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Simple Summary: Risk stratification for differentiated thyroid cancer is a well-established tool for prognostication and selection of the appropriate initial therapy for "differentiated thyroid cancers". The current risk stratification systems include a system used in current guidelines, based on surgical pathology features identified postoperatively and a more dynamic model that includes all perioperative clinical, radiologic, and pathologic data as well as the response to initial therapy information. Theranostic risk stratification is essentially based on genomic and molecular features of the patient's individual tumor, investigated perioperatively and associated or correlated with radioactive iodine theranostics. This approach allows a more rational selection of the extent of the initial surgical treatment and subsequent radioactive iodine treatment. 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. [ABSTRACT FROM AUTHOR]

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. RNASeq 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract 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.

Abstract Introduction Parallel to the advances in diagnostic imaging using positron emission tomography (PET), and availability of new systemic treatment options, the treatment paradigm in oncology has shifted towards more aggressive therapeutic interventions to include cytoreductive techniques and metastasectomies. Intraoperative localization of PET positive recurrent/metastatic lesions can be facilitated using a hand-held PET probe. Materials and methods Records of patients who underwent PET probe-guided surgery were reviewed. Surgical indications and operative targets were determined based on diagnostic PET/PET-CT images performed prior to probe-guided surgical planning. PET probe-guided surgery was performed on a separate day using a high-energy gamma probe (PET probe, Care Wise Medical, Morgan Hills CA) 2–6 hours post-injection of 5–15 mCi FDG. Probe count rates, target-to-background ratios, and lesion detection success were analyzed. Results Twenty-four patients underwent PET probe-guided surgery; one patient had two PET-probe guided surgeries resulting in a total of 25 cases (5 colorectal cancer cases, 4 thyroid cancer cases, 6 lymphoma cancer cases, and 10 other cancer cases). Surgical indication was diagnostic exploration in 6 cases with lymphoma and 1 case with head and neck cancer (28%). The remaining 18 cases (72%) underwent PET probe-guided surgery with a therapeutic intent in a recurrent or metastatic disease setting. All the lesions identified and targeted on a preoperative FDG-PET scan were detected by the PET probe with satisfactory in-vivo lesion count rates and a TBR of ≥ 1.5. PET probe allowed localization of lesions that were non-palpable and non-obvious at surgical exploration in 8 patients. Conclusion The use of the PET probe improves the success of surgical exploration in selected indications. Separate day protocol is clinically feasible allowing for flexible operating room scheduling.

Abstract Background Intraoperative localization of image or endoscopy-detected lesions occasionally pose surgical challenges due to the small lesion size and/or difficult anatomic exposure. Identification of such lesions can be facilitated using a hand-held gamma probe with utilization of Tc-99m macroaggregate albumen (MAA) localization technique. The radiopharmaceutical injection can be performed using ultrasound (US) or endoscopy guidance. Case presentations The clinical use of the Tc-99m MAA protocol gamma probe-guided surgery was discussed in three representative cases. Surgical indication was diagnostic exploration in two patients with suspicious lymphadenopathy, and determination of extent of surgical resection in a patient with polyposis. Lesion localization with 100 microcurie (3.7 MBq) Tc-99m MAA prior to surgical exploration resulted in definitive localization of lesions intraoperatively. Conclusion The use Tc-99m MAA deposition technique at the site of surgical target is a highly efficient radio-guided surgery technique with definitive impact on the success of surgical exploration in selected indications.

Abstract Background Treatment records and follow-up data on 40 patients with primary and metastatic liver malignancies who underwent a single whole-liver treatment with Y-90 resin microspheres (SIR-Spheres® Sirtex Medical, Lake Forest, IL) were retrospectively reviewed. The objective of the study was to evaluate the anatomic and physiologic determinants of radiation dose distribution, and the dose response of tumor and liver toxicity in patients with liver malignancies who underwent hepatic arterial Y-90 resin microsphere treatment. Methods Liver and tumor volume calculations were performed on pre-treatment CT scans. Fractional tumor and liver flow characteristics and lung shunt fractions were determined using hepatic arterial Tc-99m MAA imaging. Absorbed dose calculations were performed using the MIRD equations. Liver toxicity was assessed clinically and by liver function tests. Tumor response to therapy was assessed by CT and/or tumor markers. Results Of the 40 patients, 5 had hepatocellular cancer (HCC), and 35 had metastatic liver tumors (15 colorectal cancer, 10 neuroendocrine tumors, 4 breast cancer, 2 lung cancer, 1 ovarian cancer, 1 endometrial cancer, and 2 unknown primary adenocarcinoma). All patients were treated in a salvage setting with a 3 to 80 week follow-up (mean: 19 weeks). Tumor volumes ranged from 15.0 to 984.2 cc (mean: 294.9 cc) and tumor to normal liver uptake ratios ranged from 2.8 to 15.4 (mean: 5.4). Average administered activity was 1.2 GBq (0.4 to 2.4 GBq). Liver absorbed doses ranged from 0.7 to 99.5 Gy (mean: 17.2 Gy). Tumor absorbed doses ranged from 40.1 to 494.8 Gy (mean: 121.5 Gy). None of the patients had clinical venoocclusive disease or therapy-induced liver failure. Seven patients (17.5 %) had transient and 7 patients (17.5 %) had persistent LFT abnormalities. There were 27 (67.5%) responders (complete response, partial response, and stable disease). Tumor response correlated with higher tumor flow ratio as measured by Tc-99m MAA imaging. Conclusion Doses up to 99.5 Gy to uninvolved liver are tolerated with no clinical venoocclusive disease or liver failure. The lowest tumor dose producing a detectable response is 40.1 Gy. The utilization of MAA-based imaging techniques to determine tumor and liver blood flow for clinical treatment planning and the calculation of administered activity may improve clinical outcomes.