bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictors of pediatric and adult fibrosarcoma survival: Analyses of the Surveillance, Epidemiology, and End Results (SEER) program, 1973-2008.
Authors: Ognjanovic Simona , Fan Yunhua , Ognjanovic Miodrag , Skapek Stephen , Hawkins Douglas S. 
Published: March 2020

1576 Background: Fibrosarcoma (FS) is the second most common group of soft tissue sarcomas in children, however, most FS are diagnosed in adults. The goal of this study was to compare clinical features and outcomes of children and adults diagnosed with FS and identify predictors of survival. Methods: We have analyzed data from 569 children (≤ 19 years) and 5,508 adults (>19 years) diagnosed between 1973 and 2008 with FS (ICCC category IXb) available in the SEER database. Survival estimates were determined using survival time with end point death from any cause. Results: Comparison of two diagnostic periods, 1973-1989 vs. 1990-2008 showed that 5-year survival rates have improved in adults (48.4% vs 60.9%, P<0.0001), but not in children (72.3% vs. 73.9%, P=0.16). Children with FS had significantly better outcome compared to adults (5-year survival rates were 73.4% ± 2%, and 56.7% ± 0.7%, respectively, P<0.0001). Sites with survival rates higher than the median 5-year survival were grouped as favorable (extremities, head and neck, and genitourinary site); trunk, abdomen, and other sites were grouped as unfavorable. Cox proportional hazard regression model identified diagnosis in childhood, fibromyxosarcoma histologic subtype (ICD-O3 code 8811/3), favorable site, and localized stage as positive predictors of survival. Compared to fibromyxosarcoma, other histologic types had hazard ratio (HR) of 11.6 (95% CI= 1.6-83.2, P=0.01) in children, and HR of 1.8 (95%CI=1.5-2.1, P<0.0001) in adults. Diagnosis at unfavorable site was associated with HR=1.9 (95%CI=1.4-2.6) in children and HR=1.4 (95%CI=1.3-1.5) in adults. Compared to localized, distant disease had HR=4.2 in children and HR=5.1 in adults, both highly significant (P<0.0001). Conclusions: Adults diagnosed with FS had worse survival than children. Predictors of good outcome, including histiologic subtype, primary site, and stage, were valid in both children and adults.
Treatment patterns and comorbidities in a population-based cohort of glioblastoma patients diagnosed 1997-2008.
Authors: Oliveria Susan A. , Chu Laura , Casso Deborah , Wells Karen , Dong Wei , Dubrow Robert , Das Asha , Nerenz David R , Ulcickas Yood Marianne 
Published: March 2020

1591 Background: Glioblastoma multiforme (GBM) is one of the most common, most malignant and rapidly progressive forms of brain cancer. Published reports of GBM in non-trial populations are limited. The purpose of this study was to assemble a population-based cohort of GBM patients with comprehensive clinical and demographic information and to define treatment patterns and outcomes in this population. Methods: GBM patients served by Henry Ford Health System (HFHS), a major GBM referral center, were identified using ICD-O and histology codes from the HFHS tumor registry. Eligible patients were newly diagnosed with GBM between 1997 and 2008. Comprehensive, population-based data were compiled using tumor registry data (including histology and mortality) with linkages to pharmacy data (including infusion), outpatient and inpatient encounter data, and laboratory results. Results: Overall, 812 GBM patients were identified; mean age was 54 years (standard deviation 15.8). The cohort was 63% male and 84% white. Among the most common post-diagnosis comorbidities/complications, 14% of patients had venous thromboembolism (95% confidence interval [CI] 12-17), 16% had seizures (95% CI 14-19), and 6% had central nervous system hemorrhage (95% CI 4-7). Arterial thromboembolism occurred in 3% of patients (95% CI 2-4), while 7% experienced infections such as candidiasis, herpes simplex, and pneumocystis pneumonia (95% CI 5-9) and 2% experienced wound dehiscence (95% CI 1-3). 94% (95% CI 93-96) of the cohort received some form of treatment with 81% undergoing surgery (95% CI 78-84), 75% receiving radiation therapy (95% CI 72-78), and 67% receiving chemotherapy (95% CI 64-70). Median overall survival after diagnosis was 1.4 years (95% CI 1.3-1.5) among all patients, and 1.6 years (95% CI 1.4-2.0) among those diagnosed 2005-2008. Conclusions: This study presents a well-characterized population-based cohort of GBM patients. Understanding treatment patterns and comorbidities outside the clinical trial setting is important in informing and evaluating real-world treatment decisions. Additional results exploring time trends in systemic cancer therapy and Kaplan-Meier survival curves will be presented.
Secondary breast cancer (s-BC) after hematopoietic cell transplantation (HCT) for leukemia: Role of total body irradiation (TBI).
Authors: Sun Can-Lan , Berano-Teh Jennifer , Gonzales Alicia , Atencio Liezl , Kang Tongjun , Francisco Liton , Stein Anthony Selwyn , O'Donnell Margaret R. , Snyder David , Somlo George , Bhatia Ravi , Forman Stephen J. , Bhatia Smita 
Published: March 2020

1592 Background: s-BC after conventional chest radiation for histologically distinct cancer is well-recognized, and has resulted in radiologic screening recommendations by American Cancer Society. However, risk of s-BC after TBI is not well-defined. Methods: We determined the risk of s-BC in 648 consecutive females transplanted for leukemia (ALL [19%], AML/MDS [57%], CML [24%]) between 1976 and 2008 with a post-HCT survival of ≥2 years. The study was restricted to leukemia to understand the role of TBI without the influence of pre-HCT chest radiation. Near-complete ascertainment of s-BC was assured by combining institutional follow-up with California Cancer Registry data. Results: Median age at HCT was 38 years (range, 0-71); 14% had received autologous HCT, 64% related and 22% unrelated donor HCT; 70% had received TBI for myeloablative conditioning. After 5,675 person-years of observation, 16 patients developed s-BC (14 after TBI). Median latency from HCT to s-BC was 16y (2-27). Median age at s-BC was 50y (29-66). Cumulative incidence of s-BC was 6% at 20y after HCT, contributed to largely by TBI (s-BC incidence after TBI: 5.7%). Among TBI-exposed, 8.6% were projected to develop s-BC by age 65y (1.6% among non-TBI-exposed, p=0.03). TBI-exposed patients were 2.4 times more likely to develop s-BC compared with general population (p=0.001); non-TBI exposed were not at increased risk (SIR=0.9, p=0.9). Multivariate analysis (adjusted for age at HCT, follow-up and primary diagnosis) revealed a 4.7-fold (p=0.068) increased risk of s-BC among TBI-exposed. Conclusions: Risk of s-BC after TBI as the sole source of radiation to breast is increased. Nearly 9% of those exposed to TBI will develop s-BC by age 65y. Identification of vulnerable sub-populations among the TBI-exposed patients is underway to create targeted screening strategies for early detection of s-BC.
Association of p53 Arg72Pro polymorphism and HPV status with the initiation, progression, and development of cervical cancer (CC): A meta-analysis.
Authors: Habbous Steven , Pang Vincent , Eng Lawson , Mackay Helen , Amir Eitan , Liu Geoffrey 
Published: March 2020

1597 Background: CC develops through progression from normal cervical epithelium through squamous intra-epithelial lesions (SILs) to cancer. CC is classically associated with oncogenic human papillomavirus (HPV). Yet, not all CC patients demonstrate HPV infection at diagnosis. HPV+ and HPV– subsets of CC patients may thus represent distinct entities. HPV binds to P53, promoting its degradation; the Arg variant of p53 Arg72Pro binds more ardently to HPV than the Pro variant. Although there have been meta-analyses of Arg72Pro in CC risk, none has evaluated the relationship between Arg72Pro and HPV status together. We hypothesize that p53 Arg72Pro modifies aspects of the carcinogenic process in HPV+ (but not HPV-) subsets of CC. Methods: Pubmed/Embase databases identified 1494 potential studies; 51 were eligible and included. Separate analyses were performed to evaluate CC risk (CC vs normal), initiation of cancer (SIL vs normal), and progression towards cancer (CC vs SIL), by HPV status. Pooled odds ratios (pOR) were generated using RevMan 5.1 software. Results: p53 Arg72Pro was not associated with CC risk in either HPV+ or HPV- patient subsets (pORs 0.92; 95%CI, 0.6-1.3 and pORs 1.07; 95%CI, 0.7-1.7, respectively). Similarly, there was no association with the initiation of disease (SIL vs normal): pORs 0.96; 95%CI, 0.7-1.3 (HPV+ subset); 1.11; 95%CI, 0.9-1.4 (HPV- subset). There was no association with disease progression from SIL to CC in the HPV- subset (pOR, 0.98; 95%CI, 0.7-1.4). However, in the HPV+ subset, comparing the progression from SIL through to CC, there was strong and significant association: pOR, 1.37; 95%CI, 1.2-1.6 (p=4.0x10E-4), with no evidence of heterogeneity (I2 = 0%) or bias (by funnel plot). Sensitivity analyses demonstrated similarly significant results, even after taking into account differing quality of methodological designs and type of biological sample analyzed (tumour vs. blood) of the underlying studies. Associations were mainly restricted to Caucasian studies. Conclusions: In this meta-analysis, the Arg variant of p53 Arg72Pro was associated with progression of SIL to CC only in HPV+ subsets, but not to disease initiation or risk of CC.
Breast cancer survival: Is the Asian population homogenous?
Authors: Caggiano Vincent , Parise Carol 
Published: March 2020

1606 Background: Study of the ER-/PR-/HER2- (TN) subtype has generated interest in race/ethnicity with respect to breast cancer. Poor survival of African-American (AA) women with breast cancer has been reported. Less is known about the Asian population. This study examines survival of four ER/PR/HER2 subtypes among 10 self-reported race/ethnicity categories Methods: Using the California Cancer Registry 2000-2010, we examined 136,175 cases first primary female invasive breast cancer. For stages 1 and 2, Kaplan-Meier survival and the Log-Rank test were computed by stage and race for the ER+/PR+/HER2-, ER-/PR-/HER2+, ER+/PR+/HER2+ (TP) and TN subtypes. Results: When the Asian population is combined into the category Asian/Pacific Islander (API): ER+/PR+/HER2-: AAs had worse 5-year survival than whites in stages 1 and 2 but Hispanics and APIs had better survival in both stages; ER-/PR-/HER2+: AAs and Hispanics were no different from whites in stage 1 but APIs had better 5-year survival (0.96 vs 0.89, p<0.001). For stage 2, there were no differences in survival among the races. ER+/PR+/HER2+: AAs had worse and APIs had better survival in both stages; Hispanics had better survival only in stage 1 (0.93 vs 0.92, p<0.03) and were no different from whites in stage 2. ER-/PR-HER2-: AAs and Hispanics were no different from whites in stage 1 but APIs had better survival (0.93 vs 0.88, p< .003); AAs had worse survival than whites in stage 2 (0.71 vs 0.75, p< 0.04) Hispanics were no different, and APIs had better survival (0.81, p < 0.001). When the Asian population was expanded into 7 categories, Pacific Islanders and Koreans were no different than whites in stages 1 or 2 for all four subtypes examined. For Stage 1, Southeast Asians had better survival for all subtypes except for the TN whereas Filipinos had better survival for all subtypes except for TP. For the ER+/PR+/HER2- subtype, women from the Indian Continent had better survival in stage 1 (0.98 vs 0.92, p<0.003) and in stage 2 (0.94 vs 0.88, p<.001) and better survival for stage 1 of the TN subtype (1.00, vs 0.88, p <0.04). Conclusions: There is heterogeneity among the Asian population, but regardless of how categorized, Asians have either the same or better 5-year survival than whites for all subtypes in stages 1 and 2.
Long-term follow-up results of EORTC 26951: A randomized phase III study on adjuvant PCV chemotherapy in anaplastic oligodendroglial tumors (AOD).
Authors: Van Den Bent Martin J. , Hoang-Xuan Khê , Brandes Alba Ariela , Kros Johan M , Kouwenhoven Mathilde C.M. , Taphoorn Martin J. B. , Delattre Jean-Yves , Bernsen Hans J.J.B. , Frenay Marc , Tijssen Cees , Grisold Wolfgang , Sipos Laszlo , Enting Roelien H. , Dinjens Winand N.M. , French Pim , Vecht Charles J , Allgeier Anouk , Lacombe Denis A. , Gorlia Thierry 
Published: March 2020

2 The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Sunday, June 3, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Sunday edition of ASCO Daily News.
Consolidation reduced dose whole brain radiotherapy (rdWBRT) following methotrexate, rituximab, procarbazine, vincristine, cytarabine (R-MPV-A) for newly diagnosed primary CNS lymphoma (PCNSL): Final results and long-term outcome.
Authors: Curry Richard Charles , Correa Denise , Raizer Jeffrey J. , Grimm Sean Aaron , Lai Rose , Schiff David , Grant Barbara W. , Reiner Anne S. , Panageas Katherine , Yahalom Joachim , DeAngelis Lisa Marie , Abrey Lauren E. , Morris Patrick Glyn , Omuro Antonio Marcilio Padula 
Published: March 2020

2006 Background: After promising early results in the pilot phase (N= 30) reported by Shah 2007, we report on final results of a multicenter phase II study (N=52) in newly diagnosed PCNSL combining R-MPV-A and rdWBRT, expanded to address long-term disease control and cognitive outcomes in pts who actually received rdWBRT. Methods: Pts received 5 cycles of R-MPV (MTX dose: 3.5g/m2). Those with partial response (PR) received additional 2 cycles. Pts with a complete response (CR) after 5-7 cycles received rdWBRT (23.4 Gy), otherwise standard WBRT was offered (45 Gy). Consolidation cytarabine was given to all pts. Primary end-point was 2-y progression-free survival (PFS) in pts receiving rdWBRT (n=30 pts in CR required). Exploratory end-points included comprehensive neuropsychological testing, white matter changes (WMC) analysis (Fazekas scale) and apparent diffusion coefficient (ADC) on MRI. Results: Accrual was completed (N=52; 22 women); median (med) age= 60 (30-79); med KPS= 70 (50-100). In total, 31 (59%) pts were assessable for the primary endpoint (achieved a CR after induction and received rdWBRT). The 2-y PFS for this group was 78% (95% ci: 64%- 92%); med PFS= 7.7 y; the med OS was not reached (med follow-up= 6y); 3y-OS= 88% (ci 70-95); 5y-OS= 81% (ci 62-91). Cognitive testing showed improvement in executive function (P < 0.01) and verbal memory (P < 0.05) following induction chemotherapy; follow-up scores remained stable across the various domains. Minimal WMC developed in long term survivors: 36% of pts showed no change in Fazekas’ scores, 64% of pts developed scores 1 or 2 and no pt showed scores 3-6. The intent-to-treat (n=52) med PFS was 3.3y; med OS= 6.6 y. Differences in ADC values did not predict response (p=0.15), PFS (p=0.41) or OS (p=0.48). Conclusions: Consolidation rdWBRT is a highly effective and safe treatment for newly diagnosed PCNSL. Long term follow-up showed robust PFS and OS, comparable or superior to full dose WBRT, with excellent cognitive outcomes and no significant WMC over time. An RTOG randomized trial has been initiated comparing R-MPV-A with vs without rdWBRT.
Effects of cediranib (VEGF signaling inhibitor) on edema in newly diagnosed glioblastoma patients during initial chemoradiation.
Authors: Polaskova Pavlina , Pinho Marco C , Kalpathy-Cramer Jayashree , Guimaraes Alexander R , Wen Patrick Y. , Sorensen A. Gregory , Jain Rakesh K. , Batchelor Tracy , Gerstner Elizabeth Robins 
Published: March 2020

2012 Background: A significant benefit of antiangiogenic therapy is control of brain edema. We evaluated the impact of adding cediranib to standard chemoradiation (CRT) on peritumoral edema in patients with newly diagnosed glioblastoma(GBM) during the initial 6 weeks of CRT. Methods: Two cohorts of patients were enrolled in two clinical trials. The control group (N=13) received radiation for 6 weeks plus temozolomide. The cediranib (CED) group received standard CRT plus daily cediranib (N=34). MRIs were performed at baseline and weekly during CRT. Volumes of interest (VOIs) were drawn outlining the enhancing tumor on T1-weighted post contrast images and the abnormal FLAIR hyperintensity. ADC (apparent diffusion coefficient) maps were calculated from diffusion-weighted images and histograms of the distribution of ADC values created for each visit using the baseline FLAIR VOI to characterize the peritumoraledema. Patients were on stable or decreasing doses of steroids. Results: In the CED group, T1 and FLAIR VOI decreased during CRT vs controls where T1 VOI did not change and FLAIR VOI increased. By the end of CRT, the mode of the ADC histogram in the CED group shifted to the left while the mode of the controls shifted to the right. The skewness, a measure of asymmetry of the distribution, increased in the CED group and decreased in controls. Conclusions: In patients with newly diagnosed GBM treated with CRT and cediranib, tumor volume decreased on T1 and FLAIR images whereas the FLAIR volume significantly increased in the control group suggesting increased edema. The shift of mode to the right and decreasing skewness in controls (indicating an increase in the proportion of very high ADC values) suggests that adding cediranibprevented the development of edema and contributed to the resolution of existing edema. Preventing the edema by adding anti-VEGF treatment may improve the tolerability of CRT for GBM patients. [Table: see text]
Addition of upfront whole-brain radiotherapy to surgery or stereotactic radiosurgery versus surgery or stereotactic radiosurgery alone for treatment of brain metastases: A systematic review and meta-analysis.
Authors: Soon Yu Yang , Tham Ivan Weng Keong , Lim Keith Hsiu Chin , Koh Wee Yao , Lu Jiade Jay 
Published: March 2020

2016 Background: The benefits of adding upfront whole-brain radiotherapy (WBRT) to surgery or stereotactic radiosurgery (SRS) when compared to surgery or SRS alone for treatment of brain metastases are unclear. We performed a systematic review and meta-analysis of published randomized controlled trials (RCT) to determine the efficacy and safety of additional upfront WBRT. Methods: We searched MEDLINE, EMBASE, CENTRAL from date of inception and annual meeting proceedings of ASCO and ASTRO from 1999 to September 2011 for RCTs comparing surgery or SRS plus WBRT with surgery or SRS alone for treatment of brain metastases. The primary outcome was overall survival (OS). Secondary outcomes include progression free survival (PFS), local and distant intracranial disease progression, neurocognitive function (NF), quality of life (Qol) and neurological toxicity. Hazard ratios (HR), confidence intervals (CI), p values (p) were estimated with random effects models using Revman 5.1. Results: We found five RCTs including 663 patients with one to four brain metastases. Adding upfront WBRT decreased the one-year incidence of any intracranial disease progression from 73-76% to 22 - 47% but did not improve OS (HR 1.11, 95%CI 0.83 - 1.48, p = 0.47) and PFS (HR 0.76, 95%CI 0.53 - 1.10, p = 0.14). Subgroup analyses showed that the effects on overall survival are similar regardless of types of focal therapy used, number of brain metastases, dose and sequence of WBRT. The effects of upfront WBRT on NF, Qol and neurological toxicity were variable. Conclusions: Adding upfront WBRT to surgery or SRS significantly decreased any intracranial disease progression at one year but did not improve overall and progression free survival and produced variable effects on neurocognitive function, quality of life and neurological toxicity when compared with surgery or SRS alone. Future research should focus on developing more effective approaches to characterize and ameliorate the potential neurological toxicity of WBRT.
MET and ALK in glioblastoma multiforme (GBM): Comparison of IHC and FISH.
Authors: Kulig Kimary , McLendon Roger E , Locke Susan C. , Young Debra R. , Zhong Xiaoyin , Hudson Lori L. , Abernethy Amy Pickar 
Published: March 2020

2021 Background: GBM, the most common and lethal malignant primary brain tumor in adults, has an overall one-year life expectancy of 33.7%. Personalized medicine on the basis of predictive biomarkers remains elusive in GBM; however a recent case report showed clinical improvement after treatment with a mesenchymal-epithelial transition (MET) inhibitor. The authors of that report ascribe clinical response to the MET inhibitor, but the drug is also an inhibitor of anaplastic lymphoma kinase (ALK). We explored the co-expression, gain, or amplification of both MET and ALK by IHC and FISH in GBM. Methods: A convenience sample of 56 available tumors from gross-resected GBM cases within the Duke Brain Tumor tissue bank was stained for MET using clone 8F11 (Leica) and for ALK using clone 5A4 (Novocastra). FISH employed the LSI ALK (2p23) breakpoint-spanning dual-color DNA probe and the LSI D7S486 (MET)/CEP 7 dual color DNA probe (Vysis). Results: Of 56 GBM cases, MET was expressed in 69.6% and ALK in 17.9% by IHC. By FISH, gain or amplification was found in 100% of cases for MET and in 48.2% for ALK. Co-expression of MET and ALK by IHC was 14.3% and 48.2% by FISH. Co-expression by either IHC or FISH was also 48.2%. OS estimation for this cohort is premature, with 77% of patients still alive. Conclusions: MET and ALK are (co-)expressed in a significant proportion of GBM. IHC detection of MET and ALK did not correlate well with FISH results, suggesting that gene gain or amplification does not necessarily lead to abnormal MET and ALK protein expression or that IHC methods or antibodies used can be optimized. Prior studies reported MET amplification in GBM as low as 4%. Our study indicates that MET gain/amplification and protein expression may be much higher, having implications for MET-targeted therapy. Additionally, co-expression of ALK and MET has implications for dual inhibitors of these signaling pathways as well as resistance mechanisms. Our continued work will explore significance of MET and ALK as predictors of therapeutic response, with careful control for clinically relevant patient and disease characteristics. [Table: see text]