Estimating the Risk for Secondary Cancer After Targeted alpha-Therapy with At-211 Intraperitoneal Radioimmunotherapy

Intraperitoneal At-211-based targeted a-therapy (TAT) may hold great promise as an adjuvant therapy after surgery and chemotherapy in epithelial ovarian cancer to eradicate any remaining undetectable disease. This implies that it will also be delivered to patients possibly already cured by the primary treatment. An estimate of long-termrisks is therefore sought to determine whether the treatment is justified. Methods: Baseline data for risk estimates of alpha-particle irradiation were collected from published studies on excess cancer induction and mortality for subjects exposed to either Ra-224 treatments or Thorotrast contrast agent (25% ThO2 colloid, containing Th-232). Organ dosimetry for Ra-224 and Thorotrast irradiation were taken from the literature. These organ-specific risks were then applied to our previously reported dosimetry for intraperitoneal At-211-TAT patients. Results: Risk could be estimated for 10 different organ or organ groups. The calculated excess relative risk per gray (ERR/Gy) could be sorted into 2 groups. The lower-ERR/Gy group, ranging up to a value of approximately 5, included trachea, bronchus, and lung, at 0.52 (95% CI, 0.21-0.82); stomach, at 1.4 (95% CI, 25.0-7.9); lymphoid and hematopoietic system, at 2.17 (95% CI, 1.7-2.7); bone and articular cartilage, at 2.6 (95% CI, 2.0-3.3); breast, at 3.45 (95% CI, 210-17); and colon, at 4.5 (95% CI, 23.5-13). The higher-ERR/Gy group, ranging from approximately 10 to 15, included urinary bladder, at 10.1 (95% CI, 1.4-23); liver, at 14.2 (95% CI, 13-16); kidney, at 14.9 (95% CI, 3.9-26); and lip, oral cavity, and pharynx, at 15.20 (95% CI, 2.73-27.63). Applying a typical candidate patient (female, age 65 y) and correcting for the reference population mortality rate, the total estimated excess mortality for an intraperitoneal At-211-monoclonal antibody treatment amounted to 1.13 per 100 treated. More than half this excess originated from urinary bladder and kidney, 0.29 and 0.34, respectively. Depending on various adjustments in calculation and assumptions on competing risks, excess mortality could range from 0.11 to 1.84 per 100 treated. Conclusion: Published epidemiologic data on lifelong detriment after alpha-particle irradiation and its dosimetry allowed calculations to estimate the risk for secondary cancer after At-211-based intraperitoneal TAT. Measures to reduce dose to the urinary organs may further decrease the estimated relative low risk for secondary cancer from At-211-monoclonal antibody-based intraperitoneal TAT.

Automated summary

Intraperitoneal At-211-based targeted alpha-therapy (TAT) shows promise as adjuvant therapy for ovarian cancer. However, long-term risks need to be estimated to determine whether the treatment is justified.