bluuebunny/crossref_metadata_2025_split huggingface dataset:
Obesity as a prognostic factor for incidence and survival in female patients diagnosed with breast cancer.
Authors: Ramadan Islam Elsayed 
Published: March 2020

e12567 Background: The incidence of obesity in females ≥15 years of age in Egypt is one of the highest all over the world (33%)we investigated the impact of increased BMI on breast cancer incidence and survival. Methods: we reviewed files for 1873 female patients with breast cancer, presented at ACOD, from Jan. 1996 to Dec. 2005. , only 907 were eligible BMI of every patient was calculated and four groups were formed.The duration of follow-up was calculated from the date of registration to the date of death or last follow-up. The locoregional control period was between the end of treatment and failure of local control at 5 years or death or last follow-up OS was measured as the interval between the beginning of treatment and death or last follow-up evaluation. Results: patients were classified into 4 groups, the first group included 100 patients of BMI less than 18.5, the second group including 299 patients of BMI more than or equal to 18.5 and less than 25, the third group including 336 patients of BMI more than or equal to 25 and less than 30, and the fourth group including 172 patients of BMI more than 30. the highest peak of breast cancer incidence was in the age group 55-65 years (32.4%), while the lowest incidence was in the age group more than 65 (8.6%). Obese patients had the tendency to have breast cancer in younger age than normal weight patients with a mean of 38.6 years vs. 58.6 years. results showed that over weight patients constituted more than 37% while obese patients only constituted 19 %, normal weight 33% and underweight 11%. In our study, the majority of cases were staged as stage II and III (42.6 and 45.9 % respectively). Only 10.2% of patients in our series were recorded with stage IV; most of them were obese.Patients with increased BMI, in our study, had a significantly lower DFS ( p < 0.013).there was a statistically significant correlation between overall survival and BMI of patients (p=0.0015); there was an increase in mortality with increasing BMI. Conclusions: Our results report an increase in the incidence of breast cancer in overweight and obese patients in our population. Patients with high BMI were diagnosed at younger age, had more advanced stage and a statistically significant lower DFS & OS as compared to normal weight patients.
Genetic polymorphisms of EGF 5'-UTR in patients with glioma: A possible predictive marker of outcome.
Authors: Vattemi Emanuela , Cipollini Giovanna , Dealis Cristina , Rossi Lorena , Baier Susanne , Cretella Elisabetta , Di Meglio Giovanni , Sini Valentina , Lusso Maria Rita , Ruda Roberta , Petric Marija , Graiff Claudio 
Published: March 2020

e13009 Background: Epidermal growth factor (EGF) plays an important role in carcinogenesis. An adenine (A) to guanine (G) single nucleotide polymorphism at position 61 in the 5'-untranslated region (5'-UTR) of the EGF gene has been found to be associated with levels of EGF production and contribute to the risk of glioma. However, published data are contradictory. EGF +61G/A polymorphism may contribute to the risk of glioma in different ethnic group. Patients with glioma and GG genotype have been reported to have a risk of poorer otucome than patients with AA genotype. Purpose of this study is to investigate the potential role of this polymorphism in cancer progression and its role as predictive marker of outcome in glioma caucasian patients. Methods: EGF 61A/G polymorphism (rs4444903) was analyzed in glioma patients and was determined by means of Polymerase Chain Reaction and Direct Sequencing method (GenBank reference sequence-accession no. AC005509) from blood samples. Association of this genetic polymorphism with clinical and pathological data of patients was evaluated. Results: We investigated EGF +61G/A polymorphism in 24 glioma patients . EGF +61G allele has been found in 67% of glioma patients (25% G/G genotype and 42% A/G genotype). In astrocytomas, EGF +61G allele represents a 83% frequency; in glioblastomas and in oligodendrogliomas, EGF +61G allele frequency represents respectively 71% and 50%. In WHO IV gliomas, the EGF +61G allele represents a 63% frequency, (27% G/G and 36% A/G ), in WHO III gliomas a 77% frequency (33% G/G and 44% A/G ) and in WHO II gliomas a 50% frequency (100% A/G ). Median PFS of glioblastoma patients was 9 months. 83% of glioblastoma patients with a relapsing disease showed the G/G and A/G genotype. No difference was detected in the others histotypes. Conclusions: Our data conferm previous studies which reported G allele as a risk factor for glioma in Caucasian. G/A and G/G genotypes seem to be more rappresentative in high grade gliomas . Despite limited number of patients, our study supports the predictive role of EGF 61 A/G polymorphism in GBM. Additional large studies are warranted to confirm the role of EGF polymorphism as indipendent prognostic factor in glioma.
Patient-specific biomathematical model to predict benefit of resection in human gliomas.
Authors: Baldock Anne , Rockne Russell , Ahn Sunyoung , Neal Maxwell , Corwin David , Clark-Swanson Kamala , Sterin Greg , Trister Andrew Daniel , Malone Hani , Sonabend Adam , Mrugala Maciej M. , Rockhill Jason K. , Silbergeld Daniel L. , Lai Albert , Cloughesy Timothy Francis , McKhann Guy , Bruce Jeffrey N. , Rostomily Robert , Canoll Peter , Swanson Kristin 
Published: March 2020

e13017 Background: Gliomas are incurable, primary brain tumors noted for their invasion of brain parenchyma. Our goal was to apply a biomathematical model to estimate the overall tumor invasiveness on an individual basis and determine whether the estimated number of residual glioma cells after resection of any extent is predictive of survival. Methods: Estimates of net rates of proliferation (ρ) and diffusion (D) of glioma cells, based on a biomathematical model of cell density, yield a ratio describing relative invasiveness (ρ/D). This metric was derived for 185 contrast enhancing gliomas from pretreatment MRIs. The residual MRI-detectable volume was combined with the ρ/D tuned to each patient's tumor to allow estimation of the number of glioma cells remaining post-resection. The patients were split into three cohorts by ρ/D values. Within each cohort, all possible cut-off values were considered as a possible threshold between low and high residual patient groups. Log-rank tests were performed for each possible threshold to determine if the Kaplan-Meyer curves were significantly different. Results: We demonstrate that for low ρ/D tumors there was no threshold of residual tumor cell population observed that could yield a significant survival benefit. Both the mid ρ/D and high ρ/D had robust thresholds of residual tumor cell population, below which patients saw significantly higher survival than patients with similar invasiveness and more residual tumor. Conclusions: These results suggest that our patient-specific biomathematical model-based estimates of tumor invasiveness and residual tumor cells have clinical utility in driving neurosurgical decision making. Given the physicians understanding of patient-specific risk factors such as tumor location, age, and physical health, an understanding of the differential surgical benefit allows for more informed cost-benefit analysis and improved quality of life. This metric enables physicians to identify a subset of patients who do not see a survival benefit from resection, making the operation potentially not worth the risks.
Single-agent bevacizumab for recurrent high-grade glioma.
Authors: Greally Megan , Cadoo Karen Anne , Coleman Niamh , O'Brien Michelle , O'Riordan Lynda M. , Grogan William , Breathnach Oscar S. 
Published: March 2020

e13019 Background: High grade gliomas(HGG) are aggressive primary brain tumors. Most patients relapse following adjuvant therapy and treatment options are limited. Novel therapies have impacted little on overall survival (OS). Bevacizumab is approved for use following recurrence. We aimed to evaluate the extent of clinical benefit derived from this treatment, as defined by decreased steroid usage and median OS. Methods: We retrospectively reviewed medical records of consecutive patients with recurrent HGG treated with single agent Bevacizumab from May 2009 to Dec 2012 at our institution. We recorded patient demographics, histological features, therapeutic interventions, OS, steroid use and radiological response. Results: 29 patients with recurrent glioma were identified, 19 male and 10 female, with a median age at diagnosis of 47 years (16-72). All patients developed tumour recurrence following various combinations of multimodal therapies including 1-3 partial debulking surgeries, radiotherapy and chemotherapy. The median time from diagnosis of HGG to commencement of bevacizumab was 15 months (6-42). Patients received a median of 7 cycles (1-22) of therapy on a variable dosing schedule. 4 patients are alive, 2 continue on Bevacizumab. 19 patients were on steroid therapy when commencing therapy. There was a significant reduction in mean daily steroid use during therapy (7.65mg vs 3.97mg, p = 0.012). However, daily steroid use ultimately increased in some patients following treatment failure. Interval imaging appearances improved in 6 cases, deteriorated in 15, were stable in 4 and 1 patient had a mixed response. 1 patient was not re-imaged due to deterioration in performance status on therapy. The median OS was 5.5 months (0.5-16 months) from commencement of bevacizumab. Conclusions: The management of patients with recurrent HGG is challenging and prognosis remains dismal. In our unselected cohort, Bevacizumab therapy resulted in temporary or sustained steroid reduction in a majority. However, only a small number of patients demonstrated an objective radiological response and median OS was poor. Tumour response was variable and the addition of a predictive biomarker to establish which patients are likely to benefit from treatment may be helpful.
Neurotrophin signaling and melanoma brain metastases.
Authors: Fortenbery Nicole , Kenchappa Rajappa , Forsyth Peter A. J. 
Published: March 2020

e13024 Background: Adult metastatic brain tumors occur more frequently than primary intracranial neoplasms. Melanoma is the third most common tumor type that metastasizes to the brain. Therefore, elucidating the underlying biological mechanisms of melanoma metastases is critical. Melanocytes and neurons share a neural ectodermal origin, and thus, melanoma may preferentially travel to the brain due to the expression of common neurotrophin receptors, namely p75 neurotrophin receptor (p75NTR) and Trks. Further, high concentrations of neurotrophic factors present in the brain may recruit metastatic melanoma. We hypothesize that neurotrophin signaling through p75NTR is required for the malignant phenotype of melanoma and melanoma brain metastases (MBM). Methods: We investigated the expression of several neutrophin receptors, signaling molecules, and neurotrophins that we hypothesize to be important in the process of MBM. Using 14 malignant melanoma cell lines and two primary MBMs grown under neurosphere conditions, we investigated the expression of these molecules using standard western blotting, flow cytometry, and RT-PCR. We also performed an in depth microarray using of 14 primary MBM patients from Moffitt’s Total Cancer Care project. Results: All melanoma lines examined have robust expression of p75NTR, Trks, and neurotrophins. We find melanoma cell lines resistant to the BRAF inhibitor, vemurafenib, have elevated expression of neurotrophins and neurotrophin receptors when compared to lines sensitive to vemurafenib. We also detect high levels of p75NTR in patient MBM, at both mRNA and protein levels. Finally, we find a significant level of expression of all 11 genes tested by microarray. Conclusions: Previous studies have demonstrated that p75NTR has a role in melanoma cell survival in vitro. Here we demonstrate p75NTR and Trk receptors have high expression in melanoma cell lines and importantly, primary MBM. These data suggest that signaling through neurotophin receptors may be important for melanoma metastases and survival in the brain. Moreover, increased expression by vemurafenib resistant lines may suggest that these cells upregulate the expression of neurotrophin signaling as a means of treatment resistant.
Chemotherapy for adult medulloblastoma: Is it necessary for all?
Authors: El-Haddad Mostafa S. , Hawety Amr , Farag Ahmad , Badawy Abd Al-Rahman , Kaled Karim , El-Haddad Shawky 
Published: March 2020

e13025 Background: Medulloblastome is rare in adults and treatment is usually extrapolated from the pediatric age group, the aim of our study is to highlight the importance of chemotherapy both in the concurrent and adjuvant setting in adult medulloblastoma. Methods: Fourty patients between 1995 and 2011 with diagnosis of medulloblastoma were treated at both the department of clinical oncology Cairo University or Nasser Institute Cancer Center, files reviewed for demographic characteristics, radiographic findings, extent of resection, staging, computerized tomography (CT) scans or magnetic resonance (MR), histopathology, treatment received, pattern of recurrence and treament received. All patients treated with craniospinal irradiation with total dose of 36Gy followed by a boost to the posterior fossa till 54Gy. Results: Fourty patient were identified from our medical records 24 (60%) male and 16 (40%) female, mean age 25 year (range = 18 - 45), 2 patients had residual tumor more than 2cm, one patient had leptomeningeal deposits, 13 patients had weekly vincristin 2 mg weekly followed by cisplatin vepside, 27 patients didn’t receive any form of chemotherapy. Five year overall and disease free survival for the whole group was 92% (95% CI: 88-142) , 66% (95% CI: 73-135) respectively, for patients received chemotherapy OAS and DFS was 80% (CI:71-138), and 68% (48-162) for patients didn‘t receive chemotherapy OAS and DFS was 90% (CI:81-161), and 67% (C: 58-101), No statistical significance difference of survival between the two groups. univariate analysis didnt show any statistical significance correlation with chemotherapy.G3 neutropenia was more in the chemotherapy group 6 patients vs. 1 patient in the chemotherapy group. Conclusions: Chemotherapy for adult medulloblastoma should be further investigated as good survival time can be achieved with radiotherapy alone. And recurrence can be still salvage with chemotherapy
Early recurrence in glioblastoma.
Authors: New Pamela Z. , Teh Bin S. , Paulino Arnold 
Published: March 2020

e13032 Background: Current standard treatment for glioblastoma (GBM) consists of surgical resection, radiotherapy of 6000 cGy to the tumor bed and concomitant then adjuvant temozolomide (TMZ). Median survival on this regimen is 14 months. Early recurrence on imaging studies can be conflicted with treatment effect. Six patients are presented who recurred locally within 7 months of diagnosis despite optimal treatment, in an effort to determine molecular characteristics of patients with early progression. Methods: Three patients underwent gross total tumor resection, 3 underwent subtotal resection. All received IMRT totaling 6000 cGy with concomitant TMZ, followed by adjuvant TMZ. Ages ranged from 23 to 71, median 56. Time to radiographic recurrence was 3 to 7 months, median 4.8 months. There are 5 males and one female. Tumor methylation status and other markers are presented. Results: Three of the 6 patients were re-operated and pathology consistent with recurrent GBM. The remaining 3 progressed neurologically and by MRI scan. The O-6-methylguanine-DNA methyltransferase (MGMT) promoter gene of one tumor was unmethylated. This tumor specimen also expressed topoisomerase II; EGFR and EGFR VIII were negative. One tumor specimen expressed the BRAF V600e mutation. Both of these latter specimens expressed high levels of ERCC1, a DNA repair enzyme which would render these tumors unresponsive to platinum compounds. Conclusions: MGMT promoter methylation status may not be the only predicter of early recurrence. Exploring other biomarkers in more patients with glioblastoma at the time of surgery may assist in predicting true early progression verses pseudoprogression, an imaging challenge, in patients who may respond to different agents.
A phase II trial of lithium, bevacizumab, temozolomide, and radiation for newly diagnosed glioblastomas (GBM).
Authors: Narayana Ashwatha , Tam Moses M , Gruber Deborah Beth , Golfinos John , Parker Erik , Zagzag David , Gruber Michael L. 
Published: March 2020

e13033 Background: Invasion is a dominant escape mechanism following angiogenic blockade in glioblastomas (GBM). Lithium has shown anti-invasive activity in glioma cells by inhibiting Glycogen Synthetase Kinase -3. This phase II study evaluated the safety and efficacy of using lithium and bevacizumab (BEV) in newly diagnosed GBM. Methods: From 2010 through 2012, 20 GBM patients with residual disease after surgery were treated with involved-field radiation therapy to 5940 cGy and concomitant temozolomide (TMZ) (75 mg/m2 daily for 42 days) along with BEV (10 mg/kg every 2 weeks), starting 29 days after surgery. This was followed by six 28-day cycles of TMZ (150 mg/m2 on days 1-7, BEV (10 mg/kg) on days 8 and 22, and lithium 300 mg BID. Lithium was increased every 7 days up to 600 mg BID with a serum lithium goal level of 0.8 to 1.2 mEq/L. Results: The median follow-up was 9.9 months (range 1.9-24.5). Fourteen patients (70.0%) received at least one dose of lithium and three patients completed the entire course of therapy. The median number of BEV infusion was 9 (range 2-19). Five patients discontinued trial due to skin sensitivity (n = 2), pulmonary embolism (n = 1), infection (n = 1), and hematological toxicity (n=1). Two patients experienced dose limiting lithium toxicity which included drowsiness (n = 1) and tremor (n = 1). No patients experienced grade 3/4 intra-cranial hemorrhage. The median progression free survival (PFS) was 9.3 months. The 12-month PFS and OS were 31.9% and 59.3% respectively. For the 14 patients who received lithium, the 12-month PFS and OS were 42.9% and 69.2% respectively. Conclusions: The strategy of targeting angiogenesis and invasion simultaneously in newly diagnosed GBM is effective and feasible. Clinical trial information: NCT01105702.
Comparative study of six cycles versus twelve cycles of adjuvant temozolomide post concurrent chemoradiation in newly diagnosed glioblastoma.
Authors: Bhandari Menal , Gandhi Ajeet K , Julka Pramod Kumar , Sarkar Chitra , Sharma Dayanand , Rath Goura Kishor 
Published: March 2020

e13034 Background: This study assesses the impact of 6 cycles of adjuvant TMZ (conventional arm) versus 12 cycles (Extended arm) on Progression free survival (PFS), evaluate the toxicity and correlate the outcome with EGFR, P53 and MIB I labelling Index. Methods: Between December 2010 to October 2012, 36 post operative patients of Glioblastoma between age 18-65 years and Karnofsky Performance Score (KPS) ≥ 70 were included. Patients were randomized to receive Radiation with a dose of 60 Gray in 30 fractions over 6 weeks at 2 gray/fraction with concomitant TMZ (75 mg/m2/day) and Adjuvant therapy with either 6 or 12 cycles of TMZ(150 mg/m2 for 5 days, 28 days cycle). Patients were then assessed monthly clinically and imaged with MRI/CT every 3 monthly or when symptomatic. Toxicity was assessed using CTCAE version 3.0. Statistical Analysis was done using SPSS version 17.0.Kaplan Meier method was used for analysis of survival and log rank test was used for assessing the impact of variables on survival. Results: Of 36 patients, 18 patients were treated in each arm. Median age and KPS in both the arms was 47 years and 80 respectively. 44 % patients in the conventional arm and 50% patients in the Extended arm underwent complete surgical resection. 22% patients in the conventional arm and 28% in the extended arm did not complete their intended treatment. Grade ¾ Thrombocytopenia was seen in 16% in the extended arm and 0% in the conventional arm.EGFR, P 53 and MIB 1 >20% was seen in 26%, 45% and 20% patients respectively, overall. Median follow up was 18 months for both the arms (Range 10-23 months).At last follow up,8 patients in each arm had progression. Median PFS was 10 months vs.18.4 months (p 0.47) in conventional and extended arm respectively. On Univariate analysis, patients with KPS ≤ 80 had poorer survival than those >80 (Median PFS 9.5 Months vs. 16.9 Months; p 0.02).Age, extent of resection, EGFR, P53, MIB 1 did not significantly alter survival in the two treatment groups. Conclusions: Our study showed that schedule of extended Temozolomide is well tolerated by patients and tend to have better progression free survival. Further prospective randomized studies are needed to validate the findings of our study.
Prognostic value of the EGFR gene amplification by chromogenic in situ hybridization (CISH) in adult patients with glioblastoma.
Authors: Bella Santiago Rafael , Theaux Ricardo Alejandro , Lingua Alejo , Llugdar Jose Roberto , Papalini Francisco , Olocco Ricardo , Ferraris Gustavo Alberto , Magri Ignacio , Lerda Daniel 
Published: March 2020

e13036 Background: Prognosis of patients with glioblastoma is based on clinical characteristics: age, performance status (PS), neurological deficit and extent of surgery. Two prognostic scores have been developed: Medical Research Council and RTOG scores. Molecular features of the tumor may also be accurate to determine the prognosis. Amplification of EGFR is found in 35% to 40% of patients, being more common as age increases. Researches of EGFR gene amplification by PCR and FISH have reported contradictory results. Methods: Research was carried out retrospectively to determine the prognostic value on survival of EGFR gene amplification by CISH in patients with glioblastoma, as well as age, extent of resection and post-surgery neurological PS. Results: EGFR gene amplification was analyzed in 42 patients. Average age: 56 years. 12 patients were under 50 years old and 30 patients were 50 years of age or older. 20 patients (48%) underwent complete resection, 10 patients (23%) partial resection and 12 patients (29%) biopsy. Of all patients, 12 (28.6%) had EGFR gene amplification. Only 1 of the 12 patients less than 50 years old presented amplification, while 11 of the 30 patients (36.6%) older than 50 years had such amplification. There were no significant differences in survival according to age groups, extent of resection and post-surgery neurological performance status. During follow-up, 11 of 12 patients (92%) with amplification died, while 20 of the 30 patients (67%) without amplification had died. There was a difference in survival with statistical significance for patients without EGFR gene amplification: equal test survival distributions for different levels of EGFR, Log Rank (Mantel-Cox) Chi Cuadrado 7,054, Gl 1,k, Sig 0,008. Conclusions: EGFR gene amplification in adult patients with glioblastoma negatively impacts patient survival.