This article is more than 5 years old. Information may no longer be current.
Postoperative radiotherapy deferral on the rise in pediatric medulloblastoma
Click Here to Manage Email Alerts
The deferral of postoperative radiotherapy in pediatric patients with medulloblastoma has increased in recent years, according to the results of a national database survey.
Further, delaying radiotherapy appeared associated with poorer survival.
“Deferral of postoperative radiotherapy altogether in favor of adjuvant chemotherapy alone has been studied in multiple prospective trials over the past 2 decades, mostly in children younger than 3 years,” Benjamin H. Kann, MD, radiation oncology resident physician at Yale School of Medicine, and colleagues wrote. “While results of these studies have been conflicting, they have led to the acceptance of postoperative radiotherapy deferral for children younger than 3 years to avoid treatment-related morbidity. This strategy, however, is less supported in children 3 years or older.”
Benjamin H. Kann
Kann and colleagues sought to observe national treatment patterns in patients with medulloblastoma aged 3 years to 8 years, as well as the implications of treatment choices on OS.
The researchers identified 816 patients in the National Cancer Data Base diagnosed with histologically confirmed medulloblastoma between 2004 and 2012. All patients underwent surgery and adjuvant chemotherapy at Commission on Cancer–accredited U.S. hospitals, with or without postoperative radiotherapy.
The majority of patients (84.9%; n = 693) received upfront postoperative radiotherapy, defined as receiving postoperative radiotherapy within 90 days of surgery. The remaining 123 patients (15.1%) had deferred postoperative radiotherapy.
Among patients who deferred radiotherapy, 60.4% (n = 74) had no radiotherapy receipt in their medical records and 39.8% (n = 49) received radiotherapy more than 90 days after surgery.
Rates of deferment increased during the study period (OR per year = 1.15; 95% CI, 1.07-1.24), from a low of 8.1% in 2005 to a high of 27.1% in 2012.
Patient age significantly influenced the likelihood of deferral, with decreases in deferral rates seen with increasing age (OR per year = 0.63; 95% CI, 0.55-0.71). For example, 36.8% of patients aged 3 years had radiotherapy deferred, compared with 4.1% of patients aged 8 years (P < .001).
A multivariate analysis confirmed patient age (OR per year = 0.57; 95% CI, 0.49-0.67) and year of diagnosis (OR per year = 1.18; 95% CI, 1.08-1.29) as independent predictors of deferral.
Survival data were available for 474 patients (upfront, n = 391; deferred, n = 83). Eighty-nine deaths (upfront, n = 63; deferred, n = 26) occurred during a median follow-up of 4.8 years.
A greater proportion of patients who received upfront postoperative radiotherapy achieved 5-year OS (82% vs. 63.4%; P < .001).
Factors associated with poorer OS included radiotherapy deferral (HR = 1.95; 95% CI, 1.15-3.31), stage M1-3 disease (HR = 1.86; 95% CI, 1.1-3.16) and treatment at a low-volume hospital (HR = 1.75; 95% CI, 1.04-2.94).
Kann and colleagues acknowledged limitations of their study, including the potential for selection bias inherent in its retrospective design and the potential for database coding errors.
The researchers further noted that the National Cancer Data Base does not record the performance status of children, and that data on adjuvant chemotherapeutic regimens were lacking.
“Using a large national database, we found an increasing rate of postoperative radiotherapy deferring for medulloblastoma in children aged 3 years to 8 years over time, especially among younger patients,” Kann and colleagues wrote. “The analysis suggests that postoperative radiotherapy deferral is associated with worse survival in this age group, even in the modern era of chemotherapy. Further study is needed to determine reasons for postoperative radiotherapy deferral and to identify subgroups of patients who may be safely managed with postoperative radiotherapy deferral, perhaps with the aid of molecular subtyping.”
Molecular analyses are likely to influence future research and treatment in this area, Arnold C. Paulino, MD, professor in the department of radiation oncology at The University of Texas MD Anderson Cancer Center, and Jerry J. Jaboin, MD, PhD, clinical associate professor of radiation medicine at Oregon Health & Science University, wrote in a related editorial.
“Currently there are four recognized molecular variants of childhood medulloblastoma: WNT, SHH, group 3 and group 4,” Paulino and Jaboin wrote. “The WNT subtype, which comprises 10% of tumors, is associated with a greater than 90% survival rate and has the best prognosis with current therapy. The SHH subtype has an intermediate outcome and is typically seen in infants and adolescents and/or young adults. ... Current studies are looking at de-escalation for treatment for WNT pathway tumors and more aggressive therapy for non–WNT, non–SHH subtypes.”
Clinicians will likely be able to better predict which patients can forego radiotherapy as this research evolves, Paulino and Jaboin wrote.
“At present, patients age[d] 3 years to 8 years with medulloblastoma should receive postsurgical radiotherapy to the craniospinal axis and tumor bed and chemotherapy; however, future studies using molecular subgroups for determination of treatment may reveal that some of these patients may not require radiotherapy.” – by Cameron Kelsall
Disclosure: Kann reports no relevant financial disclosures. Please see the full study for a list of all other researchers’ relevant financial disclosures. Paulino and Jaboin report no relevant financial disclosures.
Click Here to Manage Email Alerts