Predictors of maximum efficacy of lenvatinib for real-world patients with differentiated thyroid carcinoma.

BACKGROUND AND OBJECTIVES: Tyrosine kinase inhibitors (TKIs) have provided excellent clinical benefits to patients with advanced differentiated thyroid cancer (DTC): however, the tumor status for which maximum efficacy can be obtained remains controversial. We conducted this study to identify effective clinical predictors, focusing on disease progression. METHODS: Using the data of 42 DTC patients treated with lenvatinib, we investigated the clinical factors related to overall survival (OS) and progression-free survival (PFS), and conducted analyses by the scoring of the factors. RESULTS: The 3 year OS and median PFS were 51% and 13.8 months, respectively. Univariate analysis identified performance status (PS), tumor-related symptoms, and tumor diameter as the only factors affecting both these outcomes. Giving 1-point for each of these three factors, a higher score was significantly related to shorter OS and PFS. Patients with two or fewer points (n = 34) had better median OS (NR vs 3.9 months, p < 0.001) and PFS (15.7 vs 2.1 months, p < 0.001) than patients with three points (n = 8). Patients with all three factors had a significantly worse prognosis than patients with two or fewer factors. CONCLUSION: DTC patients with all three indicators are unlikely to have longer survival. Therefore, it is important to commence TKIs before disease progression.

Impact of lenvatinib on renal function: long-term analysis of differentiated thyroid cancer patients.

BACKGROUND: Because lenvatinib is well known to induce proteinuria by blocking the vascular endothelial growth factor (VEGF) pathway, renal function is a concern with long-term administration of lenvatinib. The long-term effects of lenvatinib on renal function in patients with advanced differentiated thyroid carcinoma (DTC) were analyzed. METHOD: This study involved 40 DTC patients who continued lenvatinib therapy for ≥6 months. Estimated glomerular filtration rate (eGFR) was calculated as an indicator of renal function. The temporal course of eGFR, effects of baseline eGFR on eGFR changes, and factors affecting renal impairment were investigated. RESULTS: The overall cohort showed sustainable decreases in eGFR, with decreased values of 11.4, 18.3, and 21.0 mL/min/1.73 m2 at 24, 36, and 48 months after starting treatment, respectively. No differences in eGFR decrease every 6 months were seen for three groups classified by baseline eGFR ≥90 mL/min/1.73 m2 (n = 6), < 90 but ≥60 mL/min/1.73 m2 (n = 26), or < 60 but ≥45 mL/min/1.73 m2 (n = 8). Grade 3 proteinuria was associated with declines in eGFR (p = 0.0283). Long observation period was also associated with decreases in eGFR (p = 0.0115), indicating that eGFR may decrease in a time-dependent manner. CONCLUSION: Lenvatinib can induce declines in eGFR, particularly with treatment duration > 2 years, regardless of baseline eGFR. Proteinuria is a risk factor for declines in eGFR. Patients who start lenvatinib with better renal function show a renal reserve capacity, prolonging clinical outcomes. Decision-making protocols must balance the benefits of lenvatinib continuation with acceptable risks of harm.

Urinalysis by combination of the dipstick test and urine protein-creatinine ratio (UPCR) assessment can prevent unnecessary lenvatinib interruption in patients with thyroid cancer.

BACKGROUND: Proteinuria induced by lenvatinib is a class effect that occurs secondary to VEGFR suppression. Withholding of lenvatinib is required in cases with severe proteinuria. Urine protein-creatinine ratio (UPCR, g/gCre) has recently attracted attention as an alternative to 24-h urine collection for assessing proteinuria. The aim of this study was to examine the correlation between the results of proteinuria assessed by the dipstick test and UPCR, and to investigate the influence of proteinuria grading with UPCR on lenvatinib dose adjustment compared to that with only the dipstick test. METHOD: Three hundred and ten urine samples from 63 patients with advanced thyroid cancer under treatment with lenvatinib, which were tested by both the dipstick test and UPCR were analyzed. Lenvatinib was withheld when there was evidence of CTCAE grade 3 proteinuria, and restarted when it resolved. The frequency of proteinuria, correlation between the results of the dipstick test and UPCR test, and the effect of dose withholding in cases with results of 3 + in the dipstick test were calculated. RESULTS: Proteinuria was seen in 56 (88.9%) patients. Of the 154 dipstick 3 + samples, only 56 (36.4%) were judged as more than 3.5 g/gCre by UPCR (grade 3 proteinuria), although none of the 1 + and only 3.7% of 2 + samples were judged as grade 3 proteinuria. We were able to prevent unnecessary lenvatinib interruption due to proteinuria in 63.6% of dipstick 3 + samples by assessment of UPCR. CONCLUSIONS: Urinalysis by combination of the dipstick test and UPCR assessment might be a better strategy for preventing unnecessary interruption of lenvatinib.

Prognostic Impact of the Turin Criteria in Poorly Differentiated Thyroid Carcinoma.

BACKGROUND: The Turin criteria including solid, trabecular, and/or insular architecture, lack of typical nuclear features of papillary carcinoma, and mitoses, necrosis, or convoluted nuclei were adopted in the recent 4th edition of the World Health Organization classification published in 2017. MATERIALS AND METHODS: Between 2006 and 2017, 11,001 cases underwent initial surgery for primary malignant thyroid tumor derived from follicular cells. A total of 75 (0.7%) cases were diagnosed with PDTC according to the 2004 WHO classification. Based on the Turin criteria, 30 (40%) cases were re-classified as PDTC-Turin (+) and 45 (60%) cases were PDTC-Turin (-). Clinicopathological features and prognosis were compared between PDTC-Turin (+) and PDTC-Turin (-). RESULTS: Seventy-five patients (48 females and 27 males) had a median age at the time of surgery of 57 years. Preoperative diagnosis was benign in 16 (21%), follicular tumor in 40 (53%), and malignant in 19 (25%). The 5-year cause-specific survival (CSS) and disease-free survival (DFS) rates were 97% and 44% for PDTC-Turin (+) and 100% and 88% for PDTC-Turin (-). On univariate analysis, CSS and DFS rates were significantly worse in the PDTC-Turin (+) than in the PDTC-Turin (-) (p = 0.0096, and p = 0.0016). Multivariate analysis showed that Turin criteria status, Ki-67 labeling index ≥ 10%, and age 55 ≥ years were the independent prognostic factors for recurrence. CONCLUSIONS: The prevalence of PDTC diagnosed with the Turin criteria was low, but it showed more aggressive behavior. The 2017 WHO classification reflects the prognosis more accurately than the 2004 WHO classification.

Usefulness of Stereotactic Radiotherapy Using the CyberKnife for Patients with Inoperable Locoregional Recurrences of Differentiated Thyroid Cancer.

BACKGROUND: Surgical resection is the preferred treatment for locoregional recurrence of differentiated thyroid cancer (DTC). However, some recurrences are unresectable because of their aggressive invasion or severe adhesions. On the other hand, stereotactic radiotherapy (SRT) enables high-dose irradiation to target lesions, and its usefulness for various cancers has been reported. The objective of the present study was to investigate the feasibility and efficacy of SRT as salvage treatment for locoregional recurrence of DTC. METHODS: Between August 2011 and December 2017, 52 locoregional recurrent lesions in 31 patients with recurrent DTC were treated by SRT using the CyberKnife system. Information on the adverse events associated with SRT was retrospectively collected from the patients' medical records. Of the 52 lesions, 33 could be evaluated for therapeutic effectiveness by follow-up CT, and response was assessed using the RECIST criteria. RESULTS: Twenty-five patients had papillary carcinoma, 5 had follicular carcinoma, and 1 had poorly differentiated cancer. SRT was delivered in one to 20 fractions, and the median dose was 30 Gy (range 15-60 Gy). Adverse events were not frequent, but 1 patient developed bilateral vocal cord palsy that required emergent tracheostomy. The median follow-up period of 33 lesions was 14 months (range 1-54 months). Complete response, partial response, stable disease, and progressive disease were seen in 10, 11, 9, and 3 patients, respectively. The 3-year local control rate was 84.6%. CONCLUSION: SRT using the CyberKnife system was found to be a feasible and effective treatment to suppress the growth of locoregional recurrence of DTC.

Cribriform-Morular Variant of Papillary Thyroid Carcinoma: Clinical and Pathological Features of 30 Cases.

BACKGROUND: Cribriform-morular variant of papillary thyroid carcinoma (CMV-PTC) is rare; it may occur in cases of familial adenomatous polyposis (FAP) or be sporadic. To clarify the clinicopathological features of CMV-PTC, the medical records of these patients were investigated retrospectively. MATERIALS AND METHODS: Between 1979 and 2016, a total of 17,062 cases with PTC underwent initial surgery at Ito Hospital. Of these, 30 (0.2%) cases histologically diagnosed with CMV-PTC were reviewed. RESULT: The patients were all women, with a mean age at the time of surgery of 24 years. Seven (23%) cases were thought to have FAP because they had colonic polyposis or a family history of FAP or APC gene mutation. The remaining 23 (77%) were thought to be sporadic. Multiple tumors were detected in 6 cases, with a solitary tumor in 24. One patient had lung metastasis at diagnosis. Eleven patients underwent total thyroidectomy or subtotal thyroidectomy, and 19 underwent lobectomy. Twenty-six (87%) patients underwent neck lymph node dissection. Three patients had tumor metastasis in central lymph nodes, but these were incidentally detected metastatic classical PTC (cPTC) based on histological examination. In this series, there were no cases of LN metastases of CMV-PTC. During a mean follow-up of 15 years, one patient had new cPTC in the remnant thyroid after initial surgery, and the other patients showed no signs of recurrence. CONCLUSION: CMV-PTC occurred in young women, their long-term prognosis was excellent. Total thyroidectomy is recommended for FAP-associated CMV-PTC, but modified neck lymph node dissection is not necessary.

Clinical factors related to the efficacy of tyrosine kinase inhibitor therapy in radioactive iodine refractory recurrent differentiated thyroid cancer patients.

New insights in thyroid cancer biology propelled the development of targeted therapies as salvage treatment for radioiodine-refractory differentiated thyroid cancer (RR-DTC), and the tyrosine kinase inhibitor (TKI) lenvatinib has recently become available as a new line of therapy for RR-DTC. The aim of this study is to investigate clinical factors related to the efficacy of TKI therapy in recurrent RR-DTC patients and identify the optimal timing for the start of TKI therapy. The subjects consisted of 29 patients with progressive RR-DTC, 9 males and 20 females, median age 66 years. A univariate analysis was conducted in relation to progression free survival (PFS) and overall survival (OS) by the Kaplan-Meier method for the following variables: age, sex, histology of the primary tumor, thyroglobulin doubling time before the start of lenvatinib therapy, site of the target lesions, presence of a tumor-mediated symptom at the start of lenvatinib therapy, and baseline tumor size of the target lesions. Median duration of lenvatinib therapy was 14.7 months and median drug intensity was 9.5 mg. At the time of the data cut-off for the analysis, 9 patients (31.0%) have died of their disease (DOD), and a PR (partial response), SD (stable disease), and PD (progressive disease) were observed in 20 patients (69%), 6 patients (20.7%), 3 patients (10.3%), respectively. Univariate analyses showed that the presence of a symptom was the only factor significantly related to poorer PFS and OS. Clinical benefit of TKI therapy will be possibly limited when the therapy starts after tumor-mediated symptoms appear.

Lenvatinib induces early tumor shrinkage in patients with advanced thyroid carcinoma.

Although advanced thyroid carcinoma patients who cannot be cured by conventional therapy have lacked effective treatment, multitargeted tyrosine kinase inhibitors have recently become available. Phase 3 trials of lenvatinib showed a median time to objective response of 2 (95 % confidence interval (CI) 1.9-3.5) months, demonstrating that shrinks tumors rapidly. The phenomenon of immediate tumor shrink is known as early tumor shrinkage (ETS) which is related to clinical outcome in other malignancies. However, precisely when within 8 weeks lenvatinib starts to affect tumors remains unclear. In tumors near the carotid arteries, trachea, or esophagus, a rapid therapeutic effect can induce fistula formation or arterial bleeding. To prevent such treatment-emergent serious adverse events (SAE), early imaging evaluation seems to be very important. In this study, the point in time when lenvatinib started to shrink tumors was retrospectively investigated. The subjects were 16 patients who started lenvatinib administration between May and August 2015. Tumor size was evaluated by computed tomography (CT) scans frequently within the first 8 weeks according to the Response Evaluation Criteria In Solid Tumors (RECIST) guideline. Initial tumor response was defined as ≥ 10% tumor reduction. Serum thyroglobulin (Tg) level was monitored in 8 differentiated thyroid carcinoma (DTC) without TgAb patients. At the first evaluation, 13 patients (83.3 %) showed tumor reduction and that decreased with time. Thirteen patients (83.3 %) showed >10 % tumor reduction within 8 weeks. In all DTC patients, serum Tg level was markedly decreased. In conclusion, lenvatinib immediately shrinks tumors, the so-called ETS phenomenon. Therefore, careful attention should be paid to fistula formation from the early phase.

Active surveillance vs. surgery in low-risk papillary thyroid microcarcinoma patients and the risk of loss to follow-up.

BACKGROUND: Papillary thyroid microcarcinoma (PTMC) management has evolved, with active surveillance (AS) gaining prominence as a management option. However, a key concern for both clinicians and patients is the potential for patient loss to follow-up during AS. AIMS: This study aimed to determine adherence and loss-to-follow-up rates in low-risk PTMC patients undergoing AS versus surgical intervention, in order to gain insights into clinical pathways and safety profiles. MATERIALS AND METHODS: This cohort study analyzed the 2016 data from a single registered institution of Japan's public National Cancer Registry. RESULTS: We identified and retrospectively analyzed the cases of 327 patients diagnosed with low-risk PTMC; 227 patients chose to undergo AS while the other 100 underwent PTMC surgery. Main outcomes were the adherence rate and loss-to-follow-up rate of each group, factors influencing discontinuation, and safety considerations. The rate of AS adoption was substantial in the complete series of 327 low-risk PTMC patients (69.4%). There was a significantly higher loss-to-follow-up rate at 5 years in the AS group (28.6%) compared to the Surgery group (17.8%) (HR 1.62, 95% CI: 1.01-2.61; p = 0.046). Both univariate and multivariate analyses confirmed the significantly higher loss-to-follow-up rate in the AS group as well as in older patients. No deaths due to PTMC progression were observed in the cases lost to follow-up. CONCLUSION: Despite concerns about loss to follow-up, active surveillance remains a safe option for low-risk PTMCs. Consistent follow-up strategies are crucial, and further research is needed to enhance patient counseling and care for the management of patients with PTMC.

Successful dose escalation of lenvatinib for thyroid cancer after disease progression.

PURPOSE: Lenvatinib is started at a standard dose, continuing with dose reduction and interruption, balancing between efficacy and adverse events (AEs). Because few drugs are available for thyroid cancer, efforts for continuing treatment with one agent, such as "dose escalation (DE)", are made. The dose is increased, aiming to regain the anti-tumor effect after dose reduction. The effects of lenvatinib DE in differentiated thyroid carcinoma (DTC) patients are reported. PATIENTS AND METHODS: The efficacy of lenvatinib DE in DTC patients using the serum thyroglobulin (Tg) level and management of AEs was investigated. RESULTS: A total of 70 DE episodes in 33 patients were investigated. The median increased dose was 2.0 (1.0-14.0) mg, increased from 8.6 (2-16) mg to 10.1 (6-24) mg. The serum Tg level decreased in 53 DE episodes. Though the serum Tg level in 17 DE episodes was not decreased, the Tg rate of increase was decreased in 7 of these DE episodes using the Tg-doubling rate. Overall, clinical benefit was seen in 60 (86%) DE episodes. AEs that could not be controlled after DEs were seen in only 16% of cases. No intolerable AEs were observed in patients who received more drug holidays at the time of DEs compared to two times before the DEs. CONCLUSION: DE may become one of the standard treatment strategies after disease progression if AEs are well managed. Drug holidays may be a key for successfully controlling AEs with DE. DE can be useful for controlling progressive disease with increasing Tg levels.

Indications and Strategy for Active Surveillance of Adult Low-Risk Papillary Thyroid Microcarcinoma: Consensus Statements from the Japan Association of Endocrine Surgery Task Force on Management for Papillary Thyroid Microcarcinoma.

Background: The question of how to manage patients with low-risk papillary thyroid microcarcinoma (PTMC; T1aN0M0) has recently become an important clinical issue. Two Japanese centers have conducted prospective clinical trials of active surveillance (AS) for low-risk PTMC since the 1990s, reporting favorable outcomes. This policy has thus seen gradual adoption worldwide to avoid overtreatment. Not all PTMCs are suitable for AS, however, and many physicians still hesitate to apply the management policy in daily clinical practice. A task force on management for PTMC created by the Japan Association of Endocrine Surgery collected and analyzed bibliographic evidence and has produced the present consensus statements regarding indications and concrete strategies for AS to facilitate the management of adult patients diagnosed with low-risk PTMC. Summary: These statements provide indications for AS in adult patients with T1aN0M0 low-risk PTMC. PTMCs with clinical lymph node metastasis, distant metastasis, recurrent laryngeal nerve (RLN) paralysis due to carcinoma invasion, or protrusion into the tracheal lumen warrant immediate surgery. Tumors suspected of aggressive subtypes on cytology are recommended for immediate surgery. Immediate surgery is also recommended for tumors adherent to the trachea or located along the course of the RLN. Practical strategies include diagnosis, decision-making, follow-up, and monitoring related to the implementation of AS. The rate of low-risk PTMC progression is lower in older patients. However, we recommend continuing AS as long as circumstances permit. Future tasks in optimizing management for low-risk PTMC are also described, including molecular markers and patient-reported outcomes. Conclusions: An appropriate multidisciplinary team is necessary to accurately evaluate primary tumors and lymph nodes at the beginning of and during AS, and to adequately reach a shared-decision with individual patients. If appropriately applied, AS of low-risk PTMC is a safe management strategy offering favorable outcomes and preserves quality of life at low cost.

Risk Stratification of Pediatric Patients with Differentiated Thyroid Cancer: Is Total Thyroidectomy Necessary for Patients at Any Risk?

Background: In the recent American Thyroid Association (ATA) guidelines for adult differentiated thyroid carcinoma (DTC) patients, risk stratification is clearly defined and lobectomy is acceptable for low-risk DTC. However, risk stratification for children with DTC in the ATA pediatric guidelines is rather unclear, and total thyroidectomy is recommended for all patients with any risk. The aim of this study was to attempt risk stratification based on our experience and to consider the appropriate extent of thyroidectomy, especially for low-risk DTC in the pediatric population. Patients and Methods: The subjects were 153 patients with DTC ≤18 years old, including 58 patients ≤15 years old and 136 female patients, who underwent initial curative surgery in our hospital between 1979 and 2014. Underlying pathology was papillary thyroid carcinoma in 130 patients and follicular thyroid carcinoma in 23. Risk factors related to disease-free survival (DFS) were analyzed and risk stratification was performed. Results: No patient died of the disease and 34 patients (22.2%) developed recurrences. At initial surgery, 30 patients (19.6%) had lymph node metastases diagnosed before initial surgery (cN1) and 9 (5.9%) had gross extrathyroidal extension (ETE). Significant factors related to DFS on multivariate analysis were cN1, ETE, and number of metastatic lymph nodes (NMLNs) ≥10, including microscopic MLNs. According to these factors, subjects were divided into three categories: low risk (no risk factors, n = 89); intermediate risk (1 risk factor, n = 37); and high risk (≥2 risk factors, n = 27). Ten-year DFS rates in the low-, intermediate-, and high-risk groups were 96%, 83%, and 48%, respectively. Only 12% of low-risk patients underwent total thyroidectomy. Because NMLNs become obvious only after surgery, another analysis after excluding "NMLNs" as a factor showed that cN and ETE were significant factors related to poor DFS. According to these two factors, risk stratification was attempted in the same manner. Ten-year DFS rates in the low- (no risk factor, n = 117), intermediate- (one risk factor, n = 29), and high-risk (two risk factors, n = 7) groups were 92%, 59%, and 43%, respectively. Only 12% of low-risk patients underwent total thyroidectomy. Conclusions: For low-risk pediatric patients, lobectomy may be sufficient as the initial surgical procedure.

Efficacy and Limitations of Lenvatinib Therapy for Radioiodine-Refractory Differentiated Thyroid Cancer: Real-World Experiences.

Background: The ultimate clinical goal of advanced cancer treatment is improvement of survival. Tyrosine kinase inhibitors (TKIs) were recently approved for radioiodine-refractory differentiated thyroid carcinoma (RR-DTC) that is resistant to conventional therapies since they have significant potential to improve survival in patients who previously had no more treatment strategies available. However, eligible patients are limited in clinical practice, making it difficult to accurately determine the efficacy of TKIs. Patients and Methods: We retrospectively analyzed the efficacy of lenvatinib at a single institution, enrolling 42 RR-DTC patients. Results: The best overall response was partial remission in 26 (62%) patients, stable disease in 10 (24%) patients, and progressive disease (PD) in 6 (14%) patients. The results indicated three-year overall survival (OS) and progression-free survival rates of 51.0% and 32.4%, respectively. Twenty-three (55%) patients had backgrounds that did not match the inclusion criteria of the Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (SELECT) trial. Furthermore, PD-experienced patients individually decided whether to continue lenvatinib, and 17 (41%) made the decision themselves; these patients had a three-year OS of 43.0% and postprogression survival (PPS) of 13.3 [95% confidence interval 6.1-not reached] months. Conclusions: Our real-world investigation revealed that patients have wide-ranging background characteristics, and the decision regarding continuation of therapy after PD is based on the patient's general condition. Our management protocol resulted in good PPS. Furthermore, our results indicated equivalent efficacy of lenvatinib as in the SELECT trial. In conclusion, lenvatinib proved effective for RR-DTC patients in a real-world setting.

Stereotactic radiotherapy using the CyberKnife is effective for local control of bone metastases from differentiated thyroid cancer.

Differentiated thyroid cancer (DTC) is associated with a good long-term prognosis, but bone metastases can adversely affect patients' quality of life and survival. Stereotactic radiotherapy (SRT) can deliver high-dose irradiation to target lesions and it has been reported to be useful for various cancers. However, few studies have examined the efficacy of SRT for thyroid cancer. In the present study, the aim was to investigate the efficacy of SRT using the CyberKnife for bone metastases from DTC. From September 2013 to April 2018, SRT with the CyberKnife system was used to treat 60 bone metastases from DTC in 13 patients. The patients' medical records were retrospectively reviewed to obtain information about the adverse events associated with SRT. Of the 60 lesions, 40 could be evaluated by follow-up CT for therapeutic effectiveness, and the RECIST criteria were used to assess the response. The cancers were papillary cancer in 3 patients, follicular cancer in 9 and poorly differentiated cancer in 1. SRT was delivered in 1-10 fractions, with a median dose of 27 Gy (range, 8-48 Gy). Adverse events were infrequent and mild. The median follow-up of the 40 lesions was 11 (range, 2-56) months. The responses were partial response in 2 lesions, stable disease in 37 lesions and progressive disease in 1 lesion, with a 1-year local control rate of 97.1%. The present study showed that SRT using the CyberKnife system was a feasible and effective treatment for bone metastases of DTC.

Globus Symptoms in Patients Undergoing Thyroidectomy: Relationships with Psychogenic Factors, Thyroid Disease, and Surgical Procedure.

BACKGROUND: The number of patients who need thyroid surgery has increased worldwide in recent decades. Patients with thyroid disease experience globus pharyngeus as a result of direct compression and edema of the surrounding organs. Thyroid surgery is needed to improve these symptoms or as treatment for thyroid cancer. After thyroid surgery, globus symptoms may become worse and may affect the daily life of the patient for a long time. Psychogenic problems have also been thought to cause the globus sensation. A prospective analysis of globus symptoms and psychogenic factors following thyroidectomy was performed. MATERIAL AND METHODS: Patients scheduled to undergo thyroid surgery between February and September 2016 completed the foreign-body sensation in the throat score (FBST; range 0-8.2) and the self-rating depression scale (SDS; range 0-100) preoperatively and three days, one month, three months, six months, and 12 months postoperatively. RESULTS: Long-term follow-up was completed in 616 patients (491 females). A total of 365 patients had thyroid cancer, 169 had benign tumors, and 82 had diffuse goiters with Graves' disease. The percentage of patients who complained about neck discomfort (FBST >2) was 29.4% before surgery. A preoperative high FBST showed a significant direct correlation with a high SDS, but thyroid volume did not. A postoperative high FBST was seen in 75.3% of patients at two days and 78.9% at one month after surgery, and it then gradually decreased to 49.3% at 12 months after surgery. At three days after the operation, the median FBST was significantly higher in patients who had total thyroidectomy with lateral neck dissection or total thyroidectomy only compared to those who had lobectomy only (p < 0.05). These differences were still present 12 months after surgery. A higher preoperative SDS score was also identified as an independent predictor for a high FBST at 12 months after surgery, but not at one or three months postoperatively, on multivariate analyses. CONCLUSION: Preoperative globus symptoms appear directly related to psychological factors. The area of the surgical procedure and preoperative psychological factors were related to persistent neck discomfort.