Die prognostische Wertigkeit des 18F-FDG-PET-Scans bei follikulärem Lymphom nach Radioimmuntherapie: Prädiktion des Outcomes nach zwei verschiedener Ansprechkriterien IHP und D5PS

Ziel: Das Ziel dieser Studie war es, zwei Kriterien für die Evaluation des Ansprechens im 18F-FDG-PET (PET-Scan) nach Radioimmuntherapie mit 90Y Ibritumomab Tiuxetan bei Patienten mit rezidivie-rendem oder refraktärem follikulärem Non-Hodgkin-Lymphom (FL) zu vergleichen. Methode: Wir haben die Daten von 27 rezidivierenden oder refraktären FL-Patienten, die mit 90Y-ibritumomab tiuxetan (Zevalin®) in drei verschiedenen nuklearmedizinischen Abteilungen in Deutsch-land behandelt wurden, retrospektiv analysiert. Die Patienten erhielten jeweils ein PET-Scan vor und ein nach der RIT. Das Ansprechen wurde im PET-Scan 3 Monate 6 Wochen nach RIT anhand der Kriterien des internationalen Harmonisierungsprojekts (IHP) und Deauville (D5PS) bewertet. Das pro-gressionsfreie Überleben (PFS) und das Gesamtüberleben (OS) wurden mit dem Ansprechen auf RIT korreliert, welches aus den beiden oben genannten Kriterien abgeleitet wurde. Ergebnisse: Von 27 Patienten waren 12 Responder (Gruppe I), 9 waren Non-Responder nach beiden Kriterien (Gruppe II) und 6 Patienten waren Responder nach IHP, aber gleichzeitig Non-Responder nach D5PS (Gruppe III). Alle Responder nach D5PS waren auch Responder nach IHP-Kriterien. Die Patienten wurden für 8 bis 150 (Median = 49,7) Monaten beobachtet. Die PFS der Gruppen I, II und III betrugen NE (wurde nicht erreicht), 5 Monate (95%-CI: 3-8) bzw. 6 Monate (95%-CI:6-8). OS der Gruppen I, II und III waren NE (wurde nicht erreicht), 39 Monate (95%-CI: 21-77) bzw. 31 Monate (95%-CI:20-135). Die Kaplan-Meier Survival-Analyse wurde verwendet, um die PFS und OS dieser Gruppen zu vergleichen, diese für die Gruppe II und III signifikant kürzer waren als für die Gruppe I. Es gab keinen statistisch signifikanten Unterschied zwischen dem PFS oder OS der Gruppe II im Ver-gleich zu denen der Gruppe III (p=0,98 und 0,54). Schlussfolgerung: Die Evaluation des Ansprechens auf die Radioimmuntherapie bei refraktärem oder rezidivierendem FL mittels 18F-FDG-PET-Scan mit D5PS-Kriterien kann das Outcome (PFS und OS) besser prädiktieren als mit IHP-Kriterien.Aim: The aim of this study is to compare two criteria for evaluation of response on 18F-FDG-PET (PET) after radioimmunotherapy with 90Y ibritumomab tiuxetan (RIT) on patients with non-Hodgkin follicular lymphoma (FL). Materials and Methods: We retrospectively analyzed the data on 27 relapsed or refractory FL pa-tients treated with 90Y-ibritumomab tiuxetan (Zevalin) in three different nuclear medicine depart-ments of Germany, who had a PET study carried out before and after RIT. Response was assessed on PET, performed 3 months 6 weeks after RIT using the international harmonization project (IHP) and Deauville (D5PS) Criteria. Progressions-free survival (PFS) and overall survival (OS) were corre-lated with the response to RIT, derived from the two criteria stated above. Results: Out of 27 patients, 12 were responder (Group I) und 9 were non-responder based on both criteria (Group II) and 6 patients were responders based on IHP but non-responders based on D5PS (Group III). All responders based on D5PS were also responders based on IHP criteria. Patients were followed for 8 to 150 (median= 49,7) months. PFS of Groups I, II and III were NE (has not been reached), 5 months (95%-CI: 3-8) and 6 months (95%-CI:6-8), respectively. OS of Groups I, II and III were NE (has not been reached), 39 months (95%-CI: 21-77) and 31 months (95%-CI:20-135), re-spectively. Kaplan-Meier Survival analysis was used to compare the PFS and OS of these groups, which were significantly shorter for Group II and III compared to those for Group I. There was no sta-tistically significant difference between the PFS or OS of Group II in comparison to those of Group III (p=0.98 and 0.54). Conclusions: The response to radioimmunotherapy of refractory or recurrent FL using 18F-FDG-PET-Scan based on D5PS Criteria predicts outcome (PFS/OS) more accurately than the evaluation based on the IHP Criteria

Systemic Mastocytosis Treatment with Midostaurin: [18F]FDG PET/CT as a Potential Monitoring Tool for Therapy Outcome

We report the case of a 68-year-old patient with diagnosed systemic mastocytosis and histopathologically confirmed manifestations in the stomach and intestinal tract who underwent 18FFluorodeoxyglucose ([18F]FDG) positron-emission tomography/computed tomography (PET/CT) pre- and post-6-month therapy with midostaurin, an established tyrosine kinase inhibitor. Posttherapeutic [18F]FDG PET/CT showed decreased multifocal tracer uptake in the known lesions in the gastrointestinal tract, which was consistent with relief of the patient’s symptoms and decrease in serum tryptase level. [18F]FDG PET/CT may thus be considered a potential method for monitoring the outcome of midostaurin therapy in systemic mastocytosis

Strongly Radioiodine-Positive Pancreatic Adenocarcinoma Mimicking Metastasis of Differentiated Thyroid Cancer

We present an interesting image of a strikingly intense radioiodine accumulation of a histologically proven pancreatic adenocarcinoma mimicking metastasis of differentiated thyroid cancer in a 63-year-old woman with recurrence of papillary thyroid carcinoma undergoing radioiodine therapy. This interesting image should draw attention to considering pancreatic adenocarcinoma in radioiodine-positive pancreatic lesions

PSMA-Positive Follicular Thyroid Carcinoma Incidentally Detected by [68Ga]Ga-PSMA-11 PET/CT: Correlation with Immunohistology Confirms Neovascular PSMA-Expression

We present an interesting image of an intense PSMA-positive follicular thyroid carci noma incidentally detected by [68Ga]Ga-PSMA-11 PET/CT in a 76-year-old man with biochemical recurrence of prostate cancer. Immunohistochemical staining demonstrated PSMA expression in the endothelial cells of tumor tissue. This interesting image should remind colleagues to consider malignant thyroid neoplasia in PSMA-positive thyroid lesions

Complete remission of an early-stage laryngeal cancer under combined pembrolizumab and chemotherapy treatment of a synchronous lung adenocarcinoma

Background: Anti-PD1-Checkpoint inhibition (CI) is an established treatment of recurrent and/or metastatic head and neck cancer. A potential beneft from CI in early-stage disease that is usually treated by radiation or surgery has not been investigated so far and is currently not addressed in clinical trials. Case presentation: A 58-year-old man was diagnosed with a cT2 supraglottic laryngeal cancer and a synchronous metastasized adenocarcinoma of the lung. As the patient refused any treatment of his laryngeal cancer, he received combined immune-chemotherapy according to the KEYNOTE-189 protocol. After 4 cycles of pembrolizumab/carboplatin/pemetrexed, the patient showed a complete remission of his laryngeal cancer with a clear shrinkage of the mediastinal and hilar lung cancer metastases. After 21 cycles of maintenance therapy, the lung adenocarcinoma shows a stable disease status with no signs of any residual or recurrent laryngeal cancer. Conclusions: Anti-PD1-CI may be a treatment option also for early-stage HNSCC with excellent functional outcome when established therapies are not available

Molecular imaging and biochemical response assessment after a single cycle of [225Ac]Ac-PSMA-617/[177Lu]Lu-PSMA-617 tandem therapy in mCRPC patients who have progressed on [177Lu]Lu-PSMA-617 monotherapy

Rationale: Despite the promising results of prostate-specific membrane antigen (PSMA)-targeted 177Lu radioligand therapy in metastatic castration-resistant prostate carcinoma (mCRPC), some patients do not respond and other patients with initially good response develop resistance to this treatment. In this study, we investigated molecular imaging and biochemical responses after a single cycle of [225Ac]Ac-PSMA-617/[177Lu]Lu-PSMA-617 tandem therapy in patients who had progressed on [177Lu]Lu-PSMA-617 monotherapy. Methods: Seventeen patients with mCRPC were included in a retrospective, monocenter study. Molecular imaging-based response was assessed by modified PERCIST criteria using the whole-body total lesion PSMA (TLP) and molecular tumour volume (MTV) derived from [68Ga]Ga-PSMA-11 PET/CT. Biochemical response was evaluated according to PCWG3 criteria using the prostate-specific antigen (PSA) serum value. Concordance and correlation statistics as well as survival analyses were performed. Results: Based on the molecular imaging-based response assessment, 5 (29.4%) patients showed partial remission and 7 (41.2%) had stable disease. The remaining 5 (29.4%) patients had further progression, four with an increase in TLP/MTV of >30% and one with stable TLP/MTV but appearance of new metastases. Based on the biochemical response assessment, 5 (29.4%), 8 (47.1%), and 4 (23.5%) patients showed partial remission, stable disease, and progressive disease, respectively. A comparison of the response assessment methods showed a concordance of 100% (17/17) between TLP and MTV and 70.6% (12/17) between TLP/MTV and PSA. Patients with partial remission, independently assessed by each method, had better overall survival (OS) than patients with either stable or progressive disease. The difference in OS was statistically significant for the molecular imaging response assessment (median OS not reached vs. 8.3 m, p = 0.044), but not for the biochemical response assessment (median OS 18.1 m vs. 9.4 m, p = 0.468). Conclusion: Based on both assessment methods, [225Ac]Ac-PSMA-617/[177Lu]Lu-PSMA-617 tandem therapy is an effective treatment for the highly challenging cohort of patients with mCRPC who have progressed on [177Lu]Lu-PSMA-617 monotherapy. Molecular imaging response and biochemical PSA response were mostly concordant, though a considerable number of cases (29.4%) were discordant. Molecular imaging response reflecting the change in total viable tumour burden appears to be superior to PSA change in estimating survival outcome after tandem therapy

Prophylactic Peripheral Blood Stem Cell Collection in Patients with Extensive Bone-Marrow Infiltration of Neuroendocrine Tumours Prior to Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE

Peptide receptor radionuclide therapy (PRRT) of metastatic neuroendocrine tumors (NET) can be successfully repeated but may eventually be dose-limited. Since 177Lu-DOTATATE dose limitation may come from hematological rather than renal function, hematological peripheral blood stem cell backup might be desirable. Here, we report our initial experience of peripheral blood stem-cell collection (PBSC) in patients with treatment-related cytopenia and therefore high risk of bone-marrow failure. Five patients with diffuse bone-marrow infiltration of NET and relevant myelosuppression (≥grade 2) received PBSC before one PRRT cycle with 177Lu-DOTATATE (7.6 ± 0.8 GBq/cycle). Standard stem-cell mobilization with Granulocyte-colony stimulating factor (G-CSF) was applied, and successful PBSC was defined as a collection of >2 × 106/kg CD34+ cells. In case of initial failure, Plerixafor was administered in addition to G-CSF prior to apheresis. PBSC was successfully performed in all patients with no adverse events. Median cumulative activity was 44.8 GBq (range, 21.3–62.4). Three patients had been previously treated with PRRT, two of which needed the addition of Plerixafor for stem-cell mobilization. Only one of five patients required autologous peripheral blood stem-cell transplantation during the median follow up time of 28 months. PBSC collection seems to be feasible in NET with bone-marrow involvement and might be worth considering as a backup strategy prior to PRRT, in order to overcome dose-limiting bone-marrow toxicity

Addition of Standard Enzalutamide Medication Shows Synergistic Effects on Response to [177Lu]Lu-PSMA-617 Radioligand Therapy in mCRPC Patients with Imminent Treatment Failure—Preliminary Evidence of Pilot Experience

Well-received strong efficacy of prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) does not prevent patients from either early or eventual disease progression under this treatment. In this study, we investigated co-medication with enzalutamide as a potential re-sensitizer for PSMA-RLT in patients with imminent treatment failure on standard 177Lu-based PSMA-RLT. Ten mCRPC patients who exhibited an insufficient response to conventional [177Lu]Lu PSMA-617 RLT received oral medication of enzalutamide 160 mg/d as an adjunct to continued PSMA RLT. Prostate-specific antigen (PSA) and standard toxicity screening lab work-up were performed to assess the treatment efficacy and safety in these individuals. The mean PSA increase under PSMA-RLT before starting the re-sensitizing procedure was 22.4 ± 26.5%. After the introduction of enzalutamide medication, all patients experienced a PSA decrease, –43.4 ± 20.0% and –48.2 ± 39.0%, after one and two cycles of enzalutamide-augmented PSMA-RLT, respectively. A total of 70% of patients (7/10) experienced partial remission, with a median best PSA response of –62%. Moreover, 5/6 enzalutamide-naïve patients and 2/4 patients who had previously failed enzalutamide exhibited a partial remission. There was no relevant enzalutamide-induced toxicity observed in this small cohort. This pilot experience suggests the synergistic potential of adding enzalutamide to PSMA-RLT derived from the intra-individual comparison of 177Lu-based PSMA-RLT ± enzalutamide

Renal Safety of [177Lu]Lu-PSMA-617 Radioligand Therapy in Patients with Compromised Baseline Kidney Function

Background: Radioligand therapy (RLT) targeting prostate-specific membrane antigen (PSMA) is an effective antitumor-treatment in metastatic castration-resistant prostate carcinoma (mCRPC). Concerns of potential nephrotoxicity are based on renal tubular PSMA expression and the resulting radiopharmaceutical retention during RLT, but data confirming clinically significant renal toxicity are still lacking. In this study, patients with significantly impaired baseline kidney function before initiation of therapy were investigated for treatment-associated nephrotoxicity and the potential relationship with administered activities of [177Lu]Lu-PSMA-617. Methods: Twenty-two mCRPC patients with impaired renal function (glomerular filtration rate (GFR) ≤ 60 mL/min) who received more than two cycles of [177Lu]Lu-PSMA-617 RLT (median 5 cycles and median 6-week time interval between consecutive cycles) were analyzed in this study. Patients were treated within a prospective patient registry (REALITY Study, NCT04833517). Cumulative administered activities ranged from 17.1 to 85.6 GBq with a median activity of 6.5 GBq per cycle. Renal function was closely monitored during and after PSMA-RLT. Results: Mean pre-treatment GFR was 45.0 ± 10.7 mL/min. After two (22/22 patients), four (20/22 patients), and six cycles (10/22 patients) of RLT, a significant increase of GFR was noted (each p < 0.05). End-of-treatment GFR (54.1 ± 16.7 mL/min) was significantly higher than baseline GFR (p = 0.016). Only one patient experienced deterioration of renal function (change of CTCAE grade 2 to 3). The remaining patients showed no significant reduction of GFR, including follow-up assessments (6, 9, and 12 months), and even showed improved (10/22 patients) or unchanged (11/22 patients) CTCAE-based renal impairment grades during and after the end of PSMA-RLT. No significant correlation between the change in GFR and per-cycle (p = 0.605) or cumulative (p = 0.132) administered activities were found. Conclusions: As pre-treatment chronic kidney failure did not lead to detectable RLT-induced deterioration of renal function in our study, the nephrotoxic potential of [177Lu]Lu-PSMA-617 RLT may be overestimated and not of clinical priority in the setting of palliative treatment in mCRPC. We suggest not to categorically exclude patients from enrolment to PSMA-RLT due to renal impairment

Efficacy and Safety of [225Ac]Ac-PSMA-617 Augmented [177Lu]Lu-PSMA-617 Radioligand Therapy in Patients with Highly Advanced mCRPC with Poor Prognosis

The use of 225Ac in prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT), either as monotherapy or in combination with 177Lu, is a promising therapy approach in patients with metastatic castration-resistant prostate carcinoma (mCRPC). In this study, we report the efficacy and safety of [225Ac]Ac-PSMA-617 augmented [177Lu]Lu-PSMA-617 RLT in 177Lu-naive mCRPC patients (n = 15) with poor prognosis (presence of visceral metastases, high total tumor burden with diffuse bone metastases or a short PSA doubling time of <2 months). Biochemical (by PSA serum value) and molecular imaging response (by [68Ga]Ga-PSMA-11 PET/CT) was assessed after two cycles of [177Lu]Lu-PSMA-617 RLT, with at least one [225Ac]Ac-PSMA-617 augmentation. In addition, PSA-based progression-free survival (PSA-PFS), overall survival (OS) and toxicity (according to CTCAE) were analyzed. We observed a biochemical- and molecular imaging-based partial remission in 53.3% (8/15) and 66.7% (10/15) of patients, respectively. The median PSA-PFS and OS was 9.1 and 14.8 months, respectively. No serious acute adverse events were recorded. Two out of fifteen patients experienced grade 3 anemia. No other grade 3/4 toxicities were observed. RLT-related xerostomia (grade 1/2) was recorded in 2/15 patients. Our data showed a high clinical efficacy with a favorable side effects profile of [225Ac]Ac-PSMA-617 augmented [177Lu]Lu-PSMA-617 RLT in this highly challenging patient cohort