bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypofractionated radiotherapy versus conventional fractionated radiotherapy in elderly patients with glioblastoma multiforme
Authors: El-Shenshawy H. M. , El-Razek A. Abd , Bader H. 
Published: March 2020

2042 Background: To evaluate efficacy of short- course radiotherapy(RT) in elderly (>60 years) patients with glioblastoma multiforme (GBM), and compare this biological similar short -course radiotherapy with a standard radiotherapy. Methods: Forty-four elderly patients with GBM were randomly assigned after surgery to receive either a short-course of radiotherapy (45 Gy in 15 fractions over 3 weeks) or standard radiotherapy (60 Gy in 30 fractions over 6 weeks) to a target volume described as tumor visible on CT scan and a 2 cm margin. The primary end point was overall survival. Results: The overall response rate and median duration of response were 60% and 8.5 months in short-course RT versus 65% and 8 months in standard RT. Improvement in pretreatment performance status and increase in post-treatment corticosteroid dosage were observed in 50% and 25% in short-course RT versus 40% and 50% in standard RT (P=0.09, P=0.031) respectively. Median survival time was 5.9 months in short-course RT versus 5.6 months in standard RT. Six months, 1-year survival and progression-free survival rates were 40%, 15% and 30% ,10% in short-course RT versus 45%, 10% and 35%, 5% in standard RT, respectively. In both treatment groups, females did significantly better than males, patients with KPS 60–70 did significantly better than those with KPS 50, patients having tumors 4–5 cm did significantly better than those with tumors 6–8 cm as well as did those with more radical surgery when compared to those with biopsy only. On multivariate analysis, only tumor size and extent of surgery were found to independently influence survival. Acute toxicity was generally assessed as mild in the two treatment groups. While RT-induced brain necrosis appeared only in one patient received short- course RT, but this patient died from tumor recurrence. Conclusions: Hypofractionated RT is feasible and safe treatment for elderly patients with GBM. No significant financial relationships to disclose.
Phase I clinical pharmacokinetics of RTA 744: A blood brain barrier penetrating anthracycline active against high-grade glioma
Authors: Kazerooni R. , Conrad C. , Baud C. , Johansen M. , Thapar N. , Meyer C. , Priebe W. , Madden T. 
Published: March 2020

2045 Background: Preclinical studies demonstrated that RTA 744, a 4’-O benzyl anthracycline designed to circumvent P-gp and MRP1-mediated efflux, effectively crosses the BBB, is retained in brain & brain tumor tissue for >24 hrs, and has demonstrated in vivo activity against glioblastoma multiforme (GBM) in an orthotopic model. Methods: We designed a multicenter, phase I dose- escalation study of RTA 744 administered as a short intravenous infusion for 3 consecutive days, every 3 weeks. Patients enrolled in the study were adult patients with recurrent or refractory GBM, anaplastic astrocytoma, or other primary brain tumors. Peripheral blood samples for PK analysis were collected prior to and at selected timepoints from 5 min to 96 hrs after drug administration, and quantified by LC/MS/MS. PK parameters describing RTA 744 disposition were determined by fitting compartmental models to individual patient plasma concentration-time data. Results: Twenty patients have been enrolled at daily doses ranging from 1.2 to 9.6 mg/m2. Mean (range) population terminal half-life was 34.6 (20.5–89.2) hrs, plasma drug clearance was 45.0 (27.4–86.9) L/hr/m2, and Vss was 1942 (684.9–4721.7) L/m2; population PK values reported for doxorubicin are 20–32 hrs, 24–35 L/hr/m2, and 700–1100 L/m2, respectively. Regimen related toxicity has been minimal with the most common adverse event being myelosuppression. Percentage of unchanged parent drug renally eliminated was 2.4% (0.42–6.03%). Several partial responses and one complete response have been noted, even at dose levels below the observed MTD of 7.5 mg/m2/day. Conclusions: These results are similar to what we have observed in our preclinical studies, demonstrating increased lipophillicity and enhanced biodistribution of RTA 744 when compared to doxorubicin. Direct confirmation of drug penetration into the CNS has not been determined in this study, however this is the focus of an ongoing trial in patients with leptomenigeal malignancies. No significant financial relationships to disclose.
Different types of mutations in GISTs: Different clinical implications?
Authors: Braconi C. , Bearzi I. , Bianchi F. , Bracci R. , Costagliola A. , Arduini F. , Mandolesi A. , Cellerino R. 
Published: March 2020

20505 Background: Mutations of KIT or PDGFRa are associated with the pathogenesis of gastrointestinal stromal tumors (GISTs). The prognostic significance of these mutations is still controversial. Methods: We examined 125 patients diagnosed with GISTs. Genomic DNA was extracted from paraffin-embedded tumor tissues and analysed for the presence of KIT exon 9 and 11 mutations and PDGFRa exon 12 and 18 mutations. DFS (Disease Free Survival) was analysed in 92 radically resected patients. The relation between mutations and clinico-pathological factors was analysed using Fisher's exact test and Kaplan-Meyer analysis. Results: KIT mutations occurred in exon 9 in 15 cases and in exon 11 in 78 cases. PDGFRa mutations have been detected mainly in exon 18 (10 cases) and less frequently in exon 12 (3 cases). Exon 11 mutations were as follows: deletions in 58%, point mutations in 30%, insertions and duplications respectively in 4 and 5 cases. Although type of mutations within exon 11 KIT didn't correlate with DFS, a better trend was evident for duplicated and point mutated GISTs. Exon 9 KIT mutated GISTs were associated with intestinal location and higher grade. There was significant association between PDGFRa mutations, gastric location and lower mitotic index. Moreover, PDGFRa mutated and wild type GISTs seemed to have a better outcome. Conclusions: Point mutations and duplications in exon 11 KIT were associated with a better clinical trend in DFS. Exon 9 KIT mutations significantly correlated with intestinal location and higher mitotic count. PDGFRa mutated GISTs were localized in the stomach and seemed to have a favorable clinical behavior. No significant financial relationships to disclose.
Radiation-induced sarcoma: A single center experience with 36 cases
Authors: Mayer F. , Kopp H. G. , Classen J. , Kluba T. , Koenigsrainer A. , Horger M. , Bamberg M. , Hartmann J. T. 
Published: March 2020

20525 Background: Radiation-induced sarcoma (RIS) is a rare complication of radiation therapy for any cause. With increasing numbers of patients receiving radiotherapy, data concerning the incidence and treatment outcome of RIS are urgently needed. Methods: We screened our local sarcoma registry for patients with RIS. 36 cases of RIS that had developed after radiation for malignant disease were identified and analyzed retrospectively over a 12 year period (1994–2006). Results: All patients had received radiation therapy between 1968 and 2002. The most frequent primary tumors were breast cancer (n = 19) and lymphoma (including Hodgkin`s and non-Hodgkin`s lymphoma, n = 9). The remainder received radiation therapy for tumors of the female reproductive organs (n = 2), head and neck cancer (n = 4), neuroblastoma (n = 1), and seminoma (n = 1).The median of delivered total radiation dose per patient was 50 Gy (35 to 72 Gray). Sources of irradiation were photons (n = 9), cobalt (n = 6), electrons (n = 2), and unknown in 19 cases. The median time interval from the start of irradiation the detection of the sarcoma was 11 years (1 - 35 years). The tumors arose within the radiation field in 29 cases, on the border of the field in 6 cases, and out of field in 1 case. The histology of RIS was angiosarcoma in most cases (n = 12), followed by pleomorphic sarcomas (n = 11), leiomyosarcoma (n = 4), fibrosarcoma (n = 2), osteosarcoma (n = 2), and others (n =5). Most cases were detected in a localized stage of disease (n = 33), and therefore, complete surgical removal was achieved in almost 50% (n = 17). However, this did not translate into long term survival within the overall study population. Only 11 patients remain free of disease during a mean follow-up period of 29 months (range, 0 - 51). Conclusions: Angiosarcomas within or on the border of the radiation field are the most common histological subentity of RIS. Therefore, follow-up of previously irradiated patients should include examination of irradiated regions with a high level of suspicion if cutaneous atypical vascular lesions are found. However, the clinician should be aware of the fact that RIS also occurs out of field and can be of non-angiogenic subtype as well. As far as treatment is concerned, RIS is treated the same as non-radiation induced sarcoma. No significant financial relationships to disclose.
The prognostic analysis of gastrointestinal stromal tumor
Authors: Shi Y. , Du C. , Fu H. , Zhao G. , Zhou y. 
Published: March 2020

20534 Objective: To investigate the prognostic factor of gastrointestinal stromal tumor. Methods: The clinicopathological data of 103 patients with gastrointestinal stromal tumors were analyzed restrospectively. Life table, kaplan-meier survival rate and cox regression model were used to evaluate the prognostic factors. Results: The 1 year ,3 years and 5 years total survival rate of these 103 gastrointestinal stromal tumors was 86.3%, 51.7%, 42.8%. Tumor size, mitotic rate, primary organ of tumor and radical surgical excision or not were analyzed respectively, the difference is statistical significance (P<0.05). No significiant difference between the group of sex, age, immunohistochemistry expression and multi-organ resection or not. Conclusion: Flechers’ classification is rational, scientific, simple and feasible. Radical surgical excision is the best therapy to the primary gastrointestinal stomal tumor. No significant financial relationships to disclose.
Phase I trial of VNP40101M in children with recurrent brain tumors—A Pediatric Brain Tumor Consortium (PBTC) study
Authors: Gururangan S. , Turner C. , Stewart C. F. , Kocak M. , Poussaint T. Y. , Boyett J. M. , Kun L. E. , Karsten V. , Gerson S. L. , Friedman H. S. 
Published: March 2020

2059 Background: VNP40101M, a novel DNA alkylating agent and a potent inhibitor of alkylguanine alkyl transferase (AGT) in pre- clinical studies, was evaluated in a phase I study in children with recurrent brain tumors. Methods: VNP40101M was given intravenously (i.v) daily for 5 days q 6 weeks up to 8 cycles. Using the continual reassessment method, dose escalation was performed independently in pts stratified based on intensity of prior therapy (stratum I-less-heavily pre-treated; stratum II- heavily pre-treated). Dose limiting toxicities (DLTs) and responses were assessed at the end of the first and 2nd cycles of treatment, respectively. Correlative studies included pharmacokinetics and measurement of AGT activity in peripheral blood mononuclear cells (PBMC) before and after treatment. Results: 41 eligible pts (stratum I- 19, stratum II- 22; median age 9.3 yrs, range 0.9 to 21.5) were enrolled on this study. Dose levels (in mg/m2/day) evaluated in Stratum I were 45, 60, and 78 mg; In Stratum II 20, 30, 45, and 60 mg. DLT in evaluable pts was myelosuppression (grade IV neutropenia for > 7 days or any grade IV thrombocytopenia) and occurred in 4/16 pts in stratum I [45 mg (n=1/12), 60 mg (n=1/2), 78 mg (n= 2/2)] and 3/19 pts in stratum II [45 mg (n= 3/4), 60 mg (n=0/1), 30 mg (n= 0/12), and 20 mg (n= 0/2)] respectively. Other significant toxicities post first course included renal failure (n=2), pulmonary (n=2), and fatal infection (n=1). PK studies showed median (range) terminal half-life of 62 mins (7.3 to 522 min). The MTDs in stratum I and II were 45 mg/m2/day and 30 mg/m2/day daily for 5 days q 6 weeks, respectively. Objective responses were observed in one pt each with brain stem glioma and medulloblastoma respectively. PBMC AGT levels did not decrease following VNP40101M treatment. Conclusions: The recommended pediatric phase II dose of VNP40101M given i.v daily for 5 days q 6 weeks is 45 mg/m2/day in less-heavily treated and 30 mg/m2/day in heavily treated pts. [Table: see text]
Phase I dose escalation of temozolomide with thiotepa and carboplatin with autologous hematopoietic cell reinfusion in patients with recurrent/refractory malignant brain tumors
Authors: Gardner S. , Fisher M. , Belasco J. , Phillips P. , Finlay J. 
Published: March 2020

2060 Background: The prognosis for most patients with recurrent malignant brain tumors is dismal. Treatment options are limited especially for patients who have already received irradiation. TMZ is an oral alkylating agent which is approved for use in patients with high grade glioma and has also been shown to have activity in patients with recurrent medulloblastoma. It’s primary dose-limiting toxicity is non- cumulative bone marrow suppression. In the present study, TMZ is given in a dose escalation fashion with fixed doses of high dose thiotepa and carboplatin with AHCR in the treatment of patients with recurrent or refractory malignant brain tumors. Methods: Treatment consisted of TMZ twice daily on days -10 to -6 followed by thiotepa 300 mg/m2/day and carboplatin AUC=7/day on days -5 to -3 with AHCR on day 0. Filgrastim was given day +1 and continued until engraftment. Results: 27 patients (18M; 9F) ages 3–46 years were treated from 11/00 until 10/04. Diagnoses included high grade glioma (n=12); medulloblastoma/PNET (n=9); CNS germ cell tumor (GCT) (n=4); and 1 each ependymoma and spinal cord PNET. TMZ doses ranged from 50 mg/m2 twice daily (100 mg/m2/day) to 200 mg/m2 twice daily (400 mg/m2/day) for 5 days. One patient had dose limiting toxicity consisting of reversible veno-occlusive disease at dose level 3 (TMZ 100 mg/m2 twice daily). Two patients had dose limiting toxicity at dose level 7 (TMZ 200 mg/m2 twice daily) consisting of transient encephalopathy (n=1) and severe mucositis (n=1). Additional toxicities included bacteremia (n=11), C. difficile enteritis (n=6) and grade 4 elevation of bilirubin and/or liver transaminases (n=2). There were no toxic deaths. Survival included 3 patients with glioma (38–48 months); two of whom had relapsed following standard dose TMZ; 3 patients with PNET/MB (48–72 months) and 3 patients with CNS GCT (26–71 months). Conclusions: Increased doses of TMZ are feasible when given with AHCR. There is presently a phase II study underway through the Pediatric Blood and Marrow Transplant Consortium evaluating the efficacy of TMZ at a dose of 175 mg/m2/day twice daily for 5 days with high dose thiotepa and carboplatin and AHCR. No significant financial relationships to disclose.
Phase II study of ifosfamide, carboplatin and etoposide (ICE) in recurrent glioblastoma
Authors: Aoki T. , Nojima K. , Mizutani T. , Ishikawa M. , Takasu A. , Hashimoto N. 
Published: March 2020

2066 Background: To evaluate the efficacy and tolerability of ifosfamide, carboplatin and etoposide ( ICE ) in patients with recurrent glioblastoma. Methods: This was an open-label, single-center phase II trial. Forty-two patients with first recurrent glioblastoma after surgery, standard radiotherapy and a first-line temozolomide-based or ACNU-based chemotherapy, were enrolled.The primary endpoint was progression-free survival at 6 months ( PFS-6 ), and secondary endpoints were response rate, toxicity, and survival. Chemotherapy consisted of Ifosfamide ( 700 mg / m2 on day 1, 2 and 3 ), carbopaltin ( 100 mg / m2 on day 1 ), etoposide ( 70 mg / m2 on day 1, 2, and 3 ), every 6 weeks. Results: PFS-6 was 37 %. The median PFS was 17 weeks. Response rate was 27 %. Adverse events were generally mild ( grade 1 or 2 ) and consisted mainly of alopecia. Conclusions: This regimen is well tolerated and has activity in patients with recurrent glioblastoma. No significant financial relationships to disclose.
Radiation and concurrent temozolomide followed by rotational multi-agent chemotherapy for glioblastoma (GBM) patients
Authors: Affronti M. L. , Day J. M. , Herndon J. E. , Rich J. N. , Quinn J. A. , Reardon D. A. , Vredenburgh J. J. , Desjardins A. , McLendon R. E. , Friedman H. S. 
Published: March 2020

2068 Background: GBM is the most lethal type of brain tumor with a 1 yr median survival. We hypothesized that GBM patients who receive adjuvant rotational multi-agent chemotherapy (temozolomide, CCNU, and CPT-11) have improved overall survival when compared to patients receiving single agent adjuvant regimens (carmustine, temozolomide). Methods: We conducted an IRB-approved retrospective data analysis of 80 primary GBM patients who received radiation therapy and concurrent temozolomide followed by 12 mos of adjuvant rotational multi-agent chemotherapy. All patients with the intent to treat were included in the analysis. The survival experience of the Duke cohort was examined within specific patient subgroups defined by the original Radiation Therapy Oncology Group (RTOG) recursive partition analysis (RPA). These data were compared to the recently published Stupp RPA analysis (JCO 2006) and the RTOG trial (radiation alone). Results: 73% were male. Mean age was 52 yrs (range 21–76 yrs); 39 % were < 50 yrs.. 82% were white. WHO performance status was: 0, 14%; 1, 62%; 2, 20%; and 3, 4%. Overall survival was 59% (95% CI: 49%, 71%) at 1 yr and 31% (23%, 43%) at 2 yrs. Median survival was 65.1 wks (49.7, 78.9) with median follow-up of 122.1 wks.. No difference in the 2-yr overall survival rate in RPA classes III-IV was detected between the Duke and Stupp regimens (p>0.4733), but 66% (33, 77) of the Duke rotational therapy GBM patients are living longer than the RTOG patients (p > 0.0086). Univariate Cox Hazard ratio of 1.27 (0.522, 3.08) did not correlate MGMT status with survival (p > 0.60). Conclusions: (1) Concurrent Temozolomide and radiation followed by rotational chemotherapy is an effective therapy compared to recent published gold standard adjuvant regimens. (2) Concurrent Temozolomide and radiation followed by rotational chemotherapy resulted in a statistically significant survival benefit compared to RTOG trial. (3) Lack of correlation between MGMT and overall survival suggests that agents whose damage is not repaired by MGMT may be an important therapeutic approach. (4) Future prospective randomized trials with concurrent Temozolomide and radiation must compare post radiation multi-modality regimens. No significant financial relationships to disclose.
Overall survival of primary glioblastoma (GBM) patients (pts) receiving carmustine (BCNU) wafers followed by radiation (RT) and concurrent temozolomide (TMZ) plus rotational multi-agent chemotherapy
Authors: Rich J. N. , Affronti M. L. , Day J. M. , Herndon J. E. , Quinn J. A. , Reardon D. A. , Vredenburgh J. J. , Desjardins A. , Friedman H. S. 
Published: March 2020

2070 Background: Treatment of pts with primary GBM using BCNU wafer implantation at initial surgery (Westphal, 2003) as well as the administration of TMZ concurrently and after RT (Stupp, 2005) have each been shown to increase survival. Thus, we hypothesize that the use of the combination of BCNU wafer followed by RT and concurrent (TMZ) plus rotational multi-agent chemotherapy (CCNU, TMZ, CPT-11) will increase survival compared to pts that do not receive BCNU wafers. Methods: Retrospective IRB-approved analysis was conducted on 85 eligible GBM pts who received surgery with (36 pts) and without (49 pts) BCNU wafer insertion followed by RT and concurrent (TMZ) plus adjuvant rotational multi-agent chemotherapy. Survival was estimated within treatment groups using the Kaplan-Meier method. Cox regression was used to evaluate the effect of BCNU wafers on survival after controlling for covariates such as RPA (Recursive Partition Analysis) class, race, and gender. Results: Within the non-BCNU wafer cohort, 39% of patients were younger than 50 and 89% had KPS>70%. Within the BCNU cohort, 31% of patients were younger than 50 and 94% had KPS>70. Overall 1- and 2-year survival for the non-BCNU wafer cohort was 67% (95% CI: 55%, 82%) and 27% (95% CI: 17%, 42%), respectively, with a median survival of 72.7 wks (median follow-up: 123.9; range 14.3–198). Overall 1-year survival for the BCNU wafer cohort was 78% (95% CI: 65%, 93%) with a median survival of 89.6 wks (median follow-up: 118.6; range 26.7–192.1). Given the trends towards significance (p=0.092) between the two groups using a log-rank test, a Cox regression model to control for known prognostic factors was examined: Conclusions: After controlling for the effects due to RPA class, a significant difference in survival is found between treatment groups (p = 0.0325) and patients receiving BCNU wafers have a lower risk of death (HR = 0.548) than patients not receiving BCNU wafers. [Table: see text] No significant financial relationships to disclose.
Joint NABTC + NCCTG prognostic factors analysis for high grade recurrent glioma
Authors: Lamborn K. , Wu W. , Prados M. , Jaeckle K. , Chang S. , Novotny P. , Buckner J. 
Published: March 2020

2075 Background: Multiple variables may impact endpoints used to assess therapeutic efficacy for patients with recurrent gliomas. To identify prognostic factors for each of 3 outcome variables, a master analysis file was constructed by pooling datasets summarizing key baseline factors and outcomes obtained in 15 North Central Cancer Treatment Group (NCCTG) trials (n=583, 1980–2004) and 12 North American Brain Tumor Consortium (NABTC) trials (n=596, 1998–2002). Methods: In addition to traditional variables (gender, age, performance score (PS), race, extent of primary resection, year of study entry, last known histology, time since initial diagnosis, baseline steroid use, prior chemotherapy (Y/N), prior nitrosoureas, baseline anticonvulsant use), we investigated prior t (TMZ), number of relapses, academic vs. community site and low grade at initial diagnosis. Outcome variables were: (1) overall survival (OS), (2) progression free survival (PFS) and (3) PFS6 = proportion of patients alive and progression-free 6 months after start of treatment. For all 3 endpoints, Classification and Regression Tree (CART) models and bootstrap samples were used to identify prognostic variables and to look for evidence of interactions among the independent variables affecting outcome. Results: For all outcomes the initial CART analysis selected last known grade (4 vs. 3) as the most important variable. Additional factors selected as predicting poor prognosis differed with grade and outcome measure and included prior TMZ, longer time since primary diagnosis, older age and poor PS. Community vs. academic was not a strong predictor in any of the models nor was low grade at initial diagnosis. Additional analyses are planned to better describe the impact of all the variables on outcome, including use of Cox models and logistic models considering all baseline variables with backwards selection. Conclusions: The results from analyses to date are consistent with current thinking that last known histology (grade) is an important factor. Time since initial diagnosis is likely a surrogate for number of relapses. More definitive conclusions await the completion of ongoing analyses. No significant financial relationships to disclose.