bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of the functional diffusion map (fDM) as an imaging biomarker for early stratification of glioma clinical response
Authors: Ross B. D. , Hamstra D. A. , Chenevert T. L. , Moffat B. A. , Johnson T. D. , Tsein C. , Meyer C. R. , Mukherji S. , Junck L. , Rehemtulla A. , Lawrence T. S. 
Published: March 2020

1518 Background: Current assessment of glioma treatment response relies on changes in the product of the maximal perpendicular tumor diameters at 2 months following treatment. Due to the fact that patients with malignant glioma have high mortality rates and a short median survival (about 41 weeks), the ability to stratify these tumors into responsive and non-responsive categories prior to treatment completion would allow for individualization of treatment. Changes in glioma water diffusion values were quantified using diffusion MRI as a biomarker for therapeutic-induced changes in tumor cellularity. Methods: A total of 37 patients with Grade III/IV supratentorial malignant gliomas (restricted to anaplastic astrocytomas (Grade III) and glioblastomas/sarcomas (Grade IV)) into a clinical imaging study. Standard and diffusion MRI scans pre-treatment and at 3 weeks post-initiation of chemo- and/or radio-therapy were acquired. Images were co-registered to pretreatment scans, and changes in tumor water diffusion values were calculated and displayed as a functional diffusion map (fDM) for correlation with clinical response. Results: Analysis of the patient data revealed that the fDM volumes of total detected diffusion change (VT) was able to statistically discriminate (P<0.001) between the stable disease (SD) and progressive disease (PD) patient populations 3 weeks into therapy. Patients classified as PD by fDM analysis at 3 weeks were found to have a shorter OS in the PD group compared with SD patients (median survival, 8.0 versus 18.2 months; p<0.01). The fDM measurements provided an early biomarker for response, TTP and OS in malignant glioma patients. Conclusions: This novel imaging biomarker (fDM) was found to be a viable and early predictor of WHO clinical outcome. This clinical study strongly supports the hypothesis that fDM analysis provides a sensitive measure of therapeutic-induced changes in tumor cellularity, which can thereby serve as a predictive clinical surrogate marker for treatment response. Further evaluation of this imaging biomarker is ongoing. [Table: see text]
Prospective analysis of expression of circulating levels of matrix metalloproteinase-9 (MMP-9) in the serum of patients with primary central nervous system lymphoma (PCNSL)
Authors: Hottinger A. F. , Gu B. , Fleisher M. , Abrey L. E. , Holland E. , Deangelis L. M. , Hormigo A. 
Published: March 2020

1532 Background: Matrix metalloproteinases have been associated with angiogenesis, tumor infiltration and metastases formation in systemic lymphoma. Disease status in PCNSL is determined by brain MRI; however it may be inconclusive and non-invasive tests to evaluate disease status would be useful. This study was designed to determine whether circulating levels of MMP-9 could be related to disease status in PCNSL. Methods: Circulating levels of MMP-9 were determined by ELISA and correlated with disease status assessed by MRI in a prospective longitudinal study. The disease status was classified as no evidence of disease (CR) versus active disease (AD). Results: We enrolled 18 PCNSL patients and obtained 93 blood samples (median 6 per patient, range 1–10) from August 2002 to December 2005. When in CR (12 patients, 59 samples), the mean MMP-9 level was 205.5 ± 19.1 ng/ml (median 162.3 ng/ml, range: 35.9–649.1 ng/ml). MMP-9 levels were significantly higher in AD (16 patients, 34 samples), with a mean MMP-9 of 638.2 ± 140.7 ng/ml (median 287.5 ng/ml, range 24.7–3340.6 ng/ml) (p = 0.0001). Paired samples obtained before and after therapy were obtained in 10 patients. Patients in AD had a mean of 1223.9 ± 336.5 ng/ml (median 770.1 ng/ml, range 284.1–3340.6 ng/ml) before treatment and levels fell to a mean of 143.5 ± 38.4 ng/ml (median 86.7 ng/ml, range 28.1–356.5 ng/ml) (p = 0.005) when CR was reached. During follow-up, 4 of the 18 patients developed recurrent disease (total 5 recurrences). MMP-9 levels increased from 154.22 ± 34.9 ng/ml (median 162.4 ng/ml, range 64.5–260.3 ng/ml) to 324.4 ± 98.5 ng/ml (median 251.5 ng/ml, range: 159.5–709.7 ng/ml) (p = 0.14) at relapse. Conclusions: PCNSL patients in CR have circulating MMP-9 levels that are significantly lower than in patients with AD. A significant drop in MMP-9 was seen after treatment compared to baseline. MMP-9 levels increased with disease recurrence but did not reach statistical significance in this small population. MMP-9 has the potential to complement neuroimaging to confirm remission or progression. No significant financial relationships to disclose.
Radiation treatment of spinal tumors using Cyberknife radiosurgery
Authors: Liao J. J. , Nasr N. M. , Gagnon G. J. , Henderson F. C. , Collins B. T. , McRae D. , Harter K. W. 
Published: March 2020

1545 Background: Morbidity associated with spinal tumors can leave patients with functional limitations, pain, and poor quality of life. Since the integrity of the spinal column and the spinal cord must be preserved, treatments are limited especially in the setting of previous radiotherapy. We describe our experience using Cyberknife fractionated stereotactic radiosurgery in the initial treatment and retreatment of spinal tumors and its impact on patient quality of life. Methods: 152 patients with primary or metastatic spinal tumors were treated to 228 spinal sites at Georgetown University Hospital from 2002 to 2005. Neurologic examination, pain assessment by visual analog scale (0–100), and quality of life evaluations by SF-12 survey (mental and physical health scores) were performed initially and at 1, 3, 6, 9, 12, 18, and 24 months following treatment. The primary endpoints were pain and quality of life. 44 patients (109 sites) received Cyberknife radiosurgery as a component of their initial management. The median dose delivered was 2400 cGy (range 1400–8000) in 1–5 fractions (median 3). Median tumor volume was 56 mm3 (range 0.65–457.26). 108 patients (119 sites) with recurrent/persistent disease and a history of prior conventional radiation to the spine received Cyberknife radiosurgery as retreatment. Previous radiation doses ranged from 2000–5940 cGy. The median retreatment dose delivered was 2100 cGy (range 750–3500) in 1–5 fractions (median 3). Median tumor volume was 107.2 mm3 (range 0.94–838.9). Results: Optimized treatment plans were designed with the goal of limiting spinal cord doses. Median follow up is 13 months. No complications have been observed, including treatment related myelitis. Across all patients, the mean initial pain score was 73. Mean pain scores decreased significantly after the first month to 49 and remained significantly lower (40–44) for over one year. SF-12 PCS (initial mean 33) and MCS scores (initial mean 47) remained stable during the duration of the study. Conclusions: Fractionated stereotactic radiosurgery using the CyberKnife is a safe and effective treatment capable of delivering high-dose radiation to primary and recurrent spinal tumors. Follow-up data demonstrates durable pain relief and stable quality of life. No significant financial relationships to disclose.
Induction chemotherapy with S-1 plus cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN)
Authors: Chung J. , Choi Y. , Shin H. , Choi G. , Lee W. , Joo Y. , Shon C. 
Published: March 2020

15501 Background: This study was to assess the efficacy and safety profiles of the combination treatment with S-1 and Cisplatin in patients with locally advanced SCCHN. Methods: Eligible patients were defined as histologically confirmed SCCHN, stage III or IV with no evidence of distant metastasis, evaluable lesions, adequate organ function, age of 20–80 years, and performance status 0,1 or 2. Cisplatin was infused over 1 hour on day 1 (75 mg/m2) and S-1 was administered orally for 14 consecutive days (day 2–15). The dosages of S-1 were assigned according to the patients’ body surface area (BSA): 50 mg twice a day (BSA < 1.5m2), 60 mg twice a day (BSA > 1.5m2). Each course was repeated every 3 weeks. After 2 course, tumor response were evaluated by CT scan and laryngoscopy. If the patients achieved a response (complete response: CR, or partial response: PR), they received one more course of chemotherapy before undergoing the radiotherapy or operation as a definitive local treatment. Results: All 22 patients were assessable for response and toxicity. The overall response was 80.9% (CR: 3, PR: 14). The adverse reactions occurred 120 times in 54 courses of 22 cases. The most common grade 3/4 adverse events were neutropenia, which occurred in 8 patients. Non-hematological toxicity of grade 3 and 4 included nausea and vomiting in 4 patients, fever in one patient and, fatigue in one patient. Since the observation period is short, the analysis about survival rate is not obtained so far. Conclusions: S-1 plus Cisplatin combination chemotherapy is effective against locally advanced SCCHN with mild toxicity. No significant financial relationships to disclose.
Rituximab and yttrium-90 ibritumomab tiuxetan radioimmunotherapy as treatment options in patients with indolent lymphoma of the orbit
Authors: Esmaeli B. , Pro B. , Saville M. , Mc Laughlin P. 
Published: March 2020

15532 Objective: To report a cohort of patients with lymphoid tumors of the orbit whose disease responded to immunotherapy with rituximab alone or rituximab followed by Zevalin (yttrium-90 ibritumomab tiuxetan). Methods: Between October 2002 and June 2005, 9 patients with indolent non-Hodgkin’s lymphoma and 1 with orbital benign lymphoid hyperplasia were treated with monoclonal antibodies against CD20. 6 patients with orbital lymphoma (3 follicular B-cell, 2 MALT, and 1 mantle cell lymphoma) received rituximab followed by Zevalin. 2 patients with indolent orbital lymphoma (one with follicular B cell and the other with small lymphocytic lymphoma) and 1 patient with benign lymphoid hyperplasia received rituximab alone. 3 out of the 6 patients who received Zevalin were part of a prospective trial evaluating the efficacy of Zevalin for indolent B-cell lymphoma of the orbit; the rest were treated in other trials at M. D. Anderson. Clinical records and imaging studies were reviewed to document response. Results: 4 men and 5 women were between23 and 83 years old (median age, 63 years). Of the 8 patients with orbital lymphoma, 4 had stage IE, 4 had stage IV, and 6 had previously untreated disease. All 9 patients experienced resolution of the orbital tumor in response to monoclonal antibodies against CD20. Follow-up time ranged from 6 to 32 months (mean, 12 months) after completion of immunotherapy. There were no serious systemic or ocular side effects during the study period. The most common side effect was mild fatigue. All 6 patients treated with Zevalin had transient pancytopenia which normalized within 3 months. Conclusions: Rituximab and Zevalin may be considered as alternative treatment modalities to radiotherapy for indolent B-cell lymphoma or MALT of the orbit. Systemic targeted immunotherapy may potentially have the advantage of lower rate of distant (out-of-field) relapse and less ocular toxicity compared with radiotherapy; these potential advantages would have to be verified in long-term studies and in larger number of patients. [Table: see text]
Evaluating cancer treatment access in two community cancer centers in Brazil: When managerial tools turns into bad medicine
Authors: Pinto C. F. , Deboer G. B. , Marotta E. S. , Taborda M. , Mendes A. D. , Albino G. R. , Santos G. L. , Altoe L. , Mandolesi A. , Turci C. F. 
Published: March 2020

16036 Background: Despite great developments in cancer treatment, access to treatment is still an important variable that can affect individual prognosis. Phase II or III adjuvant treatment protocols require inclusion to treatment between four to eighth weeks (28 to 56 days) after the initial procedure. The “lead-time” outside clinical trials can be longer than usually recommended and the meaning of this bias over outcome cannot be measured effectively, but reduce this “gap” is considered appropriate. Methods: Two different public community cancer centers (CCC) were evaluated regarding access to a medical oncologist. Referred patients were included and different referral routines were used. Data was collected only for breast cancer patients submitted to adjuvant (or neoadjuvant) systemic therapy. Data included the date the attending physician referred the patient to the CCC and the date patient effectively went on a consultation with an oncologist. Center A referrals depends on “in Hospital” referral center, where all patients are referred and then scheduled to the “needed” specialist. Center B patients are referred promptly to a medical oncologist, regardless of indication, if, i.e., a surgical evaluation or intervention is needed, the oncologist will reschedule it. Results: 76 breast cancer patients were referred to center A and 60 to center B in 2003. Most patients received an adequate surgical intervention, more than 80% of patients were stage I or II. Median time from referral report to a medical oncologist consultation was ten (10) days in Center B and twenty eight (28) days in Center A. Table 1 show treatment variables. Conclusions: Reasons to an almost three times increase in lead-time to access a medical oncologist can be attributed to bureaucratic and managerial policies developed to grant and regulate access to public practice that, in effect, reduced access, created bottlenecks, increased patient expenditures and, potentially, can reduce the overall outcome. [Table: see text] [Table: see text]
National multi-center epidemiological study on prevalence and treatment of cancer-related symptoms in Russia
Authors: Novik A. A. , Ionova T. I. , Kalyadina S. A. , Kishtovich A. V. , Wang S. , Cleeland C. S. 
Published: March 2020

16039 To have a better understanding of the current status of symptom management the national multi-center epidemiological study among patients with advanced cancer was initiated in Russia in 2005. Specific aims of this study are to describe the prevalence of pain, fatigue, and other cancer-related symptoms among cancer patients being treated in multiple sites across Russia and to assess current symptom treatment and response to it across different centers. The expected sample size is 500 patients with advanced cancer from 10 cancer centers across Russia. Symptom status was assessed using M.D. Anderson Symptom Inventory and Brief Pain Inventory at two time points. The analysis of data from 252 patients: male/female ratio - 111/141, mean age 44.3 (SD 30.1), included in the study from all participating centers is presented. As a result, the most severe symptom was fatigue (4.3) with its prevalence of 83.7%. Other pronounced symptoms were pain (3.4), distress (3.4), and sadness (3.1) with the prevalence of 66.7%, 67.7%, and 68.7% respectively. Out of the total sample, 70 patients (27.7%) had only mild symptoms and 179 patients (71%) reported at least one symptom as moderate-to-severe. Among them there were 72 patients (40.2%) who had 5 or more moderate-to-severe symptoms and 10 patients (5.6%) who had 10 or more such symptoms. Fatigue was treated only in 66 (26.9%) patients; the decrease in fatigue level was achieved in 15 (22.7%) patients. Inadequate pain management (as confirmed by the negative value of the Pain Management Index) was provided for 38.5% of patients. In conclusion, fatigue was prevalent in the vast majority of advanced cancer patients, but the attending oncologists offered the treatment of this symptom to less than 30% of patients. In addition, two thirds of patients reported at least one moderate-to-severe symptom. The results of this symptom outcome study will provide the initial data on symptom control in Russia and will establish the framework for identifying the populations who experience poor symptom assessment and management. No significant financial relationships to disclose.
Changes in Internet utilization by cancer patients in the Veteran’s Administration (VA) hospital setting
Authors: Vachani C. , Hampshire M. K. , Whittington R. W. , Vachani A. , Metz J. M. 
Published: March 2020

16042 Background: A previous study (2002) showed only 5% of VA cancer patients access the Internet to investigate information related to their cancer or cancer treatment. Since this study was published, access to the Internet and computers has changed over the interval. This study was designed to evaluate Internet usage patterns and factors that may promote Internet usage among cancer patients at a Veteran’s Administration (VA) hospital. Methods: From 09/2005 to 12/2005 a 15-item questionnaire was administered to 44 radiation oncology patients presenting for consultation and/or daily radiation treatments. The questionnaire evaluated basic demographics, Internet access and utilization, and interest in educational programs to promote utilization. Results were compared to a questionnaire study of 201 patients performed at the same institution in 2002. Results: The population is predominantly male (98%), with a racial distribution of 39% African American and 61% Caucasians. Two-thirds of the population are between the ages of 50 and 70. The most common primary tumor sites were prostate (65%), lung (11%), and head and neck (7%). Overall, 28% reported using the Internet to find information about their cancer, compared to only 5% in 2002 (p < .0001). An additional 42% reported a friend or family member searched the Internet on behalf of the patient. Seventy-four percent of subjects knew where to gain access to the Internet, which included public library (36%), personal computer (34%), friend/family’s home (13%). Of the 44 patients 18 (42%) were interested in free classes to learn how to access information on the Internet. African-American patients were somewhat more interested in taking educational classes on Internet utilization (OR 2.6, 95% CI 0.6–11.1). Conclusions: Internet use among VA cancer patients has increased over the last 3 years. A majority of VA patients know where to access Internet resources. Many patients are interested in educational programs to teach them how to utilize cancer based Internet resources. Future studies will assess the impact of this educational intervention in the VA population. No significant financial relationships to disclose.
Phase I study utilizing an intravenous busulfan test dose to prospectively target and determine the maximum tolerated systemic exposure (MTSE) of a continuous intravenous infusion
Authors: Walko C. M. , Shea T. C. , Rao K. , Gabriel D. , Serody J. , Comeau T. , Gilman A. , Krasnov C. , Lindley C. M. 
Published: March 2020

16502 Background: Busulfan systemic concentration has correlated with toxicity and efficacy. We previously demonstrated that administration of intravenous high-dose busulfan (HD-Bu) as a 90 hour continuous infusion (CIV) has efficacy, safety, and mean daily area under the concentration curves (AUC) comparable to intermittent dosing regimens and that it is possible to use a test dose of busulfan to predict the systemic exposure with less than 10% variability. The objective of this study is to identify the MTSE of CIV HD-Bu utilizing a test dose for AUC targeting. Methods: Prior to HD-Bu, patients received a single test dose of Bu (0.8 mg/kg) by two hour infusion with blood concentrations obtained at 0, 2.5, 4, 5, and 6 hours. Serum concentrations were analyzed using GC-MS. Non-compartmental PK analysis was used to determine clearance using WIN-NONLIN software. The systemic clearance (dose/AUC) of the test dose was used to predict the 90 hour CIV dose of Bu needed to achieve the desired AUC. On days -7 to -3, the treatment dose was administered and blood samples were collected at 0, 12, 16, 18, 48, 60, 72, and 89.5 hours to verify that the desired AUC was reached. Dose adjustments were made after 18 hours if necessary. A blood sample was obtained for evaluation of polymorphisms in genes associated with busulfan metabolism and transport. Results: Five patients (4 MUD, 1 matched-sibling donor) were enrolled at the 24 hour Bu target AUC of 4800 uM*min ± 15%. One patient was not able to be evaluated due to errors in PK acquisition. 3 of the 4 patients required CIV doses different than that based on weight alone (i.e. 12.8 mg/kg). All 4 patients had AUCs within the desired range (mean 24 hour busulfan AUC of 4708 uM*min) with a mean bias and precision of −1.9% and 8.7%, respectively. No adjustments were required after 18 hours. No grade 3 or greater chemotherapy related toxicity has been identified. Conclusions: The systemic clearance determined by a busulfan test dose may be used to prospectively target the desired AUC of a 90 hour CIV. Enrollment on this Phase I study will continue beyond the first dose level which is at the upper limit of the normal range (4800 uM*min). No significant financial relationships to disclose.
Inhibition of WT1 and bcl2 in leukemic cell lines by small interfering RNA (siRNA)
Authors: Glienke W. , Milz E. , Bauer N. , Bergmann L. 
Published: March 2020

16504 The expression of Wilm‘s tumor gene-1 (wt1) and bcl-2 is considered to have a proliferating and survival supporting effect in leukemia blast cells. The downregulation of wt1 by means of antisense-oligonucleotides and ribozymes revealed an inhibition of cell proliferation and induction of cell death. Here we describe the effect of siRNA against wt1 and bcl-2 in leukemic cell lines. RT-PCR and western blot analyses were performed to examine wt1 and bcl-2 gene expression in transfected leukemia cell lines. Apoptosis was detected with FACS analysis. K562 and HL-60 cell lines transfected with wt1 siRNA showed decreasing levels of wt1 mRNA and protein expression after 24 and 48 hours. The cell proliferation was reduced between 45% and 76% 48 hours after transfection, and apoptosis increased from 6.6 % in control cells to 12.2 % 24 hours after transfection in transfected cells. 48 hours after transfection the amount of apoptotic cells increased up to 45 % in transfected cells. Bcl-2 siRNA only induced apoptosis in about 15% of the cells. The combination of wt1 and bcl-2 siRNA had no additive effect on the induction of apoptosis. The expression of wt1 seems to be more important for cell survival than expression of the anti-apoptotic gene bcl-2. We therefore consider siRNA targeting human wt1 as possible tool against leukemic cells overexpressing wt1. No significant financial relationships to disclose.