What’s new in Nuclear Medicine – January 2021

2 years ago
Radioiodine Ablation of Remaining Thyroid Lobe in Patients with Differentiated Thyroid Cancer Treated by Lobectomy: A Systematic Review and Metaanalysis

Arnoldo Piccardo, Pierpaolo Trimboli, Gianluca Bottoni, and Luca Giovanella

J Nucl Med 2020; 61(12): 1730-5.

Background: The 2015 American Thyroid Association (ATA) guidelines suggests hemithyroidectomy (lobectomy) as the first treatment for low-risk differentiated thyroid cancer (DTC). If this is the only surgical intervention needed, the risk of surgical complications is minimized. The issue with this approach is if a second completion thyroidectomy is required later, as the risk of hypoparathyroidism and transient vocal cord paralysis is increased to greater than, though similar to, that of a total thyroidectomy. Radioactive 131I ablation is typically used only for remnant thyroid tissue following total thyroidectomy, and if the management plan includes radioactive 131I then total thyroidectomy is recommended as the initial surgical plan. Radioactive 131I ablation in place of surgical completion is not routinely recommended by the ATA; however, this approach has been used in patients with low-risk DTC, for whom the completion thyroidectomy has increased risk of complications, or for whom DTC is unexpectedly diagnosed following the initial surgical lobectomy. Evidence for this is not yet well-established.

Purpose: The authors set out to complete an updated systematic review and meta-analysis of all studies evaluating the use of radioactive 131I completion therapy in post-lobectomy DTC.

Methods: Systematic review was performed using PubMED, Embase, Web of Science, and Scopus databases, with literature in all languages published up to 31 January 2020. The references of identified manuscripts were also screened. Two authors independently reviewed each article for the patient demographics, 131I activity administered and rate of successful completion ablation, as well as an assessment of the study quality.

Results: The authors initially identified 93 articles, assessed the full text of eleven studies, and ultimately included five in the meta-analysis. Four of the eleven were excluded due to missing crucial data, one due to using more than one administration of 131I, and one as it was a case series. The five included articles reported on 695 patients between 2002 and 2013. Each study included between 50 and 364 patients. Three were retrospective studies while two were prospective. The selection criteria of all studies included thyroid cancer confirmed after surgical lobectomy. Radioactive 131I activity ranged from 1.1 to 3.7 GBq. One study did not have sufficient information to determine one-year outcome post-ablation; two studies did not report side effects.

The authors identified a 69% (with 95% CI) success of ablation among the five studies, with high heterogeneity related to a higher success rate with a higher administered activity (p=0.02): studies using approximately 1 GBq found a 60% success rate, where studies with 3.5-3.7 GBq found a 75-90% success rate. Side effects were reported in three studies, including neck pain in 15% to 66% of patients. Overall, the authors determined that four of the studies had a high risk of bias. Four studies demonstrated issues with patient selection and quality of the reference standard, and three demonstrating poorly described results, including but not limited to the inability to determine the stage or pre-treatment TSH or to evaluate the number of patients exhibiting a complete or incomplete response. No publication bias was identified by Egger’s test.

Discussion: The authors present the first systematic review and meta-analysis focusing on radioactive 131I completion ablation post-lobectomy in patients with DTC. Based on the five studies included, the treatment is safe with minimal side effects seemingly limited to neck pain. The severity of the neck pain was dependent on activity administered, but largely controlled with acetaminophen. It is effective especially when higher single dose activity is used. Incomplete response rates were lower in studies using higher administered activity; these rates were slightly higher than those of traditional total thyroidectomy with 131I ablation of the remnant tissue. The authors were unable to assess long-term outcomes or infer recommendations about pre-treatment TSH values or lobe size from these studies.

Conclusion: In patients with low-risk DTC requiring completion therapy following surgical lobectomy, radioactive 131I completion ablation may be a reasonable approach in patients for whom a second surgery in undesirable, as it is safe and has a 69% success rate.


NEMESIS: Noninferiority, Individual-Patient Metaanalysis of Selective Internal Radiation Therapy with 90Y Resin Microspheres Versus Sorafenib in Advanced Hepatocellular Carcinoma

Marino Venerito, Maciej Pech, Ali Canbay, Rossella Donghia, Vito Guerra, Gilles Chatellier, Helena Pereira, Mihir Gandhi, Peter Malfertheiner, Pierce K.H. Chow, Valérie Vilgrain, Jens Ricke, and Gioacchino Leandro

J Nucl Med 2020; 61(12): 1736-42.

Background: In advanced hepatocellular carcinoma (aHCC) with preserved liver function, treatment with sorafenib systemic therapy. Use of selective internal radiation therapy with 90Y microsphere radioembolization (SIRT) for these patients has been studied in randomized control trials (RCTs) which have shown similar efficacy and overall survival with fewer adverse events. Non-inferiority has not yet been tested.

Purpose: The authors sought to perform a meta-analysis of RCTs to assess non-inferiority and safety profiles of SIRT, SIRT followed by sorafenib, and sorafenib treatment options for aHCC.

Methods: The authors searched Medline, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases for clinical trials up to February 2019, as well as the abstract books of four international hepatology and oncology conferences held in 2018, for results including sorafenib, yttrium, and hepatocellular carcinoma. Fully completed RCTs of adults with aHCC in which the treatment arm was either SIRT monotherapy or SIRT followed by sorafenib and the comparison arm was sorafenib monotherapy were included. Information about the publication in addition to the treatment regimen, sample size, and number of adverse events was collected. Non-inferiority of overall survival was tested with a margin of 1.08 as based on previous clinical trials of sorafenib.

Results: Three RCTs (33 literature results) were included in the analysis, two of which (SIRveNIB and SARAH) were fully published; the other (SORAMIC) had been presented in a conference abstract and the presenting author of the abstract provided these authors the preliminary manuscript. Overall, 1,243 patients with aHCC were included in the RCTs; 23% of the patients in the SIRT arm and 7% of those in the sorafenib arm did not undergo treatment, leaving 933 patients who received their treatments as per the study protocols.

Overall survival rates ranged between 9.9 and 14.0 (median 10.2) months for the SIRT arm and 9.9 and 11.1 (median 9.2) months for sorafenib which was not significantly different. Non-inferiority of SIRT was found in most subgroups, with superiority being demonstrated in the others (specifically, patients either without cirrhosis or with Hepatitis B).

Safety profiles were based on 1,090 patients. In two trials, there were statistically fewer total and high-grade adverse events in the SIRT arm; in the remaining trial, the rates of total and high-grade adverse events were equivalent.

Conclusions: The meta-analysis of three RCTs showed that SIRT with or without subsequent sorafenib is non-inferior to sorafenib alone, and demonstrates a better safety profile. Subgroup analysis showed superiority of SIRT for aHCC from Hepatitis B and for patients without cirrhosis.


Diagnostic accuracy of positron emission tomography/computed tomography-driven biopsy for the diagnosis of lymphoma.

Alessandro Broccoli, Cristina Nanni, Alberta Cappelli, Francesco Bacci, Alessandro Gasbarrini, Elena Tabacchi, Carlo Piovani, Lisa Argnani, Riccardo Ghermandi, Elena Sabattini, Rita Golfieri, Stefano Fanti, Pier Luigi Zinzani

EJNMMI 2020; 47(13): 3058-65.

Background: Biopsy is necessary to diagnose suspected new lymphoma. Open incisional biopsy is most invoked: it is near 100% accurate and usually without complications; however, it does require hospitalization, operating room availability, and general anesthesia. As such, minimally invasive techniques such at CT- and US-guided biopsies have become prominent. For CT- and US-guided biopsies, there is often adequate tissue to make a diagnosis without need for repeat biopsies with low incidence of complications; the accuracy, however, is 85-90% for nodes and seemingly much lower for extranodal sites, as it can be difficult to identify areas of disease on CT. For this reason, PET is used in staging to identify areas of active lymphoma earlier and more clearly than CT: hence, PET/CT-guided biopsies may show greater diagnostic accuracy.

Purpose: The authors sought to evaluate the diagnostic accuracy of minimally invasive PET-guided needled biopsy of suspected lymphoma.

Methods: Patients with FDG-avid findings suspicious for lymphoma or other lymphoproliferative disease requiring biopsy between March 2016 and December 2018 underwent whole-body PET/CT imaging up to 30 days prior to the procedure, to identify the biopsy target site and trajectory. The most metabolically active (highest SUVmax) accessible lesion was chosen. During the procedure, PET/CT scans were repeated to observe the biopsy needle. A pathologist assessed the sample during the procedure to determine if further sampling was needed, and the final report was delivered within one week of the procedure. Exclusion criteria included metabolically active superficial adenopathy which could be surgically excised and any reason the biopsy was deemed high-risk or contraindicated, such as bleeding risk. Diagnostic accuracy was defined as the diagnostic yield, calculated as the ratio of all diagnostic samples to the total completed procedures, as well as the sensitivity and specificity of the procedure. None of the patients went on to require open incisional biopsy so there is no comparison.

Results: A total of 96 PET/CT-guided biopsies were completed: 62.5% targeting a lymph node and 37.5% targeting an extranodal site, most of which were skeletal. Other sites included soft tissue, liver, kidney, and adrenal glands. The SUVmax of the chosen target ranged from 1.6 to 67.9.

84 of the 96 processed samples were adequate to provide a final diagnosis, including 30 of the 36 extranodal biopsies: diagnostic yield was 87.5% overall and 83.3% for extranodal sites, identifying 62 cases of active lymphoma, one case of chronic lymphocytic leukemia, one case of acute lymphoblastic leukemia, and eight cases of adenocarcinoma metastases. The sample was adequate to rule out malignancy in twelve cases: within the six-month follow-up, three underwent repeat biopsy, two of which confirmed a new diagnosis of lymphoma; the others remained free from malignancy in this follow-up time. The mean length of the samples was 10 mm, ranging from 3 to 30 mm. The mean pathological infiltrate of the samples was 70%, ranging from 0 to 100%: twelve sample were non-diagnostic. The sensitivity of the PET/CT-guided biopsy procedures was found to be 96% (95% CI: 0.886-0.989) with a 100% specificity (0.946-1.000).

Adverse events consisted of pain during the procedure only (4.0%), asymptomatic hematoma at the biopsy site (3.0%), contrast media extravasation (1.0%), and mild transient contrast-induced rash (1.0%).

Discussion: FDG-PET/CT is the best diagnostic tool for lymphoma and has shown promise as a means of guiding biopsy. Previous literature using the technique did not focus on lymphoproliferative disorders, instead including patients with a variety of pathologies. Nonetheless, these studies did confirm benefit of the combination of PET/CT for the biopsy, reporting diagnostic accuracies above 90%. The authors have presented the largest prospective trial of PET/CT biopsy for suspected lymphomas. They found a 96% diagnostic accuracy in the setting of intra-procedural pathological analysis of the specimens, with few minor adverse events. While it is difficult to compare with previous studies of CT-guided biopsy accuracy, the work suggests that for patients with suspicion of lymphoproliferative disease, PET/CT provides greater capacity for biopsy accuracy.

Conclusion: PET/CT-guided biopsy in the setting of suspected lymphoproliferative disease is a safe and effective technique for final tissue diagnosis from both nodal and extranodal sites.


PET/CT Integrated With CT Colonography in Preoperative Obstructive Colorectal Cancer by Incomplete Optical Colonoscopy: A Prospective Study

Nuria Sanchez-Izquierdo, Mario Pages, Maria Mayoral, Domenico Rubello, Patrick M. Colletti, Francisco Campos, Inmaculada Romero, Sebastian Casanueva, Andrea Fritsch, and David Fuster

Clin Nucl Med 2020; 45(12): 943-7.

Background: Optical colonoscopy is the diagnostic modality of choice for colorectal cancer (CRC) as it allows a biopsy to be taken simultaneously as any lesions are visually identified. There are a number of reasons why colonoscopy cannot be completed, such as obstructions, diverticulitis, adhesions, or redundant loops of colon, which renders the clinician unable to determine if there are any other suspicious lesions in the colon: this is the case in 10% of colonoscopies. CT Colonography is often used in these cases to make this determination, but of course precludes any potentially desired biopsy: the pathology of these lesions could not be identified. For staging of CRC, PET/CT is the best modality to identify distant metastases: pairing PET/CT with CT-Colonography could therefore help differentiate benign and malignant lesions seen. Currently, there is little evidence evaluating the efficacy of PET/CT-Colonography (PET/CTC).

Purpose: The authors undertook a prospective study evaluating the use of PET/CTC in the pre-operative diagnosis of suspected obstructive colorectal cancer.

Methods: Patients who underwent colonoscopy which could not be completed but revealed suspicion of CRC between June 2016 and May 2019 underwent PET/CTC. In preparation for the PET/CTC, the patients adhered to a low-residue diet with oral iodinated contrast, the colon was distended by 2-2.5 L CO2 insufflation, and patient were administered IV contrast. Images were acquired both prone and supine and evaluated with two- and three-dimension reconstructions, by both a radiologist and a nuclear medicine physician. Lesions above 4mm were reported. PET/CTC findings were correlated with the pathological results of the surgical resection or biopsy.

Results: 47 patients received PET/CTC following colonoscopy which could not be completed due to obstructive lesions. CRC was histologically confirmed in 47 polyps from 14 patients. 12 polyps were 10mm or greater, with the remaining 35 polyps being less than 10mm. 46 of these 47 CRCs were successfully diagnosed by CTC; the other was a false-negative at the ileocecal junction on CTC but was indeed FDG-avid on PET/CTC (SUVmax 16.7). All 12 large polyps were FDG-avid (SUVmax 3.08-19.5). Of the 35 small polyps, only one was FDG-avid (7mm hyperplastic polyp); the remaining 34 were not identified by PET. Whole-body PET/CTC diagnosed 100% of the nine confirmed liver metastases, whereas CTC identified 89%; PET/CTC identified one case of peritoneal seeding missed by CTC. Both modalities were 100% specific. Lymph node involvement was confirmed in 17 cases: CTC demonstrated greater sensitivity (71%) than PET/CTC (59%).

Discussion: Combined PET/CTC identified all 47 CRCs (100% sensitivity); CTC alone identified 46 of the 47 due to a false negative at the ileocecal valve. Lesions smaller than 10mm were generally not detected by PET but were detected on CTC. PET/CTC changed staging for two patients as it identified liver metastases and peritoneal seeding not identified with CTC alone. For lymph nodes, however, the sensitivity of PET/CTC was lower (59% sensitivity) than CTC alone (71%), which has been previously demonstrated in literature.

Conclusion: PET/CTC showed higher sensitivity than CTC alone for the detection of other tumors in obstructive CRC following incomplete colonoscopy.

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