Clinical characterization of adult medulloblastoma and the effect of first-line therapies on outcome; The MD Anderson Cancer Center experience

Majd, Nazanin; Mastall, Maximilan; Lin, Heather; Dibaj, Seyede Shiva; Hess, Kenneth R.; Yuan, Ying; García, Manuela Martín-Bejarano; Fuller, Gregory N.; Alfaro, Kristin; Gule-Monroe, Maria; Huse, Jason T.; Khatua, Soumen; Rao, Ganesh; Sandberg, David I.; Wefel, Jeffrey S.; Yeboa, Debra Nana; Paulino, Arnold C.; McGovern, Susan L.; Zaky, Wafik; Mahajan, Anita; Suki, Dima; Weathers, Shiao-Pei; Harriso, Rebecca A; Groo, John F De; Puduvalli, Vinay K.; Penas‐Prado, Marta

doi:10.1093/noajnl/vdab079

Cited by 8 publications

(9 citation statements)

References 39 publications

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“…In our previously published cohort of 200 patients initially diagnosed with medulloblastoma as adults (≥ 18 years of age), we observed a 5-year PFS rate of 55% and a median PFS of more than 6 years. 18 PFS for the entire cohort was driven by patients who did not have a recurrence and who had less aggressive tumors and/or more appropriate therapy. In contrast, among the 82 patients in the present analysis, who experienced tumor recurrence during follow-up, median PFS from initial surgery was less than 3 years, with a 5-year PFS rate of 17%, and there was no significant difference in PFS between patients stratified as high-risk and those stratified as standard-risk on the basis of their clinical features at presentation.…”

Section: Discussionmentioning

confidence: 99%

“… 12 , 14–16 It has been previously demonstrated that adjuvant chemotherapy led to superior outcomes and neoadjuvant chemotherapy is associated with inferior outcomes in adult medulloblastoma. 17 , 18 …”

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confidence: 99%

“… 23 , 24 In this single-institution retrospective study, we described the clinical characteristics, treatment strategies, and survival outcomes of 82 adults with recurrent medulloblastoma, a subgroup of 200 adults with medulloblastoma whose data were previously published by our group. 18 …”

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Characterization of recurrence patterns and outcomes of medulloblastoma in adults: The University of Texas MD Anderson Cancer Center experience

Gregory

Mastall

Lin

et al. 2023

Neuro-Oncology Advances

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Background Medulloblastoma in adults is rare and treatment decisions are largely driven from pediatric literature. We sought to characterize recurrent medulloblastoma in adults. Methods From a single-institution dataset of 200 adult patients diagnosed with medulloblastoma during 1978-2017, those with recurrence were analyzed for clinical features, treatment, and outcome. Results Of the 200 patients, 82 (41%) with median age 29 years (18-59) had recurrence after a median follow-up time of 8.4 years (95% CI = 7.1, 10.3). Of these, 30 (37%) were standard-risk, 31 (38%) were high-risk, and 21 (26%) had unknown-risk disease at the time of initial diagnosis. Forty-eight (58%) presented with recurrence outside the posterior fossa, of whom 35 (43%) had distant recurrence only. Median PFS and OS from initial surgery were 33.5 and 62.4 months, respectively. Neither PFS nor OS from initial diagnosis differed between the standard-risk and high-risk groups in those who experience recurrence (P = 0.505 and 0.463, respectively). Median OS from first recurrence was 20.3 months, also with no difference between the standard-risk and high-risk groups (P = 0.518). Recurrences were treated with combinations of re-resection (20 patients; 25%), systemic chemotherapy (61 patients; 76%), radiation (29 patients; 36%), stem cell transplant (6 patients; 8%), and intrathecal chemotherapy (4 patients; 5%). Patients who received radiation at recurrence had better OS (32.9 months) than those who did not (19.2 months) (P = 0.034). Conclusions Recurrent medulloblastoma in adults has a poor prognosis irrespective of initial risk stratification. Recurrence commonly arises outside the posterior fossa years after initial diagnosis.

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Characterization of recurrence patterns and outcomes of medulloblastoma in adults: The University of Texas MD Anderson Cancer Center experience

Gregory

Mastall

Lin

et al. 2023

Neuro-Oncology Advances

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“…Many guiding studies were published before widespread molecular subgroup classification in clinical practice, which will be important to incorporate into future clinical trials. 10,11,20,45,46 The main strength of our study is a large and well-characterized sample, given the rarity of this diagnosis. We provide patientspecific demographic, management, and outcome data with known molecular subgroup classification in a majority of the cohort.…”

Section: Discussionmentioning

confidence: 99%

Management and Long-term Outcomes of Adults With Medulloblastoma

Neth,

Raghunathan,

Kizilbash

et al. 2023

Neurology

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OBJECTIVE:Medulloblastomas are embryonal tumors predominantly affecting children. Recognition of molecularly defined subgroups has advanced management. Factors influencing the management and prognosis of adult patients with medulloblastoma remains poorly understood.METHODS:We examined management, prognostic factors, and when possible molecular subgroup differences (subset) in adult medulloblastoma patients (>18 years) from our center (specialty Neuro-Oncology clinic within a large academic practice) diagnosed between 1992-2020. Molecular subtyping corresponding to the 2021 WHO Classification was performed. Kaplan-Meier estimates (with Log-rank test) were performed for univariate survival analysis with cox regression used for multivariate analyses.RESULTS:We included 76 adult medulloblastoma patients (62% male), with a median age of 32 years at diagnosis (range: 18-66), and median follow-up of 7.7 years (range: 0.6-27). A subset of 58 patients had molecular subgroup characterization – 37 SHH-activated, 12 non-WNT/non-SHH, and 9 WNT-activated. 67% underwent gross total resection, 75% received chemotherapy at diagnosis, and 97% received craniospinal irradiation with boost. Median overall survival (OS) for the whole cohort was 14.8 years. The 2, 5, and 10-year OS was 93% (95% CI: 88-99%), 86% (78-94%), and 64% (53-78%), respectively. Survival was longer for younger patients (≥30 years old: 9.9 years; <30 years old: estimated >15.4 years; Log-rank p<0.001). There was no survival difference by molecular subgroup or extent of resection. Only age at diagnosis remained significant in multivariate survival analyses.CONCLUSION:We report one of the largest retrospective cohorts in adult medulloblastoma patients with molecular subtyping. Survival and molecular subgroup frequencies were similar to prior reports. Survival was better for adult patients younger than 30 years at diagnosis and was not significantly different by molecular subgroup or management characteristics (extent of resection, RT characteristics, or chemotherapy timing or regimen).

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“…The OS rates were 89% and 75.2% at 5 and 10 years [ 26 ]. Similarly, Majd et al, published a large retrospective single institution study of adult MB in which 16 of 53 patients with standard-risk MB received <30 Gy CSI and no difference in outcome was noted [ 29 ].…”

Section: Backbone Of Ambush Therapeutic Strategymentioning

confidence: 99%

The Alliance AMBUSH Trial: Rationale and Design

Mahajan

Shih

Penas‐Prado

et al. 2022

Cancers

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Unlike medulloblastoma (MB) in children, robust prospective trials have not taken place for older patients due to the low incidence of MB in adults and adolescent and young adults (AYA). Current MB treatment paradigms for older patients have been extrapolated from the pediatric experience even though questions exist about the applicability of these approaches. Clinical and molecular classification of MB now provides better prognostication and is being incorporated in pediatric therapeutic trials. It has been established that genomic alterations leading to activation of the sonic hedgehog (SHH) pathway occur in approximately 60% of MB in patients over the age of 16 years. Within this cohort, protein patched homolog (PTCH) and smoothened (SMO) mutations are commonly found. Among patients whose tumors harbor the SHH molecular signature, it is estimated that over 80% of patients could respond to SHH pathway inhibitors. Given the advances in the understanding of molecular subgroups and the lack of robust clinical data for adult/AYA MB, the Alliance for Clinical Trial in Oncology group developed the AMBUSH trial: Comprehensive Management of AYA and Adult Patients with Medulloblastoma or Pineal Embryonal Tumors with a Randomized Placebo Controlled Phase II Focusing on Sonic Hedgehog Pathway Inhibition in SHH Subgroup Patients (Adult & Adolescent MedulloBlastoma Using Sonic Hedgehog Trial). This trial will enroll patients 18 years of age or older with MB (any molecular subgroup and risk stratification) or pineal embryonal tumor. Patients will be assigned to one of three cohorts: (1) average risk non-SHH-MB, (2) average risk SHH-MB, and (3) high risk MB or pineal embryonal tumors. All patients will receive protocol-directed comprehensive treatment with radiation therapy and chemotherapy. Patients with SHH-MB in cohort 1 will be randomized to a smoothened inhibitor or placebo as maintenance therapy for one year.

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Clinical characterization of adult medulloblastoma and the effect of first-line therapies on outcome; The MD Anderson Cancer Center experience

Cited by 8 publications

References 39 publications

Characterization of recurrence patterns and outcomes of medulloblastoma in adults: The University of Texas MD Anderson Cancer Center experience

Characterization of recurrence patterns and outcomes of medulloblastoma in adults: The University of Texas MD Anderson Cancer Center experience

Management and Long-term Outcomes of Adults With Medulloblastoma

The Alliance AMBUSH Trial: Rationale and Design

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