bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II trial evaluating tumor penetration of bortezomib in patients with recurrent malignant gliomas treated prior to surgery and then treated with bortezomib and temozolomide postoperatively.
Authors: Raizer Jeffrey J. , Grimm Sean Aaron , Levy Robert M. , Muro Kenji , Rosenow Joshua M. , Chandler James , Bredel Markus 
Published: March 2020

2035 Background: NF-Kappa B is one of the mechanisms of resistance for malignant gliomas. A few trials have assessed bortezomib in the treatment of malignant gliomas with limited activity. This may in part be due to limitations in dose escalation from peripheral neuropathy. We performed a phase II trial with the goal of measuring bortezomib in tumor tissue and also its effects on NF-Kappa B. Methods: Patients felt to be surgical candidates were enrolled after signing an IRB approved consent. They were treated with bortezomib 1.7 mg/m2 IV on day 1, 4 and 8 and then had surgery on day 8 or 9. Approximately, 14 days post operatively, patients were started on temozolomide 75 mg/m2 PO on days 1-7 and 14-21; on day 7 and day 21 they received bortezomib 1.7 mg/m2 (1 cycle was 1 month). Treatment continued until progression. If <1 patient had a PFS at 6 months the trial would be stopped. Results: 10 patients were enrolled (8 M and 2 F). Median age and KPS were 50 (42-64) and 90% (70-90). All but 1 patient went to surgery, one had an intracranial hemorrhage. The median number of cycles post operatively was 2 (1-4), with two patients discontinuing for wound infection (post 3 cycles, not restarted due to prolonged delays) and meningitis (post 2 cycles then withdrew from trial). Six patients are deceased. Trial was stopped as no patient had a PFS-6. PK analysis revealed measurable drug levels in tumor tissue. Conclusions: Post operative treatment with temozolomide and Bortezomib did not have any activity. Bortezomib can achieve measurable drug levels in tumor but may not be sufficient for anti-tumor activity. Tissue will be assessed for bortezomib effects on NF-Kappa B.
Lenalidomide and irinotecan in adults with recurrent malignant gliomas: Phase I results of the phase I/II trial.
Authors: Puduvalli Vinay K. , Groves Morris D. , Gilbert Mark R. , Hess Kenneth R. , Kang Sanghee , Ictech Sandra , Conrad Charles A. , Loghin Monica Elena , De Groot John Frederick , Levin Victor A. , Yung W. K. Alfred 
Published: March 2020

2036 Background: Patients with recurrent malignant gliomas have limited treatment options. We previously reported promising results using 6 month progression free survival [PFS6] endpoint combining irinotecan and thalidomide compared to historical controls. In this study, we tested the tolerability and efficacy of Irinotecan combined with Lenalidomide, a more potent thalidomide analogue with unique antiangiogenic and immunomodulatory properties. Methods: This phase I portion of the phase I/II study aimed to determine the maximum tolerated doses (MTD) of irinotecan and lenalidomide. Eligible patients were adults (>=18 y) with recurrent WHO Grade 3 or 4 gliomas who were not on EIAED, had failed prior radiation therapy, had a KPS>=60, had adequate marrow, renal and hepatic organ function, no major medical illnesses and no other concurrent malignancies. Each cycle was designated as 4 weeks in duration. Results: Two of the 4 patients enrolled at the starting dose level of Lenalidomide 10 mg/day on days 1-21 and irinotecan 200 mg/m2 q2 weeks developed rash as dose limiting toxicity (DLT). The trial was restarted with no change in irinotecan dose but with a lowered Lenalidomide dose of 7.5 mg/day for cycle 1 with escalation to 10 mg/day for cycle 2 and beyond. Of 3 eligible patients enrolled, no DLTs were noted even after cycle 2. The dose was hence escalated to Lenalidomide 10 mg/day with unchanged irinotecan dose. Only 1/6 patients experienced a DLT (pulmonary embolism); however, it was noted that 4/6 patients required dose reduction of irinotecan to 150 mg/m2 after cycle 1. One patient died during cycle 2 of unknown causes (autopsy declined) without reports of preceding toxicities. Non DLT toxicities included neutropenia, leukopenia, hypokalemia, diarrhea, fatigue and nausea/vomiting. Lenalidomide pharmacokinetic data, obtained by serial blood draws initially after one dose of the drug on day 0 and subsequently after irinotecan and lenalidomide dose on day 1 to examine drug interactions, will be presented. Conclusions: Based on these results, the maximum tolerated dose was Lenalidomide 10 mg/day on days 1-21 and irinotecan 150 mg/m2 q 2 weeks every 28 days which will be used in the phase II study that will open shortly.
Does pilocytic astrocytoma (PA) in adults have a different prognosis than PA in children?
Authors: Marques Daniel Fernandes , Santana Iuri amorim , Guindalini Rodrigo Santa Cruz , Neto Hugo Sterman , Crosara Marcela Alves Teixeira , Teixeira Manoel Jacobsen , Hoff Paulo Marcelo , Feher Olavo 
Published: March 2020

2038 Background: Pilocytic astrocytoma (PA) accounts for up to 25% of all brain tumors in children. A 75% progression-free survival rate at 5 years and overall survival rates of 95.8% at 10 years have been reported after a complete resection. However, the incidence in adults is low and the outcome less well characterized. We conducted a retrospective analysis of adult PAs identified in order to review the clinical characteristics and outcome of this neoplasm in this age group. Methods: A descriptive, cross-sectional study was undertaken in patients over 16 y.o., diagnosed with PA between January 1990 and December 2010 at our center. Clinical characteristics, date and extent of surgery, tumor location, postoperative treatment, complications and recurrences were collected from hospital records. Results: From May, 1990 to December, 2010, 18 eligible adult patients (pts) with the diagnosis of PA were identified. Median age was 25,5 (16-52) years, 72,2% female and 83,3% had an ECOG performance status ≤ 2. The most frequent tumor sites were the cerebellum (44,4%), followed by the cerebral hemispheres (38%). All patients underwent surgery as primary treatment, 72% had a complete macroscopic resection (CMR) and 28% had a partial resection (PR). Two patients received postoperative radiotherapy: one following a PR and the other after tumor relapse following a CMR. Two patients relapsed five months and 44 months after initial complete gross resection. Salvage surgery achieved CMR in both. With a median follow-up of 89 months, all patients are alive, except for one who died in the postoperative period due to fungal meningitis. Of note, none of 5 pts undergoing a partial resection progressed and 3 are alive for more than 10 years. Conclusions: As it occurs in the pediatric population, PA in adults seems to carry a similarly favorable prognosis. It is conceivable that after initial surgical resection a watch and wait type of approach is appropriate, even following partial resection. The role of upfront radiotherapy is uncertain and it should probably be left for progressive tumors.
Use of a non-coplanar half-beam block on the lower spinal field to decrease the maximum bowel and cumulative dose in craniospinal irradiation.
Authors: Kathpal Madeera , Davis Rihan 
Published: March 2020

2039 Background: To develop and compare a non-coplanar half beam block technique that can be used in both prone and supine treatment positions with conventional beam matching for craniospinal irradiation (CSI) in order to decrease the maximum cumulative dose and dose to the bowel, while maintaining the therapeutic dose to the spinal axis. Methods: Ten treatment plans from five patients who underwent CSI were analyzed. The bowel was contoured en bloc for each patient on their simulation cat scan. Two different geometric techniques for each patient were planned and analyzed. The first technique consisted of the conventional method for CSI utilizing two coplanar beams to cover the entire spinal axis. The other technique used a non-coplanar half beam block on the lower spinal beam to exactly match the upper spinal beam’s divergence. Four “featherings” between the two spinal beams for each technique were still necessary to minimize under and overdosing which occur at abutting beam fields. Maximum doses for the plan and the bowel were compared between the two techniques on the same patient. Results: The maximum bowel dose was decreased between 10 to 35 percent when the non-coplanar half beam block was used. The maximum doses for the conventional technique were 5 to 35 percent higher than the plans using a non-coplanar half beam block. The homogeneity of the dose to the spinal axis was not altered with the use of the non-coplanar half beam block. Conclusions: Use of a non-coplanar half beam block to match the two spinal fields in craniospinal irradiation significantly reduces the maximum dose to the bowel and of the entire plan possibly resulting in reduced gastrointestinal toxicity while maintaining therapeutic dose to the spinal axis.
Relationship of cognitive function, quality of life (QOL), and neuroimaging in primary CNS lymphoma (PCNSL) survivors.
Authors: Doolittle Nancy Diane , Korfel Agnieszka , Lubow Meredith A. , Schorb Elisabeth , Schlegel Uwe S. , Rogowski Sabine , Fu Rochelle , Dosa Edit , Illerhaus Gerald , Kraemer Dale F. , Calabrese Pasquale , Hedrick Nancy A. , Muldoon Leslie L. , Maron Leeza M. , Jahnke Kristoph , Butler Robert W. , Neuwelt Edward A. 
Published: March 2020

2040 Background: Delayed treatment-related neurotoxicity in PCNSL is a significant problem since improved treatments have increased survival. The study purpose is to describe and correlate neuropsychologic (NP), QOL and neuroimaging outcomes as neurotoxicity indicators. Methods: Four centers in Germany and U.S. prospectively evaluated PCNSL patients (pts) in complete remission (CR) for 2 yrs or more, treated as shown in the Table. NP tests evaluated attention/executive function, verbal memory, motor skills, and QOL (Correa, Ann Oncol 2007). Brain MRI was obtained; the size of T2 abnormalities was determined using two perpendicular linear measurements where hyperintensities were largest and the sum of the measurements was calculated. Differences in total T2 among treatments were compared using analysis of variance; correlations between total T2 and NP or QOL results were assessed using Pearson’s correlation coefficient (r). Results: From Feb 2009 to Feb 2011, 80 pts were evaluated (43 male; median age, 59; median KPS, 80). Median follow-up from diagnosis to evaluation was 5.5 yrs. Total T2 abnormalities were significantly different among treatments (p = 0.0006). The mean area of total T2 in pts treated with WBRT was significantly higher and more than twice the mean of any of the other 3 treatments. Total T2 abnormalities were negatively associated with NP results ie. attention/executive function, r = -0.38 (p = 0.0006), verbal memory, r = -0.23 (p = 0.042), motor skills, r = -0.28 (p = 0.016), composite score, r = -0.34 (p = 0.002); and functional/global QOL (higher total T2 associated with lower QOL). Conclusions: This large PCNSL series in long-term (LT) CR reveals higher total T2 abnormalities in pts treated with WBRT, which are associated with poorer cognitive performance and lower QOL at LT follow-up. Enhanced chemotherapy results in exciting LT survival and function. [Table: see text]
The effect of the addition of chemotherapy to radiotherapy on cognitive function in patients with low-grade glioma: Secondary analysis of RTOG 98-02.
Authors: Prabhu Roshan Sudhir , Won Minhee , Shaw Edward G. , Wang Meihua , Brachman David , Mehta Minesh P. 
Published: March 2020

2047 Background: The addition of PCV chemotherapy to radiotherapy (RT) for patients with WHO grade II glioma improves progression free survival (PFS) and overall survival (OS), for patients surviving at least 2 years (Shaw, J Clin Oncol 26: 2008). The effect of therapy intensification on cognitive function (CF) remains a concern in this population with substantial long term survival. Methods: 251patients with WHO grade II glioma and age > 40 with any extent of resection, or age < 40 with subtotal resection/biopsy were randomized to RT (54Gy) or RT + PCV. 111 patients with age < 40 and gross total resection were observed. CF was assessed by mini-mental status exam (MMSE)at baseline and years 1, 3, and 5 for patients without progression. Change in MMSE score from baseline of > 3 points was considered clinically significant. Results: Overall, very few patients experienced significant decline in MMSE score, with a median follow-up time of 9.7 years for alive patients. There were no significant differences in the proportion of patients experiencing MMSE decline between study arms at any time point. The table below summarizes MMSE change from baseline over time. Neither baseline MMSE score nor change in MMSE at year 1 significantly predicted for OS or PFS, but there was a trend towards worse OS for patients with MMSE loss of ≥ 2 points [HR 1.73, 95% CI (0.86, 3.47), p=0.12]. Conclusions: The MMSE is a relatively insensitive tool that has not been validated in patients receiving cranial RT, and subtle changes in CF may have been missed. However, the addition of PCV to RT for low grade glioma did not result in significantly higher rates of MMSE decline than RT alone or observation. There was a trend towards an MMSE decline of ≥ 2 points at year 1 predicting for worse OS. [Table: see text]
First results of radiotherapy after hyperbaric oxygenation with temozolomide for high-grade gliomas.
Authors: Khelif David Hamid , Kintzinger Clement , Taha Said , Gauchez Philippe , Bintner Marc , Chirpaz Emmanuel , Harms JAN-Dirk , Magnin Valerie Florence 
Published: March 2020

2048 Background: The outcome of patients with high-grade gliomas remains poor despite modern therapeutic arsenal. The objective of this study was to assess the feasibility and efficacy of radiotherapy (RT) given immediately after hyperbaric oxygenation (HBO) with Stupp protocol. Methods: All patients with histologically confirmed high-grade gliomas from 2008 till 2011 coveraged at GHSR hospital were enrolled. Patients underwent Stupp protocol consisting in 60 Gy RT with a daily dose of 2 Gy for 5 days per week administrated immediately after HBO. Temozolomide (TMZ) was administrated at the daily dose 75 mg/m², 7 days per week followed by 6 cycles of TMZ 150 to 200 mg/m² for 5 days each 28 day-cycle. HBO schedule was approximately 15 min of compression with air, 60 min of 100% oxygen inhalation and 10 min of decompression with oxygen. Results: A total of 21 patients were diagnosed and histologically confirmed high grade gliomas. Five were excluded because of HBO contraindications. Twelve patients (75%) had undergone debulking surgery. The time interval from completion of decompression to start of irradiation was less than 15 minutes (mean 14.25, range 8-18). Twelve patients (75%) received the complete dose of RT and TMZ. HBO was completed for 7 (43.75%). Five (31.25%) were temporarily stopped and 4 (25%) were definitively stopped. One patient (6.25%) suffered from pancytopenia with grade 4 thrombopenia and grade 3 neutropenia. The median follow up was 46.95 weeks (range 5.7-108.3). Nine patients (56.25%) are still alive. Four (25%) have a survival more than 16 months. Conclusions: HBO with Stupp protocol is feasible and promising but requiring a large multicentric study.
Natural history of glioblastoma in the modern era: Longitudinal results from a large prospective Italian register.
Authors: Brandes Alba Ariela , Franceschi Enrico , Ermani Mario , Depenni Roberta , Poggi Rosalba , Pisanello Anna , Marcello Norina , Valentini Antonella , Albani Fiorenzo , Faedi Marina , Guiducci Graziano , Urbini Benedetta , Crisi Girolamo , Dascola Isabella , Mucciarini Claudia , Dazzi Claudio , Cavanna Luigi , Bartolini Stefania , Cavallo Michele , Baruzzi Agostino 
Published: March 2020

2057 Background: The role of temozolomide (TMZ) concurrent with and adjuvant to radiotherapy (RT) in the treatment of glioblastoma (GBM) has been demonstrated by the EORTC 22981/26981-NCIC CE.3 (EORTC/NCIC) randomized trial, and has been widely accepted as the standard treatment. The impact of RT/TMZ in the general patient population was assessed in the context of the Registry of the Project of Emilia-Romagna Region in Neuro-Oncology (PERNO), that represents the first italian prospectic observational population-based study in neuro-oncology. Methods: Approvals from local Ethical Committees were obtained by 8 participating centres. Patients (pts) who met the following inclusion criteria were evaluated: age ≥18 years; PS 0-3; histologically confirmed GBM, no previous or concomitant non glial tumoral disease, resident in Emilia Romagna region. The data were prospectively collected. Results: From January 2009 to January 2011, 194 GBM pts were enrolled. The median age was 62.5, with 26% of pts over 70 years. After surgery pts received RT/TMZ (73%), RT alone (19%), TMZ alone (5%) or no further treatment (3%); 22% were included in clinical trials. Median overall survival (OS) was 12.9 months. Pts <70 years received RT/TMZ in 85% of cases. In this group of pts mOS was 17 months (95%CI: 15.4–18.6). Interestingly, pts <70 years included in experimental clinical trials showed a significant OS improvement (p=0.04). In multivariate analysis, only extent of surgery (p=0.047), KPS (p=0.01) and RT/TMZ (p<0.001) were associated with OS in pts <70 years. Conclusions: Our population data reproduces the beneficial effect of RT/TMZ from the EORTC/NCIC randomized trial, confirming how this successful approach as been widely incorporated in daily practice. Interestingly, our data suggest that the survival of GBM pts treated with RT/TMZ could be greater than patients treated with RT/TMZ in the EORTC/NCIC trial at the beginning of this century.
Quality of life in patients with malignant brain tumors.
Authors: Choucair Ali K. , Shields Lisa B.E. 
Published: March 2020

2058 Background: A positive quality of life (QOL) serves as an important outcome priority in patients with malignant brain tumors whose survival is limited by tumor resistance to treatment. The FDA and ASCO have designated QOL as an outcome secondary in importance to survival. We conducted a prospective longitudinal collection of QOL measures (EORTC QLQ-C30, EORTC QLQ-BN20, and Hospital Anxiety and Depression Scale [HADS]) coupled with clinical standards of care (brain MRI and clinical history and physical examinations) in patients with newly diagnosed primary brain tumors (PBT). We also examined the QOL measures over time as related to tumor progression. Methods: Under an IRB-approved protocol, we reviewed the validated QOL measures and standard clinical measures from patients who were newly diagnosed with PBT. The patients were followed every 3 months over 2 years. No proxies were allowed. A total of 52 patients were enrolled in the study. Survey responses were compared between two tumor groups of patients: patients with tumor recurrence and/or died and patients without a recurrence (n=26 each group). A total of 17 patients succumbed to a tumor-related death. Statistical analysis utilizing non-parametric t-tests and Wilcoxon sign tests assessed QOL responses. Results: Significant group differences were noted in the questions of the QOL measures surveys with more negative responses in the recurrence group. The questions with significant group differences on the EORTC QLQ-C30 ranged from symptoms of dyspnea (p<.05) and difficulty sleeping (p<.05) as well as a poor QOL (p<.005) and pain interfering with daily activities (p<.05). Significant group differences of questions on the EORTC QLQ-BN20 included weakness of the legs (p<.05), coordination difficulties (p<.005), and unsteady gait (p<.05). Significant group differences of questions on the HADS reflected a patient who is "slowed down" (p<.01) and "frightened" (p<.05). Conclusions: Our analysis of questions answered by patients with newly diagnosed PBT may shed light on the impact of cancer and its treatment and potential recurrence on a patient's QOL. Further research is warranted to incorporate QOL measurements into improvement of patient care and their use in clinical trials and as a prognostic indicator.
Tolerance and feasibility of chemotherapy by procarbazine, lomustine, and vincristine (PCV) for oligodendroglial anaplastic gliomas (OAG).
Authors: Daros Marine , Tabouret Emeline , Barrie Maryline , Matta Mona , Autran Didier , Boucard Celine , Wertz Marie , Figarella Dominique , Honoré Stéphane , Chinot Oliver L. 
Published: March 2020

2060 Background: Chemosensitivity of OAG has been documented although their role as part of adjuvant treatment combined to radiotherapy is debated. Beside temozolomide still under investigation, several studies have underlined activity of PCV regimen in this setting. However, significant toxicity has been described and dose intensity and schedule duration are not clearly reported. Methods: This monocentric retrospective analysis included all pts with OAG treated with at least 1 cycle of PVC (lomustine 110mg/m2 every 6 weeks) at our institution from August 2007 to August 2011 (pharmacy charter). Toxicities data were collected from clinical observations and blood investigations. Results: 40 pts were identified (M/F: 23/17). Median age was 45y (20 – 72). At the time of analyses, 32 pts were still alive. Histologies were oligodendroglioma (73%) or oligoastrocytoma (27%). Codeletion 1p19q was observed in 30 % of pts. PCV was administered in first or second line of chemotherapy for 60 % and 40 % of pts respectively. Seventy five percent and 52.5% of pts completed at least of 4 and 6 cycles respectively. Discontinuation of PCV occurred in 45% of pts for toxicity (10%), progression (30%), or other reason (5%). Because of toxicity 38/196 (19%) PCV cycles were delayed. Dose was adapted for 73% of pts and decreased under 60% of theoretical dose in 30% of pts at cycle 4 and in 57% of pts at cycle 6 (table1). Grade III or IV toxicity occurred in 28% of pts and only grade I-II in 50%. Neuropathies occurred in 43 % of pts. Conclusions: Despite activity of PCV regimen, significant toxicity is associated to this schedule, that impact feasibility and compliance. PVC schedule should be redefined taking into account dose intensity applied in toxicity observed. [Table: see text]