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1.
Purpose
Up to 30% of patients with castration-resistant prostate cancer (CRPC) do not show any response to the first cycle of radioligand therapy (RLT) with [177Lu]Lu-PSMA-617 (Lu-PSMA). We evaluated patient response to the second and third cycles of RLT in patients that underwent at least three cycles. The second aim of this study was to calculate the median overall survival (OS) of responders and non-responders after the first cycle and after all three cycles of RLT.Methods
CRPC patients were treated with Lu-PSMA, with a median interval of 8 weeks between each cycle. The tumour marker prostate-specific antigen (PSA) was used as the marker for response evaluation.Results
Fifty-two patients underwent a total of 190 cycles of RLT (3–6 cycles per patient). Of these, 80.8% showed a decline in PSA 2 months after the first cycle, with 44.2% showing a PSA decline of ≥50%. When compared to baseline PSA, 73.1% showed a PSA decline after the third cycle. 50% of patients that did not show any response to the first cycle also did not respond to the second and third cycles. The median OS was 60 weeks in all patients. The median OS was significantly longer for patients that showed any PSA decline after the first cycle compared to patients without PSA decline (68 vs. 33 weeks). There was a significant difference in median OS between responders and non-responders for a change in PSA after the third cycle compared to baseline PSA.Conclusion
Patients with a positive response to RLT, regardless of the rate of decline, had a significantly longer median OS. Of the patients that did not show any response to the first cycle, 50% responded to the second or third cycles.2.
Aims
There is a controversy as to the relative efficacy of 177Lu prostate specific membrane antigen (PSMA) radioligand therapy (RLT) and third-line treatment for patients with metastatic castration-resistant prostate cancer (mCRPC). The aim of our systematic review was to elucidate whether 177Lu-PSMA RLT and third-line treatment have similar effects and adverse effects (PROSPERO ID CRD42017067743).Methods
The review followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Searches in Pubmed and Embase selected articles up to September 2017. A search in ClinicalTrials.gov indicated ongoing studies. The meta-analysis used the random-effects model.Results
Twelve studies including 669 patients reported 177Lu-PSMA RLT. Overall, 43% of the patients had a maximum decline of PSA of ≥50% following treatment with 177Lu-PSMA RLT. The treatment with 177Lu-PSMA-617 and 177Lu-PSMA for imaging and therapy (I&T) had mainly transient adverse effects. Sixteen studies including 1338 patients reported third-line treatment. Overall, 21% of the patients had a best decline of PSA of ≥50% following third-line treatment. After third-line treatment with enzalutamide and cabazitaxel, adverse effects caused discontinuation of treatment for 10% to 23% of the patients. 177Lu-PSMA RLT gave a best PSA decline ≥50% more often than third-line treatment (mean 44% versus 22%, p?=?0.0002, t test). 177Lu-PSMA RLT gave objective remission more often than third-line treatment (overall 31 of 109 patients versus 43 of 275 patients, p?=?0.004, χ2 test). Median survival was longer after 177Lu-PSMA RLT than after third-line treatment, but the difference was not statistically significant (mean 14 months versus 12 months, p?=?0.32, t test). Adverse effects caused discontinuation of treatment more often for third-line treatment than for 177Lu-PSMA RLT (22 of 66 patients versus 0 of 469 patients, p?<?0.001, χ2 test).Conclusions
As for patients with mCRPC, treatment with 177Lu-PSMA-617 RTL and 177Lu-PSMA I&T gave better effects and caused fewer adverse effects than third-line treatment.3.
Lorenza?Scarpa Sabine?Buxbaum Dorota?Kendler Katharina?Fink Jasmin?Bektic Leonhard?Gruber Clemens?Decristoforo Christian?Uprimny Peter?Lukas Wolfgang?Horninger Irene?Virgolini
Introduction
A targeted theragnostic approach based on increased expression of prostate-specific membrane antigen (PSMA) on PC cells is an attractive treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC).Methods
Ten consecutive mCRPC patients were selected for 177Lu-PSMA617 therapy on the basis of PSMA-targeted 68Ga-PSMA-HBED-CC PET/CT diagnosis showing extensive and progressive tumour load. Following dosimetry along with the first therapy cycle restaging (68Ga-PSMA-HBED-CC and 18F-NaF PET/CT) was performed after 2 and 3 therapy cycles (each 6.1?±?0.3 GBq, range 5.4–6.5 GBq) given intravenously over 30 minutes, 9?±?1 weeks apart. PET/CT scans were compared to 177Lu-PSMA617 24-hour whole-body scans and contrast-enhanced dual-phase CT. Detailed comparison of SUVmax values and absorbed tumour doses was performed.Results
177Lu-PSMA617 dosimetry indicated high tumour doses for skeletal (3.4?±?1.9 Gy/GBq; range 1.1–7.2 Gy/GBq), lymph node (2.6?±?0.4 Gy/GBq; range 2.3–2.9 Gy/GBq) as well as liver (2.4?±?0.8 Gy/GBq; range 1.7–3.3 Gy/GBq) metastases whereas the dose for tissues/organs was acceptable in all patients for an intention-to-treat activity of 18?±?0.3 GBq. Three patients showed partial remission, three mixed response, one stable and three progressive disease. Decreased 177Lu-PSMA617 and 68Ga-PSMA-HBED-CC uptake (mean SUVmax values 20.2 before and 15.0 after 2 cycles and 11.5 after 3 cycles, p?<?0.05) was found in 41/54 skeletal lesions, 12/13 lymph node metastases, 3/5 visceral metastases and 4/4 primary PC lesions.Conclusion
Due to substantial individual variance, dosimetry is mandatory for a patient-specific approach following 177Lu-PSMA617 therapy. Higher activities and/or shorter treatment intervals should be applied in a larger prospective study.4.
Purpose
Prostate-specific membrane antigen (PSMA)-targeting radioligand therapy (RLT) was introduced in 2011. The first report described the antitumor and side effects of a single dose. The aim of this analysis was to evaluate toxicity and antitumor activity after single and repetitive therapies.Methods
Thirty-four men with metastatic castration-resistant prostate cancer received PSMA-RLT with 131I-MIP-1095. Twenty-three patients received a second, and three patients a third dose, timed at PSA progression after an initial response to the preceding therapy. The applied doses were separated in three groups: <3.5, 3.5–5.0 and >5.0 GBq. Antitumor and side-effects were analyzed by blood samples and other clinical data. Follow-up was conducted for up to 5 years.Results
The best therapeutic effect was achieved by the first therapy. A PSA decline of ≥50% was achieved in 70.6% of the patients. The second and third therapies were significantly less effective. There was neither an association between the applied activity and PSA response or the time-to-progression. Hematologic toxicities were less prevalent but presented in a higher percentage of patients with increasing number of therapies. After hematologic toxicities, xerostomia was the second most frequent side effect and presented more often and with higher intensity after the second or third therapy.Conclusion
The first dose of RLT with 131I-MIP-1095 presented with low side effects and could significantly reduce the tumor burden in a majority of patients. The second and third therapies were less effective and presented with more frequent and more intense side effects, especially hematologic toxicities and xerostomia.5.
Madhav?Prasad?Yadav Sanjana?Ballal Madhavi?Tripathi Nishikant?Avinash?Damle Ranjit?Kumar?Sahoo Amlesh?Seth Chandrasekhar?Bal
Purpose
The purpose of this study was to evaluate the efficacy and safety of a novel theranostic agent, 177Lu-DKFZ-PSMA-617 therapy in metastatic castration resistant prostate cancer (mCRPC).Methods
Thirty-one mCRPC patients with progressive disease despite second-line hormonal therapy and/or docetaxel chemotherapy were recruited for the study. All patients underwent diagnostic68Ga-PSMA-HBED-CCPET/CT, prior to inclusion for therapy. Included patients then underwent quarterly 177Lu-DKFZ-PSMA-617 therapy. Hematological, kidney function, liver function tests, and serum PSA levels were recorded before and after therapy at 2 weeks, 4 weeks, and 3 month intervals. Biochemical response was assessed with trend in serum PSA levels. Metabolic response was assessed by PERCIST 1 criteria. Clinical response was assessed by visual analogue score (VASmax) analgesic score (AS), Karanofsky performance status (KPS), and ttoxicity and response criteria of the Eastern Cooperative Oncology Group (ECOG) criteria.Results
The mean age of patients was 65.93?±?9.77 years (range: 38–81 years). The mean activity administered in the 31 patients was 5069?±?1845 MBq ranging from one to four cycles. There was a decline in the mean serum PSA levels from the baseline (baseline: 275 ng/mL, post 1st cycle therapy: 141.75 ng/mL). Based on biochemical response criteria 2/31, 20/31, 3/31, and 6/31 had complete response (CR), partial response(PR), stable disease (SD), and progressive disease (PD), respectively. Metabolic response revealed 2/6 patients with CR, and the remaining 3/6 patients with PR and 1/6 patients with SD. The mean VASmax score decreased from 7.5 to 3. The mean analgesic score decreased from 2.5 to 1.8 after therapy. The mean KPS score improved from 50.32 to 65.42 after therapies. The mean ECOG performance status improved from 2.54 to 1.78 after therapy. Two patients experienced grade I and grade II hemoglobin toxicity each. None of the patients experienced nephrotoxicity or hepatotoxicity.Conclusion
177Lu-DKFZ-PSMA-617 radionuclide therapy is a safe and effective approach in the treatment of mCRPC patients.6.
Axel?Br?uer Lena Sophie?Grubert Wolfgang?Roll Andres?Jan?Schrader Michael?Sch?fers Martin?B?gemann Kambiz?Rahbar
Purpose
Radioligand therapies targeting prostate-specific membrane antigen (PSMA) have been established for the treatment of metastasized castration-resistant prostate cancer (mCRPC) in the last decade and show promising response rates and a favourable toxicity profile. The aim of this study was to evaluate the overall survival (OS) and to identify parameters predicting outcome in mCRPC patients treated with 177Lu-PSMA-617.Methods
Between December 2014 and January 2017, 59 consecutive patients (median age 72 years; interquartile range, (IQR, 66–76 years) with mCRPC, who had been treated with at least one next-generation antihormonal drug as well as chemotherapy, were included in this study. Biochemical response was evaluated using Prostate Cancer Working Group 3 (PCWG3) criteria. Survival was evaluated using Kaplan-Meier estimates and Cox regression proportional hazards model. Toxicity was assessed using Common Toxicity Criteria for Adverse Events (CTCAE). The study was approved by the local ethics committee.Results
The 59 patients were treated with a total of 159 cycles (median 3 cycles, range 1–7) of 177Lu-PSMA-617 (median dose 6.11 GBq, IQR 5.9–6.3 GBq). The median follow-up was 24 weeks (IQR 15–36 weeks). Follow-up data for at least 12 weeks (PCWG3) were available in 76% (45) of the patients. For outcome results data from all patients treated with at least one cycle were analysed. A decline in prostate-specific antigen (PSA) of ≥50% occurred in 53%, and a decline in PSA of any amount in 91% of patients. The estimated median OS was 32 weeks. An initial alkaline phosphatase (ALP) level <220 U/L and a PSA decline after the first cycle were associated with a longer OS (56 vs. 28 weeks, p < 0.01, and 56 vs. 29 weeks, p = 0.04, respectively). The median estimated PSA progression-free survival (PPFS) was 18 weeks. Only ALP level <220 U/L was significantly associated with a longer PPFS (41 vs. 18 weeks, p < 0.01).Conclusions
A PSA decline after the first cycle of 177Lu-PSMA-617 and an initial ALP level <220 U/L were predictors of a longer OS in patients with end-stage mCRPC. An ALP level <220 U/L was additionally associated with a longer PPFS.7.
Christian Mair Boris Warwitz Katharina Fink Lorenza Scarpa Bernhard Nilica Johanna Maffey-Steffan Sabine Buxbaum Irene J. Virgolini 《Annals of nuclear medicine》2018,32(7):499-502
Purpose
As radionuclide therapy is gaining importance in palliative treatment of patients suffering from neuroendocrine tumour (NET) as well as castration resistant prostate cancer (CRPC), the radiation protection of patients, staff, family members and the general public is of increasing interest. Here, we determine patient discharge dates according to European guidelines.Methods
In 40 patients with NET and 25 patients with CRPC organ and tumour doses based on the MIRD concept were calculated from data obtained during the first therapy cycle. Planar whole body images were recorded at 0.5, 4, 20, 68 und 92 h postinjection. Residence times were calculated from the respective time-activity-curves based on the conjugated view method. Residence times for critical organs were fitted into the commercially available OLINDA software to calculate the organ doses. The doses of tumours and salivary glands were calculated via their self-irradiation by approximation with spheres of equivalent volume. Kidney volumes were gained by organ segmentation, volumes of all other organs were estimated by means of OLINDA and hence were lean body mass corrected. Out of the whole body curves reference points for patient discharge were estimated.Results
In patients with NET discharge dates could be properly estimated from dosimetric data, which is not only crucial for radiation protection, but also makes therapy planning easier. For 177Lu-PSMA-617 ligand therapy it is difficult to seriously estimate a generalized discharge date due to large interpatient variation resulting from different tumor loads and heavy pre-treatment.Conclusion
Patient release is predictable for 177Lu-DOTATATE therapy but not for 177Lu-PSMA ligand therapy.8.
Background
Permanent low-dose-rate brachytherapy (BT) with iodine 125 is an established curative treatment for localized prostate cancer. After treatment, prostate-specific antigen (PSA) kinetics may show a transient rise (PSA bounce). Our aim was to investigate the association of PSA bounce with biochemical control.Patients and methods
Patients treated with BT in Switzerland were registered in a prospective database. Only patients with a follow-up of at least 2 years were included in our analysis. Clinical follow-up and PSA measurements were assessed after 1.5, 3, 6, and 12 months, and annually thereafter. If PSA increased, additional follow-up visits were scheduled. Cases of PSA bounce were defined as a rise of at least 0.2 ng/ml above the initial PSA nadir with a subsequent decline to or below the initial nadir without treatment. Biochemical failure was defined as a rise to nadir +?2 ng/ml.Results
Between March 2001 and November 2010, 713 patients with prostate cancer undergoing BT with at least 2 years of follow-up were registered. Median follow-up time was 41 months. Biochemical failure occurred in 28 patients (3.9?%). PSA bounce occurred in 173 (24.3?%) patients; only three (1.7?%) patients with PSA bounce developed biochemical failure, in contrast to 25 (4.6?%) patients without previous bounce (p?<?0.05). The median time to bounce was 12 months, the median time to biochemical failure was 30 months. The median bounce increase was 0.78 ng/ml. Twenty-eight patients with bounce (16.5?%) had a transient PSA rise of +?2 ng/ml above the nadir.Conclusion
In most cases, an early increase in PSA after BT indicates PSA bounce and is associated with a lower risk of biochemical failure.9.
Purpose
Prostate-specific antigen (PSA) flare is a well-known phenomenon in patients with prostate cancer, but its impact during radium-223 dichloride (223RaCl2) therapy is still unclear. This radioisotope has shown to improve overall survival in metastatic castration-resistant prostate cancer (mCRPC). We sought to evaluate the impact of PSA flare on survival and its relation with metabolic parameters on 18F-labeled sodium fluoride PET/CT.Methods
We conducted a retrospective study of 168 patients with mCRPC (median age 69; median PSA 29.7) receiving 223RaCl2. Overall survival (OS) and progression-free survival (PFS), estimated by the Kaplan–Meier method and compared using a log-rank test, were evaluated for patient groups corresponding to different definitions of PSA flare. Metabolic 18F-fluoride PET/CT data were analyzed as well.Results
Immediate PSA decline was observed in 49 patients (29.2%), whereas no PSA response was observed in 59 patients (35.1%). PSA flare (defined as rise after the first cycle followed by decrease below the baseline) was observed in 20 patients (11.9%) and PSA flare followed by a decrease from peak but not below baseline was observed in 40 (23.8%). The first flare subgroup had a median PFS and OS of 20.8 and 23.9 months, respectively. These outcomes were not significantly different from patients with immediate PSA decrease, but were significantly better than in patients with persistent PSA elevation (3.1 months for PFS and 11.5 months for OS, p < 0.001). Moreover, the PSA flare group showed an alkaline phosphatase (ALP) decrease significantly greater than non-responders (p = 0.003). Metabolic 18F-fluoride PET/CT data were available in 35 patients at baseline and during 233RaCl2 therapy. The tumor burden reduction, expressed by ΔTLF10 and ΔFTV10, was more evident within PSA flare group below baseline than non-responders (p = 0.005 and 0.001, respectively).Conclusions
This report suggests that a flare does not necessarily indicate lack of response to 223RaCl2 therapy.10.
Purpose
To present data from an interim analysis of a Phase II trial designed to determine the feasibility, safety, and efficacy of individualising treatment based on renal dosimetry, by giving as many cycles as possible within a maximum renal biologically effective dose (BED).Method
Treatment was given with repeated cycles of 7.4 GBq 177Lu-DOTATATE at 8-12-week intervals. Detailed dosimetry was performed in all patients after each cycle using a hybrid method (SPECT?+?planar imaging). All patients received treatment up to a renal BED of 27?±?2 Gy (α/β?=?2.6 Gy) (Step 1). Selected patients were offered further treatment up to a renal BED of 40?±?2 Gy (Step 2). Renal function was followed by estimation and measurement of the glomerular filtration rate (GFR).Results
Fifty-one patients were included in the present analysis. Among the patients who received treatment as planned, the median number of cycles in Step 1 was 5 (range 3-7), and for those who completed Step 2 it was 7 (range 5-8); 73% were able to receive >4 cycles. Although GFR decreased in most patients after the completion of treatment, no grade 3-4 toxicity was observed. Patients with a reduced baseline GFR seemed to have an increased risk of GFR decline. Five patients received treatment in Step 2, none of whom exhibited a significant reduction in renal function.Conclusions
Individualising PRRT using renal dosimetry seems feasible and safe and leads to an increased number of cycles in the majority of patients. The trial will continue as planned.11.
Aim
Our aim was to evaluate overall survival and parameters prognosticating longer survival in a large and homogeneous group of patients treated with 177Lu-PSMA-617 radioligand therapy with heavily pretreated advanced metastatic castration resistant prostate cancer.Methods
A total of 104 patients were treated with 351 cycles of 177Lu-PSMA-617. Prostate specific antigen (PSA) changes after the first cycle of therapy were documented prior to a second cycle. Patients were followed-up for overall survival (OS). Any PSA decline, PSA decline ≥50%, initial PSA, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), visceral metastases and cumulative injected activity were analyzed and evaluated according to OS. Multivariable analysis with parameters with a p-value ≤0.05 in univariate analysis was performed, additionally adjusting for age and presence of visceral metastases.Results
A total of 51 patients (49%) died during the observation period. The majority of patients (97%) presented with bone metastases, 77% with lymph node metastases and 32% with visceral metastases. All patients were treated with at least one line of chemotherapy. Either abiraterone or enzalutamide had been given in 100% of the patients. Any PSA decline occurred in 70 (67%) and a PSA decline ≥50% in 34 (33%) of patients after the first cycle. The median OS was 56.0 weeks (95%CI: 50.5–61.5). Initial PSA decline ≥50%, initial LDH, visceral metastases, second line chemotherapy or prior radium-223 did not have an effect on survival, whereas any initial PSA decline, initial ALP <220 U/L and cumulative injected activity ≥18.8 GBq were associated with a longer survival. A step-by-step analysis revealed a PSA decline ≥20.87% as the most noticeable cut-off prognosticating longer survival, which remained an independent prognosticator of improved OS in the multivariate analysis.Conclusion
177Lu-PSMA-617 RLT is a new effective therapeutic and seems to prolong survival in patients with advanced mCRPC pretreated with chemotherapy, abiraterone and/or enzalutamide.12.
Purpose
Peptide receptor radionuclide therapy (PRRT) with 177Lu-octreotate is commonly administered at empiric, fixed amounts of injected radioactivity (IA). This results in highly variable absorbed doses to critical organs and suboptimal treatment of most patients. The primary aims of this study were to design a personalized PRRT (P-PRRT) protocol based on dosimetry, and to perform a simulation of this protocol in a retrospective cohort of patients with neuroendocrine tumours, in order to assess the potential of P-PRRT to safely increase the absorbed dose to the tumour during a four-cycle induction course.Methods
Thirty-six patients underwent 122 fixed-IA 177Lu-octreotate PRRT cycles with quantitative SPECT/CT-based dosimetry. Twenty-two patients completed a four-cycle induction course (29.6?±?2.4 GBq cumulative IA), with kidney, bone marrow and maximum tumour absorbed doses of 16.2?±?5.5, 1.3?±?0.8, and 114?±?66 Gy, respectively. We simulated a P-PRRT regime in which the renal absorbed dose per IA was predicted by the body surface area and glomerular filtration rate for the first cycle, and by renal dosimetry of the previous cycle(s) for the following cycles. Personalized IA was adjusted at each cycle in order to reach the prescribed renal absorbed dose of 23 Gy over four cycles (with a 25-50% reduction when renal or bone marrow function was impaired). Simulated IA and absorbed doses were based on actual patient characteristics, laboratory values and absorbed doses per IA delivered at each cycle.Results
In the P-PRRT regime, cumulative IA could have been increased to 43.7?±?16.5 GBq over four induction cycles (10.9?±?5.0 GBq per cycle), yielding cumulative kidney, bone marrow and maximum tumour absorbed doses of 21.5?±?2.5, 1.63?±?0.61, and 163.4?±?85.9 Gy, respectively. This resulted in an average 1.48-fold increase in cumulative maximum tumour absorbed dose over empiric PRRT (range, 0.68–2.64-fold; P?=?0.0013).Conclusion
By standardizing the renal absorbed dose delivered during the induction course, P-PRRT has the potential to significantly increase tumour absorbed dose, thus to augment the therapeutic benefit while limiting toxicity.13.
Jolanta Kunikowska Dariusz Pawlak Marianna I. Bąk Beata Kos-Kudła Renata Mikołajczak Leszek Królicki 《Annals of nuclear medicine》2017,31(5):347-356
Introduction
The peptide receptor radionuclide therapy (PRRT) with 90Y and 177Lu is a form of molecular targeted therapy for inoperable or disseminated neuroendocrine tumors (NET).Aim
The aim of the study was to evaluate clinical results and long-term side effects of tandem 90Y /177Lu-DOTATATE therapy in patients with NET. Additionally, we evaluated clinical results with reference to the primary site.Materials and methods
59 patients with disseminated NET were included in the study prospectively. 3–5 cycles of combined 1:1 90Y/177Lu-DOTATATE (total injected activity 11.1–16.65 GBq) with mixed amino acids for kidney protection were performed.Results
During a median follow-up of 75.8 months, the PFS was 32.2 months, and the OS was 82 months; 25 patients died. Depending on primary tumor’s site, the PFS and the OS for pancreatic NET vs. small bowel, NET vs. large bowel, NET were 30.4 vs. 29.5 vs. 40.3 and 78.9 vs. 58.1 vs. 82.5, respectively. The observed 5-year overall survival was 63%, and a 2-year risk of progression was 39.4%. The following imaging response was observed: CR in 2%, PR in 22%, SD in 65%, and PD in 6% patients. The disease control rate was 89%. The objective response rate was 24%. The PRRT was well tolerated by all patients. One patient (2%) revealed MDS, and one patient (2%) grade 3 nephrotoxicity. No other grade 3 and 4 hematological or renal toxicity was observed.Conclusions
These results indicated the tandem 90Y/177Lu-DOTATATE therapy for patients with disseminated/inoperable NET as highly effective and safe, considering long-term side effects. In the majority of patients, clinical improvement was observed.14.
Purpose
We investigated the role of 18F-methylcholine (FCH) PET/CT in the early evaluation of patients with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide.Methods
The study group comprised 36 patients with a median age of 72 years (range 48–90 years) who were treated with enzalutamide 160 mg once daily after at least one chemotherapeutic regimen with docetaxel. Patients were evaluated monthly for serological prostate-specific antigen (PSA) response. FCH PET/CT was performed at baseline and repeated after 3–6 weeks. Univariate and multivariate Cox regression models addressed potential predictors of progression-free survival (PFS) and overall survival (OS).Results
At a median follow-up of 24.2 months (range 1.8–27.3 months), 34 patients were evaluable for early FCH PET/CT evaluation of response, and of these 17 showed progressive disease (PD) and 17 had stable disease or a partial response. A decrease in PSA level of more than 50 % was observed in 21 patients. Early FCH PET/CT PD predicted radiological PD 3 months in advance of CT in 12 of 18 patients (66 %) and was discordant with the decrease in PSA level in 13 patients. In 6 of these, biochemical PD was confirmed in 2 months. In multivariate analysis, only decrease in PSA level and FCH PET/CT were significant predictors of PFS (p?=?0.0005 and p?=?0.029, respectively), whereas decrease in PSA level alone was predictive of OS (p?=?0.007).Conclusion
This is one of the first studies to evaluate the role of FCH PET/CT as an early predictor of outcome in mCRPC patients treated with enzalutamide. Our preliminary results suggest that the combination of FCH PET/CT and decrease in PSA level could be a valid tool to predict PFS in mCRPC patients. PSA remains the single most important prognostic factor, while FCH PET/CT does not add more information on OS beyond that obtained from PSA. Further studies in larger populations are needed to confirm these data and to clarify the role of FCH PET/CT in predicting response to enzalutamide in mCRPC patients.15.
Objectives
Our aim was to provide further evidence for the efficacy/safety of radioembolization using yttrium-90-resin microspheres for unresectable chemorefractory liver metastases from colorectal cancer (mCRC).Methods
We followed 104 consecutively treated patients until death. Overall survival (OS) was calculated from the day of the first radioembolization procedure. Response was defined by changes in tumour volume as defined by Response Evaluation Criteria in Solid Tumours (RECIST) v1.0 and/or a ≥30 % reduction in serum carcinoembryonic antigen (CEA) at 3 months.Results
Survival varied between 23 months in patients who had a complete response to prior chemotherapy and 13 months in patients with a partial response or stable disease. Median OS also significantly improved (from 5.8 months to 17.1 months) if response durability to radioembolization extended beyond 6 months. Patients with a positive trend in CEA serum levels (≥30 % reduction) at 3 months post-radioembolization also had a survival advantage compared with those who did not: 15.0 vs 6.7 months. Radioembolization was well tolerated. Grade 3 increases in bilirubin were reported in 5.0 % of patients at 3 months postprocedure.Conclusions
After multiple chemotherapies, many patients still have a good performance status and are eligible for radioembolization. This single procedure can achieve meaningful survivals and is generally well tolerated.Key Points
? After multiple chemotherapies, many patients are still eligible for radioembolization (RE). ? RE can achieve meaningful survival in patients with chemorefractory liver-predominant metastatic colorectal cancer (mCRC). ? Tumour responsiveness to prior systemic treatments is a significant determinant of overall survival (OS) after RE. ? Radioembolization in patients with a good performance status is generally well tolerated.16.
Amir Sabet Torjan Haslerud Ulrich-Frank Pape Amin Sabet Hojjat Ahmadzadehfar Frank Grünwald Stefan Guhlke Hans-Jürgen Biersack Samer Ezziddin 《European journal of nuclear medicine and molecular imaging》2014,41(2):205-210
Purpose
We assessed the outcome and toxicity of salvage therapy (repeat treatment) with 177Lu-octreotate and high cumulative activities in patients with metastatic gastroenteropancreatic neuroendocrine tumours (GEP-NET).Methods
We retrospectively analysed a consecutive cohort of 33 patients with metastatic GEP-NET who underwent salvage peptide receptor radionuclide therapy (PRRT) in our institution. All patients had progressive NET prior to salvage treatment and had shown an initial response to PRRT. The mean cumulative activity was 44.3 GBq (30.0–83.7 GBq). Radiographic response was assessed using CT and/or MRI according to modified SWOG criteria. Toxicity was evaluated using laboratory data, including complete blood counts and renal function tests using CTCAE 3.0. Survival analysis was performed with the Kaplan-Meier curve method and a significance level at p?<?0.05.Results
Radiographic responses consisted of complete response in 1 patient (3.0 %), partial response in 6 patients (18.2 %), minor response in 1 patient (3.0 %), stable disease in 14 patients (42.4 %), and progressive disease in 11 patients (33.3 %). Median progression-free survival (PFS) from the start of salvage therapy was 13 months (95 % CI 9–18) and patients with a history of a durable PFS after initial PRRT tended to have long-lasting PFS after salvage treatment (p?=?0.04). None of the patients developed severe nephrotoxicity (grade 3/4) or a myelodysplastic syndrome during follow-up. Relevant albeit reversible haematotoxicity (grade 3/4) occurred in 7 patients (21.2 %). The cumulative administered activity was not associated with an increased incidence of haematotoxicity.Conclusion
PRRT with 177Lu-octreotate in the re-treatment setting is safe and effective in patients with metastatic GEP-NET.17.
Purpose
To evaluate the patterns of relapse and impact on the intended treatment when using 68Ga-prostate-specific membrane antigen (PSMA) ligand positron emission tomography/computed tomography (PET/CT) imaging for restaging of disease in patients with biochemical relapse after radical prostatectomy (RP) before salvage radiotherapy (sRT).Methods
In all, 39 patients with biochemical recurrence after RP who had no primary indication for adjuvant RT due to the absence of biologically unfavorable disease (e.g., extracapsular extension, seminal vesicle invasion, positive margins, or lymph node involvement) underwent a 68Ga-PSMA ligand PET/CT for planning of sRT.Results
PET/CT was positive in 84.6% (33/39) of patients. A total of 61 lesions were observed in these patients (on average 1.8 lesions per patient); 30.3% (10/33) of patients had locally recurrent disease in the prostatic bed. The clinical TNM stage (TNM: tumour-lymph nodes-metastasis-classification) was altered in 69.7% (23/33) of patients following PET, resulting in individualized treatment concepts. A prostate-specific antigen (PSA) >1.0?ng/mL was significantly associated with an increased risk of extrapelvic metastatic disease (p = 0.048). The PSA level at the time of PSMA ligand PET/CT correlated with the peak standardized uptake value (SUVpeak; p = 0.002). According to current clinical guidelines, the remaining 15.4% (6/39) of patients without evidence of disease on PET received sRT with a dose of 66.0?Gy.Conclusion
Our results suggest that in patients with biochemical recurrence who did not receive early sRT, a 68Ga-PSMA ligand PET/CT for restaging of disease allows for tailoring and individualizing treatment. Particularly in patients with PSA levels above 1.0?ng/mL, a 68Ga-PSMA ligand PET/CT should be performed for therapy planning, since patients often have metastases not confined to the pelvis.18.
Federica?Matteucci Emilio?Mezzenga Paola?Caroli Valentina?Di?Iorio Anna?Sarnelli Monica?Celli Lorenzo?Fantini Andrea?Moretti Riccardo?Galassi Ugo?De?Giorgi Giovanni?Paganelli
Purpose
Urea-based prostate-specific membrane antigen (PSMA) ligands labelled with 68Ga or 177Lu are new tracers with great potential for theranostic approaches in prostate cancer. However, clinical studies have shown that the kidneys are one of the off-target organs along with the salivary and lacrimal glands. In the kidneys, PSMA is physiologically expressed in the apical epithelium of the proximal tubules, and mannitol acts as an osmotic diuretic in these tubules. We investigated the potential of mannitol to reduce renal uptake of 68Ga-PSMA.Methods
Kidney uptake (SUVmax) was calculated in nine patients undergoing 68Ga-PSMA PET/CT at baseline (b-PET/CT) and after intravenous infusion of 500 ml of 10% mannitol (m-PET/CT). Two different infusion schemes for mannitol were used: (1) 500 ml mannitol was infused over 40 min after 68Ga-PSMA administration (A-infusion) and (2) 250 ml mannitol was infused over 15 min before and again after 68Ga-PSMA administration (B-infusion).Results
In patients receiving the A-infusion, mean SUVmax increased by 11.9% and 7.4% in the right and left kidney, respectively. In patients receiving the B-infusion, mean SUVmax decreased by 24.3% and 22.4% in the right and left kidney, respectively.Conclusion
Our preliminary findings indicate that mannitol may play a role in reducing off-target 68Ga-PSMA renal uptake. Administration of the osmotic diuretic should be rapid and start before 68Ga-PSMA injection. These results warrant dosimetric studies in patients treated with 177Lu-PSMA to find the best scheme for mannitol administration.19.
Tiziano Graziani Francesco Ceci Paolo Castellucci Giulia Polverari Giacomo Maria Lima Filippo Lodi Alessio Giuseppe Morganti Andrea Ardizzoni Riccardo Schiavina Stefano Fanti 《European journal of nuclear medicine and molecular imaging》2016,43(11):1971-1979
Purpose
To evaluate 11C-choline PET/CT as a diagnostic tool for restaging prostate cancer (PCa), in a large, homogeneous and clinically relevant population of patients with biochemical recurrence (BCR) of PCa after primary therapy. The secondary aim was to assess the best timing for performing 11C-choline PET/CT during BCR.Methods
We retrospectively analysed 9,632 11C-choline PET/CT scans performed in our institution for restaging PCa from January 2007 to June 2015. The inclusion criteria were: (1) proven PCa radically treated with radical prostatectomy (RP) or with primary external beam radiotherapy (EBRT); (2) PSA serum values available; (3) proven BCR (PSA >0.2 ng/mL after RP or PSA >2 ng/mL above the nadir after primary EBRT with rising PSA levels). Finally, 3,203 patients with recurrent PCa matching all the inclusion criteria were retrospectively enrolled and 4,426 scans were analysed.Results
Overall, 52.8 % of the 11C-choline PET/CT scans (2,337/4,426) and 54.8 % of the patients (1,755/3,203) were positive. In 29.4 % of the scans, at least one distant finding was observed. The mean and median PSA values were, respectively, 4.9 and 2.1 ng/mL at the time of the scan (range 0.2 – 50 ng/mL). In our series, 995 scans were performed in patients with PSA levels between 1 and 2 ng/mL. In this subpopulation the positivity rate in the 995 scans was 44.7 %, with an incidence of distant findings of 19.2 % and an incidence of oligometastatic disease (one to three lesions) of 37.7 %. The absolute PSA value at the time of the scan and ongoing androgen deprivation therapy were associated with an increased probability of a positive 11C-choline PET/CT scan (p?<?0.0001). In the ROC analysis, a PSA value of 1.16 ng/mL was the optimal cut-off value. In patients with a PSA value <1.16 ng/mL, 26.8 % of 1,426 11C-choline PET/CT scans were positive, with oligometastatic disease in 84.7 % of positive scans.Conclusion
In a large cohort of patients, the feasibility of 11C-choline PET/CT for detecting the sites of metastatic disease in PCa patients with BCR was confirmed. The PSA level was the main predictor of a positive scan with 1.16 ng/mL as the optimal cut-off value. In the majority of positive scans oligometastatic disease, potentially treatable with salvage therapies, was observed.20.