Author: Travis James McCaw, Ravi Patel, Abdelhamid Saoudi, Joseph Shields 👨🔬
Affiliation: UPMC Hillman Cancer Center, UPMC Hillman Cancer Center and University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center, UPMC 🌍
Purpose: The current treatment approach for Lu-177-based radiopharmaceutical therapy involves multiple administrations, each delivering a constant activity of 200 mCi. This study evaluates whether the therapeutic ratio—defined as the ratio of the absorbed dose in the segmented tumor to that in the kidneys—varies with the number of treatment cycles administered. This could support the consideration of a non-uniform dosage prescription or the use of alternative treatment modalities.
Methods: Dose-volume histogram data from 16 patients who underwent Lu-177 radiopharmaceutical therapy was obtained through SPECT imaging using MIM software. We developed an in-house Python script to analyze the therapeutic ratio. Exponential and linear fits were applied to the data from all patients to characterize the trend of this ratio over multiple treatment cycles.
Results: The ratio of absorbed dose between segmented tumors and healthy kidneys decreases exponentially with increasing number of cycles. The maximum ratio varied among patients, ranging from 1.5 – 18. Taking the average across all patients, the mean dose in Gy at cycles 1, 3, and 4 were 12.85+/-3.67, 5.53+/-2.80, and 3.88+/-1.71 respectively for segmented tumor; 2.58+/-0.44, 2.62+/-0.79, and 2.52+/-0.79 respectively for the left kidney; and 2.79+/-0.51, 2.88+/-0.85, and 2.8+/-0.85 respectively for the right kidney. The fits demonstrated a strong correlation, with RMSE<0.35.
Conclusion: This study presents clinical evidence showing that the highest therapeutic ratio is achieved during the early treatment cycles. While increasing the number of treatment cycles helps maintain tumor control, as evidenced by a decrease in Lu-177 uptake in tumors, it also increases the risk of kidney toxicity. These findings suggest that administering higher doses during the initial cycles can enhance efficacy while minimizing toxicity. Additionally, the observed variability in dose ratios among different patients highlights the importance of personalized dosimetry in radiopharmaceutical therapy.