bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nintedanib (BIBF 1120) plus docetaxel in NSCLC patients progressing after first-line chemotherapy: LUME Lung 1, a randomized, double-blind phase III trial.
Authors: Reck Martin , Kaiser Rolf , Mellemgaard Anders , Douillard Jean Yves , Orlov Sergey , Krzakowski Maciej Jerzy , Von Pawel Joachim , Gottfried Maya , Bondarenko Igor , Liao Meilin , Barrueco Jose , Gaschler-Markefski Birgit , Novello Silvia 
Published: February 2017

LBA8011 Background: Nintedanib (N) inhibits VEGFRs, PDGFRs, and FGFRs. LUME Lung 1 is a placebo (P) controlled phase III trial of N + docetaxel (D) in patients (pts) with locally advanced/metastatic NSCLC progressing after first-line therapy. Methods: Stage IIIB/IV or recurrent NSCLC pts (stratified by histology, ECOG PS, prior bevacizumab, and brain metastases) were randomized to N 200 mg bid + D 75 mg/m2 q21d (n=655) or P + D (n=659). 1° endpoint was centrally reviewed PFS after 713 events (2 sided stratified log-rank, α=5%, β=10%). Key 2° endpoint of OS was analyzed hierarchically after 1,121 events (2 sided, adjusted α=4.98%, β=20%), first in adenocarcinoma (adeno) pts <9 mo since start of first-line therapy (T<9mo; identified as a prognostic/predictive biomarker [ASCO ‘13]), followed by all adeno pts and then all pts. Predefined sensitivity analyses added sum of longest diameters of target lesions (SLD) to stratification factors in the Cox model. Results: Pt characteristics were balanced between the arms. N + D significantly prolonged PFS vs P + D (HR 0.79; CI: 0.68, 0.92; p=0.0019; median 3.4 vs 2.7 mo) regardless of histology (squamous HR 0.77, p=0.02; adeno HR 0.77, p=0.02). OS was significantly prolonged in all adeno pts (HR 0.83; p=0.0359; median 12.6 vs 10.3 mo) with the greatest improvement seen in T<9mo adeno pts (HR 0.75; p=0.0073; median 10.9 vs 7.9 mo). A trend for improved OS was seen in all pts (HR 0.94; p=0.272; median 10.1 vs 9.1). When adjusted for SLD, a significant OS benefit was seen in all pts (HR 0.88; CI: 0.78, 0.99; p=0.0365). Disease control rates were significantly improved with N + D in all adeno pts (odds ratio [OR] 1.93; p<0.0001), T<9mo adeno pts (OR 2.90; p<0.0001) and all pts (OR 1.68; p<0.0001). The most common AEs were diarrhea (any: 42.3 vs 21.8%; Gr ≥3: 6.6 vs 2.6%) and ALT elevations (any: 28.5 vs 8.4%; Gr ≥3: 7.8 vs 0.9%). Incidence of CTCAE Gr ≥3 AEs was 71.3 vs 64.3%. Withdrawals due to AEs (22.7 vs 21.7%) were similar in both arms, as were Gr ≥3 hypertension, bleeding or thrombosis. Conclusions: N + D significantly improved PFS independent of histology, and prolonged OS for adeno pts. AEs were generally manageable with dose reductions and symptomatic treatment. Clinical trial information: NCT00805194.
Pilot study of proton therapy for treatment of regional lymphatics in patients with breast cancer.
Authors: Bradley Julie Ann , Dagan Roi , Ho Meng Wei , Xu Natalie , Morris Christopher G. , Li Zuofeng , Mendenhall Nancy P. 
Published: February 2017

100 Background: To determine the feasibility of proton therapy (PT) for regional nodal irradiation (RNI) in women with breast cancer and to compare target coverage and normal tissue avoidance between PT and conventional radiation. Methods: From May 2012 to May 2013, 14 women were prospectively enrolled in this pilot study; 5 had right-sided and 9 had left-sided. Median age at the time of PT was 53.7 years (range 37-73). The breast or chest wall and supraclavicular, axillary, and internal mammary (IM) lymph nodes were treated in all patients. Proton and conventional plans were developed for each patient; the superior plan, as defined by organ at risk sparing and target coverage, was treated. Targets and normal tissues were delineated on treatment CT scans. Wilcoxon signed rank sum test was used to compare dose-volume parameters. Results: For all 14 patients, the proton plan better met the dosimetric goals, and was used for treatment delivery. Median heart V5 measured 0.8% for the proton plans versus 23% for the conventional plans (p=0.0005). Median mean heart dose measured 0.55 Gy (range 0– 3.2Gy) for the proton plans versus 4.9 Gy (range 2-9.1 Gy) for the conventional plans (p=0.0005). Significant difference in median lung V5 and median V20 were found: 41% and 24% for the proton plans and 67% and 38% for conventional plans, respectively. PTV breast/chest wall coverage was adequate with both plans. Coverage of the level II axilla was higher in the proton plans (D95 48 Gy vs 44 Gy, p=0.01) as was coverage of the IM nodes (D95 50 Gy vs 46 Gy, p=0.01). Acute toxicity data is available for 12 patients. The most common acute toxicity was radiation dermatitis, with 9 patients experiencing grade 2 and 3 patients experiencing grade 3 toxicity. Other grade 2 toxicities included fatigue (n=3), pain (n=2), esophagitis (n=4), and skin infection (n=1). Radiation dermatitis was the only grade 3 toxicity. No grade 4 or 5 toxicities developed. Conclusions: Adjuvant PT is a well-tolerated, technically feasible modality for RNI, with a significant decrease in cardiac V5, V20, and mean heart dose as well as lung V5 and V20. Further investigation of PT for RNI in breast cancer is warranted to improve the therapeutic ratio by decreasing radiation exposure to the heart and lung. Clinical trial information: NCT01365845.
Are high mastectomy rates associated with unwanted variation in other aspects of breast cancer treatment? An overview of practice patterns in Alberta, Canada in 2009-2010.
Authors: Morrissey Sarah , Quan May Lynn 
Published: February 2017

102 Background: The Canadian Partnership Against Cancer recently released a system performance report identifying large variation in breast cancer treatment across Canada. Contrary to provincial guidelines, Alberta had higher than average rates of mastectomy (56%); however, factors driving this variation remain unknown. We sought to (1) determine if practice patterns of primary breast surgery and adjuvant therapy adhered to guidelines and (2) to describe influencing factors on treatment practices between the two major cancer programs in Alberta to inform future knowledge translation strategies for guideline implementation. Methods: All patients diagnosed with breast cancer (ICD 9-174) between January 2009 and December 2010 were identified from the Alberta Cancer Registry. Demographic, surgical, treatment, and pathology data were abstracted from the electronic health record. Descriptive statistics and t-testing comparing mastectomy rates, axillary surgery and adjuvant therapy between the two major cancer programs were performed. Results: There were 2,817 surgeries for early breast cancer in the study cohort between 2009 and 2010. Conclusions: Practice patterns identify variance from current guidelines. Mastectomy rates are influenced by surgeon volume and tumor size. Management of positive SN and adjuvant therapy is variable and may reflect under treatment. Further investigation of drivers for mastectomy and adjuvant therapy are necessary. [Table: see text]
Prospective study of cognitive function (cog fcn) in women with early-stage breast cancer (ESBC): Predictors of cognitive decline.
Authors: Rugo Hope S. , DeLuca Amy N. , Heflin Lara , Fang Sally , Melisko Michelle E. , Moasser Mark M. , Park John W. , Chien Amy Jo , Munster Pamela N. , Esserman Laura , Landau Susan M. , Jagust William J. , Kramer Joel H. 
Published: February 2017

104 Background: Cog complaints are common among women receiving adjuvant therapy (Rx) for ESBC. Longitudinal prospective data is needed to help identify predictors of cog decline. We conducted a prospective trial to evaluate the effects of chemo- (CTX) and hormone therapy (HRx) on brain and cog fcn in pts with ESBC using multiple objective and subjective tests as well as MRI/PET imaging. Here we report evaluation of clinical characteristics that predict decline in cog fcn. Methods: Eligibility included female patients (pts) planning to receive adjuvant Rx for ESBC. Pts were enrolled in 3 Rx groups (grps): CTX, CTX and HRx, and HRx, with a 4th no Rx age/education matched control grp. All pts underwent a battery of objective and subjective cog tests before start of Rx, 1 mo after CTX or 5 mo after start of HRx (FU1), then 9 mo (FU2) and 18 mo (FU3) after CTX. Brain MRI, PET and serum estradiol (E) were performed at baseline, FU1 and FU2. Results: 81 pts were enrolled as follows, 14 CTX, 33 CTX and HRx, 22 HRx, 12 control. 90% completed FU1, 72% FU2, and 62% FU3, with 29 pts waiting to complete testing. Demographics were similar between grps, median age 54, 78% Caucasian. At each FU, ~25% of pts showed decline in cog fcn compared to the prior time point using a reliable change index; 51% showed decline at > 1 time point, primarily in tests measuring executive function and verbal memory. 62% of pts who declined from baseline to FU1 later stabilized or improved; 77% of pts who declined from FU1 to FU2 later stabilized or improved. Compared to controls, receipt of CTX and HRx (OR 3.15, p=.008), or HRx overall (OR 4.94, p=.004) but not serum E, menopausal status, or CTX, were significant predictors of decline at any time point. Rx group did not predict poorer perceived cog fcn (FACT-COG); depression and fatigue did not predict decline in objective cog fcn. Conclusions: Decline in cog fcn is common in pts receiving adjuvant Rx for ESBC. Predictors included CTX and HRx, or HRx overall but not other treatment and pt related factors. Ongoing HRx, particularly after CTX, appears to be a risk factor for worse cog fcn. Pts should be aware that HRx may be a risk factor for cog deficits, and intervention studies should be designed to focus on this group of pts. Funding: NIH R01 1AG025303-01A2. Clinical trial information: 00755313.
Prospective study of cognitive function (cog fcn) in women with early-stage breast cancer (BC): Relationship between perceived and measurable cognitive deficits.
Authors: Heflin Lara , Fang Sally , DeLuca Amy N. , Melisko Michelle E. , Moasser Mark M. , Park John W. , Chien Amy Jo , Munster Pamela N. , Landau Susan M. , Jagust William J. , Kramer Joel H. , Rugo Hope S. 
Published: February 2017

105 Background: Cognitive complaints are common among patients (pts) receiving adjuvant therapy (Rx) for early stage BC. Longitudinal prospective data is needed to help understand the relationship between measured cog fcn, patient reported cognitive changes, and patient reported depression and fatigue. We conducted a prospective trial to evaluate the effects of chemo- (CTX) and hormone therapy (HRx) on brain and cog fcn in pts with early stage BC using multiple objective and subjective tests as well as MRI/PET imaging. Here we report relationships between objective measures and patient reported outcomes (PRO). Methods: Eligibility included female pts planning to receive adjuvant Rx for ESBC. Pts were enrolled in 3 Rx groups (grps): CTX, CTX and HRx, and HRx, with a 4thno Rx age/education matched control group. All pts underwent a battery of objective and subjective cog tests before start of rx, 1 mo after CTX or 5 mo after start of HRx (FU1), then 9 mo (FU2) and 18 mo (FU3) after CTX. Brain MRI, PET and serum estradiol were performed at baseline, FU1 and FU2. Results: 81 pts were enrolled as follows: 14 CTX, 33 CTX and HRx, 22 HRx, and 12 control. 90% completed FU1, 72% FU2, and 62% FU3, with 29 pts waiting to complete testing. Demographics were similar between grps, median age was 54 (range 34-71), 78% were Caucasian. At FUP1, depression (BDI-II) and fatigue predicted poorer overall perceived cog fcn (FACT-Cog); decline in letter fluency (FAS) on cog testing also predicted poorer overall perceived cog fcn (FACT-Cog). Decline in verbal memory (CVLT-II) predicted perceived memory deficits (FACT-Cog Memory), even after controlling for depression and fatigue. Conclusions: In pts receiving adjuvant Rx for early stage BC, depression, fatigue, and decline in letter fluency predicted poorer perceived cog fcn. Decline in verbal memory independently predicted perceived memory deficits, demonstrating that PRO are related to actual deficits in cog fcn. Future intervention studies should focus on these factors. Funding: NIH R01 1AG025303-01A2. Clinical trial information: 00755313.
Patient experiences and preferences for survivorship care.
Authors: Mitchell Kelly Westbrook , Houck Kevin , Kimmick Gretchen Genevieve , Trotter Kathy J. , Peppercorn Jeffrey M. 
Published: February 2017

110 Background: The optimal method for delivery of care to over 2 million breast cancer survivors in the U.S. remains unclear, with multiple models currently in practice. This study involved a patient-centered investigation of experiences and preferences for breast cancer survivorship care. Methods: We conducted a single-institution, cross-sectional, self-administered survey of needs, experiences, and interests following initial breast cancer care at an academic multidisciplinary breast clinic. For 4 weeks, all patients presenting for routine oncology care were provided a survey at appointment check-in. Analysis is descriptive, with chi square testing used to evaluate demographic correlates of response. Results: 612 surveys were distributed, with a response rate of 66.8%. Median age of respondents was 56 (range 26-93); 71% were white, and 18% identified themselves as black. Over 55% had a college degree. Regarding ongoing care, 63% preferred to see a cancer specialist at least annually, and 30% wanted access to a cancer specialist as needed. Less than 15% preferred referral to a local practice, and less than 15% favored follow-up care from a specialized cancer survivorship clinic. Regarding visit content, over 90% felt assessment for disease recurrence was a priority on follow-up. A majority were interested in emotional and psychological support (52%). Nearly 40% of patients felt that assistance with non-cancer related health issues was very important in oncology clinic follow-up, but only 25% wanted a cancer specialist to provide general medical care. 42% reported receiving a summary of their cancer treatment. 37% reported receiving awritten plan or list of recommendations regarding care needed as a cancer survivor. White patients were less likely than non-white patients to receive a treatment summary (p < 0.02) or a care plan (p<0.005). Age and education were not correlated with receipt of these materials. Conclusions: Patients’ experiences and preferences regarding long-term management of breast cancer are varied. Many patients desire ongoing follow-up with their primary oncology team. Further evaluation of patients’ goals, needs, and an evidence-based approach to follow-up care is needed to guide optimal program design.
Mammography screening among women 40-49 years old, before and after USPSTF guideline changes.
Authors: Hsu John , Huang Jie , Fireman Bruce 
Published: February 2017

113 Background: The age at which to start breast cancer screening is controversial. The US Preventive Task Force (USPSTF) recommended against routine mammography screening in women 40-49 years old in November 2009 (the 2002 report had recommended screening), and instead suggested that women consult their physicians. We examined the frequency of screening among 40-49yo, and characteristics of the screened. Methods: We examined mammography screening among 85,650 women who were continuously enrolled in a prepaid integrated delivery system and who were between 40-45yo in 2006. We excluded women with any cancer diagnosis (2005-2009). Using logistic regression, we examined the association between screening in 2010 and several traits, e.g., mammogram cost-sharing, screening behavior before 2010, comorbidity score, race/ethnicity, and neighborhood socio-economic status indictors. In 2010, 75% of women had free mammograms; for the others, the median cost-sharing amount was $10. Results: Nearly all subjects (92%) received at least one mammogram between 2006-10: 14% received one; 37% received two; 33% received three; 6% received four; and 1% received 5+ mammograms. The unadjusted percent screened during each year increased slightly from 2006-2009 (38% to 47%) before dropping in 2010 (45%). Among women screened before the guideline changes, 47% received a mammogram in 2010. After adjustment, subjects who had any cost-sharing (OR=0.96 vs. free screening, 95%CI: 0.93-0.99) or who lived in lower SES neighborhoods (OR=0.94 vs. higher SES, 95%CI: 0.90-0.97) were less likely to receive a screening mammogram in 2010. Subjects with frequent earlier screening (e.g., OR=4.44 for four mammograms vs. none, 95%CI:3.99-4.94) and who were Asian (OR=1.05 vs. White, 95%CI: 1.01-1.09) were more likely to receive a 2010 mammogram; Black and Hispanic subjects had similar odds as Whites. Conclusions: In this integrated system, mammography screening among women 40-49 years old decreased slightly after the 2009 USPSTF recommendation against routine screening. Better alignment of insurance benefits with screening guidelines could improve adherence with recommendations.
Breast cancer patients with diabetes mellitus: Defining the population and assessing outcomes.
Authors: Karlin Nina J. , Dueck Amylou C. , Nagi Reddy Sravan K. , Verona Patricia M. , Cook Curtiss B. 
Published: February 2017

137 Background: Diabetes has been associated with an increased risk of mortality among patients with many types of cancers. Methods: We performed a case-control study of 109 breast cancer patients to determine the impact of diabetes on disease recurrence and survival. These 109 patients diagnosed with invasive breast cancer during 2007-2011 with diabetes were identified from the institutional Cancer Registry and matched to 109 breast cancer patients without diabetes according to age, race/ethnicity and year of diagnosis. Statistical tests included paired t-tests, McNemar’s tests, and stratified Cox regression. Results: The median ages of those with and without diabetes were 68 years, and 91% in both groups were white (both matched). Patients with and without diabetes were not significantly different in terms of tumor grade, cancer stage, estrogen or progesterone receptor status, HER2 neu status, marital and employment status, smoking use, use of adjuvant chemotherapy, and steroid treatment (all P >.4). Patients with diabetes reported less use of alcohol (50% vs 64%, P=.04), and had greater BMI (79% overweight/obese vs 58%, P= .002). Survival analysis demonstrated no differences in survival from initial breast cancer diagnosis (HR=1.25, 95% CI 0.49-3.17) with median follow-up of 2.2 years (range 0.1-4.9), and no differences in recurrence-free survival (HR=1.00, 95% CI 0.14-7.10) though very few deaths and recurrences were observed. Within the diabetes group, 96 (88%) had type 2 diabetes and 97/106 (92%, 3 unknown) had diabetes pre-existing to cancer diagnosis. Initial diabetes therapy included diet (33, 30%), oral therapy (48, 44%), insulin (21, 19%), or oral+insulin (6, 6%). 7 patients required a change in diabetes therapy within 1 year of cancer diagnosis with 3 patients starting insulin. 32/70 (46%) with available lab data had 1 or more A1C >/=7 within 1 year of cancer diagnosis. Conclusions: In this retrospective, carefully matched case-control study, we developed a comprehensive profile of the patient population with newly diagnosed breast cancer and diabetes. Diabetes did not appear to impact mortality or recurrence-free survival based on descriptive estimates in this small breast cancer cohort.
Neoadjuvant single and dual HER2 blockade among patients with localized HER2-positive breast cancer.
Authors: Reynolds Kerry Lynn , Cheng XingXing , Bhatia Ashmeet , Specht Michelle Connolly , Smith Barbara Lynn , Moy Beverly , Bardia Aditya 
Published: February 2017

147 Background: Dual neoadjuvant HER2 directed therapy is offered only in a clinical trial setting and is not standard of care, but emerging data suggests targeting multiple mechanisms may be more effective. We conducted a comprehensive systematic review and meta-analysis to evaluate the impact of neoadjuvant dual and single agent HER2 blockade on breast conserving surgery (BCS), and on pathological complete response (pCR) for estrogen receptor (ER)+ and ER- tumors, as well as the impact of pCR on disease-free survival (DFS) and overall survival (OS) for HER2+ breast cancer. Methods: MEDLINE, EMBASE, and Cochrane Controlled Clinical Trials Register databases were queried to identify eligible trials. Inclusion criteria were prospective, neoadjuvant trials that had at least one arm with HER2 directed therapy, and reported pCR. Pooled relative risk ratios (RRs) and p values were estimated for endpoints using the random effects statistical model. Results: We identified 36 trials (N = 4130). High pCR rates (> 40%) were seen with anthracycline-based chemotherapy and trastuzumab alone, and non-anthracycline based dual HER2 blockade. The addition of trastuzumab to chemotherapy did not improve BCS rate (RR 1.40, p = 0.15), but significantly increased rates of pCR (RR 1.91, p = 0.0001). Similarly, dual HER2 blockade compared to trastuzumab alone did not improve BCS rate (RR 1.03, p = 0.84), but significantly increased rates of pCR overall (RR 1.39, p < 0.00001), in both ER+ (RR 1.72, p = 0.01) and ER- subsets (RR 1.91, p = 0.0001), with no increase in grade 3/4 toxicity (RR:1.13, p = 0.16). Dual HER-2 blockade without chemotherapy was associated with pCR in a subset (11.2% - 27%) with minimal toxicity (incidence of grade 3/4 toxicity:1-5%). Higher pCR was associated with improved DFS (RR 2.29, p = 0.006) and OS (RR 4.61, p = 0.009). Conclusions: Neither the addition of trastuzumab to chemotherapy, nor the dual-HER2 blockade compared to trastuzumab, improves rates of BCS. However,both significantly improve rates of pCR, which is associated with improved DFS and OS. Dual HER2 blockade,with endocrine therapy for ER+, could potentially lessen or even obviate the use of chemotherapy.