Sequential Analysis of Neutrophil-to-lymphocyte Ratio for Differentiated Thyroid Cancer Patients Treated With Lenvatinib

Fukuda, N.; Wang, Xiaofei; Ohmoto, Akihiro; Urasaki, Tetsuya; Sato, Yasuyoshi; Nakano, Kenji; Nishizawa, Masatoshi; Yunokawa, Mayu; Ono, Makiko; Tomomatsu, Junichi; Takahashi, Shunji

doi:10.21873/invivo.11828

Cited by 26 publications

(27 citation statements)

References 21 publications

(14 reference statements)

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“…The NLR is reportedly higher in ATC patients than RR-DTC patients (19). Indeed, in our previous report, the median NLR at start of lenvatinib was 2.63 (range=1.35-24.35) in RR-DTC patients, which was lower than the value in the present ATC cohort (15). These results suggest that the NLR is a diagnostic marker that discriminates ATC from RR-DTC.…”

Section: Discussioncontrasting

confidence: 56%

“…A previous study described that the patients whose NLR value increased during the follow-up period had a worse OS than patients with whose NLR value did not increase (17). It is also reported that the dynamic changes of the NLR value before and during lenvatinib treatment for patients RR-DTC were associated with disease progression or treatment response (15). Taking together these results, it is suggested that the decrease of NLR value from baseline to day 14 might reflect in vivo 34: 2859-2864 (2020) Figure 2.…”

Section: Discussionmentioning

confidence: 96%

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Neutrophil-to-Lymphocyte Ratio as a Prognostic Marker for Anaplastic Thyroid Cancer Treated With Lenvatinib

Fukuda

Toda

Fujiwara

et al. 2020

In Vivo

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Background/Aim: Lenvatinib is one of the few options for patients with anaplastic thyroid cancer (ATC). However, tumor markers for ATC treated with lenvatinib is lacking. The aim of this study was to explore whether the neutrophil-to-lymphocyte ratio (NLR) can be a tumor marker for ATC treated with lenvatinib. Patients and Methods: We retrospectively analyzed the prognostic significance of the NLR in 13 ATC patients treated with lenvatinib. Results: The disease control rate was better in patients with lower NLR (<8; 89%) than higher NLR (≥8; 25%) (p=0.05). Median progression-free survival and overall survival were longer in patients with lower NLR than higher NLR (4.0 vs. 1.6 months, p<0.05; and 10.2 vs. 3.8 months, p<0.05, respectively). Patients whose NLR on day 14 decreased compared to baseline had a slightly higher overall response rate than patients without NLR decrease (42.9% vs. 0%, p=0.19). Conclusion: The baseline NLR is a potential prognostic marker, and the change of NLR can be an early indicator of response for ATC patients treated with lenvatinib. According to the GLOBOCAN, it is estimated that 567,000 patients newly diagnosed with thyroid cancer worldwide, and 41,000 of these patients died from the disease in 2018 (1). Approximately 95% of thyroid cancer cases involve differentiated thyroid cancer (DTC), including papillary thyroid cancer and follicular thyroid cancer (2, 3). The majority of DTC cases tend to be of a slow-growing nature; however, the prognosis of anaplastic thyroid cancer (ATC) is extremely poor, with a disease-specific mortality >90% (4). Although ATC comprises only 1-2% of all thyroid cancers, ATC accounts for 14-39% of all thyroid cancer deaths (5, 6). Lenvatinib is an antiangiogenic multi-kinase inhibitor (MKI) that prevents ligand-induced receptor autophosphorylation of vascular endothelial growth factor receptor (VEGF-R) 1-3, fibroblast growth factor receptor 1-4, ret proto-oncogene (RET), stem cell factor receptor (KIT), and platelet-derived growth factor receptor-alpha (PDGFRα) (7-9). A phase 3 study of lenvatinib in patients with radioactive iodine ablationrefractory (RR)-DTC showed improvement in progression-free survival (PFS) compared to placebo (10). Moreover, lenvatinib exhibited efficacy and safety for patients with ATC [objective response rate (ORR)=24%] in a phase 2 trial (11, 12). No tumor markers for ATC have been established. Thyroglobulin, a well-known tumor marker for RR-DTC, is widely used for post-operative follow-up and as a supportive indicator for starting MKIs (13). However, thyroglobulin is not suitable for use in ATC patients. In a large Japanese cohort of ATC patients, the presence of acute symptoms, leukocytosis [white blood cell (WBC) count ≥10,000/mm 3), large tumor size (≥5 cm), T stage (T4b), and presence of distant metastases were associated with a poor prognosis (14). These factors are used as a prognostic index to determine the appropriate treatment strategy for ATC, but their use in patients with recurrent or metastatic ATC receiving lenvatini...

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Section: Discussioncontrasting

confidence: 56%

Section: Discussionmentioning

confidence: 96%

Neutrophil-to-Lymphocyte Ratio as a Prognostic Marker for Anaplastic Thyroid Cancer Treated With Lenvatinib

Fukuda

Toda

Fujiwara

et al. 2020

In Vivo

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“…Similarly, elevated neutrophil-to-lymphocyte ratio (NLR) is associated with more aggressive disease and decreased survival in patients with numerous types of solid tumors, including DTC (18,19). When NLR was retrospectively analyzed in patients specifically with RR-DTC treated with lenvatinib in a real-world setting, median overall survival (OS) was significantly longer in patients with lower baseline NLR (20). The mechanism by which elevated NLR is associated with more aggressive disease is not definitively known but may, in part, be explained by tumorpromoting consequences of inflammation (21).…”

Section: Introductionmentioning

confidence: 99%

Correlation of Performance Status and Neutrophil-Lymphocyte Ratio with Efficacy in Radioiodine-Refractory Differentiated Thyroid Cancer Treated with Lenvatinib

Taylor

Takahashi

Capdevila

et al. 2021

Thyroid

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Background: Radioiodine-refractory differentiated thyroid cancer (RR-DTC) has a low 10-year patientsurvival rate and is challenging to treat. Lenvatinib is a multikinase inhibitor approved for the treatment of RR-DTC. This study aims to assess Eastern Cooperative Oncology Group performance status (ECOG PS) and neutrophil-to-lymphocyte ratio (NLR) as prognostic markers for patients with RR-DTC treated with lenvatinib. Methods: In this retrospective analysis of the Study of (E7080) LEnvatinib in Differentiated Cancer of the Thyroid (SELECT), patients randomly assigned to receive lenvatinib were classified according to baseline ECOG PS (0 or 1) or baseline NLR (£3 or >3). The effects of baseline ECOG PS and NLR on progressionfree survival (PFS), overall survival (OS), and objective response rate (ORR) were evaluated. In addition, the effects of baseline ECOG PS on the change in diameter of target lesions and correlations between baseline NLR and the sums of the diameters of target lesions were calculated. Results: Among patients who received lenvatinib, patients with a baseline ECOG PS of 0 had statistically improved PFS (hazard ratio [HR] 0.52; 95% confidence interval [CI 0.35-0.77]; p = 0.001), OS (HR 0.42 [CI 0.26-0.69]; p = 0.0004), and ORR (odds ratio [OR] 3.51 [CI 2.02-6.10]; p < 0.0001) compared with patients with a baseline ECOG PS of 1. Patients who received lenvatinib with a baseline NLR £3 also had improved PFS (HR 0.43 [CI 0.29-0.65]; p < 0.0001) and OS (HR 0.48 [CI 0.29-0.78]; p = 0.0029) versus patients with a baseline NLR >3. Moreover, patients with a baseline NLR £3 had a trend toward increased ORR (OR 1.57 [CI 0.94-2.64]; p = 0.08) compared with patients with a baseline NLR >3. Treatmentemergent adverse events were generally similar among patients who received lenvatinib, irrespective of patients' ECOG PS at baseline.

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“…In the Japanese phase 2 trial of lenvatinib for thyroid cancer including DTC, medullary thyroid cancer (MTC), and ATC, higher pre-treatment NLR was correlated with a shorter PFS following lenvatinib treatment (HR 1.07, 95% CI 1.00–1.14, p = 0.06) [ 104 ]. In a small retrospective analysis, RR-DTC patients with an elevated NLR (≥3) at baseline showed shorter OS compared with patients with a lower NLR (<3) treated with lenvatinib (11.9 months vs. 35.0 months, p < 0.05) [ 54 ]. In the post hoc analysis of the SELECT trial, patients with a lower NLR (<3) demonstrated better PFS (HR 0.43, 95% CI 0.29–0.65, p < 0.0001) and OS (HR 0.48, 95% CI 0.29–0.78, p = 0.0029) compared with those with a higher NLR (≥3) [ 55 ].…”

Section: Possible Indications For Starting Mkismentioning

confidence: 99%

“…In the post hoc analysis of the SELECT trial, patients with a lower NLR (<3) demonstrated better PFS (HR 0.43, 95% CI 0.29–0.65, p < 0.0001) and OS (HR 0.48, 95% CI 0.29–0.78, p = 0.0029) compared with those with a higher NLR (≥3) [ 55 ]. The NLR value was also demonstrated to reflect the tumor aggressiveness before and during lenvatinib treatment; thus, NLR can be a tumor marker for RR-DTC treated with lenvatinib during active surveillance [ 54 ]. An NLR value of 3 is a possible indication for lenvatinib initiation.…”

Section: Possible Indications For Starting Mkismentioning

confidence: 99%

Clinical Indications for Treatment with Multi-Kinase Inhibitors in Patients with Radioiodine-Refractory Differentiated Thyroid Cancer

Fukuda

Takahashi

2021

Cancers

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Differentiated thyroid cancer is usually a slow-growing disease, even if the patients develop distant metastasis. For recurrent or metastatic disease, radioactive iodine therapy is a standard treatment. However, the disease gradually progresses in some of the patients and can ultimately develop into life-threatening conditions. For patients with progressive radioactive iodine-refractory differentiated thyroid cancer (RR-DTC), multi-kinase inhibitors (MKIs) including sorafenib and lenvatinib prolonged progression-free survival compared with placebo in pivotal randomized phase 3 trials, although the benefit in overall survival has not been clearly confirmed, possibly because the patients who received placebo were permitted to cross-over to lenvatinib upon disease progression. Moreover, the adverse events related to MKIs were not negligible. Therefore, the optimal timing of MKI initiation has long been controversial, and physicians should consider various patient and disease factors. Herein, we comprehensively review the clinical factors that can be helpful in determining the initiation of MKIs for patients with RR-DTC.

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Sequential Analysis of Neutrophil-to-lymphocyte Ratio for Differentiated Thyroid Cancer Patients Treated With Lenvatinib

Cited by 26 publications

References 21 publications

Neutrophil-to-Lymphocyte Ratio as a Prognostic Marker for Anaplastic Thyroid Cancer Treated With Lenvatinib

Neutrophil-to-Lymphocyte Ratio as a Prognostic Marker for Anaplastic Thyroid Cancer Treated With Lenvatinib

Correlation of Performance Status and Neutrophil-Lymphocyte Ratio with Efficacy in Radioiodine-Refractory Differentiated Thyroid Cancer Treated with Lenvatinib

Clinical Indications for Treatment with Multi-Kinase Inhibitors in Patients with Radioiodine-Refractory Differentiated Thyroid Cancer

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