Dataset Information

Intraoperative MET-receptor targeted fluorescent imaging and spectroscopy for lymph node detection in papillary thyroid cancer: novel diagnostic tools for more selective central lymph node compartment dissection.

ABSTRACT:

Purpose

Patients undergoing prophylactic central compartment dissection (PCLND) for papillary thyroid cancer (PTC) are often overtreated. This study aimed to determine if molecular fluorescence-guided imaging (MFGI) and spectroscopy can be useful for detecting PTC nodal metastases (NM) and to identify negative central compartments intraoperatively.

Methods

We used a data-driven prioritization strategy based on transcriptomic profiles of 97 primary PTCs and 80 normal thyroid tissues (NTT) to identify tumor-specific antigens for a clinically available near-infrared fluorescent tracer. Protein expression of the top prioritized antigen was immunohistochemically validated with a tissue microarray containing primary PTC (n = 741) and NTT (n = 108). Staining intensity was correlated with 10-year locoregional recurrence-free survival (LRFS). A phase 1 study (NCT03470259) with EMI-137, targeting MET, was conducted to evaluate safety, optimal dosage for detecting PTC NM with MFGI, feasibility of NM detection with quantitative fiber-optic spectroscopy, and selective binding of EMI-137 for MET.

Results

MET was selected as the most promising antigen. A worse LRFS was observed in patients with positive versus negative MET staining (81.9% versus 93.2%; p = 0.02). In 19 patients, no adverse events related to EMI-137 occurred. 0.13 mg/kg EMI-137 was selected as optimal dosage for differentiating NM from normal lymph nodes using MFGI (p < 0.0001) and spectroscopy (p < 0.0001). MFGI identified 5/19 levels (26.3%) without NM. EMI-137 binds selectively to MET.

Conclusion

MET is overexpressed in PTC and associated with increased locoregional recurrence rates. Perioperative administration of EMI-137 is safe and facilitates NM detection using MFGI and spectroscopy, potentially reducing the number of negative PCLNDs with more than 25%.

Clinical trial registration

NCT03470259.

SUBMITTER: Jonker PKC

PROVIDER: S-EPMC9308606 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Publications

Intraoperative MET-receptor targeted fluorescent imaging and spectroscopy for lymph node detection in papillary thyroid cancer: novel diagnostic tools for more selective central lymph node compartment dissection.

Jonker Pascal K C PKC Metman Madelon J H MJH Sondorp Luc H J LHJ Sywak Mark S MS Gill Anthony J AJ Jansen Liesbeth L Links Thera P TP van Diest Paul J PJ van Ginhoven Tessa M TM Löwik Clemens W G M CWGM Nguyen Anh H AH Coppes Robert P RP Robinson Dominic J DJ van Dam Gooitzen M GM van Hemel Bettien M BM Fehrmann Rudolf S N RSN Kruijff Schelto S

European journal of nuclear medicine and molecular imaging 20220407 10

<h4>Purpose</h4>Patients undergoing prophylactic central compartment dissection (PCLND) for papillary thyroid cancer (PTC) are often overtreated. This study aimed to determine if molecular fluorescence-guided imaging (MFGI) and spectroscopy can be useful for detecting PTC nodal metastases (NM) and to identify negative central compartments intraoperatively.<h4>Methods</h4>We used a data-driven prioritization strategy based on transcriptomic profiles of 97 primary PTCs and 80 normal thyroid tissue ...[more]

PMID: 35389070

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Project description:BackgroundHashimoto's thyroiditis (HT) is the most prevalent inflammatory disorder of the thyroid gland. Current studies have reported the coexistence rate between HT and papillary thyroid carcinoma (PTC) is quite high. The objective of this study was to evaluate the impact of HT on the predictive factors of central compartment lymph node metastasis (CLNM) in PTC.MethodsA retrospective investigation was performed on PTC patients. They were subclassified into HT and non-HT groups. The results of preoperative neck ultrasound (US) examinations were reviewed. The clinical characteristics and the predictive value for CLNM were explored and compared between the two groups.ResultsA total of 756 patients were included in this study. There were more female patients (86.1%) in the PTC coexistent with the HT group than non-HT group. The patients with HT group had higher preoperative serum level of TSH. There was statistically significant difference between the HT patients and non-HT patients in nodular vascularization. Univariate and multivariate analyses showed that male, age ≤45 years old, tumor diameter >1 cm, and presence of suspicious central compartment lymph node on US, irregular nodular shape, multifocal carcinoma were independent predictive factors of CLNM in PTC patients. It was showed that male, age ≤45 years old, tumor diameter >1 cm, multifocality, and presence of suspicious central lymph node on US were risk factors for CLNM in non-HT patients. Only tumor diameter >1 cm and presence of suspicious central lymph node on US were independently correlated with CLNM in HT patients. The sensitivity of the multivariate model was 63.5%, and specificity was 88.9% for prediction CLNM in HT patients. For non-HT patients, the AUC was 80.6%, the sensitivity of the multivariate model was 64.5%, and specificity was 85.2.ConclusionPTC combined with HT is more common in women, and TSH level in HT group is higher than that in patients with PTC alone. Regardless of that HT is not a related risk factor of CLNM in PTC, our result suggested that different predictive systems should be used for HT and non-HT patients respectively to have a more accurate evaluation of CLNM in clinic.

Project description:BACKGROUND:Prophylactic central neck lymph-nodes dissection is still a topic of major debate in Literature. There is a lack of randomized controlled trials proving advantages in its application in terms of overall survival and local recurrence. Due to the recent rapid increase of elderly population, differentiated tumor carcinoma diagnosis increased in patients over 65?years old. The aim of this study was to compare recurrence rate, complications rate and histological features of tumors in elderly population. METHODS:A retrospective study was carried out collecting data from 371 patients with differentiated thyroid cancer without clinical evidence of lymph-nodes involvement in three Italian referral centers from 2005 to 2015. All patients were aged ??65?years and were divided in two groups based on the performed surgery (total thyroidectomy alone or associated with central lymph-nodes dissection). Moreover, patients were stratified according to the age between 65 and 74?years old and over 75?years old. RESULTS:Total thyroidectomy alone was performed in 184 patients (group A) and total thyroidectomy with prophylactic central neck dissection was performed in 187 cases (group B). There was a statistically significant difference in complications between the groups in terms of neck hematoma (0.5% group A vs 3.7% group B), temporary hypoparathyroidism (11.4% group A vs 21.4% group B), and temporary unilateral recurrent nerve injury (1.5% group A vs 6.4% group B). Lymph nodes recurrence rate was 9.2% in group A and 8.5% in group B, with no statistically significant difference. There was a statistically significant difference in patients over 75?years old in terms of temporary hypoparathyroidism (24% group A vs 11% group B), permanent hypoparathyroidism (2,7% group A vs 0,3% group B) and recurrent nerve injury (9,5% group A vs 2% group B). CONCLUSIONS:The role of prophylactic central neck dissection is still controversial, especially in elderly patients, and an aggressive surgical approach should be carefully evaluated. The Authors reported a similar low recurrence rate between total thyroidectomy and total thyroidectomy associated with prophylactic central neck dissection, with increased postoperative complications in the lymphadenectomy group and in patients over 75?years old, advocating a tailored surgical approach in elderly population.

Project description:The most frequent recurrence site of papillary thyroid carcinoma (PTC) is the cervical lymph nodes. The introduction of an electric linear probe for use with ultrasonography in 1996 improved preoperative lateral neck evaluations. Before 2006, however, our hospital routinely performed prophylactic modified neck dissection (p-MND) for N0 or N1a PTCs >1 cm to prevent node recurrence. In 2006, we changed our policy and the indications for p-MND to PTCs >3 cm and/or with significant extrathyroid extension. Here, we retrospectively compared lymph node recurrence-free survival between PTCs with/without p-MND.We examined the cases of N0 or N1 and M0 PTC patients who underwent initial surgery in 1992-2012. To compare lymph node recurrence-free survival between patients who did/did not undergo p-MND, we divided these patients into three groups (excluding those whose surgery was in 2006): the 2045 patients whose surgery was performed in 1992-1996 (Group 1), the 2989 with surgery between 1997 (post-introduction of ultrasound electric linear probes) and 2005 (Group 2), and the 5332 operated on in 2007-2012 (Group 3).The p-MND performance rate of Group 3 (9%) was much lower than that of Group 1 (80%), but the lymph node recurrence-free survival of the former was significantly better, probably due to differences in clinical features and neck evaluations by ultrasound between the two groups. Our analysis of the patients aged <75 years with 1.1-4-cm PTCs in Groups 2 and 3 showed that p-MND did not improve lymph node recurrence-free survival. p-MND did significantly improve lymph node recurrence-free survival for the extrathyroid extension-positive 3.1-4-cm PTCs, but not for the other subsets.Abolishing routine p-MND for PTCs in 2006 did not decrease lymph node recurrence-free survival, probably due to improved ultrasound preoperative neck evaluations and clinical feature changes. Selective p-MND for high-risk cases improved lymph node recurrence-free survival.

Dataset Information

Intraoperative MET-receptor targeted fluorescent imaging and spectroscopy for lymph node detection in papillary thyroid cancer: novel diagnostic tools for more selective central lymph node compartment dissection.

Purpose

Methods

Results

Conclusion

Clinical trial registration

Publications

Intraoperative MET-receptor targeted fluorescent imaging and spectroscopy for lymph node detection in papillary thyroid cancer: novel diagnostic tools for more selective central lymph node compartment dissection.

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