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1.
Chemistry ; 30(27): e202400719, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38462510

ABSTRACT

A visible-light-induced strategy has been explored for the synthesis of naphtho[2,1-d]thiazol-2-amines through ortho-C-H sulfuration of 2-isocyanonaphthalenes with elemental sulfur and amines under external photocatalyst-free conditions. This three-component reaction, which utilizes elemental sulfur as the odorless sulfur source, molecular oxygen as the clean oxidant, and visible light as the clean energy source, provides a mild and efficient approach to construct a series of naphtho[2,1-d]thiazol-2-amines. Preliminary mechanistic studies indicated that visible-light-promoted photoexcitation of reaction intermediates consisting of thioureas and DBU might be involved in this transformation.

2.
J Neurooncol ; 148(2): 291-297, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32350779

ABSTRACT

PURPOSE: PD-1 Immunotherapy is integral in treating multiple cancers, but has been associated with neurological adverse events (nAEs). Our study was aimed at identifying the clinical spectrum of nAEs associated with pembrolizumab and nivolumab. METHODS: We performed an IRB approved single-center retrospective cohort study on patients receiving either pembrolizumab or nivolumab. Patients that developed nAEs within 12 months of treatment were identified. Descriptive statistics were conducted, and differences between groups were analyzed by the Chi-square or t test method. RESULTS: In total, 649 patients were identified. Seventeen patients (2.6%) developed nAEs. Eight of those were on pembrolizumab and nine were on nivolumab. Average age was 62.1 years. Ten were males and 7 were females. Most patients had melanoma (6, 35.3%). Patients who developed nAEs more frequently had intracranial lesions at initiation of anti PD-1 therapy compared to those who did not develop nAEs (76.5% vs 27.8%; p-value < 0.001). Fifteen patients (88.2%) permanently stopped PD-1 therapy. In 8 patients, treatment termination resolved symptoms attributed to immune checkpoint blockade. The majority of patients developed grade 3 or 4 nAEs (10 patients, 58.8%), and required hospitalization (11 patients, 64.7%). Eight patients died for nAEs referable causes. CONCLUSION: Pembrolizumab and nivolumab are associated with the development of nAEs associated with increased risk of permanent discontinuation of treatment, hospitalization, and death. Melanoma patients might be at a particularly high risk of such side effects. Future studies are still required to better assess which patients benefit most from such therapies, while minimizing the risk of complications.


Subject(s)
Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Agents, Immunological/administration & dosage , Immune Checkpoint Inhibitors/adverse effects , Neoplasms/therapy , Nervous System Diseases/chemically induced , Nivolumab/adverse effects , Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Humans , Male , Middle Aged , Neoplasms/complications , Neoplasms/immunology , Retrospective Studies , Treatment Outcome , Young Adult
3.
Mol Cancer ; 18(1): 21, 2019 02 07.
Article in English | MEDLINE | ID: mdl-30732625

ABSTRACT

Vascular damage is followed by vascular endothelial growth factor (VEGF) expression at high levels, which is an important mechanism forradiation brain necrosis development. Bevacizumab alleviates brain edema symptoms caused by radiation brain necrosis through inhibiting VEGF and acting on vascular tissue around the brain necrosis area. Many studies have confirmed that bevacizumab effectively relieves symptoms caused by brain necrosis, improves patients' Karnofsky performance status (KPS) scores and brain necrosis imaging. However, necrosis is irreversible, and hypoxia and ischemia localized in the brain necrosis area may easily lead to radiation brain necrosis recurrence after bevacizumab is discontinued. Further studies are necessary to investigate brain necrosis diagnoses, bevacizumab indications, and the optimal mode of administration, bevacizumab resistance and necrosis with a residual or recurrent tumor.


Subject(s)
Angiogenesis Inhibitors/therapeutic use , Bevacizumab/therapeutic use , Brain Ischemia/drug therapy , Necrosis/drug therapy , Neovascularization, Pathologic/prevention & control , Radiation Injuries/drug therapy , Brain/blood supply , Brain/drug effects , Brain/pathology , Brain/radiation effects , Brain Ischemia/genetics , Brain Ischemia/pathology , Drug Resistance/genetics , Gamma Rays/adverse effects , Gene Expression , Humans , Necrosis/genetics , Necrosis/pathology , Neovascularization, Pathologic/genetics , Neovascularization, Pathologic/pathology , Radiation Injuries/genetics , Radiation Injuries/pathology , Recurrence , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolism
4.
Stereotact Funct Neurosurg ; 97(3): 189-194, 2019.
Article in English | MEDLINE | ID: mdl-31590165

ABSTRACT

OBJECTIVE/BACKGROUND: We report efficacy and toxicity outcomes with stereotactic radiosurgery (SRS) for intracranial and spinal ependymoma. METHODS: We analyzed adult and pediatric patients with newly diagnosed or recurrent intracranial or spinal ependymoma lesions treated with SRS at our institution. Following SRS, local failure (LF) was defined as failure within or adjacent to the SRS target volume, while distant failure (DF) was defined as failure outside of the SRS target volume. Time to LF and DF was analyzed using competing risk analysis with death as a competing risk.Overall survival (OS) was calculated from the date of first SRS to the date of death or censored at the date of last follow-up using the Kaplan-Meier method. RESULTS: Twenty-one patients underwent SRS to 40 intracranial (n = 30) or spinal (n = 10) ependymoma lesions between 2007 and 2018, most commonly with 18 or 20 Gy in 1 fraction. Median follow-up for all patients after first SRS treatment was 54 months (range 2-157). The 1-year, 2-year, and 5-year rates of survival among patients with initial intracranial ependymoma were 86, 74, and 52%, respectively. The 2-year cumulative incidences of LF and DF after SRS among intracranial ependymoma patients were 25% (95% CI 11-43) and 42% (95% CI 22-60), respectively. No spinal ependymoma patient experienced LF, DF, or death within 2 years of SRS. Three patients had adverse radiation effects. CONCLUSIONS: SRS is a viable treatment option for intracranial and spinal ependymoma with excellent local control and acceptable toxicity.


Subject(s)
Brain Neoplasms/surgery , Ependymoma/surgery , Radiosurgery/methods , Spinal Neoplasms/surgery , Adolescent , Adult , Brain Neoplasms/diagnostic imaging , Child , Child, Preschool , Ependymoma/diagnostic imaging , Female , Follow-Up Studies , Humans , Infant , Male , Middle Aged , Retrospective Studies , Spinal Neoplasms/diagnostic imaging , Young Adult
5.
Postgrad Med J ; 95(1119): 1-5, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30674619

ABSTRACT

BACKGROUND: Decreasing delays for hospitalised patients results in improved hospital efficiency, increased quality of care and decreased healthcare expenditures. Delays in subspecialty consultations and procedures can cause increased length of stay due to reasons outside of necessary medical care. OBJECTIVE: To quantify, describe and record reasons for delays in consultations and procedures for patients on the general medicine wards. METHODOLOGY: We conducted weekly audits of all admitted patients on five Internal Medicine teams over 8 weeks. A survey was reviewed with attending physicians and residents on five internal medicine teams to identify patients with a delay due to consultation or procedure, quantify length of delay and record reason for delay. RESULTS: During the study period, 316 patients were reviewed and 48 were identified as experiencing a total of 53 delays due to consultations or procedures. The average delay was 1.8 days for a combined total of 83 days. Top reasons for delays included scheduling, late response to page and a busy service. The frequency in length of consult delays vary among different specialties. The highest frequency of delays was clustered in procedure-heavy specialties. CONCLUSION: This report highlights the importance of reviewing system barriers that lead to delayed service in hospitals. Addressing these delays could lead to reductions in length of stay for inpatients.


Subject(s)
Appointments and Schedules , Inpatients/statistics & numerical data , Internal Medicine , Length of Stay/statistics & numerical data , Referral and Consultation/statistics & numerical data , Adult , Aged , Female , Humans , Male , Middle Aged , Prospective Studies , Quality Improvement , Time Factors
6.
Molecules ; 24(7)2019 Mar 28.
Article in English | MEDLINE | ID: mdl-30925755

ABSTRACT

We describe progress and obstacles in the development of novel peptide-hydrogel therapeutics for unmet medical needs in ischemia treatment, focusing on the development and translation of therapies specifically in peripheral artery disease (PAD). Ischemia is a potentially life-threatening complication in PAD, which affects a significant percentage of the elderly population. While studies on inducing angiogenesis to treat PAD were started two decades ago, early results from animal models as well as clinical trials have not yet been translated into clinical practice. We examine some of the challenges encountered during such translation. We further note the need for sustained angiogenic effect involving whole growth factor, gene therapy and synthetic growth factor strategies. Finally, we discuss the need for tissue depots for de novo formation of microvasculature. These scaffolds can act as templates for neovasculature development to improve circulation and healing at the preferred anatomical location.


Subject(s)
Angiogenic Proteins/therapeutic use , Ischemia/drug therapy , Translational Research, Biomedical , Animals , Disease Models, Animal , Drug Discovery , Humans , Neovascularization, Physiologic/drug effects
7.
J Am Chem Soc ; 137(14): 4823-30, 2015 Apr 15.
Article in English | MEDLINE | ID: mdl-25831137

ABSTRACT

Self-assembly of multidomain peptides (MDP) can be tailored to carry payloads that modulate the extracellular environment. Controlled release of growth factors, cytokines, and small-molecule drugs allows for unique control of in vitro and in vivo responses. In this study, we demonstrate this process of ionic cross-linking of peptides using multivalent drugs to create hydrogels for sustained long-term delivery of drugs. Using phosphate, heparin, clodronate, trypan, and suramin, we demonstrate the utility of this strategy. Although all multivalent anions result in good hydrogel formation, demonstrating the generality of this approach, suramin led to the formation of the best hydrogels per unit concentration and was studied in greater detail. Suramin ionically cross-linked MDP into a fibrous meshwork as determined by scanning and transmission electron microscopy. We measured material storage and loss modulus using rheometry and showed a distinct increase in G' and G″ as a function of suramin concentration. Release of suramin from scaffolds was determined using UV spectroscopy and showed prolonged release over a 30 day period. Suramin bioavailability and function were demonstrated by attenuated M1 polarization of THP-1 cells compared to positive control. Overall, this design strategy has allowed for the development of a novel class of polymeric delivery vehicles with generally long-term release and, in the case of suramin, cross-linked hydrogels that can modulate cellular phenotype.


Subject(s)
Drug Carriers/chemistry , Hydrogels/chemistry , Nanofibers/chemistry , Oligopeptides/chemistry , Pharmaceutical Preparations/chemistry , Animals , Cell Line , Delayed-Action Preparations , Drug Liberation , Female , Humans , Models, Molecular , Molecular Conformation , Rats
8.
Chem Commun (Camb) ; 59(38): 5701-5704, 2023 May 09.
Article in English | MEDLINE | ID: mdl-37083729

ABSTRACT

The conversion of paramagnetic solid iron oxides to magnetic iron oxides has drawn considerable interest, but it's still challenging to carry out without heat treatment or irradiation. In this work, solid amorphous iron oxide chrysanthemum-like nanosheets synthesized by a smart redox strategy at the interface of a soap-free emulsion are magnetized at room temperature and under ambient pressure. An amorphous FeOOH hollow shell with needles towards water is produced by the reaction of cumyl hydroperoxide (CHPO) and iron(II) sulfate (FeSO4) at the interface of the emulsion generated by ultrasound and torn up into chrysanthemum-like nanosheets simultaneously. With the presence of noble metal ions, such as Au3+, the magnetization of the nanosheets was carried out as soon as sodium borohydride (NaBH4) was introduced into the dispersion. The magnetic chrysanthemum-like nanosheets present saturation magnetization (Ms) of 32 emu g-1 and can be placed linearly in a magnetic field.

9.
Patterns (N Y) ; 3(1): 100400, 2022 Jan 14.
Article in English | MEDLINE | ID: mdl-35079716

ABSTRACT

Data labeling is often the limiting step in machine learning because it requires time from trained experts. To address the limitation on labeled data, contrastive learning, among other unsupervised learning methods, leverages unlabeled data to learn representations of data. Here, we propose a contrastive learning framework that utilizes metadata for selecting positive and negative pairs when training on unlabeled data. We demonstrate its application in the healthcare domain on heart and lung sound recordings. The increasing availability of heart and lung sound recordings due to adoption of digital stethoscopes lends itself as an opportunity to demonstrate the application of our contrastive learning method. Compared to contrastive learning with augmentations, the contrastive learning model leveraging metadata for pair selection utilizes clinical information associated with lung and heart sound recordings. This approach uses shared context of the recordings on the patient level using clinical information including age, sex, weight, location of sounds, etc. We show improvement in downstream tasks for diagnosing heart and lung sounds when leveraging patient-specific representations in selecting positive and negative pairs. This study paves the path for medical applications of contrastive learning that leverage clinical information. We have made our code available here: https://github.com/stanfordmlgroup/selfsupervised-lungandheartsounds.

10.
J Am Med Inform Assoc ; 29(11): 1908-1918, 2022 10 07.
Article in English | MEDLINE | ID: mdl-35994003

ABSTRACT

OBJECTIVE: Chest pain is common, and current risk-stratification methods, requiring 12-lead electrocardiograms (ECGs) and serial biomarker assays, are static and restricted to highly resourced settings. Our objective was to predict myocardial injury using continuous single-lead ECG waveforms similar to those obtained from wearable devices and to evaluate the potential of transfer learning from labeled 12-lead ECGs to improve these predictions. METHODS: We studied 10 874 Emergency Department (ED) patients who received continuous ECG monitoring and troponin testing from 2020 to 2021. We defined myocardial injury as newly elevated troponin in patients with chest pain or shortness of breath. We developed deep learning models of myocardial injury using continuous lead II ECG from bedside monitors as well as conventional 12-lead ECGs from triage. We pretrained single-lead models on a pre-existing corpus of labeled 12-lead ECGs. We compared model predictions to those of ED physicians. RESULTS: A transfer learning strategy, whereby models for continuous single-lead ECGs were first pretrained on 12-lead ECGs from a separate cohort, predicted myocardial injury as accurately as models using patients' own 12-lead ECGs: area under the receiver operating characteristic curve 0.760 (95% confidence interval [CI], 0.721-0.799) and area under the precision-recall curve 0.321 (95% CI, 0.251-0.397). Models demonstrated a high negative predictive value for myocardial injury among patients with chest pain or shortness of breath, exceeding the predictive performance of ED physicians, while attending to known stigmata of myocardial injury. CONCLUSIONS: Deep learning models pretrained on labeled 12-lead ECGs can predict myocardial injury from noisy, continuous monitor data early in a patient's presentation. The utility of continuous single-lead ECG in the risk stratification of chest pain has implications for wearable devices and preclinical settings, where external validation of the approach is needed.


Subject(s)
Chest Pain , Electrocardiography , Biomarkers , Chest Pain/diagnosis , Chest Pain/etiology , Dyspnea/diagnosis , Dyspnea/etiology , Electrocardiography/methods , Emergency Service, Hospital , Humans , Machine Learning , Troponin
11.
ACS Omega ; 6(11): 7558-7575, 2021 Mar 23.
Article in English | MEDLINE | ID: mdl-33778267

ABSTRACT

The Middle Permian Maokou Formation in the southeastern Sichuan Basin is a typical carbonate karst reservoir. At the end of the Middle Permian, a short-term tectonic uplift (Tungwu movement) occurred in the upper Yangtze region, causing the formation of dissolved fissures and holes. To determine the location of the high-quality reservoir, this paper calculated the eroded thickness using the Milankovitch theory. Based on the gamma logging data of the six wells in the southeastern Sichuan Basin, the dominant frequency and the astronomical time scale were evaluated via frequency spectrum analysis, continuous wavelet transform, and empirical mode decomposition. In addition, we analyzed the relationship between Fischer curve characteristics and the variation of lithology. Last, four methods were used to calculate the eroded thickness, and the rationality was analyzed. Consequently, we identified four levels of Milankovitch cycles, i.e., middle eccentricity (e2), short eccentricity (e3), long obliquity (o1), and short obliquity (o2). Also, the Fischer curves of the six wells were divided into two forms related to local structural uplift. The residual strata of the Maokou Formation comprised three complete third-order cycles, and the boundaries were the 15th, 34th, and 54th e3 cycles. The deposition rate of bioclastic limestone was the lowest (2.12-5.36 cm/ka with an average of 3.30 cm/ka), whereas the deposition rate of argillaceous limestone was the largest (2.27-5.25 cm/ka with an average of 4.09 cm/ka). Among the four methods, the missing formation deposition rate method exhibited the most precise calculation results, while that of the seismic data method was relatively low. Generally, the eroded thickness of the Maokou Formation in southeastern Sichuan was in the range of 0-140 m, i.e., the eroded thickness in the west and south of X14 was relatively large (>100 m), while the area north of LS1 experienced the weakest denudation (eroded thickness < 40 m).

12.
J Cataract Refract Surg ; 47(1): 6-10, 2021 Jan 01.
Article in English | MEDLINE | ID: mdl-32932371

ABSTRACT

Differences between target and implanted intraocular lens (IOL) power in Ethiopian cataract outreach campaigns were evaluated, and machine learning (ML) was applied to optimize the IOL inventory and minimize avoidable refractive error. Patients from Ethiopian cataract campaigns with available target and implanted IOL records were identified, and the diopter difference between the two was measured. Gradient descent (an ML algorithm) was used to generate an optimal IOL inventory, and we measured the models performance across varying surplus levels. Only 45.6% of patients received their target IOL power and 23.6% received underpowered IOLs with current inventory (50% surplus). The ML-generated IOL inventory ensured that more than 99.5% of patients received their target IOL when using only 39% IOL surplus. In Ethiopian cataract campaigns, most patients have avoidable postoperative refractive error secondary to suboptimal IOL inventory. Optimizing the IOL inventory using this ML model might eliminate refractive error from insufficient inventory and reduce costs.


Subject(s)
Cataract , Lenses, Intraocular , Ophthalmology , Artificial Intelligence , Humans , Machine Learning , Refraction, Ocular , Visual Acuity
13.
Bioengineering (Basel) ; 8(12)2021 Nov 23.
Article in English | MEDLINE | ID: mdl-34940343

ABSTRACT

Pro-angiogenic and anti-angiogenic peptide hydrogels were evaluated against the standard of care wet age-related macular degeneration (AMD) therapy, Aflibercept (Eylea®). AMD was modeled in rats (laser-induced choroidal neovascularization (CNV) model), where the contralateral eye served as the control. After administration of therapeutics, vasculature was monitored for 14 days to evaluate leakiness. Rats were treated with either a low or high concentration of anti-angiogenic peptide hydrogel (0.02 wt% 8 rats, 0.2 wt% 6 rats), or a pro-angiogenic peptide hydrogel (1.0 wt% 7 rats). As controls, six rats were treated with commercially available Aflibercept and six with sucrose solution (vehicle control). Post lasering, efficacy was determined over 14 days via fluorescein angiography (FA) and spectral-domain optical coherence tomography (SD-OCT). Before and after treatment, the average areas of vascular leak per lesion were evaluated as well as the overall vessel leakiness. Unexpectedly, treatment with pro-angiogenic peptide hydrogel showed significant, immediate improvement in reducing vascular leak; in the short term, the pro-angiogenic peptide performed better than anti-angiogenic peptide hydrogel and was comparable to Aflibercept. After 14 days, both the pro-angiogenic and anti-angiogenic peptide hydrogels show a trend of improvement, comparable to Aflibercept. Based on our results, both anti-angiogenic and pro-angiogenic peptide hydrogels may prove good therapeutics in the future to treat wet AMD over a longer-term treatment period.

14.
Chem Commun (Camb) ; 56(72): 10497-10500, 2020 Sep 16.
Article in English | MEDLINE | ID: mdl-32776053

ABSTRACT

A robust thermo-responsive polymeric Janus cage with a PNIPAM-cPVBC-PEO sandwiched shell is synthesized. The Janus cage provides a general method of thermally triggered separation of oil/water emulsions independent of the type of surfactant and emulsion. It can selectively capture organic compounds at a higher temperature and release them at a lower temperature.

15.
Neurooncol Pract ; 7(6): 626-635, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33312677

ABSTRACT

BACKGROUND: Despite putative benefits associated with proton radiotherapy in the setting of CNS tumors, numerous barriers limit treatment accessibility. Given these challenges, we explored the association of proton use with variations in treatment timing. METHODS: Pediatric and adult patients with histologically confirmed CNS tumors were identified from the National Cancer Database (2004-2015). Univariable and multivariable regression models were constructed to assess factors impacting radiation timing. Multivariable Cox regression was used to evaluate the effect of treatment delay on survival. RESULTS: A total of 76 157 patients received photon or proton radiotherapy. Compared to photons, time to proton administration was longer in multiple pediatric (embryonal, ependymal, nonependymal glial, and other) and adult (ependymal, nonependymal glial, meningeal, other) tumor histologies. On adjusted analysis, proton radiotherapy was associated with longer delays in radiotherapy administration in pediatric embryonal tumors (+3.00 weeks, P = .024) and in all adult tumors (embryonal [+1.36 weeks, P = .018], ependymal [+3.15 weeks, P < .001], germ cell [+2.65 weeks, P = .024], glial [+2.15 weeks, P < .001], meningeal [+5.05 weeks, P < .001], and other [+3.06 weeks, P < .001]). In patients with high-risk tumors receiving protons, delays in adjuvant radiotherapy were independently associated with poorer survival (continuous [weeks], adjusted hazard ratio = 1.09, 95% CI = 1.02-1.16). CONCLUSIONS: Proton radiotherapy is associated with later radiation initiation in pediatric and adult patients with CNS tumors. In patients with high-risk CNS malignancies receiving protons, delayed adjuvant radiotherapy is associated with poorer survival. Further studies are needed to understand this discrepancy to maximize the potential of proton radiotherapy for CNS malignancies.

16.
Bioact Mater ; 5(2): 233-240, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32123777

ABSTRACT

Radiation therapy to treat cancer has evolved significantly since the discovery of x-rays. Yet, radiation therapy still has room for improvement in reducing side effects and improving control of cancer. Safer and more effective delivery of radiation has led us to novel techniques and use of biomaterials. Biomaterials in combination with radiation and chemotherapy have started to appear in pre-clinical explorations and clinical applications, with many more on the horizon. Biomaterials have revolutionized the field of diagnostic imaging, and now are being cultivated into the field of theranostics, combination therapy, and tissue protection. This review summarizes recent development of biomaterials in radiation therapy in several application areas.

17.
Front Oncol ; 10: 12, 2020.
Article in English | MEDLINE | ID: mdl-32117704

ABSTRACT

Objective: This study aimed to investigate the relationship between the timing of stereotactic radiosurgery (SRS) intervention and the complications of cerebral radiation necrosis (CRN) in patients with brain metastases of lung adenocarcinoma who received tyrosine kinase inhibitor (TKI) treatment. Methods: A total of 361 targets from 257 patients with brain oligometastases of lung adenocarcinoma who received CyberKnife treatment between 2010 and 2017 were retrospectively collected from three CyberKnife centers. The difference in brain necrosis between patients with or without TKI application was statistically counted. Logistic regression analysis was used to analyze the effect of applying TKI on the occurrence of CRN in patients and the effect of SRS before and after TKI resistance on CRN. Results: The rate of CRN in the TKI group was significantly higher than that in the non-TKI group. The incidence of brain necrosis in patients undergoing SRS after drug resistance was significantly higher than that in patients undergoing SRS before drug resistance. Regression analysis showed that combination of TKI with SRS, and SRS after TKI resistance were important influencing factors for CRN. Conclusion: Performing the SRS for brain metastases after TKI resistance worsened the occurrence of CRN of patients treated with TKI. Clinical Trial Registration: Chinese clinical trial registry, http://www.chictr.org.cn/edit.aspx?pid=38395&htm=4, Registration number: ChiCTR1900022750.

18.
Front Oncol ; 10: 337, 2020.
Article in English | MEDLINE | ID: mdl-32219069

ABSTRACT

Introduction: Gliosarcomas are clinically aggressive tumors, histologically distinct from glioblastoma. Data regarding the impact of extent of resection and post-operative adjuvant therapy on gliosarcoma outcomes are limited. Methods: Patients with histologically confirmed gliosarcoma diagnosed between 1999 and 2019 were identified. Clinical, molecular, and radiographic data were assembled based on historical records. Comparisons of categorical variables used Pearson's Chi-square and Fisher's exact test while continuous values were compared using the Wilcoxon signed-rank test. Survival comparisons were assessed using Kaplan-Meier statistics and Cox regressions. Results: Seventy-one gliosarcoma patients were identified. Secondary gliosarcoma was not associated with worse survival when compared to recurrent primary gliosarcoma (median survival 9.8 [3.8 to 21.0] months vs. 7.6 [1.0 to 35.7], p = 0.7493). On multivariable analysis, receipt of temozolomide (HR = 0.02, 95% CI 0.001-0.21) and achievement of gross total resection (GTR; HR = 0.13, 95% CI 0.02-0.77) were independently prognostic for improved progression-free survival (PFS) while only receipt of temozolomide was independently associated with extended overall survival (OS) (HR = 0.03, 95% CI 0.001-0.89). In patients receiving surgical resection followed by radiotherapy and concomitant temozolomide, achievement of GTR was significantly associated with improved PFS (median 32.97 [7.1-79.6] months vs. 5.45 [1.8-26.3], p = 0.0092) and OS (median 56.73 months [7.8-104.5] vs. 14.83 [3.8 to 29.1], p = 0.0252). Conclusion: Multimodal therapy is associated with improved survival in gliosarcoma. Even in patients receiving aggressive post-operative multimodal management, total surgical removal of macroscopic disease remains important for optimal outcomes.

19.
Neurosurgery ; 86(5): E426-E435, 2020 05 01.
Article in English | MEDLINE | ID: mdl-32110805

ABSTRACT

BACKGROUND: Pediatric pineoblastomas are highly aggressive tumors that portend poor outcomes despite multimodal management. Controversy remains regarding optimal disease management. OBJECTIVE: To evaluate patterns of care and optimal clinical management of pediatric pineoblastoma. METHODS: A total of 211 pediatric (age 0-17 yr) histologically confirmed pineoblastoma patients diagnosed between 2004 and 2015 were queried from the National Cancer Database. Wilcoxon rank-sum statistics and chi-squared analyses were used to compare continuous and categorical variables, respectively. Univariable and multivariable Cox regressions were used to evaluate prognostic impact of covariates. Propensity-score matching was used to balance baseline characteristics. RESULTS: Older patients (age ≥ 4 yr) experienced improved overall survival compared to younger patients (age < 4 yr) (hazard ratio [HR] = 0.41; 95% CI 0.25-0.66). Older patients (adjusted odds ratio [aOR] = 5.21; 95% CI 2.61-10.78) and those residing in high-income regions (aOR = 3.16; 95% CI 1.21-8.61) received radiotherapy more frequently. Radiotherapy was independently associated with improved survival in older (adjusted HR [aHR] = 0.31; 95% CI 0.12-0.87) but not younger (aHR = 0.64; 95% CI 0.20-1.90) patients. The benefits of radiotherapy were more pronounced in patients receiving surgery than in those not receiving surgery (aHR [surgical patients] = 0.23; 95% CI 0.08-0.65; aHR [nonsurgical patients] = 0.46; 95% CI 0.22-0.97). Older patients experienced improved outcomes associated with aggressive resection (P = .041); extent of resection was not associated with survival in younger patients (P = .880). CONCLUSION: Aggressive tumor resection was associated with improved survival only in older pediatric patients. Radiotherapy was more effective in patients receiving surgery. Age-stratified approaches might allow for improved disease management of pediatric pineoblastoma.


Subject(s)
Brain Neoplasms/therapy , Neurosurgical Procedures/methods , Pineal Gland/pathology , Pinealoma/therapy , Radiotherapy, Adjuvant/methods , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Prognosis , Treatment Outcome
20.
Pract Radiat Oncol ; 10(5): e363-e371, 2020.
Article in English | MEDLINE | ID: mdl-32428766

ABSTRACT

PURPOSE: Although consensus guidelines for postresection stereotactic radiosurgery (SRS) for brain metastases recommend the surgical corridor leading to the resection cavity be included in the SRS plan, no study has reported patterns of tumor recurrence based on inclusion or exclusion of the corridor as a target. We reviewed tumor control and toxicity outcomes of postresection SRS for deep brain metastases based on whether or not the surgical corridor was targeted. MATERIALS AND METHODS: We retrospectively reviewed patients who had resected brain metastases treated with SRS between 2007 and 2018 and included only "deep" tumors (defined as located ≥1.0 cm from the pial surface before resection). RESULTS: In 66 deep brain metastases in 64 patients, the surgical corridor was targeted in 43 (65%). There were no statistical differences in the cumulative incidences of progression at 12 months for targeting versus not targeting the corridor, respectively, for overall local failure 2% (95% confidence interval [CI], 0%-11%) versus 9% (95% CI, 1%-25%; P = .25), corridor failure 0% (95% CI, 0%-0%) versus 9% (95% CI, 1%-25%; P = .06), cavity failure 2% (95% CI, 0%-11%) versus 0% (95% CI, 0%-0%; P = .91), and adverse radiation effect 5% (95% CI, 1%-15%) versus 13% (95% CI, 3%-30%; P = .22). Leptomeningeal disease (7%; 95% CI, 2%-18%) versus 26% (95% CI, 10%-45%; P = .03) was higher in those without the corridor targeted. CONCLUSIONS: Omitting the surgical corridor in postoperative SRS for resected brain metastases was not associated with statistically significant differences in corridor or cavity recurrence or adverse radiation effect. As seen in recent prospective trials of postresection SRS, the dominant pattern of progression is within the resection cavity; omission of the corridor would yield a smaller SRS volume that could allow for dose escalation to potentially improve local cavity control.


Subject(s)
Brain Neoplasms , Radiosurgery , Brain Neoplasms/radiotherapy , Brain Neoplasms/secondary , Brain Neoplasms/surgery , Humans , Neoplasm Recurrence, Local , Prospective Studies , Radiosurgery/adverse effects , Retrospective Studies , Treatment Outcome
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