATC and includes the characteristics, diagnosis, initial evaluation, treatment goals, recommendations and modalities for locoregional and advanced disease, palliative care options, surveillance, and long-term monitoring. Newer systemic therapies are being investigated, but more effective combinations are needed to improve patient outcomes. Though more aggressive radiotherapy has reduced locoregional recurrences, median overall survival has not improved in more than 50 years (AU)

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Radiation therapy dose is associated with improved survival for unresected anaplastic thyroid carcinoma: Outcomes from the National Cancer Data Base.

BACKGROUND: The outcomes of patients with unresected anaplastic thyroid carcinoma (ATC) from the National Cancer Data Base (NCDB) were assessed, and potential correlations were explored between radiation therapy (RT) dose and overall survival (OS). METHODS: The study cohort was comprised of patients who underwent either no surgery or grossly incomplete resection. Correlates of OS were explored using univariate analysis and multivariable analysis (MVA). RESULTS: In total, 1288 patients were analyzed. The mean patient age was 70.2 years, 59.7% of patients were women, and 47.6% received neck RT. The median OS was 2.27 months, and 11% of patients remained alive at 1 year. A positive RT dose-survival correlation was observed for the entire study cohort, for those who received systemic therapy, and for those with stage IVA/IVB and IVC disease. On MVA, older age (hazard ratio [HR], 1.317; 95% confidence interval [CI], 1.137-1.526), ≥ 1 comorbidity (HR, 1.587; 95% CI, 1.379-1.827), distant metastasis (HR, 1.385; 95% CI, 1.216-1.578), receipt of systemic therapy (HR, 0.637; 95% CI, 0.547-0.742), and receipt of RT compared with no RT (<45 grays [Gy]:HR, 0.843; 95% CI, 0.718-0.988; 45-59.9 Gy: HR, 0.596; 95% CI, 0.479-0.743; 60-75 Gy: HR, 0.419; 95% CI, 0.339-0.517) correlated with OS. The RT dose-survival correlation for patients who received higher (60-75 Gy) versus lower (45-59.9 Gy) therapeutic doses was confirmed by propensity-score matching. CONCLUSIONS: Survival was poor in this cohort of patients with unresected ATC, and more effective therapies are needed. However, the association of RT dose with OS highlights the importance of identifying patients with unresected ATC who may still yet benefit from multimodal locoregional treatment that incorporates higher dose RT. Cancer 2017;123:1653-1661. © 2017 American Cancer Society.

Prognostic Factors for Survival in Patients Treated with Multimodal Therapy for Anaplastic Thyroid Cancer.

BACKGROUND/AIM: To identify predictors of survival after multimodal treatment including surgery plus postoperative radio(chemo)therapy) for anaplastic thyroid cancer. PATIENTS AND METHODS: Nine potential factors were evaluated in nine patients regarding survival after 6, 12 and 24 months. These factors were age, gender, Karnofsky performance score, tumour stage, nodal stage, resection margin status, radiation dose, concurrent chemotherapy administered with irradiation and symptom control at the end of radiotherapy. RESULTS: Survival rates were 67% at 6 months, 56% at 12 months and 22% at 24 months. On univariate survival analysis, concurrent radiochemotherapy (p=0.018) and controlled symptoms at the end of radiotherapy (p=0.03) were associated with improved survival. A trend for better survival was seen in patients with microscopically (R1) versus macroscopically (R2) residual disease (p=0.058). CONCLUSION: Prognostic factors for survival after multimodal treatment for anaplastic thyroid cancer were identified. Concurrent radio-chemotherapy resulted in significantly better survival and should be recommended.

Low-Level Laser Therapy Promoted Aggressive Proliferation and Angiogenesis Through Decreasing of Transforming Growth Factor-ß1 and Increasing of Akt/Hypoxia Inducible Factor-1α in Anaplastic Thyroid Cancer.

OBJECTIVE: We assessed the cause of increased tumor after low-level laser therapy (LLLT) by histological analysis. BACKGROUND DATA: LLLT is a nonthermal phototherapy used in several medical applications, including wound healing, reduction of pain, and amelioration of oral mucositis. We discovered by accident that LLLT increased tumor size while testing a photodynamic therapy (PDT) model for the treatment of thyroid cancer. Although therapeutic effects of LLLT on cancer or dysplastic cells have been studied, LLLT has been recently reported to stimulate the aggressiveness of the tumor. METHODS: The anaplastic thyroid cancer cell line FRO was injected into thyroid glands of nude mice orthotopically and then laser irradiation was performed with 0, 15, and 30 J/cm(2) (100 mW/cm(2)) on the thyroid after 10 days. The tumor volume was measured for 4 weeks and the thyroid tissues underwent histological analysis. We observed that proliferation of FRO cells and macrophage infiltration was increased with energy delivery to the thyroid glands. We also assessed overproliferated FRO cells using an immunohistochemical staining with hypoxia inducible factor 1α (HIF-1α), p-Akt, vascular endothelial growth factor (VEGF), and transforming growth factor ß1 (TGF-ß1). RESULTS: HIF-1α and p-Akt were elevated after LLLT, which suggested that the phosphorylation of Akt by LLLT led to the activation of HIF-1α. Moreover, TGF-ß1 expression was decreased after LLLT, which led to loss of cell cycle regulation. CONCLUSIONS: In conclusion, LLLT led to a decrease in TGF-ß1 and increase of p-Akt/HIF-1α which resulted to overproliferation and angiogenesis of anaplastic thyroid carcinoma (ATC). Therefore, we suggest that LLLT can influence cancer aggressiveness associated with TGF-ß1 and Akt/HIF-1α cascades in some poorly differentiated head and neck cancers.

The prognostic impacts of postoperative radiotherapy in the patients with resected anaplastic thyroid carcinoma: A systematic review and meta-analysis.

BACKGROUND: Optimal postoperative managements for anaplastic thyroid carcinoma (ATC) have not yet been sufficiently clarified. We conducted a systematic review and meta-analysis focussing on the impact of postoperative radiotherapy (PORT) in the patients with resected ATC. MATERIALS AND METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, a comprehensive search was performed in the several databases. We included the studies that reported survival outcome in the patients with or without PORT following any type of surgical resection except biopsy only. Hazard ratio (HR) was extracted, and the random-effects model was used for the pooled analysis. RESULTS: Seventeen retrospective studies including 1147 analysable patients met all inclusion criteria. The overall research quality was relatively low with considerable methodological limitations. The pooled results showed that PORT significantly reduced the risk of death in all the patients with resected ATC compared with those with surgery alone (HR, 0.556; 95% confidence interval, 0.419-0.737; p < 0.001). Exploratory analyses demonstrated that patients with stage IVA (HR, 0.364; p = 0.012) and IVB (HR, 0.460; p = 0.059) may also have survival benefit from PORT, whereas stage IVC may not. No evidence of publication bias was found (p = 0.352). CONCLUSIONS: This study is the first meta-analysis assessing PORT in patients with ATC and provides convincing evidence that adequate resection followed by PORT may offer the prolonged survival. However, without evidence based on prospective randomised trials, it is still not known which subset of patients can really benefit from PORT.