bluuebunny/crossref_metadata_2025_split huggingface dataset:
RTHP-24. TRENDS IN THE UP FRONT USE OF STEREOTACTIC RADIOSURGERY FOR GLIOBLASTOMA
Authors: Wegner Rodney , Abel Stephen , Ranjan Tulika , Williamson Richard , Yu Alexander , Xu Linda , Karlovits Stephen 
Published: November 2019

Abstract

BACKGROUND
GBM is typically managed with a combined modality approach including resection followed by adjuvant chemoradiation. Despite aggressive up front treatment local failure occurs in the vast majority of patients. The concept of dose escalation through use of stereotactic radiosurgery (SRS) was tested in RTOG 9305 in the pre-temozolomide era with the hopes of improving control, ultimately showing no benefit. We used the National Cancer Database (NCDB) to examine trends in the use of up-front SRS, to see if it had truly fallen out of favor, and if it had any impact on outcome.

METHODS
We queried the NCDB from 2004–14 for GBM patients that had radiation and 2 months of follow up. Odds ratios were used to determine predictors of SRS. Univariable and multivariable Cox regressions were used to determine potential predictors of overall survival (OS). Propensity adjusted multivariable analysis was used to account for any indication bias.

RESULTS
We identified 62,681 patients meeting eligibility criteria, of which 1,046 had SRS. SRS decreased over time from 3% to less than 1%. Predictors of SRS were increased age, government insurance, lower comorbid score, treatment at an academic facility, metropolitan location, increased distance to facility, smaller tumor, lack of surgery, no chemotherapy, and more remote year of treatment. Median overall survival was 13.1 months in the non-SRS group and 12.9 months in the SRS group, p=0.28. On multivariable analysis increased age, lack of chemotherapy, higher comorbidity score, extent of surgery, non-academic facility, decreased education, government insurance, urban location, Caucasian race, male gender, larger tumor, and more remote year of treatment predicted for worse overall survival.

CONCLUSIONS
Use of up-front SRS in the management of GBM has decreased over time, in concordance with past randomized trials examining its use. Our analysis did not show any benefit in survival with its use.
RTHP-25. TTFIELDS DOSE DISTRIBUTION ALTERS TUMOR GROWTH PATTERNS: AN IMAGING-BASED ANALYSIS OF THE RANDOMIZED PHASE 3 EF-14 TRIAL
Authors: Glas Martin , Jeyapalan Suriya , Soltys Scott , Hottinger Andreas , Toms Steven A , levi Shay , Lavy-Shahaf Gitit , Urman Noa , Pollum Erqi , Ballo Matthew 
Published: November 2019

Abstract

INTRODUCTION
A recent post-hoc analysis of the EF-14 phase 3 trial showed a connection between TTFields dose at the tumor and Overall Survival in new diagnosed Glioblastoma (ndGBM) patients [1]. Here we expand the results of that study and show a connection between TTFields dose distribution in the brain and progression patterns in ndGBM patients.

METHODS
Participants of the EF-14 trial who exhibited radiological progression were included in this study (treatment: N=306/466, control: N=122/229). Enhancing tumor was segmented on T1c MRIs at baseline and progression. Regions of progression disconnected from the original lesion were defined as distal. The rates of occurrence and distances of distal progressions from primary lesions were compared between the arms. Computational head models were created and delivery of TTFields numerically simulated for n=229 patients in treatment for over 2. Dose in regions of progression was compared to dose in regions where no progression occurred.

RESULTS
The median distance between primary and distal lesions was larger in the treatment arm (control: 14.2±14.4 mm, TTFields 23.2±29.8 mm, p=0.03 Wilcoxon rank-sum). A higher rate of distal progression outside of a 20mm boundary zone around the primary lesion was observed in the treatment arm. (Control: 10/122, TTFields: 53/306 p< 0.02 chi-squared). In proximity to the primary lesion (a 3 mm ring around the tumor), TTFields dose was lower in regions of progression than in regions where no progression occurred (0.73 mW/cm^3 vs. 0.79 mW/cm^3 p< 0.0001 t-test)

DISCUSSION AND CONCLUSIONS
This study suggests that TTFields alters progression patterns and that progression is more likely to occur in regions exposed to low TTFields dose. The study emphasizes the rationale for adaptive TTFields treatment planning targeting regions of progression. [1] Ballo et. al., IJROBP (2019)
RTHP-26. DOSIMETRIC FEASIBILITY STUDY USING HIPPOCAMPAL AVOIDANCE WITH SIMULTANEOUS INTEGRATED BOOST WHOLE BRAIN RADIOTHERAPY (HA-SIB-WBRT)
Authors: Seng Hup Chia Brendan , Li Kuan Ong Ashley , Master Zubin 
Published: November 2019

Abstract

BACKGROUND
Recently Hippocampal Avoidance (HA-) WBRT has become a recommended treatment option in patients with multiple (≥ 5) brain metastases and good prognosis. We wanted to investigate the dosimetric feasibility of dose painting technique combining HA-WBRT with a simultaneous integrated boost (SIB) to tumours.

METHOD
5 patients who had a CT simulation fused with brain MRI with fine cuts, were selected for this study. Volumes were contoured on T1w contrast images. Whole brain prescription dose was 30Gy in 12 fractions. A PTV margin of 2mm was applied to lesions, except when these were ≤5mm from organs at risks (OARs). A simultaneous integrated boost (SIB) of 48Gy and 40.2Gy was prescribed to these volumes respectively. Hippocampal constraints followed RTOG 0933 protocol. For lesions ≤5mm from OARs, the acceptable D0.03cc≤42Gy was allowed. All plans were planned on EclipseTM v.13.6 TPS using 6MV photons, VMAT technique with 3 coplanar and 1 non-coplanar arcs for Varian TrueBeam machine.

RESULTS
Plans had between 6–24 lesions with GTV and PTV of 3.02–11.32cc and 7.05–31.74cc respectively. 3 of the plans had lesions within/adjacent to brainstem or hippocampus. The achieved PTV_40.2Gy D95% 37.42–39.05Gy with Conformity Index (CI)(95%) 0.63–1.06, PTV_48Gy D95% 44.64–47.04Gy with CI(95%) 0.75–0.97 and GTV_48Gy D95% 47.44–50.16Gy. Whole brain Dmean 31.87–33.15Gy with a Homogeneity Index (D2%-D98%/Dmean) 0.18–0.58. Hippocampal D100% 8.69–10.1Gy, D0.03cc 16.5–40.43Gy and Dmean 12.66–24.68Gy. SUMMARY: There was a steep learning curve when adopting this technique and multiple plan iterations were made to achieve target constraints. To meet acceptable OAR constraints, SIB coverage was compromised. Lesions ≤5mm from hippocampus resulted in higher Hippocampal average Dmean 22.8Gy vs. 12.8Gy. The significance of this value should be tested in clinical trials. Overall, HA-SIB-WBRT seems feasible even with ≥ 5 brain metastases and could result in better brain metastases control then HA-WBRT alone.
RTHP-27. RARE INTRACRANIAL PRIMARY YOLK SAC TUMORS IN ADOLESCENT PATIENTS: A REPORT OF 10 CASES DEPARTMENT OF ONCOLOGY
Authors: Hong Weiping , Yang Yanying , Cai Linbo 
Published: November 2019

Abstract

OBJECTIVE
To retrospective analyze 10 patients with intracranial primary yolk sac tumors(YST) for exploring an optimal treatment strategy.

METHODS
Ten patients with YST were confirmed by pathological diagnosis (9 male and 1 female), with a median age of 13 years. Except for 1 case was lost to follow-up, 9 patients were treated with partial resection, followed by WBRT and local boosts, and then adjuvant chemotherapy. The time it took for serum AFP to decrease to the lowest level (including abnormal situation) or to return to the normal level was recorded. The brain tumor apoplexies before and after treatment were studied. Finally, OS and PFS of the patients were analyzed.

RESULTS
The patients were followed-up to 02-2019, with a mean follow-up time of 25.44 months. The analysis showed that the mOS and mPFS were 18 months and 7 months, respectively, and that 1y-OS and 2y-OS were 77.8% and 22.2%, while 1y-PFS and 2y-PFS were 22.2% and 11.1%. The time it took for serum AFP to decrease to the lowest level or to return to the normal level was 0–382 days, with a median time of 144 days (165.22±131.71 days). After being followed-up to 02-2019, 4 patients still survived; 4 patients died of tumor recurrence; 1 patient died of severe pneumonia. Although one of the 4 patients (tumor recurrence) was treated with 3 times of surgeries, died of tumor progression, with a survival time of 17 months. The other one patient had a 1y-PFS of 3 months, and he received surgery and chemotherapy for recurrent tumors, achieving a 2y-PFS up to 71+ months.

CONCLUSION
YST has a low incidence rate and is easy to recurrence, with a poor prognosis. Resection combined with chemoradiotherapy can prolong the survival time of patients, but the optimal treatment strategy remains unclear and needs further research.
RTHP-28. TTFIELDS TREATMENT AFFECTS TUMOR GROWTH RATES: A POST-HOC ANALYSIS OF THE PIVOTAL PHASE 3 EF-14 TRIAL
Authors: Urman Noa , Lavy-Shahaf Gitit , levi Shay , Bomzon Ze’ev 
Published: November 2019

Abstract

INTRODUCTION
The pivotal EF-14 trial showed that Tumor Treating Fields (TTFields) extend Progression Free Survival (PFS) in newly Diagnosed Glioblastoma (ndGBM) patients. This leads to the hypothesis that TTFields therapy leads to local control of tumors, yielding a significant decrease in tumor growth rates. Here we present an analysis testing this hypothesis in biopsy-only patients who participated in the EF-14 trial.

METHODS
Biopsy patients of the EF-14 trial who exhibited radiological progression were included in this study (treatment: N=37/60, control: N=12/29). Volumes of enhancing tumor were segmented on T1c MRIs at baseline and at progression. Tumor growth rate was calculated as: growth_rate=(ln(v0)-ln(v1))/dt. (v0- tumor volume at baseline), v1- Tumor volume at progression, dt- days to progression), which models tumor volume as increasing exponentially over time. Median growth rates in the treatment and control arms were compared.

RESULTS
The median growth rate was lower in the treatment arm than in the control. (control: 0.14±0.12 mL/month, TTFields -0.011±0.11 mL/month, p< 0.008 Wilcoxon rank-sum)

DISCUSSION AND CONCLUSIONS
This study shows that tumor growth rates are slower in patients treated with TTFileds+Temozolomide (TMZ) than in patients treated with TMZ alone. This analysis was restricted to biopsy-only patients since the definition of tumor volume is ambiguous in patients that underwent resection since a large portion of the tumor has been removed. The negative median growth rate for patients in the treatment arm may indicate that a significant number of TTFields-treated patients a decrease in tumor volume was observed, suggesting that TTFields enhances local tumor control. References: [1] Stupp, Roger, et al. Jama 318.23 (2017): 2306–2316.[[2 Stensjøen, Anne Line, et al. Neuro-oncology 17.10 (2015): 1402–1411.
RTHP-30. DOES THE TEMPORAL LOBECTOMY CAVITY NEED TO BE IRRADIATED? PATTERNS OF RECURRENCE AND IMPLICATIONS FOR POSTOPERATIVE RADIATION TREATMENT FIELD DESIGN FOR TEMPORAL LOBE GLIOMAS.
Authors: Teyateeti Achiraya , Geno Connie , Brown Paul , Jethwa Krishan , Stafford Scott , Laack Nadia , Mahajan Anita , Yan Elizabeth , Parney Ian , Merrell Kenneth 
Published: November 2019

Abstract

BACKGROUND
Treatment of temporal lobe glioma (TLG) frequently includes partial or complete temporal lobectomy (TL) followed by radiotherapy (RT). However, there are two approaches for temporal resection cavity RT, 1) standard target volumes (STV) targeting the entire TL resection cavity, dura, and peri-tumoral brain parenchyma or 2) modified target volumes (MTV) targeting only the adjacent peri-tumoral brain parenchyma. We report patterns of failure and a dosimetric comparison of these approaches.

MATERIALS AND METHODS
This was a retrospective review of 49 patients with WHO grade II-IV TLG who underwent partial or complete TL and post-operative RT between 1998 and 2018. Progression-free survival (PFS) was estimated using the Kaplan-Meier method.

RESULTS
The median patient age was 56 years (range,21–76). Patients were diagnosed with glioblastoma (n=32,65%), anaplastic glioma (n=10,20%) and low-grade glioma (n=7,14%). Treatment included partial TL with STV (n=33,67%), partial TL with MTV (n=5,10%), complete TL with STV (n=8,16%) and complete TL with MTV (n=3,6%). Mean RT dose was 60 Gy (range,40–76) in 30 fractions (range,15–39). At median follow-up time of 18 months (range, 3–161), 44 patients (90%) experienced recurrence: 34 (77%) in-field, 5 (11%) out-of-field, and 5 (11%) both in- and out-of-field. Among the 39 in-field failures, the location of recurrence included brain parenchyma (n=38,97%), ventricle (n=6,15%), and dura (n=5,13%). No patient experienced isolated dural recurrence regardless of tumor grade, extent of TL, or radiation volume. Median PFS was 20 months (95% confidence interval [CI]: 15–24). RT volume (STV vs. MTV) was not associated with worsened PFS (hazard ratio: 1.1, 95% CI: 0.5–2.6). MTV was associated with significant reductions in mean or max doses to brain stem, optic chiasm, optic nerves, hippocampus, and pituitary compared to STV.

CONCLUSION
Omitting RT to the entire TL cavity may reduce dose to multiple normal tissues with no detriments in dural recurrence or PFS.
RTHP-36. REIRRADIATION FOR DIFFUSE INTRINSIC PONTINE GLIOMA: A SYSTEMATIC REVIEW AND META-ANALYSIS OF PATIENT OUTCOMES
Authors: Lu Victor , Welby John , Laack Nadia , Mahajan Anita , Daniels David 
Published: November 2019

Abstract

BACKGROUND
Diffuse intrinsic pontine glioma (DIPG) is a pediatric brain tumor with dismal prognosis despite initial radiation therapy (RT). The clinical consequences of attempting reirradiation (reRT) in these patients to alleviate both symptomatology and improve prognosis are currently unclear. Thus, the aim of this systematic review and meta-analysis was to clarify the efficacy and safety of reRT in DIPG.

METHODS
Searches of 7 electronic databases from inception to January 2019 were conducted following the appropriate guidelines. Articles were screened against pre-specified criteria. The incidence and duration of clinical outcomes were then extracted and pooled by means of meta-analysis from the included studies.

RESULTS
A total of 7 studies satisfied all criteria, describing 90 cases of DIPG in which reRT was attempted 11.8–14 months after initial RT. Based on a random-effects model, the incidences of clinical improvement and radiologic response following reRT were 87% (95% CI, 78–95%) and 69% (95% CI, 52–84%) respectively. The incidence of acute serious toxicity was 0% (95% CI, 0–4%). Pooled overall survivals from initial diagnosis, and time of reRT, were 18.0 months (95% CI, 14.2–21.7) and 6.2 months (95% CI, 5.5–7.0) respectively.

CONCLUSIONS
Based on these results, the clinical consequences of reRT for DIPG when administered appropriately and safely at first progression appear acceptable, and potentially favorable, based on the limited evidence in the current literature. Concerns regarding acute serious toxicity were not realized. It is likely a sub-cohort of all DIPG diagnoses will be most amenable to improved prognosis with reRT, and greater investigation is required to identify their characteristics.
RTHP-37. RE-IRRADIATION OF GLIOMATOSIS CEREBRI WITH WHOLE BRAIN PULSED REDUCED DOSE RATE RE-IRRADIATION
Authors: Burr Adam , Harari Colin , Ian Robins H , Howard Steven 
Published: November 2019

Abstract

BACKGROUND
Gliomatosis cerebri was removed from the 2016 WHO classification but the clinical problem of gliomatosis remains. For many of these patients, re-irradiation of the whole brain may be the only option. We have employed pulsed reduced dose rate (PRDR) radiation therapy to limit the toxicity of whole brain re-irradiation in this patient population.

METHODS
Consecutive patients were identified from an institutional database of patients treated with PRDR radiation to the whole brain between 2001 and 2016. Patients were treated by delivering a 20 cGy pulse of radiation every 3 minutes to opposed lateral fields with custom blocks using 6 MV photons, delivering radiation at an effective dose rate of 6.67 cGy/minute.

RESULTS
A total of sixteen patients were identified who underwent re-treated with WBRT. The median age was 45 (28–66) with a median KPS of 80 (range 60–100). 15 of 16 patients had high grade gliomas. The most common dose was 30 Gy in 15 fractions (range 24–41.4 Gy), giving a median total dose of 90.75 Gy (range 61.4–100.8 Gy). Median overall survival from re-irradiation was 3.8 months (range 0.1–17.0 months) and overall survival from first progression was 11.2 months. 25% of patients survived over 6 months following treatment and the overall response rate was 25% (3 PRs, 1 stable). No grade 4 or grade 5 toxicities were attributable to pulsed reduced dose rate radiation therapy.

CONCLUSIONS
PRDR radiation therapy provides a potential therapeutic intervention for progressive gliomatosis cerebri, providing a treatment option that can be implemented where no trial is available. As survival is short, these results will assist in counseling patients in considering re-irradiation versus supportive care.
RBTT-05. A SINGLE-ARM, OPEN-LABEL, PHASE II STUDY EVALUATING THE EFFICACY AND SAFETY OF ABEMACICLIB IN PATIENTS WITH RECURRENT OLIGODENDROGLIOMA: TRIALS IN PROGRESS
Authors: Bagley Stephen , Nasrallah MacLean , O’Rourke Donald , Hussain Jasmin , Maloney-Wilensky Eileen , Prior Timothy , Brem Steven , Desai Arati 
Published: November 2019

Abstract

BACKGROUND
Oligodendroglioma is a rare primary brain tumor characterized by mutation in the IDH1/IDH2 genes and codeletion of chromosomes 1p and 19q. Although median overall survival extends beyond 10 years for patients with oligodendroglioma who receive adjuvant radiation and alkylating chemotherapy, the disease uniformly relapses and has no other effective treatments. The CIC gene, which encodes a high-mobility group box transcriptional repressor, is mutated in about 70% of oligodendrogliomas and is associated with worse prognosis and overexpression of cyclin D1 (CCND1). Cyclin D1 assembles with the cyclin-dependent kinases CDK4 and CDK6 to cause phosphorylation of Rb protein and subsequent cell cycle progression from the G1 to S phase. Therapeutic inhibition of CDK4/6 activity, which leads to Rb dephosphorylation and cell cycle arrest, has revolutionized the care of breast cancer. The current phase 2 study will investigate the efficacy and safety of abemaciclib, a selective and potent small molecule inhibitor of CDK4 and CDK6 with significant brain-brain barrier penetration, in patients with 1p/19q codeleted oligodendroglioma that has recurred after standard radiation and alkylating chemotherapy.

METHODS
This protocol (NCT03969706) has a single-arm, open-label, single-stage phase 2 design. Subjects will be treated with abemaciclib 200mg tablet twice daily on 28-day cycles until disease progression or unacceptable toxicity. Tumor response will be assessed according to modified Response Assessment in Neuro-Oncology (mRANO) criteria. The primary objective of the study is to determine the efficacy of abemaciclib for recurrent oligodendroglioma. The primary endpoint is the progression-free survival status of the subject at 6 months after enrollment (PFS-6). The alternative hypothesis is that the proportion of subjects without an event at 6 months will be ³85%. We will test this hypothesis against a null hypothesis of PFS-6 = 50%. With enrollment of 10 planned subjects, the power to detect this difference is 82% (one-sided alpha = 0.05).
RBTT-07. A PHASE 2 TRIAL OF PEMBROLIZUMAB AND BEVACIZUMAB IN MELANOMA BRAIN MET PATIENTS
Authors: Kluger Harriet M , Forsyth Peter , Khushalani Nikhil , Eroglu Zeynep , Sznol Mario , Tran Thuy , Jilaveanu Lucia , Cohen Justine V , Hegde Upendra , Wei Wei , Mahajan Amit , Goldberg Sarah B , Chiang Veronica , Weiss Sarah A 
Published: November 2019

Abstract

BACKGROUND
Pembro monotherapy (NCT02085070) produces responses in 26% of (mel) BrM pts. VEGF inhibitors (VEGFi) enhance anti-PD-1 activity in preclinicals. Therefore, we initiated a phase 2 study (NCT02681549) of pembro plus bev in BrM pts.

METHODS
Eligibility includes advanced mel, > 1 asymptomatic BrM, diameter 5-20mm, no steroids, no prior PD-1/PD-L1 or VEGFi. Pembro IV 200mg q3 wks for < yrs with bev 7.5mg/kg for the first 4 cycles. Primary endpoint was BrM RR by modified RECIST.

RESULTS
Between 8/2016 - 1/2019, 20 mel pts were enrolled. 60% were male mdn age 62;ECOG PS was 0 in 16 and 1 in 4 pts; LDH > ULN in 20%; 4 (20%); 10 were BRAFmt; 8 pts (40%) had > 4 untreated BrM. 12 had a BrM response (7 CR, 5 PR); 1 each with SD, unevaluable and an unconfirmed PR, for an ORR BrM of 60% (12/20). All responses lasted 7+ to 30+ mths. 16 pts are alive. AEs attributable to bev include hypertension, microscopic diverticular perforation and wound dehiscence (1 pt each, all resolved). 1 had mucositis attributed to Pembro. Three d/c’d treatment for grade 3 ALT elevation. Cerebral edema decreased in all pts with baseline edema.

CONCLUSIONS
Pembro plus bev demonstrates promising activity in melanoma BrMs compared to pembro alone. The pre-specified primary endpoint (> 4 BrM responses/20) was met, supporting further study. The toxicity profile was similar to pembro alone.
RBTT-08. A RANDOMIZED PHASE 2 OPEN LABEL STUDY OF NIVOLUMAB PLUS STANDARD DOSE BEVACIZUMAB VERSUS NIVOLUMAB PLUS LOW DOSE BEVACIZUMAB IN RECURRENT GLIOBLASTOMA (GBM)
Authors: Ahluwalia Manmeet , Fallah Jaleh , Peereboom David , Schilero Cathy , Ali Assad , Forst Deborah , Wong Eric , Wen Patrick , Reardon David 
Published: November 2019

Abstract

INTRODUCTION
Initial trials with anti-PD1 in recurrent glioblastoma showed limited efficacy. Vascular endothelial growth factor (VEGF) is a highly upregulated proangiogenic growth factor in GBM that contributes to tumor-associated immunosuppression by inhibition of dendritic cell maturation and antigen presentation, induction of apoptosis of CD8+ T-cells and enhancing Treg activity. Hence, a combination of anti-PD1 and anti-VEGF is promising approach in recurrent GBM.

METHOD
This is a 90 patient randomized, open-label, phase 2 safety study of Nivolumab and bevacizumab administered according to standard and reduced dosage schedules in patients with first recurrence of GBM. Patients will undergo 1:1 randomization to receive treatment with either Nivolumab (240 mg flat dosing IV every 2 weeks) and bevacizumab administered according to standard (10 mg/kg IV every 2 weeks; Arm A) and reduced (3 mg/kg IV every 2 weeks; Arm B) dosage schedules for recurrent glioblastoma patients. The study will allow patients that require dexamethasone up to 4 mg/day to participate in the study. All subjects will be followed for safety and tolerability, tumor progression and overall survival. Tumor progression or response endpoints will be assessed using the Radiologic Assessment in Neuro-Oncology (RANO) criteria and an exploratory endpoint will evaluate the response endpoints using the Immunotherapy RANO (iRANO). Treatment with study medication will continue until confirmed tumor progression, unacceptable toxicity or death. It is expected that enrollment and follow-up of randomized subjects (45 subjects in each arm) will take approximately 12months. The one-sample log-rank test will be applied to outcomes observed for each arm individually to test the hypothesis that OS has been improved beyond the null 12-month survival rate of 45%. With N=45 patients per arm, a one-sided test provides power=0.80 to detect survival rate of 58% at 12-months following treatment at the 0.10 significance level. The study (NCT03452579) is ongoing and enrolling patients.