bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Non-Linear or Linear Aerobic Training (AT) Dosing Regimens on Impaired Cardiovascular (CV) Function in Patients with Operable Breast Cancer: A Randomized Controlled Trial (RCT).
Authors: Scott Jessica , Thomas Samantha M. , Herndon James Emmett , Peppercorn Jeffrey M. , Douglas Pamela S. , Khouri Michel , Dang Chau T. , Yu Anthony Francis , Catalina Diane , Ciolino Cristi , Capaci Catherine , Michalski Meghan , Eves Neil Derek , Jones Lee 
Published: May 2019

541 Background: Breast cancer therapy causes marked impairments in CV function predisposing to elevated risk of CV morbidity. We investigated the effects of two AT dosing regimens on CV function in post-treatment patients with operable breast cancer. Methods: In a three-arm, parallel-group RCT, 174 post-menopausal patients (2.8 years post primary adjuvant therapy) with impaired age/sex-matched peak oxygen consumption (VO2peak) were randomized to: (1) conventional linear AT (uniform dose-intensity / session), (2) nonlinear AT (variable dose-intensity / session), or (3) stretching (attention control). AT consisted of 64 supervised treadmill walking sessions delivered four times weekly at either ~70% VO2peak for 40 mins/session (linear) or 55% to 100% VO2peak for 20-45 mins/session (nonlinear) for 16 consecutive weeks. Stretching was matched to AT on the basis of location, frequency, duration, and treatment length. The primary end point was change in VO2peak. Secondary end points were other markers of CV risk profile (biochemical CV risk profile, cardiac function, body composition), patient-reported outcomes (PROs), tolerability (e.g., relative dose intensity), and safety. All analyses followed the intention-to-treat principle. Results: Rates of lost-to-follow were < 10% in all arms. Relative dose intensity of AT was 73% ± 27% and 80% ± 21% in linear and nonlinear arms, respectively. No serious adverse events were observed. In adjusted analysis, compared to control, VO2peak (ml O2.kg-1.min-1) increased 0.7 (± 0.3) ml O2.kg-1.min-1 (p = 0.06) and 0.8 (± 0.4) ml O2.kg-1.min-1 (p = 0.02) in linear and nonlinear AT, respectively. Rates of VO2peak improvement greater than the technical error of measurement (i.e., ≥1.32ml O2.kg-1.min-1) were 33% and 39% in linear and nonlinear AT (p = 0.03), respectively. Both AT regimens were associated with improvements in several secondary CV end points but only nonlinear AT improved PROs compared with control (all p’s < 0.05). There were no differences between the two AT regimens. Conclusion: AT significantly improves CV function and PROs in post-treatment breast cancer patients. The efficacy-tolerability ratio favors the non-linear regimen over the conventional linear prescription approach. Clinical trial information: NCT01186367.
PAM50 HER2-enriched subtype as an independent prognostic factor in early-stage HER2+ breast cancer following adjuvant chemotherapy plus trastuzumab in the ShortHER trial.
Authors: Conte Pier Franco , Griguolo Gaia , Dieci Maria Vittoria , Bisagni Giancarlo , Brandes Alba Ariela , Frassoldati Antonio , Cavanna Luigi , Musolino Antonino , Giotta Francesco , Rimanti Anita , Garrone Ornella , Galvan Patricia , Brasó Maristany Fara , Orvieto Enrico , Urso Loredana , Maiorana Antonino , Balduzzi Sara , D'Amico Roberto , Guarneri Valentina , Prat Aleix 
Published: May 2019

544 Background: We investigated the prognostic role of the PAM50 HER2-enriched (HER2-E) subtype in HER2+ early breast cancer enrolled in the randomized Phase III ShortHER trial. Methods: The ShortHER study randomized 1254 HER2+ early breast cancer patients to receive 9 weeks vs 1 year of adjuvant trastuzumab combined with chemotherapy. Gene expression measured using nCounter platform was available for 438 surgical samples. Intrinsic subtyping was determined using the research-based PAM50 predictor. Metastasis-free survival (MFS) was calculated from randomization to distant disease recurrence or death (median follow up 72 months). Uni- and multi-variable analysis were performed using Cox models. Results: PAM50 subtype distribution was: HER2-E 53% (N = 233), Luminal A 20% (N = 87), Luminal B 10% (N = 43), Normal-like 11% (N = 48) and Basal-like 6% (N = 27). HER2-E subtype was associated with hormone receptor-negative status (p < 0.001) and TILs ≥20% (p < 0.001), but not with stage and age ( < or ≥60 yrs). HER2-E subtype was associated with worse MFS vs other PAM50 subtypes overall (HR 2.78, p = 0.001), in the short (HR 2.24, p = 0.046), and in the long arm (HR 4.04, p = 0.011). Multivariable Cox model confirmed the independent prognostic value of HER2-E subtype (Table). HER2-E subtype added significant prognostic value on top of clinicopathological variables (Likelihood ratio test p < 0.001). Conclusions: HER2-E intrinsic subtype is an independent prognostic factor for HER2+ early breast cancer patients treated with adjuvant chemotherapy and trastuzumab. Integration of PAM50 subtype in prognostic algorithms can help refine risk stratification. These findings warrant independent validation. Clinical trial information: NCT00629278. [Table: see text]
The prognostic role of progesterone receptor in patients with rapidly proliferating, hormone receptor-positive early breast cancer.
Authors: Bravaccini Sara , Bronte Giuseppe , Scarpi Emanuela , Ravaioli Sara , Tumedei Maria Maddalena , Maltoni Roberta , Puccetti Maurizio , Mangia Anita , Amadori Dino , Rocca Andrea 
Published: May 2019

545 Background: The prognostic role of progesterone receptor (PgR) in highly proliferating early breast cancer (BC) is not well established. We retrospectively explored this biomarker in a cohort of patients with highly proliferating tumors enrolled in a phase III trial of adjuvant therapy. Methods: 1066 patients with N- or 1-3 N+ BC were randomized to receive: epirubicin followed by CMF, CMF followed by epirubicin, or CMF alone. Rapidly proliferating tumors were defined by thymidine labeling index (TLI) > 3% or histological grade 3 or S-phase > 10% or Ki67 > 20%. We analyze the subgroup of 466 patients with hormone receptor (HR)-positive tumors treated with sequential epirubicin/CMF regimens followed by tamoxifen and for whom immunohistochemical assessments of estrogen receptor (ER), PgR, HER2 and Ki67 were available. Disease-free (DFS) and overall survival (OS) curves were built with the Kaplan–Meier estimator and compared by logrank test and Cox regression models. Results: PgR expression was significantly associated with ER expression, HER2 status, age and menopausal status, but not with Ki67, tumor size and nodal status. PgR cutoff values of 10% and 20% were chosen based on a Receiver Operating Characteristics analysis and the literature data. DFS and OS figures at 5 and 10 years, as well as the relative hazard ratios, according to the different PgR cutoff values, are reported in the table. Conclusions: Our results confirm the prognostic relevance of PgR expression in a cohort of patients with highly proliferating, HR-positive early BC treated with adjuvant chemotherapy and endocrine therapy. [Table: see text]
Patterns of systemic treatment utilization in ER+/PgR+/HER2+, early-stage breast cancer (BC): An analysis of the National Cancer Database.
Authors: Nahleh Zeina A. , Hobbs Brian , Elimimian Elizabeth , Wei Wei (Auston) , Gupta Annie , Blake Cassann N. 
Published: May 2019

547 Background: The preferences and trends of treatment utilization of adjuvant endocrine therapy (ET) versus chemotherapy (CH) for small node-negative triple positive (TP) BC are unclear. We sought to determine these preferences and assess the impact on outcome. Methods: This is a retrospective study from the National Cancer Database including patients with TP stage I BC, 2004-2015. Treatment selection was evaluated for association with patient clinical and demographic characteristics using logistic regression. Overall survival (OS) was estimated using the Kaplan-Meier method and compared among patient and treatment cohorts by log-rank test and Cox regression. Results: Of 37,777 patients analyzed, 79% were White (Non-Hispanics), 10% African Americans, and 5% Hispanic/Latinos. 57% were 50-70 years old. 86% received adjuvant endocrine therapy versus 14% CH first. Around 40 % of all patients received anti-Her2 therapy. Patients younger than 70 years, with male BC, diagnosed with poorly differentiated BC, African Americans and Hispanics were more likely to be treated with chemotherapy. OS rate at 5-year was 92.3% (95% CI: 0.918-0.928). In multivariate analysis for patients with survival data, an increased rate of death was associated with: treatment in community versus academic/research centers, CH first versus ET, no treatment with anti-Her2 therapy, government versus private /no insurance, Native American ethnicity. A slight but statistically significant reduction in the in the risk of death at 5 years was evident for patients receiving anti-Her2 therapy plus ET therapy, 5-year OS 93.5% (CI: 89.2-98%), when compared to patients receiving anti-Her2 therapy plus CH 92.7 % (CI: 89.4-96). Conclusions: This study provides real world data of common practices in the US . The majority of patients with node negative Stage I, ER+/PR+/Her2+ BC received adjuvant ET and anti-Her2 therapy, not chemotherapy. These patients had a similar to slightly improved 5 year- survival when compared to anti-Her2 therapy plus CH, supporting the use ET plus anti-Her2 therapy in this setting. Future studies should focus on better selecting patients with hormone receptor positive and Her 2 + early stage BC who would benefit from adjuvant CH. Disparity in outcome also warrants further evaluation. [Table: see text]
Prognostic value of PD-L1 gene expression with Recurrence Score and 70-gene signature in patients with ER+/HER2- early breast cancer.
Authors: Zerdes Ioannis , Sifakis Emmanouil G. , Tobin Nicholas , Bergh Jonas C. S. , Matikas Alexios , Foukakis Theodoros 
Published: May 2019

550 Background: We have previously demonstrated that PD-L1 mRNA expression can serve as prognostic biomarker in breast cancer (BC). In ER+/HER2- BC, RS and 70-gene signature are used to predict the risk of recurrence and benefit from chemotherapy. Methods: Discovery cohort (cohort 1) included 302 patients diagnosed with primary ER+/HER2- BC (1997-2005) in Stockholm health care region. Gene expression profiling has been performed using DNA microarrays (GSE48091) while information regarding tumor characteristics, treatment and follow-up have been obtained. TCGA’s dataset including 590 ER+/HER2- patients, was used as validation cohort (cohort 2). Kaplan–Meier estimates and Cox regression univariate/multivariable analyses were performed using breast cancer-specific survival(BCSS) and progression-free interval (PFI) as endpoints in cohorts 1 and 2, respectively. Gene signature scores were calculated using the R genefu package. Likelihood ratio (LR) tests and concordance indices (c-indices) were used to assess each score’s added prognostic value. Results: PD-L1 mRNA expression (treated as a continuous variable) was independently associated with better BCSS in cohort 1 (HR = 0.72; 95% CI = 0.58-0.90;p = 0.003) and with better PFI in cohort 2 (HR = 0.67; 95% CI = 0.50-0.90; p = 0.008) in the multivariable analysis. PD-L1 provided significant additional prognostic information beyond that of both RS alone (LR-Δχ2= 9.6; p = 0.002 and LR-Δχ2= 9.7; p = 0.002, in cohorts 1 and 2, respectively), and 70-gene signature score alone (LR-Δχ2= 10.4; p = 0.001 and LR-Δχ2= 9.2; p = 0.002 in cohort 1 and 2, respectively). C-indices for PD-L1 + RS vs RS were 0.65 vs 0.60 (cohort 1) and 0.66 vs 0.60 (cohort 2), and for PD-L1 + 70-gene vs 70-gene were 0.65 vs 0.59 (cohort 1) and 0.64 vs 0.54 (cohort 2), respectively. Conclusions: PD-L1 gene expression was correlated with better outcomes and can provide added prognostic value to RS and 70-gene signature scores in ER+/HER2- BC.
A randomized phase 3 trial of paclitaxel (P) plus carboplatin (C) versus paclitaxel plus ifosfamide (I) in chemotherapy-naive patients with stage I-IV, persistent or recurrent carcinosarcoma of the uterus or ovary: An NRG Oncology trial.
Authors: Powell Matthew A. , Filiaci Virginia L. , Hensley Martee Leigh , Huang Helen Q , Moore Kathleen N. , Tewari Krishnansu Sujata , Copeland Larry J. , Secord Angeles Alvarez , Mutch David G , Santin Alessandro , Richards William , Warshal David Philip , Spirtos Nicola M. , Disilverstro Paul , Ioffe Olga , Miller David S. 
Published: May 2019

5500 Background: Gynecologic carcinosarcomas (CS) are rare yet aggressive epithelial malignancies for which optimal therapy is debated. PI was shown to be superior to I. PC demonstrated compelling phase 2 activity with improved safety and convenience. Methods: Main inclusion: ≥18 y; chemotherapy naïve stage I-IVB or recurrent uterine (U) or ovarian (O) CS. Treatment randomised 1:1 to PC (P 175mg/m2 with C: AUC 6 or 5 if prior RT on D1) or PI (P: 135 mg/m2; I 1.6 g/m2 D1-3; G-CSF support with dose escalation & de-escalation based on nadir counts) q21days for 6-10 cycles. Quality of life (QOL) (FACT-En TOI) and neurotoxicity (FACT/GOG-Ntx subscale) administered at 4 timepoints. A stratified log-rank test compared primary endpoint of overall survival (OS) from entry between treatment groups for non-inferiority (NI) of PC to PI. With 264 events, power was 80% for a null hazard ratio of 1.2 against a 13% greater death rate on PI when type I error is limited to 5% for a one-tail test. NCT00954174. Results: 637 pts accrued with a median follow-up of 61 months. The primary (U, n = 536) and secondary (O, n = 101) cohorts are analyzed separately and included 449 and 90 pts eligible pts, respectively. For the U cohort:PC and PI were randomly assigned to 228 and 221 eligible pts. Stage distribution: I (40%), II (6%), III (31%), IV (15%) and recurrent (8%). The study met its primary objective withPC not inferior to PI (intention-to-treat analysis;Median OS 37 vs. 29 mo, HR = 0.87; 90% CI = 0.70 to 1.075; p < 0.01 for NI, p > 0.1 for superiority (S)).PFS (median on PC 16mo vs PI 12mo; HR = 0.73; p = < 0.01 for NI, p < 0.01 for S). Toxicity (grade 1/2/3/4/5: PC 1/8/40/48/2%; PI 1/32/39/25/1%). Most of increase toxicity for PC was hematologic with G-CSF rarely used (N = 6). Confusion and genitourinary hemorrhage were significantly worse with PI. Both groups had decline in QOL and neurotoxicity scores. Similar trends were noted for the O cohort (OS: PC 30mo vs PI 25mo; and PFS: 15 mo vs 10 respectively). Conclusions: PC was not inferior to PI for OS with longer PFS and similar QOL and neurotoxicity. These results establish a new standard regimen for women with CS. Clinical trial information: NCT00954174.
Recurrence rates in cervical cancer patients treated with abdominal versus minimally invasive radical hysterectomy: A multi-institutional analysis of 700 cases.
Authors: Uppal Shitanshu , Gehrig Paola , Vetter Monica Hagan , Davidson Brittany Anne , Lees Brittany F , Brunette Laurie Leigh , Tucker Katherine , Matsuo Koji , Bixel Kristin Leigh , Staley Allison Stuart , Gotlieb Walter H. , Holloway Robert W. , Moore Kathleen N. , Rose Stephen L. 
Published: May 2019

5504 Background: Compare outcomes between open and minimally invasive radical hysterectomy. Methods: Retrospective multi-institutional review of patients undergoing radical hysterectomy for stage IA1, IA2 and IB1 squamous, adeno- or adeno-squamous carcinoma between 01/01/2010 - 12/31/2017. Results: From 704 cases that met the inclusion criteria, 185 (26.3%) underwent open and 519 (73.7%) underwent minimally invasive surgery (MIS). Women treated with open surgery were older, had larger tumors on preoperative assessment as well as on final pathology assessment, had higher proportion of patients with IB1 stage and adjuvant therapy. Patients undergoing open surgery had longer median follow-up compared to MIS (44 vs. 30.3 months, p < 0.001). The two groups were similar in regard to race distribution, body mass index, comorbidities and preoperative histology. There were 13/185 (7%) recurrences and 10/185 (5.4%) deaths in the open compared to 42/519 (8.1%) recurrences and 26/519 (5%) deaths in MIS (p = n.s for both). However, on multivariate analysis, after controlling for race, comorbidities, preoperative tumor size, histology, grade and smoking status, MIS had higher odds of recurrence (OR 2.24, 95% CI 1.04 - 4.87, p = 0.04). On a second model, in addition to prior mentioned factors, we included lymphovascular space invasion, receipt of adjuvant therapy and vaginal margin status. Undergoing MIS remained associated with higher odds of recurrence (OR 2.37, 95% CI 1.1 - 5.1, p = 0.031). On sub-group analysis of cases with preoperative tumor size less than equal to 2 cm, there were 5/121 (4.1%) recurrence in open and 25/415 (6%) recurrences in MIS group (p = 0.34). Multivariate analysis did not show a higher rate of recurrence in MIS arm in this subgroup. In 26 cases of MIS where no vaginal manipulator was used, no recurrences were noted. In comparison 19/270 (7%) recurrences were noted in intra-uterine manipulator (V-care/Zumi/Rumi) and 22/210 (11%) in vaginal manipulators (EEA sizer/Colpo Probe) groups (p = 0.119). Conclusions: In this large retrospective analysis, patients undergoing MIS for early stage cervical cancer had higher odds of recurrence. In patients with 2 cm or less tumor on preoperative assessment, recurrence rates were similar between the two groups. Role of manipulator in increasing recurrence should be further studied in this patient population.
Combination of niraparib and bevacizumab versus niraparib alone as treatment of recurrent platinum-sensitive ovarian cancer: A randomized controlled chemotherapy-free study—NSGO-AVANOVA2/ENGOT-OV24.
Authors: Mirza Mansoor Raza , Avall-Lundqvist Elisabeth , Birrer Michael J. , Christensen Rene dePont , Nyvang Gitte-Bettina , Malander Susanne , Anttila Maarit , Werner Theresa Louise , Lund Bente , Lindahl Gabriel , Hietanen Sakari , Peen Ulla , Dimoula Maria , Roed Henrik , Knudsen Anja Ør , Boufercha Louisa , Staff Synnove , Krog Vistisen Anders , Bjørge Line , Maenpaa Johanna Unelma 
Published: May 2019

5505 Background: Standard treatment of platinum-sensitive recurrent ovarian cancer (PSROC) is platinum based combination chemotherapy ± bevacizumab. However, this treatment modality is hardly curative, and is associated with significant toxicity. Both bevacizumab (BEV) and PARP inhibitors (PARPi) have demonstrated efficacy in PSROC. There is preclinical evidence of enhanced activity of the combination. This is the proof-of-concept randomized trial of PARPi-BEV combination against PARPi monotherapy as treatment in PSROC, regardless of number of previous lines of therapies. Methods: In this randomized, open-label, phase 2 study, women with measurable/evaluable, high-grade serous or endometrioid PSROC were randomized to niraparib 300mg once daily or the combination of niraparib 300mg once daily and BEV 15mg/kg IV every 3 weeks until disease progression (1:1 randomization). The primary endpoint was progression-free survival (PFS). Stratification was according to homologous recombination-deficiency(HRD) status (MyChoice HRD) and chemotherapy-free-interval (CFI)(6-12months (mo) vs. >12mo). First-line maintenance bevacizumab was permitted. Results: Of 97 enrolled patients, 48 were randomized to niraparib monotherapy and 49 to the chemotherapy-free combination. The combined treatment significantly improved PFS compared to niraparib alone: median 11.9 vs. 5.5 mo; hazard ratio (HR) adjusted for stratification factors 0.35; 95% confidence interval (CI),[0.21 to 0.57]; P<0.001. Pre-planned exploratory subgroup analyses: patients with HRD-positive tumors (n=54) HR 0.36 (CI, 0.18-0.69); HRD-negative disease (n=43) HR, 0.47 (CI, 0.24-0.95); g BRCAmut patients (n=34) HR 0.53 (CI, 0.23-1.21); non-g BRCAmut patients (n=63) HR 0.33; CI, 0.18-0.61); CFI of 6 to 12 mo (n=38) HR, 0.29 (CI, 0.14 to 0.62); CFI of ≥12 mo (n=59) HR, 0.42; (CI, 0.22 to 0.80). There was no difference in treatment-emergent grade 3-4 adverse events except for the rate of hypertension (26.5% vs. 0%) and neutropenia (12.2% vs. 2.1%). Patient-reported outcomes measured using EORTC QLQ-C30 and OV28 were similar for both treatment arms. Conclusions: Both niraparib alone and the combination had meaningful activity in PSROC. Compared to niraparib alone, the chemotherapy-free regimen of niraparib and BEV significantly improved PFS in women with PSROC,regardless of HRD status and duration of CFI. Clinical trial information: NCT02354131.
Randomized phase II CLIO study on olaparib monotherapy versus chemotherapy in platinum-resistant ovarian cancer.
Authors: Vanderstichele Adriaan , Van Nieuwenhuysen Els , Han Sileny , Concin Nicole , Van Gorp Toon , Berteloot Patrick , Neven Patrick , Busschaert Pieter , Lambrechts Diether , Vergote Ignace 
Published: May 2019

5507 Background: The CLIO trial (NCT02822157) evaluated olaparib single-agent therapy versus standard of care chemotherapy in platinum-resistant (recurrence within 6 months after last platin) ovarian cancer (PROC). Methods: Eligible patients with measurable disease and ≥1 prior line of chemotherapy were randomized 2:1 to Olaparib (OLA) monotherapy (300 mg tablets, BID) or physician’s choice chemotherapy (CT; PLD 40 mg/m2 q 4 wks; Topotecan 1.25 mg/m2 day 1—5 q 3 wks; Paclitaxel 80 mg/m2 day 1, 8,15 q 3 wks; Gemcitabine 1000 mg/m2 day 1, 8 and 15 q 4 wks). Primary endpoint was objective overall response (ORR) per RECIST v1.1. Germline BRCA status was available for all patients. Disease control rate (DCR) was defined as response for at least 12 wks. Results: 100 patients with PROC were randomized 2:1 to OLA (N = 67) or CT (N = 33). Median prior lines of treatment was 3 (range: 1—8). ORR (unconfirmed) was 18% (12/67) for OLA and 6% (2/33) for CT. ORR for OLA was 38% (5/13) in gBRCAm and 13% (7/54) in gBRCAwt patients. Of note, 2 patients with gBRIP1 mutation had no response under OLA. DCR was 35.8% (24/67) for OLA and 42% (14/33) for CT. DCR under OLA in gBRCAm was 62% (8/13) compared to 30% (16/54) in gBRCAwt disease. The median duration of response (DOR) and the median progression-free survival (PFS) was similar: 5.4 months vs 4.5 months (DOR) and 2.9 vs 3.4 months (PFS) for OLA and CT, respectively. Grade ≥3 treatment-related AEs occurred in 60% vs 52% for OLA and CT, respectively. Somatic HRR mutation analysis is ongoing and will be presented. Conclusions: Olaparib monotherapy showed a favorable response rate in PROC compared with chemotherapy also in gBRCAwt patients. Analysis of clinical endpoints in relation to HRR is ongoing and will be presented. Clinical trial information: NCT02822157.