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.

Background: Pretherapeutic chromogranin A, alkaline phosphatase (ALP), or De Ritis ratio (aspartate aminotransferase/alanine aminotransferase) are prognostic factors in patients with metastatic neuroendocrine tumors (NET) undergoing peptide receptor radionuclide therapy (PRRT). However, their value for intratherapeutic monitoring remains unclear. We evaluated if changes in plasma markers during PRRT can help identify patients with unfavorable outcomes. Methods: A monocentric retrospective analysis of 141 patients with NET undergoing PRRT with [¹⁷⁷Lu]Lu-DOTATOC was conducted. Changes in laboratory parameters were calculated by dividing the values determined immediately before each cycle of PRRT by the pretherapeutic value. Patients with low vs. high PFS were compared with the Wilcoxon rank-sum test. Results: Progression, relapse, or death after PRRT was observed in 103/141 patients. Patients with low PFS showed a significant relative ALP increase before the third (p = 0.014) and fourth (p = 0.039) cycles of PRRT. Kaplan–Meier analysis revealed a median PFS of 24.3 months (95% CI, 20.7–27.8 months) in patients with decreasing ALP values (Δ > 10%) during treatment, 12.5 months (95% CI, 9.2–15.8 months) in patients with increasing ALP values (Δ > 10%), and 17.7 months (95% CI, 13.6–21.8 months) with stable ALP values (Δ ± 10%). Conclusions: Based on these exploratory data, a rise in plasma ALP might indicate disease progression and should be interpreted cautiously during therapy.

Purpose: Therapy with [¹⁷⁷Lu]Lu-DOTATATE is well established for neuroendocrine tumors (NET), but its production generates [^177mLu], raising concerns about waste disposal due to its longer half-life. In contrast, [^177mLu] is not formed during [¹⁷⁷Lu]Lu-DOTATOC production. However, data on overall survival (OS) and prognostic factors for [¹⁷⁷Lu]Lu-DOTATOC remain limited, and its efficacy compared to [¹⁷⁷Lu]Lu-DOTATATE is uncertain. This study aimed to analyze OS and radiological response in NET patients treated with [¹⁷⁷Lu]Lu-DOTATOC. Methods: Monocentric, retrospective analysis of 141 patients with NET (grading: 21% G1, 71% G2, 4% G3, 4% grading unknown; primary: 48% small intestine (SI-NET); 27% pancreas (P-NET); 9% colon/rectum; 1% stomach, 7% lung; 9% CUP-NET) receiving PRRT with [¹⁷⁷Lu]Lu-DOTATOC. Cox and logistic regression were used to identify prognostic factors for OS or risk of primary progression. Results: Death from any cause was observed in 85 of 141 patients (60.3%). Median OS was 55.2 months (SI NET G1-G2: 62.7 months; P-NET G1-G2: 41.2 months; NET G3: 26.3 months). Multivariable Cox regression identified baseline De Ritis Ratio (p < 0.001), ALP (p < 0.001), CgA (p < 0.001) and prior therapy with mTOR-inhibitors (p = 0.005) as significant prognostic factors of OS. Overall response rate was 12% and disease control rate was 72%. In multivariable logistic regression, primary tumor location (p = 0.04) and CgA (p = 0.01) were significant prognostic factors for higher risk of primary progression. Conclusion: The analysis of OS from routine clinical practice shows that PRRT with [¹⁷⁷Lu]Lu-DOTATOC is an effective treatment option for NET patients, while generating minimal [^177mLu]. The evaluated prognostic factors could help to identify patients who particularly benefit from shorter follow-up intervals.

Background/Objectives: Peptide receptor radionuclide therapy (PRRT) is an established treatment for metastatic neuroendocrine tumors (NETs), yet long-term disease control occurs only in a subset of patients. Predicting progression-free survival (PFS) could support individualized treatment planning. This study evaluates laboratory, imaging, and multimodal deep learning models for PFS prediction in PRRT-treated patients. Methods: In this retrospective, single-center study 116 patients with metastatic NETs undergoing [177Lu]Lu-DOTATOC were included. Clinical characteristics, laboratory values, and pretherapeutic somatostatin receptor positron emission tomography/computed tomographies (SR-PET/CTs) were collected. Seven models were trained to classify low- vs. high-PFS groups, including unimodal (laboratory, SR-PET, or CT) and multimodal fusion approaches. Performance was assessed via repeated 3-fold cross-validation with area under the receiver operating characteristic curve (AUROC) and area under the precision–recall curve (AUPRC). Explainability was evaluated by feature importance analysis and gradient based saliency maps. Results: Forty-two patients (36%) displayed short PFS (≤1 year) and 74 patients displayed long PFS (>1 year). Groups were similar in most characteristics, except for higher baseline chromogranin A (p = 0.003), elevated $\gamma$-GT (p = 0.002), and fewer PRRT cycles (p < 0.001) in short-PFS patients. The Random Forest model trained only on laboratory biomarkers reached an AUROC of 0.59 ± 0.02. Unimodal three-dimensional convolutional neural networks using SR-PET or CT performed worse (AUROC 0.42 ± 0.03 and 0.54 ± 0.01, respectively). A multimodal fusion model integrating laboratory values, SR-PET, and CT—augmented with a pretrained CT branch—achieved the best results (AUROC 0.72 ± 0.01, AUPRC 0.80 ± 0.01). Explainability analyses provided insights into model predictions, with explainability patterns in the fusion model appearing physiologically plausible and predominantly tumor-focused. Conclusions: Multimodal deep learning combining SR-PET, CT, and laboratory biomarkers outperformed unimodal approaches for PFS prediction after PRRT. Upon external validation, such models may support risk-adapted follow-up strategies.

Background: Body composition (BC) analysis is performed to quantify the relative amounts of different body tissues as a measure of physical fitness and tumor cachexia. We hypothesized that relative changes in body composition (BC) parameters, assessed by an artificial intelligence–based, PACS-integrated software, between baseline imaging before the start of radioligand therapy (RLT) and interim staging after two RLT cycles could predict overall survival (OS) in patients with metastatic castration-resistant prostate cancer. Methods: We conducted a single-center, retrospective analysis of 92 patients with mCRPC undergoing [¹⁷⁷Lu]Lu-PSMA RLT between September 2015 and December 2023. All patients had [⁶⁸ Ga]Ga-PSMA-11 PET/CT at baseline (≤ 6 weeks before the first RLT cycle) and at interim staging (6–8 weeks after the second RLT cycle) allowing for longitudinal BC assessment. Results: During follow-up, 78 patients (85%) died. Median OS was 16.3 months. Median follow-up time in survivors was 25.6 months. The 1 year mortality rate was 32.6% (95%CI 23.0–42.2%) and the 5 year mortality rate was 92.9% (95%CI 85.8–100.0%). In multivariable regression, relative change in visceral adipose tissue (VAT) (HR: 0.26; p = 0.006), previous chemotherapy of any type (HR: 2.4; p = 0.003), the presence of liver metastases (HR: 2.4; p = 0.018) and a higher baseline De Ritis ratio (HR: 1.4; p < 0.001) remained independent predictors of OS. Patients with a higher decrease in VAT (< −20%) had a median OS of 10.2 months versus 18.5 months in patients with a lower VAT decrease or VAT increase (≥ −20%) (log-rank test: p = 0.008). In a separate Cox model, the change in VAT predicted OS (p = 0.005) independent of the best PSA response after 1–2 RLT cycles (p = 0.09), and there was no interaction between the two (p = 0.09). Conclusions: PACS-Integrated, AI-based BC monitoring detects relative changes in the VAT, Which was an independent predictor of shorter OS in our population of patients undergoing RLT

Ziel/Aim Die [¹⁷⁷Lu]Lu-Peptid-Rezeptor-Radionuklid-Therapie (PRRT) bildet in der Behandlung von metastasierten gastroenteropankreatischen neuroendokrinen Tumoren (GEP-NET) eine effektive Therapie. Dennoch wird ein frühzeitiger Krankheitsprogress in ca. 20-30% der mit PRRT behandelten Pat. verzeichnet. Das Ziel dieser Studie war die Analyse des Stellenwertes eines Interim-Stagings (iStaging) bzgl. der klinischen Weiterbehandlung nach 2 Zyklen PRRT. Methodik/Methods Retrospektive, unizentrische Analyse von 119 Pat. mit gut differenzierten GEP-NET (G1, n=13; G2, n=106) und Behandlung mit [¹⁷⁷Lu]Lu-DOTATOC (Median, 4 [Spannweite, 2-4] Zyklen). Das iStaging [SSR-PET/CT, n=76; SSR-PET/MR, n=18; KM-CT/-MRT+SSR-Szintigraphie, n=25] erfolgte nach 2 Zyklen PRRT und das PFS wurde anhand der RECIST 1.1 Kriterien erhoben. In einem interdisziplinären Setting ist über das weitere therapeutische Prozedere entschieden worden. Für das PFS erfolgten Kaplan-Meier-Analysen. Ergebnisse/Results 83 der 119 Pat. (70%) durchliefen 4 Zyklen PRRT, hingegen wurde die PRRT bei 36 Pat. (30%) nach 2 Zyklen abgebrochen. 27 von 36 Pat. zeigten (75%; 14 SI-NET; 4 CUP-NET; 9 P-NET) im iStaging ein PD, 3 (8%) ein PR (mit chirurg. Therapieanschluss), 5 (14%) Toxizität (Nephrotox., 3; Hämatotox., 1; Tumorlyse-Syndr., 1) und 1 Pat. (3%) ist verstorben. Im Falle eines PD wurde die PRRT abgebrochen und die Pat. einem frühzeitigen Therapiewechsel unterzogen [mTOR, 10 (37%); Chemo, 9 (33%); TKI, 3 (11%); lokalablative Verfahren, 3 (11%); BSC, 2 (7%)]. Pat. mit 4 Zyklen PRRT zeigten ein medianes PFS von 38,0 Monaten (95%-Konfidenzintervall, 30,3-45,7 Monate). [1] [2] Schlussfolgerungen/Conclusions Das iStaging führte in 23% der Pat. zu einem Abbruch der PRRT aufgrund von PD. 3 Patienten konnten einer kurativ intendierten chirurgischen Therapie zugeführt werden. Durch die frühzeitige Selektion im iStaging zeigten Pat. mit 4 Zyklen PRRT ein verlängertes medianes PFS im Vergleich zur Literatur (38,0 vs. 28,4-30,0 Monate; 1,2). Diese Ergebnisse müssen durch weitere Studien validiert werden. Article published online: 30 March 2023 © 2023. Thieme. All rights reserved. Georg Thieme Verlag Rüdigerstraße 14, 70469 Stuttgart, Germany