Factors Associated with Radiation Safety Clearance Following Lu-177 DOTATATE Therapy

Technical Summary: Factors Associated with Radiation Safety Clearance Following Lu-177 DOTATATE Therapy

Problem Statement
The implementation of radioligand therapy (RLT) using Lutetium-177 DOTATATE for neuroendocrine tumors in Japan faces significant logistical challenges, including a shortage of specialized facilities and personnel. A critical bottleneck is the management of dedicated treatment rooms, which are required to have adequate shielding and drainage. Patients can only be discharged from the controlled area once the 1 cm dose equivalent rate at 1 meter from their body surface falls below the prescribed limit of 18 µSv/h, as stipulated by the Medical Care Act. Because Lu-177 DOTATATE is primarily eliminated via the kidneys, factors influencing renal clearance may directly impact the time required to meet these discharge criteria. While oral hydration is widely practiced to promote radiopharmaceutical excretion, clinical evidence supporting its efficacy in reducing discharge times remains limited. Furthermore, few studies have systematically evaluated factors associated with radiation safety clearance in this specific patient population.

Methodology
This was a retrospective, single-center study conducted at the National Cancer Center Hospital East in Japan, covering the period from December 2021 to March 2025. The cohort consisted of 60 patients with confirmed somatostatin receptor-positive neuroendocrine tumors who underwent a total of 134 Lu-177 DOTATATE administrations.

• Primary Outcome: The study defined the primary outcome as the achievement of discharge criteria (dose rate < 18 µSv/h at 1 m) within 4 hours of administration.
• Data Collection: Researchers collected demographic data, clinical variables (including ECOG performance status, tumor grade, and metastasis status), and laboratory parameters (serum creatinine, creatinine clearance, hematological indices) before and after each treatment cycle. Oral hydration volume was recorded as the cumulative self-reported fluid intake during amino acid infusion, excluding intravenous fluids.
• Statistical Analysis: To account for repeated treatment cycles within the same patients, the authors employed Generalized Estimating Equations (GEE) using logistic regression with a binomial distribution and logit link function. The model evaluated the association between pre-treatment creatinine clearance, oral hydration volume, and other clinical variables with the likelihood of early discharge. Exploratory subgroup analyses were conducted based on renal function (creatinine clearance < 60 mL/min vs. ≥ 60 mL/min) and hydration volume (< 1500 mL vs. ≥ 1500 mL).

Key Results

• Renal Function as a Predictor: Higher pre-treatment creatinine clearance was independently associated with achieving discharge criteria within 4 hours. The odds ratio was 1.22 per 10 mL/min increase in creatinine clearance (95% CI 1.01–1.49, p = 0.044). Other variables, including age, sex, performance status, and treatment cycle, showed no significant association.
• Hydration Volume: In the multivariable GEE analysis, oral hydration volume was not an independent predictor of early discharge. However, univariate analysis showed a trend where patients consuming ≥ 1500 mL of oral fluids had less variation in discharge times compared to those consuming < 1500 mL.
• Interaction between Renal Function and Hydration: A critical finding emerged from the exploratory analysis of combined factors. Patients with both impaired renal function (Ccr < 60 mL/min) and low oral hydration (< 1500 mL) experienced the longest delays, with a median time to discharge of 21.0 hours. Conversely, patients with impaired renal function who consumed adequate hydration (≥ 1500 mL) achieved discharge within 4 hours at a rate (64.3%) comparable to patients with normal renal function who consumed lower volumes (63.6%).
• Safety and Tolerability: Renal function remained relatively stable throughout the treatment course. While gradual declines in platelet count and hemoglobin were observed with repeated administrations, no dose reductions were required. Only one patient discontinued treatment due to an adverse event (tumor lysis syndrome).

Significance and Claims
The authors claim that pre-treatment creatinine clearance is a significant predictor of the time required to achieve radiation safety discharge criteria following Lu-177 DOTATATE therapy. While oral hydration volume did not emerge as an independent statistical predictor in the multivariate model, the study suggests that adequate hydration may serve as a modifiable factor to mitigate delays, particularly in patients with compromised renal function.

The significance of these findings lies in their potential to optimize patient management and the efficient utilization of dedicated treatment rooms. Given the stringent discharge criteria in Japan (< 18 µSv/h) compared to some international standards, and the scarcity of specialized facilities, strategies that reduce the time patients occupy these rooms are crucial. The authors posit that encouraging adequate oral hydration (specifically ≥ 1500 mL) is a simple, resource-free intervention that may help prevent prolonged retention of radioactivity in patients with renal impairment, thereby facilitating faster room turnover and increasing overall treatment capacity.

Limitations
The authors acknowledge the study's limitations, including its single-center, retrospective design and the small sample size inherent to the rarity of neuroendocrine tumors. Additionally, the reliance on self-reported fluid intake and the specific institutional protocol for dose-rate measurements (routine measurement at 3–4 hours, with follow-up the next day) may influence the observed outcomes and limit direct comparability with practices in other countries.