bluuebunny/crossref_metadata_2025_split huggingface dataset:
LINC-26. ORAL VINORELBINE IN PROGRESSIVE UNRESECTABLE LOW-GRADE GLIOMA
Authors: Cappellano Andréa M , Oliveira Milena R S , Cavalheiro Sergio , Dastoli Patricia , Almeida Daniela B , Silva Frederico A , Alves Maria Teresa S , Silva Nasjla S 
Published: December 2020

Abstract

BACKGROUND
The management of progressive unresectable low-grade glioma (PULGG) remains controversial. Some series suggests that chemotherapy may delay or even avoid radiotherapy and/or surgery in a group of patients. Within this context, we performed at IOP/GRAACC/UNIFESP an institutional protocol with IV vinorelbine, a semi-synthetic vinca alkaloid that showed activity against PULGG. The objective of this study was to evaluate the response as long as the tolerability of oral vinorelbine in PULGG.

PATIENTS AND METHODS
From April 2013 to Aug 2017, 17 patients with recurrent (n=5) and newly-diagnosed (n=12) optic-pathway glioma (OPG) were treated with oral vinorelbine in a dose of 90 mg/m² days 0, 8 and 22 for 18 cycles. Response criteria used a combination of magnetic resonance imaging, physical and visual evaluation.

RESULTS
Mean age 8.6 years (4.8–17.9y). Three children with neurofibromatosis type 1. Eleven patients had neurosurgical intervention revealing grade I (n=8) and grade II astrocytoma (n=3). Twelve patients were assessable after 8 cycles of vinorelbine with 2 objective response (OR), 8 stable disease (SD) and 2 progressive disease (PD), one died after surgery and 1 alive in different protocol. After 18 cycles, eight patients were assessable to date for response with 1 OR, 7 SD. The most important toxicity was gastrointestinal observed in 12 patients- six of them switched to IV vinorelbine (3OR, 3SD). None of the patients showed neurotoxicity.

CONCLUSION
These results suggest that oral vinorelbine, as the IV formulation, may show some activity in OPG. However, gastrointestinal toxicity should be considered.
LINC-38. 500 CONSECUTIVE SURGICAL CASES FROM THE PEDIATRIC ONCOLOGY NEUROSURGERY GROUP: UNDERSTANDING THE PERSPECTIVE OF A TERTIARY CENTER IN BRAZIL
Authors: Sanders Felipe Hada , Matushita Hamilton , Teixeira Manoel Jacobsen 
Published: December 2020

Abstract
With this presentation we aim to present cases submitted to surgery by the same group of surgeons since 2010, presenting the physical structure, medical assistance, scientific production and the challenges that we need to overcome in the second decade of the twenty-first century, in a developing country.
MBCL-04. 5 – AZACYTIDINE IN TREATMENT OF CHILDREN WITH DE NOVO AND RELAPSED METASTATIC MEDULLOBLASTOMA: RESULTS OF INTERCENTER PILOT STUDY
Authors: Levashov Andrey , Khochenkov Dmitry , Stroganova Anna , Ryzhova Marina , Gorelyshev Sergey , Kadirov Shavkat , Zagidullina Svetlana , Babelyan Stepan , Subbotina Natalya , Mentkevich Georgy , Sidelnikov Dmitry , Daylidite Vidmante , Grigorenko Vasily 
Published: December 2020

Abstract
The aim of this study was to estimate treatment toxicity and event-free survival (EFS) according to therapeutic program, MYC/MYC-N gene amplification and MGMT/DNMT (1, 3a, 3b) proteins expression in tumor cells. From 2016 to 2018 twenty four patients were included in trial. Children underwent adjuvant therapy: craniospinal radiation (CSI) or local radiation therapy (RT) to the relapsed site up to 23.4Gy with 5-azacytidine, 2 cycles methotrexate/5-azacytidine/cisplatin/etoposide, 3 cycles 5-azacytidine/temozolomide - for relapsed group (arm A, n = 5); for patients with de novo medulloblastoma: arm B, n = 11 – vincristine/cyclophosphamide/cisplatin/etoposide (OPEC) - based induction, CSI 36Gy + local RT to the tumor bed up to 54Gy with 5-azacytidine, 1 cycle OPEC and 2 cycles thiophosphamide/carboplatin with auto stem cell transplantation (auto-SCT); arm C, n = 8 – cyclophosphamide/cisplatin - based induction, CSI 23.4 Gy followed by 2 cycles 5-azacytidine/thiophosphamide/carboplatin with auto-SCT, local RT with 5-azacytidine. The combination of 5-azacytidine with local RT or temozolomide was safety and tolerability. Arm C was discontinued due to severe gastrointestinal grade 3/4 toxicity, hemorrhagic syndrome after combination of 5-azacytidine with thiophosphamide/carboplatin. EFS was 0% in arm A, 53.0 ± 15.5%, 50.0 ± 17.7% in arms B and C, a median follow-up 8.8 ± 1.1 months (arm A), 18.8 ± 2.5 months (arm B), 25.0 ± 4.4 months (arm C). Addition of 5-azacytidine to RT or chemotherapy did not improve EFS of patients with MYC/MYC-N gene amplification positive tumor. There was not determined any prognostic significance of MGMT/DNMT (1, 3a, 3b) proteins expression in this cohort.
MBCL-07. NON-METASTATIC MEDULLOBLASTOMA OF EARLY CHILDHOOD: RESULTS FROM THE PROSPECTIVE CLINICAL TRIAL HIT-2000 AND AN EXTENDED VALIDATION COHORT
Authors: Mynarek Martin , von Hoff Katja , Pietsch Torsten , Ottensmeier Holger , Warmuth-Metz Monika , Bison Brigitte , Pfister Stefan , Korshunov Andrey , Sharma Tanvi , Jaeger Natalie , Ryzhova Marina , Zheludkova Olga , Golanov Andrey , Rushing Elisabeth Jane , Hasselblatt Martin , Koch Arend , Schüller Ulrich , von Deimling Andreas , Sahm Felix , Sill Martin , Riemenschneider Markus J , Dohmen Hildegard , Monoranu Camelia-Maria , Sommer Clemens , Staszewski Ori , Mawrin Christian , Schittenhelm Jens , Brück Wolfgang , Filipski Katharina , Hartmann Christian , Meinhardt Matthias , Pietschmann Klaus , Haberler Christine , Slavc Irene , Gerber Nicolas U , Grotzer Michael , Benesch Martin , Schlegel Paul-Gerhardt , Deinlein Frank , von Bueren André O , Friedrich Carsten , Obrecht Denise , Fleischhack Gudrun , Kwiecien Robert , Faldum Andreas , Kortmann Rolf-Dieter , Kool Marcel , Rutkowski Stefan 
Published: December 2020

Abstract

OBJECTIVE
To avoid craniospinal irradiation (CSI) in children younger than four years with non-metastatic medulloblastoma by chemotherapy, intraventricular methotrexate and risk-adapted local radiotherapy.

PATIENTS AND METHODS
Eighty-seven patients received systemic chemotherapy and intraventricular methotrexate. Until 2006, CSI was reserved for non-response or progression. After 2006, local radiotherapy was introduced for non-responders or classic (CMB), anaplastic or large-cell medulloblastoma (LCA). Infantile SHH-activated medulloblastomas (SHH_INF) were subdivided by DNA-methylation profiling. Survival in SHH_INF subtypes were also assessed in a validation cohort (n=71).

RESULTS
Patients with desmoplastic medulloblastoma (DMB) or medulloblastoma with extensive nodularity (MBEN) (n=42) had 93% 5-year PFS, 100% 5-year OS and 93% 5-year CSI-free survival. Patients with CMB/LCA (n=45) had 37% 5y-PFS, 62% 5y-OS and 39% 5y-CSI-free survival. Local radiotherapy did not improve survival in CMB/LCA patients. All DMB/MBEN assessed by DNA methylation profiling belonged to the SHH_INF subgroup. Group 3 patients (5y-PFS 36% [n=14]) relapsed more frequently than SHH_INF (5y-PFS 93% [n=28]) or Group 4 patients (5y-PFS 83% [n=6], p&lt;0.001). SHH_INF split into iSHH-I and iSHH-II subtypes in HIT-2000-BIS4 and the validation cohort, without prognostic impact (5y-PFS: iSHH-I 73% vs. iSHH-II 83%, p=0.25, n=99). Mean IQ was 90 (radiotherapy-free survivors) vs. 74 (patients that received CSI) [p=0.012].

CONCLUSION
Systemic chemotherapy and intraventricular methotrexate led to favorable survival in both iSHH-subtypes of SHH-activated DMB/MBEN with acceptable neurotoxicity. Survival in non-WNT/non-SHH CMB/LCA patients was not improved by local radiotherapy. Survival was more favorable in patients with Group 4 than in patients with Group 3 medulloblastoma.
MBCL-23. PRELIMINARY ANALYSIS OF TREATMENT-RELATED TOXICITIES DURING INDUCTION CHEMOTHERAPY FOR PATIENTS ON THE HEAD START 4 TRIAL
Authors: Agarwal Vibhuti , Stanek Joseph , Jaeger Megan , Dhall Girish , Finlay Jonathan 
Published: December 2020

Abstract
The currently active, prospective multi-center Head Start 4 (HS4) trial for CNS embryonal tumors differs from prior HS I-III trials by utilizing absolute phagocyte count (APC) as a measure of myeloid recovery instead of absolute neutrophil count. The aim of this study was to determine if utilization of APC resulted in unanticipated treatment-related toxicities during induction chemotherapy for patients enrolled on HS4. Review of the RedCap database was conducted for treatment-related CTCAE grade 3 and 4 toxicities. Data were summarized descriptively. Nonparametric statistical methods were used for comparisons. At the time of this most recent analysis, a total of 180 induction cycles were completed for the 57 patients enrolled. Of the 57 patients, nine voluntarily discontinued therapy after completing a median of three cycles each. These patients had a higher number of documented infections (59% versus 24%, p=0.0004). Veno-occlusive disease (VOD) occurred in five patients, three of whom voluntarily discontinued therapy. Since the protocol amendment utilizing milligram per kilogram dosing for patients less than six years of age, there have been no documented episodes of VOD. The overall toxicities for this cohort were comparable to those reported for induction chemotherapy in HS I-II trials. The toxic death rate is lower for HS4 compared to HS I-II (0.018% versus 4.7–6%) (Chi et al 2004). Other than the high rate of infection, possibly associated with shorter duration of the immediately prior cycles, the use of APC as part of a dose-compression strategy in HS4 does not appear associated with more significant toxicities.
MBCL-25. PILOT STUDY OF A SURGERY AND CHEMOTHERAPY-ONLY APPROACH IN THE UPFRONT THERAPY OF CHILDREN WITH WNT-POSITIVE STANDARD RISK MEDULLOBLASTOMA: UPDATED OUTCOMES
Authors: Cohen Kenneth , Chi Susan , Hawkins Cynthia , Rodriguez Fausto , London Wendy , Castellino Robert Craig , Aguilera Dolly , Stapleton Stacie , Ashley David , Landi Daniel , Bandopadhayay Pratiti 
Published: December 2020

Abstract

BACKGROUND
Wnt+ medulloblastoma (WPM) is a favorable subtype with EFS &gt; 90% when treating postoperatively with craniospinal irradiation and posterior fossa boost (CSI/XRT) followed by adjuvant chemotherapy. This pilot study explored the safety of omitting radiation in standard-risk WPM.

METHODS
Subjects had to meet standard-risk criteria (&lt; 1.5 cm2 residual tumor, no metastatic spread, no anaplasia) and have a WPM. Subjects received chemotherapy following the COGACNS0331 AAB-AAB-AAB (A=cisplatin/CCNU/VCR; B=cyclophosphamide/vincristine) backbone.

RESULTS
Six children were enrolled on study treatment prior to early study closure. Subject #1 completed planned protocol therapy but relapsed 3 months following the completion of therapy. Subject #2 completed planned protocol therapy but relapsed 6 months following the completion of therapy. In both cases, relapse was local and disseminated. Further accrual was halted. Both subjects were salvaged with CSI/XRT followed by adjuvant chemotherapy. Of the remaining 4 subjects, two had recently completed planned protocol therapy at the time of study closure and received CSI/XRT while in remission and remain in remission approximately one year from the completion of treatment. One subject aborted protocol therapy and transitioned to a Head Start regimen and remains in remission 10 months from completion of therapy. The final subject had just completed protocol therapy and had new areas of restricted diffusion concerning for early relapse. Went on to receive CSI/XRT but subsequently relapsed and is now receiving salvage chemotherapy.

CONCLUSIONS
Chemotherapy following ACNS0331, omitting CSI/XRT, appears to be insufficient for the treatment of non-metastatic WPM.
MBCL-29. PHASE I/II STUDY OF SEQUENTIAL HIGH-DOSE CHEMOTHERAPY WITH STEM CELL SUPPORT IN CHILDREN YOUNGER THAN 5 YEARS OF AGE WITH HIGH-RISK MEDULLOBLASTOMA
Authors: Dufour Christelle , Masliah-Planchon Julien , Delisle Marie-Bernadette , Geoffray Anne , Abbas Rachid , Bourdeaut Franck , Bertozzi Anne-Isabelle , Faure-Conter Cecile , Chappe Celine , De Carli Emilie , Entz-Werle Natacha , Fouyssac Fanny , Andre Nicolas , Soler Christine , Pluchart Claire , Palenzuela Gilles , Leblond Pierre , Grill Jacques 
Published: December 2020

Abstract

PURPOSE
To assess the 3-year EFS rate of children younger than 5 years of age with high-risk medulloblastoma (MB) treated according to the prospective multicenter trial HR MB-5.

PATIENTS AND METHODS
After surgery, all children received 2 cycles of Etoposide- Carboplatine. If partial (PR) or complete response (CR) was achieved after induction chemotherapy, children received 2 courses of thiotepa (600mg/m²) with stem cell rescue. For patients in CR after high-dose chemotherapy, they received one course of Cyclophosphamide – Busilvex with stem cell rescue (Phase I part). The others patients (not in PR after induction or in CR after thiotepa) were treated with 2 cycles of Temozolomide-Irinotecan followed by age-adapted craniospinal irradiation and maintenance treatment.

RESULTS
28 children (2 to 4 years; median: 3.0 years) were enrolled. Group 3 MB were most common (57%). The response rate to Etoposide-Carboplatine was 60.7%. Among 20 patients treated with Thiotepa, 13 children were in CR and received Cyclophosphamide – Busilvex without radiotherapy. Out of them, 9 patients (45%) are alive in CR without craniospinal irradiation (median follow-up 5 years). Among 15 patients treated with radiotherapy, 8 patients are alive (median follow-up 3.8 years). The study was prematurely stopped for an excess of events. The median follow-up was 4 years (range 1.5 - 6.1). The 3-year EFS and OS were 42.3% [25.9 - 60.6] and 71.3% [52.7 - 84.7], respectively.

CONCLUSIONS
This risk-adapted strategy did not improve EFS in young children with high-risk MB. However, the study shows that good responders to chemotherapy can be cured without recourse to irradiation.
MBCL-31. TREATMENT RESULTS AMONG 106 PATIENTS WITH MEDULLOBLASTOMA OF MOLECULAR SUBGROUP 3
Authors: Zheludkova Olga , Olkhova Lyudmila , Kushel’ Yuri , Melikyan Armen , Ryzhova Marina , Shishkina Lyudmila , Golanov Andrey , Kislyakov Alexey , Shultz Evgeny , Borodina Irina , Gorbatykh Svetlana , Popov Vladimir , Mushinskaya Marina , Polushkina Olga , Inyushkina Еugenia , Yudina Natalia , Privalova Lyudmila , Minkina Lyudmila , Zaichikov Artem , Matsekha Evgeny , Fisyun Ivan , Sakun Daniil , Dunaeva Nadezhda , Avanesyan Svetlana , Mitrofanov Vladislav , Kovalenko Sergey , Grishina Ekaterina , Chulkov Oleg , Pishchaeva Nadezhda , Vorob’ev Nikolay , Nechesnyuk Alexey , Popova Natalia , Pogorelov Dmitriy , Matitsyn Alexander , Shapochnik Alexander , Timofeeva Valentina , Korchunov Andrey , Slobina Elena 
Published: December 2020

Abstract

OBJECTIVE
To evaluate the treatment results among 106 patients of molecular subgroup 3 and to determine the factors affecting the prognosis.

PATIENTS AND METHODS
In all the patients, initial removal of the tumor was performed. All the patients got chemoradiotherapy according to the HIT protocol. There were 34girls and 72boys. Most patients were over 3 years:74 compared to 32 younger than 3. The majority of the patients had stage M+: 65; in 38 stage M0 was determined; in 3patients, stage was not specified, Mx.MYC amplification was found in 20 patients; MYCN amplification, in 4 patients. Classic medulloblastoma was predominant: 65, and 41 patients had anaplastic/large cell medulloblastoma.

RESULTS
The five-year progression-free survival was 0.51±0.05, the five-year overall survival was 0.52±0.04.The median survival was 82months,and the median progression-free survival was 37 months. There were no significant variations of PFS depending on the sex and age. The treatment results depended on the histological subtype: for classic medulloblastoma, the five-year PFS was 0.57; for the anaplastic/largecell,0.38(р = 0.02030). The presence of metastases significantly affected the survival: PFS for stage M0 was 0.77; for stage М+,0.35(р = 0.00062). Patients with MYC amplification had a significantly worse survival compared to MYCN patients and those without MYC amplification: 0.1, 0.75, and 0.58, respectively (р = 0.00002). Three patients with MYC amplification are alive: two patients had MGMT methylation detected.

CONCLUSIONS
The results of treatment among the patients with molecular subgroup 3 depended on the tumor subtype, presence of metastases, MYC amplification and MGMT methylation. In the absence of unfavorable factors, the survival was the same as in molecular subgroup 4.
MBCL-33. RARE PULMONARY TOXICITY IN THREE MEDULLOBLASTOMA PATIENTS UNDERGOING ANTIANGIOGENIC METRONOMIC COMBINATION THERAPY
Authors: Lenzen Alicia , Gryzlo Daniel , McKenzie Irene , Goldman Stewart , Pillay-Smiley Natasha 
Published: December 2020

Abstract

BACKGROUND
Metronomic and targeted anti-angiogenesis therapy (MEMMAT) has emerged as a promising treatment for recurrent/progressive medulloblastoma. This treatment includes bevacizumab, oral agents (thalidomide, celecoxib, fenofibrate, etoposide & cyclophosphamide) and intrathecal chemotherapy (etoposide & cytarabine). Common toxicities include myelosuppression, nausea, and infection. Mild respiratory toxicities can occur. We report three cases with significant respiratory toxicity.

METHODS
An IRB approved chart review was performed of three children with recurrent medulloblastoma on MEMMAT treatment and meaningful pulmonary toxicity. Literature review found no reports of similar findings.

RESULTS
Patient ages ranged from 3 to 11 years old. Patients completed a mean of 6.33 months on treatment. There was no history of chronic respiratory disease prior to starting MEMMAT. Patient #1 developed chronic cough requiring multiple respiratory and anti-infective treatments; CT scan demonstrated airspace opacities concerning for chronic inflammatory change. Each new viral infection led to significant respiratory distress. He eventually died from respiratory failure with large cystic lesions noted on CT. Patient #2 developed a chronic cough not responsive to antibiotics or respiratory treatments. Images reported airspace disease, bronchiectasis, and chronic inflammatory state. Patient #3 developed chronic cough without improvement despite antibiotics and inhaled respiratory treatments; images were suggestive of small airway disease. All three patients required numerous hospitalizations and additional treatment.

CONCLUSION
With MEMMAT, many side effects are expected though respiratory symptoms have rarely been reported. Our cases highlight the possible important correlation of pulmonary toxicity while being treated on MEMMAT, and its impact on patients’ overall health and quality of life.
MBCL-37. CHEMOTHERAPY STRATEGIES FOR YOUNG CHILDREN NEWLY DIAGNOSED WITH CLASSIC (CLMB) OR ANAPLASTIC/LARGE CELL (A/LCMB) MEDULLOBLASTOMA UP TO THE ERA OF MOLECULAR PROFILING – A COMPARATIVE OUTCOMES ANALYSIS
Authors: Finlay Jonathan , Mynarek Martin , Dhall Girish , Mazewski Claire , Grundy Richard , Cohen Bruce H , Robinson Giles , Ashley David , Stanek Joseph R , Gajjar Amar , Rutkowski Stefan 
Published: December 2020

Abstract

BACKGROUND/OBJECTIVE
The introduction of German regimens, supplementing “standard” chemotherapy with both intravenous high-dose (HD-MTX) and intraventricular (IVENT-MTX) methotrexate, and North American regimens incorporating marrow-ablative chemotherapy with autologous hematopoietic cell rescue (HDCx+AuHCR), report encouraging outcomes for young children with medulloblastoma. We performed a comparative outcomes analysis of treatment strategies for young children with ClMB or A/LCMB. DESIGN/

METHODS
Data from 12 prospective multi-center trials published between 2005 and 2019 for children &lt;six-years-old with ClMB or A/LCMB were reviewed; survivals were compared.

RESULTS
COG-9921, UKCCSG-CNS9204, COG-P9934 and SJYCO7 employing standard chemotherapy with either no or risk-based irradiation, reported 3-5-year event-free survival (EFS) of 17+/-5%, 33+/-28% (ClMB), 14+/-7% and 13.8+/-9% (ClMB) respectively, with reported EFS of 0% for A/LCMB in UKCCSG-CNS9204 and SJYCO7. HIT-SKK’87, HIT-SKK’92 and HIT-SKK’00 incorporating HD-MTX and IVENT-MTX reported 2-10-year EFS of 30–34+/-10–11% for ClMB and 33+/-27% (HIT-SSK’00) for A/LCMB. Head Start HS-I-II combined, CCG-99703 and HS-III employing induction chemotherapy, with or without HD-MTX, followed by single or tandem HDCx+AuHCR reported 3-5-year EFS of 42+/-14%, 50+/-11% and 27+/-6% for ClMB, with EFS for A/LCMB of 38+/-13% (HS-III). Finally, 5-year overall survivals for ACNS0334, without or with induction HD-MTX, are 39% and 69% respectively for ClMB and A/LCMB combined.

CONCLUSIONS
A trend towards better outcomes for young children with ClMB and A/LCMB is observed in trials including either HD-MTX and IVENT-MTX or including HD-MTX-containing induction chemotherapy and HDCx+AuHCR. Trials excluding HD-MTX, IVENT-MTX and HDCx+AuHCR have poorer outcomes.
MBCL-41. LYMPHOHEMATOPOIETIC TOXICITY IDENTIFIED IN PATIENTS WITH MEDULLOBLASTOMA RECEIVING CRANIOSPINAL IRRADIATION
Authors: Watanabe Atsuko , Shimizu Yuuki , Ohta Atsuhiko , Fukushima Takashi , Suzuki Tomonari , Nishikawa Ryo , Tanaka Ryuhei 
Published: December 2020

Abstract

BACKGROUND
Medulloblastoma (MB) is the most common malignant brain tumor of childhood. MB easily disseminates through the spinal fluid. Surgery followed by radiotherapy, applied to the entire craniospinal axis (CSI), and adjuvant chemotherapy, represent the treatment of choice for patients aged ≥3 years. Since the bone marrow of the skull and vertebral column are the major hematopoietic organs, we investigated the myelosuppressive effect of irradiation treatment in patients with MB retrospectively.

METHODS
Medical records of newly diagnosed MB patients treated at our hospital from 2007–2019 were analyzed. Children &lt;3 years old were excluded because they did not receive CSI to avoid potential neurotoxicity.

RESULTS
Medical records of 18 patients (11 males and 7 females, aged 6–26, median 11 years) were reviewed. Eight patients were stratified as high-risk disease and 10 patients with standard risk. All patients received CSI (dosage range 23.4–39.6 Gy based on disease risk) and posterior fossa boost. All patients developed lymphocytopenia (&lt;0.5×109/L) during irradiation, and for 11 of 18 patients, lymphocytopenia (&lt;0.2×109/L) was severe. Although 13 patients recovered from the lymphocytopenia before the initiation of chemotherapy, five patients underwent chemotherapy without recovery. Conversely, only six patients developed neutropenia (&lt;1.0×109/L), and five of the six patients were &lt;10 years old.

CONCLUSION
Although infectious episode associated with lymphocytopenia was not observed in this study, CSI treatment in children and adolescents may induce immunodeficient condition particularly in the lymphocytic system. Pediatric oncologists should pay attention to the impaired immunity of patients with MB who receive CSI.