bluuebunny/crossref_metadata_2025_split huggingface dataset:
Solitary fibrous tumor: A retrospective analysis on 65 patients from a reference center
Authors: Palassini E. , Stacchiotti S. , Collini P. , Pilotti S. , Pastorino U. , Cantù G. , Fiore M. , Gronchi A. , Casali P. G. 
Published: August 2020

10572 Background: Solitary fibrous tumors (SFT) are very rare mesenchymal tumors with an unpredictable malignant potential. We retrospectively reviewed the long-term outcome of patients operated on at the Istituto Nazionale Tumori (INT), Milan, in a 18-year time span. Methods: All patients who underwent surgery at INT from 1990 to 2008 for primary SFT or first local relapse were retrospectively reviewed. Clinical and pathologic data were recorded. Local recurrence, distant metastases and overall survival were analyzed both from time of diagnosis and from time of local recurrence/distant metastasis. Biomolecular studies are ongoing for those cases whose frozen material is available. Results: 65 patients were identified (M/F: 33/32 - age: mean 54 yrs, range 19–85 yrs - site: peritoneum 45%, pleura 21%, lower-limb 17%, other 18% - extension at diagnosis: localized 94%, locally-advanced/unresectable 3%, metastatic 3% - size: median 11 cm, range 2–40 cm). The median follow-up was 54 months (range 0–185 months). The overall 5/10-year survival (OS), local relapse-free survival (LRFS) and metastasis-free survival (DRFS) were, respectively, 92/91%, 89/86%, 94/89%. The 5-year OS, LRFS, DMRFS after the first local relapse were, respectively, 100%, 67%, 89%. The overall incidence of metastases was 17% (lung was the commonest site). The 5-year post-metastasis OS was 45%. Multivariate analysis on clinical and pathologic/molecular prognostic factors is ongoing. Conclusions: SFT arise from a variety of anatomic sites. Surgery is curative in most patients, and local relapse has a limited impact on prognosis. Pathologic prognostic factors are under investigation to help identify the minority of patients with a poor clinical outcome. No significant financial relationships to disclose.
Trabectedin for advanced sarcomas failing doxorubicin: Analysis of 189 unreported patients in a compassionate use program
Authors: Blay J. , Penel N. , Italiano A. , Duffaud F. , Rios M. , Collard O. , Bertucci F. , Isambert N. , Chaigneau L. , Zintl P. 
Published: August 2020

10574 Background: Between 2005 and 2008, 387 patients (pts) with advanced sarcoma failing doxorubicin were treated in a compassionate use program (ATU) of trabectedin in France using the standard 1.5mg/m2/CI 24h q21d regimen. The purpose of this study was to assess the outcome of pts treated in this program. Methods: From 2005 to 2008, 87 centers (ctrs) included at least 1 pt in the ATU program. Inclusion criteria were those of the EORTC trial (J Clin Oncol, 2005;23:5276), with no restriction on the previous number of lines. A simple CRF with 22 items was used to collect pts characteristics and outcome. One hundred eighty-nine pts files were collected as of December 20, 2008. Univariate and multivariate analyses of prognostic factors was performed. Results: Two hundred thirty-five pts were included in the 17 ctrs in which >4 pts were treated. Forty-four ctrs treated only 1 pt. Fifty-two percent were female; major histological subgroups were leiomyosarcoma (29%) and liposarcoma (20%). All pts had been treated with doxorubicin and ifosfamide, 3 (1.5%) in adjuvant setting only. Trabectedin was given in 1st, 2nd, 3rd, or 4th line in metastatic phase in n=8, 69, 66, 42 pts respectively (median: 3rd line). The median number of courses were 3 (range 1–24). Best response reported were PR, n=15 (8%), SD, n=68 (36%) and PD, n=94 (50%), NE, n=11 (6%). With a median follow-up of 805 days (d), median PFS and OS were 91 d and 309 d respectively. 27/127 (20%) evaluable pts had to be hospitalized for treatment related side effects. PFS was superior in myxoid liposarcoma (MyxLPS) (median 192 d vs 69 d, p=0.003), retroperitoneal sarcomas (median 104 d vs 69 d, p=0.006), and grade 1 tumors (median 141 d vs 70 d, p=0.01). In multivariate analysis (Cox model), tumor site, grade 1, histotype were the only independent prognostic factors for PFS. For OS, favorable prognostic factors in univariate analysis were histotypes (MyxLPS, MFH), grade 1 lesions, retroperitoneal site, no hospitalisation for toxicity (p<0.01 all) while Cox model identified female gender, tumor site, histotype as the only independent prognostic factors for OS. Conclusions: In this compassionate use program for heavily pretreated pts with advanced sarcomas, trabectedin yielded PFS and OS close to those observed in phase II and III trial. PFS and OS are superior in myxLPS, retroperitoneal sarcomas, and grade 1 tumors. [Table: see text]
The influence of bisphosphonates on bone turnover markers in patients (pts) with breast cancer (BC)
Authors: Keller A. , Heim K. , Welzel G. , Findeisen P. , Neumaier M. , Wenz F. 
Published: August 2020

1058 Background: The relevance of the bone metabolism for the prognosis of BC pts is becoming widely accepted. Bisphosphonates are increasingly used in BC pts as prophylactic (antitumor benefits) or as therapeutic agents for the prevention of skeletal related events (SREs). The bone resorption marker peptide-bound collagen type I cross-links C-telopeptides (ICTP) and the bone formation marker N-terminal propeptide of type I collagen (PINP) may become important tools to monitor the bone metabolism and may be influenced by co-medication. Methods: ICTP and PINP were measured in serum samples (n = 252) under standardized conditions. We included BC pts without (n=118, 58±11 yrs) and with bone metastases (BM, n=23, 64 + 12 yrs). For comparison 111 prostate cancer (PC) pts without (n = 84, 70 ± 6 yrs) and with BM (n = 27, 67 ± 10 yrs) were investigated. Results: The median ICTP (5.41 vs 4.34 ug/l, p = 0.04 [Mann-Whitney test]) and PINP (44.9 vs 36.3 ug/l, p = 0.08) values were higher in BC pts with BM as compared to no BM. The presence of BM (< 3 vs 1–3 mets) increased ICTP and PINP values further, whereas bisphosphonates lead to a significant reduction in PINP to normal values in these pts (58.3 vs 32.8 ug/l, p = 0.01). Tamoxifen increased ICTP (4.85 ± 1.8 ug/l) and decreased PINP (36.7 ± 14.3 ug/l), whereas aromatase inhibitors (AIs) increased ICTP (4.93 ± 1.7 ug/l) and PINP (49.4 ± 24.7 ug/l). The same effects were seen in PC pts with and without BM, LHRH had a similar effect like AIs, whereas the impact of antiandrogens was like tamoxifen. Age and gender had no significant influence on ICTP or PINP in BC and PC pts. Conclusions: Markers of bone metabolism may be useful for the diagnosis and follow-up of pts with BC and PC with and without BM. Bone metastases and aromatase inhibitors increased serum ICTP and PINP, whereas bisphosphonates induced a significant decrease in serum PINP. [Table: see text]
Phase I study of bavituximab, a novel anti-phosphatidylserine monoclonal antibody in patients with advanced refractory cancer: Preliminary results
Authors: Ibrahim N. K. , Wong L. , Rosen L. , Shan J. 
Published: August 2020

1080 Background: Aminophospholipid are normally expressed on damaged or apoptotic cells, as well as on the intravascular surface of EC of vessels feeding the tumor as a result of the tumor microenvironment (e.g., hypoxia, reactive oxygen species). Bavituximab (B), a novel monoclonal antibody against PS, has demonstrated preclinical anti-tumor activity by eliciting both innate and adaptive immune responses specific to tumor vasculature. Here we report preliminary results of the phase I study in patients (pts) with advanced solid tumors. Methods: This is a phase I, dose escalation, safety, tolerability and pharmacokinetic (PK) study, as well as to define DLT, MTD and/or maximum effective dose (MED) in pts with advanced refractory cancers. Planned cohorts of 6 pts, each were to receive 0.1, 0.3, 1 or 3 mg/kg. Escalation was permitted if mean cohort Cmax ≤ 65 mcg/mL and dose limiting toxicities (DLT) was observed in ≤ 1 of 6 pts. No premedication was planned or needed. DLT was defined as ≥ grade 3 drug-related adverse events (AE), ≥ grade 2 PT, or ≥ grade 3 aPTT. B was given as a 90 minute IV infusion (on days 0, 28, 35, 42 for the first two dose cohorts and 0, 7, 14, 21 for the third- and fourth-dose cohorts. Although not a study endpoint, tumor response was collected at day 56. Results: Data are available for the first 20 pts enrolled (10 breast, 3 colorectal, 2 pancreatic, 1 each of hepatocellular carcinoma, head and neck, melanoma, mesothelioma, and prostate cancer). Cohorts by dose: 0.1 mg/kg (8 pts), 0.3 mg/kg (6pts), and 1 mg/kg (6pts). Median age was 59 years and 70% of pts were females. (Q: see attached Excel file). No DLTs or drug-related severe AEs were reported. Common drug-related AEs were fatigue (7pts), nausea (6 pts), dry skin (3 pts), constipation (2 pts) and dyspnea (2 pts). All AEs were grade 1 or 2 and no dose relationship was observed. PK was dose proportional with mean serum Cmax of 2.3, 5.2 and 16.6 mcg/mL for the 0.1, 0.3 and 1 mg/kg groups, respectively. No accumulation of B was seen after multiple weekly dosing. Conclusions: Single agent bavituximab is well tolerated to date, with a predictable PK profile. Accrual of the last planned cohort is underway. MTD has not been reached. Final results will be available for presentation at the time of the Meeting. [Table: see text]
Multiple biomarker expression in circulating tumor cells (CTCs) from locally advanced/inflammatory (LA/IBC) and metastatic breast cancer (MBC) patients (pts)
Authors: Bruce R. H. , Hseih H. B. , Curry D. N. , Krivacic R. T. , Lazarus N. , Frankel P. , Lau S. , Somlo G. 
Published: August 2020

1092 Background: Numeration of CTCs from MBC pts is predictive of outcome. Quantitative changes in CTC-s are currently tested for their potential to monitor therapy (Rx). Biomarker characterization of CTCs may be a useful adjunctive guide for Rx selection. Methods: At the COHCC between May 1, 2008 and December 31, 2008, consecutively treated pts with LABC/IBC, or with newly diagnosed/progressing MBC were accrued. Blood samples (20–30 mL) were procured prior to initiating neoadjuvant (neo)Rx (LABC and IBC patients) or systemic Rx (MBC), and were sent to PARC for analysis. A novel high-speed scanning instrument located CTCs from cytokeratin (CK) labeling enabling high resolution images to be selectively acquired using digital microscopy. From these images, CTCs were identified by CK, DAPI (nuclear marker) and CD45, and protein expression levels were determined for HER-2, estrogen receptor (ER), Excision repair cross-complementation group 1 (ERCC1), and EGFR. Cell lines with expression of each marker were used for normalization of the cell intensities, and a scoring system was used to account for relative number and expression levels of markers on the CTCs. Results: Twenty-seven pts with LABC, 4 pts with IBC, and 11 pts with MBC were enrolled. We have observed CTCs prior to initiating neoRx in all pts with IBC relative to 39% of all LABC/IBC cases, and in 57% of pts (n:14) with HER-2+ primary BC versus 24% (n = 17) with HER-2- BC . ER status, size, or grade did not predict for CTC detection. Numeration of CTCs was seen in 45% of pts with MBC. Expression of EGFR and ERCC1 was detected in 3 of 4, and 2 of 4 tested CTC samples from MBC cases. Expression of HER-2 and ER was observed on 1 of 3 and 3 of 4 CTC samples; there was discrepancy between the CTC expression profile and HER-2 and ER status of the primary BC in one case each. Conclusions: Detecting multiple markers in CTCs from pts with MBC is feasible, and similar testing in LABC/IBC patients is needed. Such multiplex testing may allow for more personalized Rx for pts with LABC/IBC and MBC. No significant financial relationships to disclose.
Correlation of release of endothelial (progenitor) cells after chemotherapy: Kinetics with response and survival
Authors: Roodhart J. M. , Langenberg M. H. , Vermaat J. S. , Lolkema M. P. , Witteveen P. O. , Voest E. E. 
Published: August 2020

11002 Background: Recently we have shown that in preclinical models and in cancer patients certain types of chemotherapy can induce an acute release of progenitor cells (Shaked et al, Cancer Cell 2008). In the preclinical models these cells diminished the efficacy of chemotherapy. Little is known of the kinetics of circulating endothelial (progenitor) cells (CE(P)C) release after chemotherapy in humans and their respective temporal functionality. Here we investigated the temporal changes in CE(P)C release after chemotherapy. Methods: Patients with mainly advanced cancer treated with various types of MTD chemotherapy were included. Blood sampling was performed at base line, 4 hours, 7 and 21 days after start chemotherapy. The mononuclear cell fraction was analyzed for CE(P)C as previously described (Duda et al, Nature Protocols 2007) Response to chemotherapy was assessed after 3 cycles of chemotherapy following the RECIST criteria. Progression free survival (PFS) was monitored. Wilcoxon matched pairs test, Spearman correlation and the Kaplan-Meyer method were used. Results: 69 patients were included, 49 were evaluable for the complete data set. In all patients treated with paclitaxel there was an immediate increase in EPC 4 hours after start of treatment (median 246% (p<0.05). Other combinations of chemotherapy induced a decrease in EPC (53%, p < 0.01). These immediate changes did not correlate with response or PFS. At day 7, both CEC and EPC levels correlated with change in tumor volume after 3 cycles of chemotherapy (r 0.4, p<0.05). At day 21 after start of chemotherapy, we found a consistent increase in EPC (315%, p 0.01) and CEC (291%, p 0.01) levels compared to baseline, independent of the chemotherapeutic used or of the presence of a tumor. CEC levels after 7 and 21 days correlated with PFS, regardless of the type of chemotherapy (day 7: HR 0.26 (95%CI 0.05–0.52, p <0.01) and day 21: HR 0.4 (95%CI 0.1–0.9, p<0.05). EPC levels did not correlate with PFS. Conclusions: These findings indicate that the longterm release of CE(P)C is a common phenomenon after treatment with chemotherapy. The correlation with a clinical response provides further support for the biological relevance of these cells.The extend of this release may influence the response to therapy and the prognosis. No significant financial relationships to disclose.
Weekly versus 3-weekly docetaxel (D2) plus doxorubicin (D4) for first-line treatment of metastatic breast cancer (MBC)
Authors: Stemmler H. , Harbeck N. , Groell der Rivera I. , Vehling-Kaiser U. , Rauthe G. , Abenhardt W. , Sommer H. , Meerpohl H. , Kiechle M. , Heinemann V. 
Published: August 2020

1101 Background: We investigated the toxicity and efficacy of weekly applied docetaxel compared to its standard 3-weekly application in pts previously untreated with chemotherapy for MBC. Methods: In the D2 trial (>60 yrs or KPS 60–80%), pts were randomized to receive docetaxel either on a 3-weekly (75 mg/m2 q3w) or on a weekly schedule (30 mg/m2 d1, 8, 15 q4w). In the D4 study (<65 yrs or KPS 70–100%), pts received doxorubicin (50 mg/m2, d 1) in addition to docetaxel given either at q3w dose of 75 mg/m2 or at as 35 mg/m2 (days 1, 8, 15, q4w). Results: The primary endpoint (toxicity) was achieved in D2 and failed in D4. Both studies were terminated prematurely (D2 n = 102/162 D4 n = 85/242 pts). In the D2 study, leucopenia ≥grade 3 was significantly less frequent in the weekly arm (4.2% q1w versus 51.9% q3w, p < 0.0001). In the weekly versus 3-weekly arm ORR was 26.8% versus 46.9% (p = 0.08), TTP was 5.4 versus 6.3 months (p = 0.91), and OS was 22.7 versus 15.8 months (p = 0.24). In the D4 study, an unexpectedly low rate of leucopenia ≥grade 3 was observed in the 3-weekly arm (29.7% q3w versus 35.7% q1w, p = 0.21). In the weekly versus 3-weekly arm, ORR was 50.0% versus 55.0% (p = 0.82), TTP was 6.2 versus 10.3 months (p = 0.36), and OS was 20.5 versus 28.9 months (p = 0.98). Non-hematological toxicity ≥grade 3 was generally mild and comparable within the two schedules. Conclusions: The present data support the feasibility of both, the weekly and the 3-weekly regimen of docetaxel application either as a single-agent or in combination with doxorubicin. As expected, leucopenia seems avoidable in the weekly scheduled of single-agent docetaxel (D2), whereas a combined weekly schedule of docetaxel/doxorubicin as given in the D4 study failed to confirm an expected lower rate of leucopenia. [Table: see text]
Deletion of 9p21 in urine specimens collected from patients with a history of hematuria and bladder cancer
Authors: Crewell K. , Qian J. , Weber D. , Medina M. , Hossain D. , Bostwick D. G. 
Published: August 2020

11038 Background: Fluorescence in situ hybridization (FISH) of voided urine sediment is a sensitive and specific test for the detection of urothelial carcinoma. Common bladder cancer FISH testing consists of 4 DNA probes to chromosomes 3, 7, and 17 and band 9p21. The pattern of enumeration anomalies for these 4 DNA probes are not well documented. We sought to determine the incidence of chromosomal anomalies detected by these 4 probes in urine specimens. Methods: Urine samples from a total of 13,284 patients with a history of hematuria and/or bladder cancer were included for study. FISH was performed in each case using fluorescence-labeled probes to the pericentromeric regions of chromosomes 3, 7, and 17 and band 9p21; cytology was also performed in all cases. Follow-up bladder biopsy information was collected from 280 cases. Results: In total, 91.6% (12163/13284) of urine samples were sufficient for FISH analysis. The overall FISH positive rate was 5.7% (691/12163), and the most frequent patterns of chromosomal anomalies were gains of chromosomes 3 and 7 (56.5%), 7 and 17 (51.6%), and 3 and 17 (36.9%). Deletion of 9p21 was observed in only 12% of cases, and was never observed as the only chromosomal anomaly. The mean number of positive cells in FISH-positive cases was 8.8 (range 4–22). Among 280 cases with matching bladder biopsies, 178 (63.6%) had urothelial carcinoma. FISH was more sensitive than cytology for the detection of urothelial carcinoma (77.4% vs. 53.5%, respectively) (p= 0.03), but there was no significant difference in specificity (68% vs. 71.6%, respectively) (p> 0.05). Conclusions: Gains of chromosomes 3 and 7 by FISH were the most common enumeration anomalies in urine specimens, while deletion of 9p21 only was rare and never seen isolation. FISH was significantly more sensitive than cytology for the detection of urothelial carcinoma with equivalent specificity. No significant financial relationships to disclose.
Association of BRCA1 mutations with diminished ovarian reserve: A common genetic mechanism for breast/ovarian cancer, and infertility?
Authors: Oktay K. , Kim J. , Barad D. , Gleicher N. , Babayev S. 
Published: August 2020

11039 Background: 25% of all breast cancers (BC) occur prior to menopause and preservation of fertility is an important quality of life issue for these women. We recently reported an ovarian stimulation (OS) protocol utilizing letrozole for women with BC who wish to preserve their fertility by embryo freezing. Because BRCA+ young women are highly represented among those undergoing fertility preservation, and because knock out models showed a relationship between DNA repair genes and germ cell development, we hypothesized that women with BRCA mutations have diminished oocyte reserve (DOR). Methods: We analyzed the letrozole-OS data to assess the association between BRCA mutations and number of oocytes retrieved, which is the most direct non-invasive method of assessing ovarian reserve. Women with infertility history and age>37 were excluded. Results: Of 125 BC patients who underwent OS between 5/03 and 11/08, 82 met the criteria, of which 47 (57%) had BRCA testing. Of those, 14 (30%) were BRCA+; 9 BRCA1+, 4 BRCA2+, and 1 + for both. Mean ages of those untested, BRCA-, and + women were similar (33.0±2.9 vs 32.8±2.9 vs 33.0±2.8; p=0.97)). Age-adjusted poor response (PR) rate (<4 oocytes retrieved) was significantly higher in BRCA+ (28.6%; 4/14) compared to BRCA- (3%;1/33, p=0.009) and untested (2.9%; 1/35, p=0.007). All poor responders were BRCA1+ with one also having a mutation in BRCA2. A BRCA mutation was associated with 17.7 times the relative risk (RR) of PR (95% CI 1.4–214; p=0.024). The mean number of oocytes was significantly lower in BRCA1+ but not BRCA2+ compared to BRCA- and untested (p=0.05). BRCA1 but not BRCA2 mutations were associated with PR with a RR of 24.0 (95% CI 1.9–298; p=0.013). When only mutations of known clinical significance were included, the RR for PR further increased (RR=36, 95% CI 2.5–503; p=0.008) suggesting a common mechanism between BRCA-induced cancer and premature diminishment of oocyte reserve. Conclusions: Because women with BRCA1 mutations may have DOR prematurely, they should be counseled for possible higher risk of ovarian failure and infertility after chemotherapy, and referred for fertility preservation. Diminished ovarian reserve may be a new component of the Hereditary Breast Ovarian Cancer Syndrome. No significant financial relationships to disclose.
LKB1 mutations in mucinous bronchioloalveolar carcinoma occurring in Peutz-Jeghers syndrome patients
Authors: Osoegawa A. , Takeda Y. , Kometani T. , Ondo K. , Fukuyama S. , Hirai F. , Nosaki K. , Seto T. , Oda S. , Ichinose Y. 
Published: August 2020

11047 Background: Mutations in the gene encoding Liver Kinase B1, LKB1, are common in patients with Peutz-Jeghers syndrome (PJS), which is characterized by mucocutaneous pigmentation, intestinal polyps and a high incidence of cancers at variable sites (colorectal, gynecological, breast, pancreas, and lung). Although tumors occurring in PJS patients are known to contain mucin-rich conmponents, mucinous bronchioloalveolar carcinomas (mBACs) arising from the PJS background have only rarely been reported. Here we report two mBAC patients with PJS. We further explored the LKB1 gene in these two patients and, in addition, eight sporadic mBAC patients. Methods: Frozen tissue specimens were collected from ten mBAC patients who underwent surgery in our department from 2002 to 2008, and high molecular weight genomic DNA was extracted from them and stocked in the bio-bank. Written informed consent was obtained from each patient, and ethical approval was obtained from the IRB. The nucleotide sequence of LKB1 (EX01–09) was determined by genomic PCR-direct sequencing. Loss of heterozygosity (LOH) was analyzed by high resolution fluorescent microsatellite analysis (HRFMA) using two microsatellite markers that encompass the LKB1 locus, D19S886 and D19S565. Results: Among 11 tumors derived from the 10 patients, 9 distinct LKB1 mutations were found in 7 tumors (4 G:C to A:T transitions; 3 G:C to C:G transversions; 2 single nucleotide insetion/deletion). All of three tumors obtained from the two PJS patients harbored a same sequence alteration. Although LOH was not observed in these tumors, independent sequence alterations were found in two of the three tumors, which may suggest biallelic inactivation of LKB1 in tumors occurred in the PJS patients. Conclusions: The relatively high frequency of LKB1 mutation in mBAC patients may suggest its implication in lung carcinogenesis, at least in mBAC, and its potential as a therapeutic target. [Table: see text] No significant financial relationships to disclose.