Serum Tumor Marker Response Predicts Survival and Intracranial Control after Radiation Therapy for Germ Cell Tumor Brain Metastases

Abstract

<h3>Purpose/Objective(s)</h3> Patients with brain metastases (BM) from germ cell tumors (GCT) demonstrate poor overall survival (OS). However, multimodality treatment enables durable disease control in some patients. Serum tumor markers including beta-human chorionic gonadotropin (β-HCG) and alpha-fetoprotein (AFP) are used to evaluate response to systemic therapy. However, their utility in assessing the efficacy of intracranial radiation therapy (RT) is unclear. We evaluated whether changes in β-HCG and AFP after RT for GCT BM predict OS and freedom from intracranial progression (iPFS). <h3>Materials/Methods</h3> Patients with GCT BM who received intracranial RT at our institution were identified retrospectively. At least one β-HCG or AFP value before and after RT was required for inclusion. Serum tumor marker values were obtained prior to RT and 1 month after RT. Univariate and multivariate Cox regression analyses evaluated changes in β-HCG and AFP as predictors of OS and iPFS. Patients with normal tumor markers prior to RT were excluded from analyses. <h3>Results</h3> Sixty-two male patients who received RT between 2002 and 2021 were included. Median age was 30 years (range, 2 to 61). The primary tumor was testicular in 81% and mediastinal in 15%. Histology was seminoma in 10%. At diagnosis, the median number of BM was 2, and the median largest diameter was 1.8 cm. Initial RT included whole brain radiation therapy in 55%, stereotactic radiosurgery in 34%, and both in 10%. 31% had resection preceding RT. Most patients had extracranial disease (79%) and received chemotherapy within a month of RT (66%). During RT, radiographic progression of extracranial disease occurred in 34% of patients. Median OS and iPFS were 20.6 and 27.7 months, respectively. Among 41 patients with baseline β-HCG above the normal range, β-HCG decreased at 1 month after RT in 51%. Patients with decreased β-HCG, versus those with increased β-HCG, had significantly better OS (median not reached versus 5.4 months) and iPFS (median not reached versus 4.7 months). These correlations remained significant on multivariate analysis, controlling for largest BM diameter and RT modality (OS: HR = 13, 95% CI = [4.6, 37], p = 1 × 10⁻⁶; iPFS: HR = 6.4, 95% CI = [2.2, 19], p = 6 × 10⁻⁴). These correlations also remained significant whether or not patients had extracranial disease progression during RT (p < 0.05). Among 20 patients with baseline AFP above the normal range, AFP decreased at 1 month after RT in 75%. Likewise, decreased AFP was correlated with better OS on univariate regression (p = 0.04). <h3>Conclusion</h3> To our knowledge, this is the first study to evaluate changes in serum tumor markers as predictors of outcomes after RT for GCT BM. Decrease in β-HCG one month after RT was associated with better OS and iPFS on multivariate analysis, and likewise, decrease in AFP was associated with better OS on univariate analysis. These data indicate that post-RT β-HCG and AFP levels are useful predictors of outcomes in patients with GCT BM.