bluuebunny/crossref_metadata_2025_split huggingface dataset:
A randomized multicenter trial of epirubicin, oxaliplatin, and capecitabine (EOC) plus panitumumab in advanced esophagogastric cancer (REAL3).
Authors: Waddell Tom Samuel , Chau Ian , Barbachano Yolanda , Gonzalez de Castro David , Wotherspoon Andrew , Saffery Claire , Middleton Gary William , Wadsley Jonathan , Ferry David Raymond , Mansoor Wasat , Crosby Tom David Lewis , Coxon Fareeda Y , Smith David , Waters Justin S. , Iveson Timothy , Falk Stephen , Slater Sarah , Okines Alicia Frances Clare , Cunningham David 
Published: February 2017

LBA4000 Background: EGFR overexpression occurs in 27-50% of esophagogastric adenocarcinomas (OGA), and correlates with poor prognosis. The REAL3 trial evaluated the addition of the anti-EGFR antibody panitumumab (P) to epirubicin, oxaliplatin and capecitabine (EOC) in advanced OGA. Methods: Patients with untreated, metastatic or locally advanced OGA were randomised to EOC (E 50mg/m2, O 130mg/m2, C 1250mg/m2/day) or mEOC+P (E 50mg/m2, O 100mg/m2, C 1000mg/m2/day, P 9mg/kg). Primary endpoint was overall survival (OS); secondary endpoints were progression-free survival (PFS), response rate (RR), toxicity, and biomarker evaluation. Response was evaluated by RECIST after 4 and 8 cycles. Following IDMC review in October 2011 trial recruitment was halted and panitumumab withdrawn. Data for patients on treatment were censored at this timepoint. Results: 553 patients were recruited (EOC 275, mEOC+P 278), with median follow-up 5.0 and 5.2 months respectively. Median OS was 11.3 months with EOC compared to 8.8 months with mEOC+P (HR 1.37: 95% CI 1.07-1.76, p=0.013). Median PFS was 7.4 and 6.0 months respectively (HR 1.22: 95% CI 0.98-1.52, p=0.068), with RR being 42% compared to 46% (odds ratio 1.16: 95% CI 0.81-1.57, p=0.467). mEOC+P was associated with ↑ G3/4 diarrhoea (17% vs 11%), skin rash (14% vs 1%) and thrombotic events (12% vs 7%), but ↓ haem toxicity (>G3 neutropenia 14% vs 31%). In the mEOC+P arm, OS was significantly improved in patients with G1-3 rash (77%, n=209) on treatment compared to those without (23%, n=63); median OS 10.2 vs 4.3 months (p<0.001), with similar significant improvements seen in RR and PFS. Biomarker analysis in the first 200 patients has not identified other predictive markers associated with P therapy. Multivariate analysis for OS in these patients demonstrated a negatively prognostic role for KRAS mutation (HR 2.1: 95% CI 1.10-4.05, p=0.025) and PIK3CA mutation (HR 3.2: 95% CI 1.01-10.40, p=0.048). Conclusions: Addition of P to EOC chemotherapy was associated with worsening of OS in an unselected advanced OGA population. This may be in part due to lowered doses of O and C in the mEOC+P regimen. Outcomes in patients treated with P varied by grade of skin toxicity.
Interim analysis (IA) results of COU-AA-302, a randomized, phase III study of abiraterone acetate (AA) in chemotherapy-naive patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Ryan Charles J. , Smith Matthew Raymond , De Bono Johann Sebastian , Molina Arturo , Logothetis Christopher , De Souza Paul L. , Fizazi Karim , Mainwaring Paul N. , Piulats Rodriguez Jose Maria , Ng Siobhan , Carles Joan , Mulders Peter , Kheoh Thian San , Griffin Thomas W. , Small Eric Jay , Scher Howard I. , Rathkopf Dana E. ,   on behalf of the COU-AA-302 Investigators
Published: February 2017

LBA4518 Background: AA is an androgen biosynthesis inhibitor that inhibits CYP17 and improves overall survival (OS) in post-docetaxel mCRPC. The primary objective of COU-AA-302 was to compare clinical benefit of AA + prednisone (P) vs placebo (PL) + P in chemo-naive, asymptomatic/mildly symptomatic mCRPC pts. Methods: 1088 pts (151 centers; 12 countries) were randomized 1:1 to AA (1 g) + P (5 mg BID) or PL + P. Co-primary endpoints: radiographic progression-free survival (rPFS) and OS. Median times estimated using K-M method including LR statistic for inference. The Lan-DeMets α-spending function was used for OS. Results:The Independent Data Monitoring Committee concluded that the OS, rPFS and secondary endpoints (Table) all favored the AA arm and unanimously recommended unblinding the study and crossing pts from PL to AA at IA (43% of total events). Median follow up = 22.2 mos. Grade 3/4 AEs (AA + P, PL + P) (%): hypertension 3.9 vs 3.0; hypokalemia 2.4 vs 1.9; ALT↑ 5.4 vs 0.7; AST↑ 3.0 vs 0.9. Conclusions:AA + P produced a statistically significant improvement in rPFS and a strong trend for increased OS at this IA. AA resulted in clinically and statistically significant effects on all secondary endpoints. IA results confirmed the acceptable tolerability/safety profile of AA. This is the first randomized trial to demonstrate both OS and rPFS benefits in chemo-naive mCRPC and that inhibition of persistent extragonadal androgen synthesis significantly delays initiation of cytotoxic chemo. While median OS (AA arm) has not been reached, median PL arm OS (27.2 mos) is the longest measured in any phase III mCRPC study. [Table: see text]
PARAMOUNT: Final overall survival (OS) results of the phase III study of maintenance pemetrexed (pem) plus best supportive care (BSC) versus placebo (plb) plus BSC immediately following induction treatment with pem plus cisplatin (cis) for advanced nonsquamous (NS) non-small cell lung cancer (NSCLC).
Authors: Paz-Ares Luis , De Marinis Filippo , Dediu Mircea , Thomas Michael , Pujol Jean-Louis , Bidoli Paolo , Molinier Oliver , Sahoo Tarini Prasad , Laack Eckart , Reck Martin , Corral Jaime Jesus , Melemed Symantha , John William J. , Chouaki Nadia , Zimmermann Annamaria , Visseren-Grul Carla , Gridelli Cesare 
Published: February 2017

LBA7507 Background: The PARAMOUNT trial showed that pem continuation maintenance therapy significantly reduced the risk of disease progression over plb (HR=0.62; 95% CI: 0.49-0.79; p <0.0001) in patients (pts) with advanced NS NSCLC who had not progressed during pem-cis induction. Here we present the final OS data. Methods: In a double-blind, plb-controlled study, alpha-controlled for OS, 939 pts received induction (4 cycles of pem 500 mg/m2 and cis 75 mg/m2 on d1 of 21d cycles), and 539 pts who had not progressed and had an ECOG performance status (PS) of 0/1 were randomized (2:1) to maintenance pem (500 mg/m2, on day 1 of 21-day cycles) plus BSC or plb plus BSC until disease progression. All received B12, folic acid, and dexamethasone. After 397 deaths, a log-rank test compared OS between arms using anominal α level of 0.0498. Results: Pt characteristics were balanced between arms: median age 61 years; 58% men; 32% PS 0; 95% Caucasian; 86% adenocarcinoma; 45% complete/partial response (CR/PR) to induction. Pem resulted in a statistically significant 22% reduction in risk of death (HR=0.78). The HR was the same when measured from the beginning of induction. Survival improvement was similar for pts with an induction outcome of CR/PR versus stable disease. Conclusions: Pem continuation maintenance therapy offers superior OS compared with plb. These final results confirm that pem-cis induction followed by continuation pem further benefits pts compared with induction therapy alone, offering a change in the treatment paradigm for advanced NS NSCLC. [Table: see text]
Phase II study of pertuzumab, trastuzumab, and weekly paclitaxel in patients with HER2-overexpressing metastatic breast cancer (MBC).
Authors: Datko Farrah Mikhail , D'Andrea Gabriella , Dickler Maura N. , Theodoulou Maria , Goldfarb Shari Beth , Lake Diana , Fornier Monica Nancy , Modi Shanu , Sklarin Nancy T. , Comen Elizabeth Anne , Fasano Julie , Gajria Devika , Drullinsky Pamela , Murphy Conleth G. , Syldor Angemael , Patil Sujata , Liu Jennifer , Chandarlapaty Sarat , Hudis Clifford , Dang Chau T. 
Published: February 2017

134 Background: Pertuzumab (P) is a monoclonal antibody which binds to extracellular domain II of HER2 distally from trastuzumab (H), disrupting HER2 dimerization and signaling. The CLEOPATRA phase III trial showed that HP + docetaxel in HER2+ MBC prolonged progression-free survival (PFS) compared to placebo + H + docetaxel. We report preliminary results of a phase II study to evaluate the safety and efficacy of weekly paclitaxel (T) with HP (THP). Methods: Patients (pts) with HER2+ MBC with 0-1 prior treatment (Rx) are eligible. Pts receive weekly (w) paclitaxel (80mg/m2), q3w trastuzumab (loading dose 8mg/kg → 6mg/kg), and q3w pertuzumab (flat loading dose 840mg → flat dose 420mg). The primary endpoint is PFS at 6 months (mo). Secondary endpoints include response, safety (including cardiac events), and tolerability. Evaluable pts are those who have started study Rx and are assessed at 6 mo for PFS. Left ventricular ejection fraction (LVEF) is monitored by echocardiogram every 3 mo. Cardiac events are defined as symptomatic LV systolic dysfunction (LVSD), non-LVSD cardiac death, or probable cardiac death. Results: As of 5-1-12, 33 of the planned 69 pts were enrolled; 16 were evaluable at 6 mo. Of the 16 pts, G 3/4 toxicities included sepsis (1pt, 6%), cholecystitis (1pt, 6%), fatigue (1pt, 6%), skin ulceration (1pt, 6%) and cystic macular degeneration (1 pt with prior prolonged Rx with paclitaxel, 6%). G 1/2 toxicities included alopecia (16 pts, 100%), fatigue (15 pts, 94%), ALT/AST elevation (14 pts, 88%), neuropathy (14 pts, 88%), diarrhea (12 pts, 75%), rash (9 pts, 56%), nail changes (8 pts, 50%), nausea (7 pts, 44%), mucositis (7 pts, 44%), and dry skin (6 pts, 38%). Median LVEF was 63% at baseline, 60% at 3 mo and 58% at 6 mo. There were no cardiac events. At 6 mo, 12/16 pts (75%) were progression-free (2 CR, 7 PR and 3 SD); 4 pts progressed. Conclusions: Our single-center phase II study continues to accrue, with no significant diarrhea or signal of increased cardiac toxicity to date. If the estimate of activity is similar to results with docetaxel in CLEOPATRA, this will provide support for THP as an alternative option in this setting.
Sarcopenia to predict tolerance of adjuvant breast cancer chemotherapy.
Authors: Sabel Michael S. , Conlon Anna S.C. , Griffith Kent A. , Englesbe Michael , Wang Stewart 
Published: February 2017

138 Background: Despite improved survival with adjuvant chemotherapy among older women, it is less often recommended for fear they cannot complete therapy or will have excessive toxicity. Analytic morphometrics uses objective imaging measurements such as muscle size, bone mineral density (BMD) and body composition to improve risk stratification. We examined whether morphometrics might help predict toxicity of chemotherapy in breast cancer patients. Methods: Our prospective IRB-approved breast cancer database was queried for all patients who underwent adjuvant or neoadjuvant chemotherapy and had CT scans of the chest, abdomen and pelvis prior to chemo. Complications of chemotherapy were graded according to the NCI-CTC. CT scans were processed using semi-automated algorithms (MATLAB v13.0) to measure psoas area (PA) and density (PD), BMD and subcutaneous fat (SF), visceral fat (VF), and total body area (TBA. Outcome (DFS and OS) was assessed by K-M, and logistic regression models and ANOVA were used for toxicity events. Results: We identified 129 patients, ranging in age from 24 to 83 (median 52). 105 (81%) received AC/T while 19% received alternate regimens, all full weight based. T-stage, nodal status and HER2 expression were significantly associated with measures of obesity, except BMI, but not sarcopenia. After adjusting for stage and Her-2, BMI remained a significant predictor of DFS (OR 1.07 (95%CI 1.01, 1.13)) and OS (OR 1.06 (95% CI 1.00, 1.12)).After controlling for age, PD and VF were predictors of chemotherapy completion. The OR for completing chemotherapy decreased 0.95 (95% CI: 0.90, 1.01, p=0.08) for every increase of 1000 in VF and increased 1.08 (95% CI: 1.01, 1.15, p=0.03) for every unit increase in PD. Sarcopenia was associated with an increased risk of pulmonary complications (p=0.01) and anemia (p=0.06). Conclusions: Although age is a significant predictor of increased toxicity and inability to complete chemotherapy, sarcopenia is an objective, independent predictor of chemotherapy completion. Psoas density, easily obtainable from a pre-treatment CT scan, can help the clinician older breast cancer patients for adjuvant chemotherapy.
Assessing the use of routine abdominal CT in staging evaluation of patients with primary breast cancer.
Authors: Staley Stuart-Allison Moffat 
Published: February 2017

3 Background: The purpose of this study was to determine the utility of routine abdominal CT in the staging evaluation of women with newly diagnosed primary breast cancer given no detectable disease beyond the ipsilateral axillary nodes on chest CT. Methods: The chest and abdominal CT scans from 440 patients over a 10-year period were reviewed. The presence of definite or possible metastatic disease in the axillary nodes, chest wall, internal mammary nodes, mediastinal nodes, lungs, liver and adrenals were recorded for each patient. Cross tabulation bivariate analysis as well as a chi-square test were performed to characterize the relationship between detection of disease in the chest and disease in the abdomen. Results: Of the 440 patients reviewed, the following were found to have detectable metastatic disease by CT scan: axillary nodes 258 of 440 (56.46%), chest wall 40 of 440 (9.10%), internalmammary nodes 8 of 440 (1.82%), mediastinal nodes 29 of 440 (6.59%), lung 25 of 440 (5.68%), liver 12 of 437 (2.73%), and adrenals 8 of 440 (1.82%). In total, 81 patients had disease detectable in the chest beyond the ipsilateral axillary nodes, and only 12 patients had detectable disease spread in the abdomen. Of the 359 patients who had a negative chest CT, only 1 patient had detectable or possible metastatic disease spread on abdominal CT, resulting in a 99.70% negative predictive value (p < 0.001). Conclusions: The routine use of abdominal CT in women with newly diagnosed primary breast cancer and no detectable disease beyond the ipsilateral axillary nodes on staging chest CT scan has little value with a 99.70% negative predictive value. We recommend that if a negative CT scan of the patient’s chest yields no detectable disease beyond the axillary nodes, then further CT imaging of the abdomen is of no additional benefit to the patient. [Table: see text]
Comparison of molecular (BluePrint and MammaPrint) and pathological subtypes for breast cancer among the first 800 patients from the EORTC 10041/BIG 3-04 (MINDACT) trial.
Authors: Viale Giuseppe , Slaets Leen , De Snoo Femke , van 't Veer Laura J. , Rutgers Emiel J. , Bogaerts Jan , Stork-Sloots Lisette , Engelen Kristel , Russo Leila , Dell'Orto Patrizia , Cardoso Fatima , Piccart-Gebhart Martine J. 
Published: February 2017

32 Background: Biology has become the main driver of breast cancer therapy. Intrinsic biological subtypes by gene expression profiling have been identified. Pathology can be used to define surrogates of these subtypes but these are not always concordant, which may lead to different treatment plans. We investigated the concordance between BluePrint (BP) + MammaPrint (MP) (micro array based) breast cancer subtypes and pathological surrogates (based on ER, PR, HER2 and Ki67). Contrary to the Perou gene set (evolved into PAM50), BluePrint was trained using pathological data. Methods: Using available data (centrally assessed pathology and genomic) from the MINDACT pilot phase (Rutgers et al 2011) 621 tumors were analyzed. Two pathology classifications were used: one with 4 categories and one with 5 categories (Goldhirsch et al 2011). Based on BP 3 subtypes are formed: Luminal, HER2 and Basal. The Luminal subtype is further split into Luminal A (MP low risk) and Luminal B (MP high risk). Results: See table. Conclusions: All pathological Basal cases are BP Basal, apart from 1 BP HER2 case. Of the BP Basal cases, 15 are not pathological Basal: 1 is Luminal A, 11 are Luminal B (of which 8 are IHC ER/PR borderline (≥1% and < 10%)) and 3 are HER2. All pathological Luminal (A & B) that are BP HER2 are HER2- by TargetPrint. 25 of the 26 pathological HER2+ that are BP Luminal A are ER+. Most discordant cases are seen within the Luminal subtype, indicating that Ki67 discriminates Luminal A vs. B differently than MammaPrint does. The observed subtype discrepancies reveal potential important impact for treatment-decision making. MINDACT will provide important information. [Table: see text]
Clinical outcome of preoperative breast MRI for early-stage breast cancer.
Authors: Hamdan Shadi E. , Martin Leslie A. , Sunkara Rajitha 
Published: February 2017

42 Background: Preoperative breast magnetic resonance imaging MRI is used in clinical practice to improve oncologic outcome of breast cancer. Concerns over increased rate of unnecessary mastectomies and additional biopsies have been raised. The purpose of our study is to review the outcome of preoperative breast MRI at our institution. Methods: The current study is a retrospective review of 215 patients with early stage breast cancer who underwent definitive surgery. Breast MRI is being used at our institution within the context of multidisciplinary approach. Patients who had complete clinical, radiologic, and pathological data available were identified and formed the basis of this analysis. Results: 215 patients were diagnosed with breast cancer stage I-II in the period of 2006-2012 and had complete data for review. 92 patients out of 215 (43%) had breast MRI prior to definitive surgery. both groups were different in regard of age. Rate of breast conservative surgery, mastectomies, and re-excision for positive margins was similar in both groups. 6 patients out of 12 patients who had breast MRI and underwent bilateral mastectomies were found to have abnormal pathological findings (DCIS 3, LCIS 1, invasive ductal carcinoma 1, and focal epithelial atypia 1). Time from first diagnostic procedure to definitive surgery was similar in both groups (29 days vs. 27.5 days). 38 (41%) patients out of 92 who had breast MRI underwent additional breast biopsies for suspicious lesions with only 8 (21%) patients found to have abnormal pathological findings. Conclusions: Use of breast MRI prior to definitive surgery for early stage breast cancer was associated with increased rate of additional biopsies for suspicious lesions with no favorable effect on re-excision rate. [Table: see text]
A program to increase use of chemoprevention for women with high-risk breast lesions.
Authors: Roche Constance A. , Hughes Kevin S. 
Published: February 2017

46 Background: Tamoxifen, raloxifene, and exemestane have been demonstrated to reduce risk of breast cancer in high-risk women, bututilization is very low.Among the reasons cited are lack of awareness and reluctance of physicians to prescribe. Women with high-risk breast lesions are generally candidates for chemoprevention and can be evaluated and counseled in a high-risk breast clinic. Knowledge about drugs that can prevent breast cancer may increase uptake among high-risk women. Methods: In a single practice, women with a diagnosis of atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), lobular carcinoma in situ (LCIS), or severe atypical ductal hyperplasia/borderline ductal carcinoma in situ are offered an extended visit with a nurse practitioner in the Breast and Ovarian Cancer Risk and Prevention Clinic. The visit includes data collection, patient interview about relevant history and personal preferences, risk assessment, including use of relevant models (via HughesRiskApps.com), and recommendations for surveillance and prevention. Emphasis is placed on understanding of individual risk as well as risks and benefits and appropriateness of chemoprevention and surveillance modalities. Based on personal and family history, women are advised if chemoprevention is appropriate to consider, their choice is made, and they are encouraged to have surveillance in the Breast Clinic. Results: Since January 2001, 487 women with a diagnosis of ADH, ALH or LCIS, or severe ADH have been evaluated and counseled in the Breast and Ovarian Cancer Risk and Prevention Clinic. 132/487 (27%) were advised against taking chemoprevention and 355/487 (73%) were appropriate for chemoprevention. Of those for whom chemoprevention was clinically appropriate, 188/355 (53%) took one of the medications, or participated in a chemoprevention trial. 53/188 (28%) did not complete therapy (discontinued at 2 weeks to 54 months) due to preference or side effects. 75 women have completed five years of therapy and 60 are currently on therapy. Conclusions: When provided with personalized information about breast cancer risk and the pros and cons of chemoprevention, many women will choose to take medication to reduce breast cancer risk.
Determination of breast density by bioimpedance.
Authors: Bukhanov Karina , Ironstone Joel S. , Basso Cindy , Bilodeau Tina 
Published: February 2017

56 Background: Mammographic breast density is a significant risk factor for breast cancer. Women with extremely dense breasts are at 4-to-6 times the risk of developing breast cancer than women with primarily fatty breast tissue. Electrical Breast Densitometry (EBD) is a new technique that assesses breast density. EBD is non-ionizing, fast, has low cost per test ($20-$30) and may help in breast cancer risk assessment in the primary care setting. Methods: This study evaluated the feasibility of the EBD in an IRB-approved pilot study of 20 patients. The study used a custom-made self-adhesive electrode (SenoSENSE Medical Systems, Toronto, Canada) interfaced to an off-the-shelf impedance meter (Bodystat 1500, Bodystat, Isle of Man, UK) with a customized cable. On the same day as the subject’s scheduled mammogram, impedance measurements were acquired for each breast. Mammogram densities were scored by a trained radiologist using standard BiRADS breast density categories 1 to 4. Results: A high correlation coefficient was observed (Pearson correlation coefficient >0.80) between breast density determined by the EBD and the BiRADS breast density score. In addition a statistically significant difference was observed between dense categories (BiRADS 3,4) and fatty categories (BiRADS 1,2) (p<0.01), as well as between extremely dense breasts (BiRADS 4) and all other categories (p<0.01). Very high correlation (Pearson correlation coefficient >0.95) was observed between EBD measurements on the left and right breasts. Previous studies have reported a left/right correlation of 0.89 for blinded mammography readers. Conclusions: These results suggests that the EBD measure may be less variable than mammographic estimates of density. The results of the study suggest that Electrical Breast Densitometry is a promising technique for the assessment of breast density and the ability to aid in evaluation of breast cancer risk. It can be reasonably deployed at primary care facilities.