DR SAILENDRASENIOR RESIDENT

DEPT OF RADIOTHERAPYMAULANA AZAD

MEDICAL COLLEGE

ADJUVANT RADIOTHERAPY IN LOW

GRADE GLIOMA

LOW-GRADE GLIOMA

Low-grade gliomas are slow-growing tumors that are divided into

1.Pilocytic and 2.Nonpilocytic subtypes. They account for 20% and 10% of gliomas and primary intracranial tumors in adults respectively.

PILOCYTIC ASTROCYTOMA

Complete resection of pilocytic astrocytomas is associated with excellent survival, with the majority (>90%) of patients cured of the tumor

If radiotherapy is indicated the dose is typically 50 to 55 Gy (1.8- to 2-Gy fractions).

NO ADJUVANT THERAPY IS NECESSARY

EVIDENCE-BASED TREATMENT SUMMARY

Maximal surgical resection, although not tested in a prospective trial, is associated with more favorable outcome and is recommended whenever feasible.

Postoperative radiotherapy may be considered in – patients with incompletely resected tumors based on risk factors for progression(absence of 1p

deletion,19q deletion and IDH1 mutation)– On disease progression.

Chemotherapy does not have an established role in pilocytic astrocytoma in adults.

NONPILOCYTIC/DIFFUSELY INFILTRATING GLIOMAS

Factors associated with improved outcome include– young age– good neurologic status– oligodendroglial subtype– low proliferation indices(<3%)Median survival is approximately 5 years for

patients with astrocytoma and approximately 10 years for patients with oligodendroglioma

PIGNATI et al.

Multivariate analysis from EORTC 22844 and 22845 randomised trial showed that

age 40 years or olderastrocytoma histologymaximum diameter ≥6 cm,tumor crossing the midline,presence of neurologic deficits

negatively affected survival.

Patients with up to two of these factors were considered low risk (median survival, 7.7 yrs), and patients with three or more were considered high risk (median survival,3.2 yrs).In younger patients (<40 years) who have undergone complete resection, observation with serial imaging are options.In those who have undergone a subtotal resection or those with high-risk features, postoperative radiotherapy may be recommended, typically 50 Gy in 1.8-Gy fractions.

RADIOTHERAPY

3 recent phase III trials provide the best evidence with respect to the indications for radiotherapy, as well as the dose.

No Difference in OS

PFS is better in early radiotherapy arm

No significant difference in OS,PFS or TOXICITY in both the arms

LOW DOSE RT(45 Gy) VS HIGH DOSE RT(59.4 Gy)

P=0.65 P=0.48

LOW DOSE RT(50.4Gy) VS HIGH DOSE RT(64.8Gy)

PFS OS

EVIDENCE-BASED TREATMENT SUMMARY

Maximal surgical resection, although not tested in a prospective trial, is generally associated with more favorable outcome and is recommended whenever feasible. Postoperative RT - NO OS ADVANTAGE PFS AND SEIZURE CONTROL were superior.

The typical radiotherapy dose is 45 to 54 GyNo survival advantage with higher doses.In RTOG 9802, survival advantage from chemoradiotherapy was detected in patients surviving beyond 2 years. Temozolomide is being tested in phase III trials.(EORTC 22041)

Acute Toxicity within 6 weeks

Subacute Toxicity 6wks to 6 months

Late Sequelae6 months to many years

following treatment

RADIATION TOXICITY

ACUTE TOXICITYThese symptoms are believed to be the consequence of a transient peritumoral edema and usually respond to a shortterm increase or the institution of corticosteroids.Transient worsening of pretreatment deficitsfatigue, headache, and drowsinessmild dermatitisAlopecia within the irradiated areas is common and may be permanent with higher total doses.Nausea and vomitingOtitis externa and serous otitis mediaMucositis and esophagitis due to exit dose(in CSI).Hematologic toxicity in CSI

SUBACUTE TOXICITY

Attributed to changes in capillary permeability, as well as to transient demyelination due to damage to oligodendroglial cells.Headache, somnolence, fatigability, and deterioration of pre-existing deficits, usually respond to steroids.The phenomenon of pseudoprogression temporally fits within the subacute toxicity time frame.

LATE SEQUELAEUsually irreversible and progressiveDue to white matter damage from vascular injury, demyelination, and necrosis.The most serious is radiation necrosis with peak incidence at 3 years.Radiation necrosis can mimic recurrent tumor clinically by the reappearance and worsening of initial symptoms and neurologic deficitsRadiographically it shows development of a progressive, irreversible, enhancing mass with associated edema on imaging.

PET, MR spectroscopy, and nuclear and dynamic CT scanning procedures may aid in the differentiation of radiation necrosis from recurrent tumor.The best treatment for symptomatic necrosis is control of symptoms with steroids, followed by surgical debulking, although even after resection necrosis may progress.Other options are bevacizumab,anticoagulants,hyperbaric oxygenMethotrexate can also cause necrosis

OTHER LATE SEQUELES

Hearing loss and vestibular damageLoss of visual acuityHormonal deficiencyNeuropsychologic changes and neurocognitive impairmentDecline memory

RADIOTHERAPY

TECHNIQUES PARTIA

L-BRAINWHOL

E-BRAIN

CSISRS

SRT

TARGET VOLUME DELINEATION

GTV

CTV1-1.5cm

PTV.5-1cm

CHEMOTHERAPY

Alkylating agents such as carmustine (BCNU) and lomustine (CCNU) have been the most widely studied drugs in CNS tumors. These agents cross the BBB, but prolonged use is difficult because of cumulative myelotoxicity and the dose-related risk of pulmonary fibrosis.

Combination regimens, such as BCNU and temozolomide, are not more efficacious,because of the need to reduce the dose of each agent due to overlapping myelotoxicity.