Standardized treatment in pediatric patients with Hodgkin’s lymphoma (HL) follows risk stratification by tumor stage, erythrocyte sedimentation rate and tumor bulk. We aimed to identify quantitative parameters from pretherapeutic FDG-PET to assist prediction of response to induction chemotherapy. Retrospective analysis in 50 children with HL (f:18; m:32; median age, 14.8 [4–18] a) consecutively treated according to EuroNet-PHL-C1 (n = 42) or -C2 treatment protocol (n = 8). Total metabolic tumor volume (MTV) in pretherapeutic FDG-PET was defined using a semi-automated, background-adapted threshold. Metabolic (SUVmax, SUVmean, SUVpeak, total lesion glycolysis [MTV*SUVmean]) and heterogeneity parameters (asphericity [ASP], entropy, contrast, local homogeneity, energy, and cumulative SUV-volume histograms) were derived. Early response assessment (ERA) was performed after 2 cycles of induction chemotherapy according to treatment protocol and verified by reference rating. Prediction of inadequate response (IR) in ERA was based on ROC analysis separated by stage I/II (1 and 26 patients) and stage III/IV disease (7 and 16 patients) or treatment group/level (TG/TL) 1 to 3. IR was seen in 28/50 patients (TG/TL 1, 6/12 patients; TG/TL 2, 10/17; TG/TL 3, 12/21). Among all PET parameters, MTV best predicted IR; ASP was the best heterogeneity parameter. AUC of MTV was 0.84 (95%-confidence interval, 0.69–0.99) in stage I/II and 0.86 (0.7–1.0) in stage III/IV. In patients of TG/TL 1, AUC of MTV was 0.92 (0.74–1.0); in TG/TL 2 0.71 (0.44–0.99), and in TG/TL 3 0.85 (0.69–1.0). Patients with high vs. low MTV had IR in 86 vs. 0% in TG/TL 1, 80 vs. 29% in TG/TL 2, and 90 vs. 27% in TG/TL 3 (cut-off, > 80 ml, > 160 ml, > 410 ml). In this explorative study, high total MTV best predicted inadequate response to induction therapy in pediatric HL of all pretherapeutic FDG-PET parameters – in both low and high stages as well as the 3 different TG/TL. Ethics committee number: EA2/151/16 (retrospectively registered).

Heat shock protein 70 (Hsp70) is frequently overexpressed in many different tumor types. However, Hsp70 has also been shown to be selectively presented on the plasma membrane of tumor cells, but not normal cells, and this membrane form of Hsp70 (mHsp70) could be considered a universal tumor biomarker. Since viable, mHsp70-positive tumor cells actively release Hsp70 in lipid micro-vesicles, we investigated the utility of Hsp70 in circulation as a universal tumor biomarker and its potential as an early predictive marker of therapeutic failure. We have also evaluated mHsp70 as a target for the isolation and enumeration of circulating tumor cells (CTCs) in patients with different tumor entities. Circulating vesicular Hsp70 levels were measured in the peripheral blood of tumor patients with the compHsp70 ELISA. CTCs were isolated using cmHsp70.1 and EpCAM monoclonal antibody (mAb)-based bead approaches and characterized by immunohistochemistry using cytokeratin and CD45-specific antibodies. In two out of 35 patients exhibiting therapeutic failure two years after initial diagnosis of non-metastatic breast cancer, progressively increasing levels of circulating Hsp70 had already been observed during therapy, whereas levels in patients without subsequent recurrence remained unaltered. With regards to CTC isolation from patients with different tumors, an Hsp70 mAb-based selection system appears superior to an EpCAM mAb-based approach. Extracellular and mHsp70 can therefore serve as a predictive biomarker for therapeutic failure in early-stage tumors and as a target for the isolation of CTCs in various tumor diseases.

Background: The De Ritis ratio (aspartate aminotransferase [AST]/alanine aminotransferase [ALT]) has demonstrated prognostic value in various cancer entities. We evaluated the prognostic capability of the De Ritis ratio in patients with metastatic neuroendocrine tumors (NET) undergoing peptide receptor radionuclide therapy (PRRT). Methods: Unicentric, retrospective analysis of 125 patients with NET undergoing PRRT with [¹⁷⁷Lu]Lu-DOTATOC (female: 37%; median age: 66 years; G1+G2 NET: 95%). The prognostic value regarding progression-free survival (PFS) was analyzed with univariable and multivariable Cox regression. Prognostic accuracy was determined with Harrell’s C index and a likelihood ratio test. Results: Progression, relapse, or death after PRRT was observed in 102/125 patients. Median progression-free survival (PFS) was 15.8 months. Pancreatic or pulmonary origin, high De Ritis ratio, and high Chromogranin A (CgA) significantly predicted shorter PFS in univariable Cox. In multivariable Cox regression, only high De Ritis ratio >0.927 (HR: 1.7; p = 0.047) and high CgA >twice the upper normal limit (HR: 2.1; p = 0.005) remained independent predictors of shorter PFS. Adding the De Ritis ratio to the multivariable Cox model (age, Eastern Cooperative Oncology Group (ECOG) performance status, primary origin, CgA) significantly improved prognostic accuracy (p < 0.001). Conclusions: The De Ritis ratio is simple to obtain in clinical routine and can provide independent prognostic value for PFS in patients with NET undergoing PRRT.

Selective internal radiation therapy (SIRT) is a therapy option in patients with breast cancer liver metastasis (BCLM). This analysis aimed at identifying a prognostic score regarding overall survival (OS) after SIRT using routine pretherapeutic parameters. Retrospective analysis of 38 patients (age, 59 (39–84) years) with BCLM and 42 SIRT procedures. Cox regression for OS included clinical factors (age, ECOG and prior treatments), laboratory parameters, hepatic tumor load and dose reduction due to hepatopulmonary shunt. Elevated baseline ALT and/or AST was present if CTCAE grade ≥ 2 was fulfilled (>3 times the upper limit of normal). Median OS after SIRT was 6.4 months. In univariable Cox, ECOG ≥ 1 (hazard ratio (HR), 3.8), presence of elevated baseline ALT/AST (HR, 3.8), prior liver surgery (HR, 10.2), and dose reduction of 40% (HR, 8.1) predicted shorter OS (each p < 0.05). Multivariable Cox confirmed ECOG ≥ 1 (HR, 2.34; p = 0.012) and elevated baseline ALT/AST (HR, 4.16; p < 0.001). Combining both factors, median OS decreased from 19.2 months (0 risk factors; n = 14 procedures) to 5.9 months (1 factor; n = 20) or 2.2 months (2 factors; n = 8; p < 0.001). The proposed score may facilitate pretherapeutic identification of patients with unfavorable OS after SIRT. This may help to balance potential life prolongation with the hazards of invasive treatment and hospitalization.

Simultaneous positron-emission tomography (PET)-magnetic resonance (MR) imaging is a hybrid technique in oncological hepatic imaging combining soft-tissue and functional contrast of dynamic contrast enhanced MR (DCE-MR) with metabolic information from PET. In this context, respiratory motion represents a major challenge by introducing blurring, artifacts and misregistration in the liver. In this work, we propose a free-breathing 3D non-rigid respiratory motion correction framework for simultaneously acquired DCE-MR and PET data, which makes use of higher spatial resolution MR data to derive motion information used directly during image reconstruction to minimize image blurring and motion artifacts. The main aim was to increase contrast of hepatic metastases to improve their detection and characterization. DCE-MR data were acquired at 3T through a golden radial phase encoding scheme, enabling derivation of motion fields. These were used in the motion compensated image reconstruction of DCE-MR time-series (48 time-points, 6 s temporal resolution, 1.5 mm isotropic spatial resolution) and 3D PET activity map, which was subsequently interpolated to the DCE-MR resolution. The extended Tofts model was fitted to DCE-MR data, obtaining functional parametric maps related to perfusion such as the endothelial permeability ( K t ). Fifty-seven hepatic metastases were identified and analyzed. Quantitative evaluations of motion correction in PET images demonstrated average percentage increases of 16% ± 5% (mean ± SD) in Contrast ( C ), 18% ± 6% in SUV _mean and 14% ± 2% in SUV _max , while DCE-MR and K t scored contrast-to-noise-ratio increases of 64% ± 3% and 90% ± 6%, respectively. Motion-corrected data visually showed improved image contrast of hepatic metastases and effectively reduced blurring and motion artefacts. Scatter plots of SUV _mean versus K t suggested that the proposed framework improved differentiation of K t measurements. The presented motion correction framework for simultaneously acquired PET-DCE-MR data provides accurately aligned images with increased contrast of hepatic lesions allowing for improved detection and characterization.

Background: in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NET), the mTOR inhibitor everolimus is associated with significant improvement in progression-free survival (PFS). This study evaluated the lesional asphericity (ASP) in pretherapeutic somatostatin receptor (SSR) imaging as the first imaging-based prognostic marker for PFS. Methods: this retrospective bicentric cohort study included 30 patients (f = 13, median age, 66.5 (48–81) years) with pretherapeutic [¹¹¹In-DTPA⁰]octreotide scintigraphy (Octreoscan^®). ASP of functional volumes of up to three leading lesions per patient (n = 74) was calculated after semiautomatic, background-adapted segmentation. Uni- and multivariable Cox regression regarding PFS for clinical factors and the maximum ASP per patient was obtained. Results: all 30 patients showed metachronous or progressive liver metastases. ASP, primary tumor site, metastases pattern, and prior peptide receptor radionuclide therapy (PRRT) were significantly associated with PFS in univariable Cox regression. Only ASP > 12.9% (hazard ratio (HR), 3.33; p = 0.024) and prior PRRT (HR, 0.35; p = 0.043) remained significant in multivariable Cox. Median PFS was 6.7 months for ASP > 12.9% (95% confidence interval (CI), 2.1–11.4 months) versus 14.4 (12.5–16.3) months for ASP ≤ 12.9% (log-rank, p = 0.028). Conclusion: pretherapeutic ASP of SSR positive lesions independently predicted PFS for treatment with everolimus in GEP-NET. ASP may supplement risk-benefit assessment before patient inclusion to treatment.