Discussion
dysphagia, tumor, stage IVC disease, toxicity, mutated carcinoma, Cancer
DYSPHAGIA, TUMOR, METASTASIS, STILL, SIDE EFFECT, THYROID, DISEASE, METASTASES, CANCER
In our analysis, we found five predictors for longer survival: the absence of distant metastasis at the time of diagnosis, surgery, complete resection (R0), a radiation dose of 50 Gy or higher and multimodal therapy (surgery, radiotherapy and chemotherapy). According to multivariate analyses, the best predictor of survival was a high radiation dose (≥ 50 Gy). Besides, even for patients with stage IV C (distant metastases) a radiation dose of at least 50 Gy could provide longer survival, whereas surgery and chemotherapy did not.The guidelines of the National Comprehensive Cancer Network (NCCN) as well as the ATA (American Thyroid Association) guidelines recommend surgery (total thyroidectomy with therapeutic lymph node dissection), if resectable, with adjuvant radiotherapy and optional (radiosensitizing) chemotherapy for stage IVA and IVB [In the NCCN guideline aggressive treatment consists of surgery (total thyreoidectomy + lymphnode dissection, if resectable), locoregional radiation and chemotherapy plus molecular testing to check if a targeted therapy, such as dabrafenib/trametinib is considered [The ATA guidelines focuse less on surgery and more on palliative cytotoxic chemotherapy and/or radiation for aggressive therapy in stage IVC disease [In our study, a radiation dose of at least 50 Gy showed the strongest association with an improved survival, in accordance with the literature [We also aimed to explore the difference in survival time and toxicity according to the radiation method. The advantage of IMRT and VMAT lies in the fact that a higher radiation dose can be delivered to the tumor while surrounding normal tissue can be better spared when compared to 3D-conformal techniques [In our cohort, a significantly higher radiation dose of 47.5 Gy versus 41.5 Gy could be delivered when using IMRT or VMAT. The toxic side effect of radiation was significantly better when IMRT or VMAT was used. Conversely, the risk of dysphagia was lower when a higher radiation dose was applied. This finding may be explained by the use of more toxic higher single doses (hypofractionation) in the radiotherapy concepts with lower total doses. Also, the OS was not improved using VMAT or IMRT compared to conventional radiotherapy. However, it must be pointed out that just a small number of our patients (13 out of 63) received IMRT or VMAT.Moreover, surgery was a significant predictor for longer OS. Likewise, in almost every study we found, any kind of surgery extended overall survival and progression-free survival significantly, whereas radical surgery shows better outcomes [For chemotherapy, we could not find any significant benefit in terms of survival. In the literature, various, but mostly disappointing outcomes, can be found [On the other hand, regarding multimodal therapy, which includes chemotherapy as well as surgery and radiotherapy, we found a significant effect on survival, in accordance with the literature [In our observation there was no advantage of survival in the most recent treatment periods (Table Still, over the past years, treatment options have improved. Because of the high rate of BRAF V600E mutations in ATC recent advances have suggested the use of BRAF inhibitors, like dabrafenib and MEK inhibitors, such as trametinib [In our cohort, three patients received targeted therapy. However, this number is too small and the observation period too short to draw any meaningful conclusions. The NCCN and ATA guidelines suggest dabrafenib plus trametinib for BRAF V600 mutated carcinoma, larotrectinib or entrectinib if NTRK gene fusion is positive and pralsetinib or selpercatinib for RET-fusion positive ATC [Several recent studies prove the positive effect of targeted therapy and immunotherapy [In our opinion, the future of ATC-therapy will be surgery plus individually planned high-dose radiotherapy and new targeted therapy. Even neoadjuvant concepts may become part of the therapeutic options in near future.Our study was limited by the small number of patients. However, compared to other single center studies, 63 cases over 31 years still is a considerate number. Also, the results are biased by comorbidities or unresectable tumor which we tried to avoid by adjusting with Karnofsky score and building subgroups like the stage IVC group.Due to the rareness of ATC prospective studies are very hard to perform. Hence, research is important to improve the therapy options and outcome of this extremely lethal disease.