bluuebunny/crossref_metadata_2025 huggingface dataset:
RTHP-09. SINGLE INSTITUTION’S EXPERIENCE FOR PEDIATRIC INTRACRANIAL EPENDYMOMA TREATED WITH ADJUVANT RADIOTHERAPY
Authors: Lee Joongyo , Hee Choi Seo , In Yoon Hong , Woo Han Jeong , Lee Ikjae , seok Kim Dong , Suh Chang-Ok
Published: November 2019

PURPOSE

To investigate long term outcomes of pediatric intracranial ependymoma treated with maximal safe resection followed by radiotherapy in single institution.

METHODS

Between 1983 and 2016, 42 pediatric patients received adjuvant radiotherapy after surgery. There were 19 and 23 grade II and III ependymomas, and total resection could be performed in 50% of patients. There were 4 patients with initial leptomeningeal seeding, and craniospinal irradiation (CSI) was the component of adjuvant treatment in 5 patients including them. Local radiotherapy (median 54 Gy (range, 45–60 Gy) was performed in all the rest patients excluding three with whole-brain radiotherapy.

RESULTS

With a median follow-up of 89 months, 14 patients (33%) experienced recurrences after radiotherapy (m/c: intracranial, 79%, all within tumor bed). The 5- and 10-year progression-free survival (PFS) rates were 70% and 63%, and overall survival (OS) rates were 85% and 78%, respectively. The recurrence rates were significantly higher in patients younger than 3 years (64% vs. 23%, p = 0.024) or with subtotal resection (STR) (52% vs. 15%, p = 0.009). In multivariate analyses, age and STR were significant factors for PFS (p = 0.007 and 0.028, respectively). There was no independent prognostic factor for OS on multi-variate analysis. Fourteen patients experienced recurrence. Among them, all of 6 grade II cases showed local recurrence. Four grade II cases (67%) underwent aggressively salvage treatments such as resection, stereotactic radiosurgery were still under observation. However, 75% of 8 grade III recurrent cases were expired, despite aggressive salvage treatments. All 3 patients with seeding recurrent were grade III and died from disease.

CONCLUSION

Local adjuvant radiotherapy showed favorable survival in pediatric ependymoma. Even if recurrence occurs, aggressive salvage treatment would be needed for grade II ependymoma.
RTHP-14. PSEUDOPROGRESSION IN HIGH GRADE GLIOMA PATIENTS AFTER PROTON OR PHOTON THERAPY
Authors: Williams Vonetta , Halasz Lia , Rockhill Jason , Fink James
Published: November 2019

Pseudoprogression is defined as the appearance of false progression on MR imaging following radiation therapy. Proton therapy is thought to have increased relative biological effectiveness-the ratio of the doses required by two types of radiation to cause the same level of effect-near the edges of the high dose volume. This could lead to different rates of pseudoprogression for protons compared to photons. In our IRB approved study, a board-certified neuroradiologist reviewed serial imaging of 74 patients (photons: n=37, protons: n=37) treated from 2013–2018 with either proton or photon radiotherapy to 59.4–60 Gy in 30–33 fractions and temozolomide for high grade glioma. MR imaging was performed 1 month after completion of treatment and then every 3 months. True progression was scored based on updated RANO criteria. Pseudoprogression was determined if imaging improved without change in therapy. Cumulative incidences of these outcomes and survival were calculated utilizing Kaplan-Meier analyses. Patient and treatment factors were analyzed for their association with incidence of pseudoprogression. Median follow-up for alive patients in the proton and photon groups were 15 and 29 months, respectively. Median age was 49 years in the proton group and 54 years in the photon group (p=0.17). Among proton patients, 14 had grade III glioma and 23 had grade IV glioblastoma. Among photon patients, 1 had grade III glioma. Median survival was 23 and 35 months for the proton and photon groups, respectively (p=0.57). The cumulative incidence of pseudoprogression was 14.4% and 10.4% at 12 months for the proton and photon groups, respectively (p=0.53). Grade, extent of resection, age, and IDH status, were not significantly associated with development of pseudoprogression. MGMT methylated tumors showed a trend toward association with pseudoprogression compared to unmethylated tumors (p=0.058). We concluded that the incidence of pseudoprogression is similar regardless of whether proton or photon therapy was utilized.
RTHP-21. TREATMENTS FOR RECURRENT MALIGNANT GLIOMAS AND THEIR PROGNOSIS
Authors: Mori Kanji , Kumagai Tetsuya , Kobayashi Maki , Iwata Takamitsu , Nakagawa Kanji , Kudo Akira , Toyota Shingo , Kanemura Yonehiro , Taki Takuyu
Published: November 2019

For improvement of glioma therapy, advances in treatment after recurrence are essential, but no standard second line therapy has been estimated. Lately, bevacizumab (Bev) and BCNU wafer became available in Japan, we have more therapeutic choices. Since we took part in Kansai molecular diagnosis network for CNS tumors in 2013, we have referred molecular information. We retrospectively examined and report our experiment about recurrent malignant gliomas in Kansai Rossi Hospital. Twenty-two histopathologically proved grade 3 and grade 4 patients who were diagnosed as recurrence between January 2013 and December 2018 were included. We examined treatment and analyzed factors that influenced overall survival (OS) after recurrence. Glioblastoma were 14 cases (IDH wild 12 cases, IDH mutant one case, unknown one case) Median age and KPS at recurrence were 70 years old and 60%, respectively. Ten patients received any anti-cancer treatment and 2 received best supportive care (BSC). Radiation therapy (RT) with Bev were used in 9 patients (5 with gamma knife). Their median OS after first recurrence was 324 days and significantly longer than that of BSC patients (p=0.00174). Grade 3 gliomas were 8 cases (IDH-mutant 3 cases, IDHwild 5 cases, H2F3A mutant 1 case). Median age and KPS at recurrence were 45 years old and 70%, respectively. Five patients were treated with temozolomide (TMZ) and others were observed. In addition to TMZ, Bev were used for 4 patients and RT for 3. Median OS of these patients was significantly longer (p=0.0198). In both grade, patients with better KPS (>60%) statistically lived longer than poor KPS, but methylation status of MGMT promoter and IDH mutation did not influent their OS. Radiation with Bev for good KPS patients might improve prognosis. Further multicenter prospective study must be needed.
RTHP-23. PROSPECTIVE TRIAL OF CONVENTIONALLY FRACTIONATED DOSE CONSTRAINTS FOR RE-IRRADIATION OF PRIMARY BRAIN TUMORS
Authors: McGovern Susan , Luo Dershan , Johnson Michael , Nguyen Kham , Li Jing , McAleer Mary , Yeboa Debra , Grosshans David , Ghia Amol , Chung Caroline , Thall Peter , Sulman Erik , Brown Paul , Mahajan Anita
Published: November 2019

PURPOSE/OBJECTIVE

Dose constraints for re-irradiation of recurrent primary brain tumors are not well-established, especially for treatment volumes too large for stereotactic radiotherapy. This prospective trial was performed to test dose constraints for conventionally-fractionated re-irradiation of recurrent primary brain tumors

MATERIALS/METHODS

A single-institution, prospective trial of 21 adults with recurrent brain tumors was performed. Electronic dosimetry records from the first course of radiation (RT1) were obtained and deformed onto the simulation CT for the second course of radiation (RT2). Treatment plans for RT2 were developed that met protocol-assigned dose constraints for RT2 alone and the composite dose of RT1+RT2. Dose constraints were also based on histology and interval since RT1. The primary endpoint was the rate of symptomatic brain necrosis after RT2.

RESULTS

Twenty one adults enrolled from March 2017 to May 2018. Twelve had glioblastoma, four had oligodendroglioma, two had anaplastic astrocytoma, and one each had choroid plexus papilloma, hemangiopericytoma, and pleomorphic xanthroastrocytoma (PXA). Twenty patients were treated with VMAT and one was treated with proton CSI. Median RT1-RT2 interval was 45 months (range, 9–141 months). Median RT2 dose was 42.8 Gy (range, 17.5–60 Gy). Median PTV volume was 208 cc (range, 7–1537 cc). Median imaging followup was 9 months (range, 1–20 months). Two months after RT2, the patient with PXA developed a trapped temporal horn adjacent to the RT2 treatment volume; pathology from emergent resection revealed necrotic brain tissue. The patient recovered fully and lived another 18 months until dying of disease progression. No other patient developed symptomatic radionecrosis. Median overall survival from RT2 for all patients was 11 months (range, 3–20 months).

CONCLUSION

Re-irradiation can be performed with conventionally fractionated schemes. Given the low rate of symptomatic radionecrosis, the dose constraints described here are a starting point for future studies of conventionally fractionated re-irradiation.
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

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

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

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

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

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

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

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

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

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

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

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.
RBTT-09. A PHASE 1 STUDY OF CEMIPLIMAB IN PEDIATRIC PATIENTS WITH RELAPSED OR REFRACTORY (R/R) SOLID AND CENTRAL NERVOUS SYSTEM (CNS) TUMORS
Authors: Kline Cassie , Schoenfeld Jonathan D , Catalano Paul J , Li Jingjin , Paccaly Anne J , Sims Tasha N , Bredlau Amy-Lee , Prados Michael , Haas-Kogan Daphne , Mueller Sabine
Published: November 2019

DIPG and HGG lead to the majority of pediatric cancer-related deaths. Despite multimodal treatment, the 2-year survival rates for DIPG and HGG are less than 10% and 20%, respectively. Anti-PD-1 therapy combined with radiotherapy has demonstrated synergistic anti-tumor effects. Cemiplimab, a human PD-1 monoclonal antibody, has demonstrated safety and efficacy in patients with advanced malignancies. Combination of cemiplimab with radiation has the potential to be an effective treatment for pediatric patients with DIPG or HGG. This is a multicenter, Phase 1 and early efficacy study (NCT03690869). Phase 1 will enroll pediatric patients with R/R solid or CNS tumors (N≥30) into two age cohorts (0 to < 12 and 12 to < 18 years). Cemiplimab will be administered intravenously every 2 weeks as monotherapy. Primary objectives of Phase 1 are to confirm safety and assess the pharmacokinetics (PK) of cemiplimab to recommend a Phase 2 dose (RP2D) for clinical efficacy assessment. The Efficacy phase will enroll patients with newly diagnosed DIPG or HGG (dose escalation: N≥12 patients each; dose expansion: N≤40 patients each), or recurrent HGG (dose escalation: N≥6 patients; dose expansion: ≤20 patients) into two age cohorts (≥3 to < 12 years and 12 to ≤25 years). There will be two treatment arms for patients with newly diagnosed DIPG or HGG: cemiplimab in combination with conventionally fractionated (Arm 1) or hypofractionated (Arm 2) radiotherapy. Patients with recurrent HGG will receive cemiplimab concomitantly with reirradiation. All patients will continue cemiplimab as monotherapy at completion of combination therapy. Primary objectives of Efficacy Phase are to confirm safety and anticipated RP2D, assess PK, and determine survival and antitumor activity at 12 months (overall survival for newly diagnosed DIPG and recurrent HGG; progression-free survival for newly diagnosed HGG) of cemiplimab when given concomitantly with radiation. This study is currently recruiting patients across multiple sites.
RARE-01. NATIONWIDE TRENDS IN MANAGEMENT OF ADULT MYXOPAPILLARY EPENDYMOMA
Authors: Baracena Daphne , Kelly Patrick , Khudanyan Arpine , Turina Claire , Jaboin Jerry , McClelland III Shearwood
Published: November 2019

INTRODUCTION

Myxopapillary ependymomas (MPE) are WHO Grade I ependymomas that occur in the spine and have an annual incidence of 0.05–0.08 per 100,000 people. Maximal, safe surgical resection is the recommended first line therapy. Due to the rarity of the disease there is a relatively poor understanding of the use of radiotherapy (RT) in the management of disease.

METHODS

Using the National Cancer Database (NCDB), we analyzed the patterns and impact of RT on spinal MPE in adults diagnosed between 2002 and 2016.

RESULTS

Of 753 qualifying cases, the majority of patients underwent resection (n = 617, 81.9%). A relatively small portion received RT (n = 103, 13.3%) with most receiving RT after surgical resection (n = 98, 95.1%). The likelihood of patients to undergo resection and RT was significantly associated with patient age at diagnosis (p = 0.002), tumor size (p < 0.001), and race (p = 0.017). Chemotherapy was not widely utilized (only 0.27% of patients).

DISCUSSION

Although practice patterns can be highlighted from this 15-year analysis, given the high survival in this disease entity, progression-free survival (PFS) is an important outcome not available from this database. As expected, surgery is the primary means to manage adult MPE. For spinal MPE, it is understood that gross total resection (GTR) should be attempted whenever possible as GTR has been associated with improved PFS in several studies. RT and chemotherapy are used infrequently. In univariate analyses, RT was employed more often for larger tumor sizes, Latino/Hispanic ethnicity, and younger age at diagnosis. The impact of RT on overall survival is indeterminate given the 1.6% death rate in the cohort. Analyses of the impact of RT on PFS in a larger database would be beneficial for determining an algorithm for post-operative and definitive radiotherapy in this disease entity.
RARE-04. TARGETED TREATMENT OF PAPILLARY CRANIOPHARYNGIOMAS HARBORING BRAFV600E MUTATIONS
Authors: Juratli Tareq , Jones Pamela , Wang Nancy , Subramanian Megha , Aylwin Simon , Odia Yazmin , Rostami Elham , Gudjonsson Olafur , Shaw Brian , Cahill Daniel , Uhm Joon , Galanis Evanthia , Barker Fred , Santagata Sandro , Brastianos Priscilla
Published: November 2019

Craniopharyngiomas are surgically challenging brain tumors. Postoperatively, quality of life is often significantly impaired due to neurological and endocrinological complications. Currently, FDA approved systemic treatments are not available for patients in whom craniopharyngiomas recur after surgery and radiation. Papillary craniopharyngiomas are characterized by the presence of BRAFV600E mutations. To date, five case reports have been published on the treatment of BRAFV600E mutant papillary craniopharyngiomas with BRAF and/or MEK inhibitors. In this presentation, authors from all five previously published reports share their collective experience and provide updated follow-up on their patients, thus generating an overview of all currently available information on targeted therapy in patients with BRAFV600E mutant papillary craniopharyngiomas. We have also included information on an additional patient with a papillary craniopharyngioma recently treated with BRAF and MEK inhibitors after tumor biopsy alone, in the absence of recurrence, highlighting the potential for a neo-adjuvant therapeutic approach. All six cases in our series showed dramatic responses to targeted treatment with BRAF (and MEK) inhibitors. Collectively, our cases are highly promising and informative for patient treatment, although uncertainty remains with regards to the optimal timing, the specific agents (single agent or dual therapy) to be used and the duration of treatment. The ongoing multicenter phase II Alliance A071601 trial (NCT03224767) of vemurafenib and cobimetinib for patients with biopsy-proven residual or recurrent papillary craniopharyngiomas should provide additional information to help guide patient management.
RARE-05. ARE TRANSGENDER INDIVIDUALS STRONGLY PREDISPOSED TO DEVELOPMENT OF PROLACTINOMAS?
Authors: Kleinschmidt-DeMasters Bette
Published: November 2019

Transgender individuals usually receive long-term hormone treatment in the course of their sexual transition. Although the effects of this on possible development of neoplasia are largely unknown, very limited literature has suggested they may be predisposed to development of prolactinomas. We queried our databases to determine if we had encountered such cases at our tertiary care center for sellar region masses. Pathology databases from 2000–2019 were searched by the text word “transgender” to identify pituitary adenomas; cases were compared with all tissue specimens obtained from transgender persons. 2 pituitary adenomas were identified, out of approximately 1800+ sellar region masses at our institution during this same time period; neither were prolactinomas. The first occurred in a 71-year-old transgender male-to female who had undergone high-dose hormone therapy followed by orchiectomy 30 years prior; since that time various doses of estrogen had been received, most recently Premarin, .625 daily. Chronic hypertension associated with dizziness and vertigo prompted an endocrine workup which revealed an IGF-1 of 575 (normal < 150 ng/ml). MRI disclosed a 10 X 7 X 13 mm. pituitary mass which proved to be a mixed somatotroph/ lactotroph adenoma. The second occurred in a 53-year-old transgender female-to-male who was being evaluated by an endocrinologist for hormone therapy for his transition when a slightly elevated prolactin level was discovered. MRI disclosed a 10 x 7 x 13 mm. pituitary mass. Transsphenoidal hypophysectomy showed a gonadotroph adenoma with patchy immunostaining for follicle stimulating hormone (FSH). In comparison, during this same time period, 60 other surgical specimens had been received, including 33 bilateral mastectomies, 15 hysterectomies, and 4 orchiectomies, almost all for gender transition purposes. Clinicians and pathologists may wish to be aware of the occurrence of pituitary adenomas in transgender individuals, although the incidence is quite low (2/1800 sellar region masses in our system).
RARE-06. A CASE OF RECURRENT SUPRATENTORIAL EXTRAVENTRICULAR ANAPLASTIC EPENDYMOMA IN ADULT
Authors: Kang Dong-Gee , Kang Ho-Jun
Published: November 2019

Supratentorial extraventricular anaplastic ependymoma (SEAE) in adults is a relatively rare intracranial tumor. Because of very low prevalence, SEAE has been reported only a few cases. According to a recent study, SEAE is associated with a poor prognosis and there is no definite consensus of optimal treatment. We report a case of an adult SEAE patient who had no recurrence until seven years after gross total resection(GTR) followed by conventional radiotherapy. A 42- year- old male had a persistent mild headache, left facial palsy, and dysarthria. Preoperative neuroimaging revealed an anaplastic astrocytoma or supratentorial ependymoma in the right frontal lobe. A GTR was performed, followed by adjuvant radiotherapy. Histologic and immunohistochemical results revealed anaplastic ependymoma, After seven years of initial therapy, a regular follow-up MRI showed a 3-cm –sized partially cystic mass in the same area as the initial tumor. The patient underwent a craniotomy, and a GTR was performed. Histopathologic examination revealed recurrence of the SEAE. External radiotherapy was performed. The patient has been stable without any disease progression or complications for 12 months since the surgery for recurrent SEAE
RARE-07. HOW TO TREAT THE INCIDENTAL THALAMIC PRESUMED LOW-GRADE GLIOMAS
Authors: Kumabe Toshihiro , Shibahara Ichiyo , Kanamori Masayuki , Saito Ryuta , Hide Takuichiro , Sato Sumito , Sonoda Yukihiko , Tominaga Teiji
Published: November 2019

Medical intervention for patients with incidentally found presumed low grade gliomas (iLGGs) is controversial. We experienced 5 consecutive thalamic iLGGs, and discuss the follow-up methods and the timing of the intervention. Age at the initial MRI was 19, 57, 58, 70, 70, respectively. Only the bilateral thalamic iLGG of 19-year-old male was radically resected soon after the initial MRI, because of the large tumor size. The histological diagnosis was a diffuse astrocytoma, IDH-wildtype, without H3K27M mutation. This patient was treated by chemoradiation, still alive for 24 months with KPS of 90%. The other four cases were strictly followed by MRI. One case of 70-year-old female is followed for 38 months without increasing the tumor volume. The other 3 cases had been followed by MRI for 15, 91, 154 months, respectively. Stereotactic biopsy or ventriculo-peritoneal shunting (VPS) was performed after that because of the tumor progression. The histological diagnosis of 57-year-old male followed for 15 months was a diffuse astrocytoma, IDH-wildtype. This patient selected further follow-up, although volume of the tumor increased exponentially. Radical resection was performed 11 months after the stereotactic biopsy, disclosed malignant transformation. This patient was treated by chemoradiation, finally died of tumor dissemination 15 months after the radical resection. Long-term followed patients, such as 91 and 154 months, showed slow linear tumor volume increasing. The latter patient with bilateral iLGG was treated by VPS followed by radiation therapy. This patient could keep KPS of 100% for 13 years after the initial MRI and live for 20 years. Our case series suggests that conservative management and close follow-up of thalamic iLGGs is a safe and effective strategy. However, volumetric analysis must be performed for every follow-up MRI. Once the steep volume increasing is detected, surgical intervention and/or chemoradiation should be considered without delay.
RARE-09. CYSTIC GLIOBLASTOMA PRESENTATION AS A BENEFICIAL PROGNOSTIC INDICATOR FOR OVERALL SURVIVAL
Authors: Curtin Lee , Whitmire Paula , Rickertsen Cassandra , Canoll Peter D , Mrugala Maciej , Swanson Kristin , Hu Leland
Published: November 2019

Glioblastoma (GBM) is the most aggressive primary brain tumor with a median overall survival of 15 months with standard-of-care treatment. GBM patients sometimes present with a cystic component, which can be identified through magnetic resonance imaging (MRI). Previous studies suggest that cysts occur in 7–22% of GBM patients and have reported mixed results regarding whether cystic GBM have a survival benefit compared to noncystic GBM. Using our large retrospective cohort of 493 first-diagnosis GBM patients, we aim to elucidate this link between cystic GBM and survival. Within this cohort, 88 patients had a significant cystic component at presentation as identified on MRI. Compared to noncystic GBM (n=405), cystic GBM patients had significantly better overall survival (15 vs 22 months median, log-rank, p=0.001) and were significantly younger at the time of presentation (t-test, p=0.002). However, within patients that received current standard-of-care treatment (n=184), cystic GBM (n=40) was not as beneficial for outcome (22 vs 25 months, log-rank, p=0.3). We also did not observe a significant survival benefit when comparing this standard-of-care cystic cohort to cystic GBM patients diagnosed before the standard was established (n=19, 25 vs 23 months, log-rank, p=0.3), but the analogous result for noncystic GBM patients gives a sizeable benefit, as expected (n=144, n=111, respectively, 22 vs 12 months, log-rank p < 0.0001). Together, these results on current standard-of-care may explain later studies that note no significant survival benefit for cystic GBM patients receiving current standard-of-care. We also report differences in the absolute and relative sizes of imaging abnormalities on MRI and in prognostic impact of cysts based on sex. We discuss current hypotheses for these observed differences, including the possibility that the presence of a cyst could be indicative of a less aggressive tumor.