Mutation-based, short-term “neoadjuvant” treatment allows resectability in stage IVB and C anaplastic thyroid cancer

Abstract

Introduction Few available data indicate that a mutation-based “neoadjuvant” therapy in advanced anaplastic thyroid carcinoma (ATC) might convert an initially unresectable primary tumor to resectable and optimize local tumor control. We evaluated a preoperative short-term “neoadjuvant” therapy with a BRAF-directed therapy or, in case of BRAF non-mutated tumors, an mKI/checkpoint inhibitor combination in three patients with ATC stage IVB and C. Methods In the context of preoperative diagnostics, immunohistochemistry (IHC) assessment and genetic analysis was started as soon as possible. The antiangiogenetic therapy with lenvatinib was immediately after diagnosis of ATC started as bridging therapy. In case of a BRAF-mutated ATC, a combination therapy of dabrafenib and trametinib, in case of BRAF-wildtype ATC a combination of pembrolizumab and lenvatinib was given for 4 weeks. If re-staging has shown a significant therapy response due to a decrease in size of > 50%, surgical resection was reconsidered. A primary tumor resection was performed first. As a second step, limited distant metastasis have been resected approximately 4 weeks after thyroid surgery. After postoperative recovery, the targeted systemic therapy was continued. Patients Two patients presented with BRAF-wildtype ATC stage IVC, one with BRAF-mutated ATC stage IVB. All patients were evaluated by surgery, nuclear medicine and oncology upon diagnosis of ATC. Results In all three cases, the “neoadjuvant” therapy induced a dramatic response and led to local resectability in primarily non-resectable ATC stage IVB or C. We have chosen for the first time a short-term “neoadjuvant” treatment period to reduce the risk of bleeding and/or fistula due to potential rapid tumor shrinkage. The results of surgery after only short-term “neoadjuvant” therapy showed two R0 und one R1 resections. Postoperative histopathological findings confirmed an extent of tumor necrosis or regressive fibrotic tissue between 60 and > 95% in our patients. Conclusions A short-term mutation-based “neoadjuvant” therapy can achieve local resectability in initially unresectable ATC stage IVB or C. A neoadjuvant treatment period of about 4 weeks seems to show similar response as a treatment duration of at least 3 months.

Establishment and verification of the first prognostic nomograms in locally advanced thyroid cancer based on the analysis of clinical and follow-up information on 2396 patients

“…However, due to the highly specialized nature of the treatment of LATC, we recommend the application of a multi-disciplinary team (MDT) model, which uses multidisciplinary assessment to discuss the assessment of tumor resectability and the assessment of physical status prior to neoadjuvant therapy, if it is anticipated that it will be difficult to achieve R0 or R1 resection, or if it will be difficult to preserve the function of the adjacent structures or organs due to a large surgical extent, and the patient is in good physical condition, neoadjuvant therapy can be considered to improve the resection rate of subsequent surgery and the quality of life of patients. Due to the insensitivity of TC to radiotherapy, targeted therapy is currently the main neoadjuvant treatment modality [ 38 ], and targeted therapy plus immunotherapy or chemotherapy can be used for poorly differentiated LATC [ 39 ].…”

First effectiveness data of lenvatinib and pembrolizumab as first-line therapy in advanced anaplastic thyroid cancer: a retrospective cohort study

“…Two prospective trials are ongoing (DRKS00013336, NCT04171622) [ 18 , 19 ], and we hope to obtain further evidence on the efficacy of lenvatinib and pembrolizumab in treatment-naïve patients and possibly improve patient selection. Additionally, these studies may explore the potential role of the combination therapy in the neoadjuvant setting as it has recently been suggested in two ATC cases [ 20 ].To date, there are no validated biomarkers predicting the effectiveness of lenvatinib and pembrolizumab in ATC. However, Dierks et al found a PD-L1 TPS > 50% or high tumor mutational burden in patients with long-lasting responses [ 6 ].…”

Neoadjuvant treatment with lenvatinib and pembrolizumab in a BRAF V600E-mutated anaplastic thyroid cancer: a case report

“…There are also a few other reports in which P+L appeared to be effective as salvage treatment in BRAF wild-type cases ( 5 , 6 ). In another report of BRAF wild-type ATC, treatment with P+L was used as an adjuvant, enabling the resection of the lesion (an apparent R0), but the patient relapsed 4 months later ( 8 ). Finally, another study showed some efficacy of treatment with P+L as the first-line therapy (after EBRT) in five patients with ATC.…”