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Impact of Multiple Sclerosis Subtypes on Pain Management in Patients With Trigeminal Neuralgia After Stereotactic Radiosurgery: An International Multicenter Analysis

De Nigris Vasconcellos, Fernando; Mashiach, Elad; Alzate, Juan Diego; Bernstein, Kenneth; Rotman, Lauren; Levy, Sarah; Qu, Tanxia; Wegner, Rodney E; Shepard, Matthew J; Patel, Samir; Warnick, Ronald E; Moreno, Nuria Martínez; Martínez Álvarez, Roberto; Picozzi, Piero; Franzini, Andrea; Peker, Selçuk; Samanci, Yavuz; Elguindy, Ahmed N; Palmer, Joshua D; Lunsford, L Dade; Jose, Shalini G; Wei, Zhishuo; Niranjan, Ajay; Blagui, Sarra; Iorio-Morin, Christian; Mathieu, David; Briggs, Robert G; Yu, Cheng; Zada, Gabriel; Dayawansa, Samantha; Sheehan, Jason; Schulder, Michael; Goenka, Anuj; Begley, Sabrina; Khilji, Hamza; Urgošík, Dušan; Liščák, Roman; Kondziolka, Douglas
BACKGROUND AND OBJECTIVES/OBJECTIVE:Trigeminal neuralgia affects approximately 2% of patients with multiple sclerosis (MS) and often shows higher rates of pain recurrence after treatment. Previous studies on the effectiveness of stereotactic radiosurgery (SRS) for trigeminal neuralgia did not consider the different MS subtypes, including remitting relapsing (RRMS), primary progressive (PPMS), and secondary progressive (SPMS). Our objective was to investigate how MS subtypes are related to pain control (PC) rates after SRS. METHODS:We conducted a retrospective multicenter analysis of prospectively collected databases. Pain status was assessed using the Barrow National Institute Pain Intensity Scales. Time to recurrence was estimated through the Kaplan-Meier method and compared groups using log-rank tests. Logistic regression was used to calculate the odds ratio (OR). RESULTS:Two hundred and fifty-eight patients, 135 (52.4%) RRMS, 30 (11.6%) PPMS, and 93 (36%) SPMS, were included from 14 institutions. In total, 84.6% of patients achieved initial pain relief, with a median time of 1 month; 78.7% had some degree of pain recurrence with a median time of 10.2 months for RRMS, 8 months for PPMS, 8.1 months for SPMS (P = .424). Achieving Barrow National Institute-I after SRS was a predictor for longer periods without recurrence (P = .028). Analyzing PC at the last available follow-up and comparing with RRMS, PPMS was less likely to have PC (OR = 0.389; 95% CI 0.153-0.986; P = .047) and SPMS was more likely (OR = 2.0; 95% CI 0.967-4.136; P = .062). A subgroup of 149 patients did not have other procedures apart from SRS. The median times to recurrence in this group were 11.1, 9.8, and 19.6 months for RRMS, PPMS, and SPMS, respectively (log-rank, P = .045). CONCLUSION/CONCLUSIONS:This study is the first to investigate the relationship between MS subtypes and PC after SRS, and our results provide preliminary evidence that subtypes may influence pain outcomes, with PPMS posing the greatest challenge to pain management.
PMID: 38051068
ISSN: 1524-4040
CID: 5595452

Outcomes of Gamma Knife Radiosurgery for Brain Metastases in the Motor Cortex

Prasad, Shefalika; Alzate, Juan Diego; Mullen, Reed; Bernstein, Kenneth; Qu, Tanxia; Silverman, Joshua; Kondziolka, Douglas
BACKGROUND AND OBJECTIVES/OBJECTIVE:To study the clinical, imaging, and survival outcomes in patients with motor cortex brain metastases treated with stereotactic radiosurgery (SRS). METHODS:Imaging and clinical data were obtained from our prospective patient registry. Tumor volumes were obtained from serial imaging data. RESULTS:The outcomes of 208 patients with metastases involving the motor cortex who underwent SRS between 2012 and 2021 were analyzed. A total of 279 metastases (0.01 cm3-12.18 cm3, mean 0.74 cm3) were irradiated. The SRS margin dose varied from 10 to 20 Gy (mean 16.9 Gy). The overall tumor control rate was 97.8%. Perilesional edema was noted in 69 (25%) tumors at presentation. Adverse radiation effects (ARE) were noted in 6% of all tumors but were symptomatic in only 1.4%. Median time to appearance of symptomatic ARE was 8 months. Edema without ARE was observed in 13%. New focal seizures were noted in 5 patients (2%) and new generalized seizures in 1 patient (0.3%). Thirty-six patients (17%) presented with motor deficits. At final follow-up, 32 (85%) were improved or unchanged, 13 (41%) had a normal examination, 10 (31%) had mild deficits, and 9 (28%) still had moderate deficits. New remote brain metastases were found in 31% of patients at a median of 8 months. After treatment, the Karnofsky performance score distribution of the population showed an overall right shift and a median survival of 10 months. Patients with incidentally found brain metastases had significantly better survival than those presenting with deficits (median 13 vs 9 months) (P = .048). Absence of a neurological deficit, recursive partitioning analysis Class I and II, and dose >18 Gy were each associated with a significant survival advantage. CONCLUSION/CONCLUSIONS:SRS for motor cortex metastases is safe in most patients and effective in providing tumor control. Patients treated before neurological deficits develop show better outcomes.
PMID: 37823677
ISSN: 1524-4040
CID: 5604472

Quantitative Analysis of Parenchymal Effects and Flow of Large Arteriovenous Malformations Managed With Stereotactic Radiosurgery

Alzate, Juan Diego; Mashiach, Elad; Bernstein, Kenneth; De Nigris Vasconcellos, Fernando; Qu, Tanxia; Silverman, Joshua S; Shapiro, Maksim; Nelson, Peter K; Raz, Eytan; Riina, Howard A; Kondziolka, Douglas
BACKGROUND AND OBJECTIVES/OBJECTIVE:Stereotactic radiosurgery (SRS) of larger arteriovenous malformations (AVM) is associated with an elevated incidence of adverse radiation effects (ARE). To date, volume-response and dose-response models have been used to predict such effects. To understand radiological outcomes and their hemodynamic effects on the regional brain. METHODS:A retrospective analysis was conducted at our institution using a prospective registry of patients managed between 2014 and 2020. We included patients with AVM with a nidus larger than 5 cc who received either single-session or volume-staged Gamma Knife radiosurgery. AVM volume changes, volumes of parenchymal response, and obliteration were analyzed and correlated with transit times and diameters of feeding arteries and draining veins. RESULTS:Sixteen patients underwent single-session SRS, and 9 patients underwent volume-staged SRS. The average AVM volume was 12.6 cc (5.5-23). The AVM locations were predominantly lobar (80%) and 17 (68%) were in critical locations. The mean margin dose was 17.2 Gy (15-21), and the median V12Gy was 25.5 cc. Fourteen (56%) AVMs had a transit time shorter than 1 second. The median vein-artery ratio (sum diameter of the veins/sum diameter of feeding arteries) was 1.63 (range, 0.60-4.19). Asymptomatic parenchymal effects were detected in 13 (52%) patients and were symptomatic in 4 (16%) patients. The median time to ARE was 12 months (95% CI 7.6-16.4). On univariate analysis, significant predictors of ARE were lower vein-artery ratio (P = .024), longer transit time (P = .05), higher mean dose (P = .028), and higher D95 (P = .036). CONCLUSION/CONCLUSIONS:Transit times and vessel diameters are valuable predictors of the subsequent parenchymal response after SRS. A more quantitative understanding of blood flow is critical for predicting the effects on the regional brain after AVM radiosurgery.
PMID: 37235978
ISSN: 1524-4040
CID: 5508662

Low-Dose Radiosurgery for Brain Metastases in the Era of Modern Systemic Therapy

Alzate, Juan Diego; Mashiach, Elad; Berger, Assaf; Bernstein, Kenneth; Mullen, Reed; Nigris Vasconcellos, Fernando De; Qu, Tanxia; Silverman, Joshua S; Donahue, Bernadine R; Cooper, Benjamin T; Sulman, Erik P; Golfinos, John G; Kondziolka, Douglas
BACKGROUND AND OBJECTIVES/OBJECTIVE:Dose selection for brain metastases stereotactic radiosurgery (SRS) classically has been based on tumor diameter with a reduction of dose in the settings of prior brain irradiation, larger tumor volumes, and critical brain location. However, retrospective series have shown local control rates to be suboptimal with reduced doses. We hypothesized that lower doses could be effective for specific tumor biologies with concomitant systemic therapies. This study aims to report the local control (LC) and toxicity when using low-dose SRS in the era of modern systemic therapy. METHODS:We reviewed 102 patients with 688 tumors managed between 2014 and 2021 who had low-margin dose radiosurgery, defined as ≤14 Gy. Tumor control was correlated with demographic, clinical, and dosimetric data. RESULTS:The main primary cancer types were lung in 48 (47.1%), breast in 31 (30.4%), melanoma in 8 (7.8%), and others in 15 patients (11.7%). The median tumor volume was 0.037cc (0.002-26.31 cm3), and the median margin dose was 14 Gy (range 10-14). The local failure (LF) cumulative incidence at 1 and 2 years was 6% and 12%, respectively. On competing risk regression analysis, larger volume, melanoma histology, and margin dose were predictors of LF. The 1-year and 2-year cumulative incidence of adverse radiation effects (ARE: an adverse imaging-defined response includes increased enhancement and peritumoral edema) was 0.8% and 2%. CONCLUSION/CONCLUSIONS:It is feasible to achieve acceptable LC in BMs with low-dose SRS. Volume, melanoma histology, and margin dose seem to be predictors for LF. The value of a low-dose approach may be in the management of patients with higher numbers of small or adjacent tumors with a history of whole brain radio therapy or multiple SRS sessions and in tumors in critical locations with the aim of LC and preservation of neurological function.
PMID: 37326435
ISSN: 1524-4040
CID: 5613932

Automatic segmentation of vestibular schwannomas from T1-weighted MRI with a deep neural network

Wang, Hesheng; Qu, Tanxia; Bernstein, Kenneth; Barbee, David; Kondziolka, Douglas
BACKGROUND:Long-term follow-up using volumetric measurement could significantly assist in the management of vestibular schwannomas (VS). Manual segmentation of VS from MRI for treatment planning and follow-up assessment is labor-intensive and time-consuming. This study aims to develop a deep learning technique to fully automatically segment VS from MRI. METHODS:This study retrospectively analyzed MRI data of 737 patients who received gamma knife radiosurgery for VS. Treatment planning T1-weighted isotropic MR and manually contoured gross tumor volumes (GTV) were used for model development. A 3D convolutional neural network (CNN) was built on ResNet blocks. Spatial attenuation and deep supervision modules were integrated in each decoder level to enhance the training for the small tumor volume on brain MRI. The model was trained and tested on 587 and 150 patient data, respectively, from this institution (n = 495) and a publicly available dataset (n = 242). The model performance were assessed by the Dice similarity coefficient (DSC), 95% Hausdorff distance (HD95), average symmetric surface (ASSD) and relative absolute volume difference (RAVD) of the model segmentation results against the GTVs. RESULTS:Measured on combined testing data from two institutions, the proposed method achieved mean DSC of 0.91 ± 0.08, ASSD of 0.3 ± 0.4 mm, HD95 of 1.3 ± 1.6 mm, and RAVD of 0.09 ± 0.15. The DSCs were 0.91 ± 0.09 and 0.92 ± 0.06 on 100 testing patients of this institution and 50 of the public data, respectively. CONCLUSIONS:A CNN model was developed for fully automated segmentation of VS on T1-Weighted isotropic MRI. The model achieved good performance compared with physician clinical delineations on a sizeable dataset from two institutions. The proposed method potentially facilitates clinical workflow of radiosurgery for VS patient management.
PMCID:10169364
PMID: 37158968
ISSN: 1748-717x
CID: 5503302

Preoperative flow analysis of arteriovenous malformations and obliteration response after stereotactic radiosurgery

Alzate, Juan Diego; Berger, Assaf; Bernstein, Kenneth; Mullen, Reed; Qu, Tanxia; Silverman, Joshua S; Shapiro, Maksim; Nelson, Peter K; Raz, Eytan; Jafar, Jafar J; Riina, Howard A; Kondziolka, Douglas
OBJECTIVE:Morphological and angioarchitectural features of cerebral arteriovenous malformations (AVMs) have been widely described and associated with outcomes; however, few studies have conducted a quantitative analysis of AVM flow. The authors examined brain AVM flow and transit time on angiograms using direct visual analysis and a computer-based method and correlated these factors with the obliteration response after Gamma Knife radiosurgery. METHODS:A retrospective analysis was conducted at a single institution using a prospective registry of patients managed from January 2013 to December 2019: 71 patients were analyzed using a visual method of flow determination and 38 were analyzed using a computer-based method. After comparison and validation of the two methods, obliteration response was correlated to flow analysis, demographic, angioarchitectural, and dosimetric data. RESULTS:The mean AVM volume was 3.84 cm3 (range 0.64-19.8 cm3), 32 AVMs (45%) were in critical functional locations, and the mean margin radiosurgical dose was 18.8 Gy (range 16-22 Gy). Twenty-seven AVMs (38%) were classified as high flow, 37 (52%) as moderate flow, and 7 (10%) as low flow. Complete obliteration was achieved in 44 patients (62%) at the time of the study; the mean time to obliteration was 28 months for low-flow, 34 months for moderate-flow, and 47 months for high-flow AVMs. Univariate and multivariate analyses of factors predicting obliteration included AVM nidus volume, age, and flow. Adverse radiation effects were identified in 5 patients (7%), and 67 patients (94%) remained free of any functional deterioration during follow-up. CONCLUSIONS:AVM flow analysis and categorization in terms of transit time are useful predictors of the probability of and the time to obliteration. The authors believe that a more quantitative understanding of flow can help to guide stereotactic radiosurgery treatment and set accurate outcome expectations.
PMID: 36057117
ISSN: 1933-0693
CID: 5337952

Replacing gamma knife beam-profiles on film with point-detector scans

Rudek, Benedikt; Bernstein, Kenneth; Osterman, Sunshine; Qu, Tanxia
PURPOSE/OBJECTIVE:Detector arrays and profile-scans have widely replaced film-measurements for quality assurance (QA) on linear accelerators. Film is still used for relative output factor (ROF) measurements, positioning, and dose-profile verification for annual Leksell Gamma Knife (LGK) QA. This study shows that small-field active detector measurements can be performed in the easily accessed clinical mode and that they are an effective replacement to time-consuming and exacting film measurements. METHODS:Beam profiles and positioning scans for 4-mm, 8-mm, and 16-mm-collimated fields were collected along the x-, y-, and z-axes. The Exradin W2-scintillator and the PTW microdiamond-detector were placed in custom inserts centered in the Elekta solid-water phantom for these scans. GafChromic EBT3-film was irradiated with single uniformly collimated exposures as the clinical-standard reference, using the same solid-water phantom for profile tests and the Elekta film holder for radiation focal point (RFP)/patient-positioning system (PPS) coincidence. All experimental data were compared to the tissue-maximum-ratio-based (TMR10) dose calculation. RESULTS:The detector-measured beam profiles and film-based profiles showed excellent agreement with TMR10-predicted full-width, half-maximum (FWHM) values. Absolute differences between the measured FWHM and FWHM from the treatment-planning system were on average 0.13 mm, 0.08 mm, and 0.04 mm for film, microdiamond, and scintillator, respectively. The coincidence between the RFP and the PPS was measured to be ≤0.5 mm with microdiamond, ≤0.41 mm with the W2-1 × 1 scintillator, and ≤0.22 mm using the film-technique. CONCLUSIONS:Small-volume field detectors, used in conjunction with a clinically available phantom, an electrometer with data-logging, and treatment plans created in clinical mode offer an efficient and viable alternative for film-based profile tests. Position verification can be accurately performed when CBCT-imaging is available to correct for residual detector-position uncertainty. Scans are easily set up within the treatment-planning-system and, when coupled with an automated analysis, can provide accurate measurements within minutes.
PMID: 35001499
ISSN: 1526-9914
CID: 5118292

Predicting local failure of brain metastases after stereotactic radiosurgery with radiomics on planning MR images and dose maps

Wang, Hesheng; Xue, Jinyu; Qu, Tanxia; Bernstein, Kenneth; Chen, Ting; Barbee, David; Silverman, Joshua S; Kondziolka, Douglas
PURPOSE/OBJECTIVE:Stereotactic radiosurgery (SRS) has become an important modality in the treatment of brain metastases. The purpose of this study is to investigate the potential of radiomic features from planning magnetic resonance (MR) images and dose maps to predict local failure after SRS for brain metastases. MATERIALS/METHODS/METHODS:Twenty-eight patients who received Gamma Knife (GK) radiosurgery for brain metastases were retrospectively reviewed in this IRB-approved study. 179 irradiated tumors included 42 that locally failed within one-year follow-up. Using SRS tumor volumes, radiomic features were calculated on T1-weighted contrast-enhanced MR images acquired for treatment planning and planned dose maps. 125 radiomic features regarding tumor shape, dose distribution, MR intensities and textures were extracted for each tumor. Logistic regression with automatic feature selection was built to predict tumor progression from local control after SRS. Feature selection and model evaluation using receiver operating characteristic (ROC) curves were performed in a nested cross validation (CV) scheme. The associations between selected radiomic features and treatment outcomes were statistically assessed by univariate analysis. RESULTS:The logistic model with feature selection achieved ROC AUC of 0.82 ± 0.09 on 5-fold CV, providing 83% sensitivity and 70% specificity for predicting local failure. A total of 10 radiomic features including 1 shape feature, 6 MR images and 3 dose distribution features were selected. These features were significantly associated with treatment outcomes (p < 0.05). The model was validated on independent holdout data with an AUC of 0.78. CONCLUSIONS:Radiomic features from planning MR images and dose maps provided prognostic information in SRS for brain metastases. A model built on the radiomic features shows promise for early prediction of tumor local failure after treatment, potentially aiding in personalized care for brain metastases.
PMID: 34287940
ISSN: 2473-4209
CID: 5003892

Data-Driven Generation of CBCT-To-CT HU Mapping for Adaptive Radiotherapy in H&N Cancer [Meeting Abstract]

Wang, H.; Rea, A.; Xue, J.; Spuhler, K.; Qu, T.; Chen, T.; Barbee, D.; Hu, K.
ISI:000673145403232
ISSN: 0094-2405
CID: 5320842

Adaptive radiotherapy based on statistical process control for oropharyngeal cancer

Wang, Hesheng; Xue, Jinyu; Chen, Ting; Qu, Tanxia; Barbee, David; Tam, Moses; Hu, Kenneth
PURPOSE/OBJECTIVE:The purpose of this study is to quantify dosimetric changes throughout the delivery of oropharyngeal cancer treatment and to investigate the application of statistical process control (SPC) for the management of significant deviations during the course of radiotherapy. METHODS:Thirteen oropharyngeal cancer patients with daily cone beam computed tomography (CBCT) were retrospectively reviewed. Cone beam computed tomography images of every other fraction were imported to the Velocity software and registered to planning CT using the 6 DOF (degrees of freedom) couch shifts generated during patient setup. Using Velocity "Adaptive Monitoring" module, the setup-corrected CBCT was matched to planning CT using a deformable registration. Volumes and dose metrics at each fraction were calculated and rated with plan values to evaluate interfractional dosimetric variations using a SPC framework. T-tests between plan and fraction volumes were performed to find statistically insignificant fractions. Average upper and lower process capacity limits (UCL, LCL) of each dose metric were derived from these fractions using conventional SPC guidelines. RESULTS:Gross tumor volume (GTV) and organ at risk (OAR) volumes in the first 13 fractions had no significant changes from the pretreatment planning CT. The GTV and the parotid glands subsequently decreased by 10% at the completion of treatment. There were 3-4% increases in parotid mean doses, but no significant differences in dose metrics of GTV and other OARs. The changes were organ and patient dependent. Control charts for various dose metrics were generated to assess the metrics at each fraction for individual patient. CONCLUSIONS:Daily CBCT could be used to monitor dosimetric variations of targets and OARs resulting from volume changes and tissue deformation in oropharyngeal cancer radiotherapy. Treatment review with the guidance of a SPC tool allows for an objective and consistent clinical decision to apply adaptive radiotherapy.
PMID: 32770651
ISSN: 1526-9914
CID: 4560192