bluuebunny/crossref_metadata_2025 huggingface dataset:
Standardized Uptake Value of 2-[18F] Fluoro-2-Deoxy-d-Glucose in Predicting Outcome in Head and Neck Carcinomas Treated by Radiotherapy With or Without Chemotherapy
Authors: Allal Abdelkarim S. , Dulguerov Pavel , Allaoua Mohamed , Haenggeli Charles-André , El Ghazi El Abbes , Lehmann Willy , Slosman Daniel O.
Published: February 2017

PURPOSE: In patients with head and neck cancer enrolled onto a prospective study of positron emission tomography (PET), pretreatment 2-[18F] fluoro-2- deoxy-d-glucose (FDG) uptake was evaluated as a predictor of local control and disease-free survival (DFS) after treatment by radiotherapy (RT) with or without chemotherapy.

PATIENTS AND METHODS: We studied 63 patients with carcinomas of the head and neck who had an FDG-PET scan before radical RT. Tumor FDG uptake was measured with the semiquantitative standardized uptake value (SUV). All patients but one were treated with accelerated or hyperfractionated RT schedules. Thirteen patients received concomitant cisplatin-based chemotherapy.

RESULTS: In 25 patients who presented with any component of treatment failure, the SUV was significantly higher than in the remaining patients without any such failure. Patients having tumors with high FDG uptake had a significantly lower 3-year local control (55% v 86%, P = .01) and DFS (42% v 79%, P = .005) compared with patients having low uptake tumors. In the multivariate analysis, the only factor that retained its significance for DFS was SUV category, whereas T category was of borderline significance. For local control, T category remained a significant factor, whereas a lower local control was observed for tumors with a high SUV compared with those with low SUV.

CONCLUSION: FDG uptake, as measured by the SUV, has potential value in predicting local control and DFS in head and neck carcinomas treated by RT. High FDG uptake may be a useful parameter for identifying patients requiring more aggressive treatment approaches.
Elevated Serum HER-2/neu Level Predicts Decreased Response to Hormone Therapy in Metastatic Breast Cancer
Authors: Lipton Allan , Ali S.M. , Leitzel K. , Demers L. , Chinchilli V. , Engle L. , Harvey Harold A. , Brady C. , Nalin C.M. , Dugan M. , Carney W. , Allard J.
Published: February 2017

PURPOSE: To determine the effect of elevation of serum HER-2/neu on response to hormone therapy.

PATIENTS AND METHODS: Seven hundred nineteen metastatic patients with estrogen receptor–positive (ER+), progesterone receptor–positive, or both or ER status unknown breast cancer were randomized in three independent clinical trials to receive second-line hormone therapy with either megestrol acetate or an aromatase inhibitor (fadrozole or letrozole). An automated enzyme-linked immunosorbent assay specific for the extracellular domain of the HER-2/neu (c-erbB-2) oncoprotein product was used to detect serum levels.

RESULTS: Two hundred nineteen patients (30%) had elevated serum HER-2/neu protein levels, using the mean + 2 SD (15 ng/mL) from the serum of healthy women as an upper limit. Response to treatment was available for 711 patients. The response rate (complete responses plus partial responses plus stable disease) to endocrine therapy was 45% in 494 patients with nonelevated and 23% in 217 patients with elevated serum HER-2/neu levels (P < .0001). Median duration of treatment response (using the time to progression [TTP] variable for patients who responded) was shorter in the group with elevated serum HER-2/neu levels (11.7 months) compared with the patient group with nonelevated levels (17.4 months). TTP, time to treatment failure, and median survival (17.2 months v 29.6 months) were also significantly shorter in the patients with elevated serum HER-2/neu levels (P < .0001).

CONCLUSION: Patients with ER+ and serum HER-2/neu-positive metastatic breast cancer are less likely to respond to hormone treatment and have a shorter duration of response than ER+ and serum HER-2/neu–negative patients. Their survival duration is also shorter.
Clinical Characteristics of Individuals With Germline Mutations in BRCA1 and BRCA2: Analysis of 10,000 Individuals
Authors: Frank Thomas S. , Deffenbaugh Amie M. , Reid Julia E. , Hulick Mark , Ward Brian E. , Lingenfelter Beth , Gumpper Kathi L. , Scholl Thomas , Tavtigian Sean V. , Pruss Dmitry R. , Critchfield Gregory C.
Published: February 2017

PURPOSE: To assess the characteristics that correlate best with the presence of mutations in BRCA1 and BRCA2 in individuals tested in a clinical setting.

PATIENTS AND METHODS: The results of 10,000 consecutive gene sequence analyses performed to identify mutations anywhere in the BRCA1 and BRCA2 genes (7,461 analyses) or for three specific Ashkenazi Jewish founder mutations (2,539 analyses) were correlated with personal and family history of cancer, ancestry, invasive versus noninvasive breast neoplasia, and sex.

RESULTS: Mutations were identified in 1,720 (17.2%) of the 10,000 individuals tested, including 968 (20%) of 4,843 women with breast cancer and 281 (34%) of 824 with ovarian cancer, and the prevalence of mutations was correlated with specific features of the personal and family histories of the individuals tested. Mutations were as prevalent in high-risk women of African (25 [19%] of 133) and other non-Ashkenazi ancestries as those of European ancestry (712 [16%] of 4379) and were significantly less prevalent in women diagnosed before 50 years of age with ductal carcinoma in situ than with invasive breast cancer (13% v 24%, P = .0007). Of the 74 mutations identified in individuals of Ashkenazi ancestry through full sequence analysis of both BRCA1 and BRCA2, 16 (21.6%) were nonfounder mutations, including seven in BRCA1 and nine in BRCA2. Twenty-one (28%) of 76 men with breast cancer carried mutations, of which more than one third occurred in BRCA1.

CONCLUSION: Specific features of personal and family history can be used to assess the likelihood of identifying a mutation in BRCA1 or BRCA2 in individuals tested in a clinical setting.
Women Experience Greater Toxicity With Fluorouracil-Based Chemotherapy for Colorectal Cancer
Authors: Sloan Jeff A. , Goldberg Richard M. , Sargent Daniel J. , Vargas-Chanes Delfino , Nair Suresh , Cha Steven S. , Novotny Paul J. , Poon Michael A. , O’Connell Michael J. , Loprinzi Charles L.
Published: February 2017

PURPOSE: The toxicity profile of fluorouracil (5-FU)–based chemotherapy given on 5 consecutive days at doses of 370 to 450 mg/m2 has been well documented. A meta-analysis of six North Central Cancer Treatment Group (NCCTG) cancer control trials involving 786 patients indicated that women treated with this type of regimen experienced more severe stomatitis and leukopenia than men. After these findings, an additional meta-analysis of the toxicity profiles on five NCCTG colorectal cancer treatment trials was undertaken.

METHODS: Data for 1,093 women and 1,355 men from 12 different treatment arms were included. The primary end points were the incidence of stomatitis, leukopenia, alopecia, diarrhea, nausea, and vomiting, recorded with standard National Cancer Institute common toxicity criteria. Fisher’s exact test was used to compare incidence and severity across sexes, supplemented by Forrest meta-analysis plots and logistic regression.

RESULTS: The incidence of four out of six toxicities studied was significantly greater for women than men; the exceptions were severe nausea and vomiting. Overall, almost half of the women compared with a third of the men experienced severe toxicity (P < .0001). Logistic regression confirmed the univariate findings while adjusting for the effects of study, dose, body mass index, and age. The differences were consistent across treatment cycles. Response rates and survival distributions were the same for both sexes.

CONCLUSION: This study confirms an earlier finding that women receiving 5-FU–based chemotherapy in a 5-day bolus schedule experience toxicity more frequently and with more severity than men. These data raise the question of whether the recommended initial dose of 5-FU–based chemotherapy for women should be lower than that for men.
Time Spent in Hospital in the Last Six Months of Life in Patients Who Died of Cancer in Ontario
Authors: Huang J. , Boyd C. , Tyldesley S. , Zhang-Salomons J. , Groome P. A. , Mackillop W. J.
Published: February 2017

PURPOSE: To describe hospital bed utilization in the final 6 months of life in patients dying of cancer in Ontario, Canada.

PATIENTS AND METHODS: Hospital separation records were linked to a population-based cancer registry to identify factors associated with hospitalization in the 203,713 patients who died of cancer in Ontario between 1986 and 1998.

RESULTS: Between 1986 and 1998, 5.3% of all acute care beds in Ontario were devoted to the care of cancer patients in the last 6 months of life. The mean time spent in hospital in the last 6 months of life decreased from 34.3 days in 1986 to 22.7 days in 1998. Hospitalization rates increased exponentially during the last month of life. Patients younger than 50 years of age, women, and residents of poorer communities spent significantly longer in hospital than others. Hospitalization rates differed very little among the common solid tumors, but patients with CNS malignancies, the lymphomas, and the leukemias spent significantly longer in hospital than the other groups. There was significant interregional variations in hospitalization that were not explained by differences in case mix. There was a statistically significant inverse correlation between the rate of use of palliative radiotherapy and the hospital bed use in the county in which the patient resided.

CONCLUSION: The total time spent in hospital in the last 6 months of life has decreased over the last decade, but acute care hospitals continue to play a large role in the care of patients who are dying of cancer.
Predictors of Smoking Initiation and Cessation Among Childhood Cancer Survivors: A Report From the Childhood Cancer Survivor Study
Authors: Emmons Karen , Li Frederick P. , Whitton John , Mertens Ann C. , Hutchinson Raymond , Diller Lisa , Robison Leslie L.
Published: February 2017

PURPOSE: To examine the determinants of smoking behavior among participants in the Childhood Cancer Survivors Study (CCSS).

METHODS: This retrospective cohort survey study was conducted among 9,709 childhood cancer survivors. Main outcomes included smoking initiation and cessation.

RESULTS: Twenty-eight percent of patients reported ever smoking and 17% reported being current smokers. Standardized to United States population rates, the observed to expected (O/E) ratios and corresponding 95% confidence limits (95% CL) of cigarette smoking were 0.72 (95% CL, 0.69, 0.75) among all survivors and 0.71 (95% CL, 0.68 to 0.74) and 0.81 (95% CL, 0.70, 0.93) among whites and nonwhites, respectively. Significantly lower O/E ratios were present among both males (O/E, 0.73) and females (O/E, 0.70). Factors independently associated with a statistically significant relative risk of smoking initiation included older age at cancer diagnosis, lower household income, less education, not having had pulmonary-related cancer treatment, and not having had brain radiation. Blacks were less likely to start smoking. Survivors who smoked were significantly more likely to quit (O/E, 1.22; 95% CL, 1.15, 1.30). Among ever-smokers, factors associated with the likelihood of being a current smoker included age less than 13 years at smoking initiation, less education, and having had brain radiation; those age less than 3 years at cancer diagnosis were significantly more likely to be ex-smokers.

CONCLUSIONS: Although survivors in the CCSS cohort seem to be smoking at rates below the general population, interventions are needed to prevent smoking initiation and promote cessation in this distinct population.
Quality of cancer family history and referral for genetic counseling and testing among oncology practices: A pilot test of quality measures as part of the ASCO Quality Oncology Practice Initiative (QOPI).
Authors: Wood Marie , Kadlubek Pamela , Lu Karen H. , Wollins Dana , Weitzel Jeffrey N. , Neuss Michael N. , Hughes Kevin S.
Published: February 2017

CRA1505

Background: The cancer family history (CFH) is an important tool for identification of individuals for genetic counseling/testing (GC/GT). Prior studies demonstrate a low rate of family history documentation and low referral rates for genetic counseling and genetic testing. Methods: In 2011ASCO began pilot testing new measures in QOPI to evaluate the practice of family history taking and referral for genetic counseling/testing in patients with either breast cancer (BC) or colorectal cancer (CRC). The measures assessed the presence or absence of CFH in 1st/2nd degree relatives, age at cancer diagnosis, referral for GC/GT and outcomes of referral. Results: Between September and October 2011 272 practices pilot tested these measures and reported on 10,466 patients (BC 6569, CRC 3897). 77.4% of all charts reviewed documented presence or absence of CFH in 1st degree relatives (BC 81.2% (CI 80-82%), CRC 77.4% (CI 76-79%), p= <0.001) and 61.5% of charts documented presence or absence of CFH in 2nd degree relatives (BC 68.9% (CI 68-70%), CRC 57.3% (CI 56-59%) p=<0.001). Age at diagnosis was documented for all relatives with cancer in 30.7% of charts (BC 45.2% (CI 44-47%), CRC 35.4% (CI 34-37%) p=<0.001). Patients were referred for GC/GT in 22.1% of all charts reviewed (BC 29.1% (CI 28-30%), CRC 19.6% (CI, 18-21%) p=<0.001). Of patients with hereditary risk (defined by selected risk guidelines) 52.2% of BC and 26.4% CRC were referred for GC/GT. When genetic testing was performed by the practice consent was documented 77.7% of the time and discussion of results was documented 78.8% of the time. Conclusions: Appropriate referral for GC/GT requires a complete and accurate CFH. In this pilot testing of QOPI measures we identified a higher quality of CFH information than expected though with room for improvement. Significant differences were seen between BC and CRC charts with greater accuracy of CFH and higher referral rates among BC patients. To obtain improvement in the identification and management of patients at high risk, significant improvements are needed. Education is part of the answer.
Patient preference between pazopanib (Paz) and sunitinib (Sun): Results of a randomized double-blind, placebo-controlled, cross-over study in patients with metastatic renal cell carcinoma (mRCC)—PISCES study, NCT 01064310.
Authors: Escudier Bernard J. , Porta Camillo , Bono Petri , De Giorgi Ugo , Parikh Omi , Hawkins Robert E. , Sevin Emmanuel , Negrier Sylvie , Khan Sadya , McCann Lauren , Mehmud Faisal , Cella David
Published: February 2017

CRA4502

Background: Increasingly pt reported outcomes are being added to traditional efficacy outcomes to understand the clinical relevance of toxicity differences between therapies. This study investigated if tolerability differences were significant enough to lead a patient to prefer continuing their treatment with Paz or Sun. Methods: Pts with mRCC were randomized 1:1 to receive as first line treatment blinded 800mg Paz for 10 weeks followed by a 2-week washout and then 50mg Sun for 10 weeks (4/2 weeks schedule) or vice versa. Pts were stratified based on ECOG performance status (0 vs 1) and number of metastatic sites (0/1 vs 2+). The primary endpoint, patient preference assessed at 22 weeks, was compared using Prescott’s test (α=0.10). At least 102 of 160 planned pts were required to complete the preference questionnaire to provide 80% power to detect a preference for one drug over another of 50% vs 30% with 20% expressing no preference. Other endpoints included physician preference, safety, QoL, pharmacokinetics and biomarkers. Results: Of 168 randomized pts, 126 completed the preference questionnaire. In the protocol-driven primary analysis (n=114), Paz was preferred by 70% of pts, Sun by 22% and 8% had no preference. After adjusting for a modest sequence effect, the difference in preference was 49% [90% CI 37.0 – 61.5% p <0.001] in favor of Paz. All pre-planned sensitivity analyses conducted were statistically significant in favor of Paz, including one which imputed Sun for all unavailable pt preference data. The most common reasons for Paz preference were better QoL and less fatigue. 60% of physicians preferred Paz vs 21% for Sun vs 19% no preference. Adverse events (AE) were in line with known profiles for both drugs. Pts on Paz had fewer dose reductions (13% vs 20%) and interruptions (6% vs 12%) vs Sun, mostly due to AE. There was less fatigue on Paz as assessed by FACIT-Fatigue; treatment difference of 2.49, p=0.002. Investigator assessed response (RECIST 1.1) was 22% with Paz vs 24% with Sun, p=0.87. Conclusions: This innovative trial design clearly demonstrates the better tolerability of Paz compared to Sun.
Patterns of decision making about cancer clinical trial participation among the online cancer treatment community: A collaboration between SWOG and NexCura.
Authors: Unger Joseph M , Hershman Dawn L. , Burg Kenda , Moinpour Carol , Albain Kathy S. , Petersen Judith A. , Crowley John
Published: February 2017

CRA6009

Background: Studies have shown an association between socioeconomic status (SES) and quality of oncology care, but less is known about the impact of SES on decision-making about CT participation. Methods: We assessed patterns of CT treatment decision-making according to important SES and demographic factors (age, sex, race, income, education) in a large sample of patients surveyed via a web-based treatment decision tool (NexCura, The Woodlands, TX). Eligible patients had a new diagnosis of breast, lung, colorectal, or prostate cancer, and were >18. Logistic regression (conditioning on type of cancer) was used. Reasons for non-participation in CTs were assessed using pre-specified items about treatment, family, cost, and logistics. All data were self-reported. Results: 5,499 patients were surveyed from 2007-2011. 40% discussed CTs with their physician; this differed by age (42% <65 v. 29% >65), income (42% >$50k/yr v. 36% <$50k/yr), and education (42% >college degree (CD) v. 37% <CD). 45% of discussions led to offers of CT participation, and 51% of offers led to CT participation. The overall CT participation rate was 9%, differing by age, income, and education (see table below). In a multivariate model including all SES and demographic factors (plus covariates comorbidity status and “distance to clinic”, a surrogate for convenience), income remained a predictor of CT participation (OR 0.73, 95% CI, 0.57-0.94, p=.01). Even in patients >65, who are nearly universally covered by Medicare, lower income predicted reduced CT participation (age by income interaction test, p>.05). Cost concerns were much more evident among lower income patients (p=.0001). Conclusions: Lower income patients were less likely to participate in CTs, even when considering age group.A better understanding of why income is a barrier may help identify ways to make CTs better available to all patients, and would increase the generalizability of CT study results across all levels of SES. [Table: see text]
Axitinib versus sorafenib as second‑line therapy in Asian patients with metastatic renal cell carcinoma (mRCC): Results from a registrational study.
Authors: Qin Shukui , Bi Feng , Cheng Ying , Guo Jun , Ren Xiu Bao , Huang Yiran , Wang Jinwan , Ben Yong , Kim Sinil , Tang Jie , Ye Dingwei
Published: February 2017

LBA4537

Notice of Retraction: "Axitinib versus sorafenib as second-line therapy in Asian patients with metastatic renal cell carcinoma (mRCC): Results from a registrational study."

Abstract LBA4537, published in the 2012 Annual Meeting Proceedings Part II, a supplement to the Journal of Clinical Oncology, has been retracted by Shukui Qin, MD, on behalf of all authors of the abstract. The adjudication portion of the Independent Review Committee (IRC) tumor assessments were incomplete for some of the ongoing patients in the study reported in the abstract and the adjudication could not be completed in time for presentation at the 2012 ASCO Annual Meeting.

Background: An earlier phase III trial in 723 patients with previously treated mRCC demonstrated significantly longer progression-free survival (PFS) for axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors, compared with sorafenib. We conducted a multicenter, randomized, open-label trial to estimate PFS for axitinib and sorafenib in 204 Asian patients with previously treated mRCC. Methods: Patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1 and measurable, clear-cell, mRCC that had progressed after 1 prior first-line systemic regimen (sunitinib or cytokines) were randomly assigned (2:1) to 28-day cycles of axitinib 5 mg twice daily (BID) or sorafenib 400 mg BID. Axitinib dose reductions and stepwise dose titrations to 7 mg BID and then 10 mg BID, as tolerated, were allowed; sorafenib dose reductions to 400 mg daily or every other day were also allowed. Primary endpoint was PFS per independent review committee. Results: Patients were stratified by ECOG PS and prior first-line systemic therapy: 135 received axitinib and 69 received sorafenib.Baseline patient characteristics included median age 56 years, 70% male, 99% Asian, and 63% ECOG PS 0. Prior therapy included sunitinib (45%) or cytokines (53%). Median PFS was 6.4 months (95% confidence interval: 4.6, 8.3) with axitinib and 4.8 months (2.8, 6.5) with sorafenib. Objective response rates were 23.7% with axitinib and 10.1% with sorafenib. All-grade adverse events in ≥15% of patients (axitinib, sorafenib) included hypertension (50%, 36%), weight decreased (37%, 33%), diarrhea (34%, 30%), hand-foot syndrome (32%, 57%), decreased appetite (30%, 20%), hypothyroidism (28%, 23%), fatigue (27%, 23%), proteinuria (21%, 20%), dysphonia (19%, 9%), cough (16%, 16%), rash (15%, 28%), pyrexia (7%, 16%), alopecia (3%, 22%). Conclusions: Asian patients receiving axitinib as second-line therapy for mRCC had a similar PFS and objective response rate as in a previous global phase III trial, with an acceptable safety profile.
Randomized phase III study of erlotinib versus observation in patients with no evidence of disease progression after first-line platin-based chemotherapy for ovarian carcinoma: A GCIG and EORTC-GCG study.
Authors: Vergote Ignace B. , Joly Florence , Katsaros Dionyssios , Coens Corneel , Reinthaller Alexander , Hall Marcia , Steer Christopher B. , Colombo Nicoletta , Lesoin Anne , Casado Antonio , Petru Edgar , Green John , Buck Martin , Ray-Coquard Isabelle Laure , Ferrero Annamaria , Favier Laure , Reed Nicholas , Curve Herve , Jimeno Antonio , Pujade-Lauraine Eric
Published: February 2017

LBA5000

Background: The epidermal growth factor receptor (EGFR) has been found to be overexpressed in 55-98% of advanced epithelial ovarian cancer. This trial evaluated the efficacy of maintenance erlotinib, an EGFR tyrosine kinase inhibitor, after first-line chemotherapy. Methods: Eligible patients (pts) had high-risk FIGO stage I or stage II-IV epithelial ovarian, peritoneal or fallopian tube cancer and were not selected for EGFR expression. All patients underwent first line therapy (6-9 cycles of 3-weekly platinum-based chemotherapy (CT)) and showed no signs of progression at the end of CT. Patients were randomised to maintenance erlotinib 150 mg daily for 2 years or observation. Primary endpoint was progression-free survival (PFS) by RECIST in combination with GCIG CA125 criteria. The final design provided 80% power to detect a PFS hazard ratio (HR) of 0.80 with 2-sided log-rank test at 5% after 632 events in 830 patients. Stratifications factors were stage, institution, age, response to and type of first-line CT. Immunohistochemistry (IHC) and FISH for EGFR, and EGFR mutation analyses were performed in 330 patients. The study was registered as NCT00263822 and EudraCT number 2004-004333-34. Results: Between Oct 2005 and Feb 2008, 835 pts were randomised by 125 institutions from 10 countries. The most important baseline characteristics, PFS and OS are summarized in the table. Median follow-up was 51 months. 25% of the patients stopped erlotinib due to side effects (of these 67% due to rash). The predictive value of IHC and FISH for EGFR, and EGFR mutations are being evaluated and will be presented at the meeting. Conclusions: In the overall study populationmaintenance erlotinib after first-line treatment in ovarian cancer did not improve progression-free or overall survival. [Table: see text]
Evaluation of lapatinib as a component of neoadjuvant therapy for HER2+ operable breast cancer: NSABP protocol B-41.
Authors: Robidoux Andre , Tang Gong , Rastogi Priya , Geyer Charles E. , Azar Catherine A. , Atkins James Norman , Fehrenbacher Louis , Bear Harry Douglas , Baez-Diaz Luis , Kuebler J. Phillip , Margolese Richard G. , Farrar William Blair , Brufsky Adam , Shibata Henry R. , Bandos Hanna , Paik Soonmyung , Costantino Joseph P. , Swain Sandra M. , Mamounas Eleftherios P. , Wolmark Norman
Published: February 2017

LBA506

Background: The purposes of this trial are to determine the effect of substituting lapatinib (L) for trastuzumab (T) in combination with weekly paclitaxel (WP) following AC as well as adding L to T with WP following AC on pathologic complete response (pCR) rates. Methods: Women with HER2-positive operable breast cancer received standard AC q3wks x 4 cycles followed by WP (80 mg/m2) on days 1, 8, and 15 q28 days x 4 cycles. Concurrently with WP, patients received either T (4 mg/kg load, then 2 mg/kg) weekly until surgery, L (1250 mg) daily until surgery, or weekly T plus L (750 mg) daily until surgery. Following surgery, patients received trastuzumab to complete 52 wks of HER2-targeted therapy. The primary endpoint is pCR breast. For each of the two primary comparisons, the Fisher’s exact test was used to test the equality of pCR rates. A Hochberg-type step-up procedure was applied to address multiple testings and to control the family-wise error rate at 0.05. Results: 51% were clinically node positive and 63% had HR+ tumors. pCR assessments were available from 519 of 529 patients. pCR percentage was 52.5% for AC→WP+T, 53.2% (p=0.9) for AC→WP+L, and 62% (p=0.075) for AC→WP+TL. pCR percentages in the HR+ subset were 46.7%, 48% (p=0.85), and 55.6% (p=0.18), respectively, and were 65.5%, 60.6% (p=0.57), and 73% (p=0.37) in the HR- cohort. The corresponding pCR breast and nodes percentages were 49.1%, 47.4% (p=0.74), and 60.4% (p=0.04). Grade 3/4 toxicities include diarrhea in 2%, 20%, 27% (p<0.001), and symptomatic Gr 3/4 left ventricular systolic dysfunction in 4%, 4%, and 2% (p=0.49). Conclusions: Substitution of lapatinib for trastuzumab in combination with the chemotherapy program employed in this study resulted in similar high percentages of pCR in both HR+ and HR- cohorts. Combined HER2-targeted therapy produced a numerically higher pCR percentage than single agent HER2-directed therapy, but the difference was not statistically significant. Central review of HER2 and ER is being conducted to determine if subsets benefiting from the combined HER2-targeted therapy can be identified. Funding: GlaxoSmithKline.
Response and long-term outcomes after neoadjuvant chemotherapy: Pooled dataset of patients stratified by molecular subtyping by MammaPrint and BluePrint.
Authors: Gluck Stefan , De Snoo Femke , Peeters Justine , Somlo George , Stork-Sloots Lisette , van 't Veer Laura J.
Published: February 2017

10

Background: Classification of breast cancers into molecular subtypes may be important for the proper selection of therapy for patients with early breast cancer. Previous analyses had shown that breast cancer subtypes have distinct clinical outcome (Sorlie, PNAS, 2001; Esserman, BCRT, 2011). Herein, we analyze using MammaPrint together with an 80-gene molecular subtyping profile (BluePrint) the response to neo-adjuvant chemotherapy and long term outcomes. Methods: This study was carried out on data from 144 patients from the I-SPY I trial; 232 patients from biomarker discovery program at MD Anderson (133 and 99 respectively; Hess, 2006, JCO; Iwamoto, 2011, BCRT); and 68 patients from City of Hope (Somlo, ASCO, 2010). All patients were treated in the neo-adjuvant setting with standard chemotherapy. MammaPrint and BluePrint were determined on 44K Agilent arrays run at Agendia or available through the I-SPY 1 data portal, or from Affymetrix U133A arrays. MammaPrint and BluePrint resulted in 4 distinct molecular groups: Luminal A (MammaPrint Low-risk/Luminal-type), Luminal B (MammaPrint High-risk/Luminal-type), Basal-type and HER2-type. Results: The overall pCR of this patient cohort was 22% but differed substantially among the subgroups. pCR was observed in 5% of the Luminal-A samples and 10% of Luminal-B, in 39% of the HER2-type samples and in 33% of the Basal-type samples. Patients with Basal-type tumors had a 5-year DFS of 71%; HER2-type had a 5-year DFS of 67% (n=71); 69% in HER2-type subgroup not treated with HER2-targeted therapy (n=45); Luminal-B type had a 5-year DFS of 77% and Luminal-A type showed 5-year DFS of 95%. Conclusions: We observed marked differences in response and DFS to neo-adjuvant treatment in groups stratified by MammaPrint and BluePrint. These findings confirm differences in chemotherapy response among molecular subgroups and indicate that the BluePrint and MP profile used for this analysis helps to further establish a clinical correlation between molecular subtyping and treatment outcomes.
Triple-negative breast cancer (TNBC) and residual disease (non-pCR): Does size matter?
Authors: Kern Peter , Badiian Mahyar , Minckwitz Gunter , Kimmig Rainer , Liedtke Cornelia , Rezai Mahdi
Published: February 2017

106

Background: TNBC is associated with distinctly worse survival rates than non-TNBC unless a pCR is achieved (Liedtke C et al. J Clin Oncol. 2008;26:1275-1281) or almost achieved (Symmans WF. J Clin Oncol. 2007;25:4414-4422). Recent pooled analyses pointed out that pCR defined as "no invasive and no in situ residuals in breast and lymph nodes" can best discriminate between patients with favorable and unfavorable outcomes (Minckwitz von G. J Clin Oncol. 16 April 2012). However, no differentiation has been made with regard to the prognosis within the category of "gross disease" (non-pCR, > 5 mm) after primary systemic therapy (PST). Methods: In this retrospective case series study, we analyzed 506 non-pCR patients out of a cohort of 16,196 patients with neoadjuvant or adjuvant chemotherapy from breast units of the West German Breast Center (WBC) at 24 months after surgery. Results: Overall survival (OS) differed significantly between the non-pCR groups ypT1 a (88%) and ypT1b,c (both 77%) likewise the disease-free survival (DFS) was 79% versus 63% (p< 0.05) at 24 months after surgery. Beyond ypT1-stage, we found that ypT1+2 and ypT3+4 set up two significantly distinct groups in OS and DFS, with OS rates of 79% for ypT1+2 and 60% respectively 68% for ypT3 and ypT4. DFS rates were alike differing with 68 % and 62 % for ypT 1 and ypT2 from both ypT3 and ypT4 (20% and 28%). Distant disease free survival (DDFS) was markedly superior in ypT1a (93%) and ypT1b (88%) versus ypT1c (77%). Stage-dependent DDFS was 82% for ypT1 respectively 81% for ypT2 and thus significantly different from stages ypT3 and ypT4 (43% and 52%) (p< 0.05). Conclusions: Risk stratification currently is made dichotomously: pCR and non-pCR. However it does not differentiate within the group of non-pCR. This case cohort trial investigates the prognosis of non-pCR according to the actual size of the residual disease. Overall survival at 24 months after surgery has to be differentiated between the groups ypT1a and ypTb,c and moreover between ypT1+2 and ypT3+4. This is to our knowledge the largest case cohort study analyzing the effect of gross residual disease on prognosis of patients with TNBC demonstrating: size does matter.
Treatment patterns by lines of therapy in metastatic breast cancer: Evidence from a large insured population in the United States.
Authors: Ray Saurabh , Bonthapally Vijayveer , McMorrow Donna , Bonafede Machaon , Landsman-Blumberg Pamela
Published: February 2017

116

Background: Metastatic breast cancer (mBC) guidelines contain multiple lines of treatment (LOTs) and regimen options, however little data on treatment patterns is available from real world clinical practice. This study describes patterns of chemo and biologic therapy use by LOT observed within a large U.S. insured population. Methods: Adult women with newly diagnosed mBC and starting anti-neoplastic treatment were identified in the 2005-2009 MarketScan Database which contains medical, pharmacy claims of > 40 million enrollees insured with >100 health plans across the United States. The index date was the first prescription fill or administration of anti-neoplastic treatment following metastatic diagnosis. A 90-day gap in treatment or initiation of a new regimen defined the end of a LOT. Patient demographics and clinical characteristics were measured at index. Descriptive analyses included the distribution of patients, use of chemo and biologic therapies and their therapy duration, across the first 4 LOTs observed. Results: Of 7,767 patients identified (mean (SD) age=58.2 (11.9) years), ≥50% received a subsequent LOT across the 4 LOTs (2nd LOT n=4,077, 3rd LOT n=2,033, 4th LOT n=1,059). Bone (44%) was the major metastatic site at diagnosis. The days on therapy (mean, SD, median) varied across LOTs: (162.7, 176.9, 108.0) in 1st, (147.5, 146.7, 99.0) in 2nd, (139.9, 131.1, 99.0) in 3rd, and (130.9, 123.4, 94.0) in 4th LOT. The most common backbone chemotherapies were: paclitaxel (26%), capecitabine (22%), docetaxel (22%) in 1st; paclitaxel (28%), capecitabine (18%), gemcitabine (16%) in 2nd; paclitaxel (22%), gemcitabine (19%), capecitabine (16%) in 3rd, and gemcitabine (19%), paclitaxel (18%), capecitabine (16%) in 4th LOT. Trastuzumab was the most frequently used biologic across all 4 lines (20%, 19%, 19%, 19% in 1st to 4th LOT respectively) followed by bevacizumab (20%, 19%, 19%, 19% in 1st to 4th LOT respectively). Lapatinib was used in 3rd (6%) and 4thLOTs (8%) only. Conclusions: Frequency and duration of chemo and biologic therapy use varied by LOT. The most frequently used agents across the 4 LOTs were paclitaxel (chemo backbones) and trastuzumab (biologics). Number of patients halved with each subsequent LOT.
Sonodynamic and photodynamic therapy in advanced refractory breast cancer.
Authors: Wang Xiaohuai , Li Lucy Qing , Zhang Weimin , Luo Yifan , Mitchell Douglas Graham
Published: February 2017

118

Background: Sonodynamic therapy (SDT), a procedure related with photodynamic therapy, is a promising new modality for treating deep-seated cancer. Two new chlorophyll derived sono-photo-sensitizing agents, along with equipment for systemic SDT, have been developed by EEC Biotech and all approved by regulator for safety on human. Animal studies demonstrate that the sensitizers are specifically absorbed into tumor cells and SDT does inhibit growth of mouse S-180 sarcoma. An in vitro experiment with human breast cancer cell-line showed that SDT was strongly synergetic with chemotherapy. Using sono-photo-dynamic therapy (SPDT) as a supplementary or salvage treatment, we have got some positive results in advanced refractory breast cancers. Methods: Twelve patients were pathologically proven advanced breast carcinoma. Eleven had metastases in viscera including brain, and nine in bones. Ten had chemotherapy before, nine failed at least second lines of conventional chemotherapy. With SPDT, Patients took the sensitizers sublingually on days 1 and 2, red light and multiple ultrasound transducers irradiate tumor area and whole body on days 4 to 6. The treatment was repeated. Nine patients had concurrent chemo with range from moderate to ¼ conventional dosages selected to keep side effects at grade II or better. Results: The twelve patients achieved CR 3(25%), PR 6 (50%), MR 1, SD 2, with an overall response rate of 75%.Median overall survival exceeded 14.5 months. SPDT as sole therapy was effective in three cases. Four treated repeatly with SPDT also achieved positive result after tumor relapsed. One patient with brain metastases showed much reduced. The two SD were TNBC with inflammation-like metastases on the chest surface. The main SPDT side effects were easily reversible mild pain in tumor areas, tiredness and weakness.There was no skin sensitivity.SPDT/dose controlled chemo was well tolerated, even a terminally ill patient was treated safely and effectively. Conclusions: These preliminary data suggest that SPDT has almost no toxicity, and may dramatically enhance chemo efficacy in some refractory advanced breast cancer cases. SPDT has a good trend to be a new systemic, low toxicity tumor therapy and merit for further investigation.
Digital versus screen film mammography: Impact on positive predictive values following transition.
Authors: Roy Elizabeth , Motiuk David , Burrowes Paul , Docktor Bobbie
Published: February 2017

12

Background: The Calgary Health Region changed from screen film mammography (SFM) to digital mammography (DM) in 2005. This retrospective study was designed to determine the effect of this conversion on positive predictive values (PPV) for cancerous and precancerous breast lesions. Methods: In the Calgary region, biopsies for mammographic calcifications are only done at Foothills Medical Centre (FMC) by a small group of mammographers employing homogeneous techniques. From FMC’s database, we reviewed core biopsy data for mammographic calcifications in the years 2002-2004 (SFM years) and 2008-2010 (DM years). Mammographic masses were excluded. We determined PPVs for each set of years for detection of cancerous lesions (PPV3for calcifications). We further calculated the PPVs of SFM and DM for detection of high-risk lesions, including ADH, ALH, LCIS, and papilloma collectively (precancerous lesions). The detection rates of benign lesions (excluding precancerous lesions) after biopsy were also determined. Statistical analysis was performed using two-tail z-tests. Results: 3,778 biopsies in 3,544 patients were reviewed. The difference in overall detection rate of cancer after biopsy for mammographic calcification between SFM (PPV3 = 24.7%) and DM (PPV3 = 23.8%) was not statistically significant (p = .53). On further analysis, the PPV for precancerous lesions increased (p < .0001) in DM (11.6%) versus SFM (7.8%). No significant difference (p = .065) was found in detection of benign lesions. Conclusions: In comparing DM to SFM, we found no significant change in PPV3 with respect to calcifications. However, with DM, there was a statistically significant increase in detection of lesions considered at risk for future malignancy. Given that the natural history of these premalignant lesions is incompletely understood, the significance of this finding is in question. This potential trend could be further strengthened by determining PPV1for cancerous and precancerous lesions with respect to calcifications. [Table: see text]
TS-1 and docetaxel followed by 5-FU/epirubicin/cyclophosphamide (FEC) as preoperative treatment in women with stage II/III breast cancer: A phase II study.
Authors: Hayashida Tetsu , Jinno Hiromitsu , Takahashi Maiko , Kitagawa Yuko
Published: February 2017

124

Background: The sequential combination of anthracycline and docetaxel (TXT) is one of the standard regimen in the preoperative setting, however, the adverse events of TXT such as febrile neutropenia, fatigue, edema is not low at all. Several reports showed a synergistic effect of combination chemotherapy with 5-FU and TXT through down-regulation of dihydropyrimidine dehydrogenase (DPD) and thymidine synthetase (TS). (Suto et al., Oncol Rep 2006) Okazaki et al. reported the trial of pre-operative combination chemotherapy of TS-1 (80mg/m2) and TXT (40mg/m2) with 13% of pCR rates (HER2-negative), and less adverse events. This study's purpose was to determine the efficacy of TS-1 and TXT followed by FEC in preoperative setting. Methods: This was a single-arm, clinical study evaluating the patients with stage II/III and HER2 negative breast cancer received 4 cycles of TS-1 (TS-1 80 mg/m2 on days 1-14 and docetaxel 40 mg/m2 on day 1 every 3 weeks), followed by 4 cycles of FEC (fluorouracil 500 mg/m2, epirubicin 100 mg/m2, cyclophosphamide 500 mg/m2on day 1 every 3 weeks). The primary end point was the pCR rate. The secondary end points were the clinical response rate, adverse drug reactions. The sample size of this study (55 patients) was calculated based on pCR rate obtained in previous studies of the sequential combination of anthracycline and TXT in preoperative setting (HER2-negative). Results: From November 2009 to April 2010, 55 patients were enrolled and 50 patients were assessable for clinical and pathologic responses. The overall response rate (caliper) was 82.0%. The pCR rate was 12.0% (6/50). The breast-conserving rate in patients whose tumor size was larger than 3 cm was 53.3%. PgR status was significantly correlated with pCR. (p=0.024) Grade 4 neutropenia was observed in one patient (2.0%) at the first cycle. The most common grade 3/4 non-hematologic adverse event was hand-foot syndrome, observed in 12 patients (24.5%). One patient (2.0%) showed grade 4 diarrhea. Conclusions: These results indicate that the sequential combination of TS-1 and docetaxel followed by FEC is a well-tolerated, effective neoadjuvant treatment for stage II/III breast cancer.
Factors associated with local control in inflammatory breast cancer.
Authors: Brown Lindsay C. , Blanchard Miran J. , Laack Nadia N.
Published: February 2017

126

Background: Inflammatory breast cancer (IBC) is an aggressive breast cancer variant, with 5-yr overall survival (OS) typically reported at 40-45%. We recently presented our results with once-daily radiotherapy (RT) as a component of trimodality therapy, with 5-yr OS of 64%. Herein we report patient and treatment factors associated with locoregional control (LRC). Methods: With permission of the IRB, review of medical records at the Mayo Clinic in Rochester, MN was performed to identify patients treated with RT for IBC from 2000-2010. Patients with non-metastatic, clinically diagnosed IBC were included. OS, LRC and distant metastasis-free survival (DMFS) were assessed using the Kaplan-Meier method. First recurrence in the chest wall or regional lymph nodes was defined as a locoregional recurrence (LRR). Results: 52 women were included in the analysis. Median age at diagnosis was 54 years (range 23-83). Median follow-up for the population was 3.6 years (range 0.7 – 11.9). All patients were treated with adjuvant RT to the chest wall and draining nodal basins in once-daily fractions of 1.8-2.25 Gy (median 2 Gy), to a median of 50 Gy (range 46-60 Gy). Actuarial 5-yr LRC was 85%. LRR was associated with poorer DMFS and OS (p < 0.01). Factors significantly associated with improved LRC included lack of extracapsular extension (ECE) and use of adjuvant chemotherapy (p < 0.05). Factors associated with a trend towards LRC included use of bolus, absence of boost, node negativity at time of surgery and pathologic complete response (pCR). Daily bolus was employed in 90% of patients and was most commonly (68%) 1 cm in thickness. There was a trend towards improved 5-yr LRC when bolus ≥ 1 cm was employed daily (93% v. 67%, p = 0.06). Patients who received a boost to the mastectomy scar (62% of the population, median of 10 Gy, range 10-16 Gy) had poorer LRC (78% v. 100%, p = 0.08), but superior 5-yr DMFS (78% v. 34%, p = 0.035) and OS (77% v. 34%, p = 0.04). Conclusions: LRC is associated with improved OS in IBC. Lack of ECE and use of adjuvant chemotherapy are associated with improved LRC in women with IBC. Node negativity, pCR and use of daily bolus ≥1 cm in thickness are associated with a trend towards improved LRC. The impact of boost requires further analysis.
Trastuzumab-related cardiotoxicity among older breast cancer patients.
Authors: Chavez-Mac Gregor Mariana , Zhang Ning , Niu Jiangong , Zhang Yufeng , Buchholz Thomas A. , Elting Linda S. , Hortobagyi Gabriel N. , Giordano Sharon Hermes
Published: February 2017

135

Background: The use of trastuzumab in the adjuvant setting is associated with reduction in mortality and recurrence. Trastuzumab is extremely well tolerated, but its use is associated with congestive heart failure (CHF). The incidence of this complication in the general population remains largely unknown, especially in older patients. In this study we evaluated the rates and risk factors associated with trastuzumab-related CHF in a large cohort of older breast cancer patients. Methods: Breast cancer patients > 66 years with full Medicare coverage, diagnosed with stage I-III breast cancer between 2005-2007, and treated with chemotherapy were identified in the SEER-Medicare database. Chemotherapy and trastuzumab use, comorbidities and CHF were identified using ICD-9 and HCPCS codes. Analyses included descriptive statistics and Cox proportional hazard model using trastuzumab as a time-dependent variable and logistic regression. Results: From 3,983 patients included, 847 (21.7%) received trastuzumab. Median age of the entire cohort was 71 years old. Among trastuzumab users the rate of CHF was 28.6% compared to 18.1% in non-trastuzumab users (p<.0001). After adjusting for demographic and clinical characteristics, comorbidities, and type of chemotherapy used, trastuzumab users were more likely to develop CHF than non-trastuzumab users (HR 1.74; 95% CI 1.47-2.06). Among trastuzumab users, older age did not further increase the risk, however history of coronary artery disease (OR 2.23; 95%CI 1.56-3.19), heart valve disease (OR 1.41; 95%CI 1.41-2.88) and emphysema -as a proxy for smoking- (OR 2.03; 95% CI 1.13-3.63) significantly increased the risk of CHF. There was a trend for increased risk of CHF associated with anthracycline use (OR 1.36; 95% CI 0.93-2.00). Conclusions: In this large cohort of older breast cancer patients, the risk of CHF among trastuzumab users was 1.74 times higher than non-trastuzumab users, which is higher than what has been reported in younger clinical trial participants. Among older breast cancer patients treated with trastuzumab, cardiac comorbidities, and emphysema may identify high-risk patients.