bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pretreatment serum biomarkers and clinical outcome in the phase II trial of zibotentan (endothelin A receptor antagonist) in metastatic CRPC.
Authors: Shelkey Julia , Bisen Ajit Kumar , Leitzel Kim , Ali Suhail M. , Carney Walter P. , Lipton Allan 
Published: February 2017

97 Background: Three angiogenesis-related serum biomarkers [TIMP-1 (tissue inhibitor of metalloproteinase-1), CA IX (carbonic anhydrase 9), and VEGF] and PSA were correlated with outcome in the phase II zibotentan [endothelin A (ETA) receptor inhibitor] trial in metastatic CRPC. Methods: Pretreatment serum samples were available from 206 of 312 patients enrolled in the multicenter phase II trial evaluating zibotentan in patients with metastatic CRPC and bone metastases who were pain free or mildly symptomatic for pain, with a 1:1:1 randomization to zibotentan 10mg, 15mg, or placebo. The CA IX, TIMP-1, and VEGF ELISAs were from WILEX Inc./ Oncogene Science, Cambridge, MA. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox modeling. Results: In the final efficacy report, there were no statistical differences in PFS, but a trend for OS improvement was observed in the zibotentan arms compared with placebo: 15 mg (HR 0.76; 80% CI 0.61–0.94; p= 0.103) and 10 mg (HR 0.83; 80% CI 0.67–1.02; p= 0.254) (James et al, BJUI 106L966-973, 2010). In the retrospective serum biomarker analysis (206 patients), there were no apparent differences for PFS with any of the 3 novel biomarkers in the whole population, or within treatment arms. For OS in the whole population, patients with higher serum TIMP (> median) had reduced OS (17.5 mos), compared with patients who had lower serum TIMP-1 (< median) (28.4 mos). Within treatment arms, patients with higher serum CA IX (> median) treated with zibotentan had increased OS in both the 10 mg arm (median 28.4 mos), and the 15 mg arm (median 25.7 mos) compared with those in the placebo arm (median 15.4 mos). In a Cox model, including serum biomarkers and bisphosphonate use, for PFS only PSA was significant (p< 0.0001); for OS only PSA (p< 0.0001) and TIMP-1 (p< 0.002) were significant. Conclusions: Higher pretreatment serum CA IX (a marker of hypoxia) may identify a cohort of metastatic CRPC patients more sensitive to zibotentan treatment, and higher serum TIMP-1 may identify patients at risk for reduced overall survival. These serum biomarkers deserve further study in larger ETA receptor inhibitor trials.
Hemi salvage HIFU in patients with radio recurrent prostate cancer: Early experience and results.
Authors: Pasticier Gilles , Baco Eduard , Rouviere Olivier , Crouzet Sebastien , Chapelon Jean-Yves , Gelet Albert 
Published: February 2017

99 Background: One third of patients treated with External beam radiation therapy (EBRT) for localized prostate cancer (PCa) experience local recurrence. Salvage treatment options include prostatectomy, cryoablation, and High Intensity Focused Ultrasound (HIFU). Whole gland treatment in these patients offers acceptable cancer control, but carries a risk of severe urinary incontinence in at least 20% of cases and reduction of Quality of Life (QoL). In patients with unilateral local relapse, focal HIFU is feasible. The aim of this prospective study was to evaluate the effect of Hemi HIFU in patients with unilateral recurrence after radiotherapy. Methods: Between 2009 and 2012, 48 patients were prospectively included in 2 centers. Inclusion criteria were positive MRI and biopsy in one lobe diagnosing unilateral cancer after EBRT (46 patients) and after brachytherapy (2 patients). Mean age was 68.8 ± 6 years, mean pre HIFU PSA was 5.2 ± 5.2 ng/mL and the repartition of Gleason score was ≤7: 28, ≥8: 18 and not determined: 2. Median follow-up was 16.3 months [range 3-43]. Treatments were performed with Ablatherm® HIFU device. Results: The mean PSA nadir value was 0.69 ± 0.83 (median: 0.4). Disease progression occured in 16 patients (35,5%). Local recurrence was found in 4 patients in the controlateral lobe, and in 4 patients in both lobes. Six patients developped metastases and 2 had rising PSA without local recurence or proven metastasis. Fifteen of these 16 patients received salvage treatments (3 re-HIFU, 11 androgen-deprivation, and 1 re-HIFU plus androgen-deprivation). Thirthy-six patients (75%) were pad-free. Seven patients (14.6 %) required 1 pad a day. Severe incontinence occured in 5 patients (10.4%). One of them received artificial urinary sphincter. Paired results indicated no significant change in QoL and IPSS scores: EORTC-QLC-30: (from 35.7 ± 8.7 to 36.8 ± 8.6, p=0.22) and IPSS: (from 7 ± 5.6 to 8.5 ± 5.1, p=0.13) Conclusions: Hemi-salvage HIFU is efficient in patients with unilateral radio-recurrent PCa with a preserved QoL offering comparable cancer control to whole gland treatment.
Randomized comparison of adjuvant aromatase inhibitor (AI) exemestane (E) plus ovarian function suppression (OFS) vs tamoxifen (T) plus OFS in premenopausal women with hormone receptor-positive (HR+) early breast cancer (BC): Joint analysis of IBCSG TEXT and SOFT trials.
Authors: Pagani Olivia , Regan Meredith M. , Walley Barbara , Fleming Gini F. , Colleoni Marco , Lang Istvan , Gomez Henry Leonidas , Tondini Carlo , Burstein Harold J. , Perez Edith A. , Ciruelos Eva , Stearns Vered , Bonnefoi Herve R. , Martino Silvana , Geyer Charles E. , Rabaglio-Poretti Manuela , Coates Alan S. , Gelber Richard D. , Goldhirsch Aron , Francis Prudence A. ,   SOFT and TEXT Investigators and International Breast Cancer Study Group
Published: February 2017

LBA1 Background: Adjuvant endocrine therapy with AI vs T improves outcomes in postmenopausal HR+ BC. TEXT and SOFT were designed to test whether adjuvant AI improves outcomes in premenopausal women with HR+ BC treated with OFS (AI question) and to determine the value of OFS in women who remain premenopausal and are suitable for adjuvant T (OFS question). Methods: TEXT and SOFT, randomized phase 3 trials, enrolled 5,738 premenopausal women with HR+ early BC from Nov03 to Apr11 (2672 TEXT; 3066 SOFT). TEXT randomized women within 12wk of surgery to 5y E+OFS vs T+OFS; chemotherapy (CT) was optional and concurrent with OFS. SOFT randomized women to 5y E+OFS vs T+OFS vs T alone, either within 12wk of surgery if no CT planned, or within 8mo of completing (neo)adjuvant CT. OFS was by choice of 5y triptorelin, oophorectomy, or ovarian irradiation. The primary endpoint is disease-free survival (DFS: randomization until invasive local, regional, distant recurrence, or contralateral breast; 2nd malignancy; death). Due to low event rates, protocol amendments in 2011 changed the analysis plans to answer the AI question (E+OFS vs T+OFS) by joint analysis of TEXT and SOFT. By Q3’2013 with >5y median follow-up, 436 DFS events were projected, providing 84% power for HR=0.75 with E+OFS vs T+OFS (stratified logrank 2-sided α=0.05). Results: At 5.7y median follow-up, 514 (11%) DFS events were reported in the ITT population comparing E+OFS (n=2346) vs T+OFS (n=2344). Patients assigned E+OFS had significantly reduced DFS hazard (HR=0.72; 95% CI, 0.60-0.86; P=0.0002) vs T+OFS; 5y DFS was 91.1% vs 87.3%. Reductions were similar for secondary endpoints of BC-free interval (HR=0.66 (0.55-0.80) 5y BCFI 92.8% vs 88.8%) and distant recurrence-free interval (HR=0.78 (0.62-0.97)), though not overall survival (HR=1.14 (0.86-1.51)) at this early follow-up (194 (4%) deaths). Grade 3-4 targeted AEs were reported in 31% E+OFS vs 29% T+OFS patients. Conclusion: In premenopausal women with HR+ BC, adjuvant treatment with E+OFS significantly reduced the risk of recurrence compared to T+OFS. Clinical trial information: NCT00066703 / NCT00066690 .
Randomized comparison of ibrutinib versus ofatumumab in relapsed or refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma: Results from the phase III RESONATE trial.
Authors: Byrd John C. , Brown Jennifer R. , O'Brien Susan Mary , Barrientos Jacqueline Claudia , Kay Neil E. , Reddy Nishitha M. , Coutre Steven E. , Tam Constantine , Mulligan Stephen P. , Jäger Ulrich , Devereux Steve , Barr Paul M. , Furman Richard R. , Kipps Thomas J. , Cymbalista Florence , Fardis Maria , McGreivy Jesse S. , Clow Fong , James Danelle Frances , Hillmen Peter 
Published: February 2017

LBA7008 Background: Treatment options for CLL/ SLL patients (pts) who fail chemoimmunotherapy are limited. We report interim results from a phase III randomized study of ibrutinib (ibr), a first in class covalent BTK inhibitor, vs ofatumumab (ofa) in R/R CLL/SLL. The Data Monitoring Committee recommended this analysis be considered final, based on meeting the primary and a key secondary endpoint. Methods: R/R CLL/SLL pts who failed ≥1 therapy received 420 mg oral ibr daily until progression or IV ofa 300/2000mg for 12 doses. Primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). Secondary endpoints included overall survival (OS), IRC assessed overall response rate (ORR) and safety. Results: Of 391 pts enrolled (median age 67 years; 40% ≥70 years; 57% Rai stage III/IV disease; 30% del 17p), 195 were randomized to ibr and 196 to ofa. Ibr pts had median 3 prior therapies vs 2 for ofa. Median follow-up was 9.4 months (m). Ibr significantly lengthened PFS (median not reached vs 8.1 m; HR 0.215, CI 0.146–0.317, p<0.0001; 78.5% risk reduction), and significantly improved OS (median not reached; HR 0.434, CI 0.238–0.789, p=0.0049) compared with ofa. ORR was 42.6 vs 4.1% (p<0.0001) and ORR+PR with lymphocytosis was 62.6 vs 4.1% for ibr vs ofa. Similar effects were seen in del17p and purine analog refractory subsets. In each arm 2 pts had confirmed Richter’s transformation. Most frequent adverse events (AE) for ibr vs ofa were diarrhea (47.7 vs 17.8%) fatigue (27.7 vs 29.8%), and nausea (26.2 vs 18.3%). Atrial fibrillation was more frequent with ibr (5.1 vs 0.5%). Major hemorrhages were reported in 1.0 vs 1.6% for ibr vs ofa. Drug discontinuation due to AE was 4.1 vs 3.6% for ibr vs ofa. 86% of ibr pts were continuing treatment. 57 pts randomized to ofa with confirmed PD had initiated ibr at cross-over. Conclusions: Compared with ofa, ibr significantly improved PFS, OS and ORR in pts with R/R CLL/SLL. The safety profile was comparable with that previously reported (Byrd NEJM 2013). These results support ibr as a beneficial therapy for R/R CLL patients irrespective of del 17p or purine analog refractory disease. Clinical trial information: NCT01578707.
Correlation between Nottingham grade and Oncotype DX score in breast cancer: Implications for cost-effective incorporation of oncotype in the clinic.
Authors: Baxter Emily , Chia Stephen K. L. , Lohrisch Caroline A. , Hayes Malcolm , Gondara Lovedeep , Gelmon Karen A. , Davidson Ashley , Tyldesley Scott 
Published: February 2017

106 Background: Nottingham grading (NG) for breast cancer uses tubule formation (TF), nuclear polymorphism (NP), and mitotic count (MC). The Oncotype Dx recurrence score (RS) is a 21-gene assay that predicts recurrence. Both NG and RS can influence decisions about the use of adjuvant chemotherapy in patients with ER+, HER2-, T1-T2, N0 cancers. The objective was to determine the correlation of overall NG, TF, NP, MC with RS risk group in such patients. This may be useful in guiding the use of Oncotype in specific cases. Methods: 231 patients referred to the BC Cancer Agency between 2007-2011 with ER+, HER2-, T1-T2, N0 breast cancer and an Oncotype were identified. Histologic grading was assessed on the specimen used for Oncotype. Spearman’s correlation coefficients, and 95% confidence intervals (CI) were calculated for the RS risk group versus overall NG, TF, NP, and MC. This study adds to the literature as it is one of the largest cohorts examining this topic and focuses on a HER2- patient population. Results: There was a significant positive moderate correlation between RS and overall grade (Spearman coefficient 0.47, [95%CI: 0.36, 0.56])(Table 1), and RS and MC (Spearman 0.44, [95%CI: 0.33, 0.54]). There was a significant positive weak correlation between RS and TF (Spearman 0.25, [95%CI: 0.13, 0.37]) and RS and NP (Spearman 0.34, [95%CI: 0.22, 0.45]). None of the patients with low overall NG had a high risk RS. Conclusions: Patients with a low NG are unlikely to have a high risk RS (0 in 231 patients) and very few such patients would benefit from the expense of an Oncotype. Overall NG has a better correlation with RS than TF, MC, or NP components alone. [Table: see text]
Effect of a new model for multidisciplinary breast cancer care on clinical metrics leading to efficiency and timeliness of access.
Authors: Murthy Rashmi Krishna , Ferguson Susan E , Tereffe Welela , Bedrosian Isabelle , Moulder Stacy L. 
Published: February 2017

107 Background: The multidisciplinary approach to breast cancer care provides a coordinated mechanism for evaluating and treating new patients. Improving the structure of clinic models may further enhance the delivery of cancer care. Methods: In May 2013, multi-team (MT) clinics were introduced in the breast center at the University of Texas MD Anderson Cancer Center. Local patients with newly diagnosed breast cancer were scheduled to be seen in a MT clinic with testing coordinated for the same day. Patient cases were first reviewed and examined concurrently by physicians from each discipline (surgical, medical, radiation), followed by sequential visits with each clinician for a more detailed discussion. The goal of this program was to determine whether a highly integrated multidisciplinary clinic model would improve the efficient delivery of cancer treatment. Results: From 5/2013 – 5/2014, 211 newly diagnosed and untreated breast cancer patients were seen in the MT clinic. Clinical metrics were reviewed retrospectively and compared to newly diagnosed and untreated patients who entered the clinic using the standard model (non-MT patients) (n=1944). Please see Table for details of the data. Conclusions: Multi-team clinics improved clinical metrics leading to efficiency and timeliness of access. The model enriched for a population of patients who were more likely to receive treatment within the breast center, utilize institutional resources, and enroll into clinical trials. [Table: see text]
Screening and treatment of osteoporosis in breast cancer survivors treated with aromatase inhibitors: Gap between the national guidelines and real-world practice.
Authors: Kamboj Sukriti , Sharma Sandhya , Sethi Anuradha , Agheli Aref 
Published: February 2017

113 Background: Breast cancer survivors who are on adjuvant therapy with Aromatase Inhibitors (AIs) are known to have an increased risk of osteoporosis. AIs reduce estrogen levels and cause accelerated loss of bone density. Being at high risk for osteoporosis, these patients should be screened and followed up for bone mineral density (BMD) with dual energy X-ray absorptiometry (DEXA) scan as directed by national guidelines. The purpose of this study was to evaluate if this patient population is adequately screened and intervened appropriately. Methods: We conducted a two center, retrospective, clinical observational study at Guthrie cancer center at Sayre and Corning using Guthrie tumor registry. Patients with diagnosis of invasive breast cancer and on adjuvant therapy with AIs were included in this study. Patients with metastatic bone disease and those who were receiving palliative care were excluded. Results: During the study period, a total of 703 breast cancer patients were identified and 292 patients were on AIs. Baseline DXA scan for BMD was done in 54 % (158 out of 292) patients. Of these, 22% (n=35) had osteoporosis and 43% (n=68) had osteopenia. FRAX (Fracture risk assessment tool) score using WHO algorithm was calculated in patients with osteopenia. After calculating FRAX score, 28 of 68 patients were found to have ≥3% ten year probability (TYP) of a hip fracture or ≥20% TYP of a major osteoporosis-related fracture. These 28 patients with osteopenia and 35 patients (total n=64) with osteoporosis were required to be on treatment as per guideline recommendations. Only 23% (15 of 64) patients recieved treatment. Two year follow up on patients taking AI was done (n=292) and 46% (n= 137) patients had repeat BMD. Of the patients who had known osteoporosis and TYP of hip fracture ≥ 3% or a TYP of a major osteoporosis-related fracture ≥ 20%, only 54% (35 of 64) had follow up BMD. Conclusions: This study highlights the fact that osteoporosis is an under-detected and inadequately treated condition in breast cancer survivors who are on AIs. There is still a huge gap between guidelines and real world practice on prevention and treatment of osteoporosis this patient population.
Postdiagnosis social networks and lifestyle and treatment mechanisms in the Ater Breast Cancer Pooling Project (ABCPP).
Authors: Kroenke Candyce H. , Michael Yvonne , Shu Xiao-Ou , Poole Elizabeth , Kwan Marilyn L. , Caan Bette J. , Nechuta Sarah , Pierce John P. , Chen Wendy Y. 
Published: February 2017

115 Background: Larger social networks have been associated with better breast cancer survival. To investigate potential mediators, we evaluated associations of social network size and diversity with lifestyle and treatment factors associated with prognosis. Methods: We included 9,331 women from the After Breast Cancer Pooling Project who provided data on social networks within two years following diagnosis. A social network index was derived from information about the presence of a spouse or intimate partner, religious ties, community participation, friendship ties, and numbers of relatives. Diversity was assessed as variety of ties, independent of size. We used logistic regression to evaluate associations with outcomes and evaluated whether effect estimates differed using meta-analytic techniques. Results: Associations of social networks and outcomes generally did not differ by cohort. Because of the low prevalence of smoking and alcohol consumption in the Shanghai cohort, however, analyses of smoking and alcohol included US cohorts only. Women who were socially isolated (small networks) were more likely to be obese (body mass index>30 kg/m2, OR=1.21, 95% CI:1.03-1.42) and have low physical activity (<10 MET-h/wk, OR=1.53, 95% CI:1.34-1.75) compared to socially integrated women. Women with low network diversity were more likely to be current smokers (OR=3.68, 95% CI:2.19-6.19) and have high alcohol consumption (>15 g/d alcohol, OR=2.43, 95% CI:1.60-3.69). Among node positive cases, socially isolated women were more likely not to receive chemotherapy (OR=1.52, 95% CI:1.03-2.25). By contrast, low network diversity, but not social network size, was associated with greater odds of not receiving adjuvant hormonal therapy (OR=1.52, 95% CI:1.03-2.23). Associations with surgery were nonsignificant. Conclusions: In a large pooled cohort, small, less diverse social networks measured post-diagnosis were associated with more adverse lifestyle factors and less intensive cancer treatment, which may help to explain poorer breast cancer prognosis in socially isolated women.
Breast cancer survivorship care: A continuity of care model of delivery.
Authors: Klemp Jennifer R. , Ranallo Lori , Knight Catherine J , Williams Mary , Fabian Carol J. 
Published: February 2017

116 Background: With more than 2.9 million BrCa survivors in the US, it is imperative to determine how best to deliver post-treatment survivorship care. National accreditation standards are pushing survivorship care plans, while evidence supporting specific methods of delivery and outcomes are lacking. The University of Kansas Breast Cancer Survivorship Center opened in 2007 as a continuity of care, post-treatment survivorship clinic. We report prospective findings from a group of BrCa survivors from 2007-2013. Methods: Four hundred twenty-four BrCa survivors consented to an IRB approved, longitudinal survivorship registry. Baseline variables on demographics, disease history, summary of cancer treatment, late effects, medications and health status were collected. Follow-up data collection included disease status or new primary cancer, patient’s health status and late/long-term effects. Comparisons from baseline to subsequent visits provided information on changes in key variables over time. Results: Participants were ~57 years old, primarily Caucasian, attended at least some college, made >$40K per year, and 49% were premenopausal at diagnosis. Forty-five women reported having another malignancy and 10 were diagnosed with either a recurrence or a second primary breast cancer while followed in the survivorship center. Significant self-reported symptoms included menopausal symptoms: hot flashes (n=164), vaginal dryness (n=211) and a lack of sexual activity (195). 95% were seen for >1 post-baseline visit. Menopausal symptom interventions, lifestyle recommendations (weight loss and increasing physical activity), referrals to specialists (77% referred for colonoscopy completed colon ca screening; 92% referred attending cardio-oncology screening visit; 100% referred completed a bone mineral density analysis), and lymphedema education and management increased significantly. Conclusions: Multidisciplinary care facilitated through a continuity of care survivorship clinic improves compliance with recommended follow-up and cancer screening, however additional research on the cost and impact of delivering survivorship care is needed to evaluate sustainability and long-term patient outcomes.
Deep inspiration breath hold (DIBH) with electromagnetic surface transponder confirmation of chest wall (CW) position during radiation for left breast cancer.
Authors: Kathpal Madeera , Sun Kelly , Malmer Cynthia , Ninneman Stephanie , Wendt Stacie , Hughs Grant , Macdonald Dusten , Tinnel Brent 
Published: February 2017

126 Background: DIBH during radiation of left breast cancers reduces heart dose, potentially reducing late cardiac ischemic events, but requires a treatment CW position significantly different from a free-breathing (FB) position. We sought to improve the accuracy of radiation therapy during DIBH by using electromagnetic surface transponders to track the position of the CW during treatment. We examined the benefit of this technique in reducing dose to the heart and consistently reproducing the DIBH position. We also evaluated the difference between FB and DIBH CW position and compared CW movement within the plateau of each DIBH to within beam-on time. Methods: 15 patients participated in this IRB-approved study. Patients were planned and treated using DIBH. We fused treatment-position FB CT scans to DIBH scans to compare mean heart (MH) and left anterior descending coronary artery (LAD) dose. We used surface transponder tracking reports to determine CW motion at the time of daily port films, during FB, the plateau of each DIBH, and beam-on time. We summed anterior and superior motion using the Pythagorean Theorem and report our results in this combined axis. Paired t-test was used to compare heart dose with vs. without DIBH and CW motion during plateau DIBH vs. beam-on. Results: DIBH significantly reduced MH and LAD dose vs. FB plans (MH 1.26 ± 0.51 Gy v 2.84 ± 1.55 Gy, p < 0.01), (LAD 5.49 ± 4.02 Gy v 18.15 ± 8.78 Gy, p < 0.01). DIBH CW position was a mean of 13.9 ± 5.3 mm anterior and superior to FB position. The mean difference in CW position at the time of daily port film vs. beam-on was -1.0 ± 2.5 mm. Plateau DIBH CW motion was 2.8 ± 2.3 mm, significantly increased from CW motion during beam-on (1.1 ± 1.2 mm, p < 0.01). Treatment was paused in 23% of fractions to adjust for suboptimal breath hold or CW position. Conclusions: DIBH reduced the MH and LAD dose by at least 50%. Real-time tracking with electromagnetic transponders allowed us to limit treatment to the most stable portion of the DIBH plateau, significantly reducing intra-fraction motion. Electromagnetic confirmation of CW position allowed verification of breath-hold reproducibility.