bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fear of disease progression in patients with gastrointestinal stromal tumors (GIST).
Authors: Tielen Ronald , Custers Jose A.E. , Prins Judith , de Wilt Johannes HW , Gielissen Marieke F.M. , Van Der Graaf Winette T.A. 
Published: March 2020

10549 Background: GIST are rare tumors and before 2000 patients had a dismal prognosis when metastasized. Since the introduction of imatinib and other tyrosine kinase inhibitors overall survival has increased from less than 1 year before 2001 to more than 5 years now. Research on psychosocial consequences for this particular cancer type is scarce. This study focuses on quality of life and fear of disease progression in GIST patients. Methods: Eighty patients with locally advanced or metastatic GIST, being treated with imatinib or sunitinib, from the Radboud University Nijmegen Medical Centre in the Netherlands were asked to participate. Patients completed self-report questionnaires including the EORTC-QLQ-C30, the Cancer Worry Scale, and the Fear of Cancer Recurrence Inventory. Results: Fifty two patients (median age 64.2; range 22-84 years) completed the questionnaires. Two subgroups were identified: patients with locally advanced (n= 27) and metastatic GIST (n= 25). Overall, GIST patients demonstrate a good global quality of life (EORTC-QLQ-C30 mean global health 76.1). However, 50% of them (n= 26) experienced high levels of fear of cancer progression (CWS cut-off point ≥ 14). High levels of fear were not associated with age, gender or between patients with locally advanced or metastatic GIST. Subgroup analyses revealed that patients with high levels of fear of disease progression showed significantly higher levels of psychological distress related to fear of cancer progression and more functional impairments including domains that can be disturbed by fear of cancer progression (e.g. work, daily and social activities, the ability to make future plans or set life goals). Conclusions: Despite a good overall quality of life, a substantial percentage of GIST patients experience high levels of fear of cancer progression, experiencing more psychological distress and more functional impairments compared to patients with low levels of fear. No relation was found with demographic variables nor with stage of disease. This research demonstrates that it is necessary to focus on more specific rather than general quality of life of GIST patients.
Results from a phase III trial (GRID) evaluating regorafenib (REG) in metastatic gastrointestinal stromal tumour (GIST): Subgroup analysis of outcomes based on pretreatment characteristics.
Authors: Joensuu Heikki , Casali Paolo Giovanni , Reichardt Peter , Kang Yoon-Koo , Blay Jean-Yves , Rutkowski Piotr , Gelderblom Hans , Hohenberger Peter , Leahy Michael Gordon , von Mehren Margaret , Badalamenti Giuseppe , Blackstein Martin E. , Le Cesne Axel , Schoffski Patrick , Maki Robert G. , Xu Jian-Ming , Nishida Toshirou , Kappeler Christian , Kuss Iris , Demetri George D. 
Published: March 2020

10551 Background: REG, an oral receptor kinase inhibitor with activity against KIT, PDGFR, VEGFR, FGFRs, and other oncologic targets, demonstrated significant improvement in progression-free survival (PFS) over placebo (PL) in a phase III study (GRID) of patients (pts) with advanced GIST following failure of at least imatinib (IM) and sunitinib (SU). To understand the impact of pts’ baseline characteristics on outcome, we performed an exploratory analysis of REG effects across pt subgroups based on sex, age, and mitotic index of primary GIST tissue, as well as duration and number of lines of previous therapies. Methods: Adult pts with metastatic GIST (n=199) progressing after at least IM and SU were randomized 2:1 to receive oral REG 160 mg or PL once daily for the first 3 weeks of each 4-week cycle. Subgroup analysis of centrally assessed PFS was performed, based on sex, age (<65, ≥65 years), mitotic index of primary GIST (<5, ≥5 to <10, ≥10 mits/50 hpf), duration of IM and SU treatment (<6, ≥6 to <18, ≥18 months), and number of prior anticancer treatment lines (2 or ≥3). Mitotic index data on primaries were available for 119 patients. Results: REG demonstrated improvement in PFS vs PL in all subgroups, as summarized in the Table. Conclusions: REG had substantial efficacy in all patient subgroups included in this analysis. Clinical trial information: NCT01271712. [Table: see text]
A risk-based individualized follow-up after complete surgery as an effective procedure to reduce the relapse (R) impact in GIST patients (pts).
Authors: Palesandro Erica , Galizia Danilo , D'Ambrosio Lorenzo , Boccone Paola , Aliberti Sandra , Venesio Tiziana , Manca Antonio , Bertotto Ilaria , Chiara Gabriele , Russo Filippo , Campanella Delia , Pignochino Ymera , Aglietta Massimo , Grignani Giovanni 
Published: March 2020

10552 Background: FU care poses a burden on both pts and health system. FU aims to precociously identify recurrences, metastases or treatment-related adverse events so to undertake the appropriate therapy as soon as possible. Guidelines (NCCN, ESMO) admit lack of knowledge on optimal surveillance, but suggest FU based on experts’ opinion and risk stratification. Moreover, tumor burden (TB) is a well known negative prognostic factor (Van Glabbeke 2005). Therefore, low-TB at R might affect final outcome. To identify the impact, if any, of regular FU, we examined our prospectively collected database looking for Rs in which the early detection affected both clinical management and, likely, the outcome. Methods: 140 pts were stratified (AFIP classification). High risk (HR) pts had complete history + physical examination (H&P) and CT every 3 mos for 2 years, 4 mos in 3rd year, 6 mos in the 4th and 5th yrs, yearly thereafter; intermediate (IR), low (LR) and very low risk (VLR) pts had H&P + CT every 4 mos for 2 years, every 6 mos up to the 5th year, then yearly. Rs were divided in: low-TB + completely resectable R (Group 1) and high-TB + disseminated R (Group 2). The number of CT needed to detect (NND) one R and the incidence of early (<6 mos) R was calculated. Overall survival (OS) was estimated by Kaplan-Meier method. Results: In 73 male and 67 female, median age 63 (23-82), risk stratification was: HR 73, IR 31, LR 28, VLR 8. After a median FU of 63 mos we observed 58 Rs: 25 (43%) and 33 (57%) in group 2 and 1, respectively. Relapsed pts genotype was KIT Ex11 72%; Ex9 10%; Ex13 3%; wild-type 15%. Median time to R was 16 mos (1-120). 21 pts underwent surgical resection of their R. 16 pts remained free from progression for a median of 90 mos. We detected 15 (26%) early Rs. NND was 17 and 32 CT for HR and non-HR pts, respectively. Group 1 and 2 median estimated OS was 112 and 87 mos (p=.05), respectively. Conclusions: Though retrospective, this series shows that FU may detect low-TB Rs. In principle, this might affect pts final outcome and, therefore, justify this costly effort. Since it is difficult to foresee a prospective randomized trial, a confirmation of these data in a different series might increase their reliability.
Significance of the vimentin expression in triple-negative breast cancer.
Authors: Yamashita Nami , Tokunaga Eriko , Kitao Hiroyuki , Tanaka Kimihiro , Taketani Kenji , Saeki Hiroshi , Aishima Shinichi , Oki Eiji , Morita Masaru , Maehara Yoshihiko 
Published: March 2020

1056 Background: Triple-negative breast cancer (TNBC), characterized by the absence of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). The treatment of patients with TNBC has been challenging due to the absence of these molecular targets and the heterogeneity of the disease. Therefore a better understanding of the molecular and histopathological features of TNBC and its heterogeniety is important for the development of a new therapeutic strategy and to improve the prognosis of TNBC. Recent studies suggest that there are links between TNBC and the epithelial-mesenchymal transition (EMT). To identify prognostic biomarkers and novel therapeutic targets, vimentin one of the most major factors associated with EMT was investigated in TNBC. Methods: Sporadic invasive ductal carcinoma specimens were obtained from 659 Japanese patients, and 90 (14%) cases were diagnosed as TNBC. The vimentin mRNA and protein expression levels were evaluated by quantitative RT-PCR and immunohistochemistry. Results: The mRNA expression of vimentin was significantly upregulated in the basal type breast cancer cell line. Immunohistochemically, the vimentin expression was significantly higher (p=0.0042) in TNBC compared to the other subtypes. Vimentin expression was associated with a younger age (p=0.016), high nuclear grade (p=0.023) and high Ki67 expression (p<0.0001), and a poorer prognosis in terms of both the recurrence-free survival (RFS) (p=0.0058) and overall survival (OS) (p=0.013) in TNBC patients. A multivariate analysis showed that vimentin expression was an independent prognostic factor for the RFS (p=0.043). Vimentin expression was also associated with a significantly shorter RFS (p=0.021) and OS (p=0.017) in patients with basal-like breast cancer (BLBC). Conclusions: The elevated expression of vimentin contributes to the aggressive phenotype and poor prognosis in TNBC. Vimentin expression might be useful as a biomarker for the prognosis of TNBC.
Relationship of FAP-alpha, ADAM12, WISP1, and SOX11 expression to tumor activity in aggressive fibromatosis: Demonstration of heterogeneity within and between cases.
Authors: Misemer Benjamin , Skubitz Amy , Manivel Carlos , Schmechel Stephen , Cheng Edward , Henriksen Jonathan , Koopmeiners Joseph , Skubitz Keith M. 
Published: March 2020

10560 Background: Aggressive fibromatosis (AF) represents a group of tumors with an unpredictable clinical course and is characterized by a monoclonal proliferation of myofibroblasts. The optimal treatment for AF is unclear. In earlier gene expression studies we identified four genes, ADAM12, WISP1, SOX11, and FAP-alpha, that were uniquely overexpressed in AF compared with 16 different normal tissues. This study was designed to examine the expression of these four proteins in AF. Methods: Immunohistochemistry (IHC) was performed in 29 cases of AF, and analyzed by a pathologist with expertise in the field. Automated imaging analysis was performed to independently quantify IHC staining, nuclear size, and nuclear chromatin density. Nuclear size was determined on control slides. Slides were scanned using ScanScope XT (Aperio) and images were divided into tiled regions of interest (ROIs) for measurements. A nuclear chromatin density ratio (CDR), defined as the measure of nuclear area with light staining divided by nuclear area with dark staining, was quantified as a surrogate for nuclear activity. To compare the image analysis with pathologic examination, an operational definition of “morphologic tumor activity” (MTA) was determined by a pathologist using a scale of 1 (inactive), 2 (probably inactive), 3 (probably active), and 4 (active) on a random set of 322 ROIs. The MTA score was then correlated with the CDR. We also assessed the relationship of CDR to IHC staining intensity for each of the four proteins in ~26,000 ROIs derived from all 29 AF samples. Results: Different areas of AF cases had different degrees of MTA. The expression of the four proteins generally correlated with the areas of tumor that were pathologically more “active.” Staining was more intense in areas with larger more open nuclei suggesting “more active” regions. There was a significant correlation between MTA and log [CDR] (0.46, p<0.001). Conclusions: The results confirm, on the protein expression level, our earlier gene expression results, and demonstrate the regional variation of tumor activity within and among AF cases.
Prediction of metastatic behavior in high-grade pleomorphic soft tissue sarcomas by gene expression.
Authors: Skubitz Keith M. , Skubitz Amy , Xu Wayne , Luo Xianghua , Lagarde Pauline , Coindre Jean-Michel , Chibon Fred 
Published: March 2020

10561 Background: The biologic heterogeneity of soft tissue sarcomas (STS) complicates treatment. Metastatic propensity may be determined by gene expression patterns that do not correlate well with morphology. In earlier studies, gene expression patterns were identified that distinguish 2 subsets of clear cell renal carcinoma (RCC), serous ovarian carcinoma (OVCA), and aggressive fibromatosis (AF). We reported the use of a gene set derived from these three studies to separate 73 high grade STS into groups with different probabilities of developing metastatic disease (PrMet). We wished to confirm our findings using an independent data set. Methods: We utilized these gene sets, hierarchical clustering (HC), Kaplan-Meier, and log-rank analyses to examine the Affymetrix HU_133 expression profiles of 309 STS. Results: HC using a pooled gene set derived from the AF-, RCC-, and OVCA-gene sets identified subsets of the STS samples. Kaplan-Meier analysis revealed differences in PrMet between the clusters defined by the first branch point of the clustering dendrogram (p=0.048), and also among the 4 different clusters defined by the second branch points (p<0.0001). Analysis also revealed differences in PrMet between the leiomyosarcomas (LMS), dedifferentiated liposarcomas (LipoD), and undifferentiated pleomorphic sarcomas (UDS) (p=0.0004). HC of the LipoD and UDS samples with the pooled probe set divided the samples into 2 groups with different PrMet (p=0.013, and 0.0002, respectively). HC of the UDS samples also showed 4 groups with different PrMet (p=0.0007). In contrast, HC found no subgroups of the LMS samples. Each individual gene set (AF-, RCC-, and OVCA-) separated the UDS samples into subsets of different metastatic outcome, but only the AF- gene set separated the LipoD samples, and no gene set identified LMS subsets. Conclusions: These data confirm our earlier studies and suggest that this approach may allow the identification of more than 2 subsets of high grade STS, each with distinct clinical behavior, and may be useful to stratify STS in clinical trials and in patient management.
Adjuvant radiotherapy (adj RT) for extremity and trunk wall atypical lipomatous tumor/well-differentiated LPS (ALT/WD-LPS): A French Sarcoma Group (GSF-GETO) study.
Authors: Cassier Philippe Alexandre , Kantor Guy , Bonvalot Sylvie , Lavergne Emilie , Stoeckle Eberhard , Le Pechoux Cécile , Meeus Pierre , Sunyach Marie-Pierre , Coindre Jean-Michel , Dubergé Thomas , Labib Alain , Lagrange Jean-Leon , Linassier Claude , Delcambre Corinne , Bay Jacques-Olivier , Leyvraz Serge , Penel Nicolas , Chabaud Sylvie , Duret Aude , Blay Jean-Yves 
Published: March 2020

10582 Background: The role of adj RT in the management of ALT/WD-LPS remains controversial. Methods: 284 patients (pts) with operable ALT/WD-LPS, no history of previous cancer, CT or RT, treated between 1984 and 2011 and registered in the Conticabase database were included and described. Overall (OS) and local relapse free (LRF) survival were evaluated from the time of first treatment (trt). Their distributions were estimated by Kaplan-Meier method and compared between RT groups using Log-Rank test. Independent prognostic factors and adj RT, were explored with Cox model. Results: Among the 20 centers, 3 enrolled 58% of the pts. Median age at diagnosis was 61 (range 25-94), 146 pts (51%) were males, 223 (79%) pts had distal tumors while 35 (12%) and 26 (9%) had tumors involving the girdle and the trunk wall. The median size of primary tumors was 17 cm (range 2-48), 272 (96%) lesions were deep seated, 24 (9%) were multifocal within the same anatomical area. Surgery quality was unknown for 42 pts. Among the remaining pts, 102 (43%) were R0, 130 (54%) R1 and 8 (3%) R2. Adj RT was given to 129 pts (45%). Pts who received adj RT had larger tumors (p=0.034), involving more often the distal limbs (p<0.001) and were more often multifocal in the same anatomical area (p=0.009). The use of adj RT varied across centers and along the study period. Other characteristics, including margin resection, were balanced between RT groups. Median follow-up for the whole population was 38.6 months (mo) (CI 95% [34.0-47.6]): 51.9 mo [43.0-62.3] for the RT group and 30.7 mo [23.3-37.8] for the surveillance group (Surv). None of the pts developed metastasis during follow-up. With 23 LR, 4 in the RT group and 19 in the Surv group, 3-years LRF rates were 98.8% [91.8-99.8] vs 90.4% [82.3-95.0] with and without adj RT (p<0.001). Once stratified on time period (before/after 2003), adj RT, age and margin resection (R0 vsother) were independently associated with LRFS. No OS difference was observed (p=0.151). Conclusions: In this study, adj RT following resection of ALT/WD-LPS was associated with a reduction of local recurrence risk. More prolonged and homogeneous follow-up is required to confirm these results.
Incidence of brain metastases and overall survival in patients with primary cardiac sarcoma: A retrospective case series.
Authors: Shango Maryann , Zhao Lili , Leja Monika , McHugh Jonathan B. , Schuetze Scott , Chugh Rashmi 
Published: March 2020

10584 Background: Primary cardiac sarcoma (PCS) is the most common primary cardiac malignancy, but is a rare primary site of sarcoma. We present 21 cases from a tertiary care center to better understand this uncommon malignancy. Methods: A cancer center-based registry and pathology database were searched to identify pts diagnosed with PCS from 1992-2013 at University of Michigan. Kaplan-meier method was used to estimate survival. Cox proportional hazard model was used to associate variables to occurrence of metastases (mets) or death. Results: Atotal of 21 pts (F12, 9M) with PCS were identified, median age 36 (range 11-74). The most common presenting symptoms included dyspnea (16) and chest pain (6; 5 with associated pericardial effusion). Histologies included: angiosarcoma (9), leiomyosarcoma (4), undifferentiated pleomorphic (3), spindle cell (2), fibrosarcoma (1), rhabdomyosarcoma (1) and synovial (1). Sites of origin were R atrium (7), R ventricle (2), L atrium (10) and pericardium (2). Ten pts presented with mets; most common sites were lung (8), liver (2), brain (2), pancreas (2) and bone (2). Surgery was attempted in 12 pts, achieving 1 R0 resection. Pts received a median of 1 (0-7) systemic therapies. Median overall (OS) was 12.6 mos (range 3-79) from diagnosis. Pts without prior surgery were more likely to have mets or death (p=0.038). Brain mets were common, occurring in 7 of 21 pts after a median of 7 mos (range 1-75) from diagnosis. Median OS after diagnosis of brain mets was 8 mos. Of the 7 pts who developed brain metastasis, 5 had PCS originating in the left heart. Of the 2 pts with PCS in the right heart, one was evaluated for and had a right to left shunt. The likelihood of developing brain mets did not correlate with age, chemotherapy, or surgery. Conclusions: PCS portends an extremely poor prognosis, marked by inability to achieve complete resection and a high incidence of disseminated disease at diagnosis. Metastatic disease to the brain was much more common in PCS (33%) as compared to STS of any origin (approximately 1-8%), particularly in pts with PCS originating in the left heart. Clinicians should have a low threshold for brain imaging evaluation of PCS pts.
A phase II trial of novel anthracycline amrubicin in advanced soft tissue sarcoma.
Authors: Gouw Launce , Randall R Lor , Jones Kevin , Chawla Sant P. , Sharma Sunil 
Published: March 2020

10587 Background: Amrubicin is a 9-aminoanthracycline with significantly less cardiotoxicity than doxorubicin, a current standard against soft tissue sarcoma, and may represent an appealing alternative first line therapy. We report findings in a phase II study investigating tolerability and efficacy of amrubicin in patients with advanced STS. Methods: We enrolled adult patients in a single-arm open label study with locally advanced or metastatic soft tissue sarcoma, no prior systemic treatment, measurable disease, an ECOG PS <2, and adequate organ function. We administered amrubicin (40 mg/m2 IV over 10’) on D#1-3 of a 21D cycle with GCSF support. Six cycles were planned with continuation at clinician discretion. We used RECIST 1.1 to radiologically assess response to therapy. Toxicities were assessed using CTCAE 4.0. The primary objective was overall response rate (CR+PR), and clinical benefit (CR+PR+SD). We employed a 2- stage design, with 15 patients treated in the first stage. Error rates were α=5% for accepting a poor regimen and β=10% for rejecting a promising regimen, with planned enrollment of 30 patients through the second stage if activity was observed. Results: 15 of 15 planned patients enrolled in the first stage of this phase II clinical trial; 10 males and 5 females, with median age 59 (range 30-73). Of the 13 evaluable patients, at 6 cycles 3 patients achieved a PR, with best response of 78% reduction of target lesions; 4 patients demonstrated minor response/stable disease (SD), ranging from 11-28% reduction of target lesions, and 4 patients had minor progression/SD (less than 20% progression). Two patients progressed >20%. Clinical benefit is currently 85.7% (12/14). Amrubicin has been well tolerated, with primarily grade I and II AEs. A single dose adjustment has occurred but no treatment delays. No cardiac complications, ECG or significant echocardiogram changes have been noted. Conclusions: Amrubicin is a novel anthracycline with encouraging activity against STS and an extremely well tolerated side effect profile. Further study of amrubicin in STS is warranted. With minor treatment-related morbidity, amrubicin would also be a good candidate for combination therapy with other standard or experimental therapeutics. Clinical trial information: NCT01259375.
Copy number changes in triple-negative breast cancer: New molecular targets.
Authors: Koudelakova Vladimira , Radova Lenka , Svoboda Marek , Wei Wenbin , Kharaishvili Gvantsa , Bouchal Jan , Trojanec Radek , Hajduch Marian , Kolar Zdenek , Bouchalova Katerina 
Published: March 2020

1063 Background: Triple negative breast cancer (TNBC) is associated with tumor aggressiveness and high recurrence rate. Treatment options are limited due to lack of molecular-genetic markers and targeted therapy. The aim of our research is assessment of copy number changes in TNBC patients and identification of potential markers for personalized therapy. Methods: Fresh-frozen tumor tissues were collected from 148 patients with TNBC stage I-III. Genomes of these samples were profiled by Affymetrix SNP6.0 arrays. Arrays were normalized using R/Bioconductor and GISTIC 2.0 was used to identify copy number changes. Results: TNBC showed a high level of chromosomal instability and heterogeneity. More than 200 significantly altered chromosomal regions (q value < 0.25) were identified with frequency from 7.4 to 48% cases. Amplification of cell proliferation regulators (MYC, FGFR2, cyclins E1 and E2, PIK3CA, NFIB), regulators of vascularization (VEGFA) and epithelial–mesenchymal transition (CAV1 and CAV2) were found with high significance (q value < 0.1). Deletions of CDK regulators CDKN2B and CDKN2A, and tumor suppressors PTEN, RB1, APC and POT1 were also detected with highly significant q value < 0.1. Importantly, novel copy number changes of genes influencing inflammation, expression regulation and chromatin modification, localized on 1q, 7p, 8q, 9p, 17q and 19p, were found in more than 15% of samples. Conclusions: Despite the fact that TNBC is a heterogeneous group, several common copy number changes were identified. Our analysis confirmed copy number changes of important known genes as well as identified novel markers involved mainly in inflammatory and regulatory processes which could be targets of future therapies. Grant: Biomedreg CZ.1.05/2.1.00/01.0030.