bluuebunny/crossref_metadata_2025_split huggingface dataset:
RTHP-04. PEDIATRIC STEREOTACTIC RADIOSURGERY FOR BENIGN NEUROLOGIC DISEASE: A 25-YEAR INSTITUTIONAL EXPERIENCE
Authors: Sherry Alexander , Bingham Brian , Kim Ellen , Facer Benjin , Chukwuma Valentine , Luo Guozhen , Attia Albert , Vogel Jennifer , Cmelak Anthony 
Published: November 2019

Abstract
Long-term outcomes and sequalae of pediatric stereotactic radiosurgery (SRS) for benign neurologic disease are poorly understood. We sought to explore the efficacy and late effects of SRS in pediatric patients treated our institution. After institutional review board approval, we performed a retrospective analysis of patients age 21 or younger treated between 1990 and 2016. Covariates were summarized with descriptive statistics. 56 consecutive patients were enrolled. Patients were primarily Caucasian (n=51, 93%) males (n=30, 54%). Diagnoses included arterio-venous malformation (n=41, 73%) and functional pituitary adenoma (n=9, 16%) as well as vestibular schwannoma, craniopharyngioma, meningioma, papilloma, and ganglioglioma. Average age was 14 years (95% CI 13–16 years). SRS was often the first intervention (n=22, 44%); treatments prior to SRS included embolization (n=18, 36%) and surgery (n=10, 20%). SRS was typically single fraction (n=45, 94%) with a median total dose of 16 Gy (IQR 15–18 Gy). Most patients had no acute side effects of SRS (n=40, 87%). Median follow-up time after SRS was 12 years (IQR 6–18 years, max 26 years). 91% of patients had no late sequelae of SRS. One patient was diagnosed with radionecrosis one year after repeat SRS for residual malformation. Two patients had malformation hemorrhage. One patient with brainstem malformation developed focal weakness after ischemia from treatment effect; another patient with malformation developed seizures related to SRS edema. Over 673 patient-years following SRS, no patient developed radiation-induced malignancy or malignant transformation. Median disease-free survival after SRS was 6 years (IQR 3–13) with 66% overall local control; 84% of local failures occurred within 5 years of SRS. At last follow-up, 95% of patients remained without evidence of disease with 100% overall survival. These data support the long-term safety and efficacy of pediatric SRS.
RTHP-11. THE EFFECT OF PRESCRIPTION ISODOSE LINE ON LOCAL CONTROL AND RADIOGRAPHIC RESPONSE IN GAMMA KNIFE RADIOSURGERY OF VESTIBULAR SCHWANNOMA
Authors: Teyateeti Achiraya , Graffeo Christopher , Perry Avital , Brown Paul , Pollock Bruce , Michael Link 
Published: November 2019

Abstract
Traditionally, the 50% isodose line (IDL) is used for prescription dose when vestibular schwannomas (VS) are treated with Gamma Knife radiosurgery (GKRS). To compare the effect of IDL on treatment outcomes, propensity score-matched analysis according to age at time of GKRS and tumor volume (TV) between cohorts treated at 40%IDL and 50%IDL was performed. Patients with no history of neurofibromatosis, GKRS prescribed marginal dose of 12–14 Gy and TV ≤ 10 cc were identified. Patients were excluded if follow-up time was < 2 years. Eventually, 30 and 28 patients were included in 40%IDL and 50%IDL cohorts, respectively. Mean age and TV were not significantly different between 40%IDL and 50%IDL groups; 54.5 versus 54.0 years (p=0.891) and 2148.61 versus 2031.10 mm3 (p=0.844), respectively. Median prescription dose was 12 Gy in both groups. At median follow-up times of 111 and 72 months, the 2, 5 and 10-year local control were 100%, 96.4% and 96.4% for 40%IDL and 96.4%, 86.7%, and 86.7% for 50%IDL (p=0.243), respectively. Among 40 patients with accessible follow-up MRIs (40%IDL-n=19, 50%IDL-n=21), volume reduction at last follow-up MRIs and rate of reduction per year for 40%IDL and 50%IDL were 48.1% versus 38.3% (p=0.05) and 5.5% versus 6% (p=0.749), respectively. Of 21 patients with serviceable hearing prior to GKRS and available audiograms after GKRS (40%IDL-n=8, 50%IDL-n=13), the 2, 5 and 10-year hearing preservation rate were 100%, 83.3% and 62.5% for 40%IDL versus 76.2%, 57.1% and 11.4% for 50%IDL (p=0.017). Facial paresthesia, facial palsy and ataxia/gait disturbance requiring steroid and/or shunt were lower in 40%IDL compared to the 50%IDL; 6.7% versus 17.9% (p=0.208) and 3.3% versus 7.1% (p=0.532). To summarize, VS treated at 40%IDL have slightly better local control, although not statistically significant, compared to tumors treated at 50%IDL. However, hearing preservation and safety seem to be more favorable toward 40%IDL group.
RTHP-19. ANESTHETIC INDICATIONS, TECHNIQUES AND COMPLICATIONS FOR GAMMA KNIFE RADIOSURGERY
Authors: Dang Anh , Vachhani Shital , Briere Tina , Prabhu Sujit , McGovern Susan 
Published: November 2019

Abstract

PURPOSE
We sought to describe our experience regarding anesthetic indications, techniques and complications with Gamma Knife radiosurgery (GKRS).

METHODS
We retrospectively evaluated the use of anesthesia for both adult and pediatric patients at a high-volume center.

RESULTS
Twenty-two adult cases and 10 pediatric cases were identified. For adult patients, the median age was 55.5 years. Pediatric patient ages ranged from 3 to 16 years. For adult patients, indications for sedation were claustrophobia (n=16), anxiety (n=4), chronic pain (n=1), and severe comorbidity (n=1). Twenty-five patients received general anesthesia with a secure airway (GA). Seven patients received total intravenous anesthesia with spontaneous ventilation (TIVA). One of these patients required placement of an airway after initial TIVA. The median sedation to treatment ratios for pediatric patients (3.76) and adult patients (4.06) did not significantly differ (P=0.49). However, the median sedation to treatment ratios for patients who received GA (4.08) was significantly higher than patients who received TIVA (1.88, P=0.0005). Anesthetic complications included cutaneous flushing, excessive secretions and airway obstruction that required unplanned placement of an airway, wheezing attributed to propofol sedation, and unspecified anesthetic issues that resulted in a MRI scan with a suboptimal time interval. All complications occurred in adult patients.

CONCLUSIONS
Gamma Knife radiosurgery with GA was associated with a longer sedation to treatment ratio compared to TIVA. However, despite the prolonged sedation time, use of GA was associated with few complications, none of which were severe and observed only in adult patients. Practitioners should consider the need for anesthesia in adult and pediatric patients who are intolerant to GKRS due to severe claustrophobia, anxiety, or pain when evaluating patients prior to GKRS. Due to the increased risk of respiratory complications in these patients, we recommend the use of general anesthesia with a secure airway despite the prolonged sedation time.
RTHP-34. IMPROVED SURVIVAL IN CNS LYMPHOMA WITH SALVAGE LOW-DOSE WHOLE-BRAIN RADIOTHERAPY WITH FOCAL BOOST AND CONCURRENT TEMOZOLOMIDE
Authors: Selwa Katherine , Laucis Anna , Lawrence Theodore , Junck Larry , Cuneo Kyle , Kim Michelle , Wahl Daniel , Umemura Yoshie 
Published: November 2019

Abstract

OBJECTIVE
There is no standard salvage radiotherapy (RT) regimen, nor a consensus on the concurrent chemotherapy use in CNS lymphoma. We assessed the efficacy of low-dose whole-brain radiotherapy (WBRT) with focal-boost to the area of disease and concurrent temozolomide for the salvage treatment of CNS lymphoma.

METHODS
A single center retrospective study of CNS lymphoma patients seen between 01/2004 and 02/2019. The inclusion criteria were: diagnosis of CNS lymphoma, age > 18 years at diagnosis, radiation treatment to the brain, and formulation of plan at University of Michigan with at least one follow-up. Overall survival (OS) was determined by Kaplan Meier method.

RESULTS
Out of 93 patients (median age 58, 45% female), 73% were diagnosed with primary CNS lymphoma (n=68), and the remainder with secondary CNS lymphoma. Radiation modalities were WBRT alone (n=52), low-dose WBRT + focal boost (n=33) and focal RT alone (n=8). Twenty-six patients (28%) received concurrent temozolomide with radiation. Those who received WBRT+boost achieved complete response at a significantly higher rate than those who received WBRT alone (36% vs 17% respectively, p=0.047). The median OS among all groups was 45 months. There was a significant improvement in OS in patients receiving low-dose WBRT+boost compared to WBRT alone (median 65 vs 14 months respectively, p=0.016). OS was significantly longer in patients who received concurrent temozolomide than in those who did not (median 86 vs 23 months respectively, p=0.0287).

CONCLUSIONS
In CNS lymphoma salvage RT, a longer survival was observed with low-dose WBRT with focal-boost compared to WBRT alone, as well as with concurrent temozolomide. This result is limited by the selection bias to each of the treatment groups; however, the low-dose WBRT with focal-boost and concurrent temozolomide is a useful salvage alternative to standard WBRT as it may reduce long-term neurocognitive toxicity.
RTHP-39. SPINAL CORD DELINEATION BASED ON CT MYELOGRAM VERSUS T2 MRI IN SPINE SBRT CASES
Authors: Hammoudeh Lubna , Young Lee Ho , Guenette Jeffrey , Balboni Tracy 
Published: November 2019

Abstract

PURPOSE/OBJECTIVE(S)
Spinal cord (SC) delineation is critical in spine SBRT. While underestimating cord can lead to myelitis, overestimating SC may compromise PTV coverage, resulting in higher rates of tumor recurrence. CT myelogram as part of CT simulation is a radiological means of better visualizing the SC and minimizing MRI fusion error. The aim of this study is to compare SC contours based on CT simulation with myelogram and with fused MRI.

MATERIALS/METHODS
Eight patients with 9 spinal metastases treated with spine SBRT were evaluated. All patients had spinal MRI and myelogram performed prior to CT simulation. The spinal MRI was fused and the SC volume was contoured from the superior to the inferior endplate of the target vertebral body volume based on the (1) CT myelogram images and (2) fused T2 MRI images. Comparing MRI to myelogram-defined SC, centroid deviations (deviations in the center point of the cord) were assessed at every slice through the VB target volume, and maximum deviations of the cord were assessed; all are reported with descriptive statistics. The SC cc volume based on CT myelogram and MRI were compared using paired t-test.

RESULTS
Between MRI- versus myelogram- defined SC volumes, average deviations of the centroid point cord contours was 0.06cm, ranging from 0.01-0.1cm; average deviation of the outmost aspect of the contours were on average between 0.07-0.11cm. Finally, the volume of the cord was significantly smaller when defined on MRI as compared to myelogram - 2.778cc (SD=0.98) vs. 3.44cc (SD=1.43), p=0.03 - respectively There was only one case that had a SC volume based on T2 MRI that was bigger than that based on myelogram (3.5cc vs. 2.9cc).

CONCLUSIONS
These data suggest average deviations on MRI of approximately 0.1cm, largely undercontouring the SC volume based on MRI as compared to CT simulation with myelogram.
RTHP-40. EFFECT OF RIND-BASED DOSIMETRIC TECHNIQUES FOR SCALP DOSE REDUCTION IN BRAIN IRRADIATION
Authors: No Diana , Julie Diana , Knisely Jonathan 
Published: November 2019

Abstract

OBJECTIVE
Radiation-induced alopecia is an unwanted side effect causing permanent cosmetic distress if hair regrowth does not occur. Rind-based techniques can effectively control dosimetric spread. We evaluated this technique to reduce scalp dose and alopecia while maintaining tumor coverage.

METHODS
Ten consecutive brain tumor plans were retrospectively evaluated. All planning tumor volume (PTV) margins were ≤ 15.0mm from the skin surface. Departmental guidelines for fractionation were followed, with minimum 95% PTV coverage receiving 100% dose. Fractionation variation was accounted for with biologically effective dose calculation (alpha/beta=2). Rind structures encompassed 5mm depth from scalp surface; upper dose limits were customized to minimum values without PTV coverage compromise. Standard comparative plans using identical criteria, without rind structures, were calculated. Scalp dose evaluation was defined for tissue from skin to 5mm depth. Paired T-tests were used for comparative evaluation.

RESULTS
Median age: 58 (range 27–85); 70% female (n=7). Histologies included gliomas (n=7) and meningiomas (n=3). Median PTV distance to skin surface: 13.5mm (range 8.0–15.0). Median PTV minimum and mean dose for rind-based plans: 88.63% (range 73.14–95.2) and 104.39% (range 102.07–107.38) of prescription and 90.90% (range 68.64–98.21) and 103.02% (range 101.91–107.04) for standard plans, respectively. Statistically significant reduction in scalp maximum and mean dose of 19.65% (p=2.72E-06) and 0.48% (p=0.007), respectively, was seen with rind-based planning. Scalp volume receiving 1000cGy-equivalent increased 6.7cc using rind-based techniques, although insignificant (p=0.33). Volume receiving 1500cGy-equivalent was significantly reduced 3.88cc (p=0.03) using rind-based techniques. With median 28.5 day follow-up, of 5 patients treated using rind-based techniques, 40% (n=2) exhibited acute alopecia compared to 100% of those treated with standard plans.

CONCLUSION
Rind-based dosimetric techniques exhibit significant reduction of scalp dose in brain irradiation. 60% of patients treated using this technique experienced no alopecia, versus 0% receiving standard treatment. Further investigation is warranted to better evaluate correlation.
RBTT-12. A PHASE I STUDY OF EGFRVIII-DIRECTED CAR T CELLS COMBINED WITH PD-1 INHIBITION IN PATIENTS WITH NEWLY, DIAGNOSED, MGMT-UNMETHYLATED GLIOBLASTOMA: TRIAL IN PROGRESS
Authors: Bagley Stephen , Desai Arati , Binder Zev , Nasrallah MacLean , Hwang Wei-Ting , Maloney-Wilensky Eileen , Prior Timothy , Brem Steven , O’Rourke Donald 
Published: November 2019

Abstract

BACKGROUND
This study builds on the results of the University of Pennsylvania sponsored phase I study of a single peripheral infusion of chimeric antigen receptor (CAR) T cells targeting epidermal growth factor receptor variant III (EGFRvIII) in recurrent glioblastoma (GBM) (NCT02209376). A dose of 5x108 CART-EGFRvIII cells was safe, and the cells were able to expand in the host and reach the GBM tumor in the brain. In addition, there was no cross-reactivity of CART-EGFRvIII cells with wild-type EGFR normally expressed by human tissues. Some patients required tumor resection after CAR T cell infusion. In situ evaluation of the tumor microenvironment demonstrated increased and robust expression of inhibitory molecules, such as programmed death-ligand 1 (PD-L1), compared to pre–CART-EGFRvIII tumor specimens. Therefore, we hypothesized that using a combination of CART-EGFRvIII cells and a PD-1 inhibitor would improve the outcome of the treatment.

METHODS
This single-center study (NCT03726515) has a single-arm, open-label, phase 1 design and will enroll 7 patients with newly diagnosed, O6-methylguanine-methyltransferase (MGMT)-unmethylated, EGFRvIII+ GBM. Following maximal safe tumor resection, patients receive a short course of adjuvant radiation with a total dose of 40 Gy administered in 15 fractions. Peripheral IV infusions of 2x108 CART-EGFRvIII cells and 200mg pembrolizumab begin 2–3 weeks after completing radiation therapy. Thereafter, subjects receive CART-EGFRvIII cells + pembrolizumab in 3-week cycles for up to 3 infusions of CART-EGFRvIII cells and 4 infusions of pembrolizumab. The primary endpoint of the study is the safety and tolerability of administering multiple infusions of CART-EGFRvIII cells in combination with pembrolizumab, as measured by the occurrence of study-related adverse events. Secondary endpoints include overall survival, progression-free survival, and objective response rate. PROGRESS: At 5 June 2019, 2 patients have been enrolled and treated on study.
RARE-19. ASSOCIATION BETWEEN METHOTREXATE TOXICITY AND GENETIC VARIANTS OF METHIONINE AND FOLATE METABOLISM RELATED GENES IN PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA PATIENTS
Authors: Ho Ka-wai , Wu Synphen , Baser Raymond , Orlow Irene , Correa Denise 
Published: November 2019

Abstract

BACKGROUND
Methotrexate (MTX) is the backbone of therapy for primary central nervous system lymphoma (PCNSL). There have been conflicting results over whether polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) and transcobalamin 2 (TCN2) genes modulate MTX-associated toxicity.

METHODS
This is a retrospective study involving patients who underwent MTX-based chemotherapy for PCNSL and were genotyped for polymorphisms in the MTHFR (Ala222Val, C >T; Glu429Ala, A >C) and TCN (Arg259Pro, C >T) genes as part of a separate study investigating the association of genetic risk factors for treatment-related cognitive dysfunction. Renal, hepatic, and bone marrow toxicities were graded according to CTCAEv5.0, and only toxicities grade 3 or higher were considered clinically significant. MRIs of the brain during and after MTX treatment were rated for white matter changes (WMC) and cortical atrophy (CA). Genotypes were cross-tabulated with toxicities and worsening of WMC and CA. Associations were tested using Fisher’s exact tests.

RESULTS
We identified 35 PCNSL patients treated with MTX and had available genotyping data. 18 patients (51%) carried one or more MTHFR-T (c.222 Val) alleles, 16 patients (46%) had one or more MTHFR- C (c.429 Ala) alleles, and 30 patients (86%) had one or more TCN-G (c. 259 Pro) alleles. Bivariate analysis revealed that the MTHFR-T (c.222Val) allele was associated with increased hepatotoxicity (p=0.03). None of the polymorphisms tested were associated with renal or bone marrow toxicity. Though changes in CA were observed, the association of polymorphisms with WMC or CA did not reach statistical significance, potentially confounded by small sample size and limited sensitivity of rating scales.

CONCLUSION
These preliminary observations suggest that the Val on codon 222 of the MTHFR gene might be involved in the modulation of toxicity, however a larger study is required to assess whether variants involved in methionine metabolism may influence MTX-associated hepatotoxicity in PCNSL patients.
RARE-23. HIGH DOSE METHOTREXATE WITH OR WITHOUT VINCRISTINE FOR PRIMARY CNS LYMPHOMA, THE OHIO STATE UNIVERSITY EXPERIENCE
Authors: Freeman Tracelyn , Legasto Carlo , Schickli Alex , McLaughlin Eric , Giglio Pierre , Puduvalli Vinay , Gonzalez Javier 
Published: November 2019

Abstract

OBJECTIVES
1) Determine the response rate (RR) after chemotherapy with high-dose methotrexate with or without vincristine in patients with primary CNS lymphoma. 2) Determine the difference in adverse effects with the use of vincristine. 3) Determine the difference in progression-free survival (PFS) and overall survival (OS) between the 2 groups.

METHODS
Retrospective study in patients 18–89 years with primary CNS lymphoma that received chemotherapy with rituximab (R), methotrexate (M), procarbazine (P), and vincristine (V) R-MPV, R-MV, R-MP, or R-M between 2010 and 2018 at The Ohio State University. Response rate by cycle 7 was compared with odds ratio. Kaplan-Meier curves were used to compare OS and PFS.

RESULTS
29 patients were included: 16 (55%) received vincristine. 14/16 patients treated with vincristine and 4/13 in the other group also had procarbazine. 12/29 patients had a complete response after a maximum of 7 cycles. The odds of complete response were 24% higher in patients treated with vincristine but the difference did not reach statistical significance. Side effects were higher in the vincristine arm. The most common was peripheral neuropathy (75% vs 8% - all grades). Median PFS was 60.7 months for the vincristine group and 23.7 months for the non-vincristine group. Median OS was 85.3 months for the vincristine group and 67.1 months for the non-vincristine group. OS and PFS curves did not differ significantly.

CONCLUSIONS
The use of vincristine in high-dose methotrexate chemotherapy regimens for CNS lymphoma was not associated with a statistically significant difference in RR. Patients who received vincristine had more side effects and there were no significant differences in OS and PFS. The sample size and rate of procarbazine use may be confounding factors. Further studies are necessary to determine the effect of vincristine in RR and OS in these patients.
RARE-32. POLYMORPHOUS LOW-GRADE NEUROEPITHELIAL TUMOR OF THE YOUNG (PLNTY): GENETIC ANALYSIS CONFIRMS FREQUENT MAPK PATHWAY ACTIVATION
Authors: Ida Cristiane , Johnson Derek , Kollmeyer Thomas , Kim DongKun , Kaufmann Timothy , Kipp Benjamin , Jenkins Robert , Giannini Caterina 
Published: November 2019

Abstract
Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a recently described epileptogenic tumor characterized by oligodendroglioma-like components, aberrant CD34 expression, and genetic MAPK pathway activation through alterations such as BRAF V600E mutation, and FGFR2-KIAA1598/CTNNA3 and FGFR3-TACC3 fusions. We report the molecular profiling of PLNTY in 9 patients, 7 female: 2 male, median age at diagnosis of 16 years (range, 5–34). All tumors were supratentorial with diagnostic morphological features of PLNTY including oligodendroglioma-like areas and strong diffuse CD34 immunostaining. Four (of 9; 44%) tumors were positive for BRAF V600E immunostain, indicating the presence of a BRAF V600E mutation. The 6 cases evaluated for IDH status were negative by IDH1-R132H immunostain (n=5; 3 BRAF V600E-negative and 2 BRAF V600E-positive) or by NGS (n=1; BRAF V600E-negative). Oncoscan chromosomal microarray performed in 5 BRAF V600E-negative tumors showed recurrent copy number changes including gain of whole chromosomes 5, 7, 8, 9, 12, 18, 19, 20, 21 and X, and loss of chromosomes 1, 2, 10q, 13, 22 and Xq. The 10q losses (n=2) were highly suggestive of an FGFR2-KIAA1598 and of a potentially novel FGFR2 underlying fusion event in one case each. Custom targeted neuro-oncology DNA and RNA NGS panel performed in 2 cases revealed a fusion similar to fusions previously reported in pilocytic astrocytoma: one with a KIAA1549-BRAF (exon 15-exon 9) fusion associated with a 7q34 ~785 kilobase deletion rather than the characteristic ~2 megabase duplication seen in pilocytic astrocytoma, and another with a QKI-NTRK2 (exon 6-exon 15) fusion associated with a 9q21 ~191 kilobase duplication disrupting NTRK2. The KIAA1549-BRAF fusion-positive case also had a TP53 mutation with loss of whole chromosome 17, suggesting TP53 complete inactivation. This study confirms that PLNTY is a low-grade neuroepithelial tumor with frequent MAPK pathway activation and expands the spectrum of MAPK activating alterations observed in PLNTY.