Anaplastic thyroid cancer (ATC) is a rare and highly aggressive cancer for which effective systemic therapy has long been sought. Here, we assessed the efficacy and safety of lenvatinib in patients ...with unresectable ATC.
The study was investigator-initiated and conducted under a multicenter, open-label, nonrandomized, phase II design. Eligibility criteria included pathologically proven ATC; unresectable measurable lesion as defined by RECIST 1.1; age 20 years or older; ECOG PS 0–2; and adequate organ function. The primary end-point was overall survival. Secondary end-points were progression-free survival, objective response rate, disease control rate, clinical benefit rate, and safety.
Of 52 patients enrolled from 17 institutions, 42 patients who were confirmed to have ATC were included for efficacy analysis, and 50 patients were included for safety analysis. The estimated 1-year overall survival rate was 11.9% (95% CI, 4.4%–23.6%). One patient (2.4%) achieved complete response, four patients (9.5%) partial response, and 26 patients (61.9%) stable disease, including nine patients (21.4%) who demonstrated durable stable disease, giving an objective response rate of 11.9%, disease control rate of 73.8%, and clinical benefit rate of 33.3%. Adverse events of any grade were observed in 45 patients (90.0%), the most common of which of any grade included loss of appetite (48.0%), fatigue (48.0%), hypertension (44.0%), and palmar-plantar erythrodysesthesia syndrome (26.0%).
Lenvatinib treatment resulted in disappointing survival for unresectable ATC patients. Although the number of responders was small, responses were durable, indicating that lenvatinib may be beneficial for selected patients. Further investigation to identify suitable candidates for lenvatinib monotherapy is needed.
•This study assessed the efficacy and safety of lenvatinib in unresectable ATC.•The estimated 1-year overall survival rate was 11.9%.•The estimated 1-year progression free survival rate was 4.9%.•The objective response rate was 11.9%, and the disease control rate was 73.8%.•No fatal haemorrhagic side-effect was observed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Previous studies have reported an association between four or more foci of vascular invasion (VI) and thyroid cancer prognosis, while the current study aimed to investigate the association ...between extent of VI and outcome of encapsulated angioinvasive follicular thyroid carcinoma (FTC).
Methods
The records of 264 patients with encapsulated angioinvasive FTC confirmed by surgical specimens at Ito Hospital from January 2005 to December 2014 were retrospectively reviewed. Thirteen patients had distant metastasis at diagnosis and were classified as M1.
Results
Among the 251 patients with M0 encapsulated angioinvasive FTC, the 10-year disease-free survival (DFS) rate was 84.1%. Those with a VI of 1 (
n
= 116) or ≥ 2 (
n
= 135) had a 10-year DFS rate of 94.5% and 75.4% (
p
< 0.001), respectively, and those with a VI of 1–3 (
n
= 180) or ≥ 4 (
n
= 71) had a 10-year DFS rate of 84.8% and 82.1% (
p
= 0.346), respectively. Multivariate analysis identified age ≥ 55 years (
p
= 0.031) and VI ≥ 2 (
p
= 0.002) as independent negative prognostic factors for DFS. Patients with M0 encapsulated angioinvasive FTC aged ≥ 55 years and VI ≥ 2 had significantly poorer prognosis and a 10-year DFS rate of 66.4% (
p
< 0.001).
Conclusions
Patients with encapsulated angioinvasive FTC who had two or more foci of VI, especially patients aged ≥ 55 years, should be carefully followed-up.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Anaplastic thyroid carcinoma (ATC) is a malignancy with one of the highest fatality rates. Here we report a retrospective study of the treatment and other factors associated with its outcomes.
The ...medical records of 100 patients diagnosed with ATC at Ito Hospital between 1993 and 2009 were reviewed and pertinent information was extracted and analyzed.
There were 80 women and 20 men, and their median age at diagnosis was 68 years (range, 41-90 years). Thirteen patients had a history of well-differentiated thyroid carcinoma. Six patients had a small ATC focus within a differentiated carcinoma. All cases were retrospectively staged according to the Union for International Cancer Control classification system, and the results were stage IVA in 11 cases, stage IVB in 31 cases, and stage IVC in 58 cases. Seventy patients underwent surgical treatment, and complete resection was performed in 24 of them. Seventy-eight patients received radiotherapy, and 58 of them received a total dose of ≥40 Gy. Twenty-seven patients received chemotherapy. Only 15 patients received multimodal therapy (surgery, radiotherapy, and chemotherapy). The 1-year survival rates according to stage were as follows: stage IVA, 72.7%; stage IVB, 24.8%; and stage IVC, 8.2%. Multivariate analysis identified age ≥70 years, white blood cell ≥10,000 mm(3), extrathyroidal invasion, and distant metastasis at the time of diagnosis as prognostic factors. Survival after complete resection was significantly better than after incomplete resection or no resection. The results also suggested that radiation doses of ≥40 Gy were associated with significantly longer survival.
Although the prognosis of most patients with ATC continues to be poor, surgery, radiotherapy, and a combination of both improved the survival of patients with ATC.
The present study aimed to establish new reference intervals (RIs) for serum free triiodothyronine (fT3), free thyroxine (fT4), and thyroid stimulating hormone (TSH) levels in Japanese children and ...adolescents aged 4 to 19 years. A total of 2,036 (1,611 girls, 425 boys) participants were included over a 17-year period; they all tested negative for antithyroid antibodies (TgAb, TPOAb) and were found to have no abnormalities on ultrasonography. RIs were determined by nonparametric methods. The results showed that serum fT3 was significantly higher in the 4–15-year-olds than in the 19-year-olds. The serum fT4 was significantly higher in the 4–10-year-olds than in the 19-year-olds. The serum TSH was significantly higher in the 4–12-year-olds than in the 19-year-olds. All of them gradually decreased with age to approximate the adult levels. The upper limit of TSH was lower in those aged 13 to 19 years than in adults. The differences were examined by sex. The serum fT3 was significantly higher in boys than in girls between the ages of 11 and 19 years. The serum fT4 was significantly higher in boys than in girls between the ages of 16 and 19 years. There did not seem to be any sex difference in those under 10 years of age. In conclusion, serum fT3, fT4, and TSH levels in children and adolescents differ from those in adults. It is important to evaluate thyroid function using the new RIs that are appropriate for chronological age.
Appropriate administration of anti-inflammatory and immunosuppressive treatment (AIIST) is important for patients with Graves’ orbitopathy (GO). This study aimed to clarify the incidence and risk ...factors for GO treated with AIIST and propose a predictive score, among newly diagnosed Graves’ disease (GD) patients in Japan. A total of 1,553 GD patients who were newly diagnosed during the year 2011 were investigated. AIIST included local and/or systemic glucocorticoid administration and retrobulbar irradiation. A multivariable Cox proportional hazards model was used to investigate the risk factors for GO underwent AIIST during medical treatment, including at diagnosis, of GD. Then, a GO score was created by summing each point assigned to risk factors based on their coefficient obtained in the Cox model. AIIST was administered to 107 patients (6.9%). The risk factors and hazard ratios for GO underwent AIIST were: age (per 10 years), 1.32 (95% confidence interval: 1.16–1.50), p < 0.0001; TSH binding inhibitory immunoglobulin (TBII) (per 10 IU/L), 1.33 (1.15–1.54), p = 0.0001; and thyroglobulin antibody (TgAb) negativity, 2.98 (1.96–4.59), p < 0.0001. The GO score, ranging from 0 to 8 points, showed moderate performance (area under the curve: 0.71, cut-off value: 5 points, sensitivity: 0.76, specificity: 0.59, positive predictive value: 0.12, negative predictive value: 0.97). AIIST was performed for patients with active manifestations of GO in 6.9% of newly diagnosed GD patients. The risk factors for GO underwent AIIST were higher age, higher TBII, and TgAb negativity. The GO score based on these factors may be useful in managing GO.
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.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
Anaplastic thyroid carcinoma (ATC) is occasionally found on postoperative pathological examination of patients with differentiated thyroid carcinoma (DTC). There is no general consensus on ...how we should treat these incidentally diagnosed ATC (incidental ATC).
Materials and methods
A total of 675 patients with ATC were registered with the ATC Research Consortium of Japan. These patients were treated between 1995 and 2008 in 38 registered institutions. About 81 % of the ATC patients had common-type ATC and about 14 % had ATC co-existing with a metastatic DTC lesion. The remaining 5 % had incidental ATC. Among the patients with incidental ATC, we investigated 25 patients whose clinical data were fully available. We examined the clinical profile of incidental ATC, and the relationships between treatment and outcome in patients with incidental ATC.
Results
The tumor size was clearly smaller, and patients with extrathyroid invasion or distant metastasis were significantly fewer in incidental ATC than in common-type ATC. Most incidental ATC coexisted with papillary carcinoma. While the clinical course of incidental ATC was favorable compared with common-type ATC, half of the patients had disease-related deaths. The prognostic factors of incidental ATC were nearly the same as those of common-type ATC, but the tumor size alone was an independent factor on multivariate analysis. Regarding treatments, the outcome was more favorable in those who underwent curative resection, and the clinical course showed a slight improvement by the addition of external beam radiotherapy and/or chemotherapy after curative resection, but it did not reach statistical significance.
Conclusion
Incidental ATC is the only curable type of ATC, and further studies are needed to establish the effectiveness of additional postoperative radiotherapy and/or chemotherapy in incidental ATC.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract
Context
Thyroid mucosa-associated lymphoid tissue (MALT) lymphoma is a type of extranodal lymphoma with a favorable prognosis.
Objective
To provide information on long-term outcomes that ...would facilitate establishment of the optimal management strategy for thyroid lymphoma.
Design, Setting, and Participants
Medical records of 107 patients (median age 67 years, 20 males, 87 females) who were diagnosed with localized thyroid MALT lymphoma stage IE or IIE at Ito Hospital were retrospectively reviewed.
Main Outcome Measure
Overall and event-free survival (EFS).
Results
Initial treatments included radiation therapy (RT) alone (n = 58), combined modality therapy (CMT) (n = 48), or chemotherapy alone (n = 1). All 107 patients responded to the treatment, six of whom experienced relapse. Only one patient died of lymphoma. The 5-year overall survival (OS) and EFS rates were 94% 95% confidence interval (CI), 87% to 97% and 92% (95% CI, 85% to 95%), respectively, and the 10-year OS and EFS rates were 91% (95% CI, 83% to 95%) and 84% (95% CI, 74% to 90%), respectively. Of the 106 patients with information available on adverse events, 71 patients (67%) developed hypothyroidism after primary thyroid lymphoma treatment. The CMT group showed additional chemotherapy-induced adverse reactions in the form of neutropenia, neuropathy, constipation, and pneumonia. The 5-year OS rates of patients treated with CMT and RT were 93% (95% CI, 81% to 98%) and 94% (95% CI, 84% to 98%), respectively.
Conclusions
Long-term outcomes of localized thyroid MALT lymphoma are favorable with all initial treatment modalities.
We studied outcomes of 107 cases of localized thyroid MALT lymphoma. This study, the largest-scale long-term study ever, showed that outcomes are favorable with all initial treatment modalities.
More than 40 years have passed since the introduction of newborn screening (NBS) for congenital hypothyroidism (CH), and many early diagnosed patients have reached adulthood. Their thyroid morphology ...and function have been little studied. This cross-sectional, observational study was conducted to characterize the thyroid morphology and function of adult CH patients diagnosed in the framework of NBS for CH.
A total of 103 adult CH patients born after 1979 were enrolled at Ito Hospital, Tokyo, Japan, and were classified into Goiter, Normal gland, and Dysgenesis groups based on ultrasonographic findings. For 60 patients, genetic analysis was performed. Thyroid function test results and the proportion of patients with thyroid nodules were compared among the three groups and between 56 female CH patients and 168 non-CH women matched for thyrotropin levels.
A significantly low serum free triiodothyronine/free thyroxine ratio (0.22) was observed in the Dysgenesis group. Thyroid nodules were detected in 14.3% (8/56) of female CH patients, more frequently than in non-CH women. Thyroid nodules were detected most frequently in the Goiter group (71%, 10/14). Genetic defects were identified in 89% (8/9) of patients belonging to the Goiter group, including thyroglobulin defect (33%, 3/9), thyroid peroxidase defect (33%, 3/9), and dual oxidase 2 defect (22%, 2/9).
Our results suggest that adults with thyroid dysgenesis on levothyroxine replacement therapy have relative triiodothyronine deficiency. Most adults with goitrous CH have genetic dyshormonogenesis. They are at high risk of developing thyroid nodules. Our findings support the current guideline recommendation that CH patients with dyshormonogenesis should undergo periodic thyroid ultrasonography.
Propylthiouracil (PTU)-induced otitis media with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (OMAAV) is an extremely rare adverse event associated with anti-thyroid drugs and is ...not well recognized. A 42-year-old woman with Graves’ disease undergoing PTU therapy for 8 years visited our hospital because of earache and congested feeling in her left ear. Blood tests, a computed tomography scan and pure tone audiometry revealed otitis media and moderate mixed hearing impairment. Antibiotics, ear drops with antibiotics and painkillers were administered. However, her earache and hearing loss gradually got worse and symptoms of facial nerve palsy appeared. At several weeks after initiation of the treatment, a high serum level of myeloperoxidase (MPO)-ANCA, 75.6 U/mL, was revealed. After excluding other causes, she was diagnosed with OMAAV. PTU was suspected as the cause of her OMAAV and was immediately discontinued, and prednisolone was started. Hearing impairment in her left ear gradually got better and showed substantial improvement. Facial nerve palsy disappeared. Although PTU-induced OMAAV is an extremely rare disease, it is important to recognize the disease, as delayed treatment can lead to irreversible hearing loss, hypertrophic pachymeningitis, and subarachnoid hemorrhage. When patients taking anti-thyroid drugs, especially PTU, are diagnosed with refractory otitis media or hearing loss, it is possible that OMAAV might be the cause and thus serum ANCA levels should be evaluated.
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