Product information and disease description Place of product in therapy Approaches to treatment Current treatment options and standard of care

Radiotherapy

20 evidence topics · 10 sources

European standard clinical practice: radiotherapy deferred, reserved for selected cases

“Radiotherapy had previously been the mainstay of treatment for incompletely resected pLGG but nowadays remains a standard as salvage treatment or as primary treatment in selected cases in which surrounding normal tissue can be optimally preserved.” (opens the source at this quote in a new tab)
“Patients younger than 5 years of age seem to be more at risk of sequelae following conformal radiotherapy with higher risk of moya moya, increasing deficits over time and greatest decline in cognition.” (opens the source at this quote in a new tab)

NOPHO consensus guidelines on radiotherapy for pLGG

“Radiotherapy remains the most effective treatment for unresectable pLGG, but its use must be carefully weighed against the risk of long-term side effects. The guidelines emphasise a personalised treatment approach, considering the evolving field of targeted therapies and the importance of multidisciplinary input in decision-making.” (opens the source at this quote in a new tab)
“Radiotherapy should generally be avoided when treating CNS tumours in NF1-patients as they have an increased risk of both developing secondary neoplasms [20] and vasculopathies [21].” (opens the source at this quote in a new tab)

Conformal radiotherapy outcomes: COG ACNS0221

“At a median follow-up of 5.15 years, 5-year PFS was 71%±6% and OS was 93%±4%.” (opens the source at this quote in a new tab)

Late cognitive and endocrine effects of conformal radiotherapy

“The effect of age exceeded that of radiation dose; patients younger than 5 years experienced the greatest decline in cognition.” (opens the source at this quote in a new tab)
“The 10-year cumulative incidence of GH replacement was 48.9%; of thyroid hormone replacement, 64.0%; of glucocorticoid replacement, 19.2%; and of gonadotropin-releasing hormone analog therapy, 34.2%.” (opens the source at this quote in a new tab)

Optic pathway and hypothalamic LGG: vasculopathy and second neoplasms after radiotherapy

“Possible RT-induced neoplasms developed in 8 patients, including 4 with NF-1. The 10-year cumulative incidence of clinically significant vasculopathy was 7.1% (95% CI, 2.9%-13.9%); vasculopathy did not develop in any child aged >10 years at the commencement of RT.” (opens the source at this quote in a new tab)

Long-term toxicity after photon radiotherapy

“Of the 23 survivors analyzed for late toxicity, 15 (65%) developed grade 3+ toxicity. The most common Common Terminology Criteria for Adverse Events grade 3 toxicity (30% of survivors) was serious cognitive disability. Four patients (14%) died secondary to treatment complications, all occurring over a decade after completing RT.” (opens the source at this quote in a new tab)

Vision preservation with early radiotherapy in sporadic optic pathway glioma

“BFS rates were 81% at 5 years and 60% at 8 years for CT and 100% at 5 and 8 years for early RT (P = .017).” (opens the source at this quote in a new tab)

Long-term survival without upfront radiotherapy and the trade-off against early tumor control

“Despite multiple progressions, we observed >90% survival 20 to 25 years after the diagnosis in the absence of aggressive modalities such as radiotherapy and no late mortality due to tumor progression.” (opens the source at this quote in a new tab)
“Specifically, although radiotherapy may be associated with better tumor control in early years, it may lead to significant devastating sequelae affecting not only quality of life but also long-term survival during adult life.” (opens the source at this quote in a new tab)

Visual acuity at last follow-up with early radiotherapy compared with chemotherapy

“At time of last follow-up, 70% of early RT patients maintained normal to satisfactory VA (≤0.2 LogMAR) in a minimum of 1 eye and 60% maintained it in both eyes versus 36% and 18% in the CT group, respectively (P = 0.03, P = .02).” (opens the source at this quote in a new tab)
“Finally, in an analysis of all patients (N = 38) for clinical risk factors at diagnosis associated with poor long-term visual outcomes, the only statistically significant factors were blindness at presentation (P = .001) and <12 months of age at diagnosis (P = .04).” (opens the source at this quote in a new tab)

Endocrine supplementation and grade 3 toxicity after proton radiotherapy in sporadic optic pathway glioma

“As of last follow-up, 11 patients (58%) required post-RT hormonal supplementation. Of the 16 patients with long-term follow-up, 3 grade 3 toxicities were appreciated.” (opens the source at this quote in a new tab)
“One patient developed orbital edema and pain requiring surgical intervention; another 2 patients developed treatment-related vasculopathy (moyamoya disease) confirmed by angiography at 15 and 36 months from RT completion at 8 and 10 years old, respectively.” (opens the source at this quote in a new tab)

Sources of bias in comparisons of upfront radiotherapy with nonradiation approaches

“Studies comparing patients who were irradiated upfront and patients subjected to nonradiation approaches are subject to a selection bias at several levels.” (opens the source at this quote in a new tab)
“First, upfront radiation treatment is currently reserved for more aggressive PLGG; this is highlighted by the early deaths (1-3 years after the diagnosis) observed in these cohorts” (opens the source at this quote in a new tab)
“Second, these are usually deep-seated tumors for which only a small biopsy sample is available; this leads to a biopsy bias, and presumably a low-grade glioma may actually represent a heterogeneous tumor with high- and low-grade components.” (opens the source at this quote in a new tab)
“An analysis of patients who survived 5 or more years bypasses many of these limitations and enables a more accurate analysis of late deaths possibly related to radiotherapy.” (opens the source at this quote in a new tab)
“Because no plateau has been reached, the impact of vascular events and tumor-related deaths may be even higher with longer follow-up.” (opens the source at this quote in a new tab)

Residual role for radiotherapy pending targeted therapy

“While awaiting future studies performed to identify the patients who may benefit from more intensive treatment and anticipating the introduction of targeted therapies, we acknowledge that radiation therapy may have a role in the management of selected, non-NF1 patients with refractory PLGG after careful consideration of alternative lines of chemotherapy, surgery, and targeted therapies.” (opens the source at this quote in a new tab)

Cerebrovascular events, moyamoya, and secondary meningioma after cranial irradiation

“After cranial irradiation, the risk of cerebrovascular incidents is increased 16% at age 50 to 26% at age 65” (opens the source at this quote in a new tab)
“The risk of developing Moyamoya is higher in younger children, in patients with optic pathway glioma, and in those receiving higher radiation doses and occurs at a median of 40-62 months after RT with median dose of 52 Gy (range, 23-150)” (opens the source at this quote in a new tab)
“Latency periods for the development of secondary meningioma can be up to 20-40 years” (opens the source at this quote in a new tab)

Disease control by modality in sporadic optic pathway glioma

“Patients undergoing initial treatment with RT experienced no progression at any time interval (100% progression-free survival [PFS]), and all patients had over 8 years of follow-up (Fig. 3A).” (opens the source at this quote in a new tab)
“Two patients received MAPK/ERK kinase (MEK) inhibitors as first-line salvage and remain free from progression at 81 and 84 months. Three patients received temozolomide as first-line salvage with a median PFS of 19 months, whereas 20 patients received other chemotherapy (mostly vinblastine) with a median PFS of 9 months.” (opens the source at this quote in a new tab)
“Most progression overall was local; however, 4 patients in the CT group developed leptomeningeal disease during their disease course following repeated local failure.” (opens the source at this quote in a new tab)
“Of the 19 patients eventually receiving RT, none progressed locally, and only the 1 above-mentioned patient progressed distantly, developing a new intracranial lesion months after treatment.” (opens the source at this quote in a new tab)

Definition of the upfront radiotherapy analysis set and the late deaths within it

“To avoid bias, we excluded patients who had undergone gross total resection for PLGG because this is a curative intervention and abrogates the need for further radiation treatment.” (opens the source at this quote in a new tab)
“We also excluded patients who had died within the first 5 years after the diagnosis to avoid a potential biopsy bias of high-grade gliomas (which have an invariably aggressive course and, therefore, are more likely to require radiation therapy) misdiagnosed as PLGG.” (opens the source at this quote in a new tab)
“To further explore this observation, we constructed a cohort of clinically relevant Ontario PLGG patients for whom total resection was not performed and who survived the first 5 years (whole Ontario cohort, n = 607; SickKids, n = 385). There were 32 late deaths overall (>5 years after diagnosis) recorded for the Ontario cohort with an SMR of 8.9 (95% CI, 6.1-12.2).” (opens the source at this quote in a new tab)

Replication of the late mortality association in an independent SEER cohort

“The risk of late death for children undergoing radiation increased approximately 3-fold for all deaths (HR, 3.3; 95% CI, 2.3-4.7; P < .001) and tumor-related deaths (HR, 3.4; 95% CI, 2.1-5.5; P = .001).” (opens the source at this quote in a new tab)

Outcome of the four children with neurofibromatosis type 1 who received upfront radiotherapy

“A total of 4 NF1 patients received upfront radiation treatment: 2 died of tumor transformation (as discussed previously), and 2 patients were alive at 16 and 26 years.” (opens the source at this quote in a new tab)

Twenty-year overall survival stratified by upfront radiotherapy

“Patients who received upfront radiation treatment showed significantly lower survival than those who did not (OS at 20 years, 76.9% ± 11.7% vs 96.9% ± 3.1%; P = .039; Supporting Fig. 4 [see online supporting information]).” (opens the source at this quote in a new tab)
“Furthermore, for the SickKids cohort, the tumor-related survival was significantly inferior for patients who received upfront radiation (20-year OS, 87.4% ± 4.9%; SMR, 23.0; 95% CI, 10.9-39.4) versus those who did not (20-year OS, 97% ± 1.1%; SMR, 7.5; 95% CI, 4.1-12; P = .007; Fig. 2C), and upfront radiation treatment increased the risk of tumor-related death approximately 4-fold (HR, 4.4; 95% CI, 1.3-14.6; P = .013).” (opens the source at this quote in a new tab)

Twenty-year overall survival by radiotherapy in the SEER reference cohort

“For children who received upfront radiation and children who did not, the 20-year OS rates were 84.4% ± 1.9% and 95.3% ± 0.8%, respectively (P < .001; Fig. 2B). Similarly, the tumor-related 20-year OS rates were 89% ± 1.72% and 94.3% ± 0.8%, respectively (P < 0.001; Fig. 2D).” (opens the source at this quote in a new tab)

First-line radiotherapy PFS in the German SIOP LGG 2004 trial and management-strategy comparison in Fisher's series

“The 5-year PFS reported for the subgroup with first-line radiotherapy in the German SIOP LGG 2004 trial is 80 % which has to be balanced against the risk of treatmentrelated toxicity” (opens the source at this quote in a new tab)
“Furthermore, Fisher’s series showed that the overall survival of the patients receiving radiotherapy immediately following incomplete resection and those with radiation following progression was the same after 5 and 10 years” (opens the source at this quote in a new tab)
“Moreover, PFS did not differ by management (P:0.32).” (opens the source at this quote in a new tab)