Prognostic impact of incomplete surgical clearance of radioiodine sensitive local lymph node metastases diagnosed by post-operative <Superscript>124</Superscript>I-NaI-PET/CT in patients with papillary thyroid cancer

Purpose

Nodal involvement is an independent risk factor of recurrence in papillary thyroid cancer (PTC). Neither the international guidelines nor the recently introduced ongoing risk adaptation concept consider the extent of initial surgical clearance of radioiodine sensitive lymph node metastases in their stratification systems. We investigated the prognostic relevance of incomplete initial surgical clearance in patients with purely lymphogeneous metastatic PTC (pN1 M0) despite successful radioiodine therapy. Accurate assessment of pre-ablative nodal status was attempted using PET/CT studies with both ¹²⁴I-NaI and ¹⁸F-FDG along with high-resolution cervical ultrasound.

Methods

Sixty-five patients with histologically diagnosed lymph node metastases (pN1 M0) were retrospectively analyzed. Patients with iodine-negative lymph node metastases diagnosed by ¹⁸F-FDG PET/CT or distant metastases were excluded from the analysis. The association of disease recurrence with the pre-ablative nodal status, as well as other baseline characteristics, were examined applying nonparametric tests for independent samples and multiple regression analysis. Patients with persistent lymph node metastases in ¹²⁴I-NaI PET/CT were further divided according to the additional presence or absence of FDG-uptake in ¹⁸F-FDG PET/CT. Survival analyses were performed using Kaplan–Meier curves and the Cox proportional hazards model for uni- and multivariate analyses to assess the influence of prognostic factors on progression free survival (PFS).

Results

Incomplete metastatic lymph node resection captured by ¹²⁴I-NaI PET/CT (n?=?33) was an independent risk factor for recurrence (61 % vs 25 %, p?=?0.006) and shorter PFS (46 months vs not reached, HR 4.0 [95 %-CI, 1.7–9.2], p?=?0.001). Ultrasound could detect lymph node metastases only in 19/33 patients (58 %). Among patients with positive nodal status, FDG-avidity of metastatic iodine positive lymph nodes worsened the outcome (16 vs 69 months, p?=?0.047). From all other investigated factors including age, N-stage (N1a vs N1b), and T-Stage (T4 vs T1-3), only large tumor size (pT4) had a significant impact on PFS (HR 2.9 [95 %-CI, 1.3–6.4], p?=?0.007).

Conclusions

Incomplete initial surgical clearance of lymph node metastases even after successful radioiodine therapy may increase the chances of recurrence and is an independent risk factor for impaired survival of patients with PTC. Pre-ablative (dual tracer PET/CT) imaging with ¹²⁴I-Na and ¹⁸F provides a prognostic tool for these patients and may considerably complement the current risk stratification systems.

     

In vivo evaluation of PEGylated <Superscript>64</Superscript>Cu-liposomes with theranostic and radiotherapeutic potential using micro PET/CT

Purpose

The objective of this study was to evaluate the potential of PEGylated ⁶⁴Cu-liposomes in clinical diagnostic positron emission tomography (PET) imaging and PEGylated ¹⁷⁷Lu-liposomes in internal tumor radiotherapy through in vivo characterization and dosimetric analysis in a human xenograft mouse model.

Methods

Liposomes with 5 and 10 mol% PEG were characterized with respect to size, charge, and ⁶⁴Cu- and ¹⁷⁷Lu-loading efficiency. The tumor imaging potential of ⁶⁴Cu-loaded liposomes was evaluated in terms of in vivo biodistribution, tumor accumulation and tumor-to-muscle (T/M) ratios, using PET imaging. The potential of PEGylated liposomes for diagnostic and therapeutic applications was further evaluated through dosimetry analysis using OLINDA/EXM software. The ⁶⁴Cu-liposomes were used as biological surrogates to estimate the organ and tumor kinetics of ¹⁷⁷Lu-liposomes.

Results

High remote loading efficiency (>95 %) was obtained for both ⁶⁴Cu and ¹⁷⁷Lu radionuclides with PEGylated liposomes, and essentially no leakage of the encapsulated radionuclide was observed upon storage and after serum incubation for 24 h at 37 °C. The 10 mol% PEG liposomes showed higher tumor accumulation (6.2?±?0.2 %ID/g) than the 5 mol% PEG liposomes, as evaluated by PET imaging. The dosimetry analysis of the ⁶⁴Cu-liposomes estimated an acceptable total effective dose of 3.3·10^?2 mSv/MBq for diagnostic imaging in patients. A high absorbed tumor dose (114 mGy/MBq) was estimated for the potential radiotherapeutic ¹⁷⁷Lu-liposomes.

Conclusion

The overall preclinical profile of PEGylated ⁶⁴Cu-liposomes showed high potential as a new PET theranostic tracer for imaging in humans. Dosimetry results predicted that initial administered activity of 200 MBq of ⁶⁴Cu-liposomes should be acceptable in patients. Work is in progress to validate the utility of PEGylated ⁶⁴Cu-liposomes in a clinical research programme. The high absorbed tumor dose (114 mGy/MBq) estimated for ¹⁷⁷Lu-liposomes and the preliminary dosimetric studies justify further therapeutic and dosimetry investigation of ¹⁷⁷Lu-liposomes in animals before potential testing in man.

     

A Brief Version of the Quality of Life in Short Stature Youth Questionnaire - the QoLISSY-Brief

The Quality of Life in Short Stature Youth (QoLISSY) questionnaire measures health-related quality of life (HrQoL) in short statured children (8–18 years) from patient and parent perspectives. To minimize respondent burden when assessing HrQoL in clinical practice, a brief version of the currently available 22-item QoLISSY is needed. The dataset of the European QoLISSY study (N?=?268) was divided into two subdatasets at random, one to identify the items of the brief questionnaire and the other to test the operating characteristics (reliability and validity). Concept-based construction involved the selection of three items per Quality of Life (QoL)-dimension (physical, social, emotional) according to the highest corrected item-scale correlation. Psychometric properties were inspected in terms of reliability and validity supplemented by testing item fit statistics to examine item response theory (IRT) compliance. Cronbach’s alpha for the 9-item version was 0.89 for the patient- and the parent report. Pearson’s correlations with the generic KIDSCREEN questionnaire were low to moderate (children: r?=?0.17–0.58; parents: r?=?0.12–0.56). Shorter children reported significantly poorer QoL (mean difference 15.39 points; p?<?0.001) than taller children, indicating known-groups validity. Results from IRT analysis showed an acceptable fit to Masters’ Partial Credit Model. The 9-item QoLISSY brief version has satisfactory operating characteristics and is an efficient alternative for use in research and practice.     

Decline of Systolic and Diastolic 2D Strain Rate During Follow-Up of HLHS Patients After Fontan Palliation

Accurate assessment of ventricular function is particularly important in children with hypoplastic left heart syndrome (HLHS) after completion of the total cavopulmonary connection (TCPC). For this purpose, two-dimensional speckle tracking (2DST) is a promising technique as it does not depend on the angle of insonation or the geometry of the ventricle. The objective of this study was to assess changes in systolic and diastolic right ventricular (RV) function within a 5-year follow-up period of HLHS patients after TCPC using conventional and 2DST echocardiography. RV fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE), E/A, E/e′ and 2DST parameters [global longitudinal peak systolic strain (GS) and strain rate (GSRs), global strain rate in early (GSRe) and late (GSRa) diastole] of 40 HLHS patients were compared at 1.6 and at 5.1 years after TCPC. RVFAC, E/A, E/e′ and GS did not change, whereas TAPSE (13.7 ± 3.2 vs. 10.5 ± 2.4 mm/m², p < 0.001), GSRs (?1.56 ± 0.28 vs. ?1.35 ± 0.31 1/s, p < 0.001), GSRe (2.22 ± 0.49 vs. 1.96 ± 0.44 1/s, p = 0.004) and GSRa (1.19 ± 0.39 vs. 0.92 ± 0.39 1/s, p < 0.001) decreased significantly. Systolic and diastolic RV function parameters of HLHS patients decreased from 1.6 to 5.1 years after TCPC in our patients. Changes in global strain rate parameters may be signaling early RV dysfunction that is not detectable by traditional echocardiography. Further study is needed to verify this and to determine whether these changes are clinically relevant.     

Abdominal transplantation for unresectable tumors in children: the zooming out principle

Purpose

To present our experience in abdominal transplantations to manage unresectable abdominal neoplasms in children and to describe the role of extensive surgeries in such cases.

Methods

This is a retrospective study of 22 abdominal transplantations in 21 patients for abdominal tumors over 16 years. Transplantation techniques included liver transplant (LT), multivisceral transplant (MVTx), and intestinal autotransplant (IA). Follow-up intervals ranged from 0.3 to 168 months (median 20 months).

Results

LT alone was performed in 15 patients for primary malignant (11) and benign (4) liver tumors. Pathological classification included HB hepatoblastoma (6), HCC hepatocellular cancer (3), hepatic epithelioid hemangioendothelioma HEH (1), angiosarcoma (1), benign vascular tumors (3), and adenoma (1). IA was performed in four patients for lesions involving the root of the mesentery; tumors of the head of pancreas (3) and mesenteric hemangioma (1). MVTx was performed in 2 patients for malignancies; pancreaticoblastoma (1), recurrent hepatoblastoma (1), and in one patient as a rescue procedure after IA failure. Four of the eleven patients who underwent LT for malignant liver tumor had metastatic disease at presentation. Six of them died of recurrent neoplasm (3), transplant-related complications (2), and underlying disease (1). All LT patients who had benign tumors are alive with functioning grafts. All IA patients survived and are on an oral diet, with one patient requiring TPN supplementation. One of the three patients who underwent MVTx died of metastatic disease.

Conclusions

Allo/auto transplantation for abdominal tumors is a valuable modality when conventional treatments fail or are not feasible.