Main Session
Sep
29
PQA 06 - Genitourinary Cancer, Gynecological Cancer, and Health Care Access and Engagement
Presenter(s)
Srikrishna Tirumalareddy, BS - Thomas Jefferson University, Philadelphia, PA
S. Tirumalareddy1, M. Yorker2, N. Haldar1, F. Adejolu1, S. Majid3, E. Gingold4, K. Zarrabi5, J. W. DiNome1, F. Mourtada1, and L. J. Wilson1; 1Department of Radiation Oncology, Thomas Jefferson University Hospital, Philadelphia, PA, 2Department of Internal Medicine, Thomas Jefferson University Hospital, Philadelphia, PA, 3Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, 4Department of Radiology, Thomas Jefferson University Hospital, Philadelphia, PA, 5Department of Medical Oncology, Thomas Jefferson University Hospital, Philadelphia, PA
Purpose/Objective(s):
Radiopharmaceutical therapies are reshaping treatment possibilities for patients with widespread metastatic cancer. However, substantial inter-patient dose variability can limit treatment effectiveness. This study identified key clinical factors associated with 177Lu-PSMA-617 dose to kidneys and tumors and evaluated doses against conventional thresholds.Materials/Methods:
Patients received 7.4 GBq/cycle of 177Lu-PSMA-617 for up to 6 cycles. Kidney function was evaluated before treatment and after each cycle with serum creatinine and estimated glomerular filtration rate (eGFR) using the 2021 CKD-EPI Creatinine Equation. Quantitative SPECT scans were acquired 72 hours post-cycle. Tumors were manually contoured and reviewed by a radiation oncologist, and kidneys were auto-contoured with a validated tool (ProtegeAI, MIM). A commercially available Monte Carlo dosimetry platform (Torch, Voximetry) was used to calculate single-timepoint doses with Madsen time integration. Single-cycle kidney mean absorbed doses and biologically effective doses (BEDs, a/ß = 2.6) were extrapolated to 6 cycles and compared to the conventional kidney mean dose threshold of 23 Gy (40 Gy BED). Linear Mixed-Effects Models (LMEs) quantified inter- and intra-patient tumor dose variability, considering tumor volume and cycle number. Separate LMEs tested associations (a = 0.05) between tumor dose and tumor volume (controlling for cycle number) and between kidney dose and baseline eGFR (controlling for cycle number and kidney volume). Lastly, an LME tested for longitudinal eGFR changes.Results:
We calculated kidney doses for 36 cycles over 27 patients, with an average of 4.6 eGFR measurements per patient. Dosimetry was performed on 104 tumors across 9 patients over 12 cycles. Mean dose ± SD (Gy) was 6.8 ± 8.7 to tumors. Kidney doses were 2.1 ± 0.7 Gy (2.2 ± 0.8 Gy BED). 96% and 100% of patients had extrapolated kidney doses and BEDs below the respective thresholds. LME inter- and intra-patient tumor dose variability had SDs of 4.9 and 6.3 Gy, respectively. Tumor dose positively correlated with tumor volume (p = 6E-5). Kidney dose inversely correlated with baseline eGFR (p = 0.04). Lastly, eGFR did not significantly change throughout treatment (p = 0.4).Conclusion:
We examined clinical variables in relation to 177Lu-PSMA-617 dose to kidneys and tumors. Dose variability in tumors was substantial, and larger tumors received higher doses, emphasizing the importance of considering patient tumor geometry in activity administration. All but one patient had extrapolated kidney doses below conventional thresholds, posing an opportunity for dose escalation. Critically, associations between kidney dose and baseline eGFR suggest that baseline eGFR may serve as a valuable guide for personalizing administered activity while avoiding toxicity, providing a clear path toward improving outcomes in 177Lu-PSMA-617 patients.