Tumor-Absorbed Dose Predicts Progression-Free Survival Following (131)I-Tositumomab Radioimmunotherapy

Abstract

The study aimed at identifying patient-specific dosimetric and nondosimetric factors predicting outcome of non-Hodgkin lymphoma patients after (131)I-tositumomab radioimmunotherapy for potential use in treatment planning.

Methods: Tumor-absorbed dose measures were estimated for 130 tumors in 39 relapsed or refractory non-Hodgkin lymphoma patients by coupling SPECT/CT imaging with the Dose Planning Method (DPM) Monte Carlo code. Equivalent biologic effect was calculated to assess the biologic effects of nonuniform absorbed dose including the effects of the unlabeled antibody. Evaluated nondosimetric covariates included histology, presence of bulky disease, and prior treatment history. Tumor level outcome was based on volume shrinkage assessed on follow-up CT. Patient level outcome measures were overall response (OR), complete response (CR), and progression-free survival (PFS), determined from clinical assessments that included PET/CT.

Results: The estimated mean tumor-absorbed dose had a median value of 275 cGy (range, 94-711 cGy). A high correlation was observed between tracer-predicted and therapy-delivered mean tumor-absorbed doses (P < 0.001; r = 0.85). In univariate tumor-level analysis, tumor shrinkage correlated significantly with almost all of the evaluated dosimetric factors, including equivalent biologic effect. Regression analysis showed that OR, CR, and PFS were associated with the dosimetric factors and equivalent biologic effect. Both mean tumor-absorbed dose (P = 0.025) and equivalent biologic effect (P = 0.035) were significant predictors of PFS whereas none of the nondosimetric covariates were found to be statistically significant factors affecting PFS. The most important finding of the study was that in Kaplan-Meier curves stratified by mean dose, longer PFS was observed in patients receiving mean tumor-absorbed doses greater than 200 cGy than in those receiving 200 cGy or less (median PFS, 13.6 vs. 1.9 mo for the 2 dose groups; log-rank P < 0.0001).

Conclusion: A higher mean tumor-absorbed dose was significantly predictive of improved PFS after (131)I-tositumomab radioimmunotherapy. Hence tumor-absorbed dose, which can be estimated before therapy, can potentially be used to design radioimmunotherapy protocols to improve efficacy.

Keywords: SPECT/CT; dosimetry; non-Hodgkin lymphoma; progression free survival; radioimmunotherapy.

FIGURE 1

Imaging and dosimetry. Day 0 posttracer (A) and day 2 posttherapy (B) SPECT/CT images of patient with CT-defined tumor outlines. Tumor-absorbed dose distribution with isodose contours in cGy (C) and tumor dose-volume histogram (D).

FIGURE 2

Baseline (A) and follow-up (B) PET/CT scans used to assess response after radioimmunotherapy (same patient as in Fig. 1).

FIGURE 3

Estimated relative HR for each decile-defined group based on mean tumor dose. HR here was calculated relative to HR for highest-dose decile group.

FIGURE 4

PFS (with number of subjects at risk and 95% confidence limits indicated) stratified by mean tumor-absorbed dose > 200 cGy and ≤ 200 cGy. Median PFS was 13.6 vs. 1.9 mo for the 2 dose groups (log-rank P < 0.0001).