Kinase-inhibitors for iodine-refractory differentiated thyroid cancer: still far from a structured therapeutic algorithm

Objectives. Invasion of differentiated thyroid cancer (DTC) into surrounding structures can lead to morbid procedures such as laryngectomy and tracheal resection. In these patients, there is a potential role for neoadjuvant therapy.Methods. We identified three studies involving the treatment of DTC with neoadjuvant chemotherapy: two from Slovenia and one from Japan.Results. These studies demonstrate that in selected situations, neoadjuvant chemotherapy can have a good response and allow for a more complete surgical resection, the treatment of DTC. Additionally, the SELECT trial shows that the targeted therapy lenvatinib is effective in the treatment of DTC and could be useful as neoadjuvant therapy for this disease due to its short time to response. Pazopanib has also demonstrated promise in phase II data.Conclusions. Thus, chemotherapy in the neoadjuvant setting could possibly be useful for managing advanced DTC. Additionally, some of the new tyrosine kinase inhibitors (TKIs) hold promise for use in the neoadjuvant setting in DTC.

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Treatment with Tyrosine Kinase Inhibitors for Patients with Differentiated Thyroid Cancer: the M. D. Anderson Experience

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2009-1923 ◽

2010 ◽

Vol 95 (6) ◽

pp. 2588-2595 ◽

Cited By ~ 121

Author(s):

Maria E. Cabanillas ◽

Steven G. Waguespack ◽

Yulia Bronstein ◽

Michelle D. Williams ◽

Lei Feng ◽

...

Keyword(s):

Thyroid Cancer ◽

Tyrosine Kinase ◽

Tyrosine Kinase Inhibitors ◽

Differentiated Thyroid Cancer ◽

Kinase Inhibitors

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Second or none: Many patients treated for refractory differentiated thyroid cancer with small molecular kinase inhibitors do not receive a second line of therapy.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e17589 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e17589-e17589 ◽

Cited By ~ 1

Author(s):

Ronda Copher ◽

Oluwakayode Adejoro ◽

Stacey DaCosta Byfield ◽

Mary DuCharme ◽

Debanjana Chatterjee ◽

...

Keyword(s):

Thyroid Cancer ◽

Differentiated Thyroid Cancer ◽

Kinase Inhibitors ◽

The United States ◽

Treatment Patterns ◽

Second Line ◽

Medicare Advantage ◽

First Line ◽

Line Of Therapy

e17589 Background: Describe the treatment patterns of patients initiated on NCCN-recommended small molecular kinase inhibitors (SMKIs) for radioiodine-refractory differentiated thyroid cancer (DTC) approved in the United States. Methods: A large national US claims database was used to identify adult patients diagnosed with thyroid cancer (≥2 non-DX medical claims, ≥ 30 days apart) from 1/1/2006 - 6/30/2016 (study period) with claims for SMKIs from 1/1/2010 - 5/31/2016. Continuous enrollment required participation in a commercial or Medicare Advantage health plan ≥3 months before and ≥1 month following index date (date of first pharmacy claim for SMKI). Line of therapy (LOT) periods were defined by receipt and timing of SMKIs. Patient follow up was earliest disenrollment, death or end of the study period. Patient characteristics and SMKI treatment patterns were described. Results: A total of 217 DTC patients were identified; 63% commercially insured and 37% Medicare Advantage. Almost half were male (48%); mean age was 61.2 years (standard deviation SD 12.5 years) and mean follow-up period was 499 days (SD 414 days). In the study period, 35% (n = 77) of patients had ≥2 LOTs and 18% (n = 39) had ≥3 LOTs. Mean treatment duration was 5.4 months (SD 6.7 mos) for LOT1, 4.9 months (SD 3.8 mos) for LOT2, and 4.2 months (SD 4.9 mo) for LOT3. During the full study period, the most used regimens were Sorafenib for both LOT1 (37%) and LOT2 (25%), pazopanib (18%) and sunitinib (18%) in LOT3. Also, in the study period, 33 patients had sorafenib in LOT1 of which 16 were treated with sorafenib again (48%) in LOT2. Post FDA approval in 2015, Lenvatinib became the predominant first-line regimen (47%, n = 29) during study period. Across all first line therapies, for those patients with ≥12 months of follow-up, 53% (n = 60) initiated LOT2. Conclusions: Sorafenib was the most common first line of therapy for DTC, with Lenvatinib adoption increasing as first-line therapy since the drug’s approval in 2015. Depending on the period evaluated, almost half to 2/3 of patients are not receiving a second line of treatment, efficacious and patient appropriate therapy is of importance in treating this rare cancer.

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Differentiated Thyroid Cancer With Liver Metastases: Lessons Learned From Managing a Series of 14 Patients

International Surgery ◽

10.9738/intsurg-d-14-00026.1 ◽

2015 ◽

Vol 100 (3) ◽

pp. 490-496 ◽

Cited By ~ 4

Author(s):

C. Brient ◽

S. Mucci ◽

D. Taïeb ◽

M. Mathonnet ◽

F. Menegaux ◽

...

Keyword(s):

Thyroid Cancer ◽

Liver Metastasis ◽

Liver Metastases ◽

Differentiated Thyroid Cancer ◽

Kinase Inhibitors ◽

Specific Treatment ◽

Distant Metastases ◽

Differentiated Thyroid Carcinoma ◽

Lessons Learned ◽

Liver Lesions

Liver metastases from differentiated thyroid carcinoma (LMDTC) are rare and usually occur in disseminated metastatic disease. The aim of this study was to review the diagnosis and management of LMDTC. Between 1995 and 2011, 14 patients with a mean age of 59.7 years (+/-10.2) were treated for LMDTC. Data were retrospectively reviewed and analyzed. Seven patients had distant metastases at diagnosis, including 2 with synchronous liver lesions. The average time of onset of LMDTC from initial diagnosis was 52.2 months (+/49.5). All LMDTC were discovered during routine radiologic monitoring. Histologic analysis confirmed LMDTC in 5 patients. Eight patients received tyrosine kinase inhibitors, 1 patient underwent resection of their LMDTC after chemotherapy. Six patients (disseminated metastases, significant comorbidities) did not receive any specific treatment. The median survival after diagnosis of LMDTC was 17.4 months (+/-3.3): 23.6 months (+/-2.9) for patients who underwent chemotherapy versus 3.9 months (+/-0.9) for patients who did not receive any specific treatment (P < 0.001). Developing DTC liver metastasis is a very poor prognostic sign. Chemotherapy by TKIs, especially, hold promise in the cure of LMDTC for selected patients.

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Differentiated Thyroid Cancer

10.2310/cgso.16001 ◽

2019 ◽

Author(s):

Rebecca Tuttle ◽

William Cance ◽

James Howe

Keyword(s):

Thyroid Cancer ◽

Thyroid Nodule ◽

Differentiated Thyroid Cancer ◽

Radioactive Iodine ◽

Kinase Inhibitors ◽

Needle Aspiration ◽

Thyroid Stimulating Hormone ◽

Diagnostic Modality ◽

Radioactive Iodine Ablation ◽

Common Malignancy

Differentiated thyroid cancer is a common malignancy with an excellent prognosis. Patients typically present with a thyroid nodule identified on physical exam or imaging. Fine needle aspiration (FNA) is the diagnostic modality of choice; ultrasound of the neck is used preoperatively to evaluate lymphadenopathy. Surgery is the mainstay of treatment, with partial or total thyroidectomy (with or without lymphadenectomy). Intra-operatively, identification of the recurrent laryngeal nerve and preservation of the parathyroid glands is imperative. Postoperatively, patients are considered for adjuvant radioactive iodine ablation. Risk stratification systems are available to assist patient selection for therapy. Surveillance is completed with serial physical exams, laboratory studies, ultrasound, and radioactive iodine scanning. Recurrence can be managed with surgery, thyroid-stimulating hormone suppression, radioactive iodine ablation, radiation, or kinase inhibitors. This review contains 8 figures, 6 tables, and 50 references. Key Words: Bethesda classification, differentiated thyroid cancer, follicular thyroid cancer, papillary thyroid cancer, radioactive iodine, thyroid nodule, thyroidectomy

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Differentiated Thyroid Cancer

10.2310/7800.16001 ◽

2019 ◽

Author(s):

Rebecca Tuttle ◽

William Cance ◽

James Howe

Keyword(s):

Thyroid Cancer ◽

Thyroid Nodule ◽

Differentiated Thyroid Cancer ◽

Radioactive Iodine ◽

Kinase Inhibitors ◽

Needle Aspiration ◽

Thyroid Stimulating Hormone ◽

Diagnostic Modality ◽

Radioactive Iodine Ablation ◽

Common Malignancy

Differentiated thyroid cancer is a common malignancy with an excellent prognosis. Patients typically present with a thyroid nodule identified on physical exam or imaging. Fine needle aspiration (FNA) is the diagnostic modality of choice; ultrasound of the neck is used preoperatively to evaluate lymphadenopathy. Surgery is the mainstay of treatment, with partial or total thyroidectomy (with or without lymphadenectomy). Intra-operatively, identification of the recurrent laryngeal nerve and preservation of the parathyroid glands is imperative. Postoperatively, patients are considered for adjuvant radioactive iodine ablation. Risk stratification systems are available to assist patient selection for therapy. Surveillance is completed with serial physical exams, laboratory studies, ultrasound, and radioactive iodine scanning. Recurrence can be managed with surgery, thyroid-stimulating hormone suppression, radioactive iodine ablation, radiation, or kinase inhibitors. This review contains 8 figures, 6 tables, and 50 references. Key Words: Bethesda classification, differentiated thyroid cancer, follicular thyroid cancer, papillary thyroid cancer, radioactive iodine, thyroid nodule, thyroidectomy

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Radiomics-based prediction of response to multikinase inhibitors in radioiodine-refractory differentiated thyroid cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.6077 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 6077-6077

Author(s):

Valentina Corino ◽

Elena Colombo ◽

Marco Bologna ◽

Giuseppina Calareso ◽

Luca Mainardi ◽

...

Keyword(s):

Thyroid Cancer ◽

Principal Components ◽

Differentiated Thyroid Cancer ◽

Kinase Inhibitors ◽

Principal Component ◽

Early Response ◽

Radiological Evaluation ◽

K Nearest Neighbors ◽

Test Set ◽

Metastatic Sites

6077 Background: Antiangiogenic tyrosine kinase inhibitors (TKIs) represent the first-line treatment for radioiodine-refractory differentiated thyroid cancer (RR-DTC). Currently, no predictive factors for the activity of these drugs are available. We investigated whether radiomics may have a predictive role in this setting. Methods: We retrospectively identified patients (pts) affected by metastatic RR-DTC, treated with TKIs between July 2008 and January 2020 at our Institution, with availability of computed tomography (CT) scans at baseline and after at least 2 courses of TKI. Response to TKIs was evaluated according to RECIST v1.1. Pts with complete or partial response at the first radiological evaluation were considered responders (R), pts with stable or progressive disease non-responders (NR). A dedicated radiologist segmented the target lesions as regions of interest (ROIs). Radiomic features related to multiple categories (shape and size, first order statistics, textural features) were extracted from each ROI and computed using the PyRadiomics library v. 3.0. A semi-supervised form of principal component analysis estimated principal components that were then used for response classification through a k nearest neighbors (kNN) classifier. The quality of the model was assessed through train-validation-test split (55% of the data used as training set, 25% as validation set, 20% as test set), repeated 100 times. Performance of the predictive models was quantified with the mean Area Under the ROC Curve (AUC) obtained in the test set. Results: A total of 51 pts with metastatic RR-DTC who had received lenvatinib (n=37), sorafenib (n=4), axitinib (n=3), or vandetanib (n=7) were analyzed. Median age was 64.6 years, with a male prevalence (72.5%). Metastatic sites were lung (84.3%), bone (35.3%), brain (9.9%). Median time from TKI treatment start to the first radiological evaluation was 2.77 months, 24 pts (47%) were R (all partial responses) and 27 (52.9%) NR. In the radiomic analysis, 851 features were computed and 4-19 principal components were selected. Models’ performance of prediction of early response to TKIs is presented in Table. For each value of AUC, the corresponding 95% confidence interval is reported in brackets. Conclusions: Radiomics predicted the response to TKIs of RR-DTC pts with an accuracy of 71%. Radiomics technique has the potential to enable clinicians to anticipate the probability of response to TKIs at baseline, directing toward the most suitable patient-tailored therapeutic path. Prospective studies may further validate these preliminary findings.[Table: see text]

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