90 Y SPECT/CT quantitative study and comparison of uptake with pretreatment 99 m Tc-MAA SPECT/CT in radiomicrosphere therapy.

INTRODUCTION: Yttrium-90 (90 Y) microsphere post-treatment imaging reflects the true distribution characteristics of microspheres in the tumor and liver compartments. However, due to its decay spectra profile lacking a pronounced photopeak, the bremsstrahlung imaging for 90 Y has inherent limitations. The absorbed dose calculations for 90 Y microspheres radiomicrosphere therapy (RMT) sustain a limitation due to the poor quality of 90 Y imaging. The aim of this study was to develop quantitative methods to improve the post-treatment 90 Y bremsstrahlung single photon emission tomography (SPECT)/computed tomography (CT) image analysis for dosimetric purposes and to perform a quantitative comparison with the 99m Tc-MAA SPECT/CT images, which is used for theranostics purposes for liver and tumor dosimetry. METHODS: Pre and post-treatment SPECT/CT data of patients who underwent RMT for primary or metastatic liver cancer were acquired. A Jasczak phantom with eight spherical inserts of various sizes was used to obtain optimal iteration number for the contrast recovery algorithm for improving 90 Y bremsstrahlung SPECT/CT images. Comparison of uptake on 99m Tc-MAA and 90 Y microsphere SPECT/CT images was assessed using tumor to healthy liver ratios (TLRs). The voxel dosimetry technique was used to estimate absorbed doses. Absorbed doses within the tumor and healthy part of the liver were also investigated for correlation with administered activity. RESULTS: Improvement in CNR and contrast recovery coefficients on patient and phantom 90 Y bremsstrahlung SPECT/CT images respectively were achieved. The 99m Tc-MAA and 90 Y microspheres SPECT/CT images showed significant uptake correlation (r = 0.9, P = 0.05) with mean TLR of 9.4 ± 9.2 and 5.0 ± 2.2, respectively. The correlation between the administered activity and tumor absorbed dose was weak (r = 0.5, P > 0.05), however, healthy liver absorbed dose increased with administered activity (r = 0.8, P = 0.0). CONCLUSIONS: This study demonstrated correlation in mean TLR between 99m Tc-MAA and 90 Y microsphere SPECT/CT.

PET-Probe: Evaluation of Technical Performance and Clinical Utility of a Handheld High-Energy Gamma Probe in Oncologic Surgery.

BACKGROUND: Positron emission tomography (PET) has become an invaluable part of patient evaluation in surgical oncology. PET is less than optimal for detecting lesions <1 cm, and the intraoperative localization of small PET-positive lesions can be challenging as a result of difficulties in surgical exposure. We undertook this investigation to assess the utility of a handheld high-energy gamma probe (PET-Probe) for intraoperative identification of 18F-deoxyglucose (FDG)-avid tumors. METHODS: Forty patients underwent a diagnostic whole-body FDG-PET scan for consideration for surgical exploration and resection. Before surgery, all patients received an intravenous injection of 7 to 10 mCi of FDG. At surgery, the PET-Probe was used to determine absolute counts per second at the known tumor site(s) demonstrated by whole-body PET and at adjacent normal tissue (at least 4 cm away from tumor-bearing sites). Tumor-to-background ratios were calculated. RESULTS: Thirty-two patients (80%) underwent PET-Probe-guided surgery with therapeutic intent in a recurrent or metastatic disease setting. Eight patients underwent surgery for diagnostic exploration. Anatomical locations of the PET-identified lesions were neck and supraclavicular (n = 8), axilla (n = 5), groin and deep iliac (n = 4), trunk and extremity soft tissue (n = 3), abdominal and retroperitoneal (n = 19), and lung (n = 2). PET-Probe detected all PET-positive lesions. The PET-Probe was instrumental in localization of lesions in 15 patients that were not immediately apparent by surgical exploration. CONCLUSIONS: The PET-Probe identified all lesions demonstrated by PET scanning and, in selected cases, was useful in localizing FDG-avid disease not seen with conventional PET scanning.

Liver resection for metastatic disease after y90 radioembolization: a case series with long-term follow-up.

INTRODUCTION: There are only few reports of liver resections for metastatic disease in patients previously treated with Y-90 radioembolization (RE), and long-term outcome data are sparse. We reviewed our center's experience in patients undergoing hepatectomy after hepatic RE. METHODS: A retrospective chart review of patients undergoing RE from 2004 to 2011 was performed. Demographic, clinicopathologic, operative, and long-term outcomes variables were collected. Independent pathologic review of tumor necrosis and normal liver tissue grading of fibrosis and inflammation after resection was performed. Data are expressed as medians and ranges. RESULTS: RE was delivered to 106 patients with primary and metastatic disease of the liver, of whom 9 patients (6 males, 3 females, median age 54 (47-76) years) with metastatic disease ultimately underwent resection. RE was previously administered to the right liver in five, the left liver in one, and to the whole liver in three. Two patients had a second RE performed before resection. Six of the nine patients had previously received several infusions of cytotoxic therapy. The operations occurred at a median of 115 (56-245) days after RE and included right lobectomy (n = 5), left lobectomy (n = 1), left-lateral sectionectomy (n = 1), and bilobar wedge resections (n = 2). Extrahepatic sites were resected in three patients. Median blood loss was 900 (range 250-3600) ml. Grade 3 or higher complications occurred in seven cases (78 %). Follow-up was complete all nine patients. Three patients (33 %) died within 30 days of resection. All those surviving the operative period had disease recurrence (time to recurrence: 202 [range 54-315] days), and all have since died (overall survival: 584 [range 127-1230] days). Review of resected specimens demonstrated median tumor necrosis of 70 % (range 20-90 %). In nontumor-bearing liver, fibrosis grade (0-4) and inflammation score (0-4) was 2 or less in all specimens. CONCLUSIONS: In this small cohort of highly selected and heavily pretreated patients, long-term survival in patients undergoing resection after RE appears possible, but the operations may carry substantial risks-highlighting the importance of careful patient selection for these resections. The etiology of morbidity and mortality is likely multifactorial and additional reports that include long-term outcomes will be necessary to identify more clearly the impact of RE on postoperative complications and death.

Theranostic Risk Stratification for Thyroid Cancer in the Genomic Paradigm.

Theranostics define diagnostic evaluations directing patient-specific therapeutic decisions. Molecular theranostics involves genomic, transcriptomic, proteomic, metabolomic and finally phenonic definitions thyroid cancer differentiation. It is the functional differentiation that determines the sensitivity and accuracy of RAI imaging as well as the effectiveness of RAI treatment. Total thyroidectomy is performed to empower an anticipated RAI treatment. A preoperative determination of the genomic and transcriptomic profile of the tumor is a strong predictor of response to therapeutic interventions. This article discusses the oncopathophysiologic basis of the theranostic risk stratification approach.

Birth of the Beta-knife Thyroidectomy: The Radiance of Saul Hertz.

This is the story of how one man's life's work allowed for Iodine-131 (I-131) to become a therapy for hyperthyroidism and thyroid cancer. What is now a standard in our times arose from Saul Hertz's rather challenging and humble beginnings. Thyroid lobectomy and total thyroidectomy were therapeutic mainstays for thyroid disease until Hertz treated his first patient with radioactive iodine (RAI) ablation therapy at Massachusetts General Hospital (MGH) on March 31, 1941. His concepts for using beta particle emission from RAI to ablate thyroid tissue were revolutionary. Hertz's RAI therapy translated to research with thyroid cancer by the mid-1940s. The high-energy beta particles produced cytolethal effects on remnant thyroid tissue left behind by total thyroidectomy, thereby accomplishing completion thyroidectomy in some patients. Progressive surgeons from the Hertz era incorporated RAI into their practice. MGH surgery resident Francis Moore took sabbatical from clinical training to do translational research with RAI and other radioisotopes. Irving Ariel of New York became known as a nuclear surgeon in the wake of Hertz's work. George Crile Jr of Cleveland became an RAI advocate for the surgical community, implementing several paradigm-changing concepts in thyroid disease along the way. Hertz was a visionary who sparked this movement, predicting many of the molecular dilemmas with RAI-tumor avidity that clinical researchers continue to navigate today. This timely history for surgical oncologists and endocrine surgeons traces the development of RAI therapy through the life of Saul Hertz, a biographical window influenced by social stigma, political controversy, and mainstream media.

Molecular Profiling of 50 734 Bethesda III-VI Thyroid Nodules by ThyroSeq v3: Implications for Personalized Management.

CONTEXT: Comprehensive genomic analysis of thyroid nodules for multiple classes of molecular alterations detected in a large series of fine needle aspiration (FNA) samples has not been reported. OBJECTIVE: To determine the prevalence of clinically relevant molecular alterations in Bethesda categories III-VI (BCIII-VI) thyroid nodules. METHODS: This retrospective analysis of FNA samples, tested by ThyroSeq v3 using Genomic Classifier and Cancer Risk Classifier at UPMC Molecular and Genomic Pathology laboratory, analyzed the prevalence of diagnostic, prognostic, and targetable genetic alterations in a total of 50 734 BCIII-VI nodules from 48 225 patients. RESULTS: Among 50 734 informative FNA samples, 65.3% were test-negative, 33.9% positive, 0.2% positive for medullary carcinoma, and 0.6% positive for parathyroid. The benign call rate in BCIII-IV nodules was 68%. Among test-positive samples, 73.3% had mutations, 11.3% gene fusions, and 10.8% isolated copy number alterations. Comparing BCIII-IV nodules with BCV-VI nodules revealed a shift from predominantly RAS-like alterations to BRAF V600E-like alterations and fusions involving receptor tyrosine kinases (RTK). Using ThyroSeq Cancer Risk Classifier, a high-risk profile, which typically included TERT or TP53 mutations, was found in 6% of samples, more frequently BCV-VI. RNA-Seq confirmed ThyroSeq detection of novel RTK fusions in 98.9% of cases. CONCLUSION: In this series, 68% of BCIII-IV nodules were classified as negative by ThyroSeq, potentially preventing diagnostic surgery in this subset of patients. Specific genetic alterations were detected in most BCV-VI nodules, with a higher prevalence of BRAF and TERT mutations and targetable gene fusions compared to BCIII-IV nodules, offering prognostic and therapeutic information for patient management.

Fractionated radioimmunotherapy with (90) Y-clivatuzumab tetraxetan and low-dose gemcitabine is active in advanced pancreatic cancer: A phase 1 trial.

BACKGROUND: It has been demonstrated that the humanized clivatuzumab tetraxetan (hPAM4) antibody targets pancreatic ductal carcinoma selectively. After a trial of radioimmunotherapy that determined the maximum tolerated dose of single-dose yttrium-90-labeled hPAM4 ((90) Y-hPAM4) and produced objective responses in patients with advanced pancreatic ductal carcinoma, the authors studied fractionated radioimmunotherapy combined with low-dose gemcitabine in this disease. METHODS: Thirty-eight previously untreated patients (33 patients with stage IV disease and 5 patients with stage III disease) received gemcitabine 200 mg/m(2) weekly for 4 weeks with (90) Y-hPAM4 given weekly in Weeks 2, 3, and 4 (cycle 1), and the same cycle was repeated in 13 patients (cycles 2-4). In the first part of the study, 19 patients received escalating weekly (90) Y doses of 6.5 mCi/m(2) , 9.0 mCi/m(2) , 12.0 mCi/m(2) , and 15.0 mCi/m(2) . In the second portion, 19 additional patients received weekly doses of 9.0 mCi/m(2) or 12.0 mCi/m(2) . RESULTS: Grade 3/4 thrombocytopenia or neutropenia (according to version 3.0 of the National Cancer Institute's Common Terminology Criteria for Adverse Events) developed in 28 of 38 patients after cycle 1 and in all retreated patients; no grade >3 nonhematologic toxicities occurred. Fractionated dosing of cycle 1 allowed almost twice the radiation dose compared with single-dose radioimmunotherapy. The maximum tolerated dose of (90) Y-hPAM4 was 12.0 mCi/m(2) weekly for 3 weeks for cycle 1, with ≤9.0 mCi/m(2) weekly for 3 weeks for subsequent cycles, and that dose will be used in future trials. Six patients (16%) had partial responses according to computed tomography-based Response Evaluation Criteria in Solid Tumors, and 16 patients (42%) had stabilization as their best response (58% disease control). The median overall survival was 7.7 months for all 38 patients, including 11.8 months for those who received repeated cycles (46% [6 of 13 patients] ≥1 year), with improved efficacy at the higher radioimmunotherapy doses. CONCLUSIONS: Fractionated radioimmunotherapy with (90) Y-hPAM4 and low-dose gemcitabine demonstrated promising therapeutic activity and manageable myelosuppression in patients with advanced pancreatic ductal carcinoma.

An algorithm for PET tumor volume and activity quantification: without specifying camera's point spread function (PSF).

PURPOSE: The authors have developed an algorithm for segmentation and removal of the partial volume effect (PVE) of tumors in positron emission tomography (PET) images. The algorithm accurately measures functional volume (FV) and activity concentration (AC) of tumors independent of the camera's full width half maximum (FWHM). METHODS: A novel iterative histogram thresholding (HT) algorithm is developed to segment the tumors in PET images, which have low resolution and suffer from inherent noise in the image. The algorithm is initiated by manually drawing a region of interest (ROI). The segmented tumors are subjected to the iterative deconvolution thresholding segmentation (IDTS) algorithm, where the Van-Cittert's method of deconvolution is used for correcting PVE. The IDTS algorithm is fully automated and accurately measures the FV and AC, and stops once it reaches convergence. The convergence criteria or stopping conditions are developed in such a way that the algorithm does not rely on estimating the FWHM of the point spread function (PSF) to perform the deconvolution process. The algorithm described here was tested in phantom studies, where hollow spheres (0.5-16 ml) were used to represent tumors with a homogeneous activity distribution, and an irregular shaped volume was used to represent a tumor with a heterogeneous activity distribution. The phantom studies were performed with different signal to background ratios (SBR) and with different acquisition times (1 min, 3 min, and 5 min). The parameters in the algorithm were also changed (FWHM and matrix size of the Gaussian function) to check the accuracy of the algorithm. Simulated data were also used to test the algorithm with tumors having heterogeneous activity distribution. RESULTS: The results show that changing the size and shape of the ROI during initiation of the algorithm had no significant impact on the FV. An average FV overestimation of 30% and an average AC underestimation of 35% were observed for the smallest tumor (0.5 ml) over the entire range of noise and SBR level. The difference in average FV and AC estimations from the actual volumes were less than 5% as the tumor size increased to 16 ml. For tumors with heterogeneous activity profile, the overall volume error was less than 10%. The average overestimation of FV was less than 10% and classification error was around 11%. CONCLUSIONS: The algorithm developed herein was extensively tested and is not dependent on accurately quantifying the camera's PSF. This feature demonstrates the robustness of the algorithm and enables it to be applied on a wide range of noise and SBR within an image. The ultimate goal of the algorithm is to be able to be operated independent of the camera type used and the reconstruction algorithm deployed.

Radiomicrosphere Dosimetry: Principles and Current State of the Art.

Radiomicrosphere Therapy (RMT) refers to a liver-directed therapeutic modality based on the intrahepatic arterial administration of radiolabeled microspheres. There is a need for standardization of the terminology of RMT. A descriptive identifier should first name the radioisotope, then the chemical formulation of the microsphere, and lastly add the term RMT that indicates the therapeutic modality. At present, clinically available options include |Y-90| |Resin| |RMT|, |Y-90| |Glass| |RMT| and |Ho-166| |PLLA| |RMT|. The latter is available in Europe and is being considered for clearance by the FDA in the United States. Preclinical studies with |Re-188| |PLLA| |RMT| are underway. Dosimetric considerations are strongly tied to both the type of the radioisotope and the chemical composition of the microsphere type. This review will focus on Y-90 resin and glass RMT, the history, dosimetry, clinical use, and controversies.

The prognostic value of functional tumor volume and total lesion glycolysis in patients with colorectal cancer liver metastases undergoing 90Y selective internal radiation therapy plus chemotherapy.

PURPOSE: Functional tumor volume (FTV) and total lesion glycolysis (TLG) are measures of metabolic activity of tumors determined by fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT images. These parameters could potentially have clinical value in response to treatment evaluation and disease prognostication. The objectives of this study were to investigate the relationship between functional tumor parameters (FTV and TLG) and clinical outcomes in patients with colorectal cancer liver metastases (CRCLM) undergoing (90)Y-resin microsphere selective internal radiation therapy (SIRT) (SIR-Spheres®, Sirtex Medical Limited, Lane Cove, NSW, Australia). METHODS: FDG PET/CT studies of 20 patients with unresectable CRCLM who underwent (90)Y SIRT under a phase II clinical trial were analyzed. FTV and TLG were calculated using PET VCAR (GE Healthcare, Milwaukee, WI, USA) on pretreatment and 4-week posttreatment scans. The effects of pretreatment and posttreatment functional tumor activity on patient survival were evaluated using Kaplan-Meier survival curves. RESULTS: The median survival in the study group was 14.8 months (range 2.0-27.7 months). The median survival for patients with pretreatment FTV values of above and below 200 cc were 11.2 and 26.9 months, respectively (p < 0.05). The median survival for patients with 4-week posttreatment FTV values of above and below 30 cc were 10.9 and 26.9 months, respectively (p < 0.05). The median survival for patients with pretreatment TLG values of above and below 600 g were 11.2 and 26.9 months, respectively (p < 0.05). The median survival for patients with 4-week posttreatment TLG values of above and below 100 g were 10.9 and 26.9 months, respectively (p < 0.05). CONCLUSION: Pretreatment and posttreatment FTV and TLG showed very strong association with survival. These values can be useful quantitative criteria for patient selection and disease prognostication when (90)Y SIRT is contemplated in patients with CRCLM.

A Joint Statement from the American Thyroid Association, the European Association of Nuclear Medicine, the European Thyroid Association, the Society of Nuclear Medicine and Molecular Imaging on Current Diagnostic and Theranostic Approaches in the Management of Thyroid Cancer.

Background: The American Thyroid Association (ATA), the European Association of Nuclear Medicine, the European Thyroid Association, and the Society of Nuclear Medicine and Molecular Imaging have established an intersocietal working group to address the current controversies and evolving concepts in thyroid cancer management and therapy. The working group annually identifies topics that may significantly impact clinical practice and publishes expert opinion articles reflecting intersocietal collaboration, consensus, and suggestions for further research to address these important management issues. Summary: In 2019, the intersocietal working group identified the following topics for review and interdisciplinary discussion: (i) perioperative risk stratification, (ii) the role of diagnostic radioactive iodine (RAI) imaging in initial staging, and (iii) indicators of response to RAI therapy. Conclusions: The intersocietal working group agreed that (i) initial patient management decisions should be guided by perioperative risk stratification that should include the eighth edition American Joint Committee on Cancer staging system to predict disease specific mortality, the modified 2009 ATA risk stratification system to estimate structural disease recurrence, with judicious incorporation of molecular theranostics to further refine management recommendations; (ii) diagnostic RAI scanning in ATA intermediate risk patients should be utilized selectively rather than being considered mandatory or not necessary for all patients in this category; and (iii) a consistent semiquantitative reporting system should be used for response evaluations after RAI therapy until a reproducible and clinically practical quantitative system is validated.

A Review of the History of Radioactive Iodine Theranostics: The Origin of Nuclear Ontology

Studies on the first years of radioactive iodine (RAI) use in thyroid diseases have focused on hyperthyroidism. Saul Hertz's success with RAI in thyrotoxicosis fueled a seamless transition to Samuel Seidlin's investigations with RAI in thyroid cancer. These landmark events embody nuclear ontology, a philosophical foundation for the creation and existence of radio-therapeutic principles that continue to influence clinical practices today. Laying this ontological foundation, Dr. Saul Hertz who is the founding director of Massachusetts General Hospital Thyroid Clinic, affiliated with Harvard University created a framework for RAI theranostics with preclinical experiments and clinical cases from 1937 to 1942. The first thyroid cancer treatment with RAI was applied in 1942 by Samuel Seidlin. The sensational effect of the first application was interestingly powerful enough to overshadow scientific data. Seidlin and colleagues assembled a sixteen-patient series showcasing a unique entity: functional thyroid metastases that respond to RAI. Other investigations at the time demonstrated that RAI had little efficacy as a therapeutic agent, mainly because most thyroid tumors do not form colloid, and therefore cannot concentrate RAI. These findings were soon overshadowed by a mainstream article in the October 1949 issue of Life that portrayed RAI as a lifesaving therapy for thyroid cancer. The paradigm was set, and later writings by William H. Beierwaltes and other prominent nuclear medicine physicians established the primary goals and principles of RAI therapy. The developments in theoretical physics and nuclear instrumentation and the scientists who made these developments in the early years contributed greatly to the development of the concept. In the field of nuclear medicine, William H. Beierwaltes has gone down in our history as a clinical researcher with his most important contributions. The classical paradigm that started with him has carried us to today's molecular theranoistic viewpoint. This paper examines controversial topics in the advent of thyroid theranostics, and applies historical significance to current discussions on the role of RAI in thyroid cancer management. Another paradigm shift is on the horizon as thyroidology enters the age of genomics. The molecular theranostic profiles will soon be incorporated into a dynamic clinical decision-making and management algorithm for thyroid surgery and RAI therapy. From now on, nuclear oncology will gain a new ontological identity with molecular pathology and new theranostic expansions.

Complicated Surgical Removal of an Adherent Port-a-Cath After 11 Years of Implantation.

A 65-year-old woman with a medical history significant for anal cancer was referred by her primary care physician for a port-a-cath removal. The port was placed prior to treatment of squamous cell carcinoma of the anus, 11 years prior to this scheduled removal. She received chemotherapy and radiation in accordance with the Nigro protocol, treating the anal cancer to complete resolution. During port removal, a fibrous capsule was dissected and the port was removed from the left upper breast border along with proximal portion of the catheter. Significant difficulty was found in removing the remaining catheter despite sustained traction and guidewire insertion. Fluoroscopy revealed an intravascular adhesion of the catheter tip in the superior vena cava, which could not be freed. In order to prevent vascular injury, the adhesed portion of the distal catheter was left in place with three large surgical clips placed distally. This case highlights the very rare complication of complete vascular adherence of the terminal catheter tip and extended port intracorporeal time as a risk factor for adhesion. This case also highlights the importance of timely permanent central venous catheter removal following completion of its intended regimen.

Rosai-Dorfman Disease and Unusual Local Invasive Presentation.

Rosai-Dorfman disease (RDD) is a rare medical condition with bilateral painless lymphadenopathy. We present the case of a young man diagnosed with a very unique presentation of Rosai-Dorfman disease. A 40-year-old African-American man presented with a firm, non-tender, progressive chest and neck mass appeared three months ago. Imaging of the neck demonstrated an 8.6-cm anterior neck subcutaneous soft tissue mass extending into the anterior mediastinum through the sternum with erosive changes in the sternum and the lesion is abutting the right common carotid artery and innominate vein and surrounds the medial aspect of the clavicles bilaterally. Ultrasound (US)-guided biopsy showed marked polytypic-appearing plasma cell proliferation associated with relatively prominent histiocytes with hemophagocytosis/emperipolesis and focal neutrophils. There were S100+ histiocytes; however, findings were not typical for RDD. As that biopsy was not diagnostic, incisional biopsy with adequate sampling was performed. Surgical pathology demonstrated a very abnormal infiltrate with prominent histiocytes including areas with the features of extranodal RDD. BRAF V600E immunohistochemistry (IHC) was negative. Modified radical neck dissection, proximal sternal resection and superior mediastinal nodal dissection surgery was recommended. However, the patient refused the procedure. Typical manifestations are lymphadenopathy with fever that our patient did not experience. Bone involvement happens in 5-10% of cases. There is not enough data about blood vessel invasion which make our case unique. Treatment plan is still controversial. Clinical monitoring is recommended if the symptoms are tolerable as regression has been reported in many cases (20-50%). Surgery is reserved for patients with vital organ involvement or extra-nodal disease.

Biological factors, tumor growth kinetics, and survival after metastasectomy for pulmonary melanoma.

INTRODUCTION: Approximately 23% of melanoma patients will eventually develop pulmonary metastases and have a median survival of only about 7-11 months. Because pulmonary metastasectomy can improve this statistic, we investigated clinicopathologic features and biological correlates that might be used to identify surgical candidates. METHODS: Archived operative specimens and clinical records were retrieved for 20 melanoma patients who underwent resection of isolated pulmonary metastases at the John Wayne Cancer Institute, Saint John's Health Center. Five-year postmetastasectomy survival (PMS) rate was correlated with age, number of pulmonary metastases, tumor doubling time (TDT), tumor necrosis, and immunohistochemical expressions of four biological markers: Ki-67, glucose transporter-1 (Glut-1), caspase-3, and CD31. RESULTS: Median TDT was 61 days. On multivariate analysis, TDT (P = 0.008), Glut-1 intensity (P = 0.04), and CD31 expression (P = 0.004) were the significant predictors of PMS. Age, number of pulmonary metastases, tumor necrosis, and expression of Ki-67 or caspase-3 did not significantly impact survival. Median TDT was 56 days with Glut-1 expression versus 165 days without Glut-1 expression (P = 0.002), and Glut-1 staining intensity independently affected TDT (P = 0.012). CONCLUSIONS: Surgical resection may be preferable to toxic systemic therapies in melanoma patients whose isolated pulmonary metastases have a long TDT (> or = 61 days) and no biopsy evidence of Glut-1 expression.

2009 EANM parathyroid guidelines.

The present guidelines were issued by the Parathyroid Task Group of the European Association of Nuclear Medicine. The main focus was imaging of primary hyperparathyroidism. Dual-tracer and single-tracer parathyroid scintigraphy protocols were discussed as well as the various modalities of image acquisition. Primary hyperparathyroidism is an endocrine disorder with high prevalence, typically caused by a solitary parathyroid adenoma, less frequently (about 15%) by multiple parathyroid gland disease (MGD) and rarely (1%) by parathyroid carcinoma. Patients with MGD may have a double adenoma or hyperplasia of three or all four parathyroid glands. Conventional surgery has consisted in routine bilateral neck exploration. The current trend is toward minimally invasive surgery. In this new era, the success of targeted parathyroid surgery depends not only on an experienced surgeon, but also on a sensitive and accurate imaging technique. Recognizing MGD is the major challenge for pre-operative imaging, in order to not direct a patient towards inappropriate minimal surgery. Scintigraphy should also report on thyroid nodules that may cause confusion with a parathyroid adenoma or require concurrent surgical resection. The two main reasons for failed surgery are ectopic glands and undetected MGD. Imaging is mandatory before re-operation, and scintigraphy results should be confirmed with a second imaging technique (usually US for a neck focus, CT or MRI for a mediastinal focus). Hybrid SPECT/CT instruments should be most helpful in this setting. SPECT/CT has a major role for obtaining anatomical details on ectopic foci. However, its use as a routine procedure before target surgery is still investigational. Preliminary data suggest that SPECT/CT has lower sensitivity in the neck area compared to pinhole imaging. Additional radiation to the patient should also be considered. The guidelines also discuss aspects related to radio-guided surgery of hyperparathyroidism and imaging of chronic kidney disease patients with secondary hyperparathyroidism.

Preoperative Y-90 microsphere selective internal radiation treatment for tumor downsizing and future liver remnant recruitment: a novel approach to improving the safety of major hepatic resections.

BACKGROUND: Extended liver resections are being performed more liberally than ever. The extent of resection of liver metastases, however, is restricted by the volume of the future liver remnant (FLR). An intervention that would both accomplish tumor control and induce compensatory hypertrophy, with good patient tolerability, could improve clinical outcomes. CASE PRESENTATION: A 53-year-old woman with a history of cervical cancer presented with a large liver mass. Subsequent biopsy indicated poorly differentiated carcinoma with necrosis suggestive of squamous cell origin. A decision was made to proceed with pre-operative chemotherapy and Y-90 microsphere SIRT with the intent to obtain systemic control over the disease, downsize the hepatic lesion, and improve the FLR. A surgical exploration was performed six months after the first SIRT (three months after the second). There was no extrahepatic disease. The tumor was found to be significantly decreased in size with central and peripheral scarring. The left lobe was satisfactorily hypertrophied. A formal right hepatic lobectomy was performed with macroscopic negative margins. CONCLUSION: Selective internal radiation treatment (SIRT) with yttrium-90 (Y-90) microspheres has emerged as an effective liver-directed therapy with a favorable therapeutic ratio. We present this case report to suggest that the portal vein radiation dose can be substantially increased with the intent of inducing portal/periportal fibrosis. Such a therapeutic manipulation in lobar Y-90 microsphere treatment could accomplish the end points of PVE with avoidance of the concern regarding tumor progression.

A Case of Papillary Thyroid Carcinoma and Kostmann Syndrome: A Genomic Theranostic Approach for Comprehensive Treatment.

BACKGROUND Theranostics is a combined diagnostic and treatment approach to individualized patient care. Kostmann syndrome, or severe congenital neutropenia, is an autosomal recessive disease that affects the production of neutrophils. Papillary thyroid carcinoma (PTC) is the most common type of thyroid malignancy associated with gene alterations, including in the mitogen-activated protein kinase (MAPK) signaling pathway gene. Translocation of the ETS variant 6/neurotrophic receptor tyrosine kinase 3 (ETV6/NTRK3) gene has been implicated in radiation-induced and pediatric forms of thyroid carcinoma but has rarely been described in sporadic PTC. This report is of a case of PTC in a patient with Kostmann syndrome associated with ETV6/NTRK3 gene translocation. CASE REPORT A 32-year-old woman with a history of Kostmann syndrome, acute myeloid leukemia (AML), and chronic graft versus host disease (GVHD) was diagnosed with PTC with cervical lymph node metastases and soft tissue invasion following total thyroidectomy and bilateral modified radical neck dissection. Her postoperative radioactive iodine (RAI) scan confirmed lymph node metastasis. Gene expression studies identified increased expression of iodine-handling genes and ETV6/NTRK3 gene fusion. Because of the bone marrow compromise due to Kostmann syndrome and AML, a careful genomic and molecular analysis was performed to guide therapy. CONCLUSIONS This is the first reported case of the association between PTC, Kostmann syndrome, and ETV6/NTRK3 gene translocation in which multimodality treatment planning was optimized by genomic profiling.