Sestamibi SPECT/CT versus SPECT only for preoperative localization in primary hyperparathyroidism: a single institution 8-year analysis.

BACKGROUND: Primary hyperparathyroidism is caused by single gland disease in 85% of cases and by multiglandular disease in 15%. Our aim was to discover if the addition of computed tomography acquisition/fusion on a hybrid scanner to traditional dual-phase single-photon emission tomography improves localization accuracy. METHODS: A prospective database was queried for the perioperative data of patients with sporadic primary hyperparathyroidism who had initial exploration from 2006-2014 with ≥6 month follow-up to define anatomy. Prior to 2010, patients had single-photon emission tomography (n = 633); after 2010, they had single-photon emission tomography/computed tomography (n= 755). RESULTS: In 1,388 patients, the rates of single gland disease (P=.8), bilateral exploration (P=.4), and negative imaging (145 patients, P=.33) were equal between imaging cohorts. In 1,186 patients with single gland disease, the positive predictive value of single-photon emission tomography/computed tomography was somewhat greater (90% vs 85%) and the accuracy of single-photon emission tomography/computed tomography was superior (83% vs 77%, P=.02). In the 202 patients with multiglandular disease, 20% had negative imaging results with no difference by type (single-photon emission tomography/computed tomography 17%, single-photon emission tomography 23%, P=.3), but single-photon emission tomography/computed tomography was more accurate (36%) than single-photon emission tomography (22%, P=.04) in predicting multiglandular disease. CONCLUSION: In a large cohort study of patients with sporadic primary hyperparathyroidism undergoing parathyroidectomy, positive single-photon emission tomography/computed tomography results provided more reliable operative guidance than single-photon emission tomography for both single gland disease and multiglandular disease.

Use of intraoperative nuclear imaging leads to decreased anesthesia time and real-time confirmation of lesion removal.

BACKGROUND: Lymphatic mapping to guide sentinel lymph node biopsy (SLNB) typically requires lymphoscintigraphy prior to surgery. In young pediatric patients, this process often requires intubation in the nuclear medicine suite followed by transport to the operating room (OR). METHODS: We reviewed 14 pediatric cases in which a portable nuclear imaging camera was utilized to perform the entirety of the SLNB in the OR. RESULTS AND CONCLUSION: This method, utilizing intraoperative nuclear imaging, helped to confirm removal of the sentinel lymph node in real time, decreased anesthesia time, and avoided transport of a sedated or intubated child. LEVEL OF EVIDENCE: III.

Molecular Characterization of Sporadic Pediatric Thyroid Carcinoma with the DNA/RNA ThyroSeq v2 Next-Generation Sequencing Assay.

The aim of this study was to test the hypothesis that our 60-gene DNA/RNA ThyroSeq v2 next-generation sequence (NGS) assay would identify additional genetic markers, including gene fusions in sporadic pediatric differentiated thyroid carcinomas (DTC) that had no known molecular alterations. Sporadic pediatric DTCs with informative molecular testing (n=18) were studied. We previously tested 15 cases by our standard 7-gene (BRAF, NRAS, HRAS, KRAS, RET/PTC1, RET/PTC3, PAX8/PPARg) mutation panel. Three cases were not tested previously. The standard 7-gene panel identified molecular alterations in 9 of 15 tumors (60%). Cases analyzed by ThyroSeq v2 NGS included the six previously negative cases by the standard 7-gene panel and three cases not previously tested. The NGS assay revealed new gene fusions in four of six previously negative cases (67%). These gene fusions included ETV6/NTRK3 (n=3) and TPR/NTRK1 (n=1). A point mutation (BRAF-V600E) was detected in one of three untested cases. While standard testing could identify only molecular alterations in 60% of cases, with the addition of the ThyroSeq v2 NGS, this increased to 87% (n=13/15). Some cases with chromosomal rearrangements, including ETV6/NTRK3, appear to be associated with an aggressive histopathologic phenotype, but had no documented history of radiation exposure. Additional work is needed to investigate if pediatric DTCs could benefit from a reclassification based on molecular subtypes, which may better reflect their underlying biologic potential. Our data support the use of broad gene panels for the molecular diagnostics of pediatric thyroid nodules to aid future classification, treatment, and clinical management recommendations.

Can malignant thyroid nodules be distinguished from benign thyroid nodules in children and adolescents by clinical characteristics? A review of 89 pediatric patients with thyroid nodules.

BACKGROUND: Thyroid nodules are less common in children than adults, but the risk of malignancy in thyroid nodules is much higher in children. The ability to characterize pediatric thyroid nodules has improved with the use of ultrasound-guided fine-needle aspiration, the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) classification system, and expanded molecular testing. Nevertheless, stratification criteria to predict thyroid malignancy in children are poorly defined. Our objective was to determine if clinical presentation and molecular genetics could predict malignancy in pediatric thyroid nodules. METHODS: Retrospective chart review of patients ≤18 years of age at the Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center with the diagnosis of a thyroid nodule from January 2007 to January 2012 was conducted. Eighty-nine subjects fulfilled the inclusion criteria: 1) thyroid nodule ≥0.8 cm and biopsy (n=76), or 2) thyroid nodule ≥0.8 cm, no biopsy, and ultrasound follow-up for at least 2 years (n=13). RESULTS: Twenty-four (27%) of 89 patients were diagnosed with thyroid cancer (50% papillary thyroid carcinoma [PTC], 50% follicular variant of papillary thyroid carcinoma [FVPTC]). Features associated with malignancy included larger nodule size, palpable nodule, or palpable lymphadenopathy. There were no differences in presenting features between patients with PTC and those with FVPTC. Thyroid malignancy was diagnosed in all nine patients with a molecular abnormality (BRAF, RAS, RET/PTC, PAX8/PPARγ). CONCLUSIONS: Clinical features, FNA cytology, and molecular genetics are valuable tools to discriminate benign from malignant nodules in pediatric patients. This information is important to direct subsequent clinical management.

Surgeon volume and adequacy of thyroidectomy for differentiated thyroid cancer.

INTRODUCTION: We aimed to determine influence of surgeon volume on (1) frequency of appropriate initial surgery for differentiated thyroid cancer (DTC) and (2) completeness of resection. METHODS: We reviewed all initial thyroidectomies (Tx; lobectomy and total) performed in a health system during 2011; surgeons were grouped by number of Tx cases per year. For patients with histologic DTC ≥ 1 cm, surgeon volume was correlated with initial extent of the operation, and markers of complete resection including uptake on I(123) prescan, thyrotropin-stimulated thyroglobulin levels, and I(131) dose administered. RESULTS: Of 1,249 patients who underwent Tx by 42 surgeons, 29% had DTC ≥ 1 cm without distant metastasis. At a threshold of ≥ 30 Tx per year, surgeons were more likely to perform initial total Tx for DTC ≥ 1 cm (P = .01), and initial resection was more complete as measured by all 3 quantitative markers. For patients with advanced stage disease, a threshold of ≥ 50 Tx per year was needed before observing improvements in I(123) uptake (P = .004). CONCLUSION: Surgeons who perform ≥ 30 Tx a year are more likely to undertake the appropriate initial operation and have more complete initial resection for DTC patients. Surgeon volume is an essential consideration in optimizing outcomes for DTC patients, and even higher thresholds (≥ 50 Tx/year) may be necessary for patients with advanced disease.

Detection of infected liver cysts by 111In WBC SPECT/CT in polycystic liver disease.

SPECT/CT imaging can provide improved diagnostic information over traditional planar scintigraphy and SPECT, with more precise anatomic localization and observer confidence. We present 2 patients with polycystic liver disease (PCLD), both with constitutional symptoms and bacteremia. In WBC SPECT/CT images revealed increased WBC localization within a single liver cyst in each case, subsequently drained under imaging guidance. Cultures confirmed the presence of infection, allowing for appropriately directed antibiotic therapy and successful treatment outcomes. These cases illustrate the incremental value of In WBC SPECT/CT fusion imaging for the evaluation of bacteremia in complicated patients.

Unsuspected pneumonia detected by increased lung uptake on 111In-ibritumomab tiuxetan scan.

99Y-ibritumomab tiuxetan (Zevalin) is a CD20-targeted radioimmunotherapy for the treatment of B-cell non-Hodgkin lymphoma approved by the FDA in 2002. The acquisition of an 111In ibritumomab tiuxetan scan (bioscan) to confirm normal biodistribution before treatment with 99Y-ibritumomab tiuxetan was initially required in the United States until November 2011. This is the first documented example of abnormal biodistribution due to unsuspected pneumonia detected by increased lung uptake on the bioscan. The pneumonia was treated and resolved before 99Y Zevalin, avoiding potential harm and indicating that a screening chest x-ray may be appropriate when a bioscan is not performed.

Rare case of Primary Pulmonary Extranodal Non-Hodgkin's Lymphoma in a Patient with Sjogren's Syndrome: Role of FDG-PET/CT in the Initial Staging and Evaluating Response to Treatment.

UNLABELLED: A 64-year old woman with a long standing Sjogren's syndrome was undergoing evaluation for renal transplant surgery when two pulmonary opacities were detected on chest CT. Subsequent biopsy revealed extranodal marginal B-cell non-Hodgkin's lymphoma (NHL). An FDG-PET/CT scan was then performed which demonstrated isolated FDG avid pulmonary involvement. After therapy, FDG-PET/CT scans showed good response to treatment with near complete resolution of FDG avidity. This rare case illustrates the rare pulmonary manifestation of extranodal lymphoma in a patient with Sjogren's syndrome and emphasizes the value of FDG PET/CT in the initial staging and evaluation of response to treatment, which has not previously been published. CONFLICT OF INTEREST: None declared.

Thyroid: nuclear medicine update.

Nuclear medicine has been used in the evaluation and treatment of benign and malignant thyroid disease since the discovery of iodine 131 ((131)I) in the 1930s. Although traditional methods of imaging are routinely used, recent advancements such as SPECT/CT and PET/CT have greatly enhanced the ability of nuclear medicine to accurately detect and localize. Guidelines for the management of thyroid cancer continue to evolve, treatment regimens selected should balance the long-term risk of disease recurrence and cumulative risks of radiation exposure, and physicians should be aware of these updates and guidelines when caring for patients with thyroid disease.

Yttrium-90 radioembolization for colorectal cancer liver metastases: a single institution experience.

Purpose. We sought to evaluate our experience using yttrium-90 ((90)Y) resin microsphere hepatic radioembolization as salvage therapy for liver-dominant metastatic colorectal cancer (mCRC). Methods. A retrospective review of consecutive patients with unresectable mCRC who were treated with (90)Y after failing first and second line systemic chemotherapy. Demographics, treatment dose, biochemical and radiographic response, toxicities, and survival were examined. Results. Fifty-one patients underwent (90)Y treatments of which 69% were male. All patients had previously undergone extensive chemotherapy, 31% had undergone previous liver-directed therapy and 24% had a prior liver resection. Using RECIST criteria, either stable disease or a partial response was seen in 77% of patients. Overall median survival from the time of first (90)Y treatment was 10.2 months (95% CI = 7.5-13.0). The absence of extrahepatic disease at the time of treatment with (90)Y was associated with an improved survival, median survival of 17.0 months (95% CI = 6.4-27.6), compared to those with extrahepatic disease at the time of treatment with (90)Y, 6.7 months (95% CI = 2.7-10.6 CONCLUSION: (90)Y therapy is a safe locoregional therapy that provides an important therapeutic option to patients who have failed first and second line chemotherapy and have adequate liver function and performance status.

Phase II trial of short-course CHOP-R followed by 90Y-ibritumomab tiuxetan and extended rituximab in previously untreated follicular lymphoma.

PURPOSE: Radioimmunotherapy has been approved for relapsed follicular lymphoma (FL), including rituximab-refractory FL. This study was designed to determine the CR rate with short-course chemoimmunotherapy with cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab (CHOP-R) followed by 90-Y ibritumomab tiuxetan (RIT) with extended rituximab as first-line treatment. EXPERIMENTAL DESIGN: Between March 2004 and February 2007, 60 patients with stage II to IV symptomatic or bulky FL from a single institution supported by a large community network entered this phase II trial. Patients received CHOP-R for three treatment cycles before RIT followed by four additional weekly treatments with rituximab. Response was determined using fusion [(18) F] fluorodeoxyglucose-positron emission tomography (PET)-computed tomography (CT) imaging. RESULTS: Of the 60 patients entering this trial, 55 patients completed all protocol therapy. The median follow up was 19.7 months (range, 0.26-35.9 months). For intent-to-treat analysis, the complete response (CR) rate after CHOP-R, as assessed by CT and PET imaging, was 40% and 46%, respectively. After RIT, the CR rate improved, as assessed by CT and PET imaging, to 82% and 89%, respectively. Ten patients have progressed, including eight from best response of CR. Seven of 18 patients who were PET positive after CHOP-R progressed compared with 3 of 37 patients who were PET negative (P=0.010). CONCLUSIONS: In patients with previously untreated, symptomatic or bulky FL, short-course chemoimmunotherapy and consolidation RIT and extended rituximab resulted in a high CR rate. Failure to achieve an early PET CR after CHOP-R indicated high risk of relapse.

Anaphylaxis after administration of ibritumomab tiuxetan for follicular non-hodgkin lymphoma.

We report an anaphylactic reaction in a 45-year-old gentleman with an 8-year history of extensively treated, relapsing follicular lymphoma who was receiving a second treatment with ibritumomab tiuxetan. Within seconds of receiving Y-90 ibritumomab, he developed chest tightness, shallow respirations, hypotension, and incontinence. After successful resuscitation, a human antimouse antibody (HAMA) level was found to be elevated, 618 ng/mL (reference 0-188 ng/mL).

Focal radiation fibrosis after radioimmunotherapy for follicular non-Hodgkin lymphoma.

A 75-year-old man with relapsed follicular non-Hodgkin lymphoma confined to a solitary lung mass was treated with radioimmunotherapy (RIT) using yttrium 90-ibritumomab tiuxetan. Imaging with positron emission tomography/computed tomography showed a complete response 3 months after RIT. Thirteen months after RIT, his positron emission tomography/computed tomography scan showed a fluorodeoxyglucose-avid infiltrate in the area of the previous lung mass. Bronchoscopy revealed the area to be obstructed with fibrosis, and cytologic washings and brushings did not show lymphoma. The patient remains asymptomatic, and the fluorodeoxyglucoseavid pulmonary infiltrate was unchanged 19 months after RIT. In view of the lack of respiratory symptoms or progressive imaging abnormalities, we believe radiation fibrosis is the most likely etiology. Radiation-induced lung injury after therapy with yttrium 90 was previously reported in the setting of intraarterial microspheres used to treat inoperable hepatic tumors. This is the first case in which radiation-induced radiographic changes are reported after RIT for lymphoma.

18F-FDG PET/CT in patients with suspected recurrent or metastatic well-differentiated thyroid cancer.

UNLABELLED: PET using 18F-FDG has been shown to effectively detect various types of cancer by their increased glucose metabolism. The aim of this study was to evaluate the use of coregistered PET and CT (PET/CT) in patients with suspected thyroid cancer recurrence. METHODS: After total thyroidectomy followed by radioiodine ablation, 61 consecutive patients with elevated thyroglobulin levels or a clinical suspicion of recurrent disease underwent 18F-FDG PET/CT. Of these, 59 patients had negative findings on radioiodine (131I) whole-body scintigraphy (WBS). Fifty-three of the 61 patients had both negative 131I WBS findings and elevated thyroglobulin levels. PET/CT images were acquired 60 min after intravenous injection of 400-610 MBq of 18F-FDG using a combined PET/CT scanner. Any increased 18F-FDG uptake was compared with the coregistered CT image to differentiate physiologic from pathologic tracer uptake. 18F-FDG PET/CT findings were correlated with the findings of histology, postradioiodine WBS, ultrasound, or clinical follow-up serving as a reference. The diagnostic accuracy of 18F-FDG PET/CT was evaluated for the entire patient group and for those patients with serum thyroglobulin levels of less than 5, 5-10, and more than 10 ng/mL. RESULTS: Thirty patients had positive findings on 18F-FDG PET/CT; 26 were true-positive and 4 were false-positive. In 2 patients, increased 18F-FDG uptake identified a second primary malignancy. 18F-FDG PET/CT results were true-negative in 19 patients and false-negative in 12 patients. The overall sensitivity, specificity, and accuracy of 18F-FDG PET/CT were 68.4%, 82.4%, and 73.8%, respectively. The sensitivities of 18F-FDG PET/CT at serum thyroglobulin levels of less than 5, 5-10, and more than 10 ng/mL were 60%, 63%, and 72%, respectively. Clinical management changed for 27 (44%) of 61 patients, including surgery, radiation therapy, or chemotherapy. CONCLUSION: Coregistered 18F-FDG PET/CT can provide precise anatomic localization of recurrent or metastatic thyroid carcinoma, leading to improved diagnostic accuracy, and can guide therapeutic management. In addition, the findings of this study suggest that further assessment of 131I WBS-negative, thyroglobulin-positive patients by 18F-FDG PET/CT may aid in the clinical management of selected cases regardless of the thyroglobulin level.

Full-dose 90Y ibritumomab tiuxetan therapy is safe in patients with prior myeloablative chemotherapy.

PURPOSE: Targeted radioimmunotherapy with yttrium-90 (90Y)-labeled ibritumomab tiuxetan (Zevalin, IDEC-Biogen, San Diego, CA) has shown significant activity in the treatment of relapsed or refractory CD20+ non-Hodgkin's lymphoma. Eligibility criteria used in phase I trials, and adopted in phase II and III trials, excluded patients with prior myeloablative therapy. We treated eight patients with 90Y ibritumomab tiuxetan who had prior autologous stem cell transplant, but met all other treatment criteria. EXPERIMENTAL DESIGN: Eight patients with CD20+ non-Hodgkin's lymphoma had extensive prior therapy including myeloablative chemotherapy but did not receive total body irradiation. Each had bone marrow cellularity of >15%, platelet count of >100,000/mm3, and one had documented lymphomatous bone marrow involvement of <25%. The standard course of 0.3 to 0.4 mCi/kg of 90Y ibritumomab tiuxetan was administered to patients at full dose. 18-Flouro-deoxyglucose positron emission tomography/computed tomography scans were done at pretreatment and approximately 12 weeks after treatment to assess patient response. Maximum toxicities were monitored and classified according to the Common Terminology Criteria for Adverse Events (ver. 3.0). RESULTS: Toxicities observed included grade 4 thrombocytopenia in three of eight evaluable patients and grade 4 neutropenia in one of eight evaluable patients. One patient had a neutropenic fever; all patients were off blood product support 12 weeks post-zevalin. Complete response by 18-flouro-deoxyglucose positron emission tomography/computed tomography imaging occurred in one of seven evaluable patients and one patient treated as consolidation had no evidence of disease. CONCLUSION: Our experience suggests that 90Y ibritumomab tiuxetan treatment is safe for use in patients with prior myeloablative therapy when the general inclusion criteria are fulfilled. In this small series, the response rates, however, are limited. Nevertheless, 90Y ibritumomab tiuxetan treatment may provide clinical benefit in carefully selected extensively pretreated patients.