In the past decade, a growing body of literature has reported promising results for prostate-specific membrane antigen (PSMA)-targeted radionuclide imaging and therapy in prostate cancer. First ...clinical studies evaluating the efficacy of
177
LuLu-PSMA radioligand therapy (PSMA-RLT) demonstrated favorable results in prostate cancer patients.
177
LuLu-PSMA is generally well tolerated due to its limited side effects. While PSMA is highly overexpressed in prostate cancer cells, varying degrees of PSMA expression have been reported in other malignancies as well, particularly in the tumor-associated neovasculature. Hence, it is anticipated that PSMA-RLT could be explored for other solid cancers. Here, we describe the current knowledge of PSMA expression in other solid cancers and define a perspective towards broader clinical implementation of PSMA-RLT. This review focuses specifically on salivary gland cancer, glioblastoma, thyroid cancer, renal cell carcinoma, hepatocellular carcinoma, lung cancer, and breast cancer. An overview of the (pre)clinical data on PSMA immunohistochemistry and PSMA PET/CT imaging is provided and summarized. Furthermore, the first clinical reports of non-prostate cancer patients treated with PSMA-RLT are described.
Purpose
This retrospective study aimed (1) to compare the diagnostic accuracy of whole-body FDG PET/CT for initial breast cancer staging with the accuracy of a conventional, multimodal imaging ...algorithm, and (2) to assess potential alteration in patient management based on the FDG PET/CT findings.
Methods
Patients with primary breast cancer (106 women, mean age 57 ± 13 years) underwent whole-body FDG PET/CT and conventional imaging (X-ray mammography, MR mammography, chest plain radiography, bone scintigraphy and breast, axillary and liver ultrasonography). The diagnostic accuracies of FDG PET/CT and a conventional algorithm were compared. Diagnostic accuracy was assessed in terms of primary tumour detection rate, correct assessment of primary lesion focality, T stage and the detection rates for lymph node and distant metastases. Histopathology, imaging or clinical follow-up served as the standards of reference.
Results
FDG PET/CT was significantly more accurate for detecting axillary lymph node and distant metastases (
p
= 0.0125 and
p
< 0.005, respectively). No significant differences were detected for other parameters. Synchronous tumours or locoregional extraaxillary lymph node or distant metastases were detected in 14 patients (13%) solely by FDG PET/CT. Management of 15 patients (14%) was altered based on the FDG PET/CT findings, including 3 patients with axillary lymph node metastases, 5 patients with extraaxillary lymph node metastases, 4 patients with distant metastases and 3 patients with synchronous malignancies.
Conclusion
Full-dose, intravenous contrast-enhanced FDG PET/CT was more accurate than conventional imaging for initial breast cancer staging due to the higher detection rate of metastases and synchronous tumours, although the study had several limitations including a retrospective design, a possible selection bias and a relevant false-positive rate for the detection of axillary lymph node metastases. FDG PET/CT resulted in a change of treatment in a substantial proportion of patients.
Prostate cancer is the most common form of cancer among men in the Netherlands, and its treatment is increasingly expensive. Given the limited hospital budget, it is important to consider costs in ...the treatment of prostate cancer. Radiopharmaceuticals are one of the multiple treatment options for metastatic prostate cancer. The current study looked at the costs of two radiopharmaceuticals, radium-223 and 177Lu-PSMA-I&T, while using multiple treatment regimens.
The cost of radium-223 treatment is €30,905 per patient and is fully covered by insurance. The cost of 177Lu-PSMA-I&T treatment ranges from €35,866 to €47,546 per patient and is partially paid from the budget of the hospitals considering current reimbursement amounts. The study shows that, without consideration of the treatment effects, radium-223 treatment for prostate cancer leads to lower per-patient costs than treatment with 177Lu-PSMA-I&T. The detailed overview of the costs associated with radiopharmaceutical treatment provided by this study is relevant for both hospitals and healthcare insurers to manage prostate cancer treatment costs.
The radiopharmaceuticals radium-223 and the pharmacy preparation
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Lu-PSMA-I&T are reimbursed in the Netherlands for metastatic castration-resistant prostate cancer (mCRPC) treatment. Although shown to be life-prolonging in patients with mCRPC, the treatment procedures associated with these radiopharmaceuticals can be challenging for both patients and hospitals. This study investigates the costs of mCRPC treatment in Dutch hospitals for currently reimbursed radiopharmaceuticals with a demonstrated overall survival benefit.
A cost model that calculated the direct medical per-patient costs of radium-223 and
177
Lu-PSMA-I&T was developed, following clinical trial regimens. The model considered six 4-weekly administrations (i.e. ALSYMPCA regimen) of radium-223. Regarding
177
Lu-PSMA-I&T, the model used both the VISION regimen (i.e. five 6-weekly administrations) and the SPLASH regimen (i.e. four 8-weekly administrations). Based on health insurance claims, we also estimated the coverage a hospital would receive for providing treatment. No fitting health insurance claim for
177
Lu-PSMA-I&T is currently available; therefore, we calculated a break-even value for a potential health insurance claim that would exactly counterbalance the per-patient costs and coverage.
Radium-223 administration is associated with per-patient costs of €30,905, and these costs are fully covered by the coverage a hospital receives. The per-patient costs of
177
Lu-PSMA-I&T range between €35,866 and €47,546 per administration period, depending on the regimen. Current healthcare insurance claims do not fully cover the costs of providing
177
Lu-PSMA-I&T: hospitals must pay €4,414-€4,922 for each patient out of their own budget. The break-even value for the potential insurance claim covering
177
Lu-PSMA-I&T administration with a VISION (SPLASH) regimen is €1,073 (€1,215).
This study shows that, without consideration of the treatment effect, radium-223 treatment for mCRPC leads to lower per-patient costs than treatment with
177
Lu-PSMA-I&T. The detailed overview of the costs associated with radiopharmaceutical treatment provided by this study is relevant for both hospitals and healthcare insurers.
The radiopharmaceuticals radium-223 and the pharmacy preparation
Lu-PSMA-I&T are reimbursed in the Netherlands for metastatic castration-resistant prostate cancer (mCRPC) treatment. Although shown to ...be life-prolonging in patients with mCRPC, the treatment procedures associated with these radiopharmaceuticals can be challenging for both patients and hospitals. This study investigates the costs of mCRPC treatment in Dutch hospitals for currently reimbursed radiopharmaceuticals with a demonstrated overall survival benefit.
A cost model that calculated the direct medical per-patient costs of radium-223 and
Lu-PSMA-I&T was developed, following clinical trial regimens. The model considered six 4-weekly administrations (i.e. ALSYMPCA regimen) of radium-223. Regarding
Lu-PSMA-I&T, the model used both the VISION regimen (i.e. five 6-weekly administrations) and the SPLASH regimen (i.e. four 8-weekly administrations). Based on health insurance claims, we also estimated the coverage a hospital would receive for providing treatment. No fitting health insurance claim for
Lu-PSMA-I&T is currently available; therefore, we calculated a break-even value for a potential health insurance claim that would exactly counterbalance the per-patient costs and coverage.
Radium-223 administration is associated with per-patient costs of €30,905, and these costs are fully covered by the coverage a hospital receives. The per-patient costs of
Lu-PSMA-I&T range between €35,866 and €47,546 per administration period, depending on the regimen. Current healthcare insurance claims do not fully cover the costs of providing
Lu-PSMA-I&T: hospitals must pay €4,414-€4,922 for each patient out of their own budget. The break-even value for the potential insurance claim covering
Lu-PSMA-I&T administration with a VISION (SPLASH) regimen is €1,073 (€1,215).
This study shows that, without consideration of the treatment effect, radium-223 treatment for mCRPC leads to lower per-patient costs than treatment with
Lu-PSMA-I&T. The detailed overview of the costs associated with radiopharmaceutical treatment provided by this study is relevant for both hospitals and healthcare insurers.
Panobinostat, a pan-deacetylase inhibitor, overcomes imatinib resistance in preclinical models of gastrointestinal stromal tumours (GIST). Here we determined the maximum tolerated dose (MTD) and ...dose-limiting toxicities (DLT) of panobinostat in combination with imatinib (IM) for treatment of patients with refractory GIST.
Following a 7-day run-in phase of IM (400 mg per day), escalating doses of panobinostat were added following a '3 plus 3' design. Twelve heavily pretreated GIST patients were enrolled in two dose levels.
Most common adverse events were thrombocytopenia, anaemia, fatigue, creatinine elevation, nausea, emesis and diarrhoea. Twenty micrograms of panobinostat and 400 mg IM were declared the MTD. Pharmacologically active concentrations of panobinostat and IM were achieved as evidenced by histone H3 acetylation in blood mononuclear cells in vivo and inhibition of the IM-resistant KIT (D816) mutation in vitro. In FDG-PET-CT scans after IM run-in and following 3 weeks panobinostat treatment, 1 out of 11 evaluable patients showed a metabolic partial response, 7 patients were metabolically stable and 3 patients progressed. Longest treatment duration was 17 weeks (median 6).
Panobinostat and IM can be administered at doses achieving target inhibition in vivo. Further clinical exploration of patients with treatment-refractory GIST is warranted. Correlative studies in this trial may help to optimise dosing schedules in GIST.
Introduction
Precision medicine expands the treatment options for metastatic castration-resistant prostate cancer (mCRPC) by targeting druggable genetic aberrations. Aberrations can be identified ...following molecular analysis of metastatic tissue. Bone metastases, commonly present in mCRPC, hinder precision medicine due to a high proportion of biopsies with insufficient tumor cells for next-generation DNA sequencing. We aimed to investigate the feasibility of incorporating advanced target planning and needle guidance in bone biopsies and whether this procedure increases biopsy tumor yield and success rate of molecular analysis as compared to the current standards, utilizing only CT guidance.
Materials and Methods
In a pilot study, ten mCRPC patients received
68
Ga-prostate-specific membrane antigen (PSMA)-PET/CT and diffusion-weighted MRI as biopsy planning images. These datasets were fused for targeting metastatic lesions with high tumor densities. Biopsies were performed under cone-beam CT (CBCT) guidance. Feasibility of target planning and needle guidance was assessed, and success of molecular analysis and tumor yield were reported.
Results
Fusion target planning and CBCT needle guidance were feasible. Nine out of ten biopsies contained prostate cancer cells, with a median of 39% and 40% tumor cells by two different sequencing techniques. Molecular analysis was successful in eight of ten patients (80%). This exceeds previous reports on CT-guided biopsies that ranged from 33 to 44%. In two patients, important druggable aberrations were found.
Discussion
A biopsy procedure using advanced target planning and needle guidance is feasible and can increase the success rate of molecular analysis in bone metastases, thereby having the potential of improving treatment outcome for patients with mCRPC.
Level of Evidence
Level 4, case series.
Purpose
Features of polycystic ovarian syndrome (PCOS) including sonographic aspects, androgens, LH and LH/FSH ratio as well as Anti-Mullerian Hormone (AMH) were evaluated according to their ...diagnostic potency in detecting different degrees of PCOS severity.
Methods
80 women with PCOS diagnosed according to the Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group 2003 and 48 controls were enrolled between 2011 and 2013. PCOS patients fulfilling all Rotterdam criteria were defined as having severe PCOS (
n
= 59), while patients showing oligo-/amenorrhoea and polycystic ovaries but without hyperandrogenemia were defined as having mild PCOS (
n
= 21). All patients were treated at the University Hospital of Essen, Germany.
Results
The strongest group difference between controls and severe PCOS patients was observed for AMH showing an age-adjusted odds ratio of 2.56 95 % confidence interval (CI) 2.00–3.27;
p
< 0.0001. Age-adjusted receiver operating characteristic analysis showed that the area under the curve (AUC) of 0.88 (95 % CI: 0.80–0.95) for AMH and 0.94 (95 % CI 0.88–0.98) for antral follicle count did not differ significantly in their ability to discriminate between severe PCOS patients and controls. AMH showed higher AUC estimates than androgens, ovarian volume, LH and LH/FSH ratio and an AUC of 0.80 (95 % CI: 0.65–0.91) for detecting mild PCOS.
Conclusions
To our knowledge, this is the first study comparing the diagnostic potency of AMH, sonographic aspects, androgens, and LH/FSH ratio according to different PCOS subgroups while accounting for the age-dependency of AMH. In cases where vaginal scans are not feasible or in patients without hyperandrogenemia AMH may be used as a surrogate parameter in PCOS diagnosis, superior to androgens and gonadotropins.
Le 177LuLu-PSMA-617 (177Lu-PSMA-617) délivre un rayonnement de particules β- aux cellules exprimant le PSMA. et au microenvironnement de proximité. Dans l’essai de phase 3 VISION (NCT03511664), le ...177Lu-PSMA-617+standard de traitement autorisé dans le protocole (Sdt) a prolongé la survie sans progression radiographique (SSPr ; HR, 0,40 ; 99,2 % CI. : 0,29, 0,57), la survie globale (SG ; 0,62 ; 95 % CI. : 0,52, 0,74) et le temps jusqu’au premier événement squelettique symptomatique (ESS ; 0,50 ; IC. à 95 % : 0,40 ; 0,62) par rapport au Sdt seul (tous p<0,001).
VISION était une étude internationale, ouverte évaluant le 177Lu-PSMA-617 chez des hommes atteints de CPRCm PSMA-positif, précédemment traités par au moins 1 inhibiteur de la voie de signalisation des récepteurs aux androgènes et par taxane (1 ou 2). Les patients ont été randomisés en 2: 1 pour recevoir le 177Lu-PSMA-617 (7,4 GBq toutes les 6 semaines jusqu’à 6 cycles) plus le Sdt par rapport au Sdt seul. la SSPr et la SG étaient les critères d’évaluation principaux alternatifs ; le délai avant le premier ESS était un critère d’évaluation secondaire clé. Les autres critères d’évaluation secondaires comprenaient la tolérance et la qualité de vie rapportée par le patient (« Functional Assessment of Cancer Therapy–Prostate ») et la douleur (« Brief pain inventory - Short form »). Les analyses prédéfinies incluaient le délai jusqu’à la première dégradation de la qualité de vie/aggravation de la douleur, la progression de la maladie ou le décès. Nous présentons ici des analyses Ad hoc du temps d’aggravation uniquement (non inférentielles).
La qualité de vie liée à la santé a été évaluée dans la population d’analyse de la SSPr prédéfinis comprenant 581 des 831 patients randomisés (bras 177Lu-PSMA-617, n=385 ; bras contrôle, n=196). Les analyses de la qualité de vie liée à la santé et du délai d’aggravation de la douleur sont en faveur du bras 177Lu-PSMA-617, malgré une incidence plus élevée d’événements indésirables de grade 3 par rapport au Sdt seul. Aucun nouveau signal ou signal inattendu de tolérance n’a été observé, y compris au niveau des modifications de clairance de la créatinine.
177Lu-PSMA-617 plus Sdt était généralement bien toléré et retardait le temps jusqu’à la dégradation de la qualité de vie et de la douleur par rapport au Sdt seul chez les patients atteints d’un CPRCm avancé.
Rosiglitazone achieved promising results in progressive differentiated thyroid carcinoma (DTC) with redifferentiative and antiproliferative effects, but has been taken off the market. Thus we ...evaluated another glitazone, pioglitazone, expecting similar positive results. PATIENT, MATERIALS, METHODS: Five patients with progressive DTC and no or only negligible iodine uptake were enrolled. Oral pioglitazone treatment was applied for 6 months. The re-differentiative effect was assessed by 124I-NaI PET/CT dosimetry and the anti-proliferative effect by 18F-FDG PET/CT imaging.
A redifferentiative effect of pioglitazone could not be shown. Lesion dosimetry indicated that 3/5 patients had unchanged no lesion absorbed dose per administered activity (LDpA) in any tumour lesion, 2/5 patients had a deterioration of LDpA within some lesions, thus radioiodine therapy was not performed in any patient. Volumetric analysis, using RECIST criteria, revealed progressive disease in 3/5 patients and stable disease in 2/5 patients. Metabolic changes, using EORTC criteria, revealed 3/5 patients with progressive metabolic disease, 1/5 patient with stable metabolic disease and 1/5 patients with partial metabolic response. The medication was well-tolerated, and no patient developed clinically important toxicity associated with the treatment.
Pioglitazone revealed some positive effects in radioiodine negative and progressive DTC patients but it did not fulfill the expectations given by the results of rosiglitazone therapy.
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