Discussion
death, ependymoma, radionecrosis, toxicity, cancer, AML, medulloblastoma, necrosis, tumors
DISEASE PROGRESSION, EPENDYMOMA, DISEASE COURSE, CANCER, DISEASE, TUMORS, AML, REMISSION, MEDULLOBLASTOMA, NECROSIS, DISEASE, MINIMAL RESIDUAL DISEASE
Patients with recurrent primary CNS tumors unfortunately have few curative treatment options. Here, we demonstrate that long-term survival over two years is possible among patients with recurrent medulloblastoma or ependymoma treated with multimodality therapy at relapse. These patients comprise a heavily treated population at risk of toxicity. With no cases of radionecrosis in this cohort despite all patients having at least one EBRT course pre-cRIT, our findings were consistent with previously published safety data [Patients who had NED at 131-I-omburtamab cRIT initiation had improved survival outcomes. This finding parallels previously published data for medulloblastoma patients who received 131-I-3F8 showing patients treated with cRIT while in remission had a lower risk of death compared to patients who had MD [Disease status at cRIT initiation was significantly associated with PFS for medulloblastoma. Among the patients with medulloblastoma who died, nearly all died of progression or relapse, with one patient ultimately dying of treatment-related AML. Similarly, among ependymoma patients, all but one patient lost to follow-up were confirmed to have died from disease progression, highlighting the importance of achieving disease control for survival. When patients who were NED at cRIT initiation did ultimately fail, the patterns of failure tended to be more unifocal and intracranial, whereas patients with multifocal failures typically had multifocal, measurable disease at the time of cRIT. This phenomenon of achieving remission prior to cRIT parallels the consistent theme in cancer treatment to achieve CR or minimal residual disease to optimize outcomes of consolidative therapies, such autologous stem cell transplant [Despite all patients having received at least one course of EBRT prior to cRIT, 6 patients having received additional EBRT post-cRIT, and 8 patients having previously received cRIT with I-131-3F8, there was no evidence of radiation necrosis on post-cRIT MRIs. Our findings support prior safety data investigating cRIT in combination with EBRT [This study has several limitations. First, this cohort is heterogeneous with different histologies, therapies, and prognoses. Second, while these data on patients who received I-131-omburtamab were prospectively collected, delivery of EBRT and other treatments varied depending on the treating institution. Third, given patients received therapy at different institutions throughout their disease course, there is a possibility of missing records. Fourth, certain treatments included in this analysis are not widely available and may impact generalizability.In conclusion, for patients with recurrent medulloblastoma or ependyma receiving cRIT, disease status at cRIT initiation may be critical. Among patients with medulloblastoma, radiologic and cytologic remission at 131-I-omburtamab initiation was associated with significantly improved survival. Patterns of relapse also demonstrated that patients with measurable disease at cRIT initiation were likely to fail multifocally and diffusely. For patients with the goal of cure, these findings support efforts to achieve remission prior to cRIT initiation using local bridging therapy (e.g., re-irradiation) as these patients can have improved survival outcomes.