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Numerous diagnostic and therapeutic innovations in the treatment of advanced prostate cancer, both in the hormone-sensitive and in the castration-resistant situation, recently led to a new orientation in the management of this tumor. However, there are potential indications beyond the ones covered by the S3 guideline on early detection, diagnosis and therapy of prostate cancer in clinical care that might be helpful for patients.Since July 2018, an interdisciplinary group of experts from nuclear medicine, radiologists, radio-oncologists and urologists developed a consensus paper on state-of-the-art innovations in imaging diagnostics and radionuclide-based therapies for advanced prostate cancer.Provided by the working group are suggestions and strategies to improve the implementation of new imaging techniques such as multiparametric magnetic resonance imaging (mpMRI), PSMA-PET/CT (prostate-specific membrane antigen-positron emission tomography/computed tomography) and innovative therapeutic options (radium-223 dichloride, lutetium-177-PSMA) in the complex treatment of metastatic castration-resistant prostate cancer (mCRPC).HINTERGRUND: Die zahlreichen diagnostischen und therapeutischen Innovationen beim fortgeschrittenen Prostatakarzinom, sowohl in der hormonsensitiven als auch in der kastrationsresistenten Situation, haben in den letzten Jahren zu einer Neuorientierung beim Management dieses Tumors geführt. Ungeachtet der bereits in Teilen in der S3-Leitlinie zu Früherkennung, Diagnose und Therapie des Prostatakarzinoms abgebildeten neuen diagnostischen und therapeutischen Methoden, gibt es in der klinischen Versorgung darüber hinaus gehende Fälle, in denen Patienten von diesen innovativen Verfahren potenziell profitieren könnten.Seit Juli 2018 trifft sich deshalb eine interdisziplinäre Expertengruppe aus Nuklearmedizinern, Radiologen, Radioonkologen und Urologen, um ein Konsensuspapier zu Innovationen der bildgebenden Diagnostik und radionuklidbasierten Therapien des fortgeschrittenen Prostatakarzinoms vor dem Hintergrund aktueller Studien und Erfahrungen im klinischen Alltag zu erarbeiten.Der Arbeitskreis gibt Anregungen, um zu einer besseren Implementierung neuer bildgebender Techniken, wie multiparametrische Magnetresonanztomographie (mpMRT), PSMA-PET/CT (prostataspezifisches Membranantigen – Positronenemissionstomographie/Computertomographie) und innovativer therapeutischer Optionen (Radium-223-dichlorid, Lutetium-177-PSMA) bei den komplexen Therapieoptionen des fortgeschrittenen Prostatakarzinoms beizutragen.

Purpose Prostate-specific membrane antigen (PSMA) is present in the proximal tubule cells of the kidneys. This results in high renal tracer uptake in PSMA-PET, which may contain useful information on renal function. As part of the clinical evaluation for [177Lu]-PSMA therapies, patients undergo PSMA-PET and often additional [99mTc]-mercapto-acetyltriglycine (MAG3) scintigraphy to assess renal function. Aim of this study was to evaluate estimation of renal function with [18F]-PSMA-1007-PET/CT (PSMA-PET) by comparison to synchronous MAG3-scintigraphies. Methods We retrospectively investigated 73 prostate cancer patients with 93 synchronously available PSMA-PET/CT, MAG3-scintigraphies and serum creatinine. For determination of split renal function in PSMA-PET/CT, we evaluated the relative unilateral total renal PSMA uptake, i.e. SUVmean multiplied by the renal volume (SRFPSMA-TOTAL) and relative unilateral maximal standardized uptake value (SRFSUV). These were compared to MAG3 split renal function (SRFMAG3) using Pearson correlation and receiver operating characteristics analysis. For determination of global renal function, correlation of bilateral total renal PSMA uptake with MAG3 tubular excretion rate and serum creatinine was assessed. Results SRFMAG3 was strongly correlated with SRFPSMA-TOTAL (r= 0.872, pSUV (r=0.815, pMAG3 (unilateral renal function < 25 %) could be detected with sensitivities and specificities of 90% and 92% for SRFPSMA-TOTAL, and 80% and 95% for SRFSUV. Measures of absolute renal function were only weakly correlated with bilateral total renal PSMA uptake. Conclusion Renal [18F]-PSMA-1007 uptake allowed to quantify renal split function with good accuracy based on SRFPSMA-TOTAL or SRFSUV.

PET imaging using PSMA ligands is increasingly used for staging in prostate cancer patients in different clinical indications. Unlike [

Prostate-specific membrane antigen (PSMA)-based radioligand therapy (RLT) showed in a multicentre WARMTH (World Association of Radiopharmaceutical and Molecular Therapy) study that the presence of bone metastases is a negative prognosticator for the survival. The current multicentre retrospective analysis aims to evaluate the response rate to RLT, the overall survival (OS) of patients and the safety of the treatment according to the extent of bone involvement. The study included patients with progressive metastatic castration-resistant prostate cancer (mCRPC), who underwent RLT with [177Lu]Lu-PSMA-617 and a follow-up of at least 6 months. Tumour burden in the bone was classified prior to RLT as follows: less than 6 lesions, 6–20 lesions, more than 20 lesions and diffuse involvement. The response rate was evaluated using changes of the prostate-specific antigen (PSA) after the first treatment cycle. Overall survival was calculated from the date of the first treatment. Haematological adverse events were classified according to Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. A total of 319 males were included in the analysis. The extent of bone metastases and PSA response did not correlate significantly. Any PSA decline was observed in 73% patients; 44% showed a decline of ≥50%. The median OS of patient in the different subgroups was 18 months (less than 6 lesions), 13 months (6–20 lesions), 11 months (more than 20 lesions) and 8 months (diffuse involvement), respectively (p

The RAdium LUtetium (RALU) study evaluated the feasibility of sequential alpha and beta emitter use in patients with bone-predominant metastatic castration-resistant prostate cancer.This pre-planned, interim, retrospective analysis investigated safety and survival outcomes with lutetium-177-PSMA (Forty-nine patients were evaluated. Patients received a median of 6

Zusammenfassung Hintergrund Mit der zunehmenden Verbreitung der Lu-177-PSMA-RLT zur Behandlung des fortgeschrittenen Prostatakarzinoms ist von Interesse, wie sich die Versorgungssituation mit Blick auf die hierfür nötigen nuklearmedizinischen Therapiebetten angesichts hoher Fallzahlen beim fortgeschrittenen PCa hypothetisch darstellen würde, und ob es hier potenziell zu einem infrastrukturbedingten Engpass für die Patientenversorgung kommen könnte. Methodik Das in deutschen Krankenhäusern verfügbare Angebot an nuklearmedizinischen Therapiebetten wurde dem bei etwaiger Zulassung eines Therapeutikums zur Lu-177-PSMA-RLT als Letztlinientherapie für mCRPC-Patienten perspektivisch insgesamt zu rechnenden nuklearmedizinischen Nachfragepotenzial an Therapiebetten in einer Basiskalkulation gegenübergestellt. Eine mögliche Ausweitung des Lu-PSMA-Indikationsspektrums wurde dabei nicht berücksichtigt. Ergebnisse Nach der Basiskalkulation ergäbe sich bei einer bundesweit aktuellen nuklearmedizinischen Bettenkapazität von ca. 234 000 Behandlungstagen eine rechnerisch geringe Reserve von bundesweit ca. 19 000 nuklearmedizinischen Bettentagen, was umgerechnet einer Reserve von 63 Betten für die interessierende Fragestellung entspricht. Dabei zeigen sich regionale Unterschiede bei der Bettenkapazität: Während sich für einige Bundesländer eine rechnerische Unterkapazität an nuklearmedizinischen Therapiebetten bei Zulassung der Lu-177-PSMA-RLT andeutet, gilt dies für andere Bundesländer weniger. Diskussion Diese Basiskalkulation zeigt, dass die Kapazität nuklearmedizinischer Therapiebetten bei einer etwaig zugelassenen Lu-177-PSMA-RLT für mCRPC sehr gut ausgelastet sein dürfte, in einigen Bundesländern sogar an ihre Grenzen stoßen könnte. Bei einer perspektivischen Ausweitung des Indikationsspektrums oder absehbar klinischen Etablierung weiterer therapeutischer Radiopharmaka könnte die Bettenzahl mittelfristig einen Engpassfaktor für das flächendeckende Behandlungsangebot darstellen.

252 Background: A crucial requirement in prostate cancer (PCa) management is an accurate, easily measurable, liquid biopsy that can define the molecular pathology of an individual PCa. We report the development and clinical validation of a novel PCa-specific, multi-genomic biomarker. Methods: We identified candidate mRNA biomarkers in PCa-Adeno transcriptomes ( n=1,159) using several strategies: co-expression networks, differential expression, and functional enrichment. mRNA transcripts were screened in an independent tumor tissue ( n=50) set and validated as biomarkers in the TCGA-PRAD ( n=500) dataset. An amalgam of Random Forest, Gradient Boosted Machines and Support Vector Machines, all standard machine learning classifiers, was used to develop a classification algorithm and probability score in a peripheral blood gene expression test cohort ( n=430). This multigene biomarker was validated in two independent clinical blood sample sets (Set I: PCa n=77, controls n=54; Set II: PCa n=132, controls/BPH n=99) to determine as PCa-specificity and diagnostic efficacy Clinical utility was evaluated versus Gleason scores, T-staging and PSA ( n=209) and in a prostatectomy cohort ( n=47). Results: The pipeline identified 27 of PCa gene markers in the tumor tissue set and TCGA-PRAD dataset. Gene expression was significantly correlated ( r=0.72, p90%) identifies prostate cancer. It is significantly more accurate than PSA for the detection and stratification of clinically significant prostate disease. A multigenomic liquid biopsy for PCA provides a real-time, non-invasive method for detection of a PCa and may facilitate the early identification of residual/recurrent disease.

386 Background: A critical clinical concern after radical prostatectomy for prostate cancer (PCa) is the timely identification of residual disease. Recurrent disease (biochemical recurrence: BCR) develops in approximately 30% of radical prostatectomies within 5 years of surgery. Currently, clinicopathological variables, including pathological tumor stage (pT-stage), Gleason score and PSA, or algorithmic combinatorial calculations (e.g., CAPRA-S) are used to predict BCR. Early and objective prediction of individuals at high risk of BCR would enable stratification of follow-up strategies and facilitate therapeutic therapy. To achieve these goals, we developed a liquid biopsy, the PROSTest, to identify PCa. This is a 27 multigene algorithmic signature with a high sensitivity and specificity (>90%) for PCa detection. We investigated if the PROSTest had utility as a predictive biomarker for BCR. Methods: Prospective recruitment of 60 PCa for radical prostatectomy with assessment of standard pathological, clinical and biomarker (PSA) data. D’Amico Risk scores and CAPRA-S were calculated. Blood was collected for PROSTest measurement pre-surgery. Target genes were amplified using qPCR and scored (0-100) using algorithmic analysis. Pre-surgical PROSTest scores were evaluated as predictors of BCR and compared with standard criteria as well as DR and CAPRA-S scores. Data was evaluated using Mann-Whitney U-test, multiple regression analyses, Kaplan-Meier survival analysis and Cox-proportional modeling. All data: median (range). Results: Consent was obtained in 48 (80%) patients. Median age (range) was 64 (50-82). Gleason was predominantly 7 (85%; 26: 7A, 15: 7B); TNM was primarily T2c (48%) and T3a (32%) with nodal disease evident in 8% and 0% cM1 disease. Resections were R0 (85%) and 7 R1. The median follow-up was 42 days (range: 14-782). Early BCR occurred in 8 (17%) patients. This included 3/7 (43%) of R1 and 5/41 (12%) R0 resections. PSMA imaging confirmed 3 LN recurrences and new visceral ( n=1) and bone ( n=1) disease. D’Amico Risk scores were mostly “high” (88% with risk score ≥50%) and were not associated with early BCR. CAPRA-S scores were higher in those who developed early BCR (5: 1-9) than in those who did not (2: 0-5). Pre-surgical PROSTest scores were elevated in all (median 59: 15-81). Multiple regression analysis identified only PROSTest score ≥60 and nodal status were associated with BCR. The median Recurrence Free Survival (mRFS) was 89 days compared to undefined in those with baseline PROSTest scores ≥60 (HR: 9.7; 95%CI: 2.16-43.7; p=0.003). No recurrences were identified in those with scores

73 Background: 223Ra and 177Lu-PSMA-617 both prolong overall survival (OS) in different mCRPC settings. The observational, retrospective study, RALU, investigated safety and clinical outcomes of sequential 223Ra/177Lu-PSMA therapy in patients (pts) with mCRPC. This analysis evaluated the association of time interval between 223Ra and 177Lu-PSMA treatments and safety and OS outcomes of 177Lu-PSMA. Methods: Retrospective data were collected from 2021–22 in German nuclear medicine centers for all pts receiving 177Lu-PSMA with prior history of 223Ra therapy. Time intervals were 223Ra dose to first 177Lu-PSMA dose. Results: 42 pts received 177Lu-PSMA within 6 mo after 223Ra (Grp 1) and 90 pts received 223Ra ≥6 mo prior to 177Lu-PSMA (Grp 2). Baseline characteristics prior to 177Lu-PSMA therapy were, respectively: median ages 72 and 74 years; 57% and 63% with Eastern Cooperative Oncology Group performance status (ECOG PS) 1, 43% and 37% with ECOG PS 2; median prostate-specific antigen (PSA) values were 366 and 268 ng/ml, and median alkaline phosphatase (ALP) values were 133 and 149 U/L; 40% and 64% received ≥4 life prolonging therapies before starting 177Lu-PSMA. All pts had prior 223Ra; 57% and 77% received 6 223Ra injections; other prior therapies were abiraterone (60%, 77%), enzalutamide (50%, 78%), docetaxel (71%, 76%) and cabazitaxel (17%, 26%). Prior to 177Lu-PSMA, 24% and 29% of pts had visceral metastases. 45% and 52% of pts received ≥4 177Lu-PSMA cycles. From 177Lu-PSMA start to ≤30 days post last dose, 71% and 82% of pts had treatment-emergent adverse events (TEAEs) of any grade; most common were fatigue (12%, 7%), nausea (12%, 8%) and dry mouth (7%, 18%); 36% and 24% of pts had grade 3–4 TEAEs; excluding laboratory abnormalities, osteonecrosis of the jaw was the most frequent grade 3–4 TEAE (5%, 2%). Grade 3–4 laboratory abnormalities (177Lu-PSMA start to ≤90 days post last dose) are shown; treatment-related deaths were reported for 2% and 4% of pts. AEs led to treatment delays in 10% and 9% of pts. Median OS from start of 177Lu-PSMA was 12.0 mo (95% CI, 8.8–19.9) in Grp 1 and 13.2 mo (95% CI, 10.0–15.9) in Grp 2. During 177Lu-PSMA therapy, PSA response ≥50% occurred in 53% and 39% and ALP response ≥30% in 28% and 14% of pts, respectively. Conclusions: In this real-world setting, treating pts with 177Lu-PSMA within 6 mo of completing 223Ra was clinically feasible and well tolerated: no safety signals or concerns were seen. OS outcomes were similar in pts receiving 177Lu-PSMA 223Ra. [Table: see text]

Background: [¹⁷⁷Lu]-PSMA-617 (Lu-PSMA) therapy is a promising therapeutic option for end-stage prostate cancer patients. Early treatment response at the first restaging after two therapy cycles might correlate with high treatment efficacy and long overall survival (OS). Therefore, the aim of this study was to evaluate whether early reduction in tumor volume is a positive prognosticator for OS. To this end, PSMA PET prior to therapy (baseline) and at first restaging after two therapy cycles (interim; i.e., 12 weeks) were compared. Methods: Patients with metastatic castration-resistant prostate cancer who received Lu-PSMA therapy were reviewed for this analysis. All patients with available baseline and interim [68Ga]-PSMA-11 PET/CT were included in this analysis (n = 33). All PSMA avid metastases in baseline and interim PETs were semi-automatically segmented. The average PSMA expression (mean SUVmax of all metastases), total tumor volume (PSMA-TV) and TLQ (quotients of tumor volume and SUVmean summed over all metastases) were quantified at baseline and interim timepoints. Response in PSMA-TV was assumed when a decline > 30% was present. OS and biochemical response were available for all patients. Results: Baseline PSMA-TV was a statistically significant prognosticator of OS (HR = 1.618 95%CI: 1.117 - 2.343, p = 0.011). Reduction in PSMA-TV was not a statistically significant positive prognosticator of OS in the total cohort (HR = 0.829 95%CI: 0.559 - 1.230, p = 0.352). Likewise, there was no statistical difference in survival time comparing patients with PSMA-TV response to those without (13.2 vs. 15.6 months, p = 0.1). In the subgroup of patients with PSMA-TV response, mean SUVmax was a statistically significant prognosticator of OS (binarized by median; HR = 0.15; 95%CI: 0.03 - 0.83; p < 0.05). If patients with low PSMA expression at baseline were excluded from the analysis, reduction in PSMA-TV became a positive prognosticator of OS in uni- and multivariable Cox regression (HR = 0.290; 95%CI: 0.108 - 0.782; p = 0.015). Conclusion: PSMA-TV reduction was a positive prognosticator of OS only if patients with low PSMA expression were excluded. This might indicate that the PSMA-PETs of patients with low PSMA expression may not be suited for assessing PSMA-TV reduction. Future studies investigating the interplay of PSMA-TV and low PSMA expression response are warranted. CA Extern

Objective Surgical resection is the therapy of choice in head and neck paraganglioma but is associated with considerable morbidity. For treatment of inoperable or progressive disease, less aggressive adjuvant options are warranted. This study assessed effectiveness and safety of peptide receptor radionuclide therapy (PRRT) with lutetium-177–DOTATATE for head and neck paraganglioma with emphasis on response assessment. Methods A retrospective analysis of 7 patients with head and neck paraganglioma treated with PPRT between May 2014 and October 2016 was performed. Three patients had jugulotympanic paraganglioma, 3 patients had carotid body tumors, and 1 patient had a combination of both. Patients underwent PRRT after discussion in the local tumor board regarding progressive disease, inoperability, or lack of other adjuvant options. All patients underwent 3–5 cycles of PRRT. Treatment response was evaluated by gallium-68–DOTATATE positron emission tomography/computed tomography and contrast-enhanced computed tomography or magnetic resonance imaging. Outcome measures were two-dimensional tumor diameters and total tumor volumes. Results Median patient age was 60 years (interquartile range: 14–84 years). All patients had stable disease at posttherapy assessment. Decreasing tumor volumes were found in 4 patients. Clinical symptoms improved in 2 patients. No progression or adverse events occurred during a median follow-up of 39 months (interquartile range: 35–47 months). Conclusions Somatostatin receptor–targeted therapy using lutetium-177-DOTATATE shows promising effectiveness with a high safety profile. Patients in whom surgical morbidity outweighs oncologic benefit should be informed about PRRT as a treatment option.

Biomarker in metastatic castration resistant prostate cancer (mCRPC) treatment are rare. We aimed to compare the clinical value of circulating tumor cells (CTCs) and androgen receptor splice variant 7 (AR-V7) as biomarker in mCRPC patients undergoing androgen receptor-targeted agent (ARTA) treatment. Overall cohort (65 patients) was stratified regarding either CTC or AR-V7 status followed by further sub-stratification of the respective other marker. Subsequently, prostate specific antigen (PSA) response, progression free survival (PFS) and overall survival (OS)) of subgroups was compared. CTCs and AR-V7 were detected in 54 (83%) and 33 (61%) patients, respectively. All AR-V7 + were CTC +. We detected PSA response in all subgroups. For PFS and OS, biomarker stratification revealed differences between all subgroups. Interestingly, no significant differences of AR-V7 transcript copy numbers were detected between responding and non-responding patients. Additionally, multivariable analysis revealed no independent prognostic value of AR-V7 positivity. Both biomarkers show clinical value in prognosticating clinical outcome. Nonetheless, AR-V7 stratification underestimates the heterogenous subgroup of CTC - and CTC + patient, the latter requiring more intense clinical surveillance. Additionally, AR-V7 level does not correlate with clinical response. Thus, the value of AR-V7 as a clinical biomarker must be considered skeptically.

Introduction [177Lu]Lu-PSMA-617 (Lu-PSMA) radioligand therapy is an emerging treatment option for patients with end-stage prostate cancer. However, response to Lu-PSMA therapy is only achieved in approximately half of patients. It is clinically important to identify patients at risk of poor outcome. Therefore, the aim of this study was to evaluate pretherapeutic PSMA PET derived total tumor volume and related metrics as prognosticators of overall survival in patients receiving Lu-PSMA therapy. Methods A total number of 110 patients form the Departments of Nuclear Medicine Münster and Essen were included in this retrospective analysis. Baseline PSMA PET-CT was available for all patients. Employing a previously published approach, all tumor lesions were semi-automatically delineated in PSMA PET-CT acquisitions. Total lesion number, total tumor volume (PSMA-TV), total lesion uptake (PSMA-TLU = PSMA-TV * SUVmean), and total lesion quotient (PSMA-TLQ = PSMA-TV / SUVmean) were quantified for each patient. Log2 transformation was used for regressions. Results Lesion number, PSMA-TV, and PSMA-TLQ were prognosticators of overall survival (HR = 1.255, p = 0.009; HR = 1.299, p = 0.005; HR = 1.326, p = 0.002). In a stepwise backward Cox regression including lesion number, PSMA-TV, PSA, LDH, and PSMA-TLQ, only the latter two remained independent and statistically significant negative prognosticators of overall survival (HR = 1.632, p = 0.011; HR = 1.239, p = 0.024). PSMA-TLQ and LDH were significant negative prognosticators in multivariate Cox regression in contrast to PSA value. Conclusion PSMA-TV was a statistically significant negative prognosticator of overall survival in patients receiving Lu-PSMA therapy. PSMA-TLQ was an independent and superior prognosticator of overall survival compared with PSMA-TV.

Prostate-specific membrane antigen (PSMA)-ligand PET/CT is performed on patients with prostate cancer to stage the disease initially or to identify sites of recurrence after definitive therapy. On the basis of clinical results, 18F-PSMA-1007 is a promising PSMA PET tracer, but detailed histologic confirmation has been lacking. Methods: Ninety-six patients with prostate cancer underwent 18F-PSMA-1007 PET/CT followed by either radical prostatectomy with lymphadenectomy or salvage lymphadenectomy. The histologic findings of PSMA PET-positive nodes were analyzed retrospectively. A lesion-based and patient-based analysis was performed comparing all positive lesions and only lesions larger than 3 mm on histopathology. Results: Of the patients, 90.6% received 18F-PSMA-1007 PET/CT for staging before the primary treatment, whereas 9.4% underwent imaging for biochemical recurrence. In 34.4% of the cohort, positive lymph nodes were present on imaging. In total, 1,746 lymph nodes were dissected in 96 patients. 18F-PSMA-1007 PET had a lesion-based sensitivity of 81.7%, a specificity of 99.6%, a positive predictive value of 92.4%, and a negative predictive value of 98.9% for detecting positive lymph nodes larger than 3 mm. In the analysis of all malignant nodes regardless of size, the overall sensitivity, specificity, positive predictive value, and negative predictive value on lesion-based analysis were 71.2%, 99.5%, 91.3%, and 97.9%, respectively. The patient-based analysis showed a sensitivity of 85.9% and a specificity of 99.5% for lymph nodes larger than 3 mm. Conclusion:18F-PSMA-1007 PET/CT reliably detects malignant lymph nodes and has an exceptional specificity of more than 99% for nodal metastases.

Neuroendokrine Tumoren (NET) entstehen aus dem Neuroektoderm und konnen in den verschiedensten Organen des Korpers lokalisiert werden. Am haufigsten ist ihr Auftreten im gastroenteropankreatischen System. Die Heterogenitat dieser Tumorentitat sowie die zahlreichen Lokal- bzw. Systemtherapien fuhren zu einer Vielzahl von unterschiedlichen Behandlungsoptionen. Auch die Ziele einer Therapie konnen unterschiedlich sein: Sie reichen von einem kurativen Ansatz uber Kontrolle des Tumorwachstums und dem Verhindern von lokalen obstruktiven Beschwerden (z. B. bei Dunndarm-NETs) bis hin zur Kontrolle von durch vermehrte Sekretion von Peptidhormonen/-aminen ausgelosten Symptomen. Diese Ubersichtsarbeit stellt die wichtigsten Neuerungen in der Klassifikation der neuroendokrinen Neoplasien vor, insbesondere die Unterscheidung von NET-G3-Tumoren und neuroendokrinen Karzinomen (NEC). Vorgestellt werden die Optionen einer operativen Therapie, welche immer zuerst gepruft werden sollte, lokal ablativer Verfahren, die vor allem Anwendung bei kleinen (

Introduction The impact of prior therapies, especially chemotherapy, on overall survival (OS) in patients with castration-resistant prostate cancer (CRPC) receiving [177Lu]Lu-PSMA-617 therapy has been the subject of controversy. Therefore, WARMTH decided to plan a multicenter retrospective analysis (the “617 trial”) to evaluate response rate and OS as well as the impact of prior therapies on OS in more than 300 patients treated with 177Lu-PSMA-617. Materials and methods The data of 631 metastatic CRPC (mCRPC) patients from 11 different clinics were evaluated. According to the inclusion and exclusion criteria, all patients had to have received at least abiraterone or enzalutamide prior to [177Lu]Lu-PSMA-617 therapy. The patients were divided into three groups: patients who had received prior chemotherapy, patients who avoided chemotherapy, and patients for whom a chemotherapy was contraindicated. Results The analysis included the data of 416 patients, with a median age of 71.9 years. At the time of analysis, 87 patients (20,9%) were still alive. A total of 53.6% of patients had received both abiraterone and enzalutamide; 75.5% and 26.4% had a history of chemotherapy with docetaxel and cabazitaxel, respectively. A total of 20.4% had had Ra-223. The median OS was 11.1 months. Prior chemotherapy, the existence of bone and liver metastases, as well as Eastern Cooperative Oncology Group (ECOG) status, were significant prognosticators of worse overall survival in both univariate and multivariate analyses. Patients without any prior chemotherapy showed a significantly longer OS (14.6 months). The median OS in patients who received one or two lines of chemotherapy with docetaxel or docetaxel followed by cabazitaxel, respectively, was 10.9 months and 8.9 months. There was no difference in OS between patients who had not received chemotherapy and patients for whom chemotherapy was contraindicated. The other prior therapies did not have any significant impact on OS. Conclusion In the present multicenter analysis, chemotherapy-naïve mCRPC patients receiving [177Lu]Lu-PSMA-617 therapy had a significantly longer OS than patients with a history of chemotherapy. This remained independent in the multivariate analysis besides presence of bone and liver metastases as negative prognosticators for survival, whereas an ECOG of 0–1 is associated with a longer OS.

Das metastasierte kastrationsresistente Prostatakarzinom (mCRPC) kann durch Fortschritte in den letzten Jahren immer besser behandelt werden. Hierbei kommen Substanzen zum Einsatz, die effektiv die Androgenrezeptorachse blockieren, verschiedene Chemotherapeutika sowie das Radiopharmakon 223Radium. Trotzdem kommt es regelhaft zu primarer und sekundarer Resistenzbildung gegen samtliche Therapieoptionen. Daher werden neue Therapieansatze dringend benotigt. Die 177Lutetium-PSMA- (prostataspezifisches Membranantigen‑)Radioligandentherapie (177Lu-PSMA-RLT) stellt eine gute Reserveoption dar, welche bei noch fehlender Zulassung in individuellen Heilversuchen mit vielversprechenden Erfolgen eingesetzt werden kann. In diesem Beitrag wird eine Standortbestimmung der 177Lu-PSMA-RLT beim mCRPC 2020 beschrieben. Die Therapielandschaft beim mCRPC und der aktuellen Evidenz der 177Lu-PSMA-RLT nach PubMed-Recherche werden dargestellt. In verschiedenen, teils umfangreichen retrospektiven Arbeiten und in ersten prospektiven Studien zeigt sich die 177Lu-PSMA-RLT bei einem Teil der Patienten als vielversprechende Reservetherapie. Das Toxizitatsprofil stellt sich auch im Vergleich zu anderen Therapieoptionen beim mCRPC als gunstig dar. Die Phase-III-Zulassungsstudie VISION ist weit fortgeschritten und konnte zur Zulassung der 177Lu-PSMA-RLT in Kombination mit Abirateron oder Enzalutamid nach Vorbehandlung mit Enzalutamid oder Abirateron und Chemotherapie mit Docetaxel fuhren. Trotz der hoffnungsvollen Ansatze mussen die Ergebnisse der VISION-Studie vor dem breiten Einsatz der 177Lu-PSMA-RLT abgewartet werden. Bis dahin sollten nur Patienten im Sinne von individuellen Heilversuchen und den hierzu geltenden Regeln behandelt werden.

Introduction Efficient therapy of recurrent differentiated thyroid cancer (DTC) is dependent on precise molecular imaging techniques targeting the human sodium iodide symporter (hNIS), which is a marker both of thyroid and DTC cells. Various iodine isotopes have been utilized for detecting DTC; however, these come with unfavorable radiation exposure and image quality ([131I]iodine) or limited availability ([124I]iodine). In contrast, [18F]tetrafluoroborate (TFB) is a novel radiolabeled PET substrate of hNIS, results in PET images with high-quality and low radiation doses, and should therefore be suited for imaging of DTC. The aim of the present study was to compare the diagnostic performance of [18F]TFB-PET to the clinical reference standard [131I]iodine scintigraphy in patients with recurrent DTC. Methods Twenty-five patients with recurrent DTC were included in this retrospective analysis. All patients underwent [18F]TFB-PET combined with either CT or MRI due to newly discovered elevated TG levels, antiTG levels, sonographically suspicious cervical lymph nodes, or combinations of these findings. Correlative [131I]iodine whole-body scintigraphy (dxWBS) including SPECT-CT was present for all patients; correlative [18F]FDG-PET-CT was present for 21 patients. Histological verification of [18F]TFB positive findings was available in 4 patients. Results [18F]TFB-PET detected local recurrence or metastases of DTC in significantly more patients than conventional [131I]iodine dxWBS and SPECT-CT (13/25 = 52% vs. 3/25 = 12%, p = 0.002). The diagnosis of 6 patients with cervical lymph node metastases that showed mildly increased FDG metabolism but negative [131I]iodine scintigraphy was changed: [18F]TFB-PET revealed hNIS expression in the metastases, which were therefore reclassified as only partly de-differentiated (histological confirmation present in two patients). Highest sensitivity for detecting recurrent DTC had the combination of [18F]TFB-PET-CT/MRI with [18F]FDG-PET-CT (64%). Conclusion In the present cohort, [18F]TFB-PET shows higher sensitivity and accuracy than [131I]iodine WBS and SPECT-CT in detecting recurrent DTC. The combination of [18F]TFB-PET with [18F]FDG-PET-CT seems a reasonable strategy to characterize DTC tumor manifestations with respect to their differentiation and thereby also individually plan and monitor treatment. Future prospective studies evaluating the potential of [18F]TFB-PET in recurrent DTC are warranted.

Background Radioligand therapy with [177Lu]Lu-PSMA-617 is efficacious for the treatment of patients with metastasized castration-resistant prostate cancer (mCRPC). Various studies have evaluated the efficacy and safety of [177Lu]Lu-PSMA-617 using a dose of 6.0 GBq and an 8-week therapy interval. However, the first prospective phase III trial (VISION) plans to use an elevated cumulative dose by applying 7.5 GBq in a 6-week interval. The aim of the present study was to compare safety and efficacy of the two aforementioned [177Lu]Lu-PSMA-617 therapy regimes (7.5 GBq every 6 weeks vs. 6.0 GBq every 8 weeks). Methods A total number of 78 consecutive patients with mCRPC and a history of first-line chemotherapy were included in this retrospective analysis. The outcome of patients treated with 6.0 GBq [177Lu]Lu-PSMA-617 per cycle (n = 37) were compared with those treated with 7.5 GBq (n = 41) per cycle. The median therapy intervals were 8.4 weeks (6.0 GBq group) vs. 6.5 (7.5 GBq group). PSA response, PSA progression-free survival (PSA-PFS), overall survival, and adverse events were evaluated and compared between both groups. Chi-squared test, Kaplan Meier estimates, Cox regression, and log-rank test were used. The highest decline from pretherapeutic PSA levels was measured as percentage (best PSA response) and compared between groups by Wilcoxon test. Results There was no significant difference comparing the rate of > 50% PSA decline or best PSA response between the 6.0 GBq and 7.5 GBq group (35% vs. 54%, p = 0.065; and − 40.2% vs. − 57.8%, p = 0.329). The median estimated survival and PSA-PFS did not significantly differ between the 6.0 GBq and 7.5 GBq groups as well (11.3 vs. 12.7 months, p = 0.384; and 9.5 vs. 12.3 months, p = 0.258). There was no significant difference regarding the change of kidney, liver, and blood cell parameters under therapy between the treatment groups. Conclusion Higher cumulated doses of [177Lu]Lu-PSMA-617 were well tolerated and caused no significantly increased rate of adverse reactions. Moreover, 7.5 GBq of [177Lu]Lu-PSMA-617 every 6 weeks causes slightly higher, though not statistically significant, response rates and seems therefore to be the preferable treatment regime. However, future studies are needed to elucidate the dose-related efficacy of [177Lu]Lu-PSMA-617 as a way to personalized medicine.

Among the prevalent approaches in image's region segmentation, illumination level probability distribution function has been given prominent attention. Normally, there is a constant definition of illumination level probability distribution function in the basic forms of the mentioned approach. This constant definition causes the algorithms in this area encounter a severe challenge. This paper presents the use of Krawtchouk polynomial to improve the estimation of the intensity illumination function. The orthogonal terms of the Krawtchouk polynomial are considered as eigen functions of differential equations. They provide a more stable estimation in describing the image's illumination levels differentiations against environmental noises. Therefore, utilizing image stabilization functions, such as Gaussian two-dimensional filters are reduced. As a consequence, the Krawtchouk polynomial is an appropriate estimator of the illumination function for the foreground and background object in a wide variety of images. Verification results on synthesis and natural images conformed the proposed claim. The results suggest that both the proposed approach and best current solutions function are equally in the noise-free environment rather than environmental noises. Nevertheless, in the presence of imposing noise, the proposed approach maintains its accuracy and stability.

In patients with bone metastatic castration-resistant prostate cancer (bmCRPC) on systemic treatment, it is difficult to differentiate between continuous rise of prostate specific antigen (PSA) representing progression, and PSA-surge, which is followed by clinical response or stable disease. The purpose of this study was to evaluate the prognostic value of dynamic changes of alkaline phosphatase (ALP) and lactic acid dehydrogenase (LDH) levels as a predictor of clinical efficacy or therapeutic resistance of patients who do not show a sufficient initial PSA decline of ≥50% from baseline during early therapy with Enzalutamide.Forty-eight men with bmCRPC on Enzalutamide 07/2010-09/2019 with initially rising PSA were analyzed. We monitored PSA, LDH and ALP at week 0, 2, 4, and every 4 weeks thereafter and analyzed the correlation between ALP rising at 12 weeks with or without LDH-normalization and the association with survival. For this we used Kaplan Meier analysis and uni- and multivariate cox-regression models.In Kaplan-Meier analysis, ALP rising at 12 weeks with or without LDH-normalization was associated with significantly worse median progression-free survival (PFS) of 3 months vs. 5 months (Log rank P = 0.02) and 3 months vs. 5 months (P = 0.01), respectively and overall survival (OS) with 8 months vs. 15 months (P = 0.02) and 8 months vs. 17 months (P 0.01). In univariate analysis of PFS, ALP rising at 12 weeks alone, ALP rising at 12 weeks without LDH-normalization and application of Enzalutamide after chemotherapy showed a statistically significant association towards shorter PFS (hazard ratio (HR): 0.51, P = 0.04; HR: 0.48, P = 0.03; HR: 0.48, P = 0.03). Worse OS was significantly associated with ALP rising at 12 weeks alone, ALP rising at 12 weeks without LDH-normalization, and application of Enzalutamide after chemotherapy (HR: 0.47, P = 0.02; HR: 0.36, P 0.01; HR: 0.31, P 0.01). In multivariate analysis only the application of Enzalutamide after chemotherapy remained an independent prognostic factor for worse OS (HR: 0.36, P = 0.01).Dynamic changes of ALP (non-rise) and LDH (normalization) under therapy with Enzalutamide may be associated with clinical benefit, better PFS, and OS in patients with bmCRPC who do not show a PSA decline.

Simple Summary PSMA Therapy has recently become an additional therapeutic option in advanced prostate cancer. In the present study, the predictive and prognostic value of radiomic features from pretherapeutic PSMA PET-MRI are analyzed. Twenty-one patients with advanced prostate cancer underwent PSMA-therapy, including pretherapeutic PSMA PET-MRI. Radiomic features from PET- and MRI-sequences were extracted and processed to select the features differentiating responders and non-responders. Out of ten independent radiomic features differentiating between these two groups, the feature interquartile range from the T2 weighted images revealed the highest accuracy. PSA response and higher T2 interquartile range values might have impact on survival. This proof-of-concept study applies radiomic analysis to pretherapeutic PSMA PET-MRI before PSMA therapy, providing new parameters with potential predictive and prognostic value. Abstract 177Lutetium PSMA-617 (Lu-PSMA) therapy in patients with metastatic castration resistant prostate cancer (mCRPC) has gained visibility through the ongoing phase III trial. The data on prediction of therapy outcome and survival out of pretherapeutic imaging parameters is still sparse. In this study, the predictive and prognostic value of radiomic features from 68Ga-PSMA-11 PET-MRI are analyzed. In total, 21 patients with mCRPC underwent 68Ga-PSMA-11 PET-MRI before Lu-PSMA therapy. The PET-positive tumor volume was defined and transferred to whole-body T2-, T1- and contrast-enhanced T1-weighted MRI-sequences. The radiomic features from PET and MRI sequences were extracted by using a freely available software package. For selecting features that allow differentiation of biochemical response (PSA decrease > 50%), a stepwise dimension reduction was performed. Logistic regression models were fitted, and selected features were tested for their prognostic value (overall survival) in all patients. Eight patients achieved biochemical response after Lu-PSMA therapy. Ten independent radiomic features differentiated well between responders and non-responders. The logistic regression model, including the feature interquartile range from T2-weighted images, revealed the highest accuracy (AUC = 0.83) for the prediction of biochemical response after Lu-PSMA therapy. Within the final model, patients with a biochemical response (p = 0.003) and higher T2 interquartile range values in pre-therapeutic imaging (p = 0.038) survived significantly longer. This proof-of-concept study provides first evidence on a potential predictive and prognostic value of radiomic analysis of pretherapeutic 68Ga-PSMA-11 PET-MRI before Lu-PSMA therapy.

Prostate-specific membrane antigen-PET/computed tomography (PSMA-PET/CT) is the investigation of choice for imaging prostate cancer. Demonstrating high diagnostic accuracy, PSMA-PET/CT detects disease at very early stages of recurrence, where the chances of a definitive cure may be at their greatest. A number of PSMA-radioligands are in established clinical routine, and there are currently only limited data and no single tracer can clearly be advocated over the others at present. Further clinical trial data, comparing and contrasting radiotracers and reporting outcome-based data are necessary to further increase the implementation of this very promising imaging modality.

Prostate-specific membrane antigen (PSMA) has been the subject of numerous studies within the last 3 decades. PSMA-targeted imaging and therapy have significantly changed the management of patients with prostate cancer in various disease stages, especially in advanced metastasized castration-resistant prostate cancer. Lutetium-177-conjugated PSMA-617 or PSMA-IT (Lu-PSMA) has shown promising results in multicenter retrospective and monocenter prospective trials. The aim of this review is to provide an overview of the history and current and future developments of PSMA-targeted therapy. A special focus of this review is on PSMA PET-guided management of patients receiving PSMA-targeted radioligand therapy.

PURPOSE Dual-time point PET/CT scanning with [68Ga]Ga-PSMA-11 in the diagnosis of prostate cancer (PC) has been advanced as a method to increase detection of PC lesions, particularly at early stages of biochemical recurrence and as a potential means to aid the discrimination between benign and pathological prostate-specific membrane antigen (PSMA) uptake. However, the assumption that all PC lesions uniformly exhibit increasing tracer uptake at delayed imaging has not yet been investigated, which this present study aims to address. METHODS One hundred consecutive patients with biochemically recurrent PC who received standard and late [68Ga]Ga-PSMA-11 PET/CT (by local protocol at 1.5 h "standard" and 2.5 h p.i. "late") underwent retrospective evaluation. All lesions with a tracer uptake above local background were analysed with regard to their maximum standardised uptake values at standard and late images (SUVmax) and characterised according to their morphological characteristics. RESULTS Seventy-nine of 100 patients had PSMA-positive scans, in whom a total of 185 individual PSMA-positive lesions were identified. These were morphologically characterised as bone lesions (n = 48), solid organ lesions (n = 3), lymph node (LN) lesions (n = 78) and locally recurrent lesions in the prostatic fossa or seminal vesicles (n = 56). The relative uptake between standard and late imaging was considered; all lesions classified as local recurrence presented with increasing (86%) or stable patterns of tracer uptake (14%). In contrast, only 58% of bone lesions exhibited increasing tracer uptake, with 21% exhibiting a stable pattern and 21% exhibiting a decreasing tracer uptake at late imaging. CONCLUSION A heterogeneous pattern of dynamic tracer uptake was observed, with a largely increasing pattern observed for locally recurrent lesions and lymph nodes and a significant proportion of bone lesions exhibiting decreasing tracer uptake. The results are of significance not only in the imaging and identification of PC lesions, but they also have implications for PSMA-directed ligand therapy.

Prostate-specific membrane antigen (PSMA) is expressed in most prostate cancers and can be identified by PSMA-ligand imaging, which has already become clinically accepted in several countries in- and outside Europe. PSMA-directed radioligand therapy (PSMA-RLT) with Lutetium-177 (177Lu-PSMA) is currently undergoing clinical validation. Retrospective observational data have documented favourable safety and striking clinical responses. Recent results from a prospective clinical trial (phase II) have been published confirming high response rates, low toxicity and reduction of pain in metastatic castration-resistant prostate cancer (mCRPC) patients who had progressed after conventional treatments. Such patients typically survive for periods less than 1.5 years. This has led some facilities to adopt compassionate or unproven use of this therapy, even in the absence of validation within a randomised-controlled trial. As a result, a consistent body of evidence exists to support efficacy and safety data of this treatment. The purpose of this guideline is to assist nuclear medicine specialists to deliver PSMA-RLT as an "unproven intervention in clinical practice", in accordance with the best currently available knowledge.

5002 Background: In the phase 3 VISION study, gallium (68Ga) gozetotide (68Ga-PSMA-11) PET/CT imaging was used to determine eligibility for lutetium (177Lu) vipivotide tetraxetan (177Lu-PSMA-617). Given that 177Lu-PSMA-617 targets PSMA, we assessed the association between quantitative PSMA imaging parameters and treatment outcomes. Methods: In VISION, adults with mCRPC with ≥ 1 PSMA-positive (+) and no PSMA-negative lesions meeting the exclusion criteria were enrolled. In this sub-study, the association between imaging data from pre-enrollment 68Ga-PSMA-11 PET/CT scans of pts in the 177Lu-PSMA-617 group and clinical outcomes was assessed. Imaging data meeting quality requirements were analyzed for 548/551 pts. PSMA expression was quantified by 5 PET parameters: PSMA+ lesions by region, mean standardized uptake value (SUVmean), maximum SUV (SUVmax), PSMA+ tumor volume, and tumor load (PSMA+ tumor volume × SUVmean). Parameters were extracted from the whole body and 4 regions. Association between PET parameters and radiographic progression-free survival (rPFS; primary objective), overall survival (OS), objective response rate (ORR), and prostate–specific antigen 50 (PSA50) response was assessed. Results: Most pts (92.7%) had PSMA uptake in bone. In both the whole-body and regional analyses, statistically significant associations of PSMA PET parameters to clinical outcomes were observed (whole-body data shown in Table). Higher whole-body SUVmean was associated with improved clinical outcomes; pts in the highest quartile (SUVmean: rPFS, ≥ 10.2; OS, ≥ 9.9) had a median rPFS and OS of 14.1 and 21.4 months, vs 5.8 and 14.5 months for those in the lowest quartile (< 6.0; < 5.7), respectively. Absence of PSMA+ lesions in bone, liver, and lymph node, and lower PSMA+ tumor load, were indicators of good prognosis. Conclusions: Higher SUVmean is strongly associated with improved outcomes with 177Lu-PSMA-617; clinical efficacy for different SUV levels vs the SoC arm is being assessed. Data support use of 68Ga-PSMA-11 PET/CT scan to identify pts who will benefit from PSMA-targeted radioligand therapy.[Table: see text]

BACKGROUND: Metastatic castration-resistant prostate cancer remains fatal despite recent advances. Prostate-specific membrane antigen (PSMA) is highly expressed in metastatic castration-resistant prostate cancer. Lutetium-177 ((177)Lu)–PSMA-617 is a radioligand therapy that delivers beta-particle radiation to PSMA-expressing cells and the surrounding microenvironment. METHODS: We conducted an international, open-label, phase 3 trial evaluating (177)Lu-PSMA-617 in patients who had metastatic castration-resistant prostate cancer previously treated with at least one androgen-receptor–pathway inhibitor and one or two taxane regimens and who had PSMA-positive gallium-68 ((68)Ga)–labeled PSMA-11 positron-emission tomographic–computed tomographic scans. Patients were randomly assigned in a 2:1 ratio to receive either (177)Lu-PSMA-617 (7.4 GBq every 6 weeks for four to six cycles) plus protocol-permitted standard care or standard care alone. Protocol-permitted standard care excluded chemotherapy, immunotherapy, radium-223 ((223)Ra), and investigational drugs. The alternate primary end points were imaging-based progression-free survival and overall survival, which were powered for hazard ratios of 0.67 and 0.73, respectively. Key secondary end points were objective response, disease control, and time to symptomatic skeletal events. Adverse events during treatment were those occurring no more than 30 days after the last dose and before subsequent anticancer treatment. RESULTS: From June 2018 to mid-October 2019, a total of 831 of 1179 screened patients underwent randomization. The baseline characteristics of the patients were balanced between the groups. The median follow-up was 20.9 months. (177)Lu-PSMA-617 plus standard care significantly prolonged, as compared with standard care, both imaging-based progression-free survival (median, 8.7 vs. 3.4 months; hazard ratio for progression or death, 0.40; 99.2% confidence interval [CI], 0.29 to 0.57; P

Purpose The aim of this narrative review is to give an overview on current and emerging imaging methods and liquid biopsy for prediction and evaluation of response to PRRT. Current limitations and new perspectives, including artificial intelligence, are discussed. Methods A literature review of PubMed/Medline was performed with representative keywords. The search included articles published online through August 31, 2020. All searches were restricted to English language manuscripts. Results Peptide radio receptor therapy (PRRT) is a prospectively evaluated and approved therapy option in neuroendocrine tumors (NETs). Different ligands targeting the somatostatin receptor (SSTR) are used as theranostic pairs for imaging NET and for PRRT. Response assessment in prospective trials often relies on the morphological RECIST 1.1 criteria, based on lesion size in CT or MRI. The role of SSTR-PET and quantitative uptake parameters and volumetric data is still not defined. Monoanalyte tumor marker chromogranin A has a limited value for response assessment after PRRT. New emerging liquid biopsy techniques are offering prediction of response to PRRT and prognostic value. Conclusions New response criteria for NET patients undergoing PRRT will comprise multiparametric hybrid imaging and blood-based multianalyte markers. This represents tumor biology and heterogeneity.

Prostate-specific membrane antigen (PSMA)-based radioligand therapy (RLT) showed in a multicentre WARMTH (World Association of Radiopharmaceutical and Molecular Therapy) study that the presence of bone metastases is a negative prognosticator for the survival. The current multicentre retrospective analysis aims to evaluate the response rate to RLT, the overall survival (OS) of patients and the safety of the treatment according to the extent of bone involvement.The study included patients with progressive metastatic castration-resistant prostate cancer (mCRPC), who underwent RLT with [A total of 319 males were included in the analysis. The extent of bone metastases and PSA response did not correlate significantly. Any PSA decline was observed in 73% patients; 44% showed a decline of ≥50%. The median OS of patient in the different subgroups was 18 months (less than 6 lesions), 13 months (6-20 lesions), 11 months (more than 20 lesions) and 8 months (diffuse involvement), respectively (p 0.0001). Patients with prior Ra-223-therapy showed longer OS in all subgroups, especially in the subgroups with 6-20 lesions (OS: 16 vs. 12 months; p = 0.038) as well as diffuse involvement (OS: 11 vs. 7 months; p = 0.034). Significant negative prognosticators of OS were the existence of liver metastases in all subgroups and prior chemotherapy in patients with6 bone lesions. Anaemia and thrombocytopenia correlated positively with the extent of bone metastases: p 0.0001 and 0.005, respectively. No patient showed a high grade leukopenia.The extent of bone involvement correlated negatively with the OS after RLT; however, it showed no relevant correlation with the PSA response rate. Prior therapy with Ra-223 may have a positive impact on OS. Haematotoxicity was higher in patients with more than 20 bone lesions; nevertheless, the majority of these patients did not show a relevant haematotoxicity.

The role of cranio-spinal irradiation (CSI) for primary extraosseous intraspinal Ewing sarcoma (EwS) remains unclear. Here, we evaluate clinical and survival outcomes in patients with primary intraspinal EwS treated with CSI as part of multimodal primary therapy regimens. We abstracted patient information, including details on treatment application, efficacy, and tolerance from the literature and our hospital database for a cohort of 24 primary intraspinal EwS patients treated with CSI. Median age was 25.5 years, median CSI dose was 36 Gy and mean boost dose was 12.8 Gy. Sixteen patients (66.7%) achieved complete radiological remission, another 5 patients demonstrated partial response and 1 patient showed no response to treatment. Compared to a cohort of patients treated with focal radiotherapy, CSI patients were more likely to have multifocal disease at time of diagnosis (p = 0.001) and intradural tumor location (p < 0.001). Despite over-representation of these unfavorable characteristics, there was no survival difference between groups (p = 0.58). While CSI shows promising results in the treatment of primary intraspinal EwS, treatment should be considered individually based on tumor and patient characteristics in the absence of prospective trials.

The aim of the review was to evaluate patient and treatment characteristics for patients with metastatic castration-resistant prostate cancer (mCRPC) treated with PSMA radioligand therapy (PRLT) associated with above-average outcome. The systematic review and meta-analysis followed recommendations by the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA). We searched for publications in PubMed, Embase, and ClinicalTrials.gov up to 31 September 2020. Thirty-six publications and four duplicates reported 2346 patients. Nearly two-thirds of the patients had bone metastases. Median overall survival (OS) was 16 months. Asymptomatic patients and patients with only lymph node metastases lived longer than symptomatic patients and patients with more extensive metastases. Patients treated with an intensified schedule of 177Lu PRLT lived longer than those treated with a conventional schedule. Half of the patients obtained a PSA decline ≥ 50% and these patients lived longer than those with less PSA decline. Approximately 10% of the patients developed hematologic toxicity with anemia grade 3 as the most severe adverse effect. Characteristics for patients, cancer, restaging, and PRLT predict above average overall survival following treatment with PRLT.

Context Positron emission tomography (PET) targeting prostate-specific membrane antigen (PSMA) has unprecedented accuracy for localization of initial or recurrent prostate cancer (PC). There is now growing evidence regarding the value of PSMA-PET in patients with advanced PC. Objective To review the value of PSMA-PET/computed tomography (CT) in the context of castration-resistant PC (CRPC). Evidence acquisition A search of the PubMed database using the terms “PSMA PET castration resistant prostate cancer” (years 2011–2020) was performed. Reviews, case reports/series, non-English articles, preclinical studies, access-restricted studies, and studies on PSMA radioligand therapy without further analysis of PSMA-PET parameters were subsequently excluded. Evidence synthesis Compared to conventional imaging, PSMA-PET better identifies the true extent of CRPC, especially nonmetastatic CRPC. The clinical benefit of this stage migration is still unclear and needs to be evaluated in further studies. High accuracy of PSMA-PET holds promise for better, PET-guided metastasis-directed treatment in patients with oligometastatic CRPC. PSMA-PET is an essential eligibility criterion for [177Lu]-PSMA theranostic applications. Preliminary evidence indicates the value of PSMA-PET for the assessment of treatment responses. Conclusions Among other applications, PSMA-PET offers more precise staging for nonmetastatic CRPC. In particular, target localization for metastasis-directed therapy and target expression assessment for PSMA radioligand therapy also hold promise. Potential translation of this diagnostic tool into an oncologic benefit needs to be defined in future trials. Patient summary This review describes how prostate-specific membrane antigen positron emission tomography (PSMA-PET), a new sensitive imaging tool for prostate cancer, might help to guide clinicians in making treatment decisions for advanced prostate cancer.

Background In somatostatin receptor (SSTR) expressing progressive meningioma, peptide receptor radionuclide therapy (PRRT) has shown effect in small clinical series. However, standardized treatment and response assessment protocols are lacking. We present our experience on PPRT with 177Lu-DOTATATE in progressive meningioma with a special emphasis on state-of-the-art response assessment. Methods Retrospective analysis on PRRT with 177Lu-DOTATATE from 2015 to 2019. Pre- and post-therapy imaging was performed using MRI and 68Ga-DOTATATE-PET for standard bidimensional and volumetric analyses, respectively, following novel RANO guidelines. Results Seven patients with progressive intracranial meningioma (median age 73 years, interquartile range 60–76; 5 WHO II, 2 WHO I; 5 multifocal) received a median of 4 cycles 2 3 4 of PRRT with 177Lu-DOTATATE in eight-week intervals. Three patients did not undergo post-therapy 68Ga-DOTATATE-PET due to early symptomatic progression and subsequent cessation of PRRT. After completion of 4 PRRT cycles volumetric PET imaging showed stable disease in two of four patients. According to bidimensional MRI response assessment, only one patient was stable. Progression free survival at six months was 42.9 %. Conclusion In this heterogeneous collective of seven patients with progressive meningioma, 177Lu-DOTATATE therapies showed heterogeneous effectiveness. PET-based volumetric assessment should be used for response assessment in PRRT additionally to bidimensional imaging.

Purpose To analyze patients’ characteristics and reasons for not performing planned transarterial radioembolization (TARE) in liver cancer after 99mTc-labeled macroaggregated albumin (99mTc-MAA) evaluation. Methods In this retrospective single-center cohort, all patients undergoing 99mTc-MAA evaluation prior to planned TARE for primary or secondary liver cancer between 2009 and 2018 were analyzed. Patients were assigned to either “TARE” or “no TARE” group. Patients’ characteristics, arising reasons for not performing the planned TARE treatment as well as predictive factors for occurrence of these causes were analyzed. Results 436 patients [male = 248, female = 188, median age 62 (23–88) years] with 99mTc-MAA evaluation prior to planned TARE of primary or secondary liver cancer were included in this study. 148 patients (33.9%) did not receive planned TARE. Patients with a hepatic tumor burden > 50%, no liver cirrhosis, no previous therapies and a higher bilirubin were significantly more frequent in “no TARE” compared to “TARE” group. Main reasons for not performing TARE were extrahepatic tracer accumulation (n = 70, 40.5%), non-target accumulation of 99mTc-MAA (n = 27, 15.6%) or a hepatopulmonary shunt fraction of more than 20% (n = 23, 13.3%). Independent preprocedural parameters for not performing planned TARE were elevated bilirubin (p = 0.021) and creatinine (p = 0.018) and lower MELD score (p = 0.031). Conclusion A substantial number of patients are precluded from TARE following 99mTc-MAA evaluation, which is, therefore, implicitly needed to determine contraindications to TARE and should not be refrained from in pretreatment process. However, a preceding careful patient selection is needed especially in patients with high hepatic tumor burden and alteration in lab parameters.

Metastatic colorectal cancer (mCRC) is associated with different molecular biology, clinical characteristics, and outcome depending on the primary tumor localization. We aimed to evaluate the effectiveness of 90Y-radioembolization (RE) for therapy of colorectal liver metastases depending on the primary tumor side.We performed a retrospective analysis of n = 73 patients with mCRC and RE in our university liver center between 2009 and 2018. Patients were stratified according to the primary tumor side (left vs. right hemicolon), treatment response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) at follow-up after 3 months. Kaplan-Meier analysis was performed to analyze survival followed by Cox regression to determine independent prognostic factors for survival.Prior to RE, all patients had received systemic therapy, with either stable or progressive disease, but no partial or complete response. In n = 22/73 (30.1%) patients, the primary tumor side was in the right colon; in n = 51/73 (69.9%) patients, in the left colon. Hepatic tumor burden was ≤25% in n = 36/73 (49.3%) patients and25% in n = 37/73 (50.7%) patients. At 3 months, n = 21 (33.8%) patients showed treatment response (n = 2 [3.2%]; complete response, n = 19 [30.6%]; partial response), n = 13 (21.0%) stable disease, and n = 28 (45.2%) progressive disease after RE. The median survival in case of primary tumor side in the left colon was significantly higher than for primary tumors in the right colon (8.7 vs. 6.0 months, p = 0.033). The median survival for a hepatic tumor burden ≤25% was significantly higher than that of25% (13.9 vs. 4.3 months, p0.001). The median overall survival was 6.1 months.The median survival after RE in hepatic-mCRC depends on the primary tumor side and the preprocedural hepatic tumor burden.

Prostate-specific membrane antigen (PSMA)–ligand PET/CT is performed on patients with prostate cancer to stage the disease initially or to identify sites of recurrence after definitive therapy. On the basis of clinical results, 18F-PSMA-1007 is a promising PSMA PET tracer, but detailed histologic confirmation has been lacking. Methods: Ninety-six patients with prostate cancer underwent 18F-PSMA-1007 PET/CT followed by either radical prostatectomy with lymphadenectomy or salvage lymphadenectomy. The histologic findings of PSMA PET–positive nodes were analyzed retrospectively. A lesion-based and patient-based analysis was performed comparing all positive lesions and only lesions larger than 3 mm on histopathology. Results: Of the patients, 90.6% received 18F-PSMA-1007 PET/CT for staging before the primary treatment, whereas 9.4% underwent imaging for biochemical recurrence. In 34.4% of the cohort, positive lymph nodes were present on imaging. In total, 1,746 lymph nodes were dissected in 96 patients. 18F-PSMA-1007 PET had a lesion-based sensitivity of 81.7%, a specificity of 99.6%, a positive predictive value of 92.4%, and a negative predictive value of 98.9% for detecting positive lymph nodes larger than 3 mm. In the analysis of all malignant nodes regardless of size, the overall sensitivity, specificity, positive predictive value, and negative predictive value on lesion-based analysis were 71.2%, 99.5%, 91.3%, and 97.9%, respectively. The patient-based analysis showed a sensitivity of 85.9% and a specificity of 99.5% for lymph nodes larger than 3 mm. Conclusion: 18F-PSMA-1007 PET/CT reliably detects malignant lymph nodes and has an exceptional specificity of more than 99% for nodal metastases.

Introduction The impact of prior therapies, especially chemotherapy, on overall survival (OS) in patients with castration-resistant prostate cancer (CRPC) receiving [177Lu]Lu-PSMA-617 therapy has been the subject of controversy. Therefore, WARMTH decided to plan a multicenter retrospective analysis (the “617 trial”) to evaluate response rate and OS as well as the impact of prior therapies on OS in more than 300 patients treated with 177Lu-PSMA-617. Materials and methods The data of 631 metastatic CRPC (mCRPC) patients from 11 different clinics were evaluated. According to the inclusion and exclusion criteria, all patients had to have received at least abiraterone or enzalutamide prior to [177Lu]Lu-PSMA-617 therapy. The patients were divided into three groups: patients who had received prior chemotherapy, patients who avoided chemotherapy, and patients for whom a chemotherapy was contraindicated. Results The analysis included the data of 416 patients, with a median age of 71.9 years. At the time of analysis, 87 patients (20,9%) were still alive. A total of 53.6% of patients had received both abiraterone and enzalutamide; 75.5% and 26.4% had a history of chemotherapy with docetaxel and cabazitaxel, respectively. A total of 20.4% had had Ra-223. The median OS was 11.1 months. Prior chemotherapy, the existence of bone and liver metastases, as well as Eastern Cooperative Oncology Group (ECOG) status, were significant prognosticators of worse overall survival in both univariate and multivariate analyses. Patients without any prior chemotherapy showed a significantly longer OS (14.6 months). The median OS in patients who received one or two lines of chemotherapy with docetaxel or docetaxel followed by cabazitaxel, respectively, was 10.9 months and 8.9 months. There was no difference in OS between patients who had not received chemotherapy and patients for whom chemotherapy was contraindicated. The other prior therapies did not have any significant impact on OS. Conclusion In the present multicenter analysis, chemotherapy-naïve mCRPC patients receiving [177Lu]Lu-PSMA-617 therapy had a significantly longer OS than patients with a history of chemotherapy. This remained independent in the multivariate analysis besides presence of bone and liver metastases as negative prognosticators for survival, whereas an ECOG of 0–1 is associated with a longer OS. Electronic supplementary material The online version of this article (10.1007/s00259-020-04797-9) contains supplementary material, which is available to authorized users.

Introduction Efficient therapy of recurrent differentiated thyroid cancer (DTC) is dependent on precise molecular imaging techniques targeting the human sodium iodide symporter (hNIS), which is a marker both of thyroid and DTC cells. Various iodine isotopes have been utilized for detecting DTC; however, these come with unfavorable radiation exposure and image quality ([131I]iodine) or limited availability ([124I]iodine). In contrast, [18F]tetrafluoroborate (TFB) is a novel radiolabeled PET substrate of hNIS, results in PET images with high-quality and low radiation doses, and should therefore be suited for imaging of DTC. The aim of the present study was to compare the diagnostic performance of [18F]TFB-PET to the clinical reference standard [131I]iodine scintigraphy in patients with recurrent DTC. Methods Twenty-five patients with recurrent DTC were included in this retrospective analysis. All patients underwent [18F]TFB-PET combined with either CT or MRI due to newly discovered elevated TG levels, antiTG levels, sonographically suspicious cervical lymph nodes, or combinations of these findings. Correlative [131I]iodine whole-body scintigraphy (dxWBS) including SPECT-CT was present for all patients; correlative [18F]FDG-PET-CT was present for 21 patients. Histological verification of [18F]TFB positive findings was available in 4 patients. Results [18F]TFB-PET detected local recurrence or metastases of DTC in significantly more patients than conventional [131I]iodine dxWBS and SPECT-CT (13/25 = 52% vs. 3/25 = 12%, p = 0.002). The diagnosis of 6 patients with cervical lymph node metastases that showed mildly increased FDG metabolism but negative [131I]iodine scintigraphy was changed: [18F]TFB-PET revealed hNIS expression in the metastases, which were therefore reclassified as only partly de-differentiated (histological confirmation present in two patients). Highest sensitivity for detecting recurrent DTC had the combination of [18F]TFB-PET-CT/MRI with [18F]FDG-PET-CT (64%). Conclusion In the present cohort, [18F]TFB-PET shows higher sensitivity and accuracy than [131I]iodine WBS and SPECT-CT in detecting recurrent DTC. The combination of [18F]TFB-PET with [18F]FDG-PET-CT seems a reasonable strategy to characterize DTC tumor manifestations with respect to their differentiation and thereby also individually plan and monitor treatment. Future prospective studies evaluating the potential of [18F]TFB-PET in recurrent DTC are warranted.

Patients with metastatic castration-resistant prostate cancer (mCRPC) have limited therapeutic options. Following a theranostics strategy, targeting the prostate-specific membrane antigen (PSMA) by diagnostic and therapeutic radioisotopes is an evolving field in the management of mCRPC. Initial results of PSMA ligands that are conjugated with therapeutic radioisotopes show good efficacy and modest side effects. In this chapter, we present a historical outline and current clinical procedure guidelines for PSMA-targeted therapy regimes.

The skeleton is a common site for cancer metastases. Bone metastases are a major cause of morbidity and mortality and associated with pain, pathologic fractures, spinal cord compression, and decreased survival. Various radionuclides have been used for pain therapy. Recently, an α-emitter has been shown to improve overall survival of patients with bone metastases from castration-resistant prostate cancer and was approved as a therapeutic agent. The aim of this article is to provide an overview regarding state of the art radionuclide therapy options for bone metastases, with focus on the role of PET imaging in therapy planning.