bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lapatinib impact on pulmonary hypertension.
Authors: Alkhatib Yaser , Albashaireh Derar , Al-Aqtash Tameem Abdul Hamid , Awdish Rana , Hanbali Amr S. 
Published: February 2017

160 Background: Pulmonary Arterial Hypertension (PAH) and cancer share growth factor and protein kinase signaling pathways that result in smooth muscle cell proliferation and vasculopathy. A number of tyrosine kinase inhibitors (TKI) have been developed for the treatment of cancer, and some of these like Imatinib have been investigated in PAH. There is little known about the impact of other TKI on the pulmonary vasculature. After reporting a case of lapatinib-induced PAH that reversed after withdrawal of the drug, we investigated the association of lapatinib with the development of PAH in our institution. Methods: A retrospective chart review was conducted, in accordance with IRB protocol, of all patients treated with lapatinib over the past five years at our institution. Patients who had undergone 2-D echocardiogram both prior to and after treatment were included in the analysis. Systolic Pulmonary Artery Pressures (PASP), right-sided chamber dilation and function, TAPSE were each evaluated. Through chart review, patients were evaluated in terms of risk factors for non-Group 1 PAH. A Wilcoxon signed-rank sum test was used to compare the changes in PASP before and after the initiation of lapatinib. Results: A total of 27 patients were found to have 2-D echo done before and after starting treatment with lapatinib. All patients had normal PASP before starting treatment. Eight patients developed elevated PASP following treatment. Two patients had evidence of left-sided heart disease felt to contribute to their elevated pressures, while the remaining 6 patients had no evidence for Group 2 (associated with left heart disease), 3 (associated with lung disease or hypoxemia) or chronic thromboembolic PAH. Right heart catheterization was available in one patient, confirming the diagnosis of PAH. The median pre-treatment and post treatment PASP in those 6 patients was 29.5 mmHg and 65.5 mmHg respectively (N=6; p = 0.03). Conclusions: Lapatinib is a TKI with a selective inhibition to EGFR and HER2, approved by FDA in 2007 as a second line agent in advanced breast cancer. Given the potential of TKIs as anti-proliferative agents in PAH, a number are currently under study, but little is yet known. This is the first study in the literature to show that PAH is a potential side effect of lapatinib.
Hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer: Sequencing of chemotherapy and endocrine therapy.
Authors: Engel-Nitz Nicole M. , Hao Yanni , Rogerio Jaqueline Willemann , Turnbull James D. , Gomez Rey Gabriel , Sullivan Jane , Rossof Arthur H. 
Published: February 2017

164 Background: National Comprehensive Cancer Network breast cancer guidelines suggest sequencing of systemic therapy. This study examined sequencing of endocrine and chemotherapy treatments to better understand real-world treatment patterns for HR+/HER2- advanced breast cancer. Methods: A proprietary clinical cancer database with physician-reported clinical data on patients with breast cancer was linked to medical and pharmacy claims (2008-2012) from a national US health plan. Study patients had HR+ and HER2- status. Advanced cancer cohorts were defined: stage III (SIII) or IV (SIV) at initial diagnosis, or developed metastases following initial diagnosis (MET). Index date was the first date of advanced cancer diagnosis or date of metastases following initial diagnosis. Health plan enrollment for 3 months pre- and ≥ 3-months post- index date was required; patients who died within 3 months after index date and were continuously enrolled were retained. A 3-month baseline period assessed prior treatment; a variable follow-up (until disenrollment or 31 Oct 2012) assessed patterns of endocrine and chemotherapy treatments following index date. Results: A total of 954 breast cancer patients met study inclusion criteria and were HR+/HER2- with ≥ 3 months of continuous enrollment after index date, with 369 of the 954 (38.68%) SIII, 117 (12.26%) SIV, and 469 (49.16%) MET patients. In the study population, 83.65% were treated with endocrine therapy, starting an average of 179 days after index date. A total of 80.29% were treated with chemotherapy, starting an average of 53 days following the index date; 65% of patients initiated chemotherapy after index date without prior endocrine treatment. Rates varied by cohort: 90% of SIII, 57% of SIV, and 48% of MET patients had no evidence of endocrine treatment prior to initiating chemotherapy. Conclusions: This study found large proportions of HR+/HER2- advanced breast cancer patients initiated chemotherapy without prior endocrine therapy. Further investigation of patient characteristics and outcomes by therapy sequencing patterns will help illuminate the extent to which patterns adhere to NCCN guidelines.
Longer-term cardiac safety and outcomes of dose dense (dd) doxorubicin and cyclophosphamide (AC) followed by paclitaxel (T) and trastuzumab (H) with and without lapatinib (L) in patients (pts) with early breast cancer (BC).
Authors: Iyengar Neil M. , Morris Patrick Glyn , Patil Sujata , Chen Carol , Abbruzzi Alyson , Lehman Robert James , Steingart Richard , Oeffinger Kevin C. , Lin Nancy U. , Moy Beverly , Come Steven E. , Winer Eric P. , Norton Larry , Hudis Clifford , Dang Chau T. 
Published: February 2017

167 Background: The addition of H to chemotherapy has improved outcomes in HER2-positive early BC. This approach is associated with (w/) an increased risk (<4%) of congestive heart failure (CHF). Dose-dense (every 2 weeks) anthracycline-taxane therapy (Rx) improves survival compared to the every 3 week schedule and can be combined w/ anti-HER2 Rx w/ no increased risk of cardiotoxicity up to 36 months. Here we report the incidence of NYHA Class III/IV CHF in 2 phase II studies with longer follow-up. Methods: We conducted a retrospective review of pts w/ HER2 + early stage BC treated at MSKCC and DFCI on two trials: In trial A - pts received dd AC (60/600 mg/m2) x 4 → T (175mg/m2) x 4 (w/ pegfilgrastim) w/ H x 1 year. Trial B differed w/ use of weekly T (80mg/m2) x 12 and the addition of L (1000mg orally daily) x 1 year. Left ventricular ejection fraction (LVEF) was prospectively assessed by a multi-gated acquisition scan serially throughout Rx. Results: Trial A enrolled 70 pts and Trial B enrolled 95 pts w/ the median age of 46 years (range 27-73 years). Overall, the 5-year distant disease-free survival (DDFS) for trials A and B is 92% (95%Cl; 83-97%) and 89% (95%CI; 81-94%), respectively. The baseline median LVEF was 68% (range 52-81%). In total, 28 of 165 (17%) pts had pre-existing hypertension. Now at a median follow-up of 84 and 57 months respectively, only one (1.4%, 95%CI; 1.36-7.7%) and 4 (4.2%, 95%CI; 4.2-10.4%) pts developed CHF. Since our earlier report, 1 additional CHF event occurred (Trial B) at month 44. Conclusions: Longer follow-up of these 2 studies demonstrate that dd AC → TH with or without L is associated w/ a low risk of CHF. This is consistent w/ the long-term cardiac toxicity reported from the randomized phase III studies of H w/ conventionally scheduled anthracycline-based regimens (with or without taxanes). DDFS outcomes are also encouraging. Clinical trial information: NCT00591851 and NCT00482391.
Tobacco use and race as copredictors of overall survival in patients with breast cancer.
Authors: Wells Jeremy Clady , Samuel Thomas A. , Morton Kyana , Looney Stephen W. 
Published: February 2017

20 Background: Tobacco use (TOB) has been linked to the development of breast cancer (BCa), but limited data exists linking TOB with overall survival (OS) and the influence of race on this relationship. Our previous research has shown that African-American (AA) patients with BCa have worse OS compared with Caucasian (C) patients. This retrospective study examines the effect of TOB on OS in BCa patients at Georgia Regents University (GRU) and the effect of race in conjunction with TOB on OS. Methods: Data were obtained from the GRU Tumor Registry. Inclusion criteria were all female patients diagnosed with BC between 2002 and 2010. The estimated hazard ratio (HR) from Cox regression was used to measure the association between TOB and OS. Race, age at diagnosis, and stage at diagnosis were considered for inclusion as covariates. A stratified OS analysis was also performed dividing patients by race (C vs. AA). Results: Data were collected on 836 females who met inclusion criteria. TOB was categorized as "none" vs. "any" at time of BCa diagnosis The Cox regression analysis indicated a decreased OS for women with any tobacco use (unadjusted HR, 1.45; p = 0.024). Statistical significance was retained when this HR was adjusted for race (HR, 1.47; p = 0.021) and age at diagnosis (HR, 1.45; p = 0.024), but not for stage at diagnosis (HR, 1.21; p = 0.266). In the stratified analysis, the results for C patients were similar to those obtained in the complete sample (HR, 1.62; p = 0.044). Statistical significance was not retained for AA patients (HR 1.31; p = 0.244). We compared C tobacco users (n = 157) vs. AA tobacco users (n = 127) (HR, 1.10; p = 0.716) and C tobacco non-users (n = 291) vs. AA tobacco non-users (n = 261) (HR, 1.36; p= 0.156) and found no statistical significance. Conclusions: Our analysis shows that patients with history of TOB at BCa diagnosis have a 45% chance of decreased OS compared to non-TOB users. The negative impact of TOB is still noted when adjusted for race and age at diagnosis but not for stage at diagnosis. When stratifying by race, we found that any TOB is a significant risk factor among C patients but not among AA patients. We conclude that any history of TOB at BCa diagnosis is an important negative prognostic factor for OS, and this is particularly true in C patients.
Hyperactivated mTOR and JAK2/STAT3 pathways: Crucial molecular drivers and potential therapeutic targets of inflammatory breast cancer (IBC).
Authors: Teplinsky Eleonora , Valeta Amanda , Arju Rezina , Giashuddin Shah , Sarfraz Yasmeen , Alexander Melissa , Darvishian Farbod , Silvera Deborah , Levine Paul H. , Hashmi Salman , Paul Ladan , Hoffman Heather J. , Singh Baljit , Goldberg Judith D. , Hochman Tsivia , Formenti Silvia , Schneider Robert , Jhaveri Komal L. 
Published: February 2017

60 Background: IBC is an aggressive form of breast cancer with poor prognosis. Combined multi-modality Rx results in a 5 year OS of 30-50%, underscoring the unmet need for targeted Rx. Our preclinical research in cell lines and xenografts identifies a role for activated PI3K/mTOR pathway in IBC. IBC cells express IL-6 and IL-8 and recruit tumor activated macrophages (TAMs) that further induce IL-6, IL-8 and activate the JAK2/STAT3 pathway. We investigated the independent and combined activity of these pathways in IBC tissues. Methods: Archived tissues of 42 IBC pts and 13 controls (nl breast) were analyzed using IHC and scored by 3 independent pathologists. Results defined as: 0, 1+ = neg; 2+ = pos for activated mTOR (P-S6) and 0 = neg; 1+, 2+ = pos for activated nuclear JAK2/STAT3 (P-JAK2; P-STAT3), cytokine (IL-6), macrophage (mØ) infiltration (CD68) and TAM (CD163). Proportions of IBC cases with pos expression were compared with controls (Fishers exact tests). Clinical and survival data were obtained. Results: Median age at diagnosis: 46 yrs (31-62) in early-stage IBC [EIBC] (n=37) and 41 yrs (29-57) in pts with de novo metastatic IBC [MIBC] (n=5). In EIBC, 19/36: HER2+ (1 unk); 8/19: ER+/HER2+; 8/36: ER-/HER2-. In MIBC, all were ER- (1 unk) and 3/4 were HER2+ (1 unk). 88% Rx with neoadjuvant and/or adjuvant anthracycline and taxane w/o adjuvant trastuzumab. 24 pts died (5/5 MIBC). Median OS: 86 mo (95% CI lower 48 mo) for EIBC & 41 mo (95% CI 8-81 mo) for MIBC. Median RFS: 18 mo (95% CI 18-79 mo) for 23 pts (13 NED; 1 unk). All controls: neg for P-S6, JAK2, STAT3 and TAMs and 92% neg for mØ and IL-6. Proportion of IBC with pos expression when compared to controls listed in table (p <0.0001). Of 31 pts with complete biomarker data who were PS6+, 97% had activated JAK2, 58% had activated STAT3, 80% had strong mØ and TAM infiltration and 97% were IL6+. Conclusions: This is the first study that validates preclinical findings and shows a strong association between mTOR, cytokines, TAMs and JAK/STAT pathways in most IBC pt tissues. Findings suggest a key role for dual blockade of mTOR and JAK/STAT pathways in phase I trials. [Table: see text]
Ductal lavage cytology in patients with ductal carcinoma in situ (DCIS).
Authors: Behr Andrea , Brogi Edi , Heerdt Alexandra S. , Van Zee Kimberly J. , Montgomery Leslie L. 
Published: February 2017

89 Background: Ductal lavage (DL) is a procedure used to obtain epithelial cells from a breast duct for cytologic evaluation. Previous studies have investigated DL as a potential screening procedure for women at high-risk for cancer. The data, however, does not support a significant correlation between lavage cytology and the presence of invasive carcinoma. It is postulated that an invasive cancer causes destruction of the involved ducts which prevents direct sampling of the malignant intraductal cells. Because ductal carcinoma in-situ (DCIS) does not disrupt the breast ductal structure, DL may yield a more representative cytologic sample in patients with DCIS. Methods: Ductal lavage was performed in the affected breast of 32 women undergoing mastectomy with preoperative diagnosis of DCIS. The lavage procedure was done in the operating room after induction of general anesthesia by cannulating a duct yielding fluid on the nipple and instilling saline which was then aspirated and sent for cytologic evaluation. A cytopathologist classified each sample as insufficient cellular quantity, benign, mild atypia, marked atypia, or malignant. Results: A successful lavage was obtained from 22 (69%) of 32 women undergoing DL in the operating room. Of these 22 cytology samples; 4(18%) had an insufficient cellular quantity, 4 (18%) had mild atypia, 6 (27%) had marked atypia, and 8 (36%) had malignant cells. Twenty one of these 22 women had DCIS in the surgical mastectomy specimen. Seven (32%) patients were found to have invasive ductal cancer in addition to DCIS on final pathology. Conclusions: Our results show that DL reveals markedly atypical or malignant cytology in 64% of patients with DCIS who underwent a successful lavage procedure. As an office procedure, DL may have the ability to obtain viable ductal carcinoma cells repeatedly over time in the same patient. Thus, DL may have an important role in patients with DCIS who are involved in window trial studies investigating response to medical treatments prior to surgical intervention. Further studies to evaluate the reproducibility of the ductal lavage results in patients with DCIS are needed to confirm these findings.
Adequacy of lung cancer tissue samples for ancillary molecular testing in conventionally obtained biopsy material: A 3-year experience of the Louisiana State University (LSU) public hospital in New Orleans.
Authors: Narmala Shravan Kumar , Boulmay Brian C. 
Published: February 2017

105 Background: The National Comprehensive Cancer Network recommends that all patients with lung adenocarcinoma (LA) be tested for EGFR mutation and ALK gene rearrangement (EGFR/ALK). Metastatic LA is diagnosed with biopsies often sufficient only for non-molecular based diagnostic techniques; our institutional experience suggested conventionally obtained material was inadequate for EGFR/ALK. We analyzed biopsies performed only with the intent of diagnosing malignancy for adequacy for EGFR/ALK. Methods: We identified patients from LSU diagnosed with metastatic LA whose specimens were sent for EGFR/ALK from January 1, 2009, to June 30, 2013. Data collected included number of specimens sent for EGFR/ALK, number of samples with inadequate tumor, biopsy technique utilized and number of rebiopsy attempts for EGFR/ALK. Results: 54 patients were evaluated in the study time period: 58 individual biopsy specimens were sent for EGFR/ALK. 24/58 (41%) of specimens were found to be inadequate for EGFR/ALK. 11/26 (42%) of bronchoscopically obtained biopsies were inadequate, 9/18 (50%) of computed tomography guided core needle (CTGCN) biopsies were inadequate and 4/14 (28%) samples obtained via thoracentesis, wedge resection, craniotomy, spinal tumor excision, fine needle aspiration of lymph nodes or video assisted thoracoscopic surgery were inadequate. 4/54 (7%) patients underwent rebiopsy, 3 via bronchoscopy and 1 via CTGCN; 3/4 (75%) rebiopsies were sufficient for EGFR/ALK analysis. Conclusions: A substantial proportion of initial LA diagnostic biopsies were inadequate for EGFR/ALK analysis. While EGFR/ALK analysis is now standard of care for patients with LA, only a small percentage of patients in our study underwent rebiopsy. Our institutional practice will be modified to encourage additional biopsies for the specific purpose of molecular testing at the time of initial biopsy for those with suspected LA.
Determining the need and utilization of radiotherapy in cancers of the breast, cervix, lung, prostate, and rectum in Alberta, Canada.
Authors: Shack Lorraine , Lu Shuang , Weeks Lee-Anne , Craighead Peter S. , Kerba Marc 
Published: February 2017

116 Background: Determining the appropriate rate of RT is important for health care planning and resource allocation. Establishing RT shortfalls (difference between observed and estimates of RT need) could provide an estimate of the capacity expansion that would be required to address them. Our primary objective was to determine the utilization of RT for cancers of the breast, cervix, lung, prostate and rectum in Alberta (AB), Canada. To determine the burden of RT shortfalls in AB, the secondary objective was to compare the observed AB RT rates to estimates of need derived from criterion-based benchmarking (CBB) and evidence-based estimates (EBEST). Methods: All incident cases of breast (B), cervix (C), lung (L), prostate (P) and rectal (R) cancers diagnosed in 2004-8 in AB were identified from the provincial cancer registry (ACR). Ethics board approval was obtained. Patients receiving RT within one year (RT-1y) of diagnosis were identified and grouped by cancer site. The proportion of cases receiving RT-1y was then calculated. Rates were compared using a Z statistic of the normal approximation for a difference in proportions. Estimates of the appropriate RT rate were derived from CBB and EBEST methods described in the literature. Results: A total of 68,164 cancer cases of interest were identified from the ACR. RT-1y rates for AB (95%CI) were: B: 50.5%(49.5-51.4), C: 45.7%(42.2-49.3), L: 36.5%(35.5-37.3), P:26.4%(25.6-27.3) and R:38.8%(37.1-40.6). Observed rates of RT in AB were lower than estimates derived using CBB and EBEST of RT-1y for B: 60.7%(59.3-62.1) and 57.1%(52.6-62.0), C: 48.6%(39.1-58.1) and 63.4%(61.1-65.7), L: 41.3%(39.9-42.7) and 44.6%(41.0-48.2), P: 37.2%(35.8-38.7) and 32.0%(28.4-36.0), and R: 43.4%(39.1-47.6) and 69.6%(68.7-70.5). Shortfalls varied across cancer sites according to whether CBB or EBEST estimates were referenced, ranging from 4.8% in lung cancer to 30.8% in rectal cancer. Conclusions: Important shortfalls exist in the utilization of RT in Alberta, Canada despite centralized cancer care and a publically funded health care system. The magnitude of the shortfall varied according to whether a CBB or EBEST estimate of RT was applied.
30-day readmission among gastrointestinal cancer patients in Texas.
Authors: Manzano Joanna-Grace , Luo Ruili , Elting Linda S. , Suarez-Almazor Maria 
Published: February 2017

121 Background: 30 day readmission has become an important metric in healthcare delivery. Policymakers have started to factor in readmission rates in their recommendations on reimbursement algorithms. It is unclear whether these methods are applicable to cancer patients. More studies are needed in order to understand readmission in the context of cancer patients. A few studies have found that the elderly and those with gastrointestinal (GI) malignancies are at risk. Methods: We conducted a retrospective cohort study using linked Texas Cancer Registry and Medicare claims data to describe the patterns of 30 day unplanned readmission among GI cancer patients in Texas. Only short stays to acute care hospitals were included in the study. Claims data were analyzed for a period of 2 years from the date of cancer diagnosis. Modified Poisson regression model was used to identify factors associated with the outcome. Results: 30,199 patients aged 66 and above were included in our study. The incidence of unplanned readmission in our cohort was 15%. The top 10 reasons for readmission were fluid and electrolyte disorders, secondary malignancies, complications of surgical procedures and medical care, congestive heart failure, intestinal obstruction, pneumonia, sepsis, GI hemorrhage, urinary tract infections, and complications of device, implant or graft. After multivariate analysis, age >80 (OR 0.79, 0.73-0.85), regional (1.19, 1.11-1.27) and distant disease (1.16, 1.07-1.25), living in less affluent neighborhoods (1.10, 1.01-1.19), and increasing comorbidity index (p<0.0001) were associated with 30 day readmission. Esophageal cancer carried the highest risk for 30 day readmission (1.53, 1.38-1.70). Conclusions: Most of the top reasons for readmission appear to be cancer-related. This means that most of these readmissions are likely not preventable. This should be taken into consideration by policymakers when making recommendations. There are, however, some that may be amenable to outpatient management. This further underlines the importance of primary care involvement in the management of cancer patients. Risk factors identified can help risk–stratify patients who may need early follow up post-discharge, in order to prevent early readmission.