Potential role of sorafenib as neoadjuvant therapy in unresectable papillary thyroid cancer

Danilovic, Débora Lucia Seguro; Castro, Gilberto de; Roitberg, Felipe; Vanderlei, Felipe Augusto Brasileiro; Bonani, Fernanda Amarante; Freitas, Ricardo Miguel Costa de; Filho, George Coura; Camargo, Rosalinda; Kulcsar, Marco Aurélio Vamondes; Marui, Suemi; Hoff, Ana O.

doi:10.20945/2359-3997000000046

Cited by 16 publications

(12 citation statements)

References 22 publications

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“…Due to the tracheal invasion, the patient underwent cervical external beam radiotherapy and radioiodine dosing (the total activity of 300 mCi). At 52 months of follow-up, the patient has stable, persistent structural disease (23).…”

Section: Resultsmentioning

confidence: 99%

Neoadjuvant Multikinase Inhibitor in Patients With Locally Advanced Unresectable Thyroid Carcinoma

et al. 2019

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Background: Papillary thyroid carcinoma (PTC) is the most common and less aggressive thyroid cancer, but some patients may display locally advanced disease. Therapeutic options are limited in these cases, particularly for those patients with unresectable tumors. Neoadjuvant therapy is not part of the recommended work up.Methods: Report a case of an unresectable grossly locally invasive PTC successfully managed with neoadjuvant therapy and provide a systematic review (SR) using the terms “Neoadjuvant therapy” AND “Thyroid carcinoma.”Results: A 32-year-old man with a 7.8 cm (in the largest dimension) PTC was referred to total thyroidectomy, but tumor resection was not feasible due to extensive local invasion (trachea, esophagus, and adjacent structures). Sorafenib, a multikinase inhibitor (MKI), was initiated; a 70% tumor reduction was observed after 6 months, allowing new surgical intervention and complete resection. Radioactive iodine (RAI) was administered as adjuvant therapy, and whole body scan (WBS) shows uptake on thyroid bed. One-year post-surgery the patient is asymptomatic with a status of disease defined as an incomplete biochemical response. The SR retrieved 123 studies on neoadjuvant therapy use in thyroid carcinoma; of them, 6 were extracted: 4 case reports and 2 observational studies. MKIs were used as neoadjuvant therapy in three clinical cases with 70–84% of tumor reduction allowing surgery.Conclusion: Our findings, along with other reports, suggest that MKIs is an effective neoadjuvant therapy and should be considered as a therapeutic strategy for unresectable grossly locally invasive thyroid carcinomas.

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Section: Resultsmentioning

confidence: 99%

Neoadjuvant Multikinase Inhibitor in Patients With Locally Advanced Unresectable Thyroid Carcinoma

et al. 2019

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“…[ 9 ] Only recently, neoadjuvant therapy with tyrosine kinase inhibitor therapy has been reported to be effective in reducing the primary tumor size before total thyroidectomy. [ 18 ] Very recently, sorafenib [ 19 ] and lenvatinib [ 18 ] were reported as neoadjuvant therapy to reduce tumors sufficiently to enable thyroidectomy. In our patient, the left hip metastasis was initially treated by EBRT and concomitant chemotherapy with doxorubicin.…”

Section: Discussionmentioning

confidence: 99%

Graves disease and metastatic hormonal-active Hürthle cell thyroid cancer

et al. 2021

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Rationale: A hormone-active metastatic Hürthle cell thyroid carcinoma (HCTC) and Graves disease (GD) present a therapeutic challenge and is rarely reported. Patient concerns: We present a 64-year-old male patient, who had dyspnea and left hip pain lasting 4 months. He had clinical signs of hyperthyroidism and a tumor measuring 9 cm in diameter of the left thyroid lobe, metastatic neck lymph node and metastases in the lungs, mediastinum, and bones. Diagnosis: Laboratory findings confirmed hyperthyroidism and GD. Fine-needle aspiration biopsy and cytological investigation revealed metastases of HCTC in the skull and in the 8th right rib. A CT examination showed a thyroid tumor, metastatic neck lymph node, metastases in the lungs, mediastinum and in the 8th right rib measuring 20 × 5.6 × 4.5 cm, in the left acetabulum measuring 9 × 9 × 3 cm and parietooccipitally in the skull measuring 5 × 4 × 2 cm. Histology after total thyroidectomy and resection of the 8th right rib confirmed metastatic HCTC. Interventions: The region of the left hip had been irradiated with concomitant doxorubicin 20 mg once weekly. When hyperthyroidism was controlled with thiamazole, a total thyroidectomy was performed. Persistent T3 hyperthyroidism, most likely caused by TSH-R-stimulated T3 production in large metastasis in the 8th right rib, was eliminated by rib resection. Thereafter, the patient was treated with 3 radioactive iodine-131 (RAI) therapies (cumulative dose of 515 mCi). Unfortunately, the tumor rapidly progressed after treatment with RAI and progressed 10 months after therapy with sorafenib. Outcomes: Despite treatment, the disease rapidly progressed and patient died due to distant metastases. He survived for 28 months from diagnosis. Lessons: Simultaneous hormone-active HCTC and GD is extremely rare and prognosis is dismal. Concomitant external beam radiotherapy and doxorubicin chemotherapy, followed by RAI therapy, prevented the growth of a large metastasis in the left hip in our patient. However, a large metastasis in the 8th right rib presented an unresolved problem. Treatment with rib resection and RAI did not prevent tumor recurrence. External beam radiotherapy and sorafenib treatment failed to prevent tumor growth.

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“…In addition, Liu et al also reported that the 2-year overall survival rate of patients with ATC was low (26.0%) in Asia (27). In clinical settings, sorafenib provides sufficient tumor reduction to allow for thyroidectomy and radioactive iodine therapy in most types of thyroid cancer (12,28). However, Ito et al (14) reported that sorafenib appeared to be effective in the treatment of advanced medullary thyroid carcinoma but not ATC.…”

Section: Discussionmentioning

confidence: 99%

Potential synergistic effects of sorafenib and CP‑31398 for treating anaplastic thyroid cancer with p53 mutations

Lin

Huang

et al. 2020

Oncol Lett

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Thyroid cancer is the most commonly diagnosed endocrine cancer. Anaplastic thyroid cancer (ATC) is the most aggressive type of thyroid cancer and has a poor prognosis. Loss of p53 function has been reported to lead to poorly differentiated thyroid tumors; therefore, mutant p53 protein can be considered a crucial therapeutic target in patients with ATC. Sorafenib, a multi-kinase inhibitor, has been approved for the treatment of metastatic and differentiated thyroid cancer. Combined targeted therapy, including sorafenib, may be clinically significant for patients with ATC harboring p53 mutations. In the present study, CP-31398, a p53-restoring agent, was used to improve the therapeutic efficacy of sorafenib in SW579 cells, an ATC cell line harboring p53 mutations. The molecular function of CP-31398 was evaluated using western blot analysis and a luciferase reporter assay. The decreased viability of SW579 cells, following CP-31398 treatment, was augmented by sorafenib, and CP-31398 enhanced the antimitogenic effect of sorafenib; thus, sorafenib and CP-31398 synergistically inhibited the growth of SW579 cells. These results indicate a potential clinical application of CP-31398 for patients with ATC harboring p53 abnormalities, since these individuals generally respond poorly to sorafenib alone.

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Potential role of sorafenib as neoadjuvant therapy in unresectable papillary thyroid cancer

Cited by 16 publications

References 22 publications

Neoadjuvant Multikinase Inhibitor in Patients With Locally Advanced Unresectable Thyroid Carcinoma

Neoadjuvant Multikinase Inhibitor in Patients With Locally Advanced Unresectable Thyroid Carcinoma

Graves disease and metastatic hormonal-active Hürthle cell thyroid cancer

Potential synergistic effects of sorafenib and CP‑31398 for treating anaplastic thyroid cancer with p53 mutations

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