bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective study of magnetic resonance imaging (MRI) and multiparameter gene expression assay in ductal carcinoma in situ (DCIS): A trial of the ECOG-ACRIN Cancer Research Group (E4112).
Authors: Khan Seema Ahsan , Gatsonis Constantine , Snyder Brad , Lehman Constance D , Sparano Joseph A. , Solin Lawrence J. , Badve Sunil S. , Corsetti Ralph L , Rahbar Habib , Spell Derrick W , Blankstein Kenneth Bruce , Han LInda K , Sabol Jennifer L. , Bumberry John R , Miller Kathy D. , Comstock Christopher 
Published: September 2018

534 Background: Prior retrospective studies have evaluated breast MRI in DCIS, and prospective-retrospective biomarker studies have shown that the DCIS Score is prognostic for recurrence after BCS alone. E4112 is a prospective cohort study designed to assess the combined impact of breast MRI and DCIS Score on surgical and RT management. Methods: Women diagnosed with screen-detected DCIS on core biopsy, if BCS eligible, underwent breast MRI. Those remaining so following MRI and related biopsies, with no invasive disease, underwent BCS. If final surgical margins were ≥2 mm, the DCIS lesion was submitted for DCIS Score assay. Women with low DCIS Score (≤39, LS) were advised that RT could be avoided; RT was recommended to those with high/intermediate (H/I) scores. The primary objective was to estimate the fraction converting to mastectomy (Mx) following MRI. Secondary objectives included estimation of re-operation rates after first BCS, and DCIS Score distribution.A sample size of 333 evaluable women would allow estimation of Mx rate of 12% with 95% confidence interval 9-16%. Results: 334 enrolled women had completed surgery; the first surgical procedure was Mx in 54 (16.2%) and BCS in 280 (83.8%), of whom 62 (22.1%) required at least one re-excision, and 11 (3.9%) converted to Mx. DCIS Scores were obtained on 171 patients who completed BCS, of whom 82 were LS and 89 were H/I. Demographics were similar between the two groups, other features will be reported. Only 7/82 (8.5%) of the LS group received RT, whereas 82/89 (92.1%) of the H/I group received RT. Of the 98 BCS patients who did not qualify for DCIS Score-based therapy, 23 had invasive disease, 34 had final surgical margins < 2 mm, and 13 had both. There was insufficient tissue for DCIS Score in 11, and 17 did not complete follow-up. Conclusions: In this study, among DCIS patients who were BCS-eligible following MRI, total mastectomy rate was 19.5%; re-excision rate was 22.1% for women who had BCS. Approximately half had low DCIS Scores, and RT recommendations based on the DCIS Score were acceptable to most women. Clinical trial information: E4112.
Long-term outcome of breast cancer patients diagnosed ≤40 years according to breast cancer subtype in the absence of adjuvant systemic therapy: The PARADIGM initiative.
Authors: Dackus Gwen , ter Hoeve Natalie D , Opdam Mark , Vreuls Willem , Koop Esther A , Willems Stefan M. , Varga Zsuzsanna , Cordoba Alicia , Mooyaart Antien L , Groen Emilie , Broeks Annegien , Stathonikos Nikolas , Józwiak Katarzyna , Hauptmann Michael , Sonke Gabe S. , Van Der Wall Elsken , Siesling Sabine , van Diest Paul J. , Linn Sabine C. ,   PARADIGM Study Group
Published: September 2018

535 Background: Young age at breast cancer diagnosis is considered a poor prognostic factor. As a result, many treatment guidelines advice adjuvant systemic treatment for young patients. Answering prognostic questions on young patients has therefore become a challenge. The PARADIGM (PAtients with bReast cAncer DIaGnosed preMenopausally) project aims to assess the long-term outcome of women diagnosed with breast cancer ≤40 years in the absence of adjuvant systemic therapy, using real world data from the nationwide Netherlands Cancer Registry (NCR) coupled with tissue biobanking. Methods: All women ≤40 years, diagnosed in the Netherlands between 1989-2000 with a primary invasive, histologically proven, TanyN0M0 breast cancer, without adjuvant systemic treatment were identified through the NCR. Back then N0 patients were considered low risk and did not receive adjuvant systemic treatment. Tissue specimens were revised by a team of dedicated breast pathologists. Cox regression was performed to estimate hazard ratios for recurrence-free (RFS) and overall survival (OS) according to immunohistochemical (IHC) subtype. Analyses were adjusted for grade, pathological T-stage, histological subtype and radiotherapy. Results: We included 2310 patients with a mean follow-up of 15.4 years (range 0-25 years). OS for the whole cohort was 68% and RFS 58.4% at 25 years. In total 740 deaths and 1043 recurrences were observed. Hormone receptor (HR)+/HER2+ patients had a significantly worse OS when compared to HR-HER2+ patients (adjusted Hazard Ratio 1.58; 95% confidence interval 1.05-2.38; p=0.029). No difference was observed between HR-HER2+ and the triple negative and HR+/HER2- subgroups at 25-years. RFS was similar for all IHC subtypes. Conclusions: In this large cohort of non-adjuvant systemically treated young breast cancer patients with long-term follow-up HR+/HER2+ patients have a significantly worse survival when compared to triple negative, HR-/HER2+ and HR+/HER2- patients. The latter three subtypes have similar OS at 25 years. Future molecular studies have been planned to distinguish the favorable from the unfavorable prognostic patients.
Longer follow-up on cardiac safety and distant disease free survival of dose-dense doxorubicin and cyclophosphamide followed by paclitaxel and trastuzumab in patients with early-stage HER2-positive breast cancer.
Authors: Wang Rui , Yu Anthony Francis , Steingart Richard , Patil Sujata , Baselga Jose , Norton Larry , Hudis Cliff , Dang Chau T. 
Published: September 2018

540 Background: We previously reported the cardiac safety results and distant disease-free survival (DDFS) on a phase 2 trial of dose-dense (dd) doxorubicin and cyclophosphamide (AC) followed by paclitaxel (T) and trastuzumab (H) in patients with early stage, human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The incidence of congestive heart failure (CHF) was 1.4% both at a median follow-up of 2 and 7 years. Here, we report updated CHF and DDFS rates with longer follow-up. Methods: Patients were enrolled with HER2 overexpressed (immunohistochemistry 3+) or amplified (fluorescent in situ hybridization ratio > 2.0) disease, regardless of size or nodal status, and baseline left ventricular ejection fraction (LVEF) of > 55%. Patients (pts) received dd AC (60/600 mg/m2) q 2 weeks (w) x 4 →T (175 mg/m2) q 2 w x 4 with H (loading dose 4 mg/kg → 2 mg/kg q w during T → 6 mg/kg q 3 w for rest of 1 year); pegfilgrastim was administered after each chemotherapy cycle. LVEF monitoring with multigated acquisition scan occurred at baseline, months 2 (after AC), 6, 9, and 18 (after therapy completion). Results: From January 2005 to November 2005, 70 pts were enrolled; 2 (3%) and 68 (97%) were treated in neoadjuvant and adjuvant settings, respectively. In 68 pts treated in adjuvant setting, 40 (60%) and 27 (40%) had node-positive and node-negative disease, respectively. The median age was 49 years old (range 27-72); 55 (79%) had hormone-receptor positive disease, 11 (16%) had hypertension, and 21 (30%) had left sided radiation. The median baseline LVEF was 68% [range, 55%-81%]). With a median follow-up of 10.9 yrs, there was no additional CHF event. Therefore, the cumulative incidence of CHF remains to be 1.4% (95% confidence interval [95% CI], 1.36%- 7.7%). The 9 and 10 year DDFS rates were 89% (95% CI, 78%-94%) and 87% (95% CI 75%-93%), respectively. Conclusions: Longer follow-up of this study has demonstrated that ddAC →TH is associated with a low risk of CHF and promising DDFS in patients with early-stage HER2-positive breast cancer.
An estimation model for Oncotype Dx score using routine clinical and pathological parameters.
Authors: Ruiz Mendoza Rossana Esther , Namuche Fernando , Flores Claudio J. , Aguilar Alfredo , Gomez Henry Leonidas 
Published: September 2018

548 Background: Oncotype Dx(ODX) prognosticates the risk of recurrence and predicts the benefit of adjuvant chemotherapy in estrogen-receptor-positive breast cancer (BC). However, its cost makes it prohibitive for many health care systems. Our objective is to develop a model using routine clinical and pathological parameters to estimate ODX high risk category to guide adjuvant chemotherapy decisions. Methods: We retrospectively reviewed ODX and pathology reports from 190 early BC patients (2014 to 2016) in a specialized cancer center. Variables were selected through a multiple linear regression model. Coefficients of statistically significant variables were used to build an equation. Its results were divided into 2 estimated risk categories. ODX RS was also divided into 2 categories; above or below 25 (cut-off in TAILORx and RxPONDER). The final locked model was independently validated in 57 patients. Results: Among the tested variables, tumor size (pT), progesterone receptor (PR), Ki67 and Elston-Ellis grade were significantly associated with ODX RS (Table 1). The linear predictor is: (0.2544 x pT) – (0.0739 x PR) + (0.0861 x Ki67) + (5.4232 x Elston grade). The threshold score for this equation was set on 13 (median value) to discriminate low and high estimated risks. The correct classification rate (CCR) for the training and validation sets was 60% and 56%, respectively. CCR for high risk was 72% and 87% in the training and validation sets, respectively. Conclusions: An equation based on readily available variables correctly classified more than half of cases. Although the overall CCR is modest, our equation is remarkably useful for high risk cases requiring chemotherapy. With further validation, our model could provide a clinically useful estimation of high risk at lower cost. [Table: see text]
Final results of the international randomized PORTEC-3 trial of adjuvant chemotherapy and radiation therapy (RT) versus RT alone for women with high-risk endometrial cancer.
Authors: de Boer Stephanie M. , Powell Melanie E. , Mileshkin Linda R. , Katsaros Dionyssios , Bessette Paul , Haie-Meder Christine , Ottevanger Petronella B , Ledermann Jonathan A. , Khaw Pearly , Colombo Alessandro , Fyles Anthony W. , Baron Marie-Helene , Kitchener Henry C. , Nijman Hans , Kruitwagen Roy F.P.M. , Jurgenliemk-Schulz Ina M. , Nout Remi A. , Smit Vincent T.H.B.M. , Putter Hein , Creutzberg Carien L. ,   PORTEC Study Group
Published: September 2018

5502 Background: Women with high-risk endometrial cancer (HREC) are at increased risk of distant metastasis and endometrial cancer-related death. The randomized PORTEC-3 intergroup trial was initiated to investigate the benefit of adjuvant chemotherapy during and after radiotherapy (CTRT) versus pelvic radiotherapy (RT) alone for women with HREC. Methods: Women with HREC (FIGO stage I grade 3 with deep myometrial invasion and/or LVSI; stage II or III; or serous/clear cell histology) were randomly allocated (1:1) to RT (48.6 Gy in 1.8 Gy fractions) or CTRT (two cycles of cisplatin 50 mg/m² in week 1 and 4 of RT, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m² at 3-week intervals) with stratification for participating center, lymphadenectomy, stage, and histological type. The co-primary endpoints were overall survival (OS) and failure-free survival (FFS). The Kaplan-Meier method, log-rank test and Cox regression analysis were used for final analysis according to intention-to-treat. PORTEC-3 is registered with ISRCTN (ISRCTN14387080) and ClinicalTrials.gov (NCT00411138). Results: 686 women were enrolled between 2006 and 2013. 26 women were excluded; 13 withdrew consent early and 13 were ineligible, which left 660 patients in the analysis, with a median follow up time of 60.2 months (IQR 47.1–72.9): 330 CTRT and 330 RT. Three- and five-year OS for CTRT vs. RT was 84.4% versus 83.9%, and 81.8% versus 76.7%; overall HR 0.79 [95% CI 0.57-1.12, p=0.183]. Three-year FFS was 79.7% (CTRT) versus 71.8% (RT), and at 5 years 75.5% versus 68.9%, overall HR for FFS 0.77 [0.58-1.03, p=0.078]. Patients with stage III EC had lower 5-year FFS and OS compared to stage I-II (FFS 63.9% vs 78.9%, p<0.001, and OS 74.3% vs 83.1%, p=0.003). They also had greatest benefit of CTRT: 5-year FFS for stage III was 69.3% for CTRT vs 58.0% for RT [95% CI 0.45-0.97, p=0.032], and 5-year OS for stage III was 78.7 % vs 69.8% (p=0.114). Conclusions: Adjuvant chemotherapy given during and after pelvic radiotherapy for treatment of HREC did not significantly improve 5-year FFS and OS, compared with RT alone. For women with stage III EC FFS was however significantly improved with CTRT by 11% at 5 years. Follow-up will continue to evaluate long-term outcomes. Clinical trial information: NCT00411138.
Clinical utilization of Breast Cancer Index (BCI) for late recurrence risk assessment and prediction of extended endocrine therapy (EET) benefit in early stage HR+ breast cancer.
Authors: Mahtani Reshma L. , Gadi Vijayakrishna K. , Operana Theresa N. , Soifer Harris S , Schroeder Brock , Schnabel Catherine A. , Schwartzberg Lee Steven 
Published: September 2018

551 Background: Randomized trials demonstrated a modest (3-5%) absolute benefit from EET in patients (pts) with early stage HR+ breast cancer (BC), but also a risk of toxicities. BCI is a validated gene expression-based assay that provides 2 results: BCI Prognostic, based on the algorithmic combination of HoxB13/IL17BR (H/I ratio) and a set of proliferation-based genes, reports individualized risk of late distant recurrence (DR); BCI Predictive, based on H/I alone, reports a prediction of high vs low likelihood of benefit from EET. The objective of this study was to assess clinical and pathologic patient characteristics, prognostic and predictive assay results, and physician testing patterns in >14,000 clinical cases. Methods: The BCI Clinical Database for Correlative Studies is a de-identified database developed under an IRB approved protocol that contains >50 clinicopathologic and molecular variables from cases submitted for BCI in clinical practice. Clinicopathologic variables were abstracted from pathology reports, and were available for a subset of cases. Results: Across all pts (N=14,463), median age was 58.2y (range: 23-92y; 73.9% ≥50y). The majority were Stage I (47.3% IA, 3.5% IB, 29.1% IIA, 14.1% IIB, 6% III). Cases were 29%, 51%, and 20% Grade 1, 2, and 3, respectively. Most pts were ER+/PR+ (87.7%) or ER+/PR- (11.3%); 11.3% were HER2+. The majority of cases (55.7%) were ordered 4-6y postdiagnosis, with 23.1% >6y, 14.4% between 1-4y, and 6.8% <1y postdiagnosis. In LN- pts (n=3395), BCI Prognostic identified 50.6% as low risk for late DR vs 49.4% as high risk, while BCI Predictive (H/I) classified 41.0% as high vs 59.0% as low likelihood of benefit. In LN+ pts tested with the BCIN+ Prognostic algorithm (BCI + size/grade, n=818), 77.3% were classified as high risk vs 22.7% as low risk, while BCI Predictive (H/I) classified 44.6% and 55.4% as high vs low likelihood of benefit. Conclusions: Findings from this large cohort characterize utilization of BCI in clinical practice for pts with early-stage, HR+ BC. BCI stratification of pts with high risk and high likelihood of benefit from EET may facilitate selection of pts for prolonged regimens.
The prognostic value of tumor residuals indicated by surgeon, by radiology or an integrated approach by surgeons' assessment and pre-chemotherapy CT-scan in patients with advanced ovarian cancer: An exploratory analysis of the AGO Study led Intergroup trial AGO-OVAR 12.
Authors: Heitz Florian , Harter Philipp , Avall-Lundqvist Elisabeth , Reuss Alexander , Pautier Patricia , Cormio Gennaro , Colombo Nicoletta , Hell Johanna , Vergote Ignace , Poveda Andres , Ottevanger P. B. , Hanker Lars Christian , Leminen Arto Olavi , Alexandre Jerome , Canzler Ulrich , Sehouli Jalid , Herrstedt Jorn , Fiane Bent , Merger Michael , Du Bois Andreas 
Published: September 2018

5521 Background: Post-OP TR is a strong prognostic factor in AOC; the best prognosis is observed after complete resection (TR0). TR assessment is performed at the end of the surgery and may be exposed to personal bias. Pre-Chemo CT may improve post-OP assessment, however, it may also be prone to findings by post-OP tumor re-growth, tissue repair or scarring. Methods: Pts with FIGO IIB-IV AOC recruited into the double-blind randomized frontline AGO-OVAR12 trial were scheduled for baseline CT before the 1st chemo cycle. SA and RA of TR were compared. Additionally, a measurement of TR integrating both approaches were assessed (IA). For this IA information of surgical and path reports were reviewed by two of the authors. Results: 1355 pts had complete data for all 3 assessment methods. Of 689 pts with TR0 in SA, 497 (72%) and 539 (78%) had also TR0 pre-Chemo (RA and IA), but showed TR>0 in 192 (28%) and 150 pts (22%), respectively. Pts with SA defined TR0 had a similar median PFS of 27.6 mos compared to TR0 defined by RA (27.8 mos) and IA (28.9 mos). Pts with concordant TR0 (SA/ IA and SA/ RA) had a median PFS of 28.9 mos. In contrast, pts with discordant SA TR0 - RA TR>0 or SA TR0 - IA TR>0 showed inferior median PFS of 19.2 mos (HR: 1.89, 95%CI: 1.48-2.40; p<0.0001) and 16.9 mos (HR: 2.02, 95% CI: 1.57- 2.59; p<0.0001), respectively. Pts with concordant TR>0 had an even lower median PFS of 13.5 (SA and IA) and 12.9 mos (SA and RA). PFS of the experimental therapy or placebo dependent if SA, RA or IA were used, will be presented. Conclusions: Pre-Chemo CT provides information separating the group of pts with post-OP TR0 in pts with TR0 and pts with TR> 0 pre-Chemo. The latter group showed PFS values in between those with surgically assessed post-OP TR0 and those with post-OP TR> 0, forming a third prognostic group. Detailed analysis should evaluate to what extend tumor biology, surgical bias, or imperfect imaging contribute to the discrepancies. Integrating all this may lead to better definition of prognostic groups and the need for specific treatment strategies.
Association of T cell responses after vaccination with HPV16 long peptides for late stage cervical cancer with prolonged survival.
Authors: Gerritsen Winald R. , Melief Cornelis Joseph , Welters Marij , Vergote Ignace , Kroep Judith R. , Kenter Gemma , Ottevanger Nelleke , Tjalma Wiebren Age , Denys Hannelore , van Poelgeest Mariette IE , Nijman Hans , Reyners An K.L , Velu Thierry J. , Goffin Frederic , Lalisang Roy Iqbal , Stead Richard B. , Blumenstein Brent A. , van der Burg Sjoerd 
Published: September 2018

5525 Background: Therapeutic vaccination with HPV type 16 synthetic long peptides (HPV16-SLP) results in T cell–mediated regression of HPV16-induced premalignant lesions but fails to install effective immunity in patients with advanced HPV16-positive cervical cancer. We showed that HPV16-SLP vaccination in mice and in patients with advanced cervical cancer patients fosters robust HPV16-specific T cell responses, when combined with chemotherapy (Welters et al. Sci. Transl. Med., 2016). Methods: We have now completed a chemo-immunotherapy study in 70 patients with late stage HPV16+ cervical cancer (clinical trials.gov NCT02128126). Three HPV16-SLP vaccine doses were given 2 weeks after the second, third and fourth cycle of standard chemotherapy (carboplatin, AUC 6; paclitaxel 175 mg/ m2). Cohorts of 12 patients each were vaccinated with each of 4 dose levels (20, 40, 100 and 300 µg/ per peptide) of 13 overlapping HPV16 synthetic long peptides (HPV16-SLP) together covering the length of the 2 E6 and E7 proteins. Two additional cohorts of 6 patients each were vaccinated with the most promising doses of 40 and 100 µg/ peptide. Results: Robust vaccine-induced HPV16-specific T cell responses as assessed by interferon-γ Elispot were observed and were sustained until at least 30 days after the 6th cycle of chemotherapy. In addition the chemotherapy augmented recall responses to microbial antigens. Such robust T cell responses were not noted in previous trials when similar patients were vaccinated without timing of vaccination during chemotherapy. A marked and significant positive correlation was observed between the strength of the vaccine-induced immune response and overall survival. No such correlation was observed between the strength of the T cell response against common recall antigens and survival. In addition a remarkably high proportion of patients survived beyond 2 years after the start of therapy. Conclusions: The results suggest that survival duration is directly related to the strength of the vaccine-induced HPV16-specific T cell response and is not due to generally better immuno-competence. Clinical trial information: NCT 02128126.
3D HDR intracavitary brachytherapy combined with complementary applicator-guided external beam radiotherapy for 338 patients with stage IIB-IIIB uterine cervical cancer: A single-center phase II prospective study with long-term follow-up.
Authors: Lang Jin Yi , Fan Zixuan , Xu Peng , Feng Mei , Wang Weidong 
Published: September 2018

5530 Background: For uterine cervical cancer (UCC) patients with asymmetric parametric lesions, 3D HDR-intracavitary brachytherapy (HDR-ICBT) could not cover all the lesions, resulting in residual lesion and treatment failure. To settle this problem, a novel treatment modal of 3D HDR-ICBT combined with complementary applicator-guided external beam radiotherapy (EBRT) was used for UCC patients with stage IIB-IIIB in present study. Methods: Between June 2010 and June 2015, 338 patients with locally advanced cervical cancer (International Federation of Gynecology and Obstetrics stage IIB-IIIB) were treated with concurrent chemoradiotherapy. Imaged guided IMRT was used for external beam radiotherapy, 45Gy/25f. The chemotherapy was weekly cisplatin (40mg/m2). Four fractions of 3D HDR-ICBT combined with complementary applicator-guided external beam radiotherapy were used. The prescribed dose for HR-CTV and IR-CTV was 7Gy (D90) and 5Gy (D90). Dose constraints for organs at risk were D2cc <70 Gy for rectum, and D2cc<90 Gy for bladder in terms of equivalent total dose in 2 Gy fractions as GEC-ESTRO recommendations. Results: Median follow-up was 64 months (11–71 months). The D90 of GTV, HR-CTV, and IR-CTV in all cases were 93.4 (85.1-107.8) Gy, 86.4 (79.9-91.3) Gy and 72.3 (70.8-75.2) Gy, respectively. The D2CC of bladder, rectum and sigmoid were 74.3Gy、65.5Gy and 64.1Gy, respectively. 5-year LRC, DFS, and OS was 90.8%, 84.1% and 80.8%, respectively. Treatment was well tolerated. The grade ≥3 genitourinary and gastrointestinal acute and late toxicities were 2.1% and 5.2%, respectively. Conclusions: The combination of HDR-ICBT with an applicator-guided IMRT is feasible for uterine cervical cancer patients with asymmetric parametric lesions. Further study is needed to determine whether this treatment modal could be used to replace the invasive interstitial brachytherapy (ISBT) in the cases of locally advanced cervical cancer where HR-CTV coverage cannot be obtained with ICBT.