bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing a prognostic model for predicting VTE occurrence in cancer patients.
Authors: Sarma Deesha , Kim So Yeon , Henry David H. 
Published: March 2020

1577 Background: Venous thromboembolism (VTE) poses a significant health risk to cancer patients and is one of the leading causes of death among this population. The most effective way to prevent VTE and reduce its prominence as a public health burden is by identifying high-risk patients and administering prophylactic measures. In 2008, Khorana et al. developed a model that classified patients by risk based on clinical factors. Methods: We conducted a retrospective study to test this model’s efficacy, on 150 patients with cancer receiving chemotherapy at an outpatient oncology clinic between January 1 and August 1, 2011. We aggregated data and assigned points based on the five factors in the Khorana model: site of cancer with 2 points for very high-risk site and 1 point for high-risk site, 1 point each for leukocyte counts more than 11 x 109/L, platelet counts greater than 350 X 109/L, hemoglobin levels less than 100 g/L and/or the use of erythropoiesis-stimulating agents, and BMI greater than 35 kg/m2 (Khorana et al., Blood 2008). Based on this scoring system, patients with 0 points were grouped into the low-risk category, those with 1-2 points were considered intermediate-risk, and those with 3-4 points were classified as high-risk. Results: As shown in the table, VTE incidence for the low-risk group was 1.9%, intermediate-risk group was 3.9%, and high-risk group was 9.1%. Conclusions: High-risk patients were about 4.5 times more likely to develop a VTE than low risk patients. These results provide valuable insight in determining which patients might benefit from prophylaxis and in motivating the design of prospective clinical trials that assess the VTE predictive model in various ambulatory cancer settings. [Table: see text]
Factors associated with referral to medical oncology (MO) and subsequent use of adjuvant chemotherapy (ACT) among patients with resected non-small cell lung cancer (NSCLC): A population-based study.
Authors: Kankesan Janarthanan , Shepherd Frances A. , Peng Yingwei , Darling Gail Elizabeth , Li Gavin , Kong Weidong , Mackillop William J. , Booth Christopher M. 
Published: March 2020

1583 Background: ACT for NSCLC is associated with improved survival in the general population but may be underutilized. Underutilization may relate to lack of referral from surgeon to MO, MO not offering ACT, or patient declining ACT. Here we explore factors associated with referral to MO and use of ACT among patients with resected NSCLC in Ontario Canada. Methods: The Ontario Cancer Registry was used to identify all incident cases of NSCLC diagnosed in Ontario 2004-2006. We linked electronic records of treatment to identify surgery, ACT, and MO consultation. Co-morbidity was classified using the Charlson Comorbidity Index modified for administrative data. A multivariate logistic regression model was used to evaluate factors associated with referral to MO and use of ACT. Results: 3354 cases of NSCLC were resected in Ontario 2004-2006, 1830 (55%) were seen post-operatively by MO and 1032 (31%) were treated with ACT. Cases younger than 70 were more likely to have MO consultation (age 60-69 OR 1.6; 50-59 OR 2.3; 20-49 OR 2.2, p<0.001) as were cases with stage II/III (ORs 2.7 and 2.0, p<0.01) compared to stage I disease. There was substantial geographic variation in the proportion of surgical cases referred to MO (range 32-88%, p<0.001). Among cases seen by MO, patients younger than 70 were more likely to have ACT (age 60-69 OR 3.1; 50-59 OR 4.7; 20-49 OR 6.7, p<0.001) as were cases with stage II/III (ORs 2.7 and 3.0, p<0.001) compared to stage I disease. Less co-morbidity (OR 2.1, p=0.02) and shorter post-operative stay (OR 1.4, p=0.001) were also associated with use of ACT. Among cases seen by MO, there was some geographic variation (range 46-63%, p<0.001) in rates of ACT utilization. Conclusions: The upstream decision to refer to MO is associated with age and stage of disease and these factors have an even greater effect on ACT utilization once patients are seen by MO. While co-morbidity and post-operative length of stay are not associated with referral to MO, they are associated with use of ACT among cases seen by MO. There is substantial geographic variation in referral patterns to MO and less variation in ACT utilization once patients are seen by MO.
Impact of response shift on time to quality-of-life scores deterioration in patients with breast cancer.
Authors: Hamidou Zeinab , Dabakuyo Tienhan Sandrine , Guillemin Françis , Conroy Thierry , Velten Michel , Jolly Damien , Mercier Mariette , Causeret Sylvain , Cuisenier Jean , Graesslin Olivier , Gauthier Mélanie , Bonnetain Franck 
Published: March 2020

1584 Background: Time to quality of life (QoL) score deterioration (TD) is a method of longitudinal QoL data analysis that has been proposed for breast cancer (BC) patients (Hamidou et al Oncologist 2011). As for RECIST criteria, the optimal definitions dealing with reference should be explored. This study aims to study the impact of changes in internal standards (CIS) of response-shift (RS) and the influence of baseline QoL expectancies on TD. Methods: A prospective multicenter study including all women hospitalized for a primary BC was conducted. The EORTC-QLQ-C30 and BR-23 questionnaires were used to assess the QoL at baseline, at the end of 1st hospitalization, and 3 and 6 months after. CIS was investigated by the then-test method. QoL expectancy was assessed at baseline using Likert scale. Deterioration was defined as a decrease in QoL scores reaching at least the mean difference identified as minimal clinically important difference (MCID) using Jaeschke’s transition question. Sensitivity analyses were done using the then-test score as reference score, and considering 5 and 10 points as MCID. TD was estimated using Kaplan-Meier method. Cox regression analyses were used to identify factors influencing TD. Results: From February 2006 to February 2008, 381 women were included. For role functioning dimension, the median TD increased from 3.2 months [95% CI: 3.1-3.36] to 4.76 months [3.3-6.2] when adjusting on CIS. For body image when adjusting on CIS, sentinel lymph node biopsy became significantly associated with longer TD (HR: 0.64[0.43-0.94]) as compared to axillary lymph node dissection, radiotherapy to a shorter TD (HR: 0.63[0.42-0.95] and the type of surgery had no effect on TD. For global health, cognitive and social functioning dimensions, patients expecting deterioration in their QoL had a significantly shorter TD. For fatigue and breast symptom scales, patients expecting no change had a significantly shorter TD, as compared to patients expecting an improvement. Sensitivity analyses using a MDCS of 5 or 10 confirmed these results. Conclusions: Our results suggest that it would be more accurate to take into account CIS component of RS as well as QoL expectancies to estimate TD of QoL scores in patient with BC.
Renal impairment after chemotherapy in lung (LC), colorectal (CRC), and breast cancer (BC) patients (pts) from the Henry Ford Health System (HFHS) tumor registry.
Authors: Chu Laura , Ulcickas Yood Marianne , Loghman-Adham Mahmoud , Wells Karen , Casso Deborah , Oliveria Susan A. , Dong Wei 
Published: March 2020

1590 Background: Renal impairment is a common comorbidity in cancer pts. It can delay excretion and alter metabolism of anticancer drugs leading to further renal toxicity. The objective of this study was to determine the proportion of pts with renal impairment, defined as the presence of proteinuria (PR), acute kidney injury (AKI), or chronic kidney disease (CKD), after chemotherapy (chemo) initiation. Methods: LC, CRC, and BC pts newly diagnosed between 2000 and 2007 (regardless of prior renal status) were identified using the HFHS tumor registry, with follow-up through Mar 2009. AKI was defined based on RIFLE (severity categories only) using lab data within 1 to 7 days after chemo initiation. CKD was defined based on NKF-KDOQI criteria and lab data up to 1 year after chemo initiation. Proteinuria was defined as protein/creatinine >30 mg/g within 3 months after chemo initiation. Descriptive statistics include proportions stratified by renal impairment status (yes, no) at cancer diagnosis. Results: We identified 1,896 LC, 1,088 CRC, 1,611 BC chemo treated pts. Median age for all pts was 66 years. For LC and CRC, 56% and 51% were men, respectively. The proportion of pts with renal impairment after chemo by tumor type was the following: LC (AKI=23.4%; CKD=48.2%; PR=0.4%); CRC (AKI=20.3%; CKD=55.7%; PR=0.1%); BC (AKI=7.8%; CKD=63.9%; PR=0.6%). Pts with pre-existing renal impairment at cancer diagnosis were more likely to have impairment after chemo (Table). Conclusions: In LC, CRC, and BC pts, the proportion of pts with renal impairment after chemo initiation was high. Extent of renal impairment, especially AKI, appears to be associated with tumor type. Older age, as in this HFHS cohort, is associated with higher prevalence of CKD. Renal function should be closely monitored, particularly among pts with pre-existing renal impairment, and preventive measures implemented to minimize further toxicity after treatment.
Evolution and landscape of clinical trials for breast cancer patients.
Authors: Dogan Semih , Goubar Aicha , Arnedos Monica , Delaloge Suzette , Andre Fabrice 
Published: March 2020

1601 Background: Recent advances in cancer research are expected to have dramatically changed the way clinical trials are being done. In an effort to outline new trends of clinical research in the breast cancer area, we have evaluated the evolution of clinical trials started between 2006 and 2011. Methods: 622 clinical trials, started during the first semester 2006, the second semester 2008 and the first semester 2011, were analyzed. The data source was Clinicaltrials.gov. 30 items were included in the database. Results: The overall number of patients included in prospective clinical trials increased over these periods (n=67,820, n=91,429, n=98,417). However, when large epidemiological cohorts are excluded, a significant fall in the number of patients is seen (n=67,820, n=44,554, n=37,417). The absolute number of therapeutic trials also decreased during this time (n=93, n=99, n=78), mainly related to the dramatic fall in the number of trials testing conventional treatments (n=40, n=24, n=20). In the meantime, the number of trials testing targeted agents remained similar (n=46, n=67, n=50). Interestingly, in the same time, the number of trials testing a targeted agent in a population defined by a biomarker increased (n=1, n=6, n=14). At the opposite, prospective studies aimed at validating biomarkers did not increase, and remained only driven by large consortiums. As illustration, when we exclude RxPONDER trial, the biomarker-validation studies opened in 2011 planned to include only 2 493 patients, representing 2% of the breast cancer research field. Prospective trials testing social sciences and supportive care (n= 70, n=72, n=70) tend to become as important as therapeutic trials. Finally, large epidemiological cohorts opened in 2011 will represent more than 60% of the patients included in clinical trials. Conclusions: The part of cohorts and social sciences in breast cancer research is increasing and represents now the majority of the clinical research activity. When the analysis focuses on therapeutic trials, the breast cancer field recently shifted to targeted agents and early data suggest that therapeutic research is increasingly incorporating companion biomarker. Analysis on all 2,762 clinical trials done between 2006 and 2011 will be presented.
A retrospective analysis of all non-AIDS defining cancers (NADC): A subset analysis of the County Hospital AIDS Malignancy Project (CHAMP).
Authors: Gupta Shweta , Jain Prantesh , Mino Emilio Araujo , French Audrey L. , Rosen Fred R , Rubinstein Paul G. 
Published: March 2020

1611 Background: County Hospital (CCH) with its HIV clinic, the CORE Center (CC) is the largest provider for HIV patients (pts) in Chicago, treating over 5,500 HIV pts yearly. There is paucity of data on characteristics of HIV+ cancers (ca) in the inner city. The CHAMP cohort is a retrospective study of all HIV associated cancers at CC and CCH over past 14 years (yrs). We analyzed all of the NADC from this cohort. Methods: All HIV pts with NADC were identified from the CHAMP cohort and retrospectively reviewed for HIV and cancer characteristics, overall survival (OS), and pt demographics. Statistics: Survival data was analyzed using Kaplan-Meier analysis and Cox Proportional Hazards model. Results: Of 438 pts identified, 157 were NADC representing 21 ca. The average (ave) age was 48 yrs (range 44-57), with prostate ca having highest age presentation. Over the past 10 yrs, the number of NADC has risen from 10 to over 20 each yr. Unlike historical controls (HC) where lung ca is most common, anal ca (21%) was most frequent followed by lung ca (17%). Prostate, head and neck (HNSCC), liver, and colorectal ca were seen in 9, 9, 8, and 7% respectively. 65% of pts were African Americans (AA) and 18% Caucasians. 78% of all NADC were men. 45% of anal ca present with stage IIIa/b disease, moderately to poorly differentiated ca in 48%, with a median OS of 34 mo. CD4 count did not alter OS but stage predicted better outcomes. 86% lung ca presented as stage III/IV disease with ave CD4 count 204. Histologically, 36% were SCC, 28% adenosquamous and 20% adenocarcinoma. OS was 5.5 mo and did not change by histology, CD4, or age. 68% HNSCC present with stage IVa/b but no IVc. Ave age was 48 yrs with an OS of 18mo. 50% were oropharyngeal compared to 22% in HC. Conclusions: Based on data by Sheilds et. al, CCH treats just over 1% of the country’s NADC population. We demonstrate a higher incidence of NADC over time, dominated by a younger, AA and male population. Each ca presents with advanced stage 45-86% and poorly differentiated tumors ranging from 15-30%. The OS of each cancer is consistent with HC with exception of HNSCC. As HIV pts age becoming prone to cancers of elderly, education and screening of inner city HIV pts will help improve cancer rates.
Elderly patients with primary CNS lymphoma: Results from the G-PCNSL-SG-1 trial.
Authors: Roth Patrick , Martus Peter , Kiewe Philipp M. , Moehle Robert , Klasen Hermann A. , Rauch Michael , Roeth Alexander , Kaun Stephan , Thiel Eckhard , Korfel Agnieszka , Weller Michael 
Published: March 2020

2007 Background: Age is the most important therapy-independent prognostic factor in patients with primary central nervous system lymphoma (PCNSL). Here we aimed at providing an analysis of the impact of higher age on response to therapy, toxicity, and survival in the largest PCNSL trial ever performed to date. Methods: Response to therapy, toxicity and survival of PCNSL patients enrolled in the G-PCNSL-SG-1 trial evaluating the role of radiotherapy after high-dose methotrexate (HD-MTX)-based chemotherapy were monitored. Subjects aged 70 or more were compared to younger patients. Results: Of all eligible patients (n=526), 126 (24%) were aged 70 or more. In the per protocol population, 66 of 318 patients (21%) were at least 70 years old. Among the eligible patients, the rate of complete and partial responses (CR+PR) to HD-MTX-based chemotherapy was 44% in the elderly compared to 57% in the younger patients (p=0.016). A higher rate of grade III/IV leukopenia was observed in the elderly (34% versus 21%, p=0.007). Also, death on therapy was more frequent (18% versus 11%; p=0.027) in these patients. In contrast, there was no other major age-dependent toxicity. Survival analyses revealed shorter progression-free survival (PFS) (4.0 versus 7.7 months, p=0.014) and overall survival (OS) (12.5 versus 26.2 months, p<0.001) in the elderly population. The PFS of CR patients was 35.0 months in younger patients compared to 16.1 in the elderly (p=0.024). Salvage therapy was used less commonly in elderly patients. When salvage WBRT was applied in patients who had failed on HD-MTX-based chemotherapy, there was no association between age and survival (p=0.633). Conclusions: Elderly PCNSL patients have a lower response rate and higher mortality on HD-MTX-based chemotherapy. Their PFS is shorter and they receive less salvage therapy which may contribute to the poor prognosis.
Rituximab, methotrexate (MTX), procarbazine, and vincristine (R-MPV) followed by consolidation high-dose chemotherapy (HDC) and autologous stem-cell transplant (ASCT) for newly diagnosed primary CNS lymphoma (PCNSL).
Authors: Omuro Antonio Marcilio Padula , Correa Denise , Moskowitz Craig , Matasar Matthew J. , DeAngelis Lisa Marie , Kaley Thomas Joseph , Gavrilovic Igor T. , Nolan Craig , Pentsova Elena , Grommes Christian , Abrey Lauren E. , Sauter Craig Steven 
Published: March 2020

2008 Background: In our previous study in newly diagnosed PCNSL, induction chemotherapy with MTX and cytarabine followed by consolidation HDC (carmustine, etoposide, cytarabine, melphalan [BEAM]) with ASCT without radiotherapy resulted in only 50% of pts transplanted, reflecting low efficacy of induction chemotherapy, and short intent-to-treat (ITT) median PFS (=6m). In this phase II trial, we sought to optimize this strategy by utilizing a more effective induction regimen (R-MPV) and a more aggressive HDC regimen (Soussain et al). Methods: Pts received 5-7 cycles of R-MPV (MTX: 3.5g/m2) and if a partial or complete response was achieved, HDC with thiothepa, cyclophosphamide and busulfan was given, followed by ASCT and no radiotherapy. The primary endpoint was ITT 1 year event-free survival (promising: 75%, non-promising: 50%; 90% power, significance=0.05). Follow-up included comprehensive neuropsychological evaluation. Results: Accrual has been completed (N=32 pts, median age 57 [range 23-67], median KPS=80). Following R-MPV, 17 pts achieved a CR, 13 pts a PR and two pts progressed. A total of 25 (78%) pts were transplanted; the reasons for not receiving transplant were progressive disease (N=2), poor performance status/ physician’s decision (N= 2), mobilization failure (N=1) and consent withdrawn (N= 2). One pt who withdrew consent relapsed and received HDCASCT for salvage. Two (8%) pts died from early complications of ASCT (Stevens-Johnson: one, sepsis: one) and one pt experienced a fatal late colitis of unknown etiology. In the ITT population, the median EFS and OS have not been reached after a median follow-up of 22 months. The 1 year EFS was 78% (95%CI 58-90) and the 2y OS was 76% (95% CI 54-89). No pt has developed delayed neurotoxicity. Conclusions: R-MPV induction regimen resulted in improved response rates, allowing 78% of pts to receive HDC-ASCT. Although more toxic, this regimen resulted in excellent disease control and survival in the ITT population, far exceeding the efficacy of our previous transplant study. The primary endpoint was met, warranting further investigation.
Effect of antiangiogenic therapy on tumor-associated macrophages in recurrent glioblastoma.
Authors: Lu-Emerson Christine , Snuderl Matija , Davidson Christian , Kirkpatrick Nathaniel D. , Huang Yuhui , Duda Dan G. , Ancukiewicz Marek , Stemmer-Rachamimov Anat , Batchelor Tracy , Jain Rakesh K. 
Published: March 2020

2010 Background: Antiangiogenic therapy is associated with increased radiographic responses in glioblastoma (GBM), but tumors invariably recur. Tumor associated macrophages (TAMs) have been proposed as a mechanism of resistance to anti-angiogenic therapy in preclinical models. To examine the role of TAMs in recurrent GBM, we analyzed autopsy specimens from patients with or without history of antiangiogenic therapy. Methods: We compared autopsy brain specimens from 17 recurrent GBM patients who received anti-angiogenic treatment and chemoradiation (AAT+) to 7 patients who received chemotherapy and/or radiotherapy without anti-angiogenic therapy, or no treatment (AAT-). TAMs were morphologically and phenotypically identified with flow cytometry and immunohistochemistry (IHC) with CD68, CD11b, CD14, and CD163 markers. All specimens were obtained from the Department of Pathology at Massachusetts General Hospital and clinical information gained through review of the patients’ records. Results: Using flow cytometry, we observed an increase in CD11b+CD14+ cells in the AAT+ patients compared to AAT- patients. Using IHC analysis, we observed a significant increase in CD68+ macrophages in the tumor bulk (p<0.01) and infiltrative areas (p<0.05) in AAT+ versus AAT- patients. We also observed a significant increase in CD11b+ myeloid cells in the tumor bulk (p<0.01) and a significant increase in CD163+ cells in the infiltrative areas (p<0.05) in the AAT+ group. Finally, we noted a trend toward an increase in CD163+ cells in the tumor bulk (p=0.087) in the AAT+ versus the AAT- patients. Conclusions: Patients with recurrent GBM after antiangiogenic therapy showed a significant increase in CD68+ TAMs and in CD11b+ cells in the tumor bulk. Additionally, antiangiogenic treatment induced an increase in CD68+ and CD163+ TAMs in the infiltrative region. These data indicate that TAMs may participate in escape from antiangiogenic therapy and may represent a future therapeutic target in recurrent GBM.
Phase I safety and pharmacokinetic (PK) study of veliparib in combination with whole brain radiation therapy (WBRT) in patients (pts) with brain metastases.
Authors: Mehta Minesh P. , Curran Walter J. , Wang Ding , Wang Fen , Kleinberg Lawrence , Brade Anthony M. , Mostafa Nael , Zhou Xiangdong , Qian Jiang , Leahy Terri , Desai Bhardwaj , Giranda Vincent L. 
Published: March 2020

2013 Background: Veliparib is an oral PARP-1 and -2 inhibitor that enhances the antitumor activity of DNA damaging agents including radiation therapy in vivo. In pre-clinical models, veliparib crosses the blood-brain barrier. This ongoing phase I dose-escalation study evaluates the safety, PK, and provides preliminary antitumor activity of veliparib in combination with WBRT in pts with brain metastases. Methods: Pts with brain metastases from non-CNS primary solid malignancy, adequate organ function, RPA Class 2, and KPS ≥70 were treated with WBRT (37.5 Gy in 15 fractions or 30 Gy in 10 fractions) QD with veliparib BID with every fraction of WBRT in escalating doses of 10, 20, 30, 50, 100, 150, and 200 mg; the final WBRT fraction was followed by 1 extra day of veliparib. Safety, PK, and tumor response by RECIST were assessed. Results: At the time of reporting 59 pts (M/F, 21/38; median age 57 y) had been treated. Baseline KPS was 70, 80, 90, and 100 in 6.8, 32.2, 40.7, and 20.3% pts, respectively; primary tumor types were breast (n=20), NSCLC (n=20), melanoma (n=9), colorectal (n=2), and others (n=8); 71.2% pts had multiple lesions; and 18.6% had prior brain SRS. Grade 3/4 treatment-emergent adverse events (TEAEs; ≥5%) were fatigue (6.8%), anemia (5.1%), hyponatraemia (5.1%), and thrombocytopenia (5.1%); other TEAEs (≥20%) were fatigue (57.6%), headache (42.4%), nausea (40.7%), alopecia (28.8%), vomiting (22%), radiation skin reactions (22%), and decreased appetite (22%). PK of veliparib were approximately dose-proportional, with oral clearance of 21.6 ± 14.2 L/h (mean ± SD, n=45), minimal drug accumulation at day 15, and no significant effect of food on bioavailability. Tumor response was evaluable in 48 pts. Best tumor response and median survival were 37.5% and 10 months (m) for NSCLC, and 52.9% and 12.5 m for breast cancer (excluding pts with leptomeningeal disease). Conclusions: Addition of veliparib up to 200 mg BID was well tolerated with concurrent WBRT and dose escalation ongoing. The PK of veliparib was dose proportional with no food effect. Preliminary antitumor activity is encouraging and informative for the design of more definitive trials.