bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retrospective analysis on patients with male breast cancer
Authors: Alvarez A. M. , Quiroga M. N. Gandur , Cinat G. , Iturbe J. , Nissi T. Said , Lacava J. , Cuartero V. , Vallejo C. , Leone B. , Mickiewicz E. 
Published: March 2020

19681 Background: Male breast cancer is uncommon, 1%(0.7 %)of all breast cancer. Nevertheless, the incidence has climbed 26% over the past 25 years. Objetive: Analyze the form of presentation and clinical evolution of patients with male breast cancer studied from 1977 to 2005. Methods: From 1977 to 2005 53 charts were analyzed: age, clinical presentation, stage (st), histological characteristics and nodal involvement. Results: Age: 33 years to 83 years (median= 59 years). Mean durations of symptoms before presentations: 11 months (m) (range 1 - 84 m.) . Forty-six (86.7%) patients (pts) had history of breast lumps, 9 (17%) were painful. Skin involvement and ulceration were present in 5 (9.43%) and 4 (7.54 %) respectively. One case of bilateralism was found. Seven (13.2%) st. I; 18 (33.96%) st. II; 20 (37.73%) st. III and 7 (13.2%) st. IV. Radical mastectomy was done in 41 pts (77.35%). Invasive ductal carcinoma was the most common histological type in 45 (84.9%). One case of lobular carcinoma was found. 60.4% of tumours expressed hormonal receptor. Adyuvant treatment: Adriamycin-based chemotherapy in 20 pts and CMF in 8 pts. Hormonotherapy was offered in 10 (19%) pts of the previous group, radiotherapy to 12 pts. twenthy pts (37.73%) presented recurrence; most common was bone in 10. The st. I and II estimated 5-year survival rate was 68% IC 95% (44–84%), st. III was 44% IC 95% (23 - 67%), st. IV (median = 24 m) with range (16 - 56 m). The 72% IC 95% (48–88%) patients st. I and II was free of disease at the 5-years, st. III was free 24% IC 95% (9–49%), st. IV (median = 7,5 m) with range (7–14 m). Conclusions: The media age at diagnosis was 59 years (10 years less than the international bibliography). (IB). Our group had longer time to presentation: 11 vs. 6 m., (IB) and most of them where in st. III. Hormonal receptore were positive in 60%. No significant financial relationships to disclose.
Success rate and myeloid toxicity of carboplatin desensitization protocol in low grade glioma patients
Authors: Berrak S. , Beker D. B. , Canpolat C. , Cakir F. B. 
Published: March 2020

20012 The effectiveness of carboplatin and vincristine chemotherapy in the treatment of low grade glial tumors is well established. This study was retrospectively designed to investigate the success rate and myeloid toxicity of carboplatin desensitization in a group of patients with carboplatin allergy. A total of 45 patients followed between October 1998-January 2007 with low grade glial tumors were included into study. Patients with severe hypersensitivity reactions (including anaphylaxis) were given 6-step desensitization protocol with gradual increase in concentration of carboplatin over 6 hours. Weekly absolute neutrophil count (ANC) and number of febrile neutropenia episodes of each patient during treatment period were collected from patient files. Among 45 patients, eight were switched to desensitization protocol. They had received a median of 6 courses (range 1–29) of carboplatin before developing their first allergic reaction. A median number of 15 courses of desensitizations (range 3–40) were given to these patients. Desensitization was successful in 6 patients. Age, gender, diagnosis were found to be similar in patients with and without carboplatin allergy. Regarding myeloid toxicity, mean percentage of follow-up weeks with ANC values below 1,500/mm3 in patients with and without desensitization were 0.42±0.04 and 0.21±0.02, respectively (p=0.009). Mean percentage of weeks with ANC values below 500/mm3 were not significant between two groups (p=0.28). However, desensitization protocol was not found to have an impact on number and presence of febrile neutropenia episodes. In conclusion, desensitization protocol might be an alternative to complete scheduled treatment in low grade glioma patients with hypersensitivity to carboplatin. Although, the percentage of low ANC weeks seemed to be statistically higher, insignificance of febrile neutopenia episodes in our patients demonstrated safety of desensitization protocol in terms of myeloid toxicity. No significant financial relationships to disclose.
Exercise intervention for pediatric cancer survivors: Feasibility and preliminary efficacy
Authors: Collett B. , Acosta A. , Whitsett S. , McTiernan A. , Friedman D. 
Published: March 2020

20013 Background: Obesity and diminished physical activity are known sequelae of cancer and its treatment. In medical oncology, data support the efficacy of exercise interventions. We therefore evaluated such an intervention for overweight/inactive adolescent cancer survivors. Methods: Participants were randomized to an exercise or control condition. The intervention group attended exercise sessions for 12-weeks with an exercise physiologist, during which they developed an individualized program emphasizing cardiovascular fitness. Controls received written exercise and nutrition materials. Outcome measures included self-reported health-related quality of life (HRQOL), physical activity, and fatigue; and lab measures of body mass index (BMI) and VO2max. Results: Among the 36 participants (mean age = 18.0 yrs, mean = 12.0 yrs post-diagnosis), at baseline both groups had diminished HRQOL, elevated BMIs, low physical activity, decreased V02max and high levels of fatigue. Post-treatment, there was little change in BMI, while physical activity and fatigue slightly increased in both groups. Study participation among survivors was limited due to the commute and time commitment for center-based sessions. Table 1 . a7-Day Physical Activity Recall; minutes/week of moderate-intense physical activity bMultidimensional Fatigue Questionnaire; lower scores = increased fatigue Conclusions: Survivors of childhood cancer are at risk for impaired HRQOL, high BMI, decreased physical activity, and fatigue, even 10+ years after diagnosis. Preliminary data are discouraging with respect to the immediate benefits of intervention, but analyses are ongoing to assess other outcomes as well as the impact 3 months following study completion. Feasibility issues of conducting such a study in a tertiary cancer center served by a broad catchment area have been identified. Continued research is required, which includes novel approaches to overcome concerns of time commitment, which limited study participation. [Table: see text] No significant financial relationships to disclose.
Delayed cognitive, behavioral, and radiological changes related to canial irradiation for pediatric brain tumors
Authors: Wahab M. M. Abdel , Hussien H. , Maher K. M. 
Published: March 2020

20023 Purpose: To evaluate the delayed adverse changes in neuro-cognitive functions as well as white matter damage in radiated survivors of pediatric brain tumors. Methods: Forty two children (22 males) with primary brain tumors who were only treated with cranial radiation, were recruited. 28 patients were treated for low risk medulloblastoma, 10 patients for low grade astrocytoma, 3 patients for low grade ependymoma, and 1 patient for craniopharyngioma. Their ages ranged from 3 to 18 years (mean 10.3±3.98 years).They were subjected, initially just before radiotherapy and at follow-up 1–2 year after completion of cranial radiation, to serial clinical and neuropsychological assessments including Wechseler Intelligence Scale for Children, Vineland social maturity test, Benton Visual Memory Test, and Revised Behavior Problem Checklist. Magnetic resonance scans were also performed to detect the presence of white matter damage before radiotherapy and at follow up. Results: Initially, after surgery and before radiation, intelligence test scores were below normal scores for age and this was of high statistical significance (Total IQ: t= -3.02, P= 0.006). Visual memory test showed evidence of organicity in all cases. Social maturity showed a statistically significant decline as well (t= -2.11, P= 0.04). Follow-up after radiotherapy showed further decline with high statistical significance (Total IQ t= 3.228, P=0.003; visual memory t= 4.08, P= 0.001); An attentional problem has emerged (t= -6.12, P= 0.00). Both radiation dose and volume of radiation showed negative and statistically significant correlation with IQ. Age at diagnosis correlated positively and significantly with IQ ( r= 0.601, P=0.001). Multiple linear regression showed impaired neurocognitive function which was correlated with the degree of white matter damage. (standardized B= -0.577, P= 0.001) and young age at diagnosis (standardized B= -0.427, P= 0.014). Conclusions: Cranial radiation in pediatric brain tumors is associated with a decline in multiple neurocognitive functions including total IQ, visual memory, and attention; which are related to the toxic effect of cranial radiation on white matter of the brain especially in young age of childhood with high dose and whole cranial radiation. No significant financial relationships to disclose.
PRODIGE: A phase III randomized placebo-controlled trial of thromboprophylaxis using dalteparin low molecular weight heparin (LMWH) in patients with newly diagnosed malignant glioma
Authors: Perry J. R. , Rogers L. , Laperriere N. , Julian J. , Geerts W. , Agnelli G. , Malkin M. , Sawaya R. , Baker R. , Levine M. 
Published: March 2020

2011 Background: Venous thromboembolism (VTE) occurs in 20–30% of patients with malignant glioma per year of survival. We have conducted an RCT testing the efficacy and safety of long-term dalteparin for the prevention of VTE in newly diagnosed malignant glioma. Methods: Adults with newly diagnosed malignant glioma were randomized to receive dalteparin 5,000 anti-Xa units or placebo, both subcutaneously daily for 6 months starting within the first month after surgery. Patients were allowed to continue study medication for up to 12 months. Because of the poor prognosis of malignant glioma it was determined apriori that the primary outcome was 6-month VTE-free survival. In order to detect a 60% VTE hazard reduction with LMWH with 80% power, 512 patients were required. Results: Recruitment began October 2002 and was closed in May 2006 because of expiration of study medication and no further re-supply. Of the 563 patients screened at 15 centers, 174 were excluded. Of the 389 eligible patients approached for consent, 186 were randomized: 99 to LMWH, 87 to placebo. Twenty-one patients developed objectively confirmed VTE during the first 6 months: 9 on LMWH and 12 on placebo (11% and 17% respectively; HR=0.7, 95% CI: 0.37–1.5, p=0.3). Over the 12 months there were 5 (5.1%) major bleeds with LMWH and 1 (1.2%) with placebo (HR=4.0, 95%CI: 0.5–34, p=0.2). All major bleeds were intracranial. Twelve-month mortality was 48% for LMWH and 45% for placebo (HR=1.2, 95%CI: 0.7–1.9, p=0.5). Conclusions: Although there was a trend in favor of the LMWH reducing VTE this was not statistically significant, likely as a result of low power. There was also a trend for increased intracranial bleeding with LMWH. Our study confirms the high incidence of thromboembolism in these patients; however, the role of long-term anticoagulant thromboprophylaxis remains unclear. Supported in part by a grant in aid from Pfizer Inc. and the Ontario Cancer Research Network. The PRODIGE steering committee thanks Terri Finch for superb administrative support. Pfizer
Blood brain barrier disruption (BBBD) and intra-arterial methotrexate based therapy for newly diagnosed primary CNS lymphoma: The BBBD Consortium Experience
Authors: Angelov L. , Doolittle N. D. , Siegal T. , Kraemer D. F. , Peereboom D. , Jahnke K. , Ference S. , Barnett G. , McGregor J. , Neuwelt E. A. 
Published: March 2020

2014 Background: Primary central nervous system lymphoma (PCNSL) incidence in immunocompetent patients has been increasing and now represents 4% of intracranial neoplasms. Similar to systemic lymphoma, PCNSL can display considerable chemosensitivity. Most chemotherapy regimens for PCNSL use intravenous methotrexate, often in combination with whole brain radiation. We present our multi- institutional experience in the treatment of PCNSL using BBBD in conjunction with Intra-arterial methotrexate (IA MTX)-based chemotherapy. Methods: A retrospective IRB approved analysis was performed on 177 newly diagnosed PCNSL patients treated monthly with osmotic BBBD in conjunction with an IA MTX-based chemotherapy regimen (n= 2,469 procedures) at 4 institutions from 1982–2005. No patient had received prior irradiation. Descriptive summaries and Kaplan-Meier survival summaries were estimated. Results: Among 177 patients, median age at diagnosis was 59.1 years (range 5.7 to 82.7 years). 101 patients (57%) achieved a complete response and 41 (23%) achieved a partial response (overall response rate 80.2%). 67 patients (37%) are currently alive (57 [32%] with no evidence of disease). Median overall survival (OS) was 3.1 years (25% estimated survival at 11.3 years). Median progression free survival (PFS) was 1.6 years with 40% progression-free at 5 years. Evaluation of the subgroup of patients < 60 years (n= 100), demonstrated an OS of 5.2 years with a 40% survival plateau after about 8 years, suggesting that some of these patients may be cured. The procedures were generally well tolerated with the most frequently encountered complication being procedure related seizures (9.5%) without long-term sequelae. Conclusions: This large multi-center series demonstrates that BBBD/IA MTX is a generally well tolerated and effective treatment for patients with newly diagnosed PCNSL. Further, it allows for the deferral of radiation and its associated cognitive compromise in these patients. These results are comparable or superior to other published chemotherapy (± radiation) treatment regimens suggesting that BBBD/IA MTX is an excellent treatment option for PCNSL patients and can result in successful and durable tumor control. No significant financial relationships to disclose.
Metastatic neuroblastoma (NB) to the central nervous system (CNS): Improved outcome with combined modality including 131-I-8H9 or 131-I-3F8 radioimmunotherapy (RIT) delivered through the cerebrospinal fluid (CSF)
Authors: Kramer K. , Modak S. , Kushner B. H. , Souweidane M. , Wolden S. , Humm J. , Zanzonico P. , Smith-Jones P. , Larson S. , Cheung N. 
Published: March 2020

2022 Background: NB metastatic to the CNS (NB-CNS) is difficult to control. We describe a salvage regimen incorporating intra- Ommaya RIT delivered to the CSF. Methods: 37 patients (pts) with NB-CNS (parenchymal masses and/or leptomeningeal [LM] carcinomatosis) treated at MSKCC from 1988 through 2006 were reviewed. Nine (group #1) of 37 pts developed NB-CNS metastasis (median age 3.8 years) and were treated with a salvage regimen: resection of parenchymal masses, 2160 cGy craniospinal irradiation (CSI), intravenous irinotecan and oral temozolomide, and RIT with 131I-8H9 and or 131I-3F8 targeting tumor associated antigens on phase I/II studies. Immunotherapy (intravenous anti-GD2 monoclonal antibody 3F8 plus subcutaneous GM-CSF) was also given for systemic control. Survival was compared to the other 28 (group #2) pts who developed NB-CNS (median age 4.2 years) treated with combinations of surgery, chemotherapy, and radiation but without CSI + RIT. Results: All 37 pts had high risk disease at initial diagnosis of NB. 9 of 9 group #1 pts had marrow and/or bony involvement; 6 of 9 had MYCN amplification and 5 of 9 had serum LDH >1500 U/ml. All had intensive chemotherapy and radiotherapy prior to CNS relapse. Despite this, the CNS salvage regimen was well-tolerated. Myelosuppression following CSI and chemotherapy was common; 2 pts received stem cell support. All 9 pts in the RIT group are alive and well, disease-free at 3+, 11+, 15+, 18+, 18+, 20+, 22+, 31+, 42+ months since CNS relapse. In contrast, pts in group #2 had a median time to death of 5.5 months, (p<0.0001) for survival by Kaplan-Meier analysis. Conclusion: Similar to CNS metastases in most other solid tumors, conventional therapies have been ineffective for NB-CNS. The addition of RIT using 131I-3F8 or 131I-8H9 is well-tolerated and improves the prognosis for these high risk patients. No significant financial relationships to disclose.
Phase II study of combination carboplatin and erlotinib in patients with recurrent glioblastoma multiforme
Authors: Groot J. F. De , Gilbert M. R. , Hess K. R. , Hanna T. , Groves M. , Conrad C. , Aldape K. , Colman H. , Puduvalli V. , Yung W. A. 
Published: March 2020

2024 Background: Targeting the epidermal growth factor receptor (EGFR) in glioblastoma is effective in a subset of patients whose tumors express the phosphatase and tensin homolog (PTEN) tumor suppressor gene and overexpress the EGF variant vIII receptor. Therefore, this study was designed to assess the clinical activity of the EGFR inhibitor erlotinib when combined with carboplatin and to determine molecular predictors of response. The primary endpoint is progression-free survival (PFS). To be eligible for the study, patients had to have recurrent, histologically confirmed glioblastoma or gliosarcoma, no more than two prior relapses, a KPS = 60, and no enzyme-inducing anticonvulsants. Methods: In this ongoing phase II study, patients are given carboplatin intravenously on day 1 of every 28-day cycle to achieve a target AUC of 6 (mg x ml/min) based on creatinine clearance. Erlotinib is administered orally once daily throughout the 28-day cycle at 150 mg/day with dose escalation to 200 mg/day, as tolerated. Patients undergo clinical and MRI assessment every 4 weeks. The primary endpoint is median PFS using a Bayesian time-to-event design. To determine histologic correlates of response, tumor tissue is undergoing immunohistochemical evaluation for known markers of response to EGFR inhibitors, including PI3K/AKT and PTEN status. Results: Of the first 20 patients enrolled, 17 were evaluable and all had failed temozolomide-based therapy. The median age is 56 years, and the median KPS is 80. The median time to progression is 15.2 weeks with a 95% credible interval of 8.0 to 28.4 weeks. These results compare favorably with historical data (median of 9.0 weeks, 95% CI of 8.1 to 10.1 weeks). Bayesian analysis using computer-based simulations indicate a high probability (69%) that the median PFS in our study is at least 3 weeks longer than the historical median PFS. Grade 3 and 4 toxicities included fatigue, leukopenia, thrombocytopenia and rash requiring dose reductions. Conclusions: The results from this ongoing study suggest that the combination of carboplatin and erlotinib has promising activity in patients with recurrent glioblastoma who have failed temozolomide-based therapy. Tumor tissue is being analyzed to determine molecular markers of response. [Table: see text]
Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) evaluation in glioblastoma (GBM) patients treated with bevacizumab (BEV) and irinotecan (CPT-11)
Authors: Desjardins A. , Barboriak D. P. , Herndon J. E. , Reardon D. A. , Quinn J. A. , Rich J. N. , Sathornsumetee S. , Gururangan S. , Friedman H. S. , Vredenburgh J. J. 
Published: March 2020

2029 Background: Significant responses seen in GBM patients treated with BEV and CPT-11 generated the need to develop ways to predict clinical benefit. DCE-MRI can be used to evaluate the microvasculature within tumors. DCE-MRI uses Ktrans, a volume transfer constant of contrast agent between blood plasma and the extravascular extracellular space, to determine vascular permeability. A 50% reduction in Ktrans is clinically meaningful. We report a phase II trial to determine the correlation between vascular permeability and radiographic response in GBM patients treated with the combination. Methods: Eligibility included patients with recurrent GBM. Both agents were given every 14 days. All patients received BEV at 10 mg/kg IV. CPT-11 was dosed at 340 mg/m2 for patients on enzyme inducing antiepileptic drugs (EIAED) and 125 mg/m2 for patients not on EIAED. Radiographic responses were assessed every 6 weeks. DCE-MRIs were performed before administration of chemotherapy, one day after treatment and after the first cycle. The primary endpoint was to examine the effect of BEV and CPT-11 treatment on vascular permeability as measured by percent change from baseline in Ktrans. Results: Twenty patients were enrolled, with a median age of 49.5 years. Fifteen patients are assessable for response. Best responses include one patient with complete response, 8 with partial response (response rate=60%), six patients with stable disease, and one with disease progression. Ktrans values are available for 13 patients; data are not available for seven patients (too early: 4, technical difficulty: 3). A reduction in Ktrans by 50% was observed in 6 patients one day after treatment and in 12 patients at the end of cycle 1. Changes in Ktrans value were highly correlated with the percentage decline in tumor volume from baseline to end of cycle one (Pearson correlation = 0.82; p=0.0006). Fifteen patients are still on study. Five patients came off due to disease progression. Conclusions: The utilization of DCE-MRI to determine a reduction in vascular permeability following a combination of BEV and CPT-11 is feasible and correlates significantly with the degree of tumor volume decrease. No significant financial relationships to disclose.
A randomized phase II trial of concurrent temozolomide (TMZ) and radiotherapy (RT) followed by dose dense compared to metronomic TMZ and maintenance cis-retinoic acid for patients with newly diagnosed glioblastoma multiforme (GBM)
Authors: Sul J. , Panageas K. S. , Lassman A. B. , Hormigo A. , Nolan C. , Gavrilovic I. T. , Grimm S. A. , DeAngelis L. M. , Abrey L. E. 
Published: March 2020

2031 Background: Metronomic and dose dense scheduling are alternatives to conventional TMZ regimens to overcome drug resistance in part by depleting O-6 methylguanine-DNA methyltransferase (MGMT). Furthermore, metronomic TMZ may inhibit endothelial recovery and act as an anti-angiogenic therapy; dose dense TMZ increases the intensity of drug delivery. Objective: To determine the overall (OS) and progression free survival (PFS) of patients with newly diagnosed GBM treated with concurrent TMZ and RT followed by dose dense or metronomic TMZ and maintenance cis-retinoic acid. Methods: Patients with newly diagnosed, histologically confirmed GBM underwent standard RT with TMZ. Upon completion of this treatment, patients were randomized to receive dose-dense TMZ (150mg/m2, days 1–7 and 15–21 of a 28 day cycle) or metronomic TMZ (50mg/m2 daily in 28 day cycles), for 6 cycles. Maintenance cis-retinoic acid was prescribed following the 6 cycles of adjuvant TMZ. OS and PFS were calculated from date of diagnosis. Prospective correlative tissue analysis of MGMT status is planned. A Simon minimax 2-stage design was used for each cohort. If either group has 70% survival probability at 1 year, further evaluation in a phase III trial will be recommended. Results: 51 patients were randomized: 24 to metronomic, and 27 to dose dense. Median age is 57, and median KPS 90. 26 patients have progression of disease (POD), with a median follow up of 5 months. Grade 3/4 hematologic toxicity occurred in 7 patients (14%), 3 in the metronomic and 4 in the dose dense arm. Conclusions: Our patient population is comparable to that of other upfront GBM treatment trials. Metronomic and dose dense TMZ appear to be well tolerated with equivalent toxicities. Early analysis suggests that patients on the dose dense regimen may have better PFS than those on the metronomic arm. [Table: see text] No significant financial relationships to disclose.