Christina Hamisch

Comparison of Stereotactic Brachytherapy (125Iodine Seeds) with Stereotactic Radiosurgery (LINAC) for the Treatment of Singular Cerebral Metastases

AbstractPurpose:To compare stereotactic brachytherapy (SBT) with stereotactic radiosurgery (SRS) for treating singular cerebral metastases, regarding feasibility, complications, cerebral disease control, and survival.Patients and Methods:For this retrospective, single-center study, all patients treated for newly diagnosed, untreated singular cerebral metastasis with SBT using 125iodine seeds (cumulative tumor surface dose 50 Gy, applied for 42 days) were compared with patients receiving LINAC-based SRS for the same indication. Survival and actuarial local and distant disease control were evaluated using univariate Kaplan–Meier estimates and Cox regression. Results were compared using Student’s t test and the χ2 test.Results:A total of 142 patients treated with SRS were compared with 77 patients undergoing SBT. No significant differences were observed between epidemiological and disease-related features (p > 0.05), except a lower KPS (p < 0.007) and a larger tumor volume (p < 0.001) in the SBT group. Neither median survival (LINAC-SRS vs. SBT = 8.1 vs. 8.0 months, respectively) nor actuarial local/distant cerebral disease control after 12 months showed significant differences (93.6% vs. 96.7% / 42.4% vs. 46.4%). There was no treatment-related mortality and no permanent grade 3 or 4 CNS toxicity (RTOG/EORTC CNS toxicity criteria).Conclusion:For the treatment of singular cerebral metastasis, SBT represents a safe, minimally invasive, and effective local treatment option with results comparable to SRS regarding survival and cerebral disease control. Its advantage is that it allows histological (re-)evaluation and treatment within one stereotactic procedure and, compared to microneurosurgery, is almost unrestricted regarding tumor localization. Furthermore, larger metastases can be treated than with SRS. SBT, therefore, represents an alternative local treatment in selected cases.ZusammenfassungZiel:Vergleich der stereotaktischen Radiochirurgie (SRS) mit stereotaktisch geführter Jod-125-Seedimplantation zur Brachytherapie (SBT) zur Behandlung neu diagnostizierter, unbehandelter singulärer zerebraler Metastasen bezüglich Durchführbarkeit, Komplikationen, zerebraler Tumorkontrolle und Überleben.Patienten und Methodik:Für diese retrospektive Studie verglichen wir Behandlungsergebnisse von Patienten mit singulären zerebraler Metastasen, die mittels SBT (Jod-125-Seeds, kumulative Tumoroberflächendosis 50 Gy appliziert über 42 Tage) therapiert wurden, mit solchen, die LINAC-basierte SRS erhielten. Überleben, aktuarische lokale und distante Kontrolle der cerebralen Metastasen nach 12 Monaten wurden mittels Kaplan–Meier ermittelt und Ergebnisse mittels t-Test und Chi-Quadrat Test ausgewertet.Ergebnisse:142 SRS-behandelte Patienten wurden mit 77 SBT-therapierten verglichen. Bis auf schlechteren KPS (p < 0.007) und größeres Tumorvolumen (p < 0,001) in der SBT-Gruppe unterschieden sich epidemiologische und krankheitsspezifische Merkmale nicht signifikant (p > 0,05). Weder das mediane Überleben (SRS vs. SBT = 8,1 versus 8,0 Monate) noch die aktuarische lokale/ distante Tumorkontrolle (93,6% vs. 96,7%/42,4% vs. 46,4%) zeigten signifikante Unterschiede. Es gab keine behandlungsassoziierte Mortalität und keine permanenten Grad-3- und -4-Schädigungen (ZNS-Toxizitätskriterien der RTOG/EORTC).Schlussfolgerung:SBT stellt eine sichere, minimal-invasive und effektive Methode zur lokalen Behandlung singulärer zerebraler Metastasen dar. Vorteilhaft ist die Kombinationsmöglichkeit von histologischer Diagnostik und Behandlung innerhalb einer Operationssitzung. Die Ergebnisse sind bezüglich Überleben und zerebraler Tumorkontrolle mit denen nach SRS vergleichbar. Im Gegensatz zur Mikro-Neurochirurgie bestehen kaum Restriktionen bezüglich Tumorlokalisation. Im Vergleich zur SRS können auch größere Metastasen behandelt werden. Daher stellt SBT für ausgewählte Fälle eine alternative lokale Behandlungsmethode dar.

Stereotactic Brachytherapy With Iodine-125 Seeds for the Treatment of Inoperable Low-Grade Gliomas in Children: Long-Term Outcome

PURPOSE Resection is generally considered the gold standard for treatment of low-grade (WHO grades I and II) gliomas (LGGs) in childhood. However, approximately 30% to 50% of these tumors are inoperable because of their localization in highly eloquent brain areas. A few reports have suggested stereotactic brachytherapy (SBT) with implantation of iodine-125 ((125)I) seeds as a safe and effective local treatment alternative. This single-center study provides a summary of the long-term outcome after SBT in one of the largest reported patient series. PATIENTS AND METHODS All pediatric patients treated with SBT ((125)I seeds; cumulative therapeutic dose 50-65 Gy within 9 months) by our group for LGG with follow-up of more than 6 months were included. Clinical and radiologic outcome, time to progression, and overall survival were evaluated. Prognostic factors (age, sex, Karnofsky performance score, tumor volume, and histology) for survival and disease progression were investigated. RESULTS In all, 147 of 160 pediatric patients treated with SBT (from 1982 through 2009) were analyzed in detail. Procedure-related mortality was zero, and the 30-day morbidity was transient and low (5.4%). Survival rates at 5 and 10 years were 93%, and 82%, respectively, with no significant difference between WHO grades I and II tumors (median follow-up, 67.1 ± 57.7 months). Twenty-one (14.8%) of 147 patients presented with tumor relapse. The remaining 126 patients revealed complete response in 24.6%, partial response in 31.0%, and stable disease in 29.6%. Neurologic status improved (57.8%) or remained stable (23.0%). None of the evaluated factors had significant impact on the studys end points except tumor volume more than 15 mL, which caused significantly higher rates of tumor recurrence (P < .05). CONCLUSION We demonstrate that SBT represents a safe, minimally invasive, and highly effective local treatment option for pediatric patients with inoperable LGG WHO grades I and II.

Dynamic O-(2-18F-fluoroethyl)-L-tyrosine positron emission tomography differentiates brain metastasis recurrence from radiation injury after radiotherapy.

Background The aim of this study was to investigate the potential of dynamic O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET) PET for differentiating local recurrent brain metastasis from radiation injury after radiotherapy since contrast-enhanced MRI often remains inconclusive. Methods Sixty-two patients (mean age, 55 ± 11 y) with single or multiple contrast-enhancing brain lesions (n = 76) on MRI after radiotherapy of brain metastases (predominantly stereotactic radiosurgery) were investigated with dynamic 18F-FET PET. Maximum and mean tumor-to-brain ratios (TBRmax, TBRmean) of 18F-FET uptake were determined (20-40 min postinjection) as well as tracer uptake kinetics (ie, time-to-peak and slope of time-activity curves). Diagnoses were confirmed histologically (34%; 26 lesions in 25 patients) or by clinical follow-up (66%; 50 lesions in 37 patients). Diagnostic accuracies of PET parameters for the correct identification of recurrent brain metastasis were evaluated by receiver-operating-characteristic analyses or the chi-square test. Results TBRs were significantly higher in recurrent metastases (n = 36) than in radiation injuries (n = 40) (TBRmax 3.3 ± 1.0 vs 2.2 ± 0.4, P < .001; TBRmean 2.2 ± 0.4 vs 1.7 ± 0.3, P < .001). The highest accuracy (88%) for diagnosing local recurrent metastasis could be obtained with TBRs in combination with the slope of time-activity curves (P < .001). Conclusions The results of this study confirm previous preliminary observations that the combined evaluation of the TBRs of 18F-FET uptake and the slope of time-activity curves can differentiate local brain metastasis recurrence from radiation-induced changes with high accuracy. 18F-FET PET may thus contribute significantly to the management of patients with brain metastases.

Risk Factors for Chronic Subdural Hematoma Recurrence Identified Using Quantitative Computed Tomography Analysis of Hematoma Volume and Density

OBJECTIVE Chronic subdural hematoma (CSDH), a common condition in elderly patients, presents a therapeutic challenge with recurrence rates of 33%. We aimed to identify specific prognostic factors for recurrence using quantitative analysis of hematoma volume and density. METHODS We retrospectively reviewed radiographic and clinical data of 227 CSDHs in 195 consecutive patients who underwent evacuation of the hematoma through a single burr hole, 2 burr holes, or a mini-craniotomy. To examine the relationship between hematoma recurrence and various clinical, radiologic, and surgical factors, we used quantitative image-based analysis to measure the hematoma and trapped air volumes and the hematoma densities. RESULTS Recurrence of CSDH occurred in 35 patients (17.9%). Multivariate logistic regression analysis revealed that the percentage of hematoma drained and postoperative CSDH density were independent risk factors for recurrence. All 3 evacuation methods were equally effective in draining the hematoma (71.7% vs. 73.7% vs. 71.9%) without observable differences in postoperative air volume captured in the subdural space. CONCLUSIONS Quantitative image analysis provided evidence that percentage of hematoma drained and postoperative CSDH density are independent prognostic factors for subdural hematoma recurrence.

Stereotactic biopsy in elderly patients: risk assessment and impact on treatment decision

To evaluate risk profile, diagnostic yield and impact on treatment decision of stereotactic biopsy (SB) in elderly patients with unclear cerebral lesions. In this single center retrospective analysis we identified all patients aged ≥70 years receiving SB between January 2005 and December 2015. Demographic data, Karnofsky Performance Status (KPS), histology, comorbidity (by CHA2DS2-VASc Score) and use of anticoagulation were retrieved. We scrutinized diagnostic yield, procedural complications (mortality, transient and permanent morbidity), hospitalization time and therapeutic consequence. For correlation analysis Chi-Square, Mann–Whitney rank sum test and binary regression were used. Two hundred and thirty patients were included. In 229 patients SB was technically successful. Median age was 74 (70–87) years, 56.1% of patients were male and median preoperative KPS was 80% (30–100). Median CHA2DS2-VASc Score was 4 (1–9), with 29.6% receiving anticoagulation. Median hospital stay was 8 (2–29) days. Pathological diagnosis was conclusive in 97% revealing neoplastic lesions in 91.7% (high-grade glioma 62.6%, lymphoma 18.3%, metastasis 4.8%, low-grade glioma 3.0% and other tumors 3.0%) and non-neoplastic lesions in 5.3% of cases. Procedure-related mortality was 0.4%, transient and permanent morbidity occurred in 19 patients (8.3%) and eight patients (3.5%). Complication rate was not associated with any of the above-mentioned parameters. Adjuvant therapy was initiated in 171 (74.3%) patients. Decision against disease-specific therapy was only influenced by preoperative KPS (p < 0.001). SB in elderly patients is characterized by a favorable risk profile and high diagnostic yield, allowing tissue based therapeutic consequences even in patients with high comorbidity and anticoagulant medication.

Treatment strategies for recurrent and residual aneurysms after Woven Endobridge implantation

Background Woven Endobridge (WEB) embolization is a safe and efficient technique for endovascular treatment of intracranial aneurysms. However, the management of aneurysm recurrence after WEB placement has not been well described to date. We present our multicenter experience of endovascular retreatment of aneurysm recurrence after WEB implantation. Methods This is a multicenter study of patients who underwent endovascular retreatment after WEB implantation in three German tertiary care centers. Treatment strategies, complications, and angiographic outcome were retrospectively assessed. Results Among 122 aneurysms treated with the WEB device, 15 were retreated. Of these, six were initially treated with the WEB only, two were pretreated by coiling, and seven large aneurysms were treated in a multimodality approach. Ten were true aneurysm remnants and five were neck remnants. The reasons for retreatment were WEB migration (n=6), initial incomplete occlusion (n=5), and WEB compression (n=4). Retreatment strategies included coiling (n=4), stent-assisted coiling (n=7), flow diversion (n=3), and placement of an additional WEB (n=1). All procedures were technically successful and there were no procedure-related complications. Among 11 patients available for follow-up after retreatment, three were retreated again. At last angiographic follow-up, available in 11/15 cases at a median of 23 months, complete occlusion was obtained in eight cases and neck remnants in three. Conclusions This pilot study shows that endovascular retreatment of recurrent or residual aneurysms after WEB implantation can be done safely and can achieve adequate occlusion rates.

Feasibility, Risk Profile and Diagnostic Yield of Stereotactic Biopsy in Children and Young Adults with Brain Lesions

Objective To evaluate the feasibility, safety, and diagnostic yield of stereotactic biopsy (SB) in children and adolescents with cerebral lesions. Methods We performed a systematic review of the literature and a retrospective analysis of all pediatric and adolescent patients who underwent SB for unclear brain lesions at our center. We collected patient and lesion-associated parameters, analysed the rate of procedural complications and diagnostic yield. Results Our institutional series consisted of 285 SBs in 269 children and young adults between 1989 and 2016 (median age, 9 (range 1-18) years). There was no procedure-related mortality. Permanent and transient morbidity was 0.7% and 5.8%, respectively. Lesions were located in brain lobes (26.3%) and in midline structures (73.7%). The diagnostic yield was 97.5% and histology consisted low-grade gliomas (44.2%), high-grade gliomas (15.1%), non-glial tumors (22.8%), and non-neoplastic disease (15.4%). Morbidity was not associated with tumor location, age, histology or intraoperative position of the patient. In order to compare our findings with previous reports, we reviewed 25 studies with 1 109 children and young adults which had underwent SB. The diagnostic yield ranged between 83% and 100%. The reported morbidity and mortality rates range from 0-27% and 0-3.3%, respectively. Conclusions SB in this particular patient population is a safe and a high-yield diagnostic procedure and indicates therefore its importance in the light of personalized medicine with the development of individual molecular treatment strategies.

Independent predictors for functional outcome after drainage of chronic subdural hematoma identified using a logistic regression model.

BACKGROUND Chronic subdural hematoma (CSDH) is a common indication for undergoing neurosurgery, but the outcome may remain limited despite timely surgical treatment. The factors potentially associated with the functional outcome have not been sufficiently investigated. We set out to identify independent predictors associated with the functional outcome after surgical treatment of CSDH, avoiding arbitrary classifications and thresholds or subjective imaging assessment. METHODS We retrospectively reviewed 197 consecutive surgical cases of CSDH. Univariate and multivariate analyses were performed to identify the relationship between clinical plus radiographic factors and outcome. Imaging analysis was performed using computer-assisted 3D-volumetric analysis. RESULTS One-hundred and sixty four (83.2%) patients had a favorable (GOS grade 5 and 4) and 33 (16.8%) an unfavorable clinical outcome (GOS grade 1-3). The multivariate logistic regression analysis determined 4 independent prognostic factors: age over or under 77 years, preoperative clinical condition (Markwalder Score), recurrence and surgical technique applied. Patients treated with mini-craniotomy procedures had worse outcomes than those treated with single or two burr-hole craniostomies. The percentage of the hematoma drained correlated strongly with recurrence and was by itself not an independent predictor for outcome. CONCLUSIONS In our study age, pre-operative neurological status, surgical technique and recurrence were found to be independent prognostic factors for the functional outcome in patients with CSDH.

Impact of treatment on survival of patients with secondary glioblastoma

Data concerning treatment of secondary glioblastoma evolving from previously treated WHO II or III grade tumors are very scarce. The aim of this study was to evaluate the impact of surgical resection and adjuvant treatment on survival in patients with secondary glioblastoma. Thirty-nine patients with secondary glioblastoma evolving from previously treated lower grade gliomas between 2004 and 2015 were included. We evaluated the extent of resection, pathological parameters, adjuvant treatment, as well as survival after malignant transformation. The primary tumor grade was WHO II in 16 (41.0%) and WHO III in 23 (59.0%) patients. Median age was 43 years (range 23–67). Median KPS was 80 (range 60–100) before surgery, and 70 (range 50–100) after surgery. Gross total resection (GTR) of contrast-enhancing disease was achieved in 19 (48.7%) patients. Adjuvant treatment was radio-chemotherapy in 23 (59.0%), radiotherapy in three (7.7%), chemotherapy in five (12.8%) and none in eight (20.5%) patients. Median survival was 11 months (range 1–35) in the entire group. Time since initial diagnosis and previous treatment did not correlate with survival after glioblastoma. Failed GTR, poor KPS after surgery, and no adjuvant treatment were prognostic factors for shorter survival in univariate analysis (p < 0.0001, p = 0.028 and p = 0.003). In selected patients, complete resection and adjuvant treatment may prolong survival in spite of multiple previous therapies.