Introduction
The impact of prior therapies, especially chemotherapy, on overall survival (OS) in patients with castration-resistant prostate cancer (CRPC) receiving
177
LuLu-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
177
Lu-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
177
LuLu-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
177
LuLu-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.
Due to partly conflicting studies, further research is warranted with the QGS software package, with regard to the performance of gated FDG PET phase analysis as compared to gated MPS as well as the ...establishment of possible cut-off values for FDG PET to define dyssynchrony.
Gated MPS and gated FDG PET datasets of 93 patients were analyzed with the QGS software. BW, Phase SD, and Entropy were calculated and compared between the methods. The performance of gated PET to identify dyssynchrony was measured against SPECT as reference standard. ROC analysis was performed to identify the best discriminator of dyssynchrony and to define cut-off values.
BW and Phase SD differed significantly between the SPECT and PET. There was no significant difference in Entropy with a high linear correlation between methods.
There was only moderate agreement between SPECT and PET to identify dyssynchrony. Entropy was the best single PET parameter to predict dyssynchrony with a cut-off point at 62%.
Gated MPS and gated FDG PET can assess LVMD. The methods cannot be used interchangeably. Establishing reference ranges and cut-off values is difficult due to the lack of an external gold standard. Further prospective research is necessary.
Purpose
Early identification of aggressive disease could improve decision support in pancreatic neuroendocrine tumor (pNET) patients prior to peptide receptor radionuclide therapy (PRRT). The ...prognostic value of intratumoral textural features (TF) determined by baseline somatostatin receptor (SSTR)-positron emission tomography (PET) before PRRT was analyzed.
Procedures
Thirty-one patients with G1/G2 pNET were enrolled (G2,
n
= 23/31). Prior to PRRT with
177
LuDOTATATE (mean, 3.6 cycles), baseline SSTR-PET computed tomography was performed. By segmentation of 162 (median per patient, 5) metastases, intratumoral TF were computed. The impact of conventional PET parameters (SUV
mean/max
), imaging-based TF, and clinical parameters (Ki67, CgA) for prediction of both progression-free survival (PFS) and overall survival (OS) after PRRT were evaluated.
Results
Within a median follow-up of 3.7 years, tumor progression was detected in 21 patients (median, 1.5 years) and 13/31 deceased (median, 1.9 years). In ROC analysis, the TF entropy, reflecting derangement on a voxel-by-voxel level, demonstrated predictive capability for OS (cutoff = 6.7, AUC = 0.71,
p
= 0.02). Of note, increasing entropy could predict a longer survival (> 6.7, OS = 2.5 years, 17/31), whereas less voxel-based derangement portended inferior outcome (< 6.7, OS = 1.9 years, 14/31). These findings were supported in a G2 subanalysis (> 6.9, OS = 2.8 years, 9/23
vs
. < 6.9, OS = 1.9 years, 14/23). Kaplan–Meier analysis revealed a significant distinction between high- and low-risk groups using entropy (
n
= 31,
p
< 0.05). For those patients below the ROC-derived threshold, the relative risk of death after PRRT was 2.73 (
n
= 31,
p
= 0.04). Ki67 was negatively associated with PFS (
p
= 0.002); however, SUV
mean/max
failed in prognostication (n.s.).
Conclusions
In contrast to conventional PET parameters, assessment of intratumoral heterogeneity demonstrated superior prognostic performance in pNET patients undergoing PRRT. This novel PET-based strategy of outcome prediction prior to PRRT might be useful for patient risk stratification.
Introduction
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.
Methods
The study included patients with progressive metastatic castration-resistant prostate cancer (mCRPC), who underwent RLT with
177
LuLu-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.
Results
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 with <6 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.
Conclusion
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.
Purpose
There are controversial debates if patients with Hürthle cell carcinoma, also known as oxyphilic or oncocytic cell follicular thyroid carcinoma, have a poorer outcome. In this study, we ...systematically evaluated the clinical outcome in a large patient cohort following thyroidectomy and initial I-131 radioactive iodine therapy (RIT).
Methods
We retrospectively evaluated a total of 378 patients with diagnosed oncocytic follicular Hürthle cell carcinoma (OFTC) (
N
= 126) or with classical follicular thyroid carcinoma (FTC) (
N
= 252). Patients received thyroidectomy and complementary I-131 RIT. Clinical data regarding basic demographic characteristics, tumor grade, persistent disease and recurrence during follow-up, and disease-free, disease-specific, and overall survival were collected during follow-up of 6.9 years (interquartile range 3.7; 11.7 years). Univariate and multivariate analyses were used to identify factors associated with disease-related and overall survival.
Results
Before and after matching for risk factors, recurrence was significantly more frequently diagnosed in OFTC patients during follow-up (17% vs. 8%;
p
value 0.037). Likewise, OFTC patients presented with a reduced mean disease-free survival of 17.9 years (95% CI 16.0–19.8) vs. 20.1 years (95% CI 19.0–21.1) in FTC patients (
p
value 0.027). Multivariate analysis revealed OFTC (HR 0.502; 95% CI 0.309–0.816) as the only independent prognostic factor for disease-free survival. Distant metastases of OFTC patients were significantly less iodine-avid (
p
value 0.014). Mean disease-specific and overall survival did not differ significantly (
p
value 0.671 and 0.687) during follow-up of median 6.9 years (3.7; 11.7 years).
Conclusions
Our study suggests that recurrence is more often seen in OFTC patients. OFTC patients have a poorer prognosis for disease-free survival. Thus, OFTC and FTC behave differently and should be categorized separately. However, patients suffering from OFTC present with the same overall and disease-specific survival at the end of follow-up indifferent to FTC patients after initial RIT.
Purpose
Oncocytic (Hürthle cell) papillary thyroid carcinoma (OPTC) is a rare variant of the papillary thyroid carcinoma (PTC) which comprises approximately 1 to 11 % of PTC cases. Its clinical ...course and prognosis have not been comprehensively documented and the clinical outcome remains a controversial issue. Therefore, we investigated the long-term prognosis after thyroidectomy and (adjuvant) initial radioactive iodine therapy (RIT) of OPTC compared to PTC.
Methods
A total of 563 patients (47 with OPTC and 516 with PTC) with a median follow-up of 9.9 (0.3; 23.5) years were studied. All patients underwent thyroidectomy followed by (adjuvant) initial RIT. Data on the patients’ demographics, pathology, laboratory findings, imaging studies, treatment, and follow-up including recurrence, and disease-specific survival were collected. Cox’s multivariate regression model was used to identify independent prognostic factors for survival.
Results
OPTC patients were significantly older (55.2 ± 12.3 years) than PTC patients (50.3 ± 13.5) at the time of initial diagnosis (
p
value 0.016). Initial tumor size was larger in the OPTC group (2.8 ± 1.8 cm for OPTC patients, 1.5 ± 1.2 cm for PTC patients,
p
value < 0.001). Before matching, OPTC patients presented more often with evidence of disease at the last visit of follow-up (
p
value 0.046). However, this difference was not observed anymore after matching for risk factors (
p
value 0.637). Disease-specific survival did not differ significantly. Age (HR, 1.183; 95% CI, 1.097–1.276) was identified as an independent prognostic factor for disease-specific survival. OPTC patients predominantly showed a recurrence of distant metastasis within a shorter time despite being not statistically significant.
Conclusion
At initial diagnosis, OPTC shows significant differences in terms of age and initial tumor size compared to PTC. Patients suffering from OPTC present with the same clinical long-term outcome indifferent to PTC after (adjuvant) initial RIT after matching.
Purpose
Nodal recurrent prostate cancer (PCa) represents a common state of disease, amenable to local therapy. PSMA-PET/CT detects PCa recurrence at low PSA levels. The aim of this study was to ...evaluate the outcome of PSMA-PET/CT-based salvage radiotherapy (sRT) for lymph node (LN) recurrence.
Methods
A total of 100 consecutive patients treated with PSMA-PET/CT-based salvage elective nodal radiotherapy (sENRT) for LN recurrence were retrospectively examined. Patients underwent PSMA-PET/CT scan due to biochemical persistence (bcP, 76%) or biochemical recurrence (bcR, 24%) after radical prostatectomy (RP). Biochemical recurrence-free survival (BRFS) defined as PSA < post-RT nadir + 0.2 ng/ml and distant metastasis-free survival (DMFS) were calculated using the Kaplan–Meier method and uni- and multivariate analysis was performed.
Results
Median follow-up was 37 months. Median PSA at PSMA-PET/CT was 1.7 ng/ml (range 0.1–40.1) in patients with bcP and 1.4 ng/ml (range 0.3–5.1) in patients with bcR. PSMA-PET/CT detected 1, 2, and 3 or more LN metastases in 35%, 23%, and 42%, respectively. Eighty-three percent had only pelvic, 2% had only paraaortic, and 15% had pelvic and paraaortic LN metastases. Cumulatively, a total dose converted to EQD2
1.5 Gy
of 66 Gy (60–70 Gy) was delivered to the prostatic fossa, 70 Gy (66–72 Gy) to the local recurrence, if present, 65.1 Gy (56–66 Gy) to PET-positive lymph nodes, and 47.5 Gy (42.4–50.9 Gy) to the lymphatic pathways. Concomitant androgen deprivation therapy (ADT) was administered in 83% of patients. One-, 2-, and 3-year BRFS was 80.7%, 71.6%, and 65.8%, respectively. One-, 2-, and 3-year DMFS was 91.6%, 79.1%, and 66.4%, respectively. In multivariate analysis, concomitant ADT, longer ADT duration (≥ 12 vs. < 12 months) and LN localization (pelvic vs. paraaortic) were associated with improved BRFS and concomitant ADT and lower PSA value before sRT (< 1 vs. > 1 ng/ml) with improved DMFS, respectively. No such association was seen for the number of affected lymph nodes.
Conclusions
Overall, the present analysis shows that the so far, unmatched sensitivity and specificity of PSMA-PET/CT translates in comparably high BRFS and DMFS after PSMA-PET/CT-based sENRT for patients with PCa LN recurrence. Concomitant ADT, duration of ADT, PSA value before sRT, and localization of LN metastases were significant factors for improved outcome.
Purpose
Readers need to be informed about potential pitfalls of
68
GaGa-PSMA-11 PET interpretation.
Methods
Here we report
68
GaGa-PSMA-11 PET findings discordant with the histopathology/composite ...reference standard in a recently published prospective trial on 635 patients with biochemically recurrent prostate cancer.
Results
Consensus reads were false positive in 20 regions of 17/217 (8%) patients with lesion validation. Majority of the false positive interpretations (13 of 20, 65%) occurred in the context of suspected prostate (bed) relapse (T) after radiotherapy (
n
= 11); other false positive findings were noted for prostate bed post prostatectomy (T,
n
= 2), pelvic nodes (N,
n
= 2), or extra pelvic lesions (M,
n
= 5). Major sources of false positive findings were PSMA-expressing residual adenocarcinoma with marked post-radiotherapy treatment effect. False negative interpretation occurred in 8 regions of 6/79 (8%) patients with histopathology validation, including prostate (bed) (
n
= 5), pelvic nodes (
n
= 1), and extra pelvic lesions (
n
= 2). Lesions were missed mostly due to small metastases or adjacent bladder/urine uptake.
Conclusion
68
GaGa-PSMA-11 PET at biochemical recurrence resulted in less than 10% false positive interpretations. Post-radiotherapy prostate uptake was a major source of
68
GaGa-PSMA-11 PET false positivity. In few cases, PET correctly detects residual PSMA expression post-radiotherapy, originating however from treated, benign tissue or potentially indolent tumor remnants.
Trial registration number
ClinicalTrials.gov
Identifiers: NCT02940262 and NCT03353740.
To evaluate quantitative myocardial perfusion SPECT/CT datasets for routine clinical reporting and the assessment of myocardial tracer uptake in patients with severe TVCAD.
MPS scans were ...reconstructed as quantitative SPECT datasets using CTs from internal (SPECT/CT, Q_INT) and external (PET/CT, Q_EXT) sources for attenuation correction. TPD was calculated and compared to the TPD from non-quantitative SPECT datasets of the same patients. SUVmax, SUVpeak, and SUVmean were compared between Q_INT and Q_EXT SPECT datasets. Global SUVmax and SUVpeak were compared between patients with and without TVCAD.
Quantitative reconstruction was feasible. TPD showed an excellent correlation between quantitative and non-quantitative SPECT datasets. SUVmax, SUVpeak, and SUVmean showed an excellent correlation between Q_INT and Q_EXT SPECT datasets, though mean SUVmean differed significantly between the two groups. Global SUVmax and SUVpeak were significantly reduced in patients with TVCAD.
Absolute quantification of myocardial tracer uptake is feasible. The method seems to be robust and principally suitable for routine clinical reporting. Quantitative SPECT might become a valuable tool for the assessment of severe coronary artery disease in a setting of balanced ischemia, where potentially life-threatening conditions might otherwise go undetected.
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