Reduced‐volume tumor‐bed boost is not associated with inferior local control and survival outcomes in high‐risk medulloblastoma

Tian, Sibo; Sudmeier, Lisa; Chao, Zhang; Madden, N.A.; Buchwald, Zachary S.; Shu, Hui; Eaton, Bree R.; Esiashvili, Natia

doi:10.1002/pbc.28027

Cited by 3 publications

(2 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The goal of this reduction is to decrease toxicity without compromising outcome. This safe reduction had been debated since the late 1990s ( 1 , 2 , 91 , 100 , 101 ). The non-randomized trials SJMB 96 ( 49 , 79 ) and MSFOP 98 ( 80 ) had had positive results (5-year cumulative incidence of PF failure of 4.9% ( 79 ) and 0% ( 80 ), respectively).…”

Section: Discussionmentioning

confidence: 99%

Questions and answers in the management of children with medulloblastoma over the time. How did we get here? A systematic review

Osuna-Marco,

Martín-López,

Tejera

et al. 2023

Front. Oncol.

View full text Add to dashboard Cite

IntroductionTreatment of children with medulloblastoma (MB) includes surgery, radiation therapy (RT) and chemotherapy (CT). Several treatment protocols and clinical trials have been developed over the time to maximize survival and minimize side effects.MethodsWe performed a systematic literature search in May 2023 using PubMed. We selected all clinical trials articles and multicenter studies focusing on MB. We excluded studies focusing exclusively on infants, adults, supratentorial PNETs or refractory/relapsed tumors, studies involving different tumors or different types of PNETs without differentiating survival, studies including <10 cases of MB, solely retrospective studies and those without reference to outcome and/or side effects after a defined treatment.Results1. The main poor-prognosis factors are: metastatic disease, anaplasia, MYC amplification, age younger than 36 months and some molecular subgroups. The postoperative residual tumor size is controversial.2. MB is a collection of diseases.3. MB is a curable disease at diagnosis, but survival is scarce upon relapse.4. Children should be treated by experienced neurosurgeons and in advanced centers.5. RT is an essential treatment for MB. It should be administered craniospinal, early and without interruptions.6. Craniospinal RT dose could be lowered in some low-risk patients, but these reductions should be done with caution to avoid relapses.7. Irradiation of the tumor area instead of the entire posterior fossa is safe enough.8. Hyperfractionated RT is not superior to conventional RT9. Both photon and proton RT are effective.10. CT increases survival, especially in high-risk patients.11. There are multiple drugs effective in MB. The combination of different drugs is appropriate management.12. CT should be administered after RT.13. The specific benefit of concomitant CT to RT is unknown.14. Intensified CT with stem cell rescue has no benefit compared to standard CT regimens.15. The efficacy of intraventricular/intrathecal CT is controversial.16. We should start to think about incorporating targeted therapies in front-line treatment.17. Survivors of MB still have significant side effects.ConclusionSurvival rates of MB improved greatly from 1940-1970, but since then the improvement has been smaller. We should consider introducing targeted therapy as front-line therapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Questions and answers in the management of children with medulloblastoma over the time. How did we get here? A systematic review

Osuna-Marco,

Martín-López,

Tejera

et al. 2023

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…Radiation therapy consists of CSI plus a local boost, with variations based on age and risk status. High risk pediatric patients typically receive 36 Gray (Gy) of CSI followed by a posterior fossa boost, while average risk patients receive 23.4 Gy of CSI followed by a boost restricted to the tumor bed [ 28 , 29 , 30 ]. Adults typically receive 36 Gy of CSI and a boost to either the posterior fossa or the tumor bed [ 19 ].…”

Section: Treatment and Outcomesmentioning

confidence: 99%

Pediatric versus Adult Medulloblastoma: Towards a Definition That Goes beyond Age

Wooley

Penas‐Prado

2021

Cancers

View full text Add to dashboard Cite

Medulloblastoma is a rare malignant brain tumor that predominantly affects children but also occurs in adults. The incidence declines significantly after age 15, and distinct tumor molecular features are seen across the age spectrum. Standard of care treatment consists of maximal safe surgical resection followed by adjuvant radiation and/or chemotherapy. Adjuvant treatment decisions are based on individual patient risk factors and have been informed by decades of prospective clinical trials. These trials have historically relied on arbitrary age cutoffs for inclusion (age 16, 18, or 21, for example), while trials that include adult patients or stratify patients by molecular features of disease have been rare. The aim of this literature review is to review the history of clinical trials in medulloblastoma, with an emphasis on selection criteria, and argue in favor of rational and inclusive trials based on molecular features of disease as opposed to chronological age. We performed a scoping literature review for medulloblastoma and clinical trials and include a summary of those results. We also discuss some of the significant advances made in understanding the molecular biology of medulloblastoma within the past decade, most notably the identification of four distinct subgroups based on gene expression profiling. We will also cite the recent experiences of childhood leukemia and the emergence of tissue-agnostic therapies as examples of successes of rationally designed, inclusive trials translating to improved clinical outcomes for patients across the age spectrum. Despite the prior trial history and recent molecular advances outcomes remain poor for ~30% of medulloblastoma patients. We believe that defining patients by the specific molecular alterations their tumors harbor is the best way to ensure they can access potentially efficacious therapies on clinical trials.

show abstract

Revised clinical and molecular risk strata define the incidence and pattern of failure in medulloblastoma following risk-adapted radiotherapy and dose-intensive chemotherapy: results from a phase III multi-institutional study

et al. 2021

View full text Add to dashboard Cite

Background We characterize the patterns of progression across medulloblastoma (MB) clinical risk and molecular subgroups from SJMB03, a Phase III clinical trial. Methods 155 pediatric patients with newly diagnosed MB were treated on a prospective, multi-center phase III trial of adjuvant radiotherapy (RT) and dose-intense chemotherapy with autologous stem cell transplant. Craniospinal radiotherapy to 23.4 Gy (average risk, AR) or 36-39.6 Gy (high risk, HR) was followed by conformal RT with a 1 cm clinical target volume to a cumulative dose of 55.8 Gy. Subgroup was determined using 450K DNA methylation. Progression was classified anatomically (primary site failure (PSF) +/- distant failure (DF), or isolated DF), and dosimetrically. Results 32 patients have progressed (median follow-up 11.0 years (range, 0.3 – 16.5 y) for patients without progression). Anatomic failure pattern differed by clinical risk (P=0.0054) and methylation subgroup (P=0.0034). The 5-year cumulative incidence (CI) of PSF was 5.1% and 5.6% in AR and HR patients, respectively (P=0.92), and did not differ across subgroups (P=0.15). 5-year CI of DF was 7.1% vs. 28.1% for AR vs. HR (P=0.0003); and 0% for WNT, 15.3% for SHH, 32.9% for G3, and 9.7% for G4 (P=0.0024). Of 9 patients with PSF, 8 were within the primary site RT field and 4 represented SHH tumors. Conclusions The low incidence of PSF following conformal primary site RT is comparable to prior studies using larger primary site or posterior fossa boost volumes. Distinct anatomic failure patterns across MB subgroups suggest subgroup-specific treatment strategies should be considered.

show abstract

Reduced‐volume tumor‐bed boost is not associated with inferior local control and survival outcomes in high‐risk medulloblastoma

Cited by 3 publications

References 37 publications

Questions and answers in the management of children with medulloblastoma over the time. How did we get here? A systematic review

Questions and answers in the management of children with medulloblastoma over the time. How did we get here? A systematic review

Pediatric versus Adult Medulloblastoma: Towards a Definition That Goes beyond Age

Revised clinical and molecular risk strata define the incidence and pattern of failure in medulloblastoma following risk-adapted radiotherapy and dose-intensive chemotherapy: results from a phase III multi-institutional study

Contact Info

Product

Resources

About