Radiomics in radiation oncology-basics, methods, and limitations

Over the past years, the quantity and complexity of imaging data available for the clinical management of patients with solid tumors has increased substantially. Without the support of methods from the field of artificial intelligence (AI) and machine learning, a complete evaluation of the available image information is hardly feasible in clinical routine. Especially in radiotherapy planning, manual detection and segmentation of lesions is laborious, time consuming, and shows significant variability among observers. Here, AI already offers techniques to support radiation oncologists, whereby ultimately, the productivity and the quality are increased, potentially leading to an improved patient outcome. Besides detection and segmentation of lesions, AI allows the extraction of a vast number of quantitative imaging features from structural or functional imaging data that are typically not accessible by means of human perception. These features can be used alone or in combination with other clinical parameters to generate mathematical models that allow, for example, prediction of the response to radiotherapy. Within the large field of AI, radiomics is the subdiscipline that deals with the extraction of quantitative image features as well as the generation of predictive or prognostic mathematical models. This review gives an overview of the basics, methods, and limitations of radiomics, with a focus on patients with brain tumors treated by radiation therapy

Stereotactic biopsy combined with stereotactic (125)iodine brachytherapy for diagnosis and treatment of locally recurrent single brain metastases

This paper reports on stereotactic biopsy combined with stereotactic 125 iodine brachytherapy (SBT) for locally recurrent, previously irradiated cerebral metastases, focusing on feasibility, complications, cerebral disease control, and survival. All patients with suspected locally recurrent metastases detected by MRI were selected for this combined procedure. After stereotactic biopsy, all patients with a verified vital tumor underwent SBT (50 Gy surface dose applied for 42 days) during the same surgical procedure. Histological results of biopsy, complications, treatment response, local and distant disease control, and survival were evaluated. Thirty patients underwent stereotactic biopsy, and 27 were treated with SBT for histologically proved tumor recurrence. There was no treatmen-trelated mortality, and morbidity was transient and low (6.6%). Median survival was 14.8 months. After one year the actuarial incidence of local and distant relapse was 6.7 and 45.5%, respectively. There was no grade 3 or 4 CNS toxicity, even among the 18.5% of patients with tumor >30 mm. For these patients stereotactic biopsy seems to be a safe and valuable means of differentiating between radiation-induced tissue changes and tumor recurrence/progression. SBT is a safe, minimally invasive, and highly effective treatment option for cerebral disease control and survival. Furthermore, it can be performed during the same stereotactic operation

Subcortical electrophysiological activity is detectable with high-density EEG source imaging

Electroencephalography (EEG) allows the measurement of electrical signals associated with brain activity, but it is unclear if EEG can accurately measure subcortical activity. Here, the authors show that source dynamics, reconstructed from scalp EEG, correlate with activity recorded from human thalamus and nucleus accumbens

Stereotactic LINAC radiosurgery for the treatment of typical intracranial meningiomas

Purpose The efficacy and safety of stereotactic radiosurgery (SRS) for treatment of intracranial meningiomas has been demonstrated in numerous studies with short- and intermediate-term follow-up. In this retrospective single-center study, we present long-term outcomes of SRS performed with a linear accelerator (LINAC) for typical intracranial meningiomas. Patients and methods Between August 1990 and December 2007, 148 patients with 168 typical intracranial meningiomas were treated with stereotactic LINAC-SRS, either as primary treatment or after microsurgical resection. A median tumor surface dose of 12 Gy (range 7-20 Gy) and a median maximum dose of 24.1 Gy (range 11.3-58.6 Gy) was applied. The median target volume was 4.7 ml (range 0.2-32.8 ml, SD +/- 4.8 ml). Results Overall mean radiological follow-up was 12.6 years. Tumor shrinkage was seen in 75 (44.6 %) and stable disease in 85 (50.6 %) cases. Eight of 168 meningiomas (4.8 %) showed local tumor progression. The tumor control rate (TCR) after 5, 10, and 15 years was 93.6 % at each time point, and the progression-free survival (PSF) rates were 92, 89, and 89 %, respectively. The neurological symptoms existing prior to LINAC-SRS improved in 77 patients (59.7 %), remained unchanged in 42 (32.6 %), and deteriorated in 10 (7.8 %) patients. Conclusion Our study emphasizes the efficacy of LINAC-SRS for de novo, residual and recurrent typical intracranial meningiomas. A high long-term local TCR with a low morbidity rate could be achieved. LINAC-SRS should thus be considered as a primary treatment option, as one arm of a combined treatment approach for incompletely resected meningiomas, or as a salvage therapy for recurrences

Stereotactic intracavitary brachytherapy with P-32 for cystic craniopharyngiomas in children

Purpose Although microsurgery remains the first-line treatment, gross total resection of cystic craniopharyngeomas (CP) is associated with significant morbidity and mortality and the addition of external irradiation to subtotal resection proves to achieve similar tumor control. However, concern regarding long-term morbidity associated with external irradiation in children still remains. With this retrospective analysis, the authors emphasize intracavitary brachytherapy using phosphorus-32 (P-32) as a treatment option for children with cystic CP. Patients and methods Between 1992 and 2009, 17 children (median age 15.4 years; range 7-18 years) with cystic CP underwent intracavitary brachytherapy using P-32. Eleven patients were treated for recurrent tumor cysts; 6 patients were treated primarily. MR imaging revealed solitary cysts in 7 patients; 10 patients had mixed solid-cystic lesions (median tumor volume 11.1 ml; range 0.5-78.9 ml). The median follow-up time was 61.9 months (range 16.9-196.6 months). Results Local cyst control could be achieved in 14 patients (82 %). Three patients showed progression of the treated cystic formation (in-field progression) after a median time of 8.3 months (range 5.3-10.3 months), which led to subsequent interventions. The development of new, defined cysts and progression of solid tumor parts (out-of-field progression) occurred in 5 patients and led to additional interventions in 4 cases. There was neither surgery-related permanent morbidity nor mortality in this study. The overall progression-free survival was 75, 63, and 52 % after 1, 3, and 5 years, respectively. Conclusion Intracavitary brachytherapy using P-32 represents a safe and effective treatment option for children harboring cystic CP, even as primary treatment. However, P-32 does not clearly affect growth of solid tumor parts or the development of new cystic formations

Outcome and toxicity analysis of single dose stereotactic radiosurgery in vestibular schwannoma based on the Koos grading system

Stereotactic radiosurgery (SRS) has evolved as widely accepted treatment option for small-sized (Koos I up to II) vestibular schwannoma (VS). For larger tumors (prevalent Koos VI), microsurgery or combined treatment strategies are mostly recommended. However, in patients not suited for microsurgery, SRS might also be an alternative to balance tumor control, hearing preservation and adverse effects. The purpose of this analysis was to evaluate the efficacy and toxicity of SRS for VS with regard to different Koos grades. All patients with untreated VS who received SRS at our center were included. Outcome analysis included tumor control, preservation of serviceable hearing based on median pure tone averages (PTA), and procedure-related adverse events rated by the Common Terminology Criteria for Adverse Events (CTCAE; v4.03) classification. In total, 258 patients (median age 58 years, range 21-84) were identified with a mean follow-up of 52 months (range 3-228 months). Mean tumor volume was 1.8ml (range 0.1-18.5). The mean marginal dose was 12.3Gy +/- 0.6 (range 11-13.5). The cohort was divided into two groups: A (Koos grades I and II, n=186) and B (Koos grades III and IV, n=72). The actuarial tumor control rate was 98% after 2 years and 90% after 5 and 10 years. Koos grading did not show a significant impact on tumor control (p=0.632) or hearing preservation (p=0.231). After SRS, 18 patients (7%) had new transient or permanent symptoms classified by the CTCAE. The actuarial rate of CTCAE-free survival was not related to Koos grading (p=0.093). Based on this selected population of Koos grade III and IV VS without or with only mild symptoms from brainstem compression, SRS can be recommended as the primary therapy with the advantage of low morbidity and satisfactory tumor control. The overall hearing preservation rate and toxicity of SRS was influenced by age and cannot be predicted by tumor volume or Koos grading alone

Connectivity Patterns of Deep Brain Stimulation Targets in Patients with Gilles de la Tourette Syndrome

Since 1999, several targets for deep brain stimulation (DBS) in Gilles de la Tourette syndrome (GTS) have emerged showing similar success rates. Studies using different tractography techniques have identified connectivity profiles associated with a better outcome for individual targets. However, GTS patients might need individualized therapy. The objective of this study is to analyze the connectivity profile of different DBS targets for GTS. We identified standard target coordinates for the centromedian nucleus/nucleus ventro-oralis internus (CM/Voi), the CM/parafascicular (CM-Pf) complex, the anteromedial globus pallidus internus (amGPi), the posteroventral GPi (pvGPi), the ventral anterior/ventrolateral thalamus (VA/VL), and the nucleus accumbens/anterior limb of the internal capsule (Nacc/ALIC). Probabilistic tractography was performed from the targets to different limbic and motor areas based on patient-specific imaging and a normative connectome (HCP). Our analysis showed significant differences between the connectivity profiles of standard DBS targets (p < 0.05). Among all targets, the pvGPi showed the strongest connection to the sensorimotor cortex, while the amGPi showed the strongest connection to the prefrontal cortex in patient-specific imaging. Differences were observed between the connectivity profiles when using probabilistic tractography based on patient data and HCP. Our findings showed that the connectivity profiles of different DBS targets to major motor and limbic areas differ significantly. In the future, these differences may be considered when planning DBS for GTS patients employing an individualized approach. There were compelling differences in connectivity profiles when using different tractography techniques

Probabilistic mapping of deep brain stimulation effects in essential tremor

Objective: To create probabilistic stimulation maps (PSMs) of deep brain stimulation (DBS) effects on tremor suppression and stimulation-induced side-effects in patients with essential tremor (ET). Method: Monopolar reviews from 16 ET-patients which consisted of over 600 stimulation settings were used to create PSMs. A spherical model of the volume of neural activation was used to estimate the spatial extent of DBS for each setting. All data was pooled and voxel-wise statistical analysis as well as nonparametric permutation testing was used to confirm the validity of the PSMs. Results: PSMs showed tremor suppression to be more pronounced by stimulation in the zona incerta (ZI) than in the ventral intermediate nucleus (VIM). Paresthesias and dizziness were most commonly associated with stimulation in the ZI and surrounding thalamic nuclei. Discussion: Our results support the assumption, that the ZI might be a very effective target for tremor suppression. However stimulation inside the ZI and in its close vicinity was also related to the occurrence of stimulation-induced side-effects, so it remains unclear whether the VIM or the ZI is the overall better target. The study demonstrates the use of PSMs for target selection and evaluation. While their accuracy has to be carefully discussed, they can improve the understanding of DBS effects and can be of use for other DBS targets in the therapy of neurological or psychiatric disorders as well. Furthermore they provide a priori information about expected DBS effects in a certain region and might be helpful to clinicians in programming DBS devices in the future

Stereotactic Radiosurgery of Cavernous Sinus Meningiomas

Objective Microsurgical resection of cavernous sinus meningiomas (CSM) is associated with a high rate of incomplete resection, recurrence, and the risk for permanent, severe cranial nerve deficits. Stereotactic radiosurgery (SRS) has evolved as alternative treatment for primary and recurrent CSM. Here, we report about the long-term clinical and radiological follow-up (FU) of a unique cohort of patients with CSM treated with LINAC or Cyberknife based SRS. Methods In this single-center retrospective analysis, we include all patients with CSM who underwent single fraction SRS between 1993 and 2016. Clinical and radiological tumor control were evaluated by the Kaplan-Meier method. Additionally, patient data were analyzed in terms of symptom control and incidence of side effects rated by the common terminology criteria for adverse events (CTCAE; v4.03). Results 116 patients (female/male = 91/25; median age, 54 years; range, 33-82 years) were included. Mean tumor volume was 5.7 +/- 3.3 cm (3) (range, 0.6-16.2 cm (3) ), the median marginal dose was 12.6 Gy applied to isodose levels of 75%. Median clinical FU was 55 months (range, 3-226 months). Tumor control was 98% after 2 and 5 years and 90% after 10 years. Twelve patients (10.3%) had permanent or transient radiation related toxicity (CTCAE I-III). An improvement of symptoms was observed in 26.7% of the symptomatic patients ( n = 20 of 75). Conclusion SRS for CSM provides excellent long-term tumor and symptom control without considerable permanent side effects. Thus, SRS should be considered when counseling patients suffering from CSM