bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and safety of continued zoledronic acid every 4 weeks versus every 12 weeks in women with bone metastases from breast cancer: Results of the OPTIMIZE-2 trial.
Authors: Hortobagyi Gabriel N. , Lipton Allan , Chew Helen K. , Gradishar William John , Sauter Nicholas P. , Mohanlal Ramon W. , Zheng Ming , McGrain Beth , Van Poznak Catherine
Published: February 2017

LBA9500^

Background: Zoledronic acid (ZOL, 4 mg) every (q) 4 wk reduces the risk of skeletal-related events (SREs) in patients (pts) with bone metastases from breast cancer (BC). The OPTIMIZE-2 trial examined whether ZOL q12 wk was non-inferior to ZOL q4 wk in pts who had previously received monthly IV bisphosphonate (BP) therapy for ~1 year or longer. Methods: This was a prospective, randomized, double-blind, multicenter trial in female pts with bone metastases from BC who previously received ≥9 doses of IV BP (ZOL or pamidronate) during the first 10-15 months of therapy. Pts were randomized (1:1) to receive ZOL 4 mg IV q4 wk or q12 wk (placebo between ZOL doses to maintain blind) for 1 year. The primary endpoint was the proportion of pts with ≥1 SRE on study (SRE rate). Primary analysis was non-inferiority (pre-defined margin of 10%) for the difference in SRE rates. Secondary endpoints included time to first SRE, skeletal morbidity rate (SMR), bone pain score, change in bone turnover markers, and safety. Results: 403 pts were randomized to ZOL q4 wk (n = 200) or q12 wk (n = 203). Median age was 59 years, and baseline characteristics were similar between arms. The SRE rate was 22% and 23.2% in the ZOL q4 and q12 wk arms, respectively. The difference in SRE rate between arms was 1.2% (95% CI, –7.5% to 9.8%; P = .724). The upper limit of this 95% CI (9.8%) is less than the predefined margin of 10%, which indicates non-inferiority of ZOL q12 wk vs q4 wk. Times to first on-study SRE (HR, 1.06; 95% CI, 0.70 to 1.60; P = .792) were similar in the ZOL q4 and q12 wk arms, and mean SMRs were also similar (0.46 vs 0.50, respectively; P = .854). Overall, changes from baseline in bone turnover markers, and the incidence of treatment-emergent adverse events (TEAEs), were similar in the 2 arms. Numerically more renal TEAEs were reported in the ZOL q4 wk vs q12 wk arm (9.6% vs 7.9%, respectively). Two cases (1.0%) of osteonecrosis of the jaw (ONJ) were reported in the q4 wk arm. Conclusions: Among pts who had received monthly IV BP therapy for 1 year or longer, the efficacy of continuing ZOL for an additional year at q12 wk was non-inferior to ZOL q4 wk. Fewer renal AEs and none of the ONJ events were observed in the ZOL q12 wk vs ZOL q4 wk arm. Clinical trial information: NCT00320710.
Increased detection of sentinel nodes in breast cancer patients with the use of superparamagnetic iron oxide tracer.
Authors: Rubio Isabel T , Diaz-Botero Sebastian , Esgueva Antonio J , Espinosa-Bravo Martin
Published: February 2017

100

Background: The use of superparamagnetic iron oxide (SPIO) tracer for sentinel node biopsy (SLN) has shown non inferiority compared with the radioisotope technique in early breast cancer. False negative rates of SLN biopsy after neoadjuvant treatment (NAC) have decreased with dual tracer (radioisotope/dye) and with the excision of > 2 SLNs. This study was designed to evaluate the outcome of SLN after NAC using a dual tracer (SPIO-Tc99) and to compare it with the SLN by same dual tracer in the adjuvant setting. Methods: Between July 2013 and March 2014, 30 patients with invasive breast cancer (IBC) and SLN biopsy after NAC (NAC- SLN), and 118 patients with IBC not treated with NAC (adjuvant SLN), whose SLN was traced by Tc99 and SPIO were included in the study. Patients were injected subareolar with Tc99 the day before surgery and with the SPIO intraoperatively. SLN was excised if it was radioactive, magnetic or palpable. Patients signed an inform consent. Results: Detection rate by Tc 99 was successful in 113 (95.7%) patients and by SPIO in 116 (98.3%) in the adjuvant SLN (P= 0.0833) while in the NAC-SLN group detection rate by Tc-99 was successful in 28 patients (93.3%) and by SPIO in 30 patients (100%) (P =0.1573). Concordance rates per patient in the adjuvant SLN between techniques was 98.2%, while in the NAC-SLN was 100%. (p = 0.4762) Mean number of SLNs excised by 99Tc and SPIO were 1.9 and 2.21 respectively in the adjuvant SLN, (p=0.001) while 1.533 and 2.60 respectively in the NAC-SLN group. (p=0.0016) In the adjuvant SLN, the SLN was positive in 36 patients (30%), and in the NAC-SLN in 9 patients (30%). In the adjuvant SLN, both techniques detected same number of positive nodes but in the NAC-SLN, 9 patients had a positive SLN by SPIO (> 2 SLNs by SPIO and 1 SLN by Tc99) and 7 patients had a positive SLN by Tc99. Conclusions: Detection of SLNs with SPIO allows for easy identification of axillary nodes and can be used to reliably identify SLNs in breast cancer. Even though the small sample size in the NAC-SLN, the higher number of SLNs excised by the SPIO may optimize the success of SLN after NAC.
Long-term outcome results of the phase III PROMISE-GIM6 study evaluating the role of LHRH analog (LHRHa) during chemotherapy (CT) as a strategy to reduce ovarian failure in early breast cancer (BC) patients.
Authors: Lambertini Matteo , Boni Luca , Michelotti Andrea , Gamucci Teresa , Olmeo Nina , Gori Stefania , Giordano Monica , Garrone Ornella , Levaggi Alessia , Poggio Francesca , Giraudi Sara , Bighin Claudia , Pronzato Paolo , Del Mastro Lucia
Published: February 2017

105

Background: The PROMISE-GIM6 phase III randomized study showed that the use of triptorelin-induced temporary ovarian suppression during CT in premenopausal patients with early-stage BC reduced the occurrence of CT-induced early menopause (Del Mastro L, JAMA 2011). The 2013 ASCO and ESMO guidelines on fertility preservation in cancer patients consider this strategy still experimental due to the absence of data on long-term ovarian function and pregnancy rates, and some concerns exist on the safety of this procedure particularly for hormone-receptor positive BC patients. The present analysis reports long-term outcome results of the study. Methods: From October 2003 to January 2008, 281 premenopausal women with stage I through III BC who were candidates for adjuvant or neoadjuvant CT were randomized to receive CT alone or combined with triptorelin. The primary objective was to compare the incidence of CT-induced early menopause in patients treated with CT alone or combined with triptorelin. The present analysis considers data on recurrences, pregnancies and long-term ovarian function. Results: A total of 133 pts were enrolled in the CT alone arm and 148 in the CT + LHRHa arm; 82% and 79% of pts had hormone receptor positive-disease, respectively. The median follow-up at the time of the analysis was 7.3 years (interquartile range: 6.3-8.2 years). No differences in the 5-year disease-free survival (DFS) between treatment arms were observed (83.7% in CT alone arm vs 80.5% in CT plus LHRHa: HR=1.17; 95% CI 0.72-1.92, p=0.519). After the end of adjuvant treatments, 4 pregnancies (3.0%; incidence rate per 100 person-year=0.4) occurred in the CT-alone group and 8 pregnancies (5.4%; incidence rate per 100 person-year=0.8) occurred in the CT plus triptorelin group (CT + LHRHa arm vs CT alone: OR=1.84; 95% CI 0.54-6.27, p=0.39). Conclusions: The administration of LHRHa with CT was associated with the occurrence of more pregnancies; no differences in DFS were observed. The analysis on long-term ovarian function is still ongoing and will be presented at the meeting. Clinical trial information: NCT00311636.
Outcome of BRCA 1/2-mutated (BRCA+) and triple-negative, BRCA wild type (BRCA-wt) breast cancer patients in a phase I study of single-agent veliparib (V).
Authors: Pahuja Shalu , Beumer Jan Hendrik , Appleman Leonard Joseph , Tawbi Hussein Abdul-Hassan , Stoller Ronald G. , Lee James J. , Lin Yan , Kiesel Brian , Yu Jing , Tan Antoinette R. , Belani Chandra Prakash , Chew Helen K. , Garcia Agustin A. , Morgan Robert , Chen Alice P. , Giranda Vincent L. , Shepherd Stacie Peacock , Chu Edward , Puhalla Shannon
Published: February 2017

135

Background: Veliparib (V) (ABT-888) is an oral, potent inhibitor of PARP 1/2. PARP inhibitors have preclinical and clinical efficacy in BRCA+ malignancies. There are genotypic and phenotypic similarities between BRCA+ cancers, serous ovarian cancer and basal-like breast cancer and we postulated that these tumors types may be similarly sensitive to single-agent PARP inhibition. This study sought to establish the maximum tolerated dose (MTD), dose -limiting toxicities (DLT), pharmacokinetic and pharmocodynamic properties, and preliminary efficacy of chronically-dosed V in 2 cohorts of patients, BRCA+ and BRCA-wt (consisting of serous ovarian cancer and triple-negative breast cancer (TNBC). Methods: A 3+3 dose escalation phase I trial was performed. Nine dose levels (DL) were planned, and dose escalation started at 50 mg BID to a maximum of 500 mg BID to determine a maximum tolerated dose (MTD) and recommended phase II dose (RP2D). V was administered orally continuously on a 28 day cycle. BRCA+ and BRCA-wt patients were enrolled in 2 separate cohorts with 2 separate escalations. Results: 98 (70 BRCA+ and 28 BRCA-wt) pts have been enrolled. The maximum administered dose (MAD) was 500mg BID and the MTD/RP2D is 400mg BID for both cohorts. 59 BRCA+ pts and 24 BRCA-wt pts (21 TNBC and 3 ovary) were evaluable for response. ORR was defined as CR+PR and clinical benefit rate (CBR) as CR+PR+SD > 6 months. Results are summarized in the table. Conclusions: There is evidence of anti-tumor activity with V comparable to that of other PARP inhibitors in the BRCA+ population. There was indication of dose responsiveness with greater activity in this population at higher doses. There is less activity in the mostly TNBC, BRCA-wt population, although there was evidence of benefit in a small number of patients. Ongoing tissue correlative studies will help to identify potential mechanisms of sensitivity and resistance. Clinical trial information: NCT00892736. [Table: see text]
Tumor infiltrating lymphocytes (TIL) to predict response to neoadjuvant chemotherapy in breast cancer: A systemic review and meta-analysis.
Authors: Mao Yan , Qu Qing , Zhang Yuzi , Liu Junjun , Shen Kunwei
Published: February 2017

138

Background: Whether tumor-infiltrating lymphocytes (TILs) predict response to neoadjuvant chemotherapy (NAC) remains elusive. Methods: A systematic review and meta-analysis was undertook to establish the relationship between TIL and pathological complete response (pCR) rate in NAC of breast cancer. A PubMed and Web of Science literature search was designed. Studies were included, in which the predictive significance of intratumoral and/or stromal TIL, and/or CD3+, CD4+, CD8+, and FOXP3+ lymphocytes were determined . Pooled ORs and publication bias was evaluated by STATA software. Results: A total of 13 published studies (including 3,555 patients) were eligible. In pooled analysis, higher number of TIL in pre-treatment biopsy was correlated with higher pCR rate of neoadjuvant chemotherapy, and odds ratio (OR) was 3.82 (95% confidence interval (CI), 3.10-4.70), no matter tested in intratumor (OR=3.32, 95% CI: 2.52-4.37), in stroma (OR=4.15,95% CI: 2.94-5.86), or in combined sites (OR=8.98, 95% CI: 3.79,21.30). Moreover, TIL predicts higher pCR rate in triple negative (OR=5.03,95% CI: 2.31-10.97) and HER2+ (OR=5.54,95% CI: 1.39-22.12) patients, but not in hormonal receptor (HR) +/HER2- patients (OR=2.57, 95% CI: 0.20-33.24). For TIL subsets, CD8+ T-lymphocytes predict better pathological response to NAC no matter in pre- (OR=3.36,95%CI: 1.15-9.85) or post-NAC (OR=4.71,95%CI: 1.29-17.27) tissue, while FOXP3+ T-lymphocytes have similar predictive roles only when tested after NAC (OR=4.26, 95%CI: 1.83-9.92).With limited study, the predictive role of CD3+ and CD4+T-lymphoctes were unclear, more perspective studies were needed in future to establish the relationship. Conclusions: High level of TIL in pre-treatment biopsy could be a good marker indicates better pathological response to NAC in triple-negative and HER2+ breast cancer patients. Different subsets have different predictive roles in the pCR rate to NAC. However, significant heterogeneity and an insufficient number of studies underscore the need for further prospective studies on subsets of T lymphocytes and different subtypes of breast cancer to increase the robustness of the analyses.
Everolimus plus exemestane in patients with advanced invasive lobular carcinoma: Efficacy and safety results from BOLERO-2.
Authors: Hortobagyi Gabriel N. , Noguchi Shinzaburo , Neven Patrick , Puttawibul Puttisak , Heng Daniel , Brechenmacher Thomas , Ringeisen Francois Philippe , Saletan Stephen , Bachelot Thomas Denis
Published: February 2017

152

Background: In BOLERO-2 (NCT00863655), everolimus plus exemestane (EVE + EXE) more than doubled median progression-free survival (PFS) vs placebo (PBO) + EXE (by local assessment: 7.8 vs 3.2 mo; hazard ratio [HR], 0.45; P < 0.0001; by central assessment: 11.0 vs 4.1 mo; HR, 0.38; P < 0.0001) in patients (pts) with hormone-receptor–positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC). This exploratory analysis assessed the efficacy and safety of EVE + EXE in a subset of pts with baseline invasive lobular carcinoma (ILC) (elderly pts with predominantly peritoneal, gastrointestinal, and ovarian metastases [mets]). Methods: Pts with HR+, HER2– ABC recurring or progressing on/after prior nonsteroidal aromatase inhibitor therapy were randomized 2:1 to receive EVE 10 mg/day + EXE 25 mg/day or PBO + EXE. Primary efficacy end point was PFS (by local assessment). Results: Of 724 pts, 77% (n = 556) had ductal carcinoma and 14% (n = 104; EVE + EXE, n = 64; PBO + EXE, n = 40) had ILC. In ILC subset, median age was 63 years, 47.1% had measurable disease, and majority of baseline characteristics were similar to overall study population with exception of main mets sites. In pts with ILC, 36% reported visceral mets (lung, liver, pleural, pleural effusions, peritoneum, and ascites), 10% lung mets, and 23% liver mets when compared with 59% visceral mets, 31% lung mets, and 33% liver mets in overall study population. Median PFS was higher with EVE + EXE vs PBO + EXE (6.9 vs 4.2 mo; HR, 0.59; 95% CI, 0.37-0.95). Objective response rates were 14.1% (EVE + EXE arm) and 0% (PBO + EXE arm) vs 12.6% and 1.7%, respectively, among overall study population. Clinical benefit rates were 45.3% (EVE + EXE arm) and 30.0% (PBO + EXE arm); 51.3% vs 26.4% in overall study population. The safety profile of EVE + EXE in pts with ILC was similar to overall study population. Most common adverse events (all grades) in EVE-treated pts with ILC were stomatitis (50%), diarrhea (41%), nausea (36%), fatigue (34%), and rash (33%). Conclusions: EVE + EXE prolonged PFS in pts with ILC who had different patterns of mets. Other outcomes were similar to those in overall study population. Clinical trial information: NCT00863655.
Vitamin D levels, triple-negative histology, and geography in breast cancer: A retrospective analysis of a large database of oncology practices in the United States.
Authors: Habib Joyce Georges , Espirito Janet L. , Harrell Robyn K. , Turnwald Brian , O'Shaughnessy Joyce , Epstein Ervin H. , Patt Debra A.
Published: February 2017

17

Background: The UVB-vitamin D-breast cancer (BC) hypothesis is supported by ecological studies demonstrating an inverse correlation between sunlight exposure and BC incidence and mortality. Observational studies also favor an inverse association between vitamin D status and BC risk, recurrence and mortality. Yet controversies remain regarding the role of vitamin D in BC. We examined associations between vitamin D levels, geographic location, clinical, and pathologic characteristics of BC patients (pts). Methods: This was a retrospective analysis from the electronic health record database of pts diagnosed with BC between 1/2007 and 5/2013 across US Oncology Network practices categorized based on their geographic location into: northern (> 40° N), central (35 to 40°N) and southern (< 35°N) latitude. We collected age at diagnosis, BMI, smoking history, stage, estrogen receptor (ER), progesterone receptor (PR), HER2 status, and the first documented serum 25-hydroxyvitamin D (25-(OH)D) level, categorized as 30 optimal. Statistical comparison was performed using Chi-squared tests for categorical variables and Kruskal-Wallis tests for continuous variables. Logistic regression was used to predict the likelihood of vitamin D deficiency. Results: 20,338 BC pts with a documented vitamin D level were identified. Mean age at diagnosis was 58. Stage and receptor status distribution were: 8%, 41%, 32%, 11% and 4% for stage 0, I, II,III, and IV respectively; 63%, 13%, and 10% for ER+/HER-2-, HER-2+ and TNBC, respectively. 17.6% and 27.8% of pts had deficient or suboptimal vitamin D levels. The covariates of age < 60 years (OR 1.24), advanced stage (OR 1.32 stage II, OR 1.51 stage III, and OR 1.81 stage IV), TNBC (OR 1.45), BMI ≥ 25 (OR 2.02), current smoker (OR 2.11), and lower latitudes (OR 1.36 and 1.19 for central and southern latitude respectively) were independent predictors of a first documented vitamin D deficiency in a multivariate model. Conclusions: Vitamin D deficiency may be associated with TNBC and central and southern latitudes. The possible influences of differential vitamin D supplementation and timing of testing require further investigation.
DNA methylation array analyses to identify HYAL2 methylation in peripheral blood as a marker for the detection of early breast cancer.
Authors: Yang Rongxi , Pfuetze Katrin , Zucknick Manuela , Sutter Christian , Marme Frederik , Schneeweiss Andreas , Schmutzler Rita K. , Bartram Claus , Burwinkel Barbara ,   Methylation Collaboration Group
Published: February 2017

26

Background: Early detection is crucial to improve the survival rate and quality of life of breast cancer (BC) patients. Changes in DNA methylation in peripheral blood could be associated with malignancy at early stage. We aim to identify BC-associated DNA methylation signatures in peripheral blood. Methods: We identified a BC-associated differentially methylated locus by genome-wide investigation using Illumina 27K Methylation Assay. Two validation studies and replications in leucocytes and T cells were carried out using MassARRAY. The RNA expression levels were measured by real-time PCR. Results: The methylation level of CpG site cg27091787 in hyaluronoglucosaminidase 2 gene (HYAL2) in peripheral blood was significantly lower in BC cases than in controls (discovery round, 72 BC case and 24 controls, p = 2.61 × 10-9 adjusted for cell-type proportions; first validation round,338 BC case and 507 controls, p < 0.0001; second validation round,189 BC case and 189 controls, p < 0.0001). Compared to the highest quartile, the lowest quartile of cg27091787 methylation was associated with a more than 40-fold increased risk of BC (p < 0.0001). In addition to cg27091787, the decreased methylation of a 650 bp CpG island shore of HYAL2 was also associated with BC. Moreover, the expression and methylation of HYAL2 in leucocytes were inversely correlated (p = 0.006). To note, the BC-associated decreased HYAL2 methylation was replicated in T cell fraction (p = 0.034). The cg27091787 methylation level enabled a powerful discrimination of early stage BC cases from healthy controls (area under curve (AUC) = 0.88), and was also robust for the detection of BC in younger women (AUC = 0.87). Conclusions: Validating the epigenome-wide study by independent cohorts, we have revealed a strong association between decreased HYAL2 methylation in peripheral blood and BC. Our results have given an answer to the debate on the origin of BC-associated differential methylation in blood, which is not only because of the change of cell type proportions, but more importantly due to altered methylation in specific blood cell fragments, like in T cells. And thus, we provide a promising blood-based marker for the detection of early BC.
A multivariate model to predict cancer upgrade from atypical ductal hyperplasia by core needle biopsy.
Authors: Pena Alvaro , Fazzio Robert T. , Shah Sejal , Hoskin Tanya L. , Brahmbhatt Rushin D , Visscher Daniel W. , Hieken Tina J. , Jakub James W. , Boughey Judy Caroline , Degnim Amy C.
Published: February 2017

3

Background: Atypical ductal hyperplasia (ADH) is a high-risk breast lesion usually diagnosed with core needle biopsy. Although upgraded to cancer at surgical excision in ~15 to 25% of cases, routine excision is questioned due to cost and overtreatment. We evaluated clinical, imaging, and histologic features associated with cancer upgrade and developed a multivariate model to predict risk of upgrade. Methods: With IRB approval a single institution retrospective review was performed of patients who underwent surgical excision of ADH diagnosed by core biopsy from 06/2005 to 06/2013. Review was performed of electronic records, breast imagin,g and biopsy slides. Multiple imputations were used for missing data. Association of cancer upgrade with various features was assessed with logistic regression. Results: 409 biopsies with ADH on core biopsy, with later surgical excision, were included. The overall upgrade rate was (16.1%, 95% CI:12.9-20.0%); 10 patients had invasive cancer at excision and 56 DCIS only. Features on core biopsy most strongly associated with upgrade were imaging estimated percent of lesion removed (upgrade 9% for 90% removed, 14% for 50 to 75%, and 27% for < 50% removed), individual cell necrosis (upgrade 34% with necrosis vs. 9.5% without), and # foci of ADH (22% for >1 focus vs 8% for 1 focus). A multivariate predictive model (see Table) showed an average C-statistic of 0.77. Women with no necrosis and either 1 focus with ≥ 50% removal or >1 focus with 90% removal (36% of the sample) have low risk of upgrade (5.0%, 95% CI:1.3-8.7%). Conclusions: ADH on core biopsy with low risk of upgrade to cancer is defined by percent of imaging lesion removed, # of foci of ADH, and lack of individual cell necrosis. If findings are validated, women whose biopsies meet low-risk criteria might be considered for chemoprevention and surveillance rather than surgical excision.[Table: see text]
Recurrence score and clinicopathologic characteristics of TAILORx participants by race and ethnicity.
Authors: Sparano Joseph A. , Gray Robert J , Zujewski Jo Anne , Whelan Timothy Joseph , Albain Kathy S. , Hayes Daniel , Geyer Charles E , Dees Elizabeth Claire , Perez Edith A. , Keane Maccon M. , Vallejos Sologuren Carlos , Goggins Timothy F , Mayer Ingrid A. , Brufsky Adam , Toppmeyer Deborah L , Kaklamani Virginia G , Atkins James N , Berenberg Jeffrey L , Sledge George W.
Published: February 2017

36

Background: Black race is associated with worse outcomes in localized breast cancer. We evaluated the characteristics of patients enrolled in the Trial Assigning Individualized Options for Treatment (TAILORx) by race and ethnicity. Methods: The analysis included 10,071 evaluable patients with Recurrence Score (RS) data. Eligibility criteria included: (1) T1-2, N0 disease, (2) estrogen receptor (ER) and/or progesterone receptor (PR) positive disease that was also HER2/neu negative, (3) age 75 years or younger and medically appropriate for adjuvant systemic chemotherapy. Results: The study population included 8,501 whites (84%), 722 blacks (7%), 423 Asians (4%), and the remainder other/unknown race. With regard to ethnicity, 7,916 were nonHispanic (79%), 919 were Hispanic (9%), and 1,236 were of unreported ethnicity (12%). There was no significant difference in RS distribution (p = 0.14), median RS (17 vs. 17), and mean RS (19.6 vs. 18.4) in blacks compared with nonblacks. There was likewise no difference in Hispanic vs. nonHispanic ethnicity for RS distribution (p = 0.53), median RS (17 vs. 17), and mean RS (18.6 vs. 18.4). Blacks were significantly more likely to be younger (39% vs. 30% < 50 years), have larger tumors (37% vs. 31% > 2 cm), poor histologic grade (25% vs. 17%), and PR-negative disease (14% vs. 10%) (Chi square test p < 0.05). Hispanic women were also significantly younger (39% vs. 30% < 50 years), and demonstrated marginal but statistically significant differences in tumor size (65% vs. 69% > 2 cm), histologic grade (20% vs. 18% poor), and PR expression (12% vs. 10% negative) (Chi square test < 0.05). In 974 patients with information on body mass index (BMI), there was no correlation between BMI and RS (r = -0.04). BMI was higher for blacks than whites (medians 31.6 vs. 28.9, p = 0.02, Wilcoxon test), but not in Hispanics. Conclusions: In patients selected for participation in TAILORx there were no significant differences in RS by race, ethnicity, and BMI. Black and Hispanic patients were significantly younger, and blacks had tumors that were larger and more likely to be associated with poor grade. Clinical trial information: NCT00310180.
A NSQIP analysis of 30-day complications after bilateral versus unilateral mastectomy with immediate reconstruction.
Authors: Silva Amanda Kathryn , Lapin Brittany , Yao Katharine , Song David H. , Sisco Mark
Published: February 2017

62

Background: Women with breast cancer are increasingly electing to undergo contralateral prophylactic mastectomy (CPM) despite questionable survival benefit and limited data on added risks. This study seeks to assess differences in perioperative complications between those who have bilateral mastectomy with reconstruction (BM/R) and unilateral mastectomy with reconstruction (UM/R). Methods: The American College of Surgeons National Surgery Quality Improvement Program Participant Use Files (2005-2012) were used to identify women with breast cancer undergoing UM/R or BM/R. 30-day complications after implant-based or autologous reconstruction were compared between UM/R and BM/R groups. Linear and logistic regression models were used to adjust for differences in age, obesity, smoking, diabetes, and hypertension between groups. Results: 18,229 patients were identified, of whom 6,502 (35.7%) underwent BM/R. Most patients underwent implant-based reconstruction (88.6% of BM/R and 79.4% of UM/R). Among patients with implant-based reconstruction, BM/R was associated with higher rates of implant loss (adjusted odds ratio [aOR] 1.55, p=0.02), transfusion (aOR 2.20, p<0.001), and reoperation (aOR 1.14, p=0.05) than was UM/R. Patients who had BM/R with autologous reconstruction were more likely to require transfusion (aOR 2.34, p<0.001) than those who had UM/R. BM/R was associated with a greater length of hospital stay (LOS) than was UM/R for implant and autologous reconstruction groups (aOR [for LOS ≥ 2 days] 2.22 and 2.25, respectively, p<0.001). There were no significant differences in rates of medical complications, surgical site infection, or wound disruption between UM/R and BM/R groups for either type of reconstruction. Conclusions: Women who undergo implant-based BM/R have a greater risk of implant loss and reoperation then those who undergo UM/R. Those who have BM/R are also more likely to require a transfusion and have a longer hospital stay, regardless of reconstruction type. Women considering CPM with reconstruction should be educated about these increased risks.
Predictors of performing response monitoring in patients with chronic-phase chronic myeloid leukemia (CP-CML) in a prospective observational study (SIMPLICITY).
Authors: Goldberg Stuart L. , Cortes Jorge E. , Gambacorti-Passerini Carlo , Khoury Hanna Jean , Mauro Michael J. , Paquette Ronald , Simonsson Bengt , Foreman Aimee , Rasouliyan Lawrence , Mohamed Hesham , Subar Milayna , Zyczynski Teresa Maria
Published: February 2017

116

Background: Previous SIMPLICITY data (ASCO 2014) have shown, in CP-CML patients (pts) with at least 12 months (mths) follow-up, monitoring for cytogenetic response (CyR) and molecular response (MR) differs from NCCN/ ELN recommendations and shows regional and practice-type variation. Few data describe predictors of monitoring. Methods: SIMPLICITY is an ongoing observational study of CP-CML pts receiving first-line (1L) imatinib (IM), dasatinib (DAS) or nilotinib (NIL) in the United States (US) and Europe (Eu); its primary objective is to understand tyrosine kinase inhibitor (TKI) management patterns in clinical practice (NCT01244750). Frequency of testing for CyR, by FISH or karyotype, and MR, by PCR, were analyzed in 3, 6 and 12 mth increments from TKI start. Stepwise multivariable logistic regression was performed to assess predictors of monitoring (including: age, sex at birth, region, practice type, 1L TKI, ECOG performance status, still on 1L TKI). Results: 1,083 pts (US: 66%; Eu: 34%) were enrolled prospectively through 1Apr2014, receiving IM (n=415), DAS (n=343) or NIL (n=325). 1,050, 985 and 862 pts were followed for at least 3, 6 and 12 mths, respectively. Of these, 15%, 34% and 49% were tested for CyR, and 27%, 65% and 83% were tested for MR, between 0–3 mths, 0–6 mths and 0–12 mths. By 3 mths, 33% had either CyR and/or MR testing and 88% of pts underwent testing by 12 mths. None of the candidate predictors distinguished between pts who were monitored vs. those that were not by 3 mths after start of 1L TKI. Pts <65 years (yrs) at start of 1L TKI (odds ratio [OR]=1.41) and those in Eu vs. US (OR=1.45) were more likely to be monitored by 6 mths. By 12 mths, pts <65 yrs (OR=2.27), those no longer on 1L TKI (OR=1.96), and those seen in academic centers (OR=1.59) were more likely to be monitored (all p<.05). A comparison of monitoring patterns with ELN/NCCN recommendations will also be presented. Conclusions: Two-thirds of pts were not monitored for CyR or MR within 3 mths of TKI start.Although there were no predictors of monitoring for CyR or MR by 3 mths, age <65 yrs at initiation of 1L TKI was a consistent predictor of monitoring by 6 and 12 mths. Clinical trial information: NCT01244750.
Modeling and improving chemotherapy patient flow.
Authors: Lennes Inga Tolin , Zenteno Langle Ana Cecelia , Duk Michael , Levy Carlis Avital , Bloom Mara , Souza Elizabeth , Levi Retsef , Ryan David P.
Published: February 2017

175

Background: Chemotherapy administration scheduling is dependent on infusion room hours of operation, availability of oncologist, capacity for treatment, pharmacy hood time, nursing and pharmacy staffing, and physical space limitations. In 2013, the main infusion center at MGH Cancer Center had 45% room/chair utilization reported by the Ambulatory Patient Tracking System and 33% exam room utilization in the clinics. However our infusion center experienced extremely high volume during peak hours, 10am to 2pm, but was underutilized before 10am and after 2pm, making it difficult to add on additional patients. Methods: In November 2013, MGH Cancer Center began collaboration with MIT Operations Management experts to ultimately improve patient flow through the Cancer Center by flattening the bottleneck at peak hours of operation and improving utilization of the infusion area and clinics. In phase I of the project, data was reviewed and refined. Key role groups of schedulers, prescribers, pharmacists and infusion nurses were shadowed by collaborators to gain insight into complex scheduling practices. A multidisciplinary working group met weekly to discuss the progress and suggest areas for further investigation. In phase II, optimization models testing the impact of alternative scheduling practices, physical space changes and alternative clinic configurations will be created. Finally, in phase III, change implementation and measurement will take place. Results: Process flow maps of patient movement through the cancer center were created. Patient tracking data was manipulated to understand key operational metrics. Several insights include an overall same-day chemotherapy cancellation rate of 10.7%, with the majority of cancellations from thoracic, GI and GU disease centers. Our mean scheduled infusion treatment length was 2.13 hours and 25% of appointments booked into infusion are not linked with a same-day clinic appointment. Conclusions: Understanding and refining incomplete or problematic data was a key part of understanding the issues contributing to the middle of the day bottleneck in the infusion area. Future work on this project will include optimization modeling and change implementation.
Enhancing the delivery of take-home cancer therapies in Ontario.
Authors: Rae Erin , Chan Amanda , Yeung Lyndee , Gavura Scott , Arias Jessica , Kukreti Vishal , Kaizer Leonard
Published: February 2017

46

Background: The delivery of systemic cancer therapy has expanded from primarily intravenous (IV) treatment, delivered in cancer centres, to include significant use of take-home cancer therapies (THCT) (e.g., oral medications). An industry pipeline survey suggests half of new cancer drugs are expect to be THCT. While IV treatments administered in hospitals are publicly funded for Ontario residents, public funding of THCT is dependent on age, socioeconomic status, and other factors. The delivery of these therapies may also take place outside the cancer centre. While the lack of universal funding is cited as a significant barrier to access, the growing use of THCT has introduced other system delivery questions. Cancer Care Ontario recently hosted a “Think Tank” to inform public policy recommendations for system change to enhance the delivery of THCT in the province. Methods: The day was highly interactive with health professionals and patient participants, and was structured around a case study of a patient receiving both IV and THCT. Approaches taken with THCT in other Canadian provinces were examined. Participants used a multi-dimensional framework (safety and quality; reimbursement and distribution; data and information) to develop recommendations across pre-defined “checkpoints” in the patient’s treatment journey. Pre-assigned groupings of participants with common professional/patient backgrounds developed recommendations that were subsequently prioritized by reassigned multidisciplinary groups. Results: Over 80 stakeholders developed and prioritized more than 180 recommendations. Major themes included education, technology levers, and drug access model reform. This advice will inform system planning and next steps in defining opportunities for system change. The majority of participants (84%) felt the event broadened their understanding of THCT delivery issues. Conclusions: The strategic design of the “Think Tank” facilitated the development of robust recommendations for improving the delivery and reimbursement of THCT. These recommendations, along with the lessons learned from other provinces, will provide the foundation for potential policy and system changes to enhance the quality of THCT delivery in Ontario.
Evaluation of nausea control with NEPA, a novel oral combination antiemetic.
Authors: Bosnjak Snezana , Schwartzberg Lee Steven , Rizzi Giada , Borroni Maria Elisa
Published: February 2017

169

Background: The introduction of NK1 receptor antagonists (RAs) improved the control of chemotherapy-induced nausea and vomiting. However, prevention of nausea, particularly in the delayed phase remains suboptimal, with no consistent superiority seen with the addition of aprepitant over 5-HT3 RAs + dexamethasone (DEX). NEPA, a fixed-dose oral combination of the new NK1RA, netupitant (NETU 300 mg) plus palonosetron (PALO 0.50 mg) targets two main antiemetic pathways with a convenient single dose. NEPA has shown superior complete response rates (no vomiting and no rescue use) compared with PALO in pivotal trials. This analysis summarizes the nausea control seen with NEPA in all 3 pivotal trials in the clinical development program. Methods: Patients in 3 randomized, double-blind trials received a single dose of NEPA + DEX prior to a variety of either highly emetogenic (HEC) (Studies 1 and 3) or moderately emetogenic (MEC) (Studies 2 and 3) chemotherapeutic agents. Patients receiving HEC also received additional DEX on Days 2–4. Nausea was measured daily with a 100 mm visual analog scale (VAS). The proportion of patients with no significant nausea (VAS <25 mm) were summarized (Table). Results: In Studies 1 and 2, NEPA was significantly more effective in controlling delayed and overall nausea compared with PALO (Table). The greatest nausea control with NEPA was seen in the non-AC MEC and HEC settings. Conclusions: This summary suggests that NEPA + DEX improves control of nausea during the delayed and overall periods following chemotherapy. High levels of nausea control were seen and were most noteworthy in patients receiving HEC or non-AC MEC. Clinical trial information: NCT01339260; NCT01376297. [Table: see text]
Developing a decision support tool for responding to patients’ reported levels of information needs, family anxiety, depression, and breathlessness.
Authors: Vliet Liesbeth van , Harding Richard , Bausewein Claudia , Payne Sheila , Higginson Irene J. ,   EUROIMPACT
Published: February 2017

173

Background: Routine clinical use of Patient Reported Outcome Measures (PROMs) such as the Palliative Care Outcome Scale (POS) may be prevented by a lack of guidance on how to respond to reported symptoms. When using POS in clinical care, clinicians encounter the most difficulties with responding to information needs, depression and family anxiety while breathlessness remains a difficult to treat symptom. We aimed to create a Decision Support Tool (DST) on how to respond to different levels of these patient-reported symptoms. Methods: A systematic search for guidelines and systematic reviews on these topics was conducted (in Pubmed, Cochrane and York DARE databases, Googlescholar, NICE, National Guideline Clearinghouse, Canadian Medical Association, Google.com). In a two-round online Delphi study purposefully sampled international experts (clinicians, researchers, patient representatives) judged the appropriateness (1-9 scale + do not know option) of drafted recommendations for each POS answer category (0-4) and provided qualitative remarks. Recommendations with a median of 7-9 and <30% of scores between 1-3 and 7-9 were included in the DST. Quality was assessed using an adapted GRADE approach. Results: Twenty-five out of 38 (66%) experts participated in round 1, 23 out of 37 (62%) in round 2. Higher POS scores were related to more included recommendations. The DST consists of both a manual and flow-charts of included recommendations for each topic. Overall, psychosocial interventions were recommended for lower levels of depression and breathlessness than drug interventions (e.g., goal-setting/coping versus morphine for breathlessness). Good communication and emotional support were recommended for low family anxiety levels, but a social needs assessment only for higher levels. For information needs recommendations were least discriminative; almost all recommendations (e.g., assess patients’ understanding of information, show empathy) seemed always relevant. Conclusions: The developed DST can assist clinical responses to patient-reported symptoms in palliative care. Future work is needed to test the effect of using the DST on patients’ outcomes.
Preliminary results from a phase I study of substance P-saporin in terminal cancer patients with intractable pain.
Authors: Frankel Arthur E. , Nymeyer Hugh , Lappi Douglas A. , Higgins Denise , Ahn Chul , Noe Carl
Published: February 2017

191

Background: For 10-15% of cancer patients, pain cannot be controlled using existing therapies (Zech et al., Pain, 63, 65-76, 1995). SP-SAP is the first targeted toxin to undergo phase I testing for pain. SP-SAP (Wiley and Lappi, Neurosci Lett, 230, 97-100, 1997) covalently linkes substance P (SP), a neuromodulator that binds to NK1 receptors on laminae I and X of the dorsal horn, and saporin (SAP), a ribosomal toxin that ablates cells that express NK1 and endocytose the toxin. Intrathecal injections of SP-SAP in rats reduce chemically or thermally induced pain, thermal hyperalgesia, and mechanical allodynia, with no signs of motor, sensory, or behavioral dysfunction (Mantyh et al., Science, 278, 275-9, 1997; Nichols et al., Science, 286, 1558-61, 1999; Suzuki et al., Nature Neurosci, 5, 139-26, 2002; Vierck et al., Neurosci, 199, 223-32, 2003). In canines, intrathecal injections into the lumbar region – 45 mcg for 10-15 kg (Allen et al., Toxicol Sci, 91, 286-98, 2006) or 15 mcg for 8-12 kg (Wiese et al., Anesthesiol, 119, 1163-77, 2013) – produce no neurological, behavioral, or histological deficits. A double-blinded RCT of SP-SAP for the treatment of bone pain in canines (Brown and Agnello, Anesthesiol, 199, 1178-85, 2013) showed that a single injection of 60 mcg (above 30 kg) or 40 mcg (below 30 kg) significantly reduced pain as measured by time to owner unblinding (p=0.002) or number of canines unblended (p=0.001). Methods: A single intrathecal injection of SP-SAP is made at the L5-S1 interspace of cancer patients with intractable sub-umbilical pain. Single subject cohorts are at doses of 1, 2, 4, 8, 16, 32, 64, and 90 mcg. Primary outcomes are assessed by pain survey (VAS “bothersome pain”, VAS “pain intensity”, ODI, EQ-5D, and BDI) and medication use log. Patients are monitored for toxicity, neurological and cardiac abnormalities, and SP-SAP antibodies for 6 months. Results: This report presents the results from the first three subjects of the phase I study. No evidence of toxicity or neurological or cardiac abnormalities were found. No clear evidence for pain reduction was observed. Conclusions: At existing doses (< 4 mcg), SP-SAP appears safe for human use. The study is continuing with dose escalation. Clinical trial information: NCT02036281.
Reducing patient suffering and preventing readmissions via supportive care screening: The James Cancer Hospital supportive-care screening model.
Authors: Wells-Di Gregorio Sharla , Zaleta Alexandra , Porensky Emily , Graham Lisa , McDowell Kelly , Snapp Janet
Published: February 2017

33

Background: Hospital admissions create physical, financial and emotional stress for oncology patients. Hospital avoidable readmissions are considered a marker of poorer quality patient care. To reduce readmissions, cancer hospitals must understand modifiable readmission risk factors AND establish screening systems to triage at-risk patients to outpatient palliative/supportive care services. The James Cancer Hospital is in Phase II development of a model to reduce patient suffering and readmission via the James Supportive Care Screening (JSCS), a 48-item validated clinical-research instrument. Methods: In 2013, the James Cancer Hospital began implementation of Supportive Care Screening to meet Standard 3.2 (Psychosocial Distress Screening) of the Commission on Cancer. The JSCS asks patients to rate distress in six palliative care domains including emotional concerns, physical symptoms, social/practical problems, spiritual problems, cognitive concerns, and healthcare decision-making/communication issues. Between January 2011 and December 2013, one-thousand and one patients completed the JSCS in the Outpatient Palliative Care clinic. During this period, 57 patients had at least one readmission. Hierarchical linear regression was used to predict the number of future readmissions with JSCS subscales as independent variables. Results: The overall model predicting readmissions was significant, F(7,959) = 37.074, p<.001. Time to readmission, physical symptoms, emotional concerns, spiritual concerns, and social concerns were significant predictors of patient readmission. We are currently examining palliative care outcomes in these domains and have found that outpatient palliative care significantly reduces suffering related to physical and emotional distress. Conclusions: Supportive care screening, can serve to reduce oncology readmissions and prevent patient suffering in six key palliative domains. During Phase II of the James Supportive Care Screening Model, we have identified several problem areas targeted to reduce readmissions and improve patient self-reported outcomes.
Impact and timing of palliative care referral.
Authors: Blackhall Leslie J , Read Paul W , Stukenborg George , Barclay Margaret , Dillon Patrick M , James Harrison , Barclay Joshua
Published: February 2017

50

Background: Recent studies suggest that early integration of palliative care services into the care of patients with advanced cancer can improve end of life care. Unfortunately, there are insufficient resources for all advanced cancer to see palliative care from time of diagnosis. This 2012 CMS innovation award is attempting to improve identification of cancer patients in need of palliative care. Methods: In Year 1 of this award, increased staffing was added to existing palliative care resources to improve access. Patients were referred at discretion of their oncologist. A control group consisting of patients with similar diagnoses not referred to palliative care was identified including those without any contact with palliative care, and those who only saw palliative care in the hospitalization prior to death. Data regarding hospitalization in the last month of life, and hospice utilization was obtained. Results: Median time between referral to palliative care clinic and death was 72.5 days (mean 112). See table below. Conclusions: These data suggest patients referred to palliative care clinic within 3 months of death had benefits similar referral at time of diagnosis. However, many patients were never referred or referred only at the very end of life. The next phases of this award will utilize patient-reported outcome data to better identify those who need palliative care. Although most palliative care services are hospital-based, in this study, in-patient consultation only was too late to provide much benefit for these patients. Re-focusing scarce palliative care resources to the out-patient setting may have greater impact on patient care. [Table: see text]