Adjuvant chemotherapy and overall survival in adult medulloblastoma

Abstract

Medulloblastoma (MB) is the most common brain tumor in children. However, it is relatively rare in adults, with an estimated incidence of 0.6 per million. 1 The standardof-care management for pediatric MB is postoperative radiotherapy (RT) with craniospinal irradiation (CSI) and posterior fossa or resection bed boost followed by adjuvant chemotherapy. 2,3 Adoption of adjuvant chemotherapy in the pediatric setting has been associated with improved disease control and has allowed successful CSI dose deescalation in average-risk patients. [2][3][4][5] Even though chemotherapy is used routinely for pediatric patients, its benefit in adult MB is unclear. Data supporting adjuvant chemotherapy in the adult MB population are scarce. There are no randomized trials investigating the benefit of chemotherapy in adult MB, and evidence is generally limited to small retrospective series reported over several decades with conflicting results. [6][7][8][9] Furthermore, compared with children, adults may suffer less toxicity from CSI and greater morbidity from chemotherapy. This may lead to hesitancy in using postoperative chemotherapy, Adjuvant chemotherapy and overall survival in adult medulloblastoma AbstractBackground. Although chemotherapy is used routinely in pediatric medulloblastoma (MB) patients, its benefit for adult MB is unclear. We evaluated the survival impact of adjuvant chemotherapy in adult MB. Methods. Using the National Cancer Data Base, we identified patients aged 18 years and older who were diagnosed with MB in 2004-2012 and underwent surgical resection and adjuvant craniospinal irradiation (CSI). Patients were divided into those who received adjuvant CSI and chemotherapy (CRT) or CSI alone (RT). Predictors of CRT compared with RT were evaluated with univariable and multivariable logistic regression. Survival analysis was limited to patients receiving CSI doses between 23 and 36 Gy. Overall survival (OS) was evaluated using the Kaplan-Meier estimator, log-rank test, multivariable Cox proportional hazards modeling, and propensity score matching. Results. Of the 751 patients included, 520 (69.2%) received CRT, and 231 (30.8%) received RT. With median followup of 5.0 years, estimated 5-year OS was superior in patients receiving CRT versus RT (86.1% vs 71.6%, P < .0001). On multivariable analysis, after controlling for risk factors, CRT was associated with superior OS compared with RT (HR: 0.53; 95%CI: 0.32-0.88, P = .01). On planned subgroup analyses, the 5 year OS of patients receiving CRT versus RT was improved for M0 patients (P < .0001), for patients receiving 36 Gy CSI (P = .0007), and for M0 patients receiving 36 Gy CSI (P = .0008). Conclusions. This national database analysis demonstrates that combined postoperative chemotherapy and radiotherapy are associated with superior survival for adult MB compared with radiotherapy alone, even for M0 patients who receive high-dose CSI.

Adolescents and young adults with brain tumors in the context of molecular advances in neuro‐oncology

“…The need of adjuvant chemotherapy is stressed by findings in a recent large retrospective study, where analogous to children, the addition of chemotherapy to radiation conferred a survival benefit. Moreover, they emphasized that 36 Gy CSI with chemotherapy in low‐risk patients failed to exhibit a better prognosis then lower dose of CSI (23–30 Gy) and chemotherapy . As such, young adults with medulloblastoma would benefit from being treated at pediatric centers more specialized in adjuvant chemotherapy.…”

“…Moreover, they emphasized that 36 Gy CSI with chemotherapy in lowrisk patients failed to exhibit a better prognosis then lower dose of CSI (23-30 Gy) and chemotherapy. 94 As such, young adults with medulloblastoma would benefit from being treated at pediatric centers more specialized in adjuvant chemotherapy. However, we acknowledge that treatment of young adults in pediatric centers would need to overcome a myriad of complex logistical, bureaucratic, and financial barriers.…”

Adult Medulloblastoma Presenting with Extensive Supratentorial Metastasis with Radiographically Occult Infratentorial Disease: Case Report and Review of the Literature

“…Use of adjuvant chemotherapy is generally reserved for adults with high-risk disease, although to date there has not been a consensus reached on regimens, doses, and timing of chemotherapy in pediatric or adult settings. A recent retrospective analysis of large cancer database adding chemotherapy to craniospinal irradiation (CSI) showed an overall survival benefit even in patients with M0 disease [37].…”

Recurrence pattern and Survival analysis in patients undergoing radiotherapy IMRT technique for medulloblastoma

“…Lastly,Postoperative chemotherapy is an important part of the comprehensive treatment of medulloblastoma, and a number of studies have suggested that postoperative chemotherapy can improve the survival of patients with medulloblastoma [18,19]. Research from National Cancer Data Base shown that [19], the 5-year survival rate of the adjuvant chemotherapy group was significantly higher than that of radiotherapy alone, which was 86.1% and 71.6%, respectively.…”

“…Lastly,Postoperative chemotherapy is an important part of the comprehensive treatment of medulloblastoma, and a number of studies have suggested that postoperative chemotherapy can improve the survival of patients with medulloblastoma [18,19]. Research from National Cancer Data Base shown that [19], the 5-year survival rate of the adjuvant chemotherapy group was significantly higher than that of radiotherapy alone, which was 86.1% and 71.6%, respectively. Recent research suggests that preoperative chemotherapy can also yield survival benefits [20].In terms of the choice of chemotherapy regimen, the combination of three drugs may be more effective [21],lomustine(CCNU), cisplatin, and vincristine or cyclophosphamide, cisplatin, and vincristine are more commonly used.Our study indicated that there was no statistical difference in PFS and OS in the chemotherapy group,the chemotherapy-free group,the EP chemotherapy group and the TMZ chemotherapy group.…”