Increasing PORT Deferral in Medulloblastoma Raises Mortality Risk

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Increasing PORT Deferral in Medulloblastoma Raises Mortality Risk
Increasing PORT Deferral in Medulloblastoma Raises Mortality Risk

Despite the clear survival benefit of the application of postoperative radiotherapy (PORT) to the craniospinal axis in pediatric medulloblastoma (MB), analysis of a national database indicates a strong and consistent trend toward deferral of PORT in children between the ages of 3 and 8. Results from the analyses were published in JAMA Oncology.1

This trend goes against conventional standard-of-care for MB, the most common type of malignant brain tumor in children, with a high rate of recurrence despite the combination of maximal safe resection followed by PORT within 90 days and a radiotherapeutic boost to the primary site along with chemotherapy.2 Deferral of PORT, the authors stated, “is associated with worse survival in this age group, even in the modern era of chemotherapy.”

To verify this pattern, investigators led by Benjamin H. Kann, MD, of Yale University School of Medicine in New Haven, Conn., conducted a multivariate logistical regression analysis of 816 cases of MB from the National Cancer Data Base (NCDB) registry, which represents about 70% of all newly diagnosed neoplasms. Of those, PORT deferral was reported in 123 (15.1%) patients, while the remaining 693 (84.9%) underwent PORT within 90 days of surgery in accordance with the current standard of care. Deferral of PORT decreased with the age of the child, as 36.8% of 3-year-olds were deferred compared with 4.1% of 8-year-olds.

After median follow-up of 4.8 years post-surgery, 89 deaths had been reported, representing 18.8% of the total patient base. The 474 survivors included 391 patients who had PORT upfront and 83 who had PORT deferred. Of the survivors, a clear distinction was observed in survival in those who had PORT (328 of 391/85.2% survival) compared with those who had it deferred (57 of 83/68.7% survival).

Poorer overall survival (OS) was associated with PORT deferral, having stage M1-3 disease, and low facility volume. The main factors that appeared to influence the decision for PORT deferral were age and year of diagnosis.

In an accompanying editorial,3 Arnold C. Paulino, MD, of MD Anderson Cancer Center in Houston, Texas, and Jerry J. Jaboin, MD, PhD, of Knight Cancer Institute at Oregon Health and Science University in Portland, suggested that the rationale for deferral, which was not examined in the original study, was related to possible safety concerns among physicians toward the use of radiation in young children, but that other factors such as the potential for postoperative complications, poor performance status, availability of treatments, as well as socioeconomic status and familial situations may all contribute to the decision to defer PORT. They observed that some patients who had poor outcomes after deferring PORT were likely to have poor outcomes anyway as a result of postsurgical morbidity and more advanced disease status.

A better question they posed, based on the findings of this study, was whether PORT is a benefit in all children with MB between the ages of 3 and 8, or should these patients be stratified according to responses of genetic variants associated with the neoplasm?  The authors pointed to 4 genes identified in the etiology of childhood medulloblastoma known as WNT, SHH, group 3 and group 4. While the WNT subtype has the greatest response to current therapy with PORT, it is only associated with 10% of MB cases. The other 3 types that make up the MB majority have successively lower survival rates, despite treatment.

Ultimately, Drs Paulino and Joboin agreed with the investigators that until further study can better stratify treatment subgroups according to genetic type, the current standard of care including PORT should be maintained in all children aged 3 to 8 with MB, for optimal survival.

References

  1. Kann BH, Park HS, Lester-Coll NH, et al. Postoperative Radiotherapy Patterns of Care and Survival Implications for Medulloblastoma in Young Children. JAMA Oncol. 2016; doi: 10.1001/jamaoncol.2016.2547.
  2. Tabori U, Baskin B, Shago M, et al. Universal Poor Survival in Children With Medulloblastoma Harboring Somatic TP53 Mutations. JCO. 2010;28:1345-1350.
  3. Paulino AC, Jaboin JJ. Radiotherapy Deferral in Medulloblastoma. JAMA Oncol. 2016; doi:10.1001/jamaoncol.2016.2546.
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