Publications by authors named "Cheng-Chia Lee"

241 Publications

The dialysis facility levels and sizes are associated with outcomes of incident hemodialysis patients.

Sci Rep 2021 Oct 18;11(1):20560. Epub 2021 Oct 18.

Department of Nephrology, Kidney Research Center, Linkou Chang Gung Memorial Hospital, No.5, Fuxing Street, Guishan District, Taoyuan, 33305, Taiwan.

The outcomes of patients with incident kidney failure who start hemodialysis are influenced by several factors. Whether hemodialysis facility characteristics are associated with patient outcomes is unclear. We included adults diagnosed as having kidney failure requiring hemodialysis during January 1, 2001 to December 31, 2013 from the Taiwan National Health Insurance Research Database to perform this retrospective cohort study. The exposures included different sizes and levels of hemodialysis facilities. The outcomes were all-cause mortality, cardiovascular death, infection-related death, hospitalization, and kidney transplantation. During 2001-2013, we identified 74,406 patients and divided them in to three groups according to the facilities where they receive hemodialysis: medical center (n = 8263), non-center hospital (n = 40,008), and clinic (n = 26,135). The multivariable Cox model demonstrated that a larger facility size was associated with a low mortality risk (hazard ratio [HR] 0.991, 95% confidence interval [95% CI] 0.984-0.998; every 20 beds per facility). Compared with medical centers, patients in non-center hospitals and clinics had higher mortality risks (HR 1.13, 95% CI 1.09-1.17 and HR 1.11, 95% CI 1.06-1.15, respectively). Patients in medical centers and non-center hospitals had higher risk of hospitalization (subdistribution HR [SHR] 1.11, 95% CI 1.10-1.12 and SHR 1.22, 95% CI 1.21-1.23, respectively). Patients in medical centers had the highest rate of kidney transplantation among the three groups. In patients with incident kidney failure, a larger hemodialysis facility size was associated with lower mortality. Overall, medical center patients had a lower mortality rate and higher transplantation rate, whereas clinic patients had a lower hospitalization risk.
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http://dx.doi.org/10.1038/s41598-021-00177-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8523705PMC
October 2021

yReirradiation with stereotactic radiosurgery after local or marginal recurrence of brain metastases from previous radiosurgery.

Int J Radiat Oncol Biol Phys 2021 Oct 10. Epub 2021 Oct 10.

Department of Neurosurgery, University of Virginia Health System, Charlottesville, VA, USA.

Background: Brain metastases represent a major indication for stereotactic radiosurgery (SRS), but further study is needed regarding repeat SRS (SRS2) after local or marginal recurrence after prior SRS (SRS1). We report local tumor control (LC) after SRS2 and identify predictors of radiation necrosis (RN) and symptomatic RN (SRN).

Methods: Patients had biopsy-proven non-small cell lung cancer and at least one brain metastasis previously treated with SRS. SRS2 was performed from 2015-2020 and required overlap of the prescription isodose lines with those from SRS1. Patients treated with preoperative SRS were excluded. Primary endpoints were LC by RANO criteria, RN, and SRN.

Results: From 8 institutions, 102 patients with 123 treated lesions were included. SRS2 was performed at a median 12 months after SRS1. SRS2 delivered a median 18 Gy (IQR: 16-18) margin dose to the 50% (IQR: 50-70%) isodose line, maximum dose of 30.5 Gy (IQR: 25.0-36.0), and V12Gy of 3.38 cc (IQR: 0.83-7.64). 1-year and 2-year LC were 79% and 72%. Local tumor control was improved with tumor volume ≤ 1 cc (p < 0.005). There were 25 (20%) cases of RN and 9 (7%) cases of SRN. For SRS1 and SRS2, SRN rates were higher with maximum doses ≥ 40 Gy or SRS2 V12Gy > 9 cc (p < 0.025 for each). SRS1 and SRS2 maximum dose ≥ 40 Gy was also predictive of increased RN (p < 0.05 for each). Prior immunotherapy was not predictive of RN or SRN.

Conclusions: Repeat SRS afforded a high rate of local tumor control and a low rate of SRN. At SRS2, V12Gy ≤ 9 cc and maximum dose < 40 Gy may reduce the risks of RN and SRN. These results are most applicable to lesions with approximately 1 cc volume and 1 year interval between SRS courses.
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http://dx.doi.org/10.1016/j.ijrobp.2021.10.008DOI Listing
October 2021

Prognostic Performance of Existing Scoring Systems among Critically Ill Patients Requiring Continuous Renal Replacement Therapy: An Observational Study.

J Clin Med 2021 Oct 6;10(19). Epub 2021 Oct 6.

Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan.

Background: Among critical patients, few studies have evaluated the discrimination of current illness scoring systems in predicting outcomes after continuous renal replacement therapy (CRRT) initiation.

Methods: Patients receiving CRRT in the ICU between 2005 and 2018 from the Chang Gung Research Database were extracted. All the components of the Acute Physiology Assessment and Chronic Health Evaluation (APACHE) III, Sequential Organ Failure Assessment (SOFA), qSOFA, and MOSAIC scoring systems on days 1, 3, and 7 of CRRT were recorded. Patients older than 80 years were identified and analyzed separately.

Results: We identified 3370 adult patients for analysis. The discrimination ability of the scoring systems was acceptable at day 7 after CRRT initiation, including SOFA (area under the receiver operating characteristic curve, 74.1% (95% confidence interval, 71.7-76.5%)), APACHEIII (74.7% (72.3-77.1%)), and MOSAIC (71.3% (68.8%-73.9%)). These systems were not ideal on days 1 and 3, and that of qSOFA was poor at any time point. The discrimination performance was slightly better among patients ≥80 years.

Conclusions: APACHE III, MOSAIC, and SOFA can be intensivists and families' reference to make their decision of withdrawing or withholding CRRT after a short period of treatment, especially in adults ≥80 years old.
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http://dx.doi.org/10.3390/jcm10194592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8509572PMC
October 2021

Intravenous CT Contrast Media and Acute Kidney Injury: A Multicenter Emergency Department-based Study.

Radiology 2021 Oct 12:204446. Epub 2021 Oct 12.

From the Department of Emergency Medicine (T.H.S., C.H.H., Y.L.C., C.H.L., H.Y.C.), Division of Emergency and Critical Care Radiology, Department of Medical Imaging and Intervention (Y.C.W.), Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine (C.F.K.), and Kidney Research Center, Department of Nephrology (C.C.L.), Linkou Chang Gung Memorial Hospital, Linkou Main Branch, No. 5 Fu-Hsing Street, Kweishan, Taoyuan 333, Taiwan; College of Medicine (T.H.S., Y.L.C., C.H.L., H.Y.C.), Department of Medical Imaging and Radiological Sciences, College of Medicine (Y.C.W.), and Graduate Institute of Clinical Medical Science, College of Medicine (C.C.L.), Chang Gung University, Taoyuan, Taiwan.

Background Although the historical risk of acute kidney injury (AKI) after intravenous administration of contrast media might be overstated, the risk in patients with impaired kidney function remains a concern. Purpose To investigate whether intravenous contrast media administration during CT is associated with a higher risk of AKI and further hemodialysis compared with the risk in patients undergoing unenhanced CT. Materials and Methods This retrospective study evaluated patients who underwent contrast-enhanced or unenhanced CT in five Taiwanese emergency departments between 2009 and 2016. The outcomes were AKI within 48-72 hours after CT, AKI within 48 hours to 1 week after CT, or further hemodialysis within 1 month after CT. The associations between contrast media exposure and outcome were estimated by using an overlap propensity score weighted generalized regression model. Subgroup analyses were performed according to the estimated glomerular filtration rate (eGFR). Results The study included 68 687 patients (median age, 68 years; interquartile range, 53-74 years; 39 995 men) with ( = 31 103) or without ( = 37 584) exposure to contrast media. After propensity score weighting, contrast media exposure was associated with higher risk of AKI within 48-72 hours after CT (odds ratio [OR], 1.16; 95% CI: 1.04, 1.29; = .007) but no significant risk at 48 hours to 1 week after CT (OR, 1.00; 95% CI: 0.93, 1.08; = .90). Among patients with eGFR less than 30 mL/min/1.73 m, exposure to contrast media was associated with a higher AKI risk (48-72 hours after CT: OR, 1.36; 95% CI: 1.09, 1.70; = .007) (48 hours-1 week after CT: OR, 1.49; 95% CI: 1.27, 1.74; < .001) and a higher risk of hemodialysis (OR, 1.36; 95% CI: 1.09, 1.70; = .008). For patients with eGFR greater than 45 mL/min/1.73.m, contrast media exposure was not associated with higher AKI risk ( > .05). Conclusion Contrast-enhanced CT was associated with higher risk of acute kidney injury and further hemodialysis among Taiwanese patients with an estimated glomerular filtration rate (eGFR) of less than 30 mL/min/1.73 m but not those with an eGFR of more than 45 mL/min/1.73 m. © RSNA, 2021
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http://dx.doi.org/10.1148/radiol.2021204446DOI Listing
October 2021

Neutrophil-to-lymphocyte ratio is a marker for acute kidney injury progression and mortality in critically ill populations: a population-based, multi-institutional study.

J Nephrol 2021 Oct 8. Epub 2021 Oct 8.

Department of Nephrology, Chang Gung Memorial Hospital, Linkou, Taiwan.

Backgrounds: Neutrophil-to-lymphocyte ratio (NLR), a surrogate marker of systemic response to physiological stress, is used for prognosis prediction in many diseases. However, the usefulness of this marker for predicting acute kidney injury (AKI) progression is unclear.

Methods: This retrospective study was based on the Chang Gung Research Database. Patients admitted to the intensive care unit with a diagnosis of stage 1 or 2 AKI were identified. The primary outcome was a composite of progression to stage 3 AKI, requirement of renal replacement therapy, or 14-day in-hospital mortality. The association between NLR and the primary outcome was examined using a logistic regression model and multivariable analysis. The nonlinearity and cutoff points of this relationship were determined using a restricted cubic spline model.

Results: A total of 10,441 patients were enrolled. NLR level at the time of stage 1-2 AKI diagnosis was a marker of adverse outcomes. After adjustment for confounders, NLR was independently associated with the composite outcome of AKI progression, renal replacement therapy, or mortality. The restricted cubic spline model revealed a J-shaped curve, with the lowest odds ratio for an NLR between 7 and 38. Subgroup analysis revealed linear and J-shaped relationships between NLR and the primary outcome in patients admitted to the intensive care unit for medical reasons and for cardiovascular surgery, respectively.

Conclusions: NLR is an independent marker of AKI progression and in-hospital mortality. Because it is readily available in daily practice, it might be used for risk stratification in the AKI population.
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http://dx.doi.org/10.1007/s40620-021-01162-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8498757PMC
October 2021

Stereotactic radiosurgery for prostate cancer cerebral metastases: an international multicenter study.

J Neurosurg 2021 Oct 1:1-7. Epub 2021 Oct 1.

1Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia.

Objective: As novel therapies improve survival for men with prostate cancer, intracranial metastatic disease has become more common. The purpose of this multicenter study was to evaluate the safety and efficacy of stereotactic radiosurgery (SRS) in the management of intracranial prostate cancer metastases.

Methods: Demographic data, primary tumor characteristics, SRS treatment parameters, and clinical and imaging follow-up data of patients from nine institutions treated with SRS from July 2005 to June 2020 for cerebral metastases from prostate carcinoma were collected and analyzed.

Results: Forty-six patients were treated in 51 SRS procedures for 120 prostate cancer intracranial metastases. At SRS, the mean patient age was 68.04 ± 9.05 years, the mean time interval from prostate cancer diagnosis to SRS was 4.82 ± 4.89 years, and extracranial dissemination was noted in 34 (73.9%) patients. The median patient Karnofsky Performance Scale (KPS) score at SRS was 80, and neurological symptoms attributed to intracranial involvement were present prior to 39 (76%) SRS procedures. Single-fraction SRS was used in 49 procedures. Stereotactic radiotherapy using 6 Gy in five sessions was utilized in 2 procedures. The median margin dose was 18 (range 6-28) Gy, and the median tumor volume was 2.45 (range 0.04-45) ml. At a median radiological follow-up of 6 (range 0-156) months, local progression was seen with 14 lesions. The median survival following SRS was 15.18 months, and the 1-year overall intracranial progression-free survival was 44%. The KPS score at SRS was noted to be associated with improved overall (p = 0.02) and progression-free survival (p = 0.03). Age ≥ 65 years at SRS was associated with decreased overall survival (p = 0.04). There were no serious grade 3-5 toxicities noted.

Conclusions: SRS appears to be a safe, well-tolerated, and effective management option for patients with prostate cancer intracranial metastases.
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http://dx.doi.org/10.3171/2021.4.JNS21246DOI Listing
October 2021

Quantification of tumor response of cystic vestibular schwannoma to Gamma Knife radiosurgery by using artificial intelligence.

J Neurosurg 2021 Oct 1:1-9. Epub 2021 Oct 1.

1Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital.

Objective: Gamma Knife radiosurgery (GKRS) is a common treatment modality for vestibular schwannoma (VS). The ability to predict treatment response is important in patient counseling and decision-making. The authors developed an algorithm that can automatically segment and differentiate cystic and solid tumor components of VS. They also investigated associations between the quantified radiological features of each component and tumor response after GKRS.

Methods: This is a retrospective study comprising 323 patients with VS treated with GKRS. After preprocessing and generation of pretreatment T2-weighted (T2W)/T1-weighted with contrast (T1WC) images, the authors segmented VSs into cystic and solid components by using fuzzy C-means clustering. Quantitative radiological features of the entire tumor and its cystic and solid components were extracted. Linear regression models were implemented to correlate clinical variables and radiological features with the specific growth rate (SGR) of VS after GKRS.

Results: A multivariable linear regression model of radiological features of the entire tumor demonstrated that a higher tumor mean signal intensity (SI) on T2W/T1WC images (p < 0.001) was associated with a lower SGR after GKRS. Similarly, a multivariable linear regression model using radiological features of cystic and solid tumor components demonstrated that a higher solid component mean SI (p = 0.039) and a higher cystic component mean SI (p = 0.004) on T2W/T1WC images were associated with a lower SGR after GKRS. A larger cystic component proportion (p = 0.085) was associated with a trend toward a lower SGR after GKRS.

Conclusions: Radiological features of VSs on pretreatment MRI that were quantified using fuzzy C-means were associated with tumor response after GKRS. Tumors with a higher tumor mean SI, a higher solid component mean SI, and a higher cystic component mean SI on T2W/T1WC images were more likely to regress in volume after GKRS. Those with a larger cystic component proportion also trended toward regression after GKRS. Further refinement of the algorithm may allow direct prediction of tumor response.
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http://dx.doi.org/10.3171/2021.4.JNS203700DOI Listing
October 2021

Clinical and radiologic outcomes after stereotactic radiosurgery for meningiomas in direct contact with the optic apparatus: an international multicenter study.

J Neurosurg 2021 Sep 24:1-7. Epub 2021 Sep 24.

17Department of Radiation Oncology, University of Southern California, Los Angeles, California.

Objective: Resection of meningiomas in direct contact with the anterior optic apparatus carries risk of injury to the visual pathway. Stereotactic radiosurgery (SRS) offers a minimally invasive alternative. However, its use is limited owing to the risk of radiation-induced optic neuropathy. Few SRS studies have specifically assessed the risks and benefits of treating meningiomas in direct contact with the optic nerve, chiasm, or optic tract. The authors hypothesized that SRS is safe for select patients with meningiomas in direct contact with the anterior optic apparatus.

Methods: The authors performed an international multicenter retrospective analysis of 328 patients across 11 institutions. All patients had meningiomas in direct contract with the optic apparatus. Patients were followed for a median duration of 56 months after SRS. Neurological examinations, including visual function evaluations, were performed at follow-up visits. Clinical and treatment variables were collected at each site according to protocol. Tumor volumes were assessed with serial MR imaging. Variables predictive of visual deficit were identified using univariable and multivariable logistic regression.

Results: SRS was the initial treatment modality for 64.6% of patients, and 93% of patients received SRS as a single fraction. Visual information was available for 302 patients. Of these patients, visual decline occurred in 29 patients (9.6%), of whom 12 (41.4%) had evidence of tumor progression. Visual decline in the remaining 17 patients (5.6%) was not associated with tumor progression. Pre-SRS Karnofsky Performance Status predicted visual decline in adjusted analysis (adjusted OR 0.9, 95% CI 0.9-1.0, p < 0.01). Follow-up imaging data were available for 322 patients. Of these patients, 294 patients (91.3%) had radiographic evidence of stability or tumor regression at last follow up. Symptom duration was associated with tumor progression in adjusted analysis (adjusted OR 1.01, adjusted 95% CI 1.0-1.02, adjusted p = 0.02).

Conclusions: In this international multicenter study, the vast majority of patients exhibited tumor control and preservation of visual function when SRS was used to treat meningioma in direct contact with the anterior optic pathways. SRS is a relatively safe treatment modality for select patients with perioptic meningiomas in direct contact with the optic apparatus.
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http://dx.doi.org/10.3171/2021.3.JNS21328DOI Listing
September 2021

Dose to neuroanatomical structures surrounding pituitary adenomas and the effect of stereotactic radiosurgery on neuroendocrine function: an international multicenter study.

J Neurosurg 2021 Sep 24:1-9. Epub 2021 Sep 24.

20Centro Gamma Knife Dominicano and Radiology Department, CEDIMAT, Santo Domingo, Dominican Republic.

Objective: Stereotactic radiosurgery (SRS) provides a safe and effective therapeutic modality for patients with pituitary adenomas. The mechanism of delayed endocrine deficits based on targeted radiation to the hypothalamic-pituitary axis remains unclear. Radiation to normal neuroendocrine structures likely plays a role in delayed hypopituitarism after SRS. In this multicenter study by the International Radiosurgery Research Foundation (IRRF), the authors aimed to evaluate radiation tolerance of structures surrounding pituitary adenomas and identify predictors of delayed hypopituitarism after SRS for these tumors.

Methods: This is a retrospective review of patients with pituitary adenomas who underwent single-fraction SRS from 1997 to 2019 at 16 institutions within the IRRF. Dosimetric point measurements of 14 predefined neuroanatomical structures along the hypothalamus, pituitary stalk, and normal pituitary gland were made. Statistical analyses were performed to determine the impact of doses to critical structures on clinical, radiographic, and endocrine outcomes.

Results: The study cohort comprised 521 pituitary adenomas treated with SRS. Tumor control was achieved in 93.9% of patients over a median follow-up period of 60.1 months, and 22.5% of patients developed new loss of pituitary function with a median treatment volume of 3.2 cm3. Median maximal radiosurgical doses to the hypothalamus, pituitary stalk, and normal pituitary gland were 1.4, 7.2, and 11.3 Gy, respectively. Nonfunctioning adenoma status, younger age, higher margin dose, and higher doses to the pituitary stalk and normal pituitary gland were independent predictors of new or worsening hypopituitarism. Neither the dose to the hypothalamus nor the ratio between doses to the pituitary stalk and gland were significant predictors. The threshold of the median dose to the pituitary stalk for new endocrinopathy was 10.7 Gy in a single fraction (OR 1.77, 95% CI 1.17-2.68, p = 0.006).

Conclusions: SRS for the treatment of pituitary adenomas affords a high tumor control rate with an acceptable risk of new or worsening endocrinopathy. This evaluation of point dosimetry to adjacent neuroanatomical structures revealed that doses to the pituitary stalk, with a threshold of 10.7 Gy, and doses to the normal gland significantly increased the risk of post-SRS hypopituitarism. In patients with preserved pre-SRS neuroendocrine function, limiting the dose to the pituitary stalk and gland while still delivering an optimal dose to the tumor appears prudent.
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http://dx.doi.org/10.3171/2021.3.JNS203812DOI Listing
September 2021

Adverse radiation effects in volume-staged radiosurgery for large arteriovenous malformations: a multiinstitutional study.

J Neurosurg 2021 Aug 27:1-9. Epub 2021 Aug 27.

2Department of Radiation Oncology, University of California, San Francisco, California.

Objective: The optimal treatment paradigm for large arteriovenous malformations (AVMs) is controversial. One approach is volume-staged stereotactic radiosurgery (VS-SRS). The authors previously reported efficacy of VS-SRS for large AVMs in a multiinstitutional cohort; here they focus on risk of symptomatic adverse radiation effects (AREs).

Methods: This is a multicentered retrospective review of patients treated with a planned prospective volume staging approach to stereotactically treat the entire nidus of an AVM, with volume stages separated by intervals of 3-6 months. A total of 9 radiosurgical centers treated 257 patients with VS-SRS between 1991 and 2016. The authors evaluated permanent, transient, and total ARE events that were symptomatic.

Results: Patients received 2-4 total volume stages. The median age was 33 years at the time of the first SRS volume stage, and the median follow-up was 5.7 years after VS-SRS. The median total AVM nidus volume was 23.25 cm3 (range 7.7-94.4 cm3), with a median margin dose per stage of 17 Gy (range 12-20 Gy). A total of 64 patients (25%) experienced an ARE, of which 19 were permanent. Rather than volume, maximal linear dimension in the Z (craniocaudal) dimension was associated with toxicity; a threshold length of 3.28 cm was associated with an ARE, with a 72.5% sensitivity and a 58.3% specificity. In addition, parietal lobe involvement for superficial lesions and temporal lobe involvement for deep lesions were associated with an ARE.

Conclusions: Size remains the dominant predictor of toxicity following SRS, but overall rates of AREs were lower than anticipated based on baseline features, suggesting that dose and size were relatively dissociated through volume staging. Further techniques need to be assessed to optimize outcomes.
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http://dx.doi.org/10.3171/2020.12.JNS201866DOI Listing
August 2021

Enhancement of Radiosurgical Treatment Outcome Prediction Using MRI Radiomics in Patients with Non-Small Cell Lung Cancer Brain Metastases.

Cancers (Basel) 2021 Aug 10;13(16). Epub 2021 Aug 10.

Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan.

The diagnosis of brain metastasis (BM) is commonly observed in non-small cell lung cancer (NSCLC) with poor outcomes. Accordingly, developing an approach to early predict BM response to Gamma Knife radiosurgery (GKRS) may benefit the patient treatment and monitoring. A total of 237 NSCLC patients with BMs (for survival prediction) and 256 patients with 976 BMs (for prediction of local tumor control) treated with GKRS were retrospectively analyzed. All the survival data were recorded without censoring, and the status of local tumor control was determined by comparing the last MRI follow-up in patients' lives with the pre-GKRS MRI. Overall 1763 radiomic features were extracted from pre-radiosurgical magnetic resonance images. Three prediction models were constructed, using (1) clinical data, (2) radiomic features, and (3) clinical and radiomic features. Support vector machines with a 30% hold-out validation approach were constructed. For treatment outcome predictions, the models derived from both the clinical and radiomics data achieved the best results. For local tumor control, the combined model achieved an area under the curve (AUC) of 0.95, an accuracy of 90%, a sensitivity of 91%, and a specificity of 89%. For patient survival, the combined model achieved an AUC of 0.81, an accuracy of 77%, a sensitivity of 78%, and a specificity of 80%. The pre-radiosurgical radiomics data enhanced the performance of local tumor control and survival prediction models in NSCLC patients with BMs treated with GRKS. An outcome prediction model based on radiomics combined with clinical features may guide therapy in these patients.
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http://dx.doi.org/10.3390/cancers13164030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392266PMC
August 2021

Stereotactic radiosurgery for clinoid meningiomas: a multi-institutional study.

Acta Neurochir (Wien) 2021 10 24;163(10):2861-2869. Epub 2021 Aug 24.

Gamma Knife Center, Mayfield Clinic, Cincinnati, OH, USA.

Purpose: Resection of clinoid meningiomas can be associated with significant morbidity. Experience with stereotactic radiosurgery (SRS) for clinoid meningiomas remains limited. We studied the safety and effectiveness of SRS for clinoid meningiomas.

Methods: From twelve institutions participating in the International Radiosurgery Research Foundation, we pooled patients treated with SRS for radiologically suspected or histologically confirmed WHO grade I clinoid meningiomas.

Results: Two hundred seven patients (median age: 56 years) underwent SRS for clinoid meningiomas. Median treatment volume was 8.02 cm, and 87% of tumors were immediately adjacent to the optic apparatus. The median tumor prescription dose was 12 Gy, and the median maximal dose to the anterior optic apparatus was 8.5 Gy. During a median post-SRS imaging follow-up of 51.1 months, 7% of patients experienced tumor progression. Greater margin SRS dose (HR = 0.700, p = 0.007) and pre-SRS radiotherapy (HR = 0.004, p < 0.001) were independent predictors of better tumor control. During median visual follow-up of 48 months, visual function declined in 8% of patients. Pre-SRS visual deficit (HR = 2.938, p = 0.048) and maximal radiation dose to the optic apparatus of ≥ 10 Gy (HR = 11.297, p = 0.02) independently predicted greater risk of post-SRS visual decline. Four patients experienced new post-SRS cranial nerve V neuropathy.

Conclusions: SRS allows durable control of clinoid meningiomas and visual preservation in the majority of patients. Greater radiosurgical prescription dose is associated with better tumor control. Radiation dose to the optic apparatus of ≥ 10 Gy and visual impairment before the SRS increase risk of visual deterioration.
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http://dx.doi.org/10.1007/s00701-021-04972-3DOI Listing
October 2021

Stereotactic Radiosurgery for Olfactory Groove Meningiomas: An International, Multicenter Study.

Neurosurgery 2021 Oct;89(5):784-791

Department of Neurosurgery, University of Southern California, Los Angeles, California, USA.

Background: Stereotactic radiosurgery (SRS) is increasingly considered for selected olfactory groove meningiomas (OGMs).

Objective: To investigate the safety and efficacy of SRS for OGMs.

Methods: From 20 institutions participating in the International Radiosurgery Research Foundation, we pooled patients who underwent SRS for histologically confirmed or radiologically suspected WHO grade I OGMs and were followed for 6 mo or more after the SRS.

Results: In total, 278 (median age 57 yr) patients underwent SRS for histologically confirmed (29%) or radiologically suspected (71%) WHO grade I OGMs Median treatment volume was 4.60 cm3 (range: 0.12-27.3 cm3), median prescription dose was 12 Gy, and median dose to the olfactory nerve was 11.20 Gy. During median post-SRS imaging follow-up of 39 mo (range: 6-240 mo), 43% of patients had partial or marginal response, 54% of patients had stable disease, and 3% of patients experienced progression. During median post-SRS clinical follow-up of 51 mo (range: 6-240 mo), 36 (13%) patients experienced clinical and/or radiological adverse radiation events (AREs). Elevated risk of AREs was associated with larger OGM volume (P = .009) and pre-SRS peritumoral T2/fluid-attenuated inversion-recovery signal abnormalities (P < .001). After the SRS, olfaction remained stable, improved, or deteriorated in 90%, 8%, and 2% of patients, respectively. Complete post-SRS anosmia was predicted by partial/complete anosmia before the SRS (odds ratio [OR] = 83.125; 95% CI [24.589-281.01], P < .001) and prior resection of OGM (OR = 3.919; 95% CI [1.713-8.970], P = .001).

Conclusion: SRS is associated with durable local control of the majority of OGM patients with acceptable safety profile. SRS allows preservation or improvement of olfactory function in the majority of OGM patients.
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http://dx.doi.org/10.1093/neuros/nyab291DOI Listing
October 2021

Effect of Prior Embolization on Outcomes After Stereotactic Radiosurgery for Pediatric Brain Arteriovenous Malformations: An International Multicenter Study.

Neurosurgery 2021 09;89(4):672-679

Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia, USA.

Background: Pediatric brain arteriovenous malformations (AVMs) are a significant cause of morbidity but the role of multimodal therapy in the treatment of these lesions is not well understood.

Objective: To compare the outcomes of stereotactic radiosurgery (SRS) with and without prior embolization for pediatric AVMs.

Methods: We retrospectively evaluated the International Radiosurgery Research Foundation pediatric AVM database. AVMs were categorized, based on use of pre-embolization (E + SRS) or lack thereof (SRS-only). Outcomes were compared in unadjusted and inverse probability weight (IPW)-adjusted models. Favorable outcome was defined as obliteration without post-SRS hemorrhage or permanent radiation-induced changes (RIC).

Results: The E + SRS and SRS-only cohorts comprised 91 and 448 patients, respectively. In unadjusted models, the SRS-only cohort had higher rates of obliteration (68.5% vs 43.3%,  < .001) and favorable outcome (61.2% vs 36.3%, P < .001) but a lower rate of symptomatic RIC (9.0% vs 16.7%, P = .031). The IPW-adjusted rates of every outcome were similar between the 2 cohorts. However, cumulative obliteration rates at 3, 5, 8, and 10 yr remained higher in the absence of prior embolization (46.3%, 64.6%, 72.6%, and 77.4% for SRS-only vs 24.4%, 37.2%, 44.1%, and 48.7% for E + SRS cohorts, respectively; SHR = 0.449 [0.238-0.846], P = .013).

Conclusion: Embolization appears to decrease cumulative obliteration rates after SRS for pediatric AVMs without affecting the risk of post-treatment hemorrhage or adverse radiation effects arguing against the routine use of pre-SRS embolization. While endovascular therapy can be considered for occlusion of high-risk angioarchitectural features prior to SRS, future studies are necessary to clarify its role.
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http://dx.doi.org/10.1093/neuros/nyab245DOI Listing
September 2021

The Irradiated Brain Volume Within 12 Gy Is a Predictor for Radiation-Induced Changes After Stereotactic Radiosurgery in Patients With Unruptured Cerebral Arteriovenous Malformations.

Int J Radiat Oncol Biol Phys 2021 Nov 21;111(3):785-793. Epub 2021 Jul 21.

Institute of Brain Science, National Yang-Ming Chiao Tung University, Taipei, Taiwan; School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan; Departments of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan; Departments of Critical Care Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. Electronic address:

Purpose: Our purpose was to determine whether the coverage of brain parenchyma within the 12 Gy radiosurgical volume (V12) correlates with the development of radiation-induced changes (RICs) in patients with unruptured cerebral arteriovenous malformations (AVM) after undergoing stereotactic radiosurgery (SRS).

Methods And Materials: This study conducted regular follow-up examinations of 165 patients with unruptured AVMs who had previously undergone SRS. The RICs identified in T2-weighted magnetic resonance imaging (MRI) scans at any time point in the first 3 years after SRS were labeled "early RICs." The RICs identified in T2-weighted MRI scans at 5-year follow-up brain images were labeled "late RICs." Fully automated segmentation was used to analyze the MRI scans from these patients, whereupon the volume and proportion of brain parenchyma within the V12 was calculated. Logistic regression analysis was used to characterize the factors affecting the incidence of early and late RICs of any grade after SRS.

Results: The median duration of follow-up was 70 months (range, 36-222). Early RICs were identified in 124 of the 165 patients with the highest grades as followed: grade 1 (103 patients), grade 2 (19 patients), and grade 3 (2 patients). Only 103 patients had more than 5 years follow-up, and late RICs were identified in 70 of 103 patients. Seventeen of 70 patients with late RICs were symptomatic. The median volume and proportion of brain parenchyma within the V12 was 22.4 cm (range, 0.6-63.9) and 58.7% (range, 18.4-76.8). Univariate analysis revealed that AVM volume and the brain volume within the V12 were correlated with the incidence of both early and late RICs after SRS. Multivariable analysis revealed that only the brain volume within the V12 was significantly associated with the incidence of early and late RICs after SRS.

Conclusions: In patients with unruptured AVM, the volume of brain parenchyma within the V12 was an important factor associated with the incidence of early and late RICs after SRS. Before SRS, meticulous radiosurgical planning to reduce brain parenchyma coverage within the V12 could reduce the risk of complications.
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http://dx.doi.org/10.1016/j.ijrobp.2021.05.135DOI Listing
November 2021

Assessment of Cardiopulmonary Bypass Duration Improves Novel Biomarker Detection for Predicting Postoperative Acute Kidney Injury after Cardiovascular Surgery.

J Clin Med 2021 Jun 22;10(13). Epub 2021 Jun 22.

Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 33305, Taiwan.

Urinary liver-type fatty acid binding protein (L-FABP) is a novel biomarker with promising performance in detecting kidney injury. Previous studies reported that L-FABP showed moderate discrimination in patients that underwent cardiac surgery, and other studies revealed that longer duration of cardiopulmonary bypass (CPB) was associated with a higher risk of postoperative acute kidney injury (AKI). This study aims to examine assessing CPB duration first, then examining L-FABP can improve the discriminatory ability of L-FABP in postoperative AKI. A total of 144 patients who received cardiovascular surgery were enrolled. Urinary L-FABP levels were examined at 4 to 6 and 16 to 18 h postoperatively. In the whole study population, the AUROC of urinary L-FABP in predicting postoperative AKI within 7 days was 0.720 at 16 to 18 h postoperatively. By assessing patients according to CPB duration, the urinary L-FABP at 16 to 18 h showed more favorable discriminating ability with AUROC of 0.742. Urinary L-FABP exhibited good performance in discriminating the onset of AKI within 7 days after cardiovascular surgery. Assessing postoperative risk of AKI through CPB duration first and then using urinary L-FABP examination can provide more accurate and satisfactory performance in predicting postoperative AKI.
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http://dx.doi.org/10.3390/jcm10132741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268369PMC
June 2021

An International Multicenter Matched Cohort Analysis of Incidental Meningioma Progression During Active Surveillance or After Stereotactic Radiosurgery: The IMPASSE Study.

Neuro Oncol 2021 Jun 9. Epub 2021 Jun 9.

Department of Neurosurgery, University of Liverpool & The Walton Centre NHS Trust, Lower Lane, Liverpool, UK.

Background: The optimal management of patients with an incidental meningiomas remains unclear. The aim of this study was to characterize the radiologic and neurological outcomes of expectant and SRS management of asymptomatic meningioma patients.

Methods: Using data from 14 centers across 10 countries, the study compares SRS outcomes to active surveillance of asymptomatic meningiomas. Local tumor control of asymptomatic meningiomas and development of new neurological deficits attributable to the tumor were evaluated in the SRS and conservatively managed groups.

Results: In unmatched cohorts, 727 meningioma patients underwent SRS and were followed for a mean of 57.2 months. In the conservatively managed cohort, 388 patients were followed for a mean of 43.5 months. Tumor control was 99.0% of SRS and 64.2% of conservatively managed patients (p<0.001; OR 56.860 (95%CI 26.253-123.150))). New neurological deficits were 2.5% in the SRS and 2.8% of conservatively managed patients (p=0.764; OR 0.890 (95% CI 0.416-1.904)). After 1:1 propensity matching for patient age, tumor volume, location, and imaging follow-up, tumor control in the SRS and conservatively managed cohorts was 99.4% and 62.1%, respectively (p<0.001; OR 94.461 (95% CI 23.082-386.568)). In matched cohorts, new neurological deficits were noted in 2.3% of SRS treated and 3.2% of conservatively managed patients (p=0.475; OR 0.700 (95% CI 0.263-1.863)).

Conclusions: SRS affords superior radiologic tumor control compared to active surveillance without increasing the risk of neurological deficits in asymptomatic meningioma patients. While SRS and active surveillance are reasonable options, SRS appears to alter the natural history of asymptomatic meningiomas including tumor progression in the majority of patients treated.
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http://dx.doi.org/10.1093/neuonc/noab132DOI Listing
June 2021

A validation study comparing existing prediction models of acute kidney injury in patients with acute heart failure.

Sci Rep 2021 05 27;11(1):11213. Epub 2021 May 27.

Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Linkou branch, No. 5, Fuxing Street, Guishan Dist., Taoyuan City, 33305, Taiwan ROC.

Acute kidney injury (AKI) is a common complication in acute heart failure (AHF) and is associated with prolonged hospitalization and increased mortality. The aim of this study was to externally validate existing prediction models of AKI in patients with AHF. Data for 10,364 patients hospitalized for acute heart failure between 2008 and 2018 were extracted from the Chang Gung Research Database and analysed. The primary outcome of interest was AKI, defined according to the KDIGO definition. The area under the receiver operating characteristic (AUC) curve was used to assess the discrimination performance of each prediction model. Five existing prediction models were externally validated, and the Forman risk score and the prediction model reported by Wang et al. showed the most favourable discrimination and calibration performance. The Forman risk score had AUCs for discriminating AKI, AKI stage 3, and dialysis within 7 days of 0.696, 0.829, and 0.817, respectively. The Wang et al. model had AUCs for discriminating AKI, AKI stage 3, and dialysis within 7 days of 0.73, 0.858, and 0.845, respectively. The Forman risk score and the Wang et al. prediction model are simple and accurate tools for predicting AKI in patients with AHF.
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http://dx.doi.org/10.1038/s41598-021-90756-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159983PMC
May 2021

Effects of stereotactic radiosurgery versus conventional radiotherapy on body mass index in patients with craniopharyngioma.

J Neurosurg Pediatr 2021 May 14:1-7. Epub 2021 May 14.

1Department of Neurosurgery, Neurological Institute.

Objective: Hypothalamic obesity is common among patients with craniopharyngioma. This study examined whether precise stereotactic radiosurgery reduces the risk of hypothalamic obesity in cases of craniopharyngioma with expected long-term survival.

Methods: This cohort study included 40 patients who had undergone Gamma Knife radiosurgery (GKRS; n = 22) or fractionated radiotherapy (FRT; n = 18) for residual or recurrent craniopharyngioma. Neurological presentations, tumor volume changes, and BMI values were meticulously reviewed. The median clinical follow-up durations were 9.7 years in the GKRS group and 10.8 years in the FRT group.

Results: The median ages at the time of GKRS and FRT were 9.0 years and 10.0 years, respectively. The median margin dose of GKRS was 12.0 Gy (range 10.0-16.0 Gy), whereas the median dose of FRT was 50.40 Gy (range 44.1-56.3 Gy). Prior to GKRS or FRT, the median BMI values were 20.5 kg/m2 in the GKRS cohort and 20.0 kg/m2 in the FRT cohort. The median BMIs after radiation therapy at final follow-up were 21.0 kg/m2 and 24.0 kg/m2 for the GKRS and FRT cohorts, respectively. In the FRT cohort, BMI curves rapidly increased beyond the 85th percentile of the upper limit of the general population. BMI curves in the GKRS cohort increased more gradually, and many of the patients merged into the normal growth curve after adolescence. However, the observed difference was not statistically significant (p = 0.409).

Conclusions: The study compared the two adjuvant radiation modalities most commonly used for recurrent and residual craniopharyngioma. The authors' results revealed that precise radiosurgery dose planning can mediate the subsequent increase in BMI. There is every indication that meticulous GKRS treatment is an effective approach to treating craniopharyngioma while also reducing the risk of hypothalamic obesity.
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http://dx.doi.org/10.3171/2020.12.PEDS20165DOI Listing
May 2021

Stereotactic Radiosurgery for Differentiated Thyroid Cancer Brain Metastases: An International, Multicenter Study.

Thyroid 2021 08 11;31(8):1244-1252. Epub 2021 May 11.

Department of Neurosurgery, University of Virginia, Charlottesville, Virginia, USA.

Brain metastases (BM) from differentiated thyroid cancer are rare. Stereotactic radiosurgery (SRS) is commonly used for the treatment of BMs; however, the experience with SRS for thyroid cancer BMs remains limited. The goal of this international, multi-centered study was to evaluate the efficacy and safety of SRS for thyroid cancer BMs. From 10 institutions participating in the International Radiosurgery Research Foundation, we pooled patients with established papillary or follicular thyroid cancer diagnosis who underwent SRS for histologically confirmed or radiologically suspected BMs. We investigated patient overall survival (OS), local tumor control, and adverse radiation events (AREs). We studied 42 (52% men) patients who underwent SRS for 122 papillary (83%) or follicular (17%) thyroid cancer BMs. The mean age at SRS was 59.86 ± 12.69 years. The mean latency from thyroid cancer diagnosis to SRS for BMs was 89.05 ± 105.49 months. The median number of BMs per patient was 2 (range: 1-10 BMs). The median SRS treatment volume was 0.79 cm (range: 0.003-38.18 cm), and the median SRS prescription dose was 20 Gy (range: 8-24 Gy). The median survival after SRS for BMs was 14 months (range: 3-58 months). The OS was significantly shorter in patients harboring ≥2 BMs, when compared with patients with one BM (Log-rank = 5.452,  = 0.02). Two or more BMs (odds ratio [OR] = 3.688; confidence interval [CI]: 1.143-11.904;  = 0.03) and lower Karnofsky performance score at the time of SRS (OR = 0.807; CI: 0.689-0.945;  = 0.008) were associated with shorter OS. During post-SRS imaging follow-up of 25.21 ± 30.49 months, local failure (progression and/or radiation necrosis) of BMs treated with SRS was documented in five (4%) BMs at 7.2 ± 7.3 months after the SRS. At the last imaging follow-up, the majority of patients with available imaging data had stable intracranial disease (33%) or achieved complete (26%) or partial (24%) response. There were no clinical AREs. Post-SRS peritumoral T2/fluid attenuated inversion recovery signal hyperintensity was noted in 7% BMs. The SRS allows durable local control of papillary and follicular thyroid cancer BMs in the vast majority of patients. Higher number of BMs and worse functional status at the time of SRS are associated with shorter OS in patients with thyroid cancer BMs. The SRS is safe and is associated with a low risk of AREs.
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http://dx.doi.org/10.1089/thy.2020.0947DOI Listing
August 2021

Using lipocalin as a prognostic biomarker in acute kidney injury.

Expert Rev Mol Diagn 2021 May 19;21(5):455-464. Epub 2021 Apr 19.

Department of Nephrology, Chang Gung Memorial Hospital, Taipei, Taiwan.

: Human lipocalin-2, known as neutrophil gelatinase-associated lipocalin (NGAL), is a widely studied biomarker of acute kidney injury (AKI).: NGAL can serve as a predictor of AKI, disease progression, and mortality and can help in differentiating between AKI etiologies. We conducted a systematic review in the PubMed and Medline databases involving the clinical application of NGAL in patients with AKI.: In this review, we explored the usefulness of NGAL for AKI or clinical outcome prediction. The use of urine or blood NGAL levels alone or in combination with a clinical prediction model may facilitate AKI prediction, severity prediction, AKI etiological differentiation, and mortality prediction. For AKI prediction, urine and plasma NGAL levels have an area under the curve (AUC) ranging from 0.71 to 0.90 and from 0.71 to 0.89, respectively, in different populations. The diagnostic performance of NGAL alone for renal replacement therapy or successful discontinuation prediction is suboptimal (AUC range: 0.65-0.81). Sepsis limits the application of NGAL as a clinical predictor, and the prediction performance of NGAL is affected by baseline renal function, timing of sample collection, and underlying comorbidities. The lack of internationally approved reference material also limits the usefulness of NGAL.
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http://dx.doi.org/10.1080/14737159.2021.1917384DOI Listing
May 2021

Fenofibrate Delays the Need for Dialysis and Reduces Cardiovascular Risk Among Patients With Advanced CKD.

J Clin Endocrinol Metab 2021 05;106(6):1594-1605

Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan.

Context: Fenofibrate provides limited cardiovascular (CV) benefits in the general population; however, little is known about its benefit among advanced chronic kidney disease (CKD) patients.

Objective: This study compared outcomes among advanced CKD patients treated with fenofibrate, statins, a combination of both, and none of these.

Methods: This national cohort study was based on Taiwan's National Health Insurance Research Database. Patients younger than 20 years with advanced CKD were identified and further divided into 4 groups according to treatment. The inverse probability of treatment weighting was used to balance baseline characteristics. Patients received fenofibrate, statins, a combination of fenofibrate and statins, or none of these in the 3 months preceding the advanced CKD date. Main outcome measures included all-cause mortality, CV death, and incidence of permanent dialysis.

Results: The fenofibrate and statin groups exhibited a lower risk of CV death (fenofibrate vs nonuser: hazard ratio [HR]: 0.84; 95% CI, 0.75-0.94; statins vs nonuser: HR: 0.94; 95% CI, 0.90-0.97) compared with the nonuser group. The fenofibrate group further exhibited the lowest incidence of permanent dialysis (fenofibrate vs nonuser: subdistribution HR [SHR]: 0.78; 95% CI, 0.77-0.80; statins vs fenofibrate: SHR: 1.27; 95% CI, 1.26-1.29; combination vs fenofibrate: SHR: 1.15; 95% CI, 1.13-1.17). Furthermore, the combined administration of fenofibrate and high-intensity statins exhibited a lower risk of major adverse cardiac and cerebrovascular events.

Conclusion: For patients with advanced CKD, continuing fenofibrate may provide a protective effect on CV outcomes equal to that of statins, and it may further delay the need for permanent dialysis. The combination of fenofibrate and high-intensity statins may have additional benefits.
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http://dx.doi.org/10.1210/clinem/dgab137DOI Listing
May 2021

Cerebrospinal fluid diversion and outcomes for lung cancer patients with leptomeningeal carcinomatosis.

Acta Neurochir (Wien) 2021 Mar 1. Epub 2021 Mar 1.

Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.

Objective: To investigate the outcomes of cerebrospinal fluid (CSF) diversion in lung cancer patients with leptomeningeal carcinomatosis (LMC).

Methods: A retrospective review of consecutive lung cancer patients with LMC suffering from increased intracranial pressure (IICP) and hydrocephalus between February 2017 and February 2020. We evaluated the survival benefit of CSF diversion surgery and assessed the outcomes of treatments administered post-LMC in terms of overall survival and shunt-related complications.

Results: The study cohort included 50 patients (median age: 59 years). Ventricular peritoneal (VP) shunts were placed in 33 patients, and lumbar peritoneal (LP) shunts were placed in 7 patients. Programmable shunts were placed in 36 patients. Shunt adjustment was performed in 19 patients. Kaplan-Meier analysis revealed that shunt placement increased overall survival from 1.95 months to 6.21 months (p = 0.0012) and increased Karnofsky Performance Scores (KPS) from 60 to 70. Univariate analysis revealed no difference between VP or LP shunts in terms of survival. No differences in post-shunt systemic treatments (tyrosine kinase inhibitors (TKIs) or systemic treatments) were observed in overall survival. Shunt-related complications were noted in 7 patients, including shunt obstruction (n = 4), infection (n = 1), and over-drainage (n = 2).

Conclusion: CSF diversion (VP or LP shunt) appears to be an effective and safe treatment for lung cancer patients with LMC and hydrocephalus. Programmable shunts should be considered for complex cases, which commonly require pressure adjustments as the disease progresses.
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http://dx.doi.org/10.1007/s00701-021-04763-wDOI Listing
March 2021

Outcomes of hippocampus-sparing lesionectomy for temporal lobe epilepsy and the significance of intraoperative hippocampography.

Clin Neurophysiol 2021 03 31;132(3):746-755. Epub 2020 Dec 31.

Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Brain Science, Brain Research Center, National Yang-Ming University, Taipei, Taiwan.

Objectives: We investigated hippocampal-sparing lesionectomy (HSL) outcomes in temporal lobe epilepsy (TLE) and the significance of high-frequency oscillations (HFOs) detected by hippocampography in HSL.

Methods: We retrospectively reviewed data from patients who underwent HSL for lesional TLE. Patients were included when MRI confirmed (i) a lesion limited to the temporal lobe with normal hippocampi preoperatively and (ii) hippocampal integrity postoperatively. Factors possibly related to outcomes were collected. Intraoperative hippocampography was reviewed, and spikes, ripples, and fast ripples were marked. Seizure outcomes were tracked ≥ 2 years. Postoperative neuropsychological tests were performed and analyzed.

Results: We included 67 patients (35 males/32 females, median age at surgery 28 years, 57 seizure-free). Complete resection was significantly associated with being seizure-free without aura, an outcome achieved by 32 (69.6%) patients with complete resection vs 1 (12.5%) with incomplete resection (p = 0.004). Spikes/ripples/fast ripples appeared frequently in the hippocampus, occurring in 86.4%/82.4%/75.0% of cases before resection and 76.7%/78.1%/63.0% after resection. The presence and rate were unconnected to seizure outcome. Postoperative neuropsychological outcomes in intelligence and visual memory improved overall.

Conclusions: HSL in lesional TLE can produce satisfactory seizure and cognitive outcomes. Intraoperative hippocampography-guided resection of apparently normal hippocampi should be performed cautiously and might not be necessary.

Significance: This study provided evidence in decision making for patients with lesional TLE with a radiologically normal hippocampus.
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http://dx.doi.org/10.1016/j.clinph.2020.12.008DOI Listing
March 2021

Utility of Cerebrospinal Fluid Cell-Free DNA in Patients with EGFR-Mutant Non-Small-Cell Lung Cancer with Leptomeningeal Metastasis.

Target Oncol 2021 03 10;16(2):207-214. Epub 2021 Feb 10.

Department of Chest Medicine, Taipei Veterans General Hospital, 201, Section 2, Shih-Pai Road, Taipei, 112, Taiwan.

Background: Leptomeningeal metastasis (LM) is a fatal complication of advanced non-small-cell lung cancer (NSCLC).

Objective: The aim of this study was to evaluate the utility of cerebrospinal fluid (CSF) as a medium for epidermal growth factor receptor (EGFR) mutation testing in clinical practice.

Patients And Methods: We prospectively enrolled patients with EGFR-mutant NSCLC who underwent CSF sampling for suspected LM. The supernatant of CSF after routine cytology examination was collected. The diagnosis of LM was established according to EANO-ESMO criteria. CSF and plasma cell-free DNA (cfDNA) were retrieved for EGFR mutation testing.

Results: Fifty-one patients with a median age of 62.7 years were enrolled. The median duration from initial diagnosis to CSF sampling was 23.0 months and most patients (94.1%) had received at least one EGFR-tyrosine kinase inhibitor. Adenocarcinoma cells were found in 37 CSF samples (72.5%), and 48 (94.1%) patients had confirmed or probable LM. Thirty-five of these 48 patients (72.9%) had valid EGFR mutation-testing results using CSF cfDNA and tended to have higher white blood cell counts and positive cytology in their CSF compared to those with invalid mutation testing results. The overall detection rate of EGFR mutation in CSF cfDNA was 68.8%, and the T790M detection rate was 14.6%. In 37 patients with paired CSF and plasma samples, the concordance rate of the EGFR mutation results was 29.7%.

Conclusions: For patients with EGFR-mutant NSCLC with LM, CSF supernatant is a valuable source for EGFR mutation testing and may provide important information.
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http://dx.doi.org/10.1007/s11523-021-00791-9DOI Listing
March 2021

Treatment of WHO Grade 2 Meningiomas With Stereotactic Radiosurgery: Identification of an Optimal Group for SRS Using RPA.

Int J Radiat Oncol Biol Phys 2021 07 3;110(3):804-814. Epub 2021 Feb 3.

Department of Neurologic Surgery, University of Virginia Health System, Charlottesville, Virginia.

Purpose: This study assesses a large multi-institutional database to present the outcomes of World Health Organization grade 2 meningiomas treated with stereotactic radiosurgery (SRS). We also compare the 3-year progression-free survival (PFS) to that reported in the Radiation Therapy Oncology Group 0539 phase 2 cooperative group meningioma trial.

Methods And Materials: From an international, multicenter group, data were collected for grade 2 meningioma patients treated with SRS for demonstrable tumor from 1994 to 2019. Statistical methods used included the Kaplan-Meier method, Cox proportional hazards analysis, and recursive partitioning analysis.

Results: Two hundred thirty-three patients treated at 12 institutions were included. Patients presented at a median age of 60 years (range, 13-90), and many had at least 2 prior resections (30%) or radiation therapy (22%). Forty-eight percent of patients had prior gross total resection. At SRS, the median treatment volume was 6.1 cm (0.1-97.6). A median 15 Gy (10-30) was delivered to a median percent isodose of 50 (30-80), most commonly in 1 fraction (95%). A model was developed using recursive partitioning analysis, with one point attributed to age >50 years, treatment volume >11.5 cm, and prior radiation therapy or multiple surgeries. The good-prognostic group (score, 0-1) had improved PFS (P < .005) and time to local failure (P < .005) relative to the poor-prognostic group (score, 2-3). Age >50 years (hazard ratio = 1.85 [95% confidence interval, 1.09-3.14]) and multiple prior surgeries (hazard ratio = 1.80 [1.09-2.99]) also portended reduced PFS in patients without prior radiation therapy. Two hundred eighteen of 233 patients in this study qualified for the high-risk group of Radiation Therapy Oncology Group 0539, and they demonstrated similar outcomes (3-year PFS: 53.9% vs 58.8%). The good-prognostic group of SRS patients demonstrated slightly improved outcomes (3-year PFS: 63.1% vs 58.8%).

Conclusions: SRS should be considered in carefully selected patients with atypical meningiomas. We suggest the use of our good-prognostic group to optimize patient selection, and we strongly encourage the initiation of a clinical trial to prospectively validate these outcomes.
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http://dx.doi.org/10.1016/j.ijrobp.2021.01.048DOI Listing
July 2021

Applying artificial intelligence to longitudinal imaging analysis of vestibular schwannoma following radiosurgery.

Sci Rep 2021 02 4;11(1):3106. Epub 2021 Feb 4.

Department of Radiology, Taipei Veteran General Hospital, Taipei, Taiwan.

Artificial intelligence (AI) has been applied with considerable success in the fields of radiology, pathology, and neurosurgery. It is expected that AI will soon be used to optimize strategies for the clinical management of patients based on intensive imaging follow-up. Our objective in this study was to establish an algorithm by which to automate the volumetric measurement of vestibular schwannoma (VS) using a series of parametric MR images following radiosurgery. Based on a sample of 861 consecutive patients who underwent Gamma Knife radiosurgery (GKRS) between 1993 and 2008, the proposed end-to-end deep-learning scheme with automated pre-processing pipeline was applied to a series of 1290 MR examinations (T1W+C, and T2W parametric MR images). All of which were performed under consistent imaging acquisition protocols. The relative volume difference (RVD) between AI-based volumetric measurements and clinical measurements performed by expert radiologists were + 1.74%, - 0.31%, - 0.44%, - 0.19%, - 0.01%, and + 0.26% at each follow-up time point, regardless of the state of the tumor (progressed, pseudo-progressed, or regressed). This study outlines an approach to the evaluation of treatment responses via novel volumetric measurement algorithm, and can be used longitudinally following GKRS for VS. The proposed deep learning AI scheme is applicable to longitudinal follow-up assessments following a variety of therapeutic interventions.
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http://dx.doi.org/10.1038/s41598-021-82665-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862268PMC
February 2021

Outcomes after stereotactic radiosurgery for schwannomas of the oculomotor, trochlear, and abducens nerves.

J Neurosurg 2021 Jan 22:1-7. Epub 2021 Jan 22.

1Division of Neurosurgery, Department of Surgery, Université de Sherbrooke, Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Québec, Canada.

Objective: Cranial nerve (CN) schwannomas are intracranial tumors that are commonly managed by stereotactic radiosurgery (SRS). There is a large body of literature supporting the use of SRS for vestibular schwannomas. Schwannomas of the oculomotor nerves (CNs III, IV, and VI) are rare skull base tumors, occurring close to the brainstem and often involving the cavernous sinus. Resection can cause significant morbidity, including loss of nerve function. As for other schwannomas, SRS can be used to manage these tumors, but only a handful of cases have been published so far, often among reports of other uncommon schwannoma locations.

Methods: The goal of this study was to collect retrospective multicenter data on tumor control, clinical evolution, and morbidity after SRS. This study was performed through the International Radiosurgery Research Foundation. Patients managed with single-session SRS for an oculomotor cranial nerve schwannoma (CN III, IV, or VI) were included. The diagnosis was based on diplopia or ptosis as the main presenting symptom and anatomical location on the trajectory of the presumed cranial nerve of origin, or prior resection confirming diagnosis. Demographic, SRS dose planning, clinical, and imaging data were collected from chart review of the treated patients. Chi-square and Kaplan-Meier analyses were performed.

Results: Seven institutions submitted data for a total of 25 patients. The median follow-up time was 41 months. The median age at the time of treatment was 52 years. There were 11 CN III schwannomas, 11 CN IV schwannomas, and 3 CN VI schwannomas. The median target volume was 0.74 cm3, and the median marginal dose delivered was 12.5 Gy. After SRS, only 2 patients (including the only patient with neurofibromatosis type 2) had continued tumor growth. Crude local control was 92% (23/25), and the 10-year actuarial control was 86%. Diplopia improved in the majority of patients (11/21), and only 3 had worsening following SRS, 2 of whom also had worsened ptosis, both in the context of tumor progression.

Conclusions: SRS for schwannomas of the oculomotor, trochlear, and abducens nerves is effective and provides tumor control rates similar to those for other cranial nerve schwannomas. SRS allows improvement of diplopia in the majority of patients. SRS should therefore be considered as a first-line treatment option for oculomotor nerve schwannomas.
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http://dx.doi.org/10.3171/2020.8.JNS20887DOI Listing
January 2021

Stereotactic Radiosurgery for Perioptic Meningiomas: An International, Multicenter Study.

Neurosurgery 2021 03;88(4):828-837

Department of Radiation Oncology, University of Colorado, Denver, Colorado.

Background: Stereotactic radiosurgery (SRS) is increasingly used for management of perioptic meningiomas.

Objective: To study the safety and effectiveness of SRS for perioptic meningiomas.

Methods: From 12 institutions participating in the International Radiosurgery Research Foundation (IRRF), we retrospectively assessed treatment parameters and outcomes following SRS for meningiomas located within 3 mm of the optic apparatus.

Results: A total of 438 patients (median age 51 yr) underwent SRS for histologically confirmed (29%) or radiologically suspected (71%) perioptic meningiomas. Median treatment volume was 8.01 cm3. Median prescription dose was 12 Gy, and median dose to the optic apparatus was 8.50 Gy. A total of 405 patients (93%) underwent single-fraction SRS and 33 patients (7%) underwent hypofractionated SRS. During median imaging follow-up of 55.6 mo (range: 3.15-239 mo), 33 (8%) patients experienced tumor progression. Actuarial 5-yr and 10-yr progression-free survival was 96% and 89%, respectively. Prescription dose of ≥12 Gy (HR: 0.310; 95% CI [0.141-0.679], P = .003) and single-fraction SRS (HR: 0.078; 95% CI [0.016-0.395], P = .002) were associated with improved tumor control. A total of 31 (10%) patients experienced visual decline, with actuarial 5-yr and 10-yr post-SRS visual decline rates of 9% and 21%, respectively. Maximum dose to the optic apparatus ≥10 Gy (HR = 2.370; 95% CI [1.086-5.172], P = .03) and tumor progression (HR = 4.340; 95% CI [2.070-9.097], P < .001) were independent predictors of post-SRS visual decline.

Conclusion: SRS provides durable tumor control and quite acceptable rates of vision preservation in perioptic meningiomas. Margin dose of ≥12 Gy is associated with improved tumor control, while a dose to the optic apparatus of ≥10 Gy and tumor progression are associated with post-SRS visual decline.
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http://dx.doi.org/10.1093/neuros/nyaa544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8517876PMC
March 2021

Stereotactic Radiosurgery for Atypical (World Health Organization II) and Anaplastic (World Health Organization III) Meningiomas: Results From a Multicenter, International Cohort Study.

Neurosurgery 2021 04;88(5):980-988

Department of Neurologic Surgery, Mayfield Clinic, Cincinnati, Ohio.

Background: Atypical and anaplastic meningiomas have reduced progression-free/overall survival (PFS/OS) compared to benign meningiomas. Stereotactic radiosurgery (SRS) for atypical meningiomas (AMs) and anaplastic meningiomas (malignant meningiomas, MMs) has not been adequately described.

Objective: To define clinical/radiographic outcomes for patients undergoing SRS for AM/MMs.

Methods: An international, multicenter, retrospective cohort study was performed to define clinical/imaging outcomes for patients receiving SRS for AM/MMs. Tumor progression was assessed with response assessment in neuro-oncology (RANO) criteria. Factors associated with PFS/OS were assessed using Kaplan-Meier analysis and a Cox proportional hazards model.

Results: A total of 271 patients received SRS for AMs (n = 233, 85.9%) or MMs (n = 38, 14.0%). Single-fraction SRS was most commonly employed (n = 264, 97.4%) with a mean target dose of 14.8 Gy. SRS was used as adjuvant treatment (n = 85, 31.4%), salvage therapy (n = 182, 67.2%), or primary therapy (1.5%). The 5-yr PFS/OS rate was 33.6% and 77.0%, respectively. Increasing age (hazard ratio (HR) = 1.01, P < .05) and a Ki-67 index > 15% (HR = 1.66, P < .03) negatively correlated with PFS. MMs (HR = 3.21, P < .05), increased age (HR = 1.04, P = .04), and reduced KPS (HR = 0.95, P = .04) were associated with shortened OS. Adjuvant versus salvage SRS did not impact PFS/OS. A shortened interval between surgery and SRS improved PFS for AMs (HR = 0.99, P = .02) on subgroup analysis. Radiation necrosis occurred in 34 (12.5%) patients. Five-year rates of repeat surgery/radiation were 33.8% and 60.4%, respectively.

Conclusion: AM/MMs remain challenging tumors to treat. Elevated proliferative indices are associated with tumor recurrence, while MMs have worse survival. SRS can control AM/MMs in the short term, but the 5-yr PFS rates are low, underscoring the need for improved treatment options for these patients.
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April 2021
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