Prevalence and Risk Factors of Developing Fistula or Organ Perforation in Patients Treated with Lenvatinib for Radioiodine-Refractory Thyroid Cancer

Introduction: Tyrosine kinase inhibitors represent a better treatment in patients with radioiodine-refractory differentiated thyroid cancer (RAI-R DTC). Lenvatinib is usually well-tolerated, but sometimes, it is associated with serious and even life-threatening side effects. The aim of this study was to evaluate the prevalence of and the potential risk factors for fistula and/or organ perforation in RAI-R DTC patients treated with lenvatinib. Methods: This study included data from advanced and progressive RAI-R DTC patients treated with lenvatinib from February 2011 to February 2020 who were followed up at a single center. The clinical-pathological features and the biochemical and morphological results of the patients were collected at the time of starting lenvatinib and during the follow-up. Results: Fourteen of 95 (14.7%) locally advanced or metastatic RAI-R DTC patients treated with lenvatinib developed a fistula or organ perforation. Nine of 14 (64.3%) patients had tumor infiltration of the trachea, bronchus, esophagus, pleura, or bladder. Five of 14 (35.7%) had a bowel perforation, but only 2 had preexisting diverticulosis. Evaluation of the risk factors for developing a fistula or organ perforation showed that the presence of tumor infiltration and the tumor histology (papillary and poorly differentiated vs. follicular and Hurthle thyroid cancer) were significantly correlated with the development of a fistula or organ perforation (p = 0.003 and p = 0.02, respectively). In the subgroup of patients with tumor infiltration, we found that the papillary thyroid cancer histotype was the only potential predictor of fistula development. External beam radiation therapy (EBRT), the starting dose of lenvatinib, and the duration of treatment were not relevant for the development of fistula. Conclusions: In metastatic thyroid cancer patients treated with lenvatinib, the presence of tumor infiltration and histological type should be considered as potential risk factors for the development of fistula or organ perforation, although they do not represent an absolute contraindication. Although EBRT and the presence of diverticulosis were not significantly associated with the development of fistula and organ perforation, they should be regarded as potential additional reasons for the development of these complications. According to our findings, there is no reason to start lenvatinib at a lower daily dose when tumor infiltration is present.

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A phase II study of axitinib (AG-013736 [AG]) in patients (pts) with advanced thyroid cancers

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.6008 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 6008-6008 ◽

Cited By ~ 11

Author(s):

E. E. Cohen ◽

E. E. Vokes ◽

L. S. Rosen ◽

M. S. Kies ◽

A. A. Forastiere ◽

...

Keyword(s):

Thyroid Cancer ◽

Tumor Regression ◽

Locally Advanced ◽

Thyroid Tumor ◽

External Beam Radiation ◽

Vegf Receptors ◽

Beam Radiation ◽

Thyroid Cancers ◽

Advanced Thyroid Cancer ◽

Multi Center Study

6008 Background: Elevated VEGF-A and VEGF-C have been reported in thyroid tumor tissue compared with normal thyroid. AG is a potent, small molecule inhibitor of VEGF receptors 1, 2 and 3. The efficacy and safety of AG therapy in pts with advanced thyroid cancers was examined in this single-arm, multi-center study. Methods: 60 pts with metastatic or unresectable locally-advanced thyroid cancer refractory to, or not suitable candidates for, 131iodine (131I) treatment, with measurable disease received AG at a starting dose of 5 mg orally BID. The primary endpoint was response rate (RR) by RECIST criteria. A Simon 2-stage minimax design was used (a=0.1; β=0.1; null RR=5%; alternative RR=20%). Samples were collected pretreatment and q8wks to explore relationships between clinical response and plasma soluble proteins. Results: Median age was 59 yrs (26–84), 35 (58%) were male. Histological subtypes included papillary: 29 pts (48%); follicular: 15 pts (25%)-11 (18%) with Hurthle cell variant; medullary: 12 pts (20%); anaplastic: 2 pts (3%), and other/unknown: 2 pts (3%). 53 pts (88%) had prior surgery, 42 (70%) had prior 131I treatment, 27 (45%) had prior external beam radiation, and 9 (15%) had prior chemotherapy. Partial response (PR) by investigator report was achieved in 13 pts (22% CI: 12.1, 34.2), with 31- 68% maximum tumor regression and duration of response (DOR) of 1–16 months. 30 pts (50%) have stable disease with a duration range of 4–13 months and 13–67% maximum tumor regression in 28 pts. Response assessments are ongoing. The treatment duration range is 6–670 days with 38 pts currently on study. Median PFS has not been reached with a median follow up of 273 days. The most common treatment-related adverse events were fatigue (37%), proteinuria (27%), stomatitis/mucositis (25%), diarrhea (22%), hypertension (20%) and nausea (18%). AG therapy consistently decreased soluble VEGFR2 and VEGFR3, and increased VEGF in the blood, demonstrating pharmacodynamic activity against targeted VEGF receptors. Conclusions: AG has substantial anti-tumor activity in advanced thyroid cancer with demonstrated pharmacodynamic activity. A global pivotal trial testing AG in doxorubicin refractory thyroid cancer is ongoing. [Table: see text]

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

Radiation ◽

10.3390/radiation1030016 ◽

2021 ◽

Vol 1 (3) ◽

pp. 174-182

Author(s):

Yuki Wada ◽

Akira Anbai ◽

Satoshi Kumagai ◽

Eriko Okuyama ◽

Noriko Takagi ◽

...

Keyword(s):

Radiation Therapy ◽

Thyroid Cancer ◽

Treatment Outcomes ◽

Group Performance ◽

Locally Advanced ◽

External Beam Radiation Therapy ◽

External Beam Radiation ◽

External Beam ◽

Beam Radiation ◽

Advanced Thyroid Cancer

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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The Role of Radiation Therapy in the Treatment of Medullary Thyroid Cancer

Journal of the National Comprehensive Cancer Network ◽

10.6004/jnccn.2010.0041 ◽

2010 ◽

Vol 8 (5) ◽

pp. 532-541 ◽

Cited By ~ 12

Author(s):

Stephanie A. Terezakis ◽

Nancy Y. Lee

Keyword(s):

Thyroid Cancer ◽

Medullary Thyroid Cancer ◽

Radiation Treatment ◽

Locally Advanced ◽

External Beam Radiation ◽

Beam Radiation ◽

Medullary Thyroid ◽

Adequate Dose ◽

Radiation Technique

Medullary thyroid cancer (MTC) is a neuroendocrine tumor derived from parafollicular or C cells of the thyroid gland. Surgical resection is the mainstay of treatment for MTC. External-beam radiation treatment (EBRT) has traditionally played a limited role in the management of MTC. Despite aggressive surgery, patients at high risk for local recurrence may benefit from adjuvant EBRT. With improvements in radiation technique, adequate dose can be effectively delivered to the region at risk while minimizing dose to surrounding critical structures. Although the role of EBRT in the management of these tumors has thus far been poorly defined, EBRT should be considered as a treatment option for patients with locally advanced MTC to optimize locoregional control.

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External Beam Radiation for Locally Advanced and Metastatic Differentiated Thyroid Cancer

Management of Thyroid Nodules and Differentiated Thyroid Cancer ◽

10.1007/978-3-319-43618-0_26 ◽

2017 ◽

pp. 419-431

Author(s):

James D. Brierley ◽

Meredith E. Giuliani ◽

Richard W. Tsang

Keyword(s):

Thyroid Cancer ◽

Differentiated Thyroid Cancer ◽

Locally Advanced ◽

External Beam Radiation ◽

External Beam ◽

Beam Radiation

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Premature Arterial Disease Associated with Familial Antithrombin III Deficiency

Thrombosis and Haemostasis ◽

10.1055/s-0038-1645677 ◽

1990 ◽

Vol 63 (01) ◽

pp. 013-015 ◽

Cited By ~ 15

Author(s):

E J Johnson ◽

C R M Prentice ◽

L A Parapia

Keyword(s):

Risk Factors ◽

Venous Thromboembolism ◽

Potential Risk ◽

Antithrombin Iii ◽

Arterial Disease ◽

Coagulation System ◽

Early Age ◽

Arterial Thromboembolism ◽

Potential Risk Factors ◽

Antithrombin Iii Deficiency

SummaryAntithrombin III (ATIII) deficiency is one of the few known abnormalities of the coagulation system known to predispose to venous thromboembolism but its relation to arterial disease is not established. We describe two related patients with this disorder, both of whom suffered arterial thrombotic events, at an early age. Both patients had other potential risk factors, though these would normally be considered unlikely to lead to such catastrophic events at such an age. Thrombosis due to ATIII deficiency is potentially preventable, and this diagnosis should be sought more frequently in patients with arterial thromboembolism, particularly if occurring at a young age. In addition, in patients with known ATIII deficiency, other risk factors for arterial disease should be eliminated, if possible. In particular, these patients should be counselled against smoking.

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