Immediate Side Effects of Cranial Stereotactic Radiosurgery and ...

328 Immediate Side Effects of Cranial Stereotactic Radiosurgeryexperienced nausea and vomiting as immediateside effects of cranial streotactic irradiation, ahighly significant positive correlation with thedose delivered to the region harboring areapotrema (Vomiting Center) with cut off point at2 Gy was found. After 2 Gy dose, all patientsTable (1): Post-radiosurgery injury expression (PIE) scoresfor location of arteriovenous malformation (Flickingeret al., 1997) [10].developed nausea and vomiting (Pearson’s ChiSquare) (p value < 0.0001) [3] as shown in Table(11). Poor correlation data were obtained onanalyzing other encountered immediate sideeffects in relation to any of the disease or therapyrelated parameters.Table (4): Karnofsky performance scale among 163 patientstreated by stereotactic radiosurgery and radiotherapy(NEMROCK 1999-2002).PIE scoreLocationPerformance statusNumber%1 (Low risk)234 (High risk)Frontal lobeCerebellum, temporal lobe, partietal lobeOccipital lobe or basal gangliaMedulla, thalamus, intraventricular, ponsor corpus callosum100-9080-7060-50Total65712716339.843.616.6100Table (2): Radiation therapy oncology group (RTOG)radiosurgery quality assurance guidelines [15].Per protocolMinor(acceptabledeviation)Major(unacceptableConformity≤ 2> 2 & < 2.5> 2.5Dosehomogenity1-2> 0.9 & < 1or> 2 & < 2.5< 0.9 & > 2.5Dosegradient≥ 0.3–Conformity: Prescription Isodose Surface Volume to Target Volume(TV) Ratio.Dose homogenity: Maximum Dose (MD) to Prescription Dose(PD) Ratio.Dose gradient: Target Volume (TV) to Volume Enclosed by 50%(V50%) Ratio.Table (3): Initial diagnosis among 163 patients treated bystereotactic radiosurgery and radiotherapy (NEM-ROCK 1999-2002).CatgeoryBenignDiseasesTumorsTotalDiagnosisMeningiomasArteriovenousMalformationsAcuosticNeuromasLow gradeGliomasHigh gradeGliomasPituitaryAdenomasMetastaticBrain diseaseOthers*Number2922*Others include; haemangiopericytoma in 2 patients (1%), chordomaof skull base in 4 patients (2%), ependymoma in 4 patients(2%), pineal body tumor in 3 patients (1.5%), glomus jugularein 3 patients (1.5%) and medulloblastoma in 3 patients (1.5%).2139208519163–1913132812.553%9.5100Table (5): Lesion volume, multiplicity and treatment scheduleamong 163 patients treated by stereotacticradiosurgery and radiotherapy (NEMROCK1999-2002).ItemVolume:Range (cc)Median volume (cc)Standard deviationMultiplicity:One lesionTwo lesionsThree lesionsTreatment schedule:SRSSRTValues0.21-65.3112.5±13.6160 patients2 patients1 patient101 (61.9%)62 (38.1%)Table (6): Dose scheme adopted among (101) patientstreated by stereotactic radiosurgery (NEM-ROCK 1999-2002).Volume< 1 cc1-5 cc> 5-125 ccN113357% Dose (Gy)10.932.756.4201510Table (7): Dose contribution to risk structures and conformityindex among 163 patients treated by stereotacticradiosurgery and radiotherapy (NEMROCK1999-2002).RiskstructureLeft eyeRight eyeBrain stemChiasmaConformityIndexDose range(Gy)0-4.40-3.60-19.40-17.2Range1-2.95Mean dose(Gy)0.470.424.601.30Mean value1.44Standarddeviation±0.75±0.59±4.84±4.08StandardDeviation±0.39

Mohamad Abdulla 329Table (8): Incidence of immediate side effects “of mild &moderate severity” reported among 163 patientstreated by stereotactic radiosurgery and radiotherapy(NEMROCK 1999-2002).Immediate sideeffectsNaudea and vomitingHeadacheWorsening of pretreat. DeficitsConvulsive fitsNumber of patientswith side effects392352% oftotal23.9143.061.2Table (9): Incidence of immediate side effects accordingto initial diagnosis among 163 patients treatedby stereotactic radiosurgery and radiotherapy(NEMROCK 1999-2002).DiagnosisAcuostic neuromaLow grade gliomaHigh grade gliomaArteriovenous malformationMeningiomaMetastatic brain diseasePituitary adenomaOthersNumber10/2113/3914/204/229/293/50/84/19%433370203160021.1Table (10): Distribution of immediate side effects (I.S.E.)within different disease entities among 163patients treated by stereotactic radiosurgeryand radiotherapy (EMROCK 1999-2002).AcuosticNeuromaLow G.GliomaHigh G.GliomaAVMMeningiomaMetastasesOthersHeadache4553321Nausea &vomiting78101634Worsening ofpretreatmentdeficits0120200FitsTable (11): Incidence to develop nausea and vomitingaccording to radiation dose delivered to areapostrema among 163 patients treated by stereotacticradiosurgery and radiotherapy (NEM-ROCK 1999-2002).DoseN/VNoYeTotal0-≤ 2 Gy124613095.44.6100> 2 GyNo. % No. %0333301001000010010p-value< 0.0001Fig. (1): Cut section in human brain showing area postrema“vomiting center”.Vol. (%)100% = 0.49 cm 3 LesionNormal Tissue140Min. dose = 15.80 GyMax. dose = 20.00 Gy12010080604020Dose (%)00 20 40 60 80 100 120 140 160 180 200100% = 20.00 GyNo dose delivery for:Rt eye mri (12.64 cm 3 ) Lt eye mri (11.94 cm 3 )Fig. (2): Dose volume histogram showing adequate lesionvolume coverage without dose contribution tosurrounding normal structures and conformityindex approaching value 1.Vol. (%)100% = 28.20 cm 3 Brain Stem MRIMin. dose = 0.00 Gy140Max. dose = 7.50 Gy12010080604020Dose (%)00 20 40 60 80 100 120 140 160 180 200Fig. (3): Dose volume histogram of brain stem denotingsparing of the major part of its volume, keepingthe maximum dose (7.50 Gy) to less than 1% ofbrain stem volume. The treated lesion is locatedat the cerebello-pontine angle.

Mohamad Abdulla 331receive a radiation dose ranging from 0-8.1 Gywith a median value of 1.21 Gy to the regionlocated at the floor of the 4th ventricle andharboring area postrema, but the onset of vomitingwas correlated only with doses greater than2 Gy, contrasting to data reported by Alexanderet al. [1].The discrepancy with data reported by Alexanderand co-workers [1] could be attributed todifferent disease entities treated in our study,where he treated only cases with acuostic neuromas.However, further analysis of our datarevealed that 33% (7/21 patients) with acuosticneuromas had developed nausea and vomitingbut at a lower threshold dose level (2 versus6.18 Gy) to area postrema, a finding whichrequires further clarification via future studiesenrolling higher number of patients to establishthe threshold radiation dose to area postremaabove which, nausea and vomiting are anticipatedas immediate post-stereotxay morbid events.Also, inspite of the relatively close results withthose of Bodis et al. [4]; (2 versus 2.75 Gy) asa threshold dose level to area postrema, none ofour patients had received ondansetron as a premedication;only metclopramide and steroidswhich were effecive in alleviating such manifestations.The incidence of developing immediate sideeffects among patients with malignant craniallesions was clearly higher than those with benigndiseases, 70% versus 43% indicating the needto pay more attention to proper patient selectionand adequate pre- as well a post-treatment medicationsfor patients with high grade gliomasand brain metastases.Only two patients had developed epilepticepisodes following stereotaxy. They had thediagnoses of high grade glioma and brainmetastasis, also they had a past history of convulsivefits during their disease course and coulddirect attention to the importance of employingmore potent anti-convulsive measures whenattempting to treat similar patients.Worsening of pre-therapy manifestations wasreported in one, two and two patients with diagnosesof low grade glioma, high garde gliomaand meningioma respectively. All lesions werenoted to be located near the motor cortex whichcould be compromised by either direct radiationeffect or more likely due to cerebral oedemamandating the adequate use of dehydrating measuresin both pre- and post-therapy periods.Moreover, It is difficult to conclude that patientswith pituitary adenomas are not anticipated todevelop immediate post-stereotaxy side effects,as this conclusion cannot be emphasized withthe small number of patients enrolled in our trial(8 Patients).The location of lesions and dose are criticalparameters related to the development of poststereotacticradiosurgery and radiotherapy edema.It is well known that parasagittal meningiomasare a risk group in this respect. Occlusion ofbridging veins is a possible though unprovenmechanism for this phenomenon. However, thisedema did not occur within the time frame ofthe present study.Further clinical trials are clearly neededincluding higher numbers of patients with homogenouscharacteristics aiming at obtainingmore informative data about stereotaxy sideeffects and its proper management. Also, it shouldbe emphasized to avoid radiation doses greaterthan 2 Gy to the region in the floor of the 4thventricle harboring area potrema with the possibleuse of H3 antagonists if higher dose deliveryis an inevitable event.Acknowledgment: I am grateful to Prof. KamalA. El-Ghamrawi for critical review of Themainscript. Also, I would like to express mydeep appreciation to Prof. Ehsan El-Ghoneimy& Prof. Magda Moustafa as well as NEMROCKradiosurgery team for devotion and help.REFERENCES1- Alexander E. 3rd, Siddon R and Loeffler J.: The AcuteOnset of Nausea and Vomiting Following StereotacticRadiosurgery: Correlation with Total Dose to AreaPostrema. Surg. Neurol., 32 (1): 40-44, 1989.2- Alexander E. III, Loeffler J.S., Lunsford L.D., et al.:Stereotactic Radiosurgery. New York: McGraw Hill,1993.3- Altman D.G.: Practical statistics for medical research.London, Chapman & Hall, 115-231, 1991.4- Bodis S., Alexander E. III, Kooy H., et al.: The Preventionof Radiosurgery-Induced Nausea and Vomitingby Ondansetron: Evidence of a Direct Effect on TheCentral Nervous System Chemoreceptor Trigger Zone.Surg. Neurol., 42: 249-252, 1994.5- Brenner D.J., Martel M.K. and Hall E.J.: FractionatedRegimens For Stereotactic Radiotherapy of RecurrentTumors in The Brain. Int. J. Radiat. Oncol. Biol. Phys.,21: 819-824, 1991.

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