Evidence Based Questions Flashcards
Is there a role for concurrent and adj TMZ in DIPG?
No. Despite glioblastoma being the most common histology of DIPG, a COG study did not find a benefit of concurrent/adj TMZ. (Cohen KJ et al., Neuro Oncol 2011)
Is there any benefit with other chemos in DIPG?
No. Although multiple chemo regimens have been tried, RT is the only modality that alters the course of DIPG.
Is there a role for hyperfx or dose escalation in DIPG?
No. Both did not improve survival in multiple POG/CCG trials (only better radiographic response at higher doses with greater radionecrosis and steroid dependence).
Is there a role for hypofx in BSG?
Yes. For pts with DIPG, RT over 3–4 wks offers equal OS and PFS as conventional RT with less Tx burden. (Janssens et al., IJROBP 2013; Zaghloul et al., Radiotherapy & Oncology 2014)
Is there a role for brachytherapy or GK boost after RT in BSG?
No. There is no role for brachytherapy or gamma knife boost after RT.
Does RT dose escalation and/or altered fractionation improve outcomes?
No benefit to dose escalation or altered fractionation was observed across multiple studies.
Is there a benefit from brachytherapy?
Dose escalation with brachytherapy does not appear to improve outcomes.
Does stereotactic radiosurgery (SRS) improve outcomes?
Data are very limited and do not imply any improvement relative to conventionally fractionated RT.
Fuchs, Austria (Acta Neurochir Suppl, PMID 12379009): RR of 21 pts (8–56 years of age) treated with GKRS for BSG. Twelve lesions were located primarily in the pons, two in the medulla, and seven in the midbrain. Median SRS dose was 12 Gy (9–20 Gy) to the tumor margin by the median isodose of 45%. Prior to SRS, four pts had received conventional RT, one had RT and CHT, one pt underwent CHT, and one pt was shunted due to hydrocephalus. Of the 19 pts with follow-up imaging, tumor progression was seen in two pts, stable disease in ten pts, and regression in three cases. MFU was 29 mos. The neurological state improved in five pts. Microsurgical cyst fenestration was performed in one pt after SRS and shunting was necessary for two pts. Nine pts died unrelated to SRS at a median of 20.7 mos. Conclusion: SRS may be feasible in selected pts, but the very limited sample size and substantial heterogeneity in pts, tumors, and treatments limit interpretation.
Is there a role for re-irradiation?
Limited data show feasibility and suggest symptomatic benefit in selected pts.
Fontanilla, MDACC (Am J Clin Oncol 2012, PMID 21297433): RR of six pts who received re-irradiation for progressive DIPG. TTP after the first course of RT was 4 to 18 mos, and all pts had further progression on salvage CHT. The interval between courses of RT was 8 to 28 mos. Initial RT dose was 54 to 55.8 Gy. Re-irradiation was given with concurrent CHT. RT was given in 2 Gy fractions to 20 Gy (n = 4), 18 Gy (n = 1), and 2 Gy (one pt withdrew care after a single fraction). Four pts had substantial clinical improvement in symptoms (three in speech, three in ataxia, and two in swallowing). Three pts showed renewed ability to ambulate after re-irradiation. Four pts had decreased tumor size on post-treatment MRI. The median clinical PFS was 5 mos. Acute radiation-related toxicities were fatigue (n = 2), alopecia (n = 2), and decreased appetite (n = 1). No grade ≥3 toxicities were reported. Conclusion: Re-irradiation with CHT is feasible and may improve symptoms with minimal toxicity. Those with prolonged response to initial therapy may be most suitable.
Is there a benefit from systemic therapy in diffuse intrinsic tumors?
The preponderance of evidence suggests that there is no benefit to systemic therapy. The most notable exception comes from the final results of the French BSG 98 study, which suggested possible improvement in survival relative to historical controls. However, this regimen required protracted CHT, was quite toxic, and involved prolonged hospitalizations.
Does histology have prognostic significance in adult diffuse intrinsic BSGs?
Adult BSGs appear to behave somewhat differently from those in children, particularly diffuse intrinsic low-grade gliomas, which carry a substantially better prognosis than those in children.
Guillamo, France (Brain 2001, PMID 11701605): French RR of 48 adult pts with BSG. Mean age 34 years (range 16–70). MRI demonstrated nonenhancing, diffusely infiltrative tumors (50%), contrast-enhancing localized masses (31%), isolated tectal tumors (8%), and other patterns (11%). Treatment included subtotal resection (8%), RT (94%), and CHT (56%). MS 5.4 years. Significant prognostic factors on MVA included histologic grade, duration of symptoms, and the appearance of “necrosis” on MRI. 85% could be classified into one of the following three groups on the basis of clinical, histological, and radiological characteristics:
Diffuse intrinsic low-grade gliomas (46%): in young adults with a long clinical history before diagnosis and a diffusely enlarged nonenhancing brainstem on MRI. Improved with RT in 62% and had a long survival (MS 7.3 years).
Focal tectal gliomas (8%): in young adults, often presenting with isolated hydrocephalus. Indolent course with estimated MS >10 years (similar to children for this type of tumor).
Malignant gliomas (31%): in elderly pts with short clinical history, as well as contrast enhancement and “necrosis” on MRI. Poor prognosis despite treatment: MS 11.2 mos.
Are there roles for dose escalation or hyperfractionation in brainstem gliomas?
No. In various trials (POG, CHOP/NYU, CCG, UCSF), dose escalation to anywhere from 66 to 78 Gy showed no benefit in disease control or survival. For example, POG 9239 compared conventional fractionation of 54 Gy at 1.8 Gy/fx versus a twice-daily regimen of 1.17 Gy for a total dose of 70.2 Gy. Cisplatin was used as a radiation sensitizer. There was no difference in median time to progression (6 months in the standard arm vs. 5 months in the hyperfractionated arm) and median overall survival (8.5 months in the standard arm vs. 8 months in the hyperfractionated arm).
Freeman, CR, Krischer, JP, Sanford, RA, et al. Final results of a study of escalating doses of hyperfractionated radiotherapy in brain stem tumors in children: a Pediatric Oncology Group study. Int J Radiat Oncol Biol Phys. 1993;27:197-206.
What kind of impact does radiation therapy have on disease progression of brainstem glioma?
About 60% to 70% of those with classic pontine glioma show improvement of functional status. Ultimately, radiotherapy can delay median time to progression by 6 to 8 months.
