bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of intermittent (I) first-line docetaxel (D)-based chemotherapy on quality of life (QL) of patients (pts) with castration-resistant prostate cancer (CRPC): Results of a phase II randomized trial.
Authors: Caffo Orazio , Sava Teodoro , Basso Umberto , Buti Sebastiano , Lo Re Giovanni , Sacco Cosimo , Lodde Michele , Facchini Gaetano , Zustovich Fable , Perin Alessandra , Russo Lucianna , Veccia Antonello , Galligioni Enzo
Published: February 2017

90

Background: Eight consecutive courses of D are usually considered a standard first line treatment for CRPC pts. The pts quality of life (QL) may be worsened and an I administration could mitigate this effect. We verified if an I therapy may reduce the impact on pts’ QL compared to continuous (C) treatment. Methods: The treatment was D 70 mg/m2IV q 3 wks ± estramustine (E) 280 mg/TID PO for 5 days. Pts were randomized to receive 8 courses D±E continuously (C) or intermittently, with a 3-month rest period after the first 4 courses. QL was evaluated by EORTC QLQ C30 at baseline and every 6 weeks. For the study aim, we considered evaluable for QL pts who received at least 5 D±E courses and filled the QL instruments. Results: 148 CRPC pts were enrolled from 11/06 to 10/10 with 94 pts evaluable for QL (53 and 41 treated with I with C therapy, respectively). No statistically differences were observed between C and I treatments for QL outcomes: the table shows the median value of single EORTC QLQ C30 scales scores at each assessment time-point. Conclusions: The present study failed to demonstrate that I treatment may produce a QL advantage compared to C treatment which remains the reference therapy for first-line of CRPC pts. Clinical trial information: 2006-005728-17. [Table: see text]
Effect of generation 2.5 antisense inhibitor of androgen receptor on MDV3100-resistant prostate cancer cell growth in vitro and in vivo.
Authors: Yamamoto Yoshiaki , Beraldi Eliana , Loriot Yohann , Zhou Tianyuan , Kim Youngsoo , Monia Brett P. , MacLeod A. Robert , Fazli Ladan , Zoubeidi Amina , Gleave Martin Edwin
Published: February 2017

94

Background: MDV3100 is a potent androgen receptor (AR) antagonist with activity in castration resistant prostate cancer (CRPC); however, progression to MDV3100-resistant (MDV-R) CRPC frequently occurs with rising serum PSA levels, implicating AR full length or variants in disease progression. We studied the activity of Generation 2.5 antisense oligonucleotide (ASO) targeting the AR full length (ARfl) and splice variants in MDV-R CRPC models. Methods: and Results: ThreeASOs targeting exon 1, intron 1, or exon 8 were designed to suppress ARfl and known AR splice variants. We generated by selection MDV-R LNCaP-derived sub-lines that uniformly expressed high levels of both ARfl and AR-V7 compared to CRPC LNCaP cell lines. MDV-3100 induced time- and dose-dependent increases in ARfl and AR-V7 protein levels; ARfl levels were ~20-fold higher than AR-V7. All 3 AR-ASO decreased ARfl and PSA expression. Exon 1 ASO decreased expression of both ARfl and AR-V7 in MDV-R-LNCaP cells; in contrast, exon 8 ASO decreased ARfl without reducing AR-V7 levels. Exon 1 ASO also most potently suppressed ARfl and splice variants in M12 cells stably overexpressing AR splice variants AR-V7 and AR-V567es. Despite these differential effects on ARfl and splice variant knockdown, the AR ASO similarly inhibited cell growth and induced apoptosis and G1 cell cycle arrest in LNCaP-derived CRPC and MDV-R cell lines. In 22RV-1 cells (which express endogenous ARfl and AR-V7), exon 1 ASO more potently suppressed ARfl and AR-V7 levels, AR transcriptional activity and AR-regulated gene expression compared to exon 8 ASO, but inhibition of cell growth did not differ significantly. Exon 1 ASO was evaluated in vivo in MDV-R49F CRPC LNCaP xenografts; mean tumor volume and serum PSA levels decreased significantly by 40% and 50%, respectively, compared to controls. Conclusions: While MDV-3100 induces both ARfl and AR-V7 levels, the biologic consequences appear cell line dependent and mainly driven by ARfl. AR-ASO knockdown of ARfl and its splice variants suppresses MDV-R LNCaP tumor growth, providing pre-clinical proof of principle to support clinical evaluation in post-AR pathway inhibitor CRPC.
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.
Docetaxel and cyclophosphamide as neoadjuvant chemotherapy in HER2- primary breast cancer.
Authors: Nakatsukasa Katsuhiko , Taguchi Tetsuya , Koyama Hiroshi , Imanishi Seiichi , Sakaguchi Kouichi , Hujita Yoshihumi , Oouchi Yoshimi , Oohashi Mahiro , Okamoto Akiko , Hamaoka Asako , Sugimoto Riho , Tomita Hitomi , Hujiwara Ikuya , Hukuda Kenichirou , Morita Midori , Matsuda Takayuki , Kotani Tatsuya , Kawakami Sadao , Kadotani Yayoi
Published: February 2017

141

Background: Recently, docetaxel plus cyclophosphamide (TC) has been established as a standard regimen for adjuvant chemotherapy in HER2- operable breast cancer. However, the efficacy and tolerability of TC as neoadjuvant chemotherapy (NAC) remains unclear. We performed a prospective study of TC NAC in HER2- primary breast cancer. Methods: Eligible patients had HER2- invasive breast cancer that measured more than 1cm, less than 7cm and N0~N1 clinically between July, 2011 and February, 2014. Four cycles of TC(75 and 600 mg/m2) were administered intravenously every 3 weeks as NAC. We investigated the pathological complete response(pCR) of primary breast tumors. pCR was defined as no histological evidence of invasive carcinoma, or the appearance of only ductal carcinoma in situ. The cut-off value of Ki67 index between luminal A and luminal B was defined 20%. Results: We enrolled 52 patients. The completion rate for 4 cycles of TC was 94.2% ( 49 of 52). Relative dose intensity was 99.1% for TC therapy. Forty nine patients were classified according to breast cancer subtype before the estimation. Overall pCR rate was 16.3 %( 8 of 49 ) . pCR rate for patients with luminal A ( ER+, Ki67 low and HER2- ), luminal B ( ER+, Ki67 high and HER2- ) and triple negative ( ER- and HER2- ) were 0%( 0 of 12 ), 4.3 %( 1 of 23 ) and 50.0 %( 7 of 14 ), respectively pCR was achieved in almost triple negative patients. Conclusions: The pCR rate of TC was not so high, regardless of the high completion rate. In this study, TC was effective against triple negative subtype, showing a high pCR rates, compared with luminal subtype. In conclusion, the efficacy of TC NAC in HER2- primary breast cancer is limited, and triple negative subtype might be the good target. Clinical trial information: UMIN000013261.
Evaluation of risk factors associated with denosumab induced hypocalcemia.
Authors: Trevino Manllo Sergio Alberto , Khalon Pushpinderdeep , Thind Ravneet , Bhatia Roma , Ali Haythem Y.
Published: February 2017

144

Background: Denosumab is a monoclonal antibody that neutralizes RANKL preventing osteoclast activation. It has been shown to be superior to zoledronic acid in preventing skeletal-related events in breast cancer with bone metastases. Hypocalcemia has been reported as a common side effect. The aim is to evaluate the risk factors associated with denosumab induce hypocalcemia. Methods: Retrospective study in which 144 charts were reviewed. Baseline characteristics: age, gender, race, type of cancer, calcium, phosphate, vitamin D, PTH, creatinine levels, GFR and corrected calcium were obtained. Tumors were classified in hormone sensitive versus non-sensitive. Charts were reviewed to evaluate for the development and severity of hypocalcemia as defined by the international review criteria. A multivariant analysis to evaluate the relationship between hypocalcemia and the variables of interest was done. Results: Hypocalcemia was observed in 71 of 144 patients. Grade 2 hypocalcemia was the most common. Significantly lower levels of GFR at baseline were detected in patients withhypocalcemia. Hormone responsive tumors were significantly less likely to develop hypocalcemia. Conclusions: Despite adequate supplementation of vitamin D and calcium, hypocalcemia is a common side effect of Denosumab. Careful monitoring of calcium levels is necessary especially in chronic kidney disease and hormone insensitive tumors. [Table: see text]
Impact of chemotherapy and radiation therapy on local control and survival of metastatic breast cancer to the brain: Single-institution review of 792 cases.
Authors: Bugano Diniz Gomes Diogo , Deeba Rita Elias , Valero Vicente , Moulder Stacy L. , Arun Banu , Alvarez Ricardo H. , Hsu Limin , Ibrahim Nuhad K.
Published: February 2017

146

Background: There are various treatment modalities for metastatic breast cancer to the brain (MBC-b), with wide variation of reported outcomes. Methods: There were 1,513 patients (pts) with MBC-b treated at MD Anderson Cancer Center October 2009-December 2012. We reviewed medical records of the first consecutive 1015 and included 792 with confirmed brain metastases (BM). A Cox multivariate model was used to identify the effect of treatment on time-to-progression in the brain (TTP-b) and overall survival (OS). Results: Disease subtypes: ER+/HER2- (27%); ER+/HER2+ (16%); ER-/HER2+ (18%); ER-/HER2- (29%), missing (10%). Number of BM: 1 (20%), >1 (73%), missing (7%). Local treatment: metastasectomy (S) (13%), radio-surgery (SRS) (12%), whole-brain radiation (WBRT) (57%), combination of S/SRS with WBRT (11%), no treatment (7%). Systemic treatment: Any (64%), HER2 directed (24%). Median OS was 11.33 months(m) (4.4-25.8). Clinical characteristics associated with OS in multivariate analysis: ER+, HER2+, age < 60, ECOG 0-1, single BM, controlled systemic disease at time of BM and <3 treatment lines before BM. After correction for covariates, use of systemic therapy was associated with longer OS (HR 0.35 CI 0.20-0.60, p < 0.001) regardless of subgroup: HER2+ (19.9 vs 3.5m), ER+/HER2- (12.7 vs 2.2m), ER-/HER- (10.5 vs 2.3m). In pts receiving trastuzumab at diagnosis of BM, continuation of HER2 therapy increased OS (HR 0.44 CI 0.25-0.77, p = 0.004) regardless of agent used (lapatinib vs trastuzumab p=0.7). OS was the same for S and SRS (p=0.7) and either one increased OS (HR 0.41 CI 0.21-0.79 p=0.008). WBRT prolonged OS in multiple BM (HR 0.61 CI 0.38-0.96); Median TTP-b was 11.07m (5-24). WBRT added to S/SRS had longer TTP-b than either modality alone (17.6m vs 10.4m HR 0.56 CI 0.37-0.85 p=0.006). Use of systemic therapy after diagnosis of BM increased TTP-b (11.8 vs 5.1m HR 0.55 CI 0.33-0.92 p = 0.024), but there was no difference between agents used (lapatininib vs trastuzumab p=0.79; capecitabine vs others p= 0.96). Conclusions: WBRT improved local control when done after S/SRS. The use of chemotherapy after local therapy improved time to progression in the brain and survival.
Subsequent endocrine therapy after resistance to ethinylestradiol treatment for the late-stage metastatic breast cancer: A retrospective cohort study.
Authors: Yamashita Toshinari , Yamamoto Yutaka , Ibusuki Mutsuko , Inao Touko , Hayashi Mitsuhiro , Sueta Aiko , Takeshita Takashi , Kuroi Katsumasa , Iwase Hirotaka
Published: February 2017

148

Background: Aromatase inhibitor (AI) is a most commonly used as the endocrine therapy in postmenopausal hormone-dependent breast cancer. Paradoxically, estrogen additive therapy using ethinylestradiol can be useful after long-term estrogen deprivation therapies with AI. Furthermore, there is a possibility of the beneficial effect of AI or fulvestrant as a subsequent endocrine therapy after EE2 failure. Methods: Ethinylestradiol (EE2; 3mg/day, TID) therapy was performed in 20 patients with metastatic breast cancer (median; 62 years-old, the mean observation time: 13.6 months.), who were heavily treated by sequential endocrine therapies (3rd or more line) including cytotoxic chemotherapies. We examined the efficacy of a subsequent endocrine therapy of AI or fulvestrant after becoming resistance to the EE2 therapy in the patients who got the disease control by the prior EE2 therapy. The primary endpoint was clinical benefit rate (CBR) and the secondary endpoint was time to treatment failure (TTF). (Registration number; UMIN 000002831, additional analysis). Results: Median TTF of EE2 treatment was 46 weeks (23-62+, 2 cases were ongoing). The response rate was 41% (9/22), the clinical benefit rate was 50% (11/22). The stable disease (< 6 months) was 18% (4/22) and another 3 cases were judged as progressive disease. Four cases withdrew due to nausea, fatigue and muscle-skeletal pain. In 20 cases progressed after disease control (SD or more) of EE2, a subsequent endocrine therapy, fulvestrant for 10 cases and AI for 10 cases, was performed. Fulvestrant group showed 50% (3 in 6) of CBR and 15 weeks (5-55+) of TTF, and AI-treated group showed 43% (3 in 7) of CBR and 19 weeks (5-33+) of TTF. Two in three cases, who became resistance to anti-estrogen treatment, got long SD by further EE2 re-therapy. Conclusions: Some cases showed clinical benefits of a subsequent therapy by AI or fulvestrant after becoming to EE2 failure. Taken together, sequential use of estrogen and anti-estrogen therapy (vice versa) could be one of the options as a salvage endocrine therapy for the patients with end-stage breast cancer.
Feasibility study of TS-1 additional therapy for the triple-negative breast cancer received neoadjuvant or adjuvant chemotherapy (SBCCSG14).
Authors: Futsuhara Kazushige , Inoue Kenichi , Nagai Shigenori E. , Saito Tsuyoshi , Sakurai Takashi , Kimizuka Kei , Kurozumi Masafumi , Tabei Toshio , Yamada Hirofumi , Kojima Masato , Hata Satoshi , Yamazaki Yasuo ,   Saitama Breast Cancer Clinical Study Group
Published: February 2017

162

Background: Prospective randomized clinical trials have demonstrated a significant advantage from postoperative adjuvant chemotherapy for patients with breast cancer. However, triple-negative breast cancer is high rate of early recurrence. Therefore, patients who do not achieve pathological complete response (pCR) for neoadjuvant chemotherapy have worse long-term survival than patients who achieve pCR. Treatment after adjuvant chemotherapy and neoadjuvant chemotherapy is not established yet. We notice that TS-1 improve early recurrent rate of breast cancer. TS-1 proved good response for advanced breast cancer and long-term therapy is possible. We planned the study for the purpose of inspecting it about the safety, completion and efficacy of giving TS-1 after standard therapy of triple negative breast cancer for one year. Methods: The patients with stage ±/II/ III triple negative breast cancer received neoadjuvant or adjuvant chemotherapy and surgery and/or radiotherapy. Furthermore, the cases of neoadjuvant chemotherapy did not achieved pCR. After that, dose of TS-1 is 80mg/m² administered orally daily for 2 weeks followed by a 1-week rest period given as 3-week cycles. Results: 63 patients were enrolled, including 44 patients received neoadjuvant chemotherapy and 19 patients received adjuvant chemotherapy. The average age is 50 years (28-68 years). 38 cases (60.3%) brought oral administration for one year to completion. The reasons of discontinuance were 15 cases of toxicity and 10 cases of recurrence. Average relative dose intensity was 80%. The compliance of TS-1 was 70.1% (222.4 days). Overall survival of 3 years was 86.47%, progression-free survival 50.8%. The overall incidence of toxicity was 54 cases (85.7%), and grade 3 toxicity occurred in 21 cases (33.3%). Conclusions: The compliance of TS-1 was approximately equal to the compliance for gastric cancer in spite of receiving treatments of anthracycline and/or taxane. The toxicity was approximately equal to the results for metastatic breast cancer. TS-1 administered orally for one year was feasible for triple negative breast cancer received standard therapy. Clinical trial information: UMIN000001414.
HER2Δ16 expression in HER2-positive breast cancer.
Authors: De Yao Jocelyn Torres , Sun Danyu , Galehouse Donna , Shorten Scott , Haller Nairmeen Awad , Rehmus Esther Hoogland
Published: February 2017

31

Background: HER2Δ16 isoform was detected in breast cancer and showed similar increased transforming activity to somatic mutation or deletion activated rat HER2 oncogene with 89% of HER2-positive breast cancer with this mutation developing local lymph node positive disease progression. This is the first study characterizing and determining the prevalence of HER2Δ16 isoform in patients from a NAPBC-accredited cancer center. Methods: 95 HER2-positive breast cancer tissue samples from 2002 to 2008 were obtained from Akron General Medical Center. Total RNA from cancer cells were isolated and RT-PCR was performed using primers to amplify the wild-type HER2 and HER2Δ16 isoform. DNA products from RT-PCR were then loaded in agarose gel electrophoresis with the HER2Δ16 isoform band being shorter compared to the wild type HER2. Results: Preliminary results from our ongoing study showed 39% (12 of 31) of our HER2 samples has HER2Δ16 isoform. Out of the 12 HER2Δ16 isoform samples, 17% are Stage I, 50% are Stage II, 25% are Stage III, and 8% are Stage IV breast cancer at diagnosis. Patient age ranges from 34 to 87, with 50% of the HER2Δ16 isoform patients having lymph–node positive disease at the time of diagnosis. This is in contrast to patients with HER2 wild type for which 26% (5 of 19) are diagnosed with Stage I disease and 42% have lymph node positive disease at the time of diagnosis. Conclusions: Transgenic mice that overexpressed rat HER2 oncogene with small extracellular domain deletion promoted transforming activity of this protein. HER2Δ16 isoform is detected in 39% of HER2 positive breast cancer based on our preliminary results with 50% having lymph node–positive breast cancer on initial diagnosis. Immunohistochemistry and FISH could not distinguish the wild type HER2 from the HER2Δ16 isoform. Further study is recommended for possible prognosticating utility of HER2Δ16 isoform in breast cancer.
The DCIS score: Potential for health care savings?
Authors: Young Rebekah , Kalnicki Shalom , Fox Jana Lauren
Published: February 2017

35

Background: The Oncotype Dx Recurrence Score for DCIS (DCIS Score) is a 12-gene assay derived from the original Oncotype DX test. The DCIS Score provides a local recurrence risk estimate at 10 years after lumpectomy for DCIS. Results can guide decisions regarding adjuvant radiation (RT). Foregoing RT can be a source of significant healthcare savings. We investigated the actual healthcare dollar savings to-date in our patients. Methods: We evaluated patients in whom the DCIS Score was ordered (x) and calculated total cost of testing. Potential cost of RT was that of IMRT as reimbursed by Medicare for a 16 fraction course, multiplied by x. Many of our patients with large breasts require IMRT for dose homogeneity and normal tissue parameters. We also calculated potential cost with 3D conformal (3D-CRT). Total potential cost was the sum of testing and treatment costs, determined for each modality. The number of patients ultimately treated (y) was also multiplied by these costs. Total actual cost was the sum of test expenses and actual treatment costs. Savings was the difference between total actual and total potential cost. Results: From 2/2012 to 5/ 2014 the DCIS Score was performed in 38 patients (x = 38). Median age was 66 (40 to 85). Grade was low in 39%, intermediate in 45%, and high in 16%. Fifty percent had necrosis and median size was 0.5 cm (0.1 to 3.1cm). The total cost of testing was $4125 * 38 = $156,750. IMRT reimburses at $23, 000 and 3D-CRT at $11,000. Potential total cost of RT ranged from $418,000 to $874, 000; testing brought total potential costs to $574, 750 to $1,030, 750. Upon receipt of test results, 12 (y) patients ultimately underwent therapy. IMRT was given in 11 patients and 3D-CRT in 1, for a total treatment cost of $264, 000. Therefore, total actual expenditures were $420, 750. Savings amounted to (574, 750 – 420, 750) = $154, 000 to (1,030, 750 – 420, 750) = $610, 000. Conclusions: In the era of rising healthcare costs, it is imperative to examine instances of possible overtreatment. The DCIS Score has the potential to save not only healthcare dollars, but to spare patients radiation side effects, time lost from work, and transportation expenses. While there are costs associated with the assay, if ordered judiciously, these can be offset by the subsequent savings from eliminating treatment.
Genetic counseling and testing of an underserved population at a large city hospital.
Authors: Joseph Kathie-Ann P. , Dhage Shubhada , Rifkind Kenneth
Published: February 2017

38

Background: Genetic counseling and testing for hereditary breast and ovarian cancer is underutilized in low-income and racial/ethnic women. We examine the number of patients referred for genetic counseling over from 2011-2012, clinic referral pattern, and number of patients tested in a population of largely underserved, immigrant patient population. Methods: The study was conducted in Bellevue Hospital. A retrospective review of patients referred to this institution’s high-risk clinic was analyzed. Demographics, insurance status, BRCA status, if tested, and source of referral were collected. Results: Between 2011-2012, 196 patients were referred for genetic counselling. The majority of the referrals came from specialty clinics: Breast Surgery (42%), Medical Oncology (24%) and Gyn (8.7%). 17.5% were classified as other. One percent of consults came from internal medicine, 0.5% from women’s clinic, 4% were referred from family members. Of those patients counseled, 83 were tested. Breast surgery had the highest yield with 49% of the patients tested, followed by med onc (33%). One patient refused testing. Forty-seven of our patients were able to receive genetic testing through Myriad hardship, thirty-three through Medicaid, two paid by Bellevue Hospital, and one by private insurance. Five patients were BRCA1 positive, five patients were BRCA2 positive (12% of patients tested); An additional five patients were BRCA2 MUS. Racial/ethnic breakdown of the BRCA positive patients were 40% Asian, 20% Latina, 30% African American, 10% White. Four patients had a personal history of BrCa, two patients personal history of OvCa, one patient personal history of BCa/OvCa, and three patients FHBCa/OvCa. Conclusions: Genetic testing for HBOC can be underutilized in low-income and racial/ethnic women due to lack of insurance and lack of education. It is possible to get many high-risk women tested and most patients are receptive to testing when the benefits of testing are clearly explained. Our results indicate that while cancer specialists are referring high-risk patients, there may be room for education on the part of primary care specialists to refer more unaffected high risk patients. This may afford patients the opportunity to make better informed screening and treatment decisions.