E.H. Balagamwala

Principles of Radiobiology of Stereotactic Radiosurgery and Clinical Applications in the Central Nervous System

Stereotactic radiosurgery (SRS) has become an important treatment option for intracranial lesions and has recently been adapted to treat lesions outside the brain. Many studies have shown the effectiveness of SRS for the treatment of benign and metastatic tumors. Although DNA damage has been thought to be the principal form of radiation-induced damage, recent studies have shown that vascular endothelial damage is perhaps more important in the setting of high radiation doses per fraction such as those used in SRS. Furthermore, it has been shown that molecular responses to radiation differ based on dose per fraction. The principles of classical radiobiology are reviewed with explanation on why fractionation of radiotherapy allows optimization of the therapeutic ratio. The current understanding of the molecular responses that occur soon after the delivery of high radiation doses per fraction is also reviewed. A summary of current clinical evidence of radiation tolerance to SRS of brain, brainstem, optic chiasm and spinal cord is also provided. Recent advances in understanding the molecular basis of SRS response have uncovered a different biological response than previously thought. Further understanding of these molecular mechanisms will allow for the development of targeted radiosensitizers and radioprotectors to optimize the therapeutic ratio.

The importance of the conformality, heterogeneity, and gradient indices in evaluating Gamma Knife radiosurgery treatment plans for intracranial meningiomas.

PURPOSEnTo investigate the relationship between the conformality index (CIn), heterogeneity index (HIn), and gradient index (GIn) and the development of toxicity in patients treated with Gamma Knife radiosurgery (GKRS) for intracranial meningiomas.nnnMETHODS AND MATERIALSnTreatment records of patients treated from 1997 to 2009 with at least 6 months of follow-up were reviewed. The following parameters were collected: CIn, HIn, GIn (ratio of the volume receiving half the prescription isodose to the volume receiving the full prescription isodose), brainstem (BS) maximum dose (MD), BS volume receiving ≥ 12 Gy (V12), optic apparatus (OA) MD, OA V8 Gy, OA V10, number of isocenters, number of isocenters outside target volume, and the occurrence of six toxicities. Univariate and multivariate logistic regression modeling were used for analysis.nnnRESULTSnThis study included 145 patients (148 meningiomas) with a median follow-up time of 27 months (range, 6-113.9 months). The majority of meningiomas were located in the skull base (53%). The median prescription dose was 13 Gy (range, 10-24 Gy) to the 51.50% (range, 50-92%) isodose. A lower HIn was correlated with a higher GIn (p = 0.007). CIn was not associated with any toxicity. Higher HIn was associated with the development of dizziness (odds ratio [OR] 1.9; p = 0.02), whereas a lower GIn was associated with motor deficits (OR 0.38; p = 0.04) and auditory changes (OR 0.59; p = 0.04). The OA MD, V8, and V12 were not associated with visual changes, but visual changes were associated with a higher number of isocenters outside the target volume (OR 1.93; p = 0.07). BS V12 was correlated with the development of auditory changes (OR 1.05; p = 0.05), whereas patients with higher BS MD tended to have increased toxicity.nnnCONCLUSIONSnClose attention must be paid to all three indices (CIn, HIn, GIn) when optimal treatment plans are determined. We recommend that the target CIn should be ≤ 2.0, the HIn ≤ 2.0, and the GIn ≥ 3.0 for intracranial meningiomas.

Postoperative stereotactic radiosurgery for resected brain metastasis

Despite therapeutic advances in management, the prognosis of patients with brain metastasis remains dismal. Treatment options include surgical resection, whole brain radiation therapy (WBRT), and stereotactic radiosurgery (SRS). Patients who undergo surgical resection typically receive WBRT as adjuvant therapy. However, several studies have demonstrated an association between WBRT and neurotoxicity. Thus, clinicians are increasingly delaying WBRT in favor of postoperative use of SRS. In this review, we will discuss the current literature exploring the efficacy and toxicity of postoperative SRS in the treatment of patients with resected brain metastasis.