Lenvatinib in multimodal therapy for unresectable radioactive iodine-naïve differentiated thyroid cancer: A case report with literature review.

BACKGROUND: Patients with unresectable or metastatic differentiated thyroid carcinoma (DTC) are rare and require individualized therapy. This may require approaches not typically used in resectable disease. We report a patient treated with lenvatinib and external beam radiation therapy. CASE: An 87-year-old woman presented with cT4N1aM1 papillary thyroid carcinoma with tracheal invasion. She was not a candidate for surgery, radioactive-iodine, or radiation, so a trial of lenvatinib was offered. Her tumor showed clinical, biochemical, and radiological response after 5 months of lenvatinib, and she subsequently received external beam radiation. She enjoys good quality of life without evidence of cancer progression off therapy 21 months post-initiation of treatment. CONCLUSION: Lenvatinib may be effective in RAI-naïve advanced DTC patients as a component of individualized multimodal therapy when conventional options are not feasible.

Defining radio-recurrent intra-prostatic target volumes using PSMA-targeted PET/CT and multi-parametric MRI.

PURPOSE: Our purpose was to evaluate intra-prostatic cancer volumes for salvage radiotherapy in men with recurrent prostate cancer confined to the prostate post-primary radiotherapy using mpMRI and 18F-DCFPyL PET/CT (PET). METHODS: Men with biochemical failure post-primary radiotherapy were enrolled in a multi-centre trial investigating mpMRI and PET. All men with isolated intra-prostatic recurrence are included in this secondary analysis. The intra-prostatic gross tumour volume (GTV) was manually delineated on mpMRI and was also delineated on PET using three methods: 1. manually, 2. using a 30% threshold of maximum intra-prostatic standard uptake value (SUVmax), and 3. using a 67% threshold of this SUVmax. Clinical target volumes (CTV) including expansions on each GTV were generated. Conformity indices were performed between the mpMRI CTV and each PET CTV. Correlation with biopsy and clinical outcomes were performed. RESULTS: Of the 36 men included, 30 (83%) had disease in two quadrants or less using the combination of mpMRI and PET. Mean target volume (union of CTV on mpMRI and CTV manually delineated on PET) was 12.2 cc (49% of prostate gland volume). 12/36 (33%) men had a biopsy. Per-patient sensitivity was 91% for mpMRI and 82% for PET. CONCLUSIONS: mpMRI and PET provide complementary information for delineation of intra-prostatic recurrent disease. Union of CTV on mpMRI and PET is often less than 50% of the prostate, suggesting this imaging could help define a target for focal salvage therapy.

Short-duration dynamic [18F]DCFPyL PET and CT perfusion imaging to localize dominant intraprostatic lesions in prostate cancer: validation against digital histopathology and comparison to [18F]DCFPyL PET/MR at 120 minutes.

PURPOSE: Localized prostate cancer (PCa) in patients is characterized by a dominant focus in the gland (dominant intraprostatic lesion, DIL). Accurate DIL identification may enable more accurate diagnosis and therapy through more precise targeting of biopsy, radiotherapy and focal ablative therapies. The goal of this study is to validate the performance of [18F]DCFPyL PET and CT perfusion (CTP) for detecting and localizing DIL against digital histopathological images. METHODS: Multi-modality image sets: in vivo T2-weighted (T2w)-MRI, 22-min dynamic [18F]DCFPyL PET/CT, CTP, and 2-h post-injection PET/MR were acquired in patients prior to radical prostatectomy. The explanted gland with implanted fiducial markers was imaged with T2w-MRI. All images were co-registered to the pathologist-annotated digital images of whole-mount mid-gland histology sections using fiducial markers and anatomical landmarks. Regions of interest encompassing DIL and non-DIL tissue were drawn on the digital histopathological images and superimposed on PET and CTP parametric maps. Logistic regression with backward elimination of parameters was used to select the most sensitive parameter set to distinguish DIL from non-DIL voxels. Leave-one-patient-out cross-validation was performed to determine diagnostic performance. RESULTS: [18F]DCFPyL PET and CTP parametric maps of 15 patients were analyzed. SUVLate and a model combining Ki and k4 of [18F]DCFPyL achieved the most accurate performance distinguishing DIL from non-DIL voxels. Both detection models achieved an AUC of 0.90 and an error rate of < 10%. Compared to digital histopathology, the detected DILs had a mean dice similarity coefficient of 0.8 for the Ki and k4 model and 0.7 for SUVLate. CONCLUSIONS: We have validated using co-registered digital histopathological images that parameters from kinetic analysis of 22-min dynamic [18F]DCFPyL PET can accurately localize DILs in PCa for targeting of biopsy, radiotherapy, and focal ablative therapies. Short-duration dynamic [18F]DCFPyL PET was not inferior to SUVLate in this diagnostic task. CLINICAL TRIAL REGISTRATION NUMBER: NCT04009174 (ClinicalTrials.gov).

Prostate specific membrane antigen positron emission tomography for lesion-directed high-dose-rate brachytherapy dose escalation.

BACKGROUND AND PURPOSE: Prostate specific membrane antigen positron emission tomography imaging (PSMA-PET) has demonstrated potential for intra-prostatic lesion localization. We leveraged our existing database of co-registered PSMA-PET imaging with cross sectional digitized pathology to model dose coverage of histologically-defined prostate cancer when tailoring brachytherapy dose escalation based on PSMA-PET imaging. MATERIALS AND METHODS: Using a previously-developed automated approach, we created segmentation volumes delineating underlying dominant intraprostatic lesions for ten men with co-registered pathology-imaging datasets. To simulate realistic high-dose-rate brachytherapy (HDR-BT) treatments, we registered the PSMA-PET-defined segmentation volumes and underlying cancer to 3D trans-rectal ultrasound images of HDR-BT cases where 15 Gray (Gy) was delivered. We applied dose/volume optimization to focally target the dominant intraprostatic lesion identified on PSMA-PET. We then compared histopathology dose for all high-grade cancer within whole-gland treatment plans versus PSMA-PET-targeted plans. Histopathology dose was analyzed for all clinically significant cancer with a Gleason score of 7or greater. RESULTS: The standard whole-gland plans achieved a median [interquartile range] D98 of 15.2 [13.8-16.4] Gy to the histologically-defined cancer, while the targeted plans achieved a significantly higher D98 of 16.5 [15.0-19.0] Gy (p = 0.007). CONCLUSION: This study is the first to use digital histology to confirm the effectiveness of PSMA-PET HDR-BT dose escalation using automatically generated contours. Based on the findings of this study, PSMA-PET lesion dose escalation can lead to increased dose to the ground truth histologically defined cancer.

Canadian consensus statement on the management of radioactive iodine-resistant differentiated thyroid cancer.

Radioactive iodine-resistant differentiated thyroid cancer (RAIRTC) is an aggressive form of thyroid cancer that is uncommon and heterogeneous in its clinical behavior. With the emergence of more effective systemic therapy, the need for guidance in decision-making was recognized and a consensus committee of national experts was assembled. The consensus committee consisted of 13 clinicians involved in treating RAIRTC from across Canada and included endocrinologists, nuclear medicine physicians, surgeons, and radiation and medical oncologists. Domains of interest were identified by consensus, and evidence gathered using systematic reviews. Consensus recommendations for the diagnosis and management of RAIRTC were developed. It was recognized that the rarity of RAIRTC in practice and heterogeneous patterns of thyroid cancer care could limit access to effective therapy for some RAIRTC patients. This document offers guidance to manage RAIRTC patients in a multidisciplinary manner.

Renal Infarcts-A Perplexing Case in the Middle of the COVID-19 Pandemic.

Renal infarction is a rare finding in children. Associations between SARS-CoV-2 infections and thromboembolic events including renal infarcts have been described in adults. Although a similar association in children has not yet been described with this pandemic, the pediatric literature is still evolving with the recognition of new manifestations including the post-infectious Multisystem Inflammatory Syndrome in Children (MIS-C). We report the rare event of multiple renal infarcts in a 6-year-old boy manifesting several features of MIS-C 9 weeks following a self-limiting febrile illness characteristic of COVID-19. An underlying Factor V Leiden mutation was identified in this child but felt to be insufficient on its own to explain his clinical presentation. As SARS-CoV-2 testing was delayed, the failure to identify viral RNA or antibodies may not exclude the virus' potential role in precipitating the infarct in this host. Given that renal infarcts have been described in adult patients with COVID-19, reporting this perplexing case where SARS-CoV-2 may have played a role, may help identify this potential complication.

Utilization of Salvage and Systemic Therapies for Recurrent Prostate Cancer as a Result of 18F-DCFPyL PET/CT Restaging.

PURPOSE: Our purpose was to investigate the effect of the addition of prostate-specific membrane antigen (PSMA)-targeted positron emission tomography/computed tomography (PET/CT) in patients with recurrent prostate cancer post-primary radiation therapy. METHODS AND MATERIALS: A prospective, multi-institutional clinical trial evaluated 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (18F-DCFPyL) PET/CT restaging in 79 men with recurrent prostate cancer post-primary radiation therapy. We report actual patient management and compare this with proposed management both before and after PSMA-targeted PET/CT. RESULTS: Most patients (59%) had a major change in actual management compared with pre-PET/CT proposed management. The rate of major change was underestimated by immediately post-PET/CT surveys (32%). Eighteen patients with PSMA avidity in the prostate gland suspicious for malignancy had a prostate biopsy. Sensitivity, specificity, and positive predictive values of PSMA uptake in the prostate were 86%, 67%, and 92%, respectively. Thirty percent of patients had directed salvage therapy and 41% underwent systemic therapy. Eleven out of 79 patients (14%) had high-dose-rate brachytherapy alone for local recurrence, and 91% were free of recurrence at a median follow-up of 20 months. CONCLUSIONS: Most patients had a major change in actual management compared with pre-PSMA-targeted PET/CT planned management, and this was underestimated by post-PET/CT questionnaires.

Kinetic analysis of dominant intraprostatic lesion of prostate cancer using quantitative dynamic [18F]DCFPyL-PET: comparison to [18F]fluorocholine-PET.

PURPOSE: Identification of the dominant intraprostatic lesion(s) (DILs) can facilitate diagnosis and treatment by targeting biologically significant intra-prostatic foci. A PSMA ligand, [18F]DCFPyL (2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid), is better than choline-based [18F]FCH (fluorocholine) in detecting and localizing DIL because of higher tumour contrast, particularly when imaging is delayed to 1 h post-injection. The goal of this study was to investigate whether the different imaging performance of [18F]FCH and [18F]DCFPyL can be explained by their kinetic behaviour in prostate cancer (PCa) and to evaluate whether DIL can be accurately detected and localized using a short duration dynamic positron emission tomography (PET). METHODS: 19 and 23 PCa patients were evaluated with dynamic [18F]DCFPyL and [18F]FCH PET, respectively. The dynamic imaging protocol with each tracer had a total imaging time of 22 min and consisted of multiple frames with acquisition times from 10 to 180 s. Tumour and benign tissue regions identified by sextant biopsy were compared using standardized uptake value (SUV) and tracer kinetic parameters from kinetic analysis of time-activity curves. RESULTS: For [18F]DCFPyL, logistic regression identified Ki and k4 as the optimal model to discriminate tumour from benign tissue (84.2% sensitivity and 94.7% specificity), while only SUV was predictive for [18F]FCH (82.6% sensitivity and 87.0% specificity). The higher k3 (binding) of [18F]FCH than [18F]DCFPyL explains why [18F]FCH SUV can differentiate tumour from benign tissue within minutes of injection. Superior [18F]DCFPyL tumour contrast was due to the higher k4/k3 (more rapid washout) in benign tissue compared to tumour tissue. CONCLUSIONS: DIL was detected with good sensitivity and specificity using 22-min dynamic [18F]DCFPyL PET and avoids the need for delayed post-injection imaging timepoints. The dissimilar in vivo kinetic behaviour of [18F]DCFPyL and [18F]FCH could explain their different SUV images. Clinical Trial Registration NCT04009174 (ClinicalTrials.gov).

SEVERE HYPERCALCEMIA SECONDARY TO PARAFFIN OIL INJECTIONS IN A BODYBUILDER WITH SIGNIFICANT FINDINGS ON SCINTIGRAPHY.

OBJECTIVE: Non-parathyroid hormone (PTH) mediated hypercalcemia in young patients is rare. It encompasses a broad differential including malignancy, granulomatous diseases, Addison disease, and toxicity of vitamin A and D. We present an unusual case of non-PTH mediated hyper-calcemia in a previously healthy bodybuilder, secondary to multifocal granulomatous disease from paraffin oil injections. METHODS: The patient was evaluated with laboratory tests including serum calcium, 25-hydroxyvitamin D, 1,25-hydroxyvitamin D, parathyroid hormone, and parathyroid hormone-related peptide. Imaging studies such as thorax computed tomography and bone scans were also performed. RESULTS: A 31-year-old male bodybuilder presented with severe hypercalcemia (corrected calcium 3.1 mmol/L) and renal failure (creatinine 840 µmol/L), with suppressed PTH 1.0 pmol/L (normal, 1.6 to 6.9 pmol/L), and 1,25-vitamin D 205 pmol/L (normal, 60 to 208 pmol/L). He had used anabolic steroids for bodybuilding purposes for 8 years, with the possibility that he may also have used paraffin oil injections. Computed tomography imaging along with patient history suggested multiple paraffinomas in the pectoralis muscles causing granulomatous foreign body reaction as a potential cause for his hypercalcemia. He was prescribed a trial of prednisone, but he discontinued it due to symptoms of acne. Unfortunately, due to poor adherence with medical direction, management of his hypercalcemia remains challenging with inconsistent use of steroids and pamidronate infusions. CONCLUSION: Granulomatous foreign-body reactions are a rare side effect of paraffin oil injections used for muscle augmentation. These can lead to serious long-term side effects of severe hypercalcemia and renal failure, as seen in our patient. Prognosis is generally poor, with long term steroids as the preferred treatment.

Histologic validation of auto-contoured dominant intraprostatic lesions on [18F] DCFPyL PSMA-PET imaging.

BACKGROUND: PSMA-PET1 has shown good concordance with histology, but there is a need to investigate the ability of PSMA-PET to delineate DIL2 boundaries for guided biopsy and focal therapy planning. OBJECTIVE: To determine threshold and margin combinations that satisfy the following criteria: ≥95% sensitivity with max specificity and ≥95% specificity with max sensitivity. DESIGN, SETTING AND PARTICIPANTS: We registered pathologist-annotated whole-mount mid-gland prostatectomy histology sections cut in 4.4 mm intervals from 12 patients to pre-surgical PSMA-PET/MRI by mapping histology to ex-vivo imaging to in-vivo imaging. We generated PET-derived tumor volumes using boundaries defined by thresholded PET volumes from 1-100% of SUV3max in 1% intervals. At each interval, we applied margins of 0-30 voxels in one voxel increments, giving 3000 volumes/patient. OUTCOME MEASUREMENTS: Mean and standard deviation of sensitivity and specificity for cancer detection within the 2D oblique histologic planes that intersected with the 3D PET volume for each patient. RESULTS AND LIMITATIONS: A threshold of 67% SUV max with an 8.4 mm margin achieved a (mean ± std.) sensitivity of 95.0 ± 7.8% and specificity of 76.4 ± 14.7%. A threshold of 81% SUV max with a 5.1 mm margin achieved sensitivity of 65.1 ± 28.4% and specificity of 95.1 ± 5.2%. CONCLUSIONS: Preliminary evidence of thresholding and margin expansion of PSMA-PET images targeted at DILs validated with histopathology demonstrated excellent mean sensitivity and specificity in the setting of focal therapy/boosting and guided biopsy. These parameters can be used in a larger validation study supporting clinical translation.

Microscopic Positive Tumor Margin Increases Risk for Disease Persistence but Not Recurrence in Patients with Stage T1-T2 Differentiated Thyroid Cancer.

INTRODUCTION: Differentiated thyroid cancer (DTC) has an overall excellent prognosis. Patients who develop recurrent disease have a more unfavorable disease course than those with no recurrence. Higher recurrence rates are seen with incomplete surgical resection and gross positive margins. It is unclear whether microscopic positive margin affects disease recurrence rates as much as grossly positive margin. Aim of the Study. To assess whether microscopic positive margin is an independent predictor of disease recurrence in patients with overall low-risk DTC. Patients and Methods. We conducted a retrospective single-center institutional review of 1,583 consecutive patients' charts from 1995-2013 using the Canadian Thyroid Cancer Consortium Registry. We included adult patients with nonmetastasizing T1 and T2 DTC with a minimum of three years follow-up. Univariate and multivariate analyses were used to study factors that may influence the risk of persistent/recurrent disease. Strict definitions of persistent versus recurrent disease were applied. RESULTS: 963 patients (152 men and 811 women) were included in the study with a mean age of 46 years. Microscopic positive margins were present in 12% of the specimens and were associated with an increased rate of persistent disease (8% versus 2% in the controls) but not with an increased risk of recurrent disease (1% in both groups). T2 tumors had a significantly higher incidence of positive margins than T1 tumors (48% versus 36%) and significantly higher nodal staging. CONCLUSIONS: Microscopic positive margin in the histopathology report in patients with low-risk DTC was associated with a higher rate of persistent disease but did not increase the risk of disease recurrence. A close follow-up of biomarkers and occult residual cancerous lesions is needed, especially in the first year. Further studies are needed to determine whether additional therapeutic measures to prevent recurrence are indicated in T1 and T2 DTC with positive microscopic surgical margins.

Risk for Thyroid Cancer Recurrence Is Higher in Men Than in Women Independent of Disease Stage at Presentation.

Background: Well-differentiated thyroid cancer (DTC) presents at a more advanced stage in men than in women, and the mortality in men is higher than that in women. However, it is not clear whether DTC recurrence is affected by sex independent of stage at presentation. The objective of the present study was to assess if male sex is an independent risk factor for recurrence of DTC. Methods: The Canadian Collaborative Network for Cancer of the Thyroid (CANNECT) is a collaborative registry to describe patterns of care for thyroid cancer. We included patients from the CANNECT registry with DTC diagnosed at age 18 or older between 2000 and 2010. We compared men and women with respect to presentation, management, and recurrence risk, stratified for American Joint Committee on Cancer (AJCC) stage. Results: We included 2595 patients, 2067 (79.7%) women and 528 (20.3%) men. Men presented with more advanced AJCC stage (p < 0.001), T stage (p < 0.001), N stage (p < 0.001), and M stage (p = 0.002) There was no difference in follow-up duration between women (7.7 ± 4.0 [mean ± standard deviation] years) and men (7.7 ± 4.0 years, p = 0.985). Overall recurrence was 2.2% (n = 46) for women and 8.5% (n = 45) for men (p < 0.001). In multivariate analysis adjusted for AJCC stage, men were at significantly greater risk for DTC recurrence than women (adjusted hazard ratio 2.72 [95% confidence interval [CI] 1.78-4.20]; p < 0.001). In multivariate analysis adjusted for tumor-node-metastasis (TNM) stage, men were at significantly greater risk for DTC recurrence than women (adjusted hazard ratio 2.31 [CI 1.48-3.60]; p < 0.001). Conclusions: Our study confirms that the risk for recurrence of DTC is higher in men than in women. Although men tend to present with more advanced-stage disease, the difference in recurrence risk persists when adjusted for stage of presentation. It needs to be determined whether sex should influence follow-up intensity and/or duration.

A Prospective Study of 18F-DCFPyL PSMA PET/CT Restaging in Recurrent Prostate Cancer following Primary External Beam Radiotherapy or Brachytherapy.

PURPOSE: Radio-recurrent prostate cancer is typically detected by a rising prostate-specific antigen and may reflect local or distant disease. Positron emission tomography (PET) radiotracers targeting prostate-specific membrane antigen, such as 18F-DCFPyL have shown promise in restaging men with recurrent disease postprostatectomy but are less well characterized in the setting of radio-recurrent disease. METHODS AND MATERIALS: A prospective, multi-institutional study was conducted to evaluate the effect of 18F-DCFPyL PET/computed tomography (CT) when added to diagnostic imaging (DI; CT abdomen and pelvis, bone scan, multiparametric magnetic resonance imaging pelvis) for men with radio-recurrent prostate cancer. All men were imaged with DI and subsequently underwent 18F-DCFPyL PET/CT with local and central reads. Tie break reads were performed as required. Management questionnaires were completed after DI and again after 18F-DCFPyL PET/CT. Discordance in patterns of disease detected with 18F-DCFPyL PET/CT versus DI and changes in management were characterized. RESULTS: Seventy-nine men completed the study. Most men had T1 disease (62%) and Gleason score <7 (95%). Median prostate-specific antigen at diagnosis was 7.4 ng/mL and at relapse was 4.8 ng/mL. DI detected isolated intraprostatic recurrence in 38 out of 79 men (48%), regional nodal recurrence in 9 out of 79 (11%), distant disease in 12 out of 79 (15%), and no disease in 26 out of 79 (33%). 18F-DCFPyL PET/CT detected isolated intraprostatic recurrence in 38 out of 79 men (48%), regional nodal recurrence in 21 out of 79 (27%), distant disease in 24 out of 79 (30%), and no disease in 10 out of 79 (13%). DI identified 8 out of 79 (10%) patients to have oligometastatic disease, compared with 21 out of 79 (27%) with 18F-DCFPyL PET/CT. 18F-DCFPyL PET/CT changed proposed management in 34 out of 79 (43%) patients. CONCLUSIONS: 18F-DCFPyL PET/CT identified extraprostatic disease in twice as many men with radio-recurrent prostate cancer compared with DI and detected a site of recurrence in 87% of men compared with 67% with DI. Furthermore, 18F-DCFPyL PET/CT identified potentially actionable disease (prostate only recurrence or oligometastatic disease) in 75% of men and changed proposed management in 43% of men.

Performance of the American Thyroid Association Risk Classification in a Single Center Cohort of Pediatric Patients with Differentiated Thyroid Cancer: A Retrospective Study.

INTRODUCTION: Differentiated thyroid cancer (DTC) is the most common endocrine malignancy in children. Retrospective studies show conflicting results regarding predictors of persistent and recurrent disease after initial therapy. In 2015, the American Thyroid Association (ATA) proposed a clinical classification system to identify pediatric thyroid cancer patients at risk for persistent/recurrent disease. MATERIAL AND METHODS: We retrospectively included all patients in our registry diagnosed with papillary DTC at ≤ 18 years of age. We analyzed the prognostic performance of the ATA classification and other risk factors for predicting response to initial treatment and final outcome in pediatric DTC. RESULTS: We included 41 patients, 34 females and 7 males, diagnosed with papillary DTC at a mean (SD) age of 16.2 (1.8) years. Based on the ATA pediatric risk classification, patients were categorized as low (61%), intermediate (10%), or high risk (29%). The median follow-up period was 7.3 (1-41) years. After initial treatment, disease free status was achieved in 92%, 50%, and 42% of the low, intermediate, and high risk groups, respectively (P <0.01). At the last visit, persistent disease was present in 12%, 25%, and 33% (P=0.27). Assessing other risk factors, only the presence of distant metastases at diagnosis resulted in increased presence of persistent disease at last follow-up (P=0.03). CONCLUSION: This study supports the clinical relevance of the ATA risk classification for predicting the response to initial treatment. There was no clear prediction of long-term outcome, but this may be due to limited power caused by the small number of patients.

[18F]-DCFPyL Positron Emission Tomography/Magnetic Resonance Imaging for Localization of Dominant Intraprostatic Foci: First Experience.

An ongoing prospective study is acquiring preoperative imaging data for men with prostate cancer (PCa) using the molecular imaging agent [18F]-DCFPyL targeted against prostate-specific membrane antigen (PSMA). To date, six men (of a planned accrual of 24) with clinically localized, biopsy-proven PCa have undergone preoperative [18F]-DCFPyL positron emission tomography (PET) imaging and multiparametric magnetic resonance imaging acquired using a hybrid PET/MRI system. Lesions identified by [18F]-DCFPyL uptake on PET/MRI were characterized in terms of maximum standardized uptake value (SUVmax) and volume using a boundary threshold of 40% SUVmax. Following surgery, all prostatectomy specimens were processed using a whole-mount technique for accurate deformable co-registration and correlation with PCa foci defined on digitized pathology images. Well-defined intraprostatic dominant lesions were identified by [18F]-DCFPyL PET/MRI (mean SUVmax 11.4±8.25; mean volume 2.2±2.4cm3) in all six men. Co-registered digitized whole-mount pathology for the first case revealed that intense [18F]-DCFPyL uptake (SUVmax 27±1.1cm3) and multiparametric MRI changes (Prostate Imaging Reporting and Data System score of 4) were highly correlated with a 0.5-cm3 dominant (largest) lesion with Gleason pattern 4 PCa in the right mid peripheral zone. A smaller focus (0.01cm3) of lower-grade PCa (Gleason pattern 3) had much lower uptake (SUV 2.7). These early prospective data show that dominant intraprostatic lesions could be identified in all six men using [18F]-DCFPyL as an imaging probe. Trial accrual will continue to quantify in terms of spatial concordance the ability of [18F]-DCFPyL to identify the location and characterize the grade of intraprostatic cancer foci in clinically localized PCa. PATIENT SUMMARY: Positron emission tomography using a novel probe called [18F]-DCFPyL directed against the prostate-specific membrane antigen protein was able to identify locations of prostate cancer in the prostate glands of men undergoing imaging before surgery. In the future, such imaging may allow better targeting of treatment to the portion of the prostate containing the most aggressive components of cancer rather than treating the whole prostate in a uniform fashion.

Recombinant Human Thyroid Stimulating Hormone versus Thyroid Hormone Withdrawal for Radioactive Iodine Treatment of Differentiated Thyroid Cancer with Nodal Metastatic Disease.

Introduction. Recombinant human thyroid stimulating hormone (rhTSH) is approved for preparation of thyroid remnant ablation with radioactive iodine (RAI) in low risk patients with well differentiated thyroid cancer (DTC). We studied the safety and efficacy of rhTSH preparation for RAI treatment of thyroid cancer patients with nodal metastatic disease. Methods. A retrospective analysis was performed on 108 patients with histopathologically confirmed nodal metastatic DTC, treated with initial RAI between January 1, 2000, and December 31, 2007. Within this selected group, 31 and 42 patients were prepared for initial and all subsequent RAI treatments by either thyroid hormone withdrawal (THW) or rhTSH protocols and were followed up for at least 3 years. Results. The response to initial treatment, classified as excellent, acceptable, or incomplete, was not different between the rhTSH group (57%, 21%, and 21%, resp.) and the THW group (39%, 13%, and 48%, resp.; P = 0.052). There was no significant difference in the final clinical outcome between the groups. The rhTSH group received significantly fewer additional doses of RAI than the THW group (P = 0.03). Conclusion. In patients with nodal-positive DTC, preparation for RAI with rhTSH is a safe and efficacious alternative to THW protocol.

Acute obstruction of a chronic organoaxial gastric volvulus detected on blood pool imaging of a bone scan.

Acute obstruction of a chronic gastric volvulus was incidentally detected on blood pool imaging of a total body bone scan performed for an elevated prostate-specific antigen level. The patient had been diagnosed with an organoaxial gastric volvulus within a paraesophageal hernia 4.5 years previously, with no evidence for obstruction. The patient remained asymptomatic until becoming acutely obstructed on the day of his bone scan. This case gives further evidence for the additive utility of routine total body blood pool imaging for detecting and characterizing both osseous and nonosseous pathology.

Long-term efficacy of modified-release recombinant human thyrotropin augmented radioiodine therapy for benign multinodular goiter: results from a multicenter, international, randomized, placebo-controlled, dose-selection study.

BACKGROUND: Enhanced reduction of multinodular goiter (MNG) can be achieved by stimulation with recombinant human thyrotropin (rhTSH) before radioiodine ((131)I) therapy. The objective was to compare the long-term efficacy and safety of two low doses of modified release rhTSH (MRrhTSH) in combination with (131)I therapy. METHODS: In this phase II, single-blinded, placebo-controlled study, 95 patients (57.2 ± 9.6 years old, 85% women, 83% Caucasians) with MNG (median size 96.0 mL; range 31.9-242.2 mL) were randomized to receive placebo (n=32), 0.01 mg MRrhTSH (n=30), or 0.03 mg MRrhTSH (n=33) 24 hours before a calculated (131)I activity. Thyroid volume (TV) and smallest cross-sectional area of trachea (SCAT) were measured (by computed tomography scan) at baseline, six months, and 36 months. Thyroid function and quality of life (QoL) was evaluated at three-month and yearly intervals respectively. RESULTS: At six months, TV reduction was enhanced in the 0.03 mg MRrhTSH group (32.9% vs. 23.1% in the placebo group; p=0.03) but not in the 0.01 mg MRrhTSH group. At 36 months, the mean percent TV reduction from baseline was 44 ± 12.7% (SD) in the placebo group, 41 ± 21.0% in the 0.01 mg MRrhTSH group, and 53 ± 18.6% in the 0.03 mg MRrhTSH group, with no statistically significant differences among the groups, p=0.105. In the 0.03 mg MRrhTSH group, the subset of patients with basal (131)I uptake <20% had a 24% greater TV reduction at 36 months than the corresponding subset of patients in the placebo group (p=0.01). At 36 months, the largest relative increase in SCAT was observed in the 0.03 mg MRrhTSH group (13.4 ± 23.2%), but this was not statistically different from the increases observed in the placebo or the 0.01 mg MRrhTSH group (p=0.15). Goiter-related symptoms were reduced and QoL improved, without any enhanced benefit from using MRrhTSH. At three years, the prevalence of permanent hypothyroidism was 13%, 33%, and 45% in the placebo, 0.01 mg, and 0.03 mg MRrhTSH groups respectively. The overall safety profile of the study was favorable. CONCLUSIONS: When used as adjuvant to (131)I, enhanced MNG reduction could not be demonstrated with MRrhTSH doses ≤ 0.03 mg, indicating that the lower threshold for efficacy is around this level.

Is lower socioeconomic status associated with more advanced thyroid cancer stage at presentation? A study in two Canadian centers.

BACKGROUND: Some studies have shown a higher incidence of thyroid cancer in patients with insurance coverage and higher socioeconomic status (SES), and a higher thyroid cancer stage in patients with lower SES, suggesting SES-related health disparity in thyroid cancer. However, it is not known if the same is evident under a universal healthcare system such as that in Canada. METHODS: We used data from the Canadian Thyroid Cancer Consortium, a large thyroid cancer registry that collects data from two major thyroid cancer referral centers (London, Ontario, and Halifax, Nova Scotia). We included patients who presented with thyroid cancer between 1998 and 2011. We determined age at presentation, sex, and thyroid cancer status using the American Joint Committee on Cancer (AJCC) staging criteria. Individuals' postal codes were used to retrieve data from the Canadian census for the years 1996, 2001, and 2006 to approximate household income. Ordered logistic regression was used to determine odds ratios of presenting with more advanced stage thyroid cancer as they relate to income, age, and sex. RESULTS: We included 1701 patients: 1334 cases from London and 367 from Halifax. Thyroid cancer was diagnosed more frequently in the higher SES groups (p<0.001). Compared to patients in the top income quintile, patients in the lowest and second-lowest income quintiles had significantly higher odds of having more advanced stage thyroid cancer at presentation (OR 1.58, p=0.002; 1.37, p=0.024 respectively). CONCLUSIONS: Our study suggests that, similar to countries that lack a universal healthcare system, health disparity in thyroid cancer also exists in Canada. It appears that while thyroid cancers were diagnosed more frequently in Canadian patients of higher SES, Canadian patients in the lower SES groups had more advanced stage thyroid cancer at presentation.