Clinicopathologic risk factors of radioactive iodine therapy based on response assessment in patients with differentiated thyroid cancer: a multicenter retrospective cohort study.

PURPOSE: We investigated whether predictive clinicopathologic factors can be affected by different response criteria and how the clinical usefulness of radioactive iodine (RAI) therapy should be evaluated considering variable factors in patients with differentiated thyroid carcinoma (DTC). METHODS: A total of 1563 patients with DTC who underwent first RAI therapy after total or near total thyroidectomy were retrospectively enrolled from 25 hospitals. Response to therapy was evaluated with two different protocols based on combination of biochemical and imaging studies: (1) serum thyroglobulin (Tg) and neck ultrasonography (US) and (2) serum Tg, neck US, and radioiodine scan. The responses to therapy were classified into excellent and non-excellent or acceptable and non-acceptable to minimize the effect of non-specific imaging findings. We investigated which factors were associated with response to therapy depending on the follow-up protocols as well as response classifications. Multivariate logistic regression analysis was performed to identify factors significantly predicting response to therapy. RESULTS: The proportion of patients in the excellent response group significantly decreased from 76.5 to 59.6% when radioiodine scan was added to the follow-up protocol (P < 0.001). Preparation method (recombinant human TSH vs. thyroid hormone withdrawal) was a significant factor for excellent response prediction evaluated with radioiodine scan (OR 2.129; 95% CI 1.687-2.685; P < 0.001) but was not for other types of response classifications. Administered RAI activity, which was classified as low (1.11 GBq) or high (3.7 GBq or higher), significantly predicted both excellent and acceptable responses regardless of the follow-up protocol. CONCLUSIONS: The clinical impact of factors related to response prediction differed depending on the follow-up protocol or classification of response criteria. A high administered activity of RAI was a significant factor predicting a favorable response to therapy regardless of the follow-up protocol or classification of response criteria.

PROGNOSTIC VALUE OF LYMPH NODE UPTAKE ON PRETREATMENT F-18 FDG PET/CT IN PATIENTS WITH N1B PAPILLARY THYROID CARCINOMA.

Objective: The aim of this study was to investigate the prognostic value of metabolic characteristics of metastatic lymph node (LN) using pretreatment F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for patients with papillary thyroid carcinoma (PTC) and metastatic lateral LN (N1b). Methods: Ninety-six PTC patients (female:male = 72:24; median age, 44.5 years) with pathologic N1b who underwent pretreatment FDG PET/CT, total thyroidectomy, and radioactive iodine ablation were retrospectively reviewed. To predict responses to initial therapy and recurrence, clinicopathologic factors and metabolic parameters were reviewed, such as sex, age, tumor size, extranodal extension, number and ratio of metastatic LNs, serum thyroglobulin, and maximum standardized uptake value (SUVmax). Results: Among the 96 PTC patients, 81 (84.4%) were classified into the acceptable response (58 excellent; 23 indeterminate) and 15 (15.6%) into the incomplete response (8 biochemical incomplete; 7 structural incomplete) by the 2015 American Thyroid Association management guideline for differentiated thyroid carcinoma. The multivariate analysis showed that SUVmax of N1b (P = .018), pre-ablation stimulated thyroglobulin level (P = .006), and the ratio of metastatic LNs (P = .018) were related to incomplete response. The cutoff value of each variable was determined by receiver operating characteristic analysis. Nine (9.4%) patients experienced recurrences (median follow-up: 50 months). The Kaplan-Meier analysis revealed that SUVmax of N1b (cutoff value: 2.3; P = .025) and ratio of metastatic LNs (cutoff value: 0.218; P = .037) were significant prognostic factors for recurrence. Conclusion: High SUVmax of N1b cervical LN on pretreatment FDG PET/CT could predict incomplete responses to initial therapy and recurrence in patients with N1b PTC. Abbreviations: ATA = American Thyroid Association; DTC = well-differentiated thyroid carcinoma; FDG = F-18 fluorodeoxyglucose; IQR = interquartile range; LN = lymph node; N1b = metastatic lateral cervical lymph node; PET/CT = positron emission tomography/computed tomography; PTC = papillary thyroid carcinoma; RAI = radioactive iodine; ROC = receiver operating characteristic; SUVmax = maximum standardized uptake value; Tg = thyroglobulin; USG = ultrasonography.

Correction to: a risk stratification model for nodal peripheral T-cell lymphomas based on the NCCN-IPI and posttreatment Deauville score.

Unfortunately, the original version of this article contained several errors made during final step of article production. In the results section (fourth sentence) of the Abstract, the incomplete sentence,", 31.4% in high-risk group and 4.7% in treatment failure group.

A risk stratification model for nodal peripheral T-cell lymphomas based on the NCCN-IPI and posttreatment Deauville score.

PURPOSE: The aim of this study was to establish a risk-stratification model integrating posttreatment metabolic response using the Deauville score and the pretreatment National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) in nodal PTCLs. METHODS: We retrospectively analysed 326 patients with newly diagnosed nodal PTCLs between January 2005 and June 2016 and both baseline and posttreatment PET/CT data. The final model was validated using an independent prospective cohort of 79 patients. RESULTS: Posttreatment Deauville score (1/2, 3, and 4/5) and the NCCN-IPI (low, low-intermediate, high-intermediate, and high) were independently associated with progression-free survival: for the Deauville score, the hazard ratios (HRs) were 1.00 vs. 2.16 (95% CI 1.47-3.18) vs. 7.86 (5.66-10.92), P < 0.001; and for the NCCN-IPI, the HRs were 1.00 vs. 2.31 (95% CI 1.20-4.41) vs. 4.42 (2.36-8.26) vs. 7.09 (3.57-14.06), P < 0.001. Based on these results, we developed a simplified three-group risk model comprising a low-risk group (low or low-intermediate NCCN-IPI with a posttreatment Deauville score of 1 or 2, or low NCCN-IPI with a Deauville score of 3), a high-risk group (high or high-intermediate NCCN-IPI with a Deauville score of 1/2 or 3, or low-intermediate NCCN-IPI with a Deauville score of 3), and a treatment failure group (Deauville score 4 or 5). This model was significantly associated with progression-free survival (5-year, 70.3%, 31.4%, and 4.7%; P < 0.001) and overall survival (5-year, 82.1%, 45.5%, and 14.7%; P < 0.001). Similar associations were also observed in the independent validation cohort. CONCLUSION: The risk-stratification model integrating posttreatment Deauville score and pretreatment NCCN-IPI is a powerful tool for predicting treatment failure in patients with nodal PTCLs.

Drug Discovery by Molecular Imaging and Monitoring Therapy Response in Lymphoma.

Molecular imaging allows a noninvasive assessment of biochemical and biological processes in living subjects. Treatment strategies for malignant lymphoma depend on histology and tumor stage. For the last two decades, molecular imaging has been the mainstay diagnostic test for the staging of malignant lymphoma and the assessment of response to treatment. This technology enhances our understanding of disease and drug activity during preclinical and clinical drug development. Here, we review molecular imaging applications in drug development, with an emphasis on oncology. Monitoring and assessing the efficacy of anti-cancer therapies in preclinical or clinical models are essential and the multimodal molecular imaging approach may represent a new stage for pharmacologic development in cancer. Monitoring the progress of lymphoma therapy with imaging modalities will help patients. Identifying and addressing key challenges is essential for successful integration of molecular imaging into the drug development process. In this review, we highlight the general usefulness of molecular imaging in drug development and radionuclide-based reporter genes. Further, we discuss the different molecular imaging modalities for lymphoma therapy and their preclinical and clinical applications.

Targeting GLI1 Transcription Factor for Restoring Iodine Avidity with Redifferentiation in Radioactive-Iodine Refractory Thyroid Cancers.

Radioactive-iodine (RAI) therapy is the mainstay for patients with recurrent and metastatic thyroid cancer. However, many patients exhibit dedifferentiation characteristics along with lack of sodium iodide symporter (NIS) functionality, low expression of thyroid-specific proteins, and poor RAI uptake, leading to poor prognosis. Previous studies have demonstrated the effect of GLI family zinc finger 1 (GLI1) inhibition on tumor growth and apoptosis. In this study, we investigated the role of GLI1 in the context of redifferentiation and improvement in the efficacy of RAI therapy for thyroid cancer. We evaluated GLI1 expression in several thyroid cancer cell lines and selected TPC-1 and SW1736 cell lines showing the high expression of GLI. We performed GLI1 knockdown and evaluated the changes of thyroid-specific proteins expression, RAI uptake and I-131-mediated cytotoxicity. The effect of GANT61 (GLI1 inhibitor) on endogenous NIS expression was also assessed. Endogenous NIS expression upregulated by inhibiting GLI1, in addition, increased expression level in plasma membrane. Also, GLI1 knockdown increased expression of thyroid-specific proteins. Restoration of thyroid-specific proteins increased RAI uptake and I-131-mediated cytotoxic effect. Treatment with GANT61 also increased expression of endogenous NIS. Targeting GLI1 can be a potential strategy with redifferentiation for restoring RAI avidity in dedifferentiated thyroid cancers.

Combination Treatment with the BRAFV600E Inhibitor Vemurafenib and the BH3 Mimetic Navitoclax for BRAF-Mutant Thyroid Carcinoma.

BACKGROUND: Vemurafenib is a selective BRAF inhibitor (BRAFi) that has shown promising activity in BRAFV600E-positive papillary thyroid cancer (PTC). However, adverse events and resistance to a single-agent BRAFi often require discontinuation of the targeted therapy in BRAFV600E-positive PTC. Thus, this study investigated the expression of anti-apoptotic B-cell lymphoma 2 (BCL-2) family members, which are frequently overexpressed in many human cancers to inhibit apoptosis, in PTC harboring the BRAFV600E mutation after BRAFi treatment, and then evaluated the cytotoxic effects of a homology 3 domain (BH3)-mimetic in combination with a BRAFi. METHODS: K1 cells (BRAFV600E-positive human PTC) were treated with various concentrations of vemurafenib to investigate the effect of the BRAFi. In addition, the study analyzed the protein expression profiles of phosphorylated ERK1/2 (p-ERK 1/2) and anti-apoptotic BCL-2 family after vemurafenib treatment and selected the target anti-apoptotic protein. Antitumor effects were measured by cell counting, and effects on apoptosis were determined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay and Western blot analysis. RESULTS: At a concentration of 10 µM, vemurafenib inhibited the growth of K1 cells by 49.4%. Western blot analysis following exposure to 10 µM vemurafenib revealed that p-ERK1/2 gradually decreased over 24 hours, but the expression of B-cell lymphoma-extralarge (BCL-XL) and BCL-2 increased after 12 hours of treatment. Based on this result, the K1 cells were treated with navitoclax (BCL-2/BCL-XL inhibitor) for 24 hours up to a concentration of 4 µM, which resulted in negligible effects on cell survival. However, a combination treatment of 0.5 µM navitoclax with 1 µM vemurafenib resulted in significantly enhanced cell growth inhibition and increased apoptosis. CONCLUSIONS: The results of the present study show that vemurafenib increased the expression of anti-apoptotic proteins of the BCL-2 family. Thus, the combination of vemurafenib with navitoclax may be effective in BRAFV600E-positive PTC treatment.

Serum thyroglobulin elevation after needle aspiration of the lymph nodes: the predictive value for detecting metastasis in papillary thyroid cancer patients - a pilot study.

Ultrasonography (USG)-guided fine needle aspiration (FNA) is widely used for diagnosis of lymph node (LN) metastasis in papillary thyroid cancer (PTC). However, FNA cytology sometimes shows inconclusive results. Recently, the measurement of thyroglobulin (Tg) in FNA washout fluid (aspirate-Tg) has been widely adopted, but there are some difficulties in the preparation of the sample and standardization of the procedure. Here, we examined serum Tg after FNA as a new predictive marker for LN metastasis of PTC. We performed USG-guided FNA cytology and examined aspirate-Tg in PTC patients showing suspicious metastatic LNs during follow-up. We measured baseline serum thyroid stimulating hormone (TSH), Tg, and Tg antibody levels before FNA, and serum Tg level within an hour after FNA. We defined aspirate-Tg level above 0.9 ng/mL as positive, and a 30% increase in serum Tg level after FNA compared to the baseline as elevation of serum Tg. Twenty-two patients were included in our study. Nine patients (40.9%) showed elevation of Tg level after FNA, and the mean value of Tg elevation was 24.8 ±â€Š48.0 ng/mL. Among these 9 patients, 8 were diagnosed with PTC and 1 patient showed cellular atypia on cytopathology. All these patients showed positive aspirate-Tg. Thirteen patients (59.1%) did not show elevation of Tg level after FNA. Among these patients, 2 had PTC, 2 had cellular atypia, and 9 yielded negative results for malignancy on cytopathology. Elevation of serum Tg level after FNA might have a diagnostic role for predicting LN metastasis of PTC.

Development and Validation of an 18 F-Fluorodeoxyglucose-Positron Emission Tomography With Computed Tomography-Based Tool for the Evaluation of Joint Counts and Disease Activity in Patients With Rheumatoid Arthritis.

OBJECTIVE: Clinical joint count assessment is important for detecting synovitis but its reliability is a subject of controversy. This study was undertaken to assess the correlation of positron emission tomography (PET)-derived parameters in 68 joints with disease activity and to compare the reliability of joint counts between PET with computed tomography (CT) and clinical assessment in patients with rheumatoid arthritis (RA). METHODS: We enrolled 91 patients with active RA (69 in a development group and 22 in a validation group) who underwent concurrent 18 F-fluorodeoxyglucose (18 F-FDG)-PET-CT and clinical disease activity evaluation. PET-derived parameters were compared with disease activity assessed using clinical joint count parameters. A Disease Activity Score (DAS) using counts of PET-positive joints was developed, and then validation studies were performed in an independent group. RESULTS: The number of PET-positive joints (of 28 and 68 joints) was significantly correlated with the swollen joint count (SJC) and tender joint count (TJC) and the DAS in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR). Intraobserver and interobserver reliability of PET for the affected joint counts were excellent. Interobserver reliability between nuclear medicine physicians and rheumatologists was good for the SJC and TJC in both 28 joints and 68 joints. After multivariate analyses, including ESR and patient's global assessment of disease activity (PtGA) in addition to PET-derived parameters, the PET/DAS was derived as (0.063 × number of PET-positive joints in 28 joints) + (0.011 × ESR) + (0.030 × PtGA). A significant correlation between the PET/DAS and the DAS28-ESR was confirmed in the validation group (P < 0.001). CONCLUSION: PET-CT could serve as a sensitive and reliable method in the evaluation of disease activity in RA patients, and may be applicable as a research tool, particularly in clinical trials.

Enhancing prognosis prediction using pre-treatment nodal SUVmax and HPV status in cervical squamous cell carcinoma.

BACKGROUND: This study was to evaluate the prognostic value of metabolic parameters on F-18-FDG PET/CT and the status of human papillomavirus (HPV) infection and known prognostic variables for predicting tumor recurrence and investigating a prognostic model in patients with locally advanced cervical cancer treated with concurrent chemoradiotherapy (CCRT). METHODS: A total of 129 patients with cervical squamous cell carcinoma who underwent initial CCRT were eligible for this study. Univariate and multivariate analyses were performed using traditional prognostic factors, metabolic parameters, and HPV infection. Classification and regression decision tree (CART) was used to establish new classification. RESULTS: Among 129 patients, 29 patients (22.5%) had recurrence after a median follow-up of 60 months (range, 3-125 months). Tumor size, para-aortic lymph node metastasis, nodal SUVmax, and HPV infection status were identified as independent prognostic factors by multivariate analysis. The CART analysis classified the patients into three groups. The first node was nodal SUVmax, and HPV status was the second node for patients with nodal SUVmax ≤7.49; Group A (nodal SUVmax ≤7.49 and HPV positive, HR 1.0), Group B (nodal SUVmax ≤7.49 and HPV negative, HR 3.56), and Group C (nodal SUVmax > 7.49, HR 10.13). Disease-free survival was significantly different among the three groups (p < 0.001). CONCLUSION: The nodal SUVmax on F-18 FDG PET/CT and HPV infection status before CCRT are powerful independent prognostic factors for the prediction of disease-free survival in patients with cervical squamous cell carcinoma who underwent initial CCRT. We also suggest a simple prognosis prediction model using pre-treatment FDG PET/CT and HPV genotyping; however, it needs further validation in an independent dataset.

The Preventive Effect of Parotid Gland Massage on Salivary Gland Dysfunction During High-Dose Radioactive Iodine Therapy for Differentiated Thyroid Cancer: A Randomized Clinical Trial.

PURPOSE: To evaluate the preventive effect of parotid gland (PG) massage for PG damage during the I therapy, we prospectively investigated the serum amylase value and salivary gland scintigraphy (SGS) after I therapy. MATERIALS AND METHODS: One hundred patients with thyroidectomized differentiated thyroid cancer who underwent high-dose I therapy were enrolled in the clinical trial and randomized into 2 groups (PG massage group and nonmassage group). The serum amylase value was obtained before and 24 hours after I therapy, and the SGSs were also taken just before and at 8 months after the I therapy. Change in serum amylase value and SGS was compared between PG massage and nonmassage groups. RESULTS: The difference value of serum amylase was significantly lower in PG massage group than in nonmassage group (P = 0.0052). Worsening of PG function on SGS was observed in 43 (45.3%) of the 95 patients. The incidence rate of PG abnormality on F/U SGS was significantly lower in PG massage group than in nonmassage group (odds ratio, 0.3704; P = 0.0195). In the multiple regression analysis, PG massage significantly affected the abnormality on the 8-month F/U SGS (rpartial = -0.2741, P = 0.0090) after adjusting for clinical variables (age, sex, TNM stage, TSH preparation methods for the I therapy, and I dose). CONCLUSIONS: PG gland massage significantly reduced the incidence rates of salivary gland dysfunction on the 8-month F/U SGS and the level of the serological marker of salivary gland destruction after I therapy. Therefore, PG gland massage could alleviate salivary gland damage related to I therapy.

Risk factors for radioactive iodine-avid metastatic lymph nodes on post I-131 ablation SPECT/CT in low- or intermediate-risk groups of papillary thyroid cancer.

OBJECTIVE: Post I-131 ablation single-photon emission computed tomography (SPECT)/CT can show radioactive iodine (RAI)-avid cervical metastatic lymph nodes (mLN) in differentiated thyroid cancer. This study aimed to evaluate the incidence of RAI-avid mLN on post I-131 ablation SPECT/CT and the risk factors related to metastasis among patients with papillary thyroid cancer (PTC) in the low- or intermediate-risk groups. STUDY DESIGN AND SETTING: Among 339 patients with PTC who underwent total thyroidectomy followed by I-131 ablation, 292 (228 women, 64 men) belonging to the low- or intermediate-risk groups before I-131 ablation, and with sufficient clinical follow-up data were enrolled. The risk groups were classified based on the American Thyroid Association 2015 guideline. Each patient was followed-up for at least 24 months after the ablation (median: 30 months). The clinical, pathologic, and biochemical factors of PTC were reviewed, and their relationships to RAI-avid mLN on SPECT/CT were analyzed. RESULTS: Of the 292 patients, 61 and 231 belonged to the low-and intermediate-risk groups, respectively. Four (6.5%) patients in the low-risk group and 31 (13.0%) patients in the intermediate-risk group had RAI-avid mLN. A high preablation TSH-stimulated serum thyroglobulin (Tg) level in the low- or intermediate-risk group predicted the presence of RAI-avid mLN (cut-off = 0.5; hazard ratio (HR): 2.96; p = 0.04). In the subgroup analysis by risk group, TSH-stimulated serum Tg only predicted RAI-avid mLN in the low-risk group (cut-off = 1.0; HR: 5.3; p = 0.03). CONCLUSION: The incidence of RAI-avid mLN on postablation SPECT/CT was relatively high in both low- and intermediate-risk patients with PTC, and high preablation TSH-stimulated serum Tg level was a predictor of metastasis, especially in the low-risk group. A selective treatment approach should be considered in patients with high preablation TSH-stimulated serum Tg level.

Prevalence and Risk Factors of Atypical Femoral Fracture Bone Scintigraphic Feature in Patients Experiencing Bisphosphonate-Related Osteonecrosis of the Jaw.

PURPOSE: Bisphosphonate (BP) is the first-line therapy for the management of osteoporosis. BP-related osteonecrosis of the jaw (BRONJ) and atypical femoral fracture (AFF) are increasingly common comorbidities in patients with osteoporosis under long-term BP treatment. The aim of this study was to evaluate the incidence and risk factors for AFF features on bone scintigraphy in patients with BRONJ. METHODS: Among total of 373 BRONJ patients treated between September 2005 and July 2014, 237 (220 women, 17 men; median age 73 years) who underwent three-phase bone scintigraphy were enrolled for this retrospective study. AFF features on bone scintigraphy and the related clinical factors were assessed. RESULTS: Among 237 patients with BRONJ, 11 (4.6%) showed AFF features on bone scintigraphy. BP medication duration (p = 0.049) correlated significantly with AFF features on bone scintigraphy in patients with BRONJ. BP intake duration of 34 months was the cutoff value for predicting the presence of AFF features on bone scintigraphy. Among the patients with BRONJ, all those with AFF features on bone scintigraphy were female patients with osteoporosis who were on oral BP medication; however, these factors were not significantly different along with AFF features on bone scintigraphy. CONCLUSION: The incidence of AFF features on bone scintigraphy was relatively high in patients with BRONJ. A careful observation of patients presenting with the AFF features on bone scintigraphy may be needed, particularly for female BRONJ patients with osteoporosis who have been on BP medication for over 34 months.

Prognostic Value of Pretreatment Metabolic PET Parameters in Cervical Cancer Patients With Metabolic Complete Response After Concurrent Chemoradiotherapy.

PURPOSE: Cervical cancer may recur after concurrent chemoradiotherapy (CCRT), even in patients with metabolic complete response (mCR) on post-CCRT F-FDG PET. We retrospectively analyzed the value of metabolic parameters, measured by pretreatment PET, as prognostic factors for predicting recurrence and death in cervical cancer patients with mCR. METHODS: In 61 patients who reached mCR on post-CCRT, metabolic PET parameters including SUVmax, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumors, as well as those of the metastatic lymph nodes, were measured by pre-CCRT PET. Total MTV and total TLG were also measured from primary tumors and metastatic lymph nodes. Survival analyses for disease-free survival (DFS) and overall survival (OS) were performed. RESULTS: Eleven patients (18.0%) presented with recurrence of cervical cancer, and 12 (19.7%) died during follow-up. SUVmax, MTV, TLG of metastatic lymph nodes, and total TLG could significantly predict DFS, and nodal SUVmax could predict OS. Para-aortic lymph node metastasis also significantly correlated with both DFS and OS. In multivariate analysis, nodal SUVmax and para-aortic lymph nodes metastasis were prognostic factors for DFS, and the best predictor was nodal SUVmax. For OS, nodal MTV and para-aortic lymph node metastasis were significant prognostic factors in multivariate analysis, and the best predictor was para-aortic lymph node metastasis. CONCLUSIONS: Metabolic PET parameters, SUVmax or MTV values of metastatic lymph nodes, may be surrogate prognostic markers for recurrence or death in patients with locally advanced cervical cancer who reached mCR after definitive CCRT.

High Prevalence of Thyroid Disease and Role of Salivary Gland Scintigraphy in Patients with Xerostomia.

PURPOSE: Although Sjögren's syndrome (SS) is the most common disease causing xerostomia, autoimmune thyroid diseases can also affect the salivary glands. The aim of our study was to estimate the prevalence of thyroid diseases (TD) in subjects with symptoms of xerostomia and evaluate the efficacy of salivary gland scintigraphy (SGS) in the detection of TD in patients with SS and without SS. METHODS: We retrospectively reviewed the SGS findings of 173 subjects (men:women, 29:144) with symptoms of xerostomia. Ejection fractions (EF) in the parotid and submandibular glands were calculated. Thyroid disease was diagnosed on the basis of the results of the visual assessment of tracer uptake in the thyroid gland on SGS images as well as serological thyroid function tests. RESULTS: Based on the American-European Criteria, 94 patients were diagnosed with SS. Hashimoto's thyroiditis was diagnosed in 63 patients, subacute thyroiditis in 23, subclinical hypothyroidism in five, and Graves' disease in one. There were significant differences in the EF values of the parotid and submandibular glands between patients with TD and those with undetermined diagnoses. CONCLUSIONS: More than half of patients with xerostomia exhibited TD. Thyroid assessment by SGS is feasible, and SGS appears to be useful for the patients with xerostomia caused by TD. SGS may be the first imaging modality capable of evaluating both salivary gland function and thyroid gland status in patients with xerostomia. This strategy would make the requirement for additional workup for thyroid disease.

Clinical outcomes of low-dose and high-dose postoperative radioiodine therapy in patients with intermediate-risk differentiated thyroid cancer.

PURPOSE: Recent studies have suggested that a low dose (LD) of radioiodine (RAI) is sufficient to treat differentiated thyroid cancer (DTC) even in patients with intermediate risk. However, these studies evaluated the efficacy of RAI therapy, irrespective of the results of the whole-body scan (WBS). The aim of the present study was to evaluate the response to LD and high-dose (HD) RAI therapy using two different criteria (with and without WBS results) and the reclassification system according to the revised 2015 guidelines of the American Thyroid Association in Korean intermediate-risk DTC patients. In addition, we evaluated the long-term clinical outcomes of treatment with LD and HD RAI. MATERIALS AND METHODS: In total, 204 intermediate-risk DTC patients who underwent postoperative RAI therapy at two tertiary referral hospitals from 2003 to 2004 were enrolled in the present retrospective study. One hundred and twenty-four patients were treated with 3.7 and 5.55 GBq (HD) of RAI in one center and 80 patients were treated with 1.11 GBq (LD) in the other center. The success rate of RAI therapy was assessed with or without the inclusion of WBS results in the analysis. In addition, the response to therapy during the first 2 years of follow-up after the initial RAI therapy was categorized according to the reclassification system of 2015 American Thyroid Association guidelines as excellent response, indeterminate response, biochemical incomplete response, or structural incomplete response. Recurrence was defined as a newly detected cytologically or pathologically confirmed lesion. RESULTS: There were no significant differences between the success rates of the HD and LD groups irrespective of the inclusion of WBS results in the analysis (with WBS: 54.84 vs. 45.0%, P=0.23; without WBS: 60.48 vs. 62.5%, P=0.77). The response to HD and LD RAI therapy was excellent in 54.84 and 45.0% of the patients, respectively; indeterminate in 34.68 and 30.0% of the patients, respectively; biochemical incomplete in 4.03 and 13.75% of the patients, respectively; and structural incomplete in 6.45% and in 11.25% of the patients, respectively (P=0.04). In particular, the biochemical or structural incomplete response rate was lower in patients treated with HD than in patients treated with LD (HD, 10.48%; LD, 25.0%, P=0.01). At the last follow-up (HD, median 11 years; LD, median 10 years), patients who achieved an excellent response showed no evidence of disease. After the initial RAI therapy, eight patients in the HD group and 18 patients in the LD group who achieved either indeterminate response or biochemical incomplete response received additional RAI therapy. Seven patients (indeterminate response in five patients; biochemical incomplete response in two patients) in the HD group and seven patients (indeterminate response in five patients; biochemical incomplete response in two patients) in the LD group showed recurrences. CONCLUSION: LD RAI therapy after thyroidectomy appears to be insufficient in Korean DTC patients with intermediate risk. The patients in the LD group predominantly showed biochemical or structural incomplete response to initial RAI therapy and additional RAI therapy was required.

Clinical impact of 18 F-FDG positron emission tomography/CT on adenoid cystic carcinoma of the head and neck.

BACKGROUND: The purpose of this retrospective study was to assess the diagnostic value of 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT and the prognostic value of metabolic PET parameters in patients with adenoid cystic carcinoma of the head and neck (ACCHN). METHODS: Forty patients with newly diagnosed ACCHN were enrolled in this study. We investigated the diagnostic value of 18 F-FDG PET/CT for detecting and staging compared to conventional CT. Kaplan-Meier survival analysis for progression-free survival (PFS) was performed with clinicopathological factors and metabolic PET parameters. RESULTS: The 18 F-FDG PET/CT showed comparable sensitivity (92.3%) to conventional CT for lesion detection, and changed staging and management plan in 6 patients (15.0%). Lower PFS rates were associated with advanced T classification, advanced TNM classification, high maximum standardized uptake value (SUVmax; >5.1), and high total lesion glycolysis (>40.1) of the primary tumor. CONCLUSION: The 18 F-FDG PET/CT can provide additional information for initial staging, and metabolic PET parameters may serve as prognostic factors of ACCHN. © 2016 Wiley Periodicals, Inc. Head Neck 39: 447-455, 2017.

I-131 biokinetics of remnant normal thyroid tissue and residual thyroid cancer in patients with differentiated thyroid cancer: comparison between recombinant human TSH administration and thyroid hormone withdrawal.

OBJECTIVE: The aim of this study was to assess I-131 biokinetics in thyroid cancer and remnant tissue in patients with differentiated thyroid cancer using whole-body scan (WBS) and SPECT images acquired after I-131 therapy. The influence of thyroid stimulating hormone (TSH) stimulation method on the kinetics was also evaluated. METHODS: A total of 57 patients who received I-131 therapy (2.96-7.4 GBq) were retrospectively included. TSH stimulation was achieved by recombinant human thyrotropin (rhTSH) or by thyroid hormone withdrawal (THW). Each patient received three sequential WBSs on days 1, 2, and 4 (or 5) after I-131 administration. All lesions were classified either as thyroid remnant (ThyR) or as metastatic lymph nodes (mLN) after considering the SPECT/CT images acquired during the last WBS. The lesion-based retention rate and absorbed dose of ThyR and mLN were calculated using a commercial dosimetric toolkit combined with the OLINDA software. RESULTS: The retention rate and the effective half-time of mLN were lower than that of ThyR (p < 0.001, p = 0.003). In addition, the retention rate and the effective half-time of ThyR in the rhTSH group were higher than those in the THW group (p < 0.001, p < 0.001). The differences in the retention rate and the effective half-time of mLN were not statistically significant between the THW group and rhTSH group (p = 0.549, p = 0.571). CONCLUSIONS: Radioiodine therapy using rhTSH delivered an at least similar radiation dose to target lesions compared to using THW in thyroid remnants and metastatic lymph nodes.

Correlation Between Apparent Diffusion Coefficients and Standardized Uptake Values in Hybrid (18)F-FDG PET/MR: Preliminary Results in Rectal Cancer.

PURPOSE: Fluorine-18-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) and diffusion-weighted magnetic resonance imaging (DWI) share the same role in clinical oncology and it is feasible to obtain the standardized uptake value (SUV) and apparent diffusion coefficient (ADC) simultaneously by emerging the hybrid positron emission tomography/magnetic resonance (PET/MR). This study investigated the correlation between the ADCs of rectal cancer lesions and their SUVs derived from hybrid PET/MR. METHODS: Nine patients with histologically proven rectal adenocarcinoma (5 men, 4 women; mean age, 70 ± 15.91 years) underwent torso (18)F-FDG PET/CT and regional hybrid (18)F-FDG PET/MR sequentially. A fixed threshold value of 40 % of maximum uptake was used to determine tumor volume of interest (VOI) on PET image; SUVmax, SUVpeak, and SUVmean were calculated automatically. A single freehand region of interest (ROI) was drawn on high b-value (b1000) DWI image and copied to corresponding ADC map to determine the ADCmean of rectal cancer lesion. Spearman's rank correlation coefficient (ρ) was calculated to determine the correlation between SUVs and ADC values. RESULTS: SUVmax, SUVpeak, and SUVmean derived by hybrid PET/MR were 12.35 ± 4.66 (mean ± standard deviation), 9.66 ± 3.15 and 7.41 ± 2.54, respectively. The ADCmean value of rectal cancer lesions was 1.02 ± 0.08 × 10(-3)mm(2)/s. ADCmean was significantly and inversely correlated with SUV values (SUVmax, ρ = -0.95, p < 0.001; SUVpeak, ρ = -0.93, p < 0.001; SUVmean, ρ = -0.91, p = 0.001). CONCLUSIONS: This preliminary hybrid PET/MR study demonstrates a significant inverse correlation exists between metabolic activity on (18)F-FDG PET and water diffusion on DWI in rectal cancer.

Evaluation of Dixon Sequence on Hybrid PET/MR Compared with Contrast-Enhanced PET/CT for PET-Positive Lesions.

PURPOSE: Hybrid positron emission tomography and magnetic resonance (PET/MR) imaging performs a two-point Dixon MR sequence for attenuation correction. However, MR data in hybrid PET/MR should provide anatomic and morphologic information as well as an attenuation map. We evaluated the Dixon sequence of hybrid PET/MR for anatomic correlation of PET-positive lesions compared with contrast-enhanced PET/computed tomography (CT) in patients with oncologic diseases. METHODS: Twelve patients underwent a single injection, dual imaging protocol. PET/CT was performed with an intravenous contrast agent (85 ± 13 min after (18)F-FDG injection of 403 ± 45 MBq) and then (125 ± 19 min after injection) PET/MR was performed. Attenuation correction and anatomic allocation of PET were performed using contrast-enhanced CT for PET/CT and Dixon MR sequence for hybrid PET/MR. The Dixon MR sequence and contrast-enhanced CT were compared for anatomic correlation of PET-positive lesions (scoring scale ranging from 0 to 3 for visual ratings). Additionally, standardized uptake values (SUVs) for the detected lesions were assessed for quantitative comparison. RESULTS: Both hybrid PET/MR and contrast-enhanced PET/CT identified 55 lesions with increased FDG uptake in ten patients. In total, 28 lymph nodes, 11 bone lesions, 3 dermal nodules, 3 pleural thickening lesions, 2 thyroid nodules, 1 pancreas, 1 liver, 1 ovary, 1 uterus, 1 breast, 1 soft tissue and 2 lung lesions were present. The best performance was observed for anatomic correlation of PET findings by the contrast-enhanced CT scans (contrast-enhanced CT, 2.64 ± 0.70; in-phase, 1.29 ± 1.01; opposed-phase, 1.29 ± 1.15; water-weighted, 1.71 ± 1.07; fat weighted, 0.56 ± 1.03). A significant difference was observed between the scores obtained from the contrast-enhanced CT and all four coregistered Dixon MR images. Quantitative evaluation revealed a high correlation between the SUVs measured with hybrid PET/MR (SUVmean, 2.63 ± 1.62; SUVmax, 4.30 ± 2.88) and contrast-enhanced PET/CT (SUVmean, 3.88 ± 2.30; SUVmax, 6.53 ± 4.04) in PET-positive lesions (SUVmean, ρ = 0.93; SUVmax, ρ = 0.95), although hybrid PET/MR presented a decrease of SUVs compared with contrast-enhanced PET/CT (mean reduction; SUVmean, 32.44 ± 15.64 %; SUVmax, 35.16 ± 12.59 %). CONCLUSIONS: Despite different attenuation correction approaches, the SUV of PET-positive lesions correlated well between hybrid PET/MR and contrast-enhanced PET/CT. However Dixon MR images acquired for attenuation correction were insufficient to provide anatomic information of PET images because of low spatial resolution. Thus, additional MR sequence with fast and higher resolution may be necessary for anatomic information.