Tumor Sink Effect with Prostate-Specific Membrane Antigen-Targeted Theranostics in Patients with Metastatic Castration-Resistant Prostate Cancer: Intra-Individual Evaluations
Abstract
:Simple Summary
Abstract
1. Introduction
2. Patients and Methods
2.1. Study Design and Endpoints
2.2. Patients and Ethics
2.3. 68Ga-PSMA-11 PET/CT
2.4. Calculation of TLP
2.5. 177Lu-PSMA-617 RLT
2.6. Selection of Responders to 177Lu-PSMA-617 RLT
2.7. Statistics
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
18F-FDG | 18-fluoride-fluorodeoxyglucose |
68Ga | 68-gallium |
177Lu | 177-lutetium |
∆TLP | Change from baseline to post-RLT in total lesion PSMA |
∆SUVmean | Change in mean standardized uptake value |
ADT | Androgen deprivation therapy |
ALP | Alkaline phosphatase |
CT | Computed tomography |
ECOG | Eastern Cooperative Oncology Group |
mCRPC | Metastatic castration-resistant prostate cancer |
MIP | Maximum intensity projection |
NA | Not available |
NAAD | Novel androgen axis drugs |
NS | Not studied |
PERCIST | PET Response in Solid Tumor Criteria |
PET | Postron emission tomography |
PR | Partial response |
PSA | Prostate-specific antigen |
PSMA | Prostate-specific membrane antigen |
RLT | Radioligand therapy |
SUVmax | Maximum standardized uptake value |
SUVmean | Mean standardized uptake value |
TLP | Total lesion PSMA |
References
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Patient Characteristics | Value |
---|---|
Age | |
Median (minimum–maximum), yrs | 72.5 (53–88) |
Age ≥ 75 yrs, % (n) | 42% (14) |
PSA [ng/mL] | |
Median (minimum–maximum) | 208 (21–3025) |
ALP [U/L] | |
Median (minimum–maximum) | 133 (35–1753) |
Hemoglobin [g/dL] | |
Median (minimum–maximum) | 12 (6–16) |
<13 g/dL, % (n) | 48% (16) |
ECOG performance status, % (n) | |
0 | 21% (7) |
1 | 36% (12) |
≥2 | 43% (14) |
Sites of metastasis a, % (n) | |
Bone | 88% (29) |
Lymph node | 67% (22) |
Liver | 12% (4) |
Other | 18% (6) |
Prior therapies a, % (n) | |
Radical prostatectomy | 45% (15) |
Radiation | 58% (19) |
ADT | 100% (33) |
Any NAAD | 88% (29) |
Abiraterone | 73% (24) |
Enzalutamide | 61% (20) |
Abiraterone and enzalutamide | 45% (15) |
Any chemotherapy | 73% (24) |
Docetaxel | 73% (24) |
Cabazitaxel | 21% (7) |
Docetaxel and cabazitaxel | 21% (7) |
[223Ra]Ra-dichloride | 21% (7) |
Other | 15% (5) |
Variable | Value | Spleen | Right Parotid Gland |
---|---|---|---|
% (n) | p | p | |
N Age a | 100% (33) | - | - |
≤75 years | 58% (19) | ||
>75 years | 42% (14) | 0.957 | 0.321 |
PSA a | |||
≤200 ng/mL | 45% (15) | ||
>200 ng/mL | 55% (18) | 0.215 | 0.957 |
Performance status a | |||
ECOG 0–1 | 58% (19) | ||
ECOG 2–3 | 42% (14) | 0.123 | 0.255 |
Cumulative 177Lu-PSMA-617 activity: first two cycles | |||
≤12.5 GBq | 48% (16) | ||
>12.5 GBq | 52% (17) | 0.873 | 0.873 |
TLP a | |||
≤500 mL × SUV | 48% (16) | ||
>500 mL × SUV | 52% (17) | 0.063 | 0.217 |
Prior chemotherapy a | |||
No | 27% (9) | ||
Yes | 73% (24) | 0.592 | 0.921 |
Study (N) | Design | Main Healthy-Organ-Related Endpoint(s) | Healthy Organ | |||||
---|---|---|---|---|---|---|---|---|
Salivary Glands | Spleen | Liver | Kidney | Lacrimal Glands | Red Marrow | |||
Gaertner et al., 2017 [14] (N = 135) | Retrospective inter-patient comparison a | SUVmean | √ | √ | √ | √ | √ | NS |
Filss et al. 2018 [15] (N = 11) | Retrospective inter-patient evaluation a | Kidney dose from one course of 177Lu-PSMA-617 RLT | √ | NS | NS | √ | NS | NS |
Begum et al., 2018 [1] (N = 13) | Simulation study using a physiologically-based pharmacokinetic model to analyze actual patient data a | Biologically-effective doses to the kidneys, salivary glands, and red marrow under simulated PSMA+ total tumor volumes of 0.1–10L | √ | Non-significant | Non- significant | √ | NS | The dose increased along with the total PSMA-positive tumor volume; this observation was attributed to higher whole-body retention with greater tumor burden |
Violet et al., 2019 [16] (N = 30) | Prospective inter-patient evaluation a | Mean absorbed dose | √ | Non-significant | Non-significant | √ | NS | Non-significant |
Werner et al., 2020 [17] (N = 40) | Retrospective evaluation b | Spearman’s rank correlation between tumor volume and organ uptake corrected to lean body mass or body weight | Non-significant | Non-significant | Non-significant | Non-significant | Non-significant | NS |
Cysouw et al., 2020 [20] (N = 1) | Case report of one patient a | Visual uptake in organs | √ | √ | √ | √ | NS | NS |
Tuncel et al., 2021 [2] (N = 65) | Retrospective inter-patient comparison a | Correlation of the SUVmax in the tumor and healthy tissue with the metabolic tumor volume (sum of volumes of tissue suspicious for malignancy with increased PSMA uptake) and the total lesion PSMA index (metabolic tumor volume x SUVmean) | √ d | NS | √ d | √ d | NS | NS |
Peters et al., 2022 [18] (N = 10) | Prospective dosimetry study embedded in a prospective clinical study c | Correlation of the SUVmax in the tumor and healthy tissue with the metabolic tumor volume (sum of volumes of tissue suspicious for malignancy with increased PSMA uptake) and the total lesion PSMA index (metabolic tumor volume x SUVmean) | Non-significant | Non-significant | Non-significant | Non-significant | NS | NS |
Gafita et al., 2022 [19] (N = 356) | International, multicenter retrospective analysis with inter-patient comparison a | Correlation of the total PSMA-positive tumor volume as a continuous variable and by quintiles with organ SUVmean | √ | √ | √ | √ | NS | NS |
Present study (N = 33, n = 25 for 1 comparison) | Retrospective intra-individual comparison a | Correlation of ∆TLP and organ ∆SUVmean after two courses of 177Lu-PSMA-617; correlation of the baseline and post-RLT organ SUVmean in RLT molecular imaging responders; correlation of the baseline TLP and the baseline organ SUVmean | √ | √ | Possible trend or trend towards significance | Non-significant | NS | NS |
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Burgard, C.; Rosar, F.; Marlowe, R.J.; Bartholomä, M.; Dewes, S.; Schaefer-Schuler, A.; Linxweiler, J.; Khreish, F.; Ezziddin, S. Tumor Sink Effect with Prostate-Specific Membrane Antigen-Targeted Theranostics in Patients with Metastatic Castration-Resistant Prostate Cancer: Intra-Individual Evaluations. Cancers 2023, 15, 2592. https://doi.org/10.3390/cancers15092592
Burgard C, Rosar F, Marlowe RJ, Bartholomä M, Dewes S, Schaefer-Schuler A, Linxweiler J, Khreish F, Ezziddin S. Tumor Sink Effect with Prostate-Specific Membrane Antigen-Targeted Theranostics in Patients with Metastatic Castration-Resistant Prostate Cancer: Intra-Individual Evaluations. Cancers. 2023; 15(9):2592. https://doi.org/10.3390/cancers15092592
Chicago/Turabian StyleBurgard, Caroline, Florian Rosar, Robert J. Marlowe, Mark Bartholomä, Sebastian Dewes, Andrea Schaefer-Schuler, Johannes Linxweiler, Fadi Khreish, and Samer Ezziddin. 2023. "Tumor Sink Effect with Prostate-Specific Membrane Antigen-Targeted Theranostics in Patients with Metastatic Castration-Resistant Prostate Cancer: Intra-Individual Evaluations" Cancers 15, no. 9: 2592. https://doi.org/10.3390/cancers15092592