Risk factors for glioblastoma therapy associated complications.
OBJECTIVE
Thromboembolic events, seizures, neurologic symptoms and adverse effects from corticosteroids and chemotherapies are frequent clinical complications seen in Glioblastoma (GB) patients. The exact impact these have on dismal patient outcome has not been fully elucidated. We aimed at assessing treatment associated complications, evaluating the impact on survival and defining risk factors.


METHODS
Two hundred and thirty three consecutive adult patients operated on for newly diagnosed GB at a single tertiary institution over a 5-year-period (2006-2011) were assessed. Demographic parameters (age, gender, comorbidity status quantified by the Charlson-comorbidity-index (CCI), functional status computed by the Karnofsky Performance Scale (KPS), tumor characteristics (size, location, IDH-1 mutation and MGMT-Promotor-methylation-status) and treatment parameters (volumetrically quantified extent of resection and adjuvant therapy) were retrospectively reviewed. Complications assessed were recorded as neurological (N), surgical (S) and medical (M). Independent risk factor analysis was performed by the univariate and multivariate logistic regression method. Survival analysis was plotted by the Kaplan-Meier-method, influence of complication occurrence was evaluated by the log-rank test.


RESULTS
One hundred and fifty nine (68.2%) patients had a total of 281 complications (90 N, 174 M and 17 S). Univariate analysis identified age (P=0.003), KPS<70 (P=0.002), CCI>3 (P=0.03), eloquent tumor location (P=0.001) and therapy other than the standard radio-chemotherapy with temozolomide therapy (P=0.034) as risk factors for complications. Multivariate analysis extracted the eloquent tumor location (P=0.007, odds ratio 1.94) as a significant predictor for complications. Having a complication significantly decreased patient survival (P=0.015).


CONCLUSIONS
Complications significantly decrease GB patient survival. Age, poor functional status, other than standard adjuvant therapy and eloquent tumor location proved as significant risk factors for encountering a therapy associated complication. Not extensive surgery or tumor size but surgery at eloquent locations impacts complication occurrence the strongest with a 2 fold increased complication occurrence risk.
Department of Neurosurgery, Knappschafts-Krankenhaus Bochum-Langendreer, Ruhr-University of Bochum, In der Schornau 23-25, 44892 Bochum, Germany; Department of Neurosurgery, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1, 68167 Mannheim, Germany. Electronic address: genevieve.ening@gmail.com.
Genevieve
G
Ening
Department of Neurosurgery, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1, 68167 Mannheim, Germany.
Fransiska
F
Osterheld
Department of Neuropathology, Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany; Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 224, 69120 Heidelberg, Germany.
David
D
Capper
Department of Neurosurgery, Knappschafts-Krankenhaus Bochum-Langendreer, Ruhr-University of Bochum, In der Schornau 23-25, 44892 Bochum, Germany; Department of Neurosurgery, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1, 68167 Mannheim, Germany.
Kirsten
K
Schmieder
Department of Neurosurgery, Knappschafts-Krankenhaus Bochum-Langendreer, Ruhr-University of Bochum, In der Schornau 23-25, 44892 Bochum, Germany; Department of Neurosurgery, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1, 68167 Mannheim, Germany.
Christopher
C
Brenke
D000367:Age Factors; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D059186:Chemoradiotherapy, Adjuvant / Q000009:adverse effects*; D015331:Cohort Studies; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives; D005260:Female; D005909:Glioblastoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006801:Humans; D020300:Intracranial Hemorrhages / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D017567:Karnofsky Performance Status; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D000068079:Motor Disorders / Q000453:epidemiology / Q000209:etiology; D015999:Multivariate Analysis; D019635:Neurosurgical Procedures; D016017:Odds Ratio; D011183:Postoperative Complications / Q000453:epidemiology*; D019106:Postoperative Hemorrhage / Q000453:epidemiology; D011379:Prognosis; D011618:Psychotic Disorders / Q000453:epidemiology / Q000209:etiology; D012189:Retrospective Studies; D012307:Risk Factors; D012640:Seizures / Q000453:epidemiology / Q000209:etiology; D013530:Surgical Wound Infection / Q000453:epidemiology; D000077204:Temozolomide
D000970:Antineoplastic Agents; D003606:Dacarbazine; D000077204:Temozolomide
Glioblastoma; Medical; Neurological; Surgical complications; Survival