bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase IIa trial of cilengitide (EMD121974) single-agent therapy in patients (pts) with recurrent glioblastoma (GBM): EMD 121974-009
Authors: Reardon D. , Fink K. , Nabors B. , Cloughesy T. , Plotkin S. , Schiff D. , Raizer J. , Krueger S. , Picard M. , Mikkelsen T. 
Published: March 2020

2002 Background: Our phase IIa study evaluated the safety, toxicity, and clinical activity of the cyclic RGD pentapeptide cilengitide (EMD121974), an inhibitor of integrins avβ3 and avβ5, as a single agent at doses of 500 and 2000 mg in pts with recurrent GBM. Methods: In this multicenter, open-label, randomized, uncontrolled study, pts with GBM and measurable disease that had relapsed after previous temozolomide and radiotherapy were randomized to receive cilengitide at either 500 mg or 2000 mg i.v., 2x/week, until progression. Neurologic exams were performed after every cycle (4 weeks) and MRIs were performed every other cycle. Central, blinded pathology and radiology reviews were performed. The primary endpoint was Progression Free Survival (PFS) at 6 months (6-mth PFS). Secondary endpoints included response, survival, time to disease progression, safety, tolerability and pharmacokinetics (PK). Results: 81 pts accrued (median Karnofsky Performance Status 80%; median age 57 yrs) at 15 sites including 41 at the 500 mg and 40 at the 2000 mg dose levels. Demographic and pretreatment variables were comparable between dose level cohorts. The median number of infusions was 16 [range, 4–179]. PK studies revealed significantly greater exposures among the 2000 mg cohort. Treatment related NCI CTC grade 3 adverse events (AEs) included elevated transaminases (at 500 mg), arthralgia/ myalgia (at 500 mg), and weight increase/ edema (at 2000 mg) in 1 patient, respectively. No grade 4 therapy related AEs were reported. One CTC grade 2 cerebral hemorrhage was reported in a pt at progression. The 6- mth PFS was 16.1% (n=13/81 pts). 10 pts (12.3 %, n=4 with 500 mg, n=6 with 2000 mg) received 12 or more cycles. Six pts (7.4%) remain progression-free and on treatment. Median Overall Survival (mOS) was 6.5 mths [95% CI: 5.2–9.3 mths] in the 500 mg arm and 9.9 mths [95% CI, 6.3–15.7 mths] in the 2000 mg arm. Although not statistically significant, there was a trend towards better tumor control in pts receiving 2000 mg 2x/week. Conclusions: Cilengitide was well tolerated and demonstrated single agent activity in recurrent GBM, with long term disease stabilization in a subset of pts. [Table: see text]
Imatinib mesylate in the treatment of paediatric chronic myeloid leukaemia (CML): A study of 30 cases from a regional cancer centre in western India
Authors: Parikh AP S. K. , Shukla S. N. , Shah P. M. , Patel K. M. , Parikh B. J. , Addl A. S. Anand , Asso S. S. Talati , Shah S. A. , Panchal H. P. , Patel A. A. 
Published: March 2020

20021 Background: CML is a very rare disease in childhood. There are scant data available concerning the use of Imatinib in the paediatric patients. Methods: Thirty cases of paediatric CML (25 males, 5 females; median age-11, range: 4–14 years, 23 Interferon naive, 1 interferon resistant) during the period of September 2003 to October 2006 were analyzed. Results: There were 28 patients in chronic phase (CP), 1 accelerated phase (AP) and 1 with blast crisis (BC). All patients were Philadelphia positive (Ph+) (20 by G-banding, 10 by fluorescence in situ hybridization [FISH]) and treated with imatinib using 260 mg/m2 daily for CP and 340 mg/m2 for AP/BC. The median time from diagnosis to imatinib therapy was 4 months (range: 0.5–91 months). Twenty-five (92.5%) of 27 evaluable patients achieved complete haematological remission (CHR) (World literature 95% in adult) at a median duration of 60 days (range: 25–150 days). Two patients did not respond; one of them with BC died due to progressive disease and three patients were not evaluable (2 patients loss to follow up and in 1 patient imatinib started recently). Complete cytogenetic response (CyGR) was achieved in 7 of 15 patients studied; 2 patients had partial CyGR while 4 had no CyGR while in 2 patients result was inconclusive. In 2 patients molecular remission was studied with RT-PCR, had attained it at 12 months. Overall, the drug was well tolerated and none of the patients had to permanently discontinue the drug. There were no treatment related deaths. The common adverse events were thrombocytopenia (6.6%), neutropenia (16.6%), skin rash (6.6%), anaemia (3.3%), superficial oedema (6.6%), weight gain (6.6%) and muscle cramps (3.3%). Severe (grade III-IV) events were infrequent except 1 patient with grade IV febrile neutropenia. At median follow up of 24 months (range: 1–35 months, 11 patients followed >24 months), one patient has haematological relapse while one patient has disease progression in form of myeloblastic crisis. Conclusions: The Imatinib mesylate treatment is safe and it achieves rapid and higher CHR in paediatric CML. No significant financial relationships to disclose.
Identification of novel candidate genes for ependymoma progression in chromosomal regions over-represented at recurrence and detected by CGH array
Authors: Puget S. , Valent A. , Bieche I. , Dessen P. , Kauffmann A. , Peyre M. , Dirven C. , Sainte-Rose C. , Vassal G. , Grill J. 
Published: March 2020

2008 Background: The biology and genetics of ependymomas remain poorly understood. As opposed to other pediatric tumors, few recurrent chromosomal abnormalities or relevant pathways have been identified. Method: In order to gain new insight into the molecular mechanisms involved in ependymoma progression, we performed BAC array-based comparative genomic hybridization (aCGH) in a series of 59 tumors at diagnosis and at relapse (42 posterior fossa and 17 supratentorial). Specific chromosomal imbalances were confirmed by FISH. Expression of candidate genes was evaluated by RT-PCR and immunohistochemistry. Results: As compared to CGH (Cancer Genet Cytogenet 2002), aCGH detected more abnormalities since 18/33 samples at diagnosis and 22/26 at recurrence showed chromosomal imbalances. Three distinct patterns were observed : no imbalance (15 at diagnosis, 4 at relapse), large and numerous imbalances (7 at diagnosis, 12 at relapse) and small and rare imbalances (11 at diagnosis, 10 at relapse). At diagnosis, absence of chromosomal imbalance was correlated with young age (p=0.034) and shorter progression-free survival (p=0.014). At relapse, patients with large and numerous imbalances had a shorter survival (p=0.026). Specific chromosomal imbalances were significantly more frequent at recurrence: 9 qter gain (54% vs 21%), 1q gain (12% vs 0%) and 6q loss (27% vs 6%). Samples were available both at diagnosis and relapse for 16 patients. Whole genome changes were towards increase of genomic abnormalities (n=10) but also simplification (n=6), the former being associated with a higher risk of death from disease (Fisher exact, p=0.03). A candidate gene strategy was focussed on the frequently gained 9qter locus. Significant overexpression compared to normal brain was identified for Tenascin-C (median 35 fold, max 220 fold, p<0.0001) and Notch1 (median 6 fold, max 45 fold, p<0.0001). Notch pathway analysis by RT-PCR revealed potential regulatory loops between JAG1/2 or DLL1/3 and Notch1/2. Conclusion: aCGH pattern may identify subgroups of ependymomas with respect to prognosis. Notch pathway and Tenascin-C are important regulatory genes in ependymoma progression and may represent interesting new targets for therapy. No significant financial relationships to disclose.
F-18-labeled fluorodeoxyglucose positron emission tomography for evaluation of disease extent, response to treatment and follow-up in primary CNS lymphoma
Authors: Kiewe P. M. , Maza S. , Munz D. , Korfel A. , Thiel E. 
Published: March 2020

2015 Background: Fluorine-18-labeled (18F) fluorodeoxyglucose (FDG) positron emission tomography (PET) has demonstrated remarkable sensitivity in the detection and follow-up of malignant lymphoma. The aim of this study was the prospective evaluation of potential benefits of FDG-PET including whole-body PET for evaluation of disease extent, response to treatment and follow-up of patients with primary CNS lymphoma (PCNSL). Methods: Extent of disease and response to therapy were evaluated using homologous scans of MR imaging and a total number of 36 18F-FDG-PET examinations in 10 immunocompetent patients with newly diagnosed or recurrent PCNSL before and repeatedly during treatment and follow-up. Results: In 4 of 10 patients before treatment, MRI findings lacked a PET correlative, and in two patients each one additional lesion not visualized by MRI was detected by PET. Additional systemic spots of activity in whole-body PET were found in two patients and confirmed as asymptomatic lymphoma manifestations by computed tomography (CT) in one patient. Under treatment, tumor response was congruent on PET and MRI in 4 of 6 patients. In two patients, however, PET indicated complete disappearance of vital tumor while findings persisted on MRI. During follow-up in a series of 5 patients, pathologic FDG-uptake had been found in one patient on PET 34 weeks after therapy and 9 weeks before relapse was diagnosed on MRI. In another patient, relapse was suspected on PET 76 weeks after therapy without a correlative on MRI performed 2 and 6 weeks thereafter. Conclusions: In PCNSL, FDG-PET may contribute additional information regarding the extent of disease and response to treatment. Relapse can probably be detected earlier than with MRI. No significant financial relationships to disclose.
Leptomeningeal disease from oligodendroglioma: Clinical and molecular analysis
Authors: Roldán G. B. , Scott J. , George D. , Easaw J. , Yan E. , Parney I. , Cairncross G. , Forsyth P. 
Published: March 2020

2019 Background: Leptomeningeal disease (LMD) is a late complication of malignant glioma, mostly of glioblastoma, that usually responds poorly to treatment and is rapidly fatal. A long surviving case led us to review our experience with LMD in patients with oligodendrogliomas. Methods: A 10-year retrospective chart review was performed. Patients with both oligodendroglial tumors and LMD were identified. A single neuro-pathologist reviewed all histological sections, a single neuro-radiologist reviewed all available images and 1p/19q status was assessed. Results: Seven patients with an oligodendroglioma and LMD were identified. Six were male. Median age at tumor diagnosis was 41 years (range, 28–50). None had radiographic or pathological evidence of leptomeningeal or subependymal tumor at initial diagnosis. Most patients had pure anaplastic oligodendrogliomas (4/7); 6/7 had 1p/19q co-deletion. The median time to first relapse was 41 months (range, 19–127). LMD was diagnosed at first relapse in one case and subsequently in six. The median time to LMD was 76 months (range, 19–151) from initial diagnosis and 28 months (range, 0–36) from first relapse, respectively. LMD treatments included spinal radiation and intrathecal and systemic chemotherapy. After progression, some patients with LMD remained stable clinically. The median survival from initial diagnosis was 104 months (range, 19–183) and from LMD diagnosis was 32 months (range, 2–43). Conclusions: LMD is a complication of oligodendroglioma that may occur preferentially in long surviving patients with 1p/19q co-deletion. LMD in patients with oligodendrogliomas appears to be relatively indolent which may have implications for their treatment and be related to 1p/19q status. No significant financial relationships to disclose.
Leptomeningeal metastases: Results of different therapeutic approaches
Authors: de Wit M. , Lange-Brock V. , Kruell A. , Bokemeyer C. 
Published: March 2020

2047 Background: The aim of this study was to compare different treatment options for patients with leptomeningeal metastases (LM). Method: In this retrospective single center study all patients (n=135) between 1985 and 2005 diagnosed with leptomeningeal metastases (LM) showing malignant cells in the cerebrospinal fluid (CSF) were evaluated. Results: 135 patients, 80 females and 55 males, were treated for LM, 73 patients with solid tumors and 62 patients with hematological malignancies. Of the total 135 patients 28% received combined chemotherapy and intrathecal chemotherapy (ITC), 22% only ITC, 3% received only systemic chemotherapy, 28.5% radiochemotherapy and 1.5% radiotherapy only. 13% patients were treated with supportive therapy only and in 4% therapy could not be evaluated. Median overall survival (OS) was 2.5 months (3 days- 58.2 months). According to univariate analysis age > 50 years and Karnofsky status < 80 were predictors of poor survival. Response to therapy and application of systemic therapy were correlated with longer survival. In this study, time of survival varied considerably depending on the type of primary tumor. Univariate analysis of Kaplan-Meier plots revealed age >50 years and Karnofsky performance status <80 as therapy-independent predictors of poor survival. Positive prognostic factors were response to therapy as measured by malignant cell count in the CSF, and application of systemic chemotherapy alone or in combination with other therapy-modalities in the entire cohort. Difference through systemic therapy was extremely relevant for the two entities NHL (n=37) and breast cancer (BC) (n=35). The median OS was 4.4 months for NHL and 7.0 months for BC following systemic therapy compared to 1.8 months for NHL and 1.4 months for BC without systemic treatment thus demonstrating a significant better OS using systemic therapy. Conclusion: The results suggest that systemic chemotherapy has the main impact on improved survival in patients with LM and chemosensitive disease. Still the prognosis for patients with LM is poor and treatment is aimed at palliation of symptoms and preservation of neurologic function. Future randomized studies of therapies should include quality-of-life assessment and provide additional data on this important outcome. No significant financial relationships to disclose.
A phase III trial of topotecan and whole brain radiation (WBRT) therapy for patients with CNS metastases due to lung cancer
Authors: Ko Y. , Neuhaus T. , Müller R. , Grabenbauer G. , Hedde J. , Schüller H. , Kocher M. , Stier S. , Ullrich R. , Fietkau R. 
Published: March 2020

2049 Background: Brain metastases represent an important cause of morbidity in patients (pts) with lung cancer and are associated with a mean survival of less than 6 months. Thus studies to improve outcome are urgently needed. Methods: Based on promising data raised in a phase I/II trial, in which WBRT was combined with topotecan (ASCO #444, 2003), we initiated an open, randomized, prospective, multicentric phase III trial, comparing WBRT (20 x 2 Gy; arm A) alone with WBRT + topotecan (0.4 mg/m2/d x 20; arm B). 320 pts with CNS-metastases due to SCLC or NSCLC were projected. Primary endpoint was overall survival (OS), secondary endpoints were local response and progression-free survival (PFS). However, since until the cut off date of study completion (i.e. a study duration of 34 months) only a total of 96 (A: 49, B: 47) pts have been recruited, an interim analysis was performed at that time point. Results: The demographic data (ø age 59 (34–75), 64% male, 66% NSCLC, mainly (64%) ECOG 0–1, extracerebral metastases in 75% and more than 4 cerebral lesions in 26% of pts) were evenly distributed in the two groups. Also the rate of grade 3/4 toxicities (besides alopecia 115 non-hematological (A/B: 60/55) and 43 hematological events (18/25)) did not differ remarkably between the arms. Early deaths (within 6 weeks after recruitment) occurred in 24% of the patients (A/B: 30%/18%), mainly due to tumor progression. Local response, evaluated 2 weeks after treatment, was assessable in 44 (A/B: 21/23) pts, showing CR in 8 (5/3), PR in 17 (6/11), SD in 14 (6/8) and PD in 5 (4/1) pts (all differences n.s.). Neither PFS (median A/B; days: 76/97, range, 24–251/20–428) nor OS (median A/B; days: 95/87, range 4–433/3–752) differed significantly (Cox-Mantel test; p=0.82 and 0.43, respectively). Conclusions: The available data, gained from the only phase III trial regarding concurrent WBRT and topotecan, show no significant advantage for concurrent radiochemotherapy for patients with lung cancer, however due to the limited number of recruited patients a possible small advantage of a combined treatment could not be demonstrated. Based on these results and the slow recruitment a continuation of the study did not seem reasonable. No significant financial relationships to disclose.
Can we predict therapy outcome in patients with high risk soft tissue sarcoma using positron emission tomography?
Authors: Kasper B. , Dimitrakopoulou-Strauss A. , Wuchter P. , Egerer G. , Ho A. D. 
Published: March 2020

20511 Background: We used 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (FDG) studies to evaluate the FDG metabolism kinetics in patients (pts.) with high risk soft tissue sarcomas receiving an induction or neoadjuvant chemotherapy. The treatment effect was assessed with regard to the prediction of therapy outcome. Methods: The ongoing evaluation includes 25 pts. with high grade soft tissue sarcoma with different histologies: 14 pts. received an induction chemotherapy consisting of adriamycin 75 mg/m2/day 1 and ifosfamide 1500 mg/m2/day 1–4 (AI-G regimen, six cycles) prior to peripheral blood stem cell transplantation, and 11 pts. were treated with pre-operative chemotherapy consisting of etoposide 125 mg/m2/day 1+4, ifosfamide 1500 mg/m2/day 1–4 and doxorubicin 50 mg/m2/day 1 (EIA regimen, 4 cycles). Pts. were examined prior to onset of therapy and after completion of the first cycle of AI-G and after two cycles of EIA chemotherapy, respectively. The restaging data of 21 patients (11 pts with AI-G and 10 patients with EIA treatment) served for reference. Restaging was performed using computed tomography and magnetic resonance tomography after six cycles of AI-G or four cycles of EIA chemotherapy. Results: 21 pts. were evaluable by the time of data evaluation. According to RECIST criteria, clinical outcome was as follows: 3 pts. showed no evidence of disease (NED), 6 partial remissions (PR), 5 stable diseases (SD), and 7 pts. with progressive disease (PD). Due to the small number of pts., we dichotomized the data in pts. with NED/PR (n = 9) and pts. with SD/PD (n = 12). Median average standard uptake value (SUV) prior therapy was 5.4 in comparison to 4.1 after chemotherapy. Median maximum SUV was 8.3 prior to chemotherapy in comparison to 6.6 following therapy. We used discriminant analysis and four predictor variables, namely the average and maximum SUV of both the baseline and the follow-up study to classify the pts. into responders and non-responders. Discriminant analysis revealed a correct classification rate of 70 %. Conclusions: On the basis of these data, prediction of chemo-sensitivity of the tumor and moreover of the therapy outcome might be possible. No significant financial relationships to disclose.
A case of synchronous relapse of breast cancer and uterine mullerian adenosarcoma after adjuvant tamoxifen in a pre-menopausal woman
Authors: Farhat F. S. , Fakhredin N. A. , Sraj A. A. 
Published: March 2020

20533 Background: Uterine müllerian adenosarcoma is a rare tumor of postmenopausal women. An increase in its incidence with the use of tamoxifen therapy for breast carcinoma is reported in several studies. Methods: We report a case of 42 years multigravida, premenopaused woman with breast carcinoma, who presented - after four years of use of adjuvant tamoxifen - a synchronous liver, bone, and lung metastasis of breast cancer with müllerian adenosarcoma. Results: Immunohistochemical stains on uterine tumor for estrogen and progesterone receptors showed positivity for both epithelial and stromal cells, actin, desmin and proliferative index (MIB-1) showed positivity for stromal cells only. The patient underwent a hysterectomy followed by palliative chemotherapy. The patient deceased at 14 months after her relapse because of progressive disease (cerebral, bone, liver and lung metastasis). Conclusion: Our case is the only one reported in the literature with synchronous relapse of the breast adenocarcinoma and a Müllerian adenosarcoma. Also it's of the rare cases occurring in a pre-menopaused woman since all except two cases were postmenopausal. [Table: see text] No significant financial relationships to disclose.
Phase II trial of high dose imatinib in recurrent glioblastoma multiforme (GBM) with platelet derived growth factor receptor (PDGFR) expression
Authors: Viola F. S. , Katz A. , Arantes A. , Gaiger A. , Vasconcellos C. , Passos V. , Barrios C. H. 
Published: March 2020

2056 Background: GBM are the most common primary brain tumors in adults. Despite available treatment they carry a poor prognosis with recurrences in most patients (pts) after initial therapy. PDGF signaling has been postulated to play a role in GBM transformation. We have demonstrated that PDGFRβ is expressed in tumor cells in 50% and in peritumoral endothelial cells in 65% of GBM (Barrios et al, abstract 11518, Proc ASCO 2006). Imatinib, an inhibitor of PDGFRa/β kinase activity could have therapeutic activity in these cases. Methods: We evaluated Imatinib in pts with recurrent GBM (previous radiation and chemotherapy) selected by PDGFR expression. Analysis of PDGFRa/β was performed by standard IHC. Positivity was considered in case of any qualitative expression. Pts were treated with 800 mg/day of Imatinib until tumor progression. All were on steroids and taking enzyme inducing antiepileptic drugs. Response was determined by MRI with spectroscopy and perfusion every 8 weeks according to RECIST criteria. Results: Twenty pts were enrolled (18 GBM, 2 AA). Median age: 51 (21–74), 7 were females. ECOG-PS at inclusion: 0 (3), 1 (10), 2 (7). All pts had expression of PDGFRa and 55% expressed PDGFRβ. Response data are available for all 20 pts. Main adverse events (all grade 1–2) were: edema (55%), nausea (50%), diarrhea and fatigue (35% each). We did not observe any PR but 13 pts (65%) showed disease stabilization. Median progression-free survival was 7.8 months with 60.8% of pts alive at 6 months; 6 months PFS was 52.2%. Conclusions: Imatinib was well tolerated in this group of poor prognosis highly pre-treated GBM pts demonstrating disease stabilization in a significant proportion of cases. These results, in a limited sample, compare favorably with historical data in similar populations. Selection of pts according to the specific molecular expression of their tumor may lead to better therapeutic results. No significant financial relationships to disclose.