Combination therapy with lenvatinib and radiation significantly inhibits thyroid cancer growth by uptake of tyrosine kinase inhibitor

Suzuki, Kensuke; Iwai, Hiroshi; Utsunomiya, Keita; Kono, Yumiko; Kobayashi, Yoshiki; Bui, Dan Van; Sawada, Shunsuke; Yun, Yasutaka; Mitani, Akitoshi; Kondo, Naoyuki; Katano, Tayo; Tanigawa, Noboru; Akama, Tomoya O.; Kanda, Akira

doi:10.1016/j.yexcr.2020.112390

Cited by 13 publications

(14 citation statements)

References 34 publications

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“…As such, the indication for this systemic approach is generally limited to progressive disease with distant metastases. However, the potentially beneficial effect of combining TKIs with EBRT seems to be a promising new therapeutic strategy for these patients ( 38 ). Although relatively rare, we should be aware of bleeding and development of tracheo-oesophageal fistulas in patients treated subsequently with TKIs after radiotherapy ( 39 ).…”

Section: Discussion/conclusionmentioning

confidence: 99%

Postoperative external beam radiotherapy for locoregional control in iodine refractory differentiated thyroid cancer

Groen

Dijk

Sluiter

et al. 2022

European Thyroid Journal

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Background: The role of postoperative external beam radiotherapy (EBRT) in patients with residual iodine refractory differentiated thyroid cancer (IR-DTC) is still inconclusive. The aim of this retrospective study was to evaluate locoregional control (LRC) and overall survival (OS), and potential side effects after postoperative EBRT for both microscopic and macroscopic non-radically resected locally advanced IR-DTC. Methods: Between 1990 and 2016, 49 patients with locally advanced IR-DTC received EBRT for microscopic (R1; n=28) or macroscopic (R2; n=21) locoregional residual disease. For more insight into the added effect of EBRT we performed an intra-patient sub-analysis in 32 patients who had undergone more than one surgical intervention, comparing LRC after primary, curative-intended surgery with LRC after repeated surgery plus EBRT. To estimate LRC and OS we used Kaplan Meier curves. From 2007 onwards, we prospectively recorded toxicity data in our head and neck cancer database (n=10). Results: LRC rates five years after EBRT were higher for R1 (84.3%) than for R2 (44.9%) residual disease (p=0.016). The five-year OS rate after EBRT was 72.1% for R1 and 33.1% for R2 disease (p=0.003). In the intra-patient analysis (n=32) LRC rates were 6.3% five years after only initial surgery, and 77.9% after repeated surgery with EBRT (p=<0.001). Acute toxicity was limited to grade I and II xerostomia, mucositis, and hoarseness; only one patient developed late grade III dysphagia. Conclusions: Postoperative EBRT is associated with long-lasting locoregional control and overall survival with acceptable toxicity in patients with locally advanced IR-DTC, especially in microscopic residual disease.

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Section: Discussion/conclusionmentioning

confidence: 99%

Postoperative external beam radiotherapy for locoregional control in iodine refractory differentiated thyroid cancer

Groen

Dijk

Sluiter

et al. 2022

European Thyroid Journal

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“…Few studies have investigated the concurrent or sequential use of TKI with EBRT for LATC. In vitro studies have reported that combination therapy with irradiation and lenvatinib significantly inhibited thyroid cancer growth by inducing apoptosis and G2/M phase cell cycle arrest and increasing cellular uptake of lenvatinib into cancer cells [19]. Some clinical reports have highlighted the positive treatment effects with the concurrent use of TKI and EBRT for thyroid cancer without severe toxicities [20,21].…”

Section: Discussionmentioning

confidence: 99%

“…In vitro studies have reported that combination therapy with irradiation and lenvatinib significantly inhibited thyroid cancer growth by inducing apoptosis and G2/M phase cell cycle arrest and increasing cellular uptake of lenvatinib into cancer cells [19]. Some clinical reports have highlighted the positive treatment effects with the concurrent use of TKI and EBRT for thyroid cancer without severe toxicities [20,21]. However, other reports have shown that TKI could induce severe toxicities in patients with extended tumor invasion to the carotid artery or a history of neck irradiation [7,22].…”

Section: Discussionmentioning

confidence: 99%

Treatment Outcomes of External Beam Radiation Therapy for Unresectable Locally Advanced Thyroid Cancer with or without Metastasis: A Retrospective Single-Center Study

et al. 2021

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We evaluated treatment outcomes of external beam radiation therapy (EBRT) for unresectable locally advanced thyroid cancer (LATC) with or without metastasis. We enrolled 11 LATC patients who underwent EBRT (median age: 76 (45–83) years; six males and five females). Eastern Cooperative Oncology Group performance statuses of 0 (n = 3), 1 (n = 1), 2 (n = 6), and 3 (n = 1) were observed. Histologic types included papillary carcinoma (n = 5), anaplastic carcinoma (n = 3), and squamous cell carcinoma (n = 3). The organs invaded by the tumor that caused it to be deemed unresectable were common carotid artery (n = 5), trachea (n = 4), aorta (n = 1) and larynx (n = 1). The median follow-up time was 6 months. One, seven, two, and one patient showed complete response (CR), partial response (PR), stable disease, and progressive disease, respectively. The rate of local CR+PR was 73%; moreover, 75% of patients achieved a >30% tumor size reduction within 6 months. The median local progression-free survival of patients with local CR+PR was 11.5 (4–68) months. The median overall survival was 6 (1–68) months. Grade 3 acute complications occurred in five (45%) patients. No patients had Grade 4 or 5 complications. In conclusion, EBRT reduced the tumor volume in 75% of LATC patients without inducing severe toxicity. This therapy should be considered as a treatment option for LATC.

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“…In the recently reported preliminary studies on a small, randomized, multi-institutional phase II study (NCT02143726), where everolimus (mTOR inhibitor) and sorafenib co-therapy was applied for patients with RAI refractory HCC, improved PFS was observed [ 129 ]. Similarly, in a preclinical study, DTC cells treated with a combined therapy, including lenvatinib and radiation, synergistically induced apoptosis and G2/M phase arrest, as well as inhibited colony formation in vitro (cell lines) and tumor growth in nude mice [ 130 ].…”

Section: Currently Used and Investigated Targeted Therapies In Tcsmentioning

confidence: 99%

Novel Inhibitor-Based Therapies for Thyroid Cancer—An Update

Ratajczak

Gawel

Godlewska

2021

IJMS

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Thyroid cancers (TCs) are the most common tumors of the endocrine system and a constant rise in the number of TC cases has been observed for the past few decades. TCs are one of the most frequent tumors in younger adults, especially in women, therefore early diagnosis and effective therapy are especially important. Ultrasonography examination followed by fine needle biopsy have become the gold standard for diagnosis of TCs, as these strategies allow for early-stage detection and aid accurate qualification for further procedures, including surgical treatment. Despite all the advancements in detection and treatment of TCs, constant mortality levels are still observed. Therefore, a novel generation line of targeted treatment strategies is being developed, including personalized therapies with kinase inhibitors. Recent molecular studies on TCs demonstrate that kinase inhibitor-based therapies might be considered as the most promising. In the past decade, new kinase inhibitors with different mechanisms of action have been reported and approved for clinical trials. This review presents an up-to-date picture of new approaches and challenges of inhibitor-based therapies in treatment of TCs, focusing on the latest findings reported over the past two years.

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Combination therapy with lenvatinib and radiation significantly inhibits thyroid cancer growth by uptake of tyrosine kinase inhibitor

Cited by 13 publications

References 34 publications

Postoperative external beam radiotherapy for locoregional control in iodine refractory differentiated thyroid cancer

Postoperative external beam radiotherapy for locoregional control in iodine refractory differentiated thyroid cancer

Treatment Outcomes of External Beam Radiation Therapy for Unresectable Locally Advanced Thyroid Cancer with or without Metastasis: A Retrospective Single-Center Study

Novel Inhibitor-Based Therapies for Thyroid Cancer—An Update

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