bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of molecular classification combined with p53 and topoisomerase IIa expression to identify tumors highly responsive to FEC regimen: A tissue microarray
Authors: Berrada N. , Conforti R. , Delaloge S. , Spielmann M. , Andre F. 
Published: August 2020

546 Background: Identification of highly responsive tumors to specific regimen is needed in order to better tailor post-operative chemotherapy regimen. We previously reported using a tissue microarrays that basal-like and HER2-overexpressing tumors derive higher benefit from adjuvant chemotherapy than luminal-like tumors. Previous studies have reported that p53+/basal-like tumors, and HER2+/topoisomerase IIa + tumors were highly sensitive to alkylating agents and anthracyclines respectively. In the present study, we have evaluated whether p53+/basal-like and HER2+TopIIa+ tumors derive high benefit from an alkylating/anthracyclines based chemotherapy. Methods: A tissue microarrays was built with tumor samples from 823 patients randomized between FEC/FAC regimen and no chemotherapy. Basal-like breast cancers were defined as HER2-/ER-/EGFR+ and/or CK5/6+ tumors. HER2-overexpressing were defined using HER2 expression by IHC (3+ score). P53 and topoisomerase IIa expression were assessed by IHC. Treatment effect was assessed by Cox model that included prognostic parameters and stratification variables. Predictive value for treatment effect were assessed by interaction test and test for heterogeneity. Results: 823 patients were included. 12.5% and 12.9% patients presented a basal-like and HER2-overexpressing breast cancer respectively. P53 and topoisomerase IIa were expressed in 20% and 35% patients. Hazard ratio for relapse associated with FEC/FAC regimen was 0.79 (95%CI: 0.62–1). Hazard ratio associated with FEC/FAC were 0.31 (0.1–0.97 ) and 1.19 (0.38–3.7 ) in patients with p53+/basal-like and p53- basal-like breast cancer. A p53/basal-based classification was associated with a trend for heterogeneity (p = 0.15). Hazard ratio associated with FEC/FAC were 0.34 (0.11–1.0 ) and 1.27(0.32–4.9) in patients with topIIa+/HER2+ and topIIa-/HER2+ breast cancer. A HER2/TopIIa classification was associated with a trend for heterogeneity (p = 0.07). Conclusions: The present study suggest that p53+/basal-like cancer and TopIIA+/HER2 cancers derive high benefit from adjuvant FEC/FAC regimen. This finding requires further validation given multihypothesis testing and subgroup analysis. No significant financial relationships to disclose.
Triple-negative receptor status and the 2007 St. Gallen consensus guidelines for early breast cancer
Authors: Caggiano V. , Bauer K. R. , Parise C. A. 
Published: August 2020

547 Background: The 2007 St Gallen consensus statement describes three risk categories and provides guidelines for treatment. We previously described the distribution of ER/PR/HER2 in breast cancer and analyzed the triple-negative subtype. We now examine the 2007 St Gallen consensus-risk categories with respect to the ER/PR/HER2 subtypes. Methods: Using the population-based California Cancer Registry from 2000 through 2006, we identified 63,925 cases of stages I-III first primary invasive female breast cancer with known status of ER, PR, and HER2. We retrospectively assigned cases to risk categories using pathologic tumor size and grade, age, and status of ER, PR, HER2, and lymph nodes. Extensive peritumoral vascular invasion was not readily available and could not be utilized. We determined the ER/PR/HER2 subtypes for each risk category and performed five-year relative survival. Results: Five year relative survival was 95% or greater for the low risk (LR), node-negative intermediate risk (NNIR), and node positive (1–3) intermediate risk (NPIR) categories. The 5-year relative survival for the node positive (1–3) high-risk (NPHR) category was 85% and 74% for the node positive (> 3) high-risk (NPHR4) category; both had significantly worse survival than the low- and intermediate-risk categories. Classification of the risk categories by ER/PR/HER2 subtype showed no differences between the subtypes in the low risk category and clear differences in all other risk categories. All ER-negative subtypes had the worst survival within the NNIR, NPHR, and NPHR4 categories. The triple negative subtype had the worst survival in all of these risk categories. The greatest differences in 5-year relative survival were noted in the NPHR4 category with survival ranging from 85% in the ER+/PR+/HER2- subtype to 50% in the triple negative subtype. Conclusions: The St Gallen risk model clearly separates early breast cancer into three risk categories and helps with treatment decisions. Use of the ER/PR/HER2 subtypes within these categories clearly illustrates the heterogeneity of the intermediate and high risk categories and may prove to be important in this era of tailored therapy. No significant financial relationships to disclose.
Combretastatin A-4 phosphate (CA4P) carboplatin and paclitaxel in patients with platinum-resistant ovarian cancer: Final phase II trial results
Authors: Zweifel M. , Jayson G. , Reed N. , Osborne R. , Hassan B. , Shreeves G. , Poupard L. , Walicke P. A. , Balkissoon J. , Chaplin D. , Rustin G. 
Published: August 2020

5502 Background: CA4P is a vascular disrupting agent that in pre-clinical models can increase the efficacy of a variety of therapies. A dose escalation trial of CA4P given prior to carboplatin, paclitaxel or both showed the combination was well tolerated and responses were seen in several tumor types including 6/17 with relapsed ovarian cancer. The trial was therefore extended into a phase II trial in patients with platinum resistant ovarian cancer. Methods: Patients with ovarian cancer that had relapsed and could start trial therapy within 6 months of their last platinum chemotherapy were given CA4P 63mg/m2 18–20 hours prior to paclitaxel 175mg/m2 and carboplatin AUC 5 repeated 3 weekly. If > 2 responses were seen in first 18 patients 43 patients were to be treated to confirm response rate>19%. Results: Five of the first 18 patients responded so the study was extended and closed after 44 patients were recruited, with full data available to date on 34. Weekly blood counts have demonstrated grade 3/4 neutropenia in 11 and thrombocytopenia in only 1 patient. Other grade > 2 toxicity seen in > 1 patient was fatigue, nausea / vomiting, pain, alopecia, rapidly reversible ataxia, diarrhoea, neuropathy and was little different to what would be expected with paclitaxel and carboplatin. Hypertension is the commonest CA4P related toxicity and was easily controlled by GTN, then prophylactic amlodipine. Responses according to GCIG criteria, have been seen in 11/34 (32%) patients with an additional unconfirmed PR. Conclusions: The addition of CA4P to paclitaxel and carboplatin is well tolerated and appears to produce a higher response rate in this patient population than if the chemotherapy was given without CA4P. A planned randomised trial will hopefully confirm this. [Table: see text]
Tau expression as a predictive marker in ovarian cancer patients (pts) treated with platinum/paclitaxel chemotherapy
Authors: Smoter M. , Grala B. , Bodnar L. , Szczylik C. 
Published: August 2020

5529 Background: Ovarian cancer is the most lethal gynecologic cancer and its standard treatment consists of cytoreductive surgery followed by paclitaxel/platinum-based chemotherapy. Additional prognostic biomarkers may allow for more tailored chemotherapy and an improved outcome. Recently, microtubule associated protein tau was identified as a marker of response to paclitaxel in breast cancer. Its predictive value in ovarian cancer has not been established. We evaluated the relevance of tau expression in ovarian cancer. Methods: Tissue specimens were obtained from 74 ovarian cancer patients (stage I-IV) who underwent cytoreductive surgery followed by standard paclitaxel/platinum (cisplatin or carboplatin) chemotherapy. Tau expression was determined by immunohistochemistry using semiquantitative DAKO test. Statistical analysis included long rank test and Mann Whitney test. Results: Median age of pts was 54 years (range 31–73). 25.7% and 74.3% of the pts were classified as tau-negative and tau-positive, respectively. In the univariate analysis 2-year progression free survival in tau-negative and tau-positive groups was 75.0% and 30.6%, respectively (p = 0.0153). This relationship was confirmed in the multivariate analysis including age, disease stage, histology type, and grade (HR 2.68; 95%CI [1.13–6.37]; p = 0.0255). Among the 46 pts with measurable disease, overall response rate in tau-negative and tau-positive groups was 90.9 and 54.5%, respectively (p = 0.0299, Z = 2.17). Conclusions: Tau protein expression seems to be a strong predictor of clinical outcome in ovarian cancer pts applied paclitaxel/platinum-based chemotherapy. No significant financial relationships to disclose.
Phase II study of intravenous (IV) bevacizumab and paclitaxel, and intraperitoneal (IP) cisplatin, followed by bevacizumab consolidation for advanced ovarian (O) or peritoneal (P) cancers
Authors: McMeekin D. D. , Lanneau G. , Curiel J. , Moore K. , Walker J. , Mannel R. 
Published: August 2020

5540 Background: Excessive toxicity and difficulty in completing prescribed cycles are cited as factors behind the lack of routine acceptance of IP therapy in O/P cancer. In an effort to increase the probability of completing 6 cycles of IP therapy, we evaluated a modified IP regimen with the addition of bevacizumab to determine the proportion of patients able to receive 6 cycles successfully. Methods: An open label phase II study was conducted in patients (pts) with stage II-III O/P cancers with residual disease < 1 cm. The primary outcome measure the feasibility of delivering 6 cycles of IP therapy with a completion rate of > 80% being clinically relevant. Pts received paclitaxel 135 mg/m2 IV on day 1 followed by cisplatin 75 mg/m2 IP day 2. Bevacizumab 15 mg/kg day 1 IV was started with the second cycle. Cycles were administered every 21 days for a total of 6 cycles. Following completion of primary therapy, bevacizumab @ 15mg/kg IV was given in consolidation every 21 days for 12 cycles. Pts were assessed for toxicity and disease status. This preliminary analysis reports data from experience with 6 cycles of IP therapy. Results: 22 patients have been enrolled (21-O, 1-P) with a median age of 58 yrs. Two pts discontinued therapy due to IP port problems (following cycle 1 and 4) and per protocol, were replaced. Two pts are on active treatment (completed cycle 5). Of 20 evaluable pts, 2 pts discontinued prematurely (1 after cycle 1 due to elevated liver function tests, 1 after cycle 4 due to grade 3 neuropathy), and 1 pt received cycle 6 by IV route secondary to abdominal pain with IP infusion. The proportion of patients successfully completing 5 cycles of IP therapy was 18/20 (90%), and to date 15/18 (83%) pts have completed 6 cycles. One patient developed a DVT, one had an intra-abdominal fistula requiring surgical intervention after cycle 6. Conclusions: The addition of bevacizumab to an IP regimen for O/P cancers did not add to enhanced acute toxicity. The present regimen using 75 mg/m2 CDDP IP and no day 8 paclitaxel appears to be tolerable, with >80% of pts able to receive 6 cycles of therapy. [Table: see text]
Intraperitoneal chemotherapy (IPC) in older women with epithelial ovarian cancer (EOC)
Authors: Tew W. P. , O'Cearbhaill R. , Zhou Q. , Thaler H. , Konner J. , Hensley M. L. , Sabbatini P. , Spriggs D. , Aghajanian C. , Lichtman S. M. 
Published: August 2020

5541 Background: Over half of patients (pts) diagnosed with EOC are ≥ 65 yrs of age. GOG 172 showed a significant survival advantage with post-operative IPC in all women with newly diagnosed stage III EOC, regardless of age. Toxicity can be significant and there is limited data for pts ≥ 65 yrs. Methods: A descriptive intention-to-treat analysis of pts ≥ 65yrs treated with IPC for EOC at our center from 1994–2008. Medical records were reviewed retrospectively to detail toxicity (CTCAEv3.0), compliance and outcome. Results: 118 pts with a median age of 70 yrs (range 65–83), KPS 90% (range 70–90), and co-morbidities 2 (range 0–6) were treated with IPC: 27 pts (23%) as primary postoperative IPC (IV paclitaxel 135mg/m2 D1, IP cisplatin 75mg/m2 D2 & IP paclitaxel 60mg/m2 D8) and 91 pts (77%) as consolidation (IP cisplatin regimen, alone or combined with IV paclitaxel or with IP gemcitabine). Median no. of cycles was 3 (range 0–7) with 55% pts completed total no. planned. 18% were switched to IV treatment. 14% had treatment delays. 32% required dose reductions, 22% at cycle 1. Toxicities included: 32% had IP port complications, 42% functional decline, 43% new ≥ Gr1 neuropathy (4% Gr3), 12% Gr2 hearing impairment, 60% ≥ Gr1 nausea/vomiting (4% Gr3), 57% ≥ Gr1 diarrhea/constipation (0% Gr3), 37% ≥ Gr1 abdominal pain (2% Gr3). For evaluable pts, 78% had ≥ Gr1 electrolyte disturbance (5% Gr3–4), 71% ≥ Gr1 nephrotoxicity (5% Gr2; 1% Gr3), 20% ≥ Gr2 neutropenia (6%Gr3; 3% Gr4). Ca125 normalized in 90% (pts with elevated baseline Ca125). Kaplan-Meier estimated median PFI was 1.2yrs (95% CI: 1–1.6yrs). Conclusions: Rate of completed full IPC cycles and toxicity is similar to published data. IPC can be safely administered in pts ≥ 65yrs with adequate support and dose modifications. Older patients must be adequately represented in future prospective trials. No significant financial relationships to disclose.
Phase I/feasibility trial of dose-dense carboplatin (C) and paclitaxel (P) in patients (pts) with ovarian cancer: A Gynecologic Oncology Group study
Authors: Tiersten A. , Sill M. , Muggia F. , Elera C. , Garcia A. , Fracasso P. , Swensen R. , Warshal D. , Mannel R. ,   Gynecologic Oncology Group
Published: August 2020

5544 Background: Dose-dense regimens improve outcome for women with breast cancer. We investigated the feasibility of dose-dense CP for women with ovarian cancer. Methods: Pts with untreated stage III/IV ovarian cancer received C AUC 5 and P 175 mg/m2 day 1, pegfilgrastim 6 mg day 2 every 2 weeks for 6 cycles. Dose-limiting toxicity (DLT) was defined as: febrile neutropenia, grade 4 neutropenia ≥7 days, grade 4 thrombocytopenia (tcp), grade 3 tcp with bleeding, dose delay >2 weeks, grade 3/4 non-hematologic toxicity (excluding fatigue, hypersensitivity, nausea/vomiting, alopecia, constipation, diarrhea or bone pain), and any treatment related death. The study utilized a 2-stage sequential design (20 pts/stage) with DLTs in 6 cycles determining regimen feasibility. Results: Between September 2006 and September 2008, 43 pts enrolled. Twenty and 17 patients were evaluable for toxicity over 6 cycles in stages 1 and 2 respectively. Six DLT's were observed for both stages. Thirty pts completed treatment and 12 did not [DLTs (6), paclitaxel hypersensitivity reactions (2), progression (1), patient choice (1), infection (1) and death unrelated to treatment (1)]. One pt remains on treatment. The 6 DLTs resulting in treatment discontinuation included grade 3 neuropathy (2), grade 4 neuropathy (1), grade 4 tcp (1), grade 4 tcp/grade 3 febrile neutropenia (1), and grade 4 SVT (1). Six other DLTs not preventing treatment completion included grade 3 infection (1), grade 3 AST/ALT elevation (1), grade 3 confusion (1), grade 3 dehydration (1), grade 3 neuropathy (1) and grade 4 tcp (1). Other toxicities resulting in treatment delays included grade 3 tcp (1), grade 3 fatigue (1) and grade 2 neuropathy (2). There were 5 P dose reductions and 4 C dose reductions. Conclusions: Seventy-two percent pts completed 6 cycles of dose-dense CP. Based on DLTs (at least 12 in 37 evaluable pts), this regimen is not feasible. Given the neuropathy and tcp, we do not recommend further investigation in a phase III trial. No significant financial relationships to disclose.
Preliminary results of a phase II study of oxaliplatin, docetaxel, and bevacizumab as first-line therapy of advanced cancer of the ovary, peritoneum, and fallopian tube
Authors: Rose P. G. , Drake R. , Braly P. S. , Bell M. C. , Wenham R. M. , Hines J. H. , Alvarez-Secord A. , Soltes-Rak E. , Childs B. H. , Herzog T. J. 
Published: August 2020

5546 Background: Objectives are to estimate efficacy and safety of a novel taxane/platinum chemotherapy doublet in combination with bevacizumab (B), as first-line treatment of advanced cancer of the ovary, peritoneum or fallopian tube (FT), after initial debulking surgery. Methods: Eligibility criteria included histological confirmation of primary disease, previous debulking surgery, and normal renal, hepatic, hematological, and neurological function. Subjects were treated with 6 cycles of oxaliplatin (85 mg/m2), docetaxel (75 mg/m2) and B (15 mg/kg) Q3W, followed by maintenance B (15 mg/kg Q3W) to complete one year of therapy. The primary endpoint is progression-free survival (PFS) of pts with measurable disease at 1 year. Results: A total of 110 subjects are included in safety and 95 in efficacy analyses (55 with measurable disease). Median age was 58 years. Tumors were mostly ovary as primary site (84%), poorly differentiated (65%), serous adenocarcinoma pathology (73%) and FIGO stage IIIC (68.2%) or IV (14.6%). 61% of subjects were optimally debulked. 95 (86%) of subjects had completed the chemotherapy cycles with 87 of the 95 having started on the B-only maintenance cycles. 85 (77%) subjects have stopped study treatment [including 33 completed study treatment, 29 disease progression, 15 adverse event (AE), 8 other reasons]. The most common grade 3–4 AEs were: neutropenia (39%), leukopenia (11%), hypertension (9%), and fatigue (7%) Grade 3–4 peripheral sensory neuropathy (PSN) occurred in 2 patients (1.3%). There was one case of colonic perforation associated with B. Investigator-determined best overall confirmed response rates were: complete response 32.8%; partial response, 29.1%; stable disease 32.7%; and progressive disease (PD), 1.8%. The 1-year PFS probability is 70.1% (95% C.I., 56.8%-83.4%) in the 55 patients with measurable disease. Conclusions: This preliminary data supports feasibility of this novel regimen, with an acceptable safety profile and a low incidence of PSN and colonic perforation. Preliminary 1-year PFS is promising. The trial completed accrual to 132 patients in August 2008. Updated results will be presented. [Table: see text]
Patterns of use of tamoxifen and aromatase inhibitors: A population-based observational study
Authors: Huiart L. , Dell'Aniello S. , Suissa S. 
Published: August 2020

556 Background: Few data are available outside clinical trials on the use of aromatase inhibitors (AI) as adjuvant treatment for early breast cancer (BC). We therefore used a large population-based database to describe patterns of use of AI over time, in comparison with tamoxifen, as well as switches between these regimens. Methods: We identified 13,479 women treated for BC with tamoxifen, anastrazole, letrozole, or exemestane between 1998 and June 2008 in the UK General Practice Research Database (GPRD). Patients were followed from their first prescription for 5 years or until recurrence, death, switch to another treatment or occurrence of a major thromboembolic or uterine event. Results: Mean age at cohort entry was 62 years (SD=14.0) in the tamoxifen group (n=10,806) and 70.8 (SD = 12.4) in the AI group (n=2,673). Overall, in the first year of treatment 88.8% of patients had prescriptions covering more than 80% of the year (88.3% and 90.8% in tamoxifen and in AI group respectively). Table 1 describes prescriptions covering less than 80% of the days for each year of treatment in 3 subgroups. Among women started on AI therapy diagnosed with BC after 2006, 9.6% switched treatment. Half of them switched from one AI to another AI, the other half switched from AI to tamoxifen. Switches occurred within the first year of treatment in 76% of cases. Among women over 50 years of age who started a tamoxifen therapy after 2000, 31% of women switched to AI in the course of the study, of which 12% within the first year of treatment (11.1% and 13.7% for women diagnosed in 2000–2004 and after 2005 respectively). Conclusions: The real-life patterns of use of tamoxifen and AI therapy demonstrate high rates of adherence. However, the relatively high percentage of switchers among AI users is suggestive of an association with side-effects. [Table: see text] No significant financial relationships to disclose.
Ovarian cancer treatment in the New York City municipal hospital system
Authors: Boyd L. R. , Novetsky A. P. , Curtin J. P. 
Published: August 2020

5569 Background: OC patients (pts) from minority groups/lower socioeconomic strata are reported to have poorer outcomes. New York City (NYC) Health and Hospitals Corporation (HHC) has 11 municipal hospitals. We evaluated surgical management of OC pts in HHC hospitals. Methods: The New York State SPARCS database of admissions was queried for OC pts in the years 2001 to 2006. Pts from HHC were compared to pts from all other NYC hospitals (other cohort). Pt demographics, procedure performed, emergent vs. scheduled admission, length of stay, and hospital charges were compared utilizing chi-square. A comorbidity index was applied to both cohorts. Surgeons were stratified by subspecialty training and OC case volume. Results: 6,010 admissions for OC were identified. 3,624 were major surgical procedures: 187 from the HHC cohort and 3,436 from the other cohort. Demographics for HHC vs other cohort, respectively: Caucasian 37 (20%) vs 2,224 (65%); African-American (AA): 64 (34%) vs 460 (13%); Asian 20 (11%) vs 181 (5%); other: 66 (35%) vs 286 (8%); unknown 0 vs. 286 (8%) (p< 0.001). Payors for the HHC vs other cohort, respectively: Medicaid 108/187 (57%) vs 279/3,437 (8%); Medicare 22/187 (12%) vs 872/3,437 (25%); private insurance 38/187 (20%) vs 2,244/3,437 (65%); self-pay 18/187 (10%) vs 40/3,437 (1%) (p < 0.001). Urgent admissions were 96/187 (51%) of HHC cohort vs 902/3,436 (26%) of other cohort (p < 0.001). There were no differences in comorbidity rating or procedures performed. Subspecialty surgeons were documented for 59/187 (32%) of HHC cohort vs 1,839/3,437 (53%) of other cohort (p < 0.001). The majority of surgeons performed less than two OC cases over the six year period, however surgeons with cases at HHC hospitals were more likely to be represented in the top 15% of total case volume (25% vs 14%, p < 0.01) due to affiliations with academic centers. Conclusions: Pts in HHC cohort were more likely to be AA, have an urgent admission and less likely to have insurance or have a gynecologic oncologist as a surgeon. However there is evidence of centralized care for some in the HHC cohort. Despite the limitations associated with using a large database, clear differences were seen in the patterns of care between municipal and all other NYC OC pts. Studies to document outcomes and further optimize care within the HHC hospital system are ongoing. No significant financial relationships to disclose.