Summary Background Any benefit of adjuvant interferon alfa-2b for melanoma could depend on dose and duration of treatment. Our aim was to determine whether pegylated interferon alfa-2b can facilitate ...prolonged exposure while maintaining tolerability. Methods 1256 patients with resected stage III melanoma were randomly assigned to observation (n=629) or pegylated interferon alfa-2b (n=627) 6 μg/kg per week for 8 weeks (induction) then 3 μg/kg per week (maintenance) for an intended duration of 5 years. Randomisation was stratified for microscopic (N1) versus macroscopic (N2) nodal involvement, number of positive nodes, ulceration and tumour thickness, sex, and centre. Randomisation was done with a minimisation technique. The primary endpoint was recurrence-free survival. Analyses were done by intention to treat. This study is registered with ClinicalTrials.gov , number NCT00006249. Findings All randomised patients were included in the primary efficacy analysis. 608 patients in the interferon group and 613 patients in the observation group were included in safety analyses. The median length of treatment with pegylated interferon alfa-2b was 12 (IQR 3·8–33·4) months. At 3·8 (3·2–4·2) years median follow-up, 328 recurrence events had occurred in the interferon group compared with 368 in the observation group (hazard ratio 0·82, 95% CI 0·71–0·96; p=0·01); the 4-year rate of recurrence-free survival was 45·6% (SE 2·2) in the interferon group and 38·9% (2·2) in the observation group. There was no difference in overall survival between the groups. Grade 3 adverse events occurred in 246 (40%) patients in the interferon group and 60 (10%) in the observation group; grade 4 adverse events occurred in 32 (5%) patients in the interferon group and 14 (2%) in the observation group. In the interferon group, the most common grade 3 or 4 adverse events were fatigue (97 patients, 16%), hepatotoxicity (66, 11%), and depression (39, 6%). Treatment with pegylated interferon alfa-2b was discontinued because of toxicity in 191 (31%) patients. Interpretation Adjuvant pegylated interferon alfa-2b for stage III melanoma has a significant, sustained effect on recurrence-free survival. Funding Schering Plough Research International.
Interferon (IFN) -based adjuvant therapy in melanoma is associated with significant side effects, which necessitates evaluation of health-related quality of life (HRQOL). Our trial examined the HRQOL ...effects of adjuvant pegylated IFN-alpha-2b (PEG-IFN-alpha-2b) versus observation in patients with stage III melanoma.
A total of 1,256 patients with stage III melanoma were randomly assigned after full lymphadenectomy to receive either observation (n = 629) or PEG-IFN-alpha-2b (n = 627): induction 6 micrograms/kg/wk DOSAGE ERROR CORRECTED for 8 weeks then maintenance 3 micrograms/kg/wk DOSAGE ERROR CORRECTED for an intended total duration of 5 years. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 was used to assess HRQOL.
At 3.8 years of median follow-up, for the primary end point, recurrence-free survival (RFS), risk was reduced by 18% (hazard rate = 0.82; P = .01) in the PEG-IFN-alpha-2b arm compared with observation. Significant and clinically meaningful differences occurred with the PEG-IFN-alpha-2b treatment arm compared with the observation group, showing decreased global HRQOL at month 3 (-11.6 points; 99% CI, -8.2 to -15.0) and year 2 (-10.5 points; 99% CI, -6.6 to -14.4). Many of the other scales showed statistically significant differences between scores when comparing the two arms. From a clinical point of view, important differences were found for five scales: two functioning scales (social and role functioning) and three symptom scales (appetite loss, fatigue, and dyspnea), with the PEG-IFN-alpha-2b arm being most impaired.
PEG-IFN-alpha-2b leads to a significant and sustained improvement in RFS. There is an expected negative effect on global HRQOL and selected symptoms when patients undergo PEG-IFN-alpha-2b treatment.
The early identification of aggressive forms of cancer is of high importance in treating papillary thyroid cancer (PTC). Disease dissemination is a major factor influencing patient survival. Mutation ...status of
oncogene,
V600E, is proposed to be an indicator of disease recurrence; however, its influence on PTC dissemination has not been deciphered. This study aimed to explore the association of the frequency of
V600E alleles in PTC with disease dissemination. In this study, 173 PTC samples were analyzed, measuring the proportion of
V600E alleles by qPCR, which was then normalized against the proportion of tumor cells. Semiquantitative analysis of BRAF V600E mutant protein was performed by immunohistochemistry. The
V600E mutation was present in 60% of samples, while the normalized frequency of mutated
alleles ranged from 1.55% to 92.06%. There was no significant association between the presence and/or proportion of the
V600E mutation with the degree of PTC dissemination. However, the presence of the
mutation was significantly linked with angioinvasion. This study's results suggest that there is a heterogeneous distribution of the
mutation and the presence of oligoclonal forms of PTC. It is likely that the
mutation alone does not significantly contribute to PTC aggressiveness.
Objective
To assess efficiency of various I-131 activities on thyroid remnant ablation in thyroid cancer patients. The significance of patients’ characteristics, pathologic features and levels of Tg ...were analyzed.
Patients and methods
This study included 259 consecutive differentiated thyroid cancer patients, with disease confined to the thyroid, treated with I-131 after total thyroidectomy. Patients were divided into the three groups: 80 patients receiving low 1110–1850 MBq (30–50 mCi), 121 intermediate 2775 MBq (75 mCi) and 58 high 3700 MBq (100 mCi) postoperative I-131 activities. Six to eight months after the application of radioiodine, measurements of TSH, Tg, anti-Tg antibodies (in hypothyroid state) together with ultrasound exam and whole-body scintigraphy were performed.
Results
The ablation was significantly more effective (after the first application) in patients receiving 100 mCi of I-131—89.7 % than in patients receiving lower activities (
P
= 0.016). There was no significant difference in ablation rate between the 30–50 mCi (77.5 %) and 75 mCi (70.2 %) groups. In the group receiving 30–50 mCi, patients with solitary tumors had significantly higher ablation rate (
P
= 0.038). In patients receiving 75 mCi ablation rates were higher among older patients (
P
= 0.005), with infiltration of the single lobe (
P
= 0.005), and with solitary tumor (
P
= 0.012). The rates of successful ablation after the second application of I-131 (after 12–16 months) amounted to 96, 97 and 96 % in the 30–50, 75 and 100 mCi groups, respectively. The activity of I-131 and age were independent factors for thyroid ablation failure after the first application of I-131 (model of binary logistic regression).
Conclusion
The results of remnant ablation were satisfactory with all activities applied. Although after the first application of I-131 the activity of 100 mCi is significantly more effective in thyroid ablation than the administration of 30–50 mCi and 75 mCi, the ablation rates between all the three groups are similar (almost equal) after the second application. Thus, the activity to be administered may depend on patients’ characteristics and a detailed consideration of the merits and demerits of each I-131 activity.
Context:
The median urinary iodine concentration (UIC) is a biomarker of iodine intake. According to the World Health Organization, a median UIC in the range 100–199 μg/L indicates adequate and ...200–299 μg/L more than adequate intake. Thyroglobulin (Tg) may be a promising functional biomarker of both iodine deficiency and excess.
Objectives:
Using a standardized dried blood spots-Tg assay in children, we evaluated the Tg response to both low- and high-iodine intake and estimated the population cutoff point for iodine deficiency or excess. Also, we compared thyroid functions within the UIC ranges of 100–199 vs 200–299 μg/L.
Design and Setting:
We conducted a cross-sectional study in primary schools in 12 countries.
Subjects:
Subjects were 6 to 12 years old (n = 2512).
Main Outcome Measures:
We measured UIC, TSH, total T4, Tg, and thyroid antibodies.
Results:
Over a range of iodine intakes from severely deficient to excessive, Tg concentrations showed a clear U-shaped curve. Compared with iodine-sufficient children, there was a significantly higher prevalence of elevated Tg values in children with iodine deficiency (UIC <100 μg/L) and iodine excess (UIC >300 μg/L). There was no significant change in the prevalence of elevated Tg, TSH, T4, or thyroid antibodies comparing children within the UIC ranges of 100–199 vs 200–299 μg/L.
Conclusions:
In school-aged children, 1) Tg is a sensitive indicator of both low and excess iodine intake; 2) a median Tg of <13 μg/L and/or <3% of Tg values >40 μg/L indicates iodine sufficiency in the population; 3) the acceptable range of median UIC in monitoring iodized salt programs could be widened to a single category of sufficient iodine intake from 100 to 299 μg/L.
Backgroud/Aim: To assess the clinical significance of nodules in multinodular thyroid if one nodule is diagnosed as papillary carcinoma (PC), we investigated 97 patients with a multinodular thyroid ...and histopathological diagnosis of PC.
We assessed the following variables: age and gender, fine-needle aspiration diagnosis, PC nodule size and dominance, intraglandular dissemination (ID), regional lymph node (RLN) status, and distribution of diagnoses of the other nodules.
Among 97 patients with PC, additional diagnoses were: nodular goiter (NG) in 64 patients, ID in 28, Hashimoto's thyroiditis (HT) in 26, and follicular or Hürthle cell adenoma in seven.
Patients with ID, and without NG or HT more often had RLN metastases. Lower rates of RLN metastases in patients with NG and HT are probably due to smaller PC nodule sizes found during routine follow-up of these benign diseases.
To evaluate the significance of plasma free serotonin (5-hydroxytryptamine) and Ca15.3 for the early detection of breast cancer recurrence.
Free serotonin and Ca15.3 levels were measured by ...I-125-Serotonin RIA (DDV Diagnostica, Marburg, Germany) in plasma and an ELISA kit (Roche Diagnostic GmbH, Mannheim, Germany) in serum, respectively in women (N=29) who responded to primary treatment for breast cancer and who were followed-up for recurrence. For analysis, patients were sub-divided according to TNM staging into groups with localized (T1-2N0-M0) and advanced (T1-2N1-2M0-1) disease. The control group were healthy blood donors.
Patients with advanced disease had a significantly higher plasma serotonin level than those with localized disease or controls, whereas Ca15.3 levels remained in normal range in all groups. At the time of serotonin measurement, radiological findings were negative for all patients in the localized-disease group, but positive in nine patients in the advanced-disease group.
Plasma free serotonin may be used for the early detection of recurrent/metastatic breast cancer disease, but validation on a larger number of patients is needed.
- Initial treatment of the majority of patients with differentiated thyroid cancer (DTC) includes total thyroidectomy. Postoperative ablation therapy with radioactive iodine (I-131) is indicated in ...all high-risk patients, however, there is disagreement regarding its use in low- and intermediate-risk patients. Over the last few decades, thyroglobulin (Tg) has been established as the primary biochemical tumor marker for patients with DTC. Thyroglobulin can be measured during thyroid hormone therapy or after thyroid-stimulating hormone (TSH) stimulation, through thyroid hormone withdrawal or the use of human recombinant TSH. In many studies, the cut-off value for adequate Tg stimulation is a TSH value ≥30 mIU/L. However, there is an emerging body of evidence suggesting that this long-established standard should be re-evaluated, bringing this threshold into question. Recently, a risk stratification system of response to initial therapy (with four categories) has been introduced and Tg measurement is one of the main components. The relationship between the Tg/TSH ratio and the outcome of radioiodine ablation has also been studied, as well as clinical significance of serum thyroglobulin doubling-time. The postoperative serum Tg value is an important prognostic factor that is used to guide clinical management, and it is the most valuable tool in long term follow-up of patients with DTC.
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