Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines on the Role of Whole Brain Radiation Therapy in Adults With Newly Diagnosed Metastatic Brain Tumors

• Published in: Neurosurgery Vol. 84; no. 3; pp. E159 - E162
• Main Authors: Gaspar, Laurie E, Prabhu, Roshan S, Hdeib, Alia, McCracken, D Jay, Lasker, George F, McDermott, Michael W, Kalkanis, Steven N, Olson, Jeffrey J
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01-03-2019; Copyright by the Congress of Neurological Surgeons; Wolters Kluwer Health, Inc
• Subjects: Adult; Adults; Brain; Brain - radiation effects; Brain cancer; Brain Neoplasms - diagnosis; Brain Neoplasms - radiotherapy; Brain Neoplasms - surgery; Brain tumors; Cancer; Cancer metastasis; Clinical practice guidelines; Congresses as Topic - standards; Cranial Irradiation - methods; Cranial Irradiation - standards; Dose Fractionation, Radiation; Elderly patients; Evidence-based medicine; Female; Fractionation; Histochemistry; Histopathology; Humans; Lung cancer; Male; Medical diagnosis; Memantine; Metastasis; Neurosurgeons - standards; Physicians; Practice guidelines (Medicine); Practice Guidelines as Topic - standards; Prognosis; Radiation (Physics); Radiation therapy; Radiosurgery - adverse effects; Radiosurgery - standards; Radiotherapy; Retirement benefits; Schedules; Small cell lung cancer; Surgery; Systematic review; Time; Toxicity; Tumors; Practice guideline; Whole brain radiation therapy; Fractionation; Histopathology; Cerebral metastases; Surgical resection; Brain metastases; Radiotherapy
• ISSN: 0148-396X; 1524-4040
• DOI: 10.1093/neuros/nyy541

Abstract
TARGET POPULATION
Adult patients (older than 18 yr of age) with newly diagnosed brain metastases.
QUESTION
If whole brain radiation therapy (WBRT) is used, is there an optimal dose/fractionation schedule?
RECOMMENDATIONS
Level 1:  A standard WBRT dose/fractionation schedule (ie, 30 Gy in 10 fractions or a biological equivalent dose [BED] of 39 Gy10) is recommended as altered dose/fractionation schedules do not result in significant differences in median survival or local control.
Level 3: Due to concerns regarding neurocognitive effects, higher dose per fraction schedules (such as 20 Gy in 5 fractions) are recommended only for patients with poor performance status or short predicted survival.
Level 3: WBRT can be recommended to improve progression-free survival for patients with more than 4 brain metastases.
QUESTION
What impact does tumor histopathology or molecular status have on the decision to use WBRT, the dose fractionation scheme to be utilized, and its outcomes?
RECOMMENDATIONS
There is insufficient evidence to support the choice of any particular dose/fractionation regimen based on histopathology. Molecular status may have an impact on the decision to delay WBRT in subgroups of patients, but there is not sufficient data to make a more definitive recommendation.
QUESTION
Separate from survival outcomes, what are the neurocognitive consequences of WBRT, and what steps can be taken to minimize them?
RECOMMENDATIONS
Level 2: Due to neurocognitive toxicity, local therapy (surgery or SRS) without WBRT is recommended for patients with ≤4 brain metastases amenable to local therapy in terms of size and location.
Level 2:  Given the association of neurocognitive toxicity with increasing total dose and dose per fraction of WBRT, WBRT doses exceeding 30 Gy given in 10 fractions, or similar biologically equivalent doses, are not recommended, except in patients with poor performance status or short predicted survival.
Level 2: If prophylactic cranial irradiation (PCI) is given to prevent brain metastases for small cell lung cancer, the recommended WBRT dose/fractionation regimen is 25 Gy in 10 fractions, and because this can be associated with neurocognitive decline, patients should be told of this risk at the same time they are counseled about the possible survival benefits.
Level 3: Patients having WBRT (given for either existing brain metastases or as PCI) should be offered 6 mo of memantine to potentially delay, lessen, or prevent the associated neurocognitive toxicity.
QUESTION
Does the addition of WBRT after surgical resection or radiosurgery improve progression-free or overall survival outcomes when compared to surgical resection or radiosurgery alone?
RECOMMENDATIONS
Level 2: WBRT is not recommended in WHO performance status 0 to 2 patients with up to 4 brain metastases because, compared to surgical resection or radiosurgery alone, the addition of WBRT improves intracranial progression-free survival but not overall survival.
Level 2: In WHO performance status 0 to 2 patients with up to 4 brain metastases where the goal is minimizing neurocognitive toxicity, as opposed to maximizing progression-free survival and overall survival, local therapy (surgery or radiosurgery) without WBRT is recommended.
Level 3: Compared to surgical resection or radiosurgery alone, the addition of WBRT is not recommended for patients with more than 4 brain metastases unless the metastases’ volume exceeds 7 cc, or there are more than 15 metastases, or the size or location of the metastases are not amenable to surgical resection or radiosurgery.
The full guideline can be found at: https://www.cns.org/guidelines/guidelines-treatment-adults-metastatic-brain-tumors/chapter_3.