tbuckley/cabot-search huggingface dataset:
Correlation of Notch1 expression with clinical characteristics, signaling biomarkers, and survival in breast cancer patients.
Authors: Aleksandra Filipovic, He Zhu, Antonio Pannuti, Ingrid Espinoza, Andrew Green, Lucio Miele
Journal: Journal of Clinical Oncology (2014)

1129 Background: Notch1 signalling plays an important oncogenic role in breast cancer and represents a therapeutic target amenable to targeting with small-molecule gamma secretase inhibitors and specific anti-Notch1 monoclonal antibodies. Canonical Notch1 signaling is mediated by nuclear Notch1 cleaved fragment. Some evidence suggests non-nuclear, non-canonical signalling from cytoplasmic or membrane Notch1. Current study aims to investigate the clinical relevance of Notch1 expression in invasive breast cancer. Methods: A well-characterised Nottingham Tenovus cohort of invasive breast cancers (n = 1078), with long-term follow up data, was analysed using immunohistochemistry for Notch1 (Santa Cruz, C-20). X-tile software was used to generate cut-off values for further correlation of the Notch1: nuclear (≥ 20% positive cells) and membrane/juxtamembrane staining (≥ 50% cells). Results: High Notch1 membrane staining was correlated with high grade (p = 0.001), size > 2cm (p = 0.001), ductal histotype, advanced disease stage (p = 0.044), triple negative phenotype (p = 0.001), HER2 positive status (p = 0.02), HER3 positivity (p = 0.019), basal cytokeratin CK5 expression (p = 0.001) and PI3K activity (p = 0.008). High membrane Notch1 predicted worse breast cancer specific overall survival at 25 years of follow up (p = 0.017). Conversely, nuclear Notch1 was predominantly present in lobular carcinomas and correlated inversely with the triple negative subtype ( p = 0.019) as well as PI3K (p = 0.014), thereby its higher expression was predictive of favourable survival outcome (p = 0.008). Conclusions: Different subtypes of breast cancer may rely on different Notch1 signaling pathways, including nuclear and non-nuclear signalling. For the first time, we emphasize the clinical relevance of Notch membrane expression in highly aggressive disease. Therefore, our findings bear significant translational relevance, as we propose that Notch1 membrane expression assessment may be used for stratification of patients who may derive particular benefit from anti-Notch1 monoclonal antibody therapy or other Notch inhibitors in the clinic.
The consistency of effect of ziv-aflibercept (Z) in the bevacizumab (B) pre-treated subgroup of patients (pts) in the velour trial stratified by first-line progression ≥ 9 months (mos) versus &lt; 9 mos.
Authors: Paulo Marcelo Hoff, Guy Van Hazel, David Cunningham, Dirk Arnold, Hans Schmoll, Albert J. Ten Tije, Sarah Naoshy, Florence Joulain, Joseph McKendrick, Raghu L. Vishwanath, Emmanuelle Dochy, Edith P. Mitchell
Journal: Journal of Clinical Oncology (2014)

3639 Background: The addition of B to an oxaliplatin-based regimen in 1st line metastatic colorectal cancer (mCRC) pts has shown a median progression free survival (PFS) of 9.4 mos as seen in NO16966. In the ML18147 study, the benefit of B added to chemotherapy (CT) in 2nd line mCRC following 1st line CT + B combinations, was evaluated in pts pre-stratified by 1st line PFS ≤9 mos and >9 mos. We evaluated the consistency of the treatment effect of Z+FOLFIRI (F) vs placebo (P)+F according to the timing of progression from 1st line therapy (<9 mos vs. ≥9 mos) in the subgroup of pts treated with an oxaliplatin containing regimen and B in 1stline from VELOUR (NCT00561470). Methods: In VELOUR, 186 pts in the Z+F and 187 in the P+F groups were stratified to prior B. There were 17 pts (9 in Z+F and 8 in P+F arm) who experienced recurrence during or within 6 mos of completing adjuvant oxaliplatin-based therapy – (a population excluded from ML18147), who were excluded from this analysis. The prior B treated subgroup was analyzed by the timeframe of 1stline progression ([PFS] ≥9 vs <9 mos) in this post-hoc analysis. Hazard Ratio (HR) was adjusted on the baseline value of: Performance Status, prior B, age, hypertension, and number of metastatic organs. Results: Z+F had an overall survival (OS) benefit in B pre-treated pts both with 1st line PFS ≥9 mos and in pts with 1stline PFS < 9 mos, as shown by the median difference (MD) in OS (Table). A similar benefit was observed with PFS. Conclusions: In this post hoc analysis, pts benefited from Z+F therapy regardless of the timing of their 1st line progression <9 months or ≥9 months on a 1st line oxaliplatin + B containing regimen. Clinical trial information: NCT00561470. Prior B Subgroup P+F [95% CI] N = 168 Z+F [95% CI] N=161 Median difference (mo) HR [95% CI] 1st line PFS ≥9 mos Pts, n 92 86 Median OS, mos 14.23 [11.6; 18.9] 17.94 [14.5; 21.5] 3.71 aHR 0.772 [0.52; 1.15] Median PFS, mos 4.24 [3.9; 5.5] 7.26 [6.5; 8.7] 3.02 aHR 0.588 [0.391; 0.89] 1st line PFS <9 mos Pts, n 76 75 Median OS, mos 7.11 [5.2; 10.3] 9.92 [7.3; 11.4] 2.81 aHR 0.825 [0.57; 1.18] Median PFS, mos 2.79 [2.5; 3.2] 5.65 [3.9; 7.2] 2.86 aHR 0.57 [0.39; 0.83]
Multidisciplinary team (MDT) care by neuroendocrine tumor (NET) type: Results from the first global NET patient (pt) survey—A collaboration between the International Neuroendocrine Cancer Alliance (INCA) and Novartis.
Authors: John Leyden, Grace Goldstein, Maia Sissons, Teodora Kolarova, Edward M. Wolin
Journal: Journal of Clinical Oncology (2015)

e17738 Background: International guidelines support an MDT approach to NETs. The impact of MDT care on NET pts has not been examined globally. We present global data on the NET pt perspective regarding MDT care by tumor type. Methods: In 2014 a survey on the NET pt experience involving NET pts from > 12 countries (Americas, Asia, Europe, Oceania) was conducted by Hall & Partners on behalf of INCA/Novartis and funded by Novartis. Comparisons significant at P< .05. Results: 1928 pts participated (54% gastrointestinal [GI] NETs; 22% pancreatic NET [pNETs]; 12% lung NETs). 63% reported visiting a specialty center (mean 4.3 visits/y) but only 18% were diagnosed there. Notably, more pts diagnosed < 5 y ago received their diagnoses at a specialty center (20%) than those diagnosed ≥5 y ago (16%). GI/pNET pts (65%/70%) were more likely than lung NET pts (45%) to visit a specialty center, and pNET pts (30%) were more likely than GI/lung NET pts (15%/10%) to be diagnosed at a specialty center. Consistent with overall findings, a mean of 3 health care providers (HCPs) were involved in ongoing management of pts with GI, lung, and pNETs. Those who visited a specialty center ≥1 time/y saw more HCPs, received a wider range of tests, had more access to treatments, and were more likely to participate in clinical trials. Overall, GI/pNET pts underwent more tests/y (mean 5.2/6.5) than lung NET pts (mean 4.1), were less likely to regard quality of available treatments as poor or very poor (GI/pNET, 26%/27%; lung NET, 36%), and were more likely to participate in clinical trials (GI/pNET, 48%/47%; lung NET, 29%). While pts visiting (vs not visiting) specialty centers were better able to get answers to questions (63% vs 54%) and felt they had sufficient information (54% vs 45%), GI/pNET pts were more satisfied with getting answers and sufficient information (63%/60% and 53%/52%; lung NET, 44% and 36%) and less likely to express the need for immediate access to HCPs experienced with NETs (53%/45%; lung NET, 64%). Conclusions: This survey demonstrated differences in MDT impact on NET pts (overall and based on NET type) and identified the need for improvements.
Success and failure rates of tumor genotyping techniques in routine pathologic samples with non-small cell lung cancer.
Authors: Paul A VanderLaan, Norihiro Yamaguchi, Erik Folch, Michael S Kent, Sidharta P Gangadharan, Adnan Majid, Michael Goldstein, Mark Huberman, Daniel Botelho Costa
Journal: Journal of Clinical Oncology (2013)

8050 Background: Identification of somatic molecular alterrations in NSCLC has become evidence-based practice. The success and failure rate of using commercially-available tumor genotyping techniques in routine day-to-day NSCLC pathology samples is not well described. We sought to evaluate the success and failure rate of EGFR mutation, KRAS mutation and ALK FISH. Methods: Clinicopathologic data, tumor genotype success and failure rates were retrospectively compiled and analyzed from 381 patient-tumor samples sent for routine tumor genotype in clinical practice. Results: Mean age was 65, 61.2% women, 75.9% white, 27.8% never-smokers, 73.8% had advanced NSCLC and 86.1% adenocarcinoma histology. Tumor tissue was obtained from surgical biopsies in 48.8%, core biopsies in 17.9% and as cell blocks from aspirates/fluid in 33.3%. Anatomic sites for tissue collection included lung (49.3%), lymph nodes (22.3%), pleura (11.8%), bone (6.0%), brain (6.0%), among others. In the 207 tumors in which the three tests were ordered concurrently, the success rate for EGFR was 92.3%, for KRAS 91.8% and for ALK FISH 89.9%. The highest failure rates were observed when the tissue was obtained from core biopsies (30.8%, 20.5% and 30.8% for EGFR, KRAS and ALK tests, respectively) and bone specimens (23.1%, 15.4% and 23.1% for EGFR, KRAS and ALK tests, respectively). In specimens obtained from bone, the failure rate was significantly higher in non-surgical than surgical specimens (40% vs 0%, p=0.024 for EGFR) and decalcified than non-decalcified samples (60% vs 5.5%, p=0.021 for EGFR). Conclusions: The success rate of multiple tumor genomic analyses techniques for EGFR, KRAS and ALK gene abnormalities using routine lung cancer tissue samples was ~90%. The highest failure rates occurred in tumors obtained from core biopsies and in bone samples from core biopsies with decalcification; specimens that may need to be scrutinized before submission to molecular studies. Tumor genotype techniques are feasible in most other samples obtained with current tumor acquisition methods, and therefore expansion of routine tumor genotype into the care of patients with NSCLC may not require special tissue acquisition or manipulation.
The effect of changes in the treatment paradigm for chronic lymphocytic leukemia: A tumor registry study
Authors: S. Waheed, B. McClune, F. Buadi, K. Wright, D. Przepiorka
Journal: Journal of Clinical Oncology (2006)

16000 Background: In the early 1990s, several new agents became available for treatment of chronic lymphocytic leukemia (CLL), leading to a shift in the treatment paradigm with the hope of improving long-term survival. To determine if that outcome has been achieved, we performed a retrospective analysis of survival of patients in our community. Methods: The hospital tumor registry was queried to identify patients with CLL diagnosed 1980 to 2004. Zip code at diagnosis was used to assign a median household income based on census data. Survival was estimated by the method of Kaplan and Meier. Comparisons between the two groups were made by chi square. Hazard ratios for mortality were calculated in a Cox proportional hazard model using a backward stepping procedure retaining factors having a p-value &lt; 0.1. Results: There were 192 patients with a diagnosis of CLL for analysis. The study cohort was comprised of 58% males and 42% females of median age 67 years (range, 39–96 years) at diagnosis. Fifty-three (28%) were &lt;60 years of age, 29% were 60–69 years old, 26% were 70–79 years old, and 18% were &gt;79 years at diagnosis. The group was 71% caucasian and 29% African American. Seventy-five (39%) patients had a household income greater than the median for the state, and the remainder had lesser incomes. There was a significant increase in the proportion of African Americans diagnosed &gt;1990 compared to those diagnosed ≤1990 (40% vs 19%, p = 0.002), but there were no differences between time periods in gender, age, age category or income category. On multivariate analysis, factors predicting mortality differed between time periods as shown in the table. Median survival was 4.0 years for all patients, 3.9 years for the early group and 4.1 years for the later group (p = NS). Conclusion: We conclude that with changes in the treatment paradigm for CLL, gender and race are no longer prognostic for mortality, and the relative hazard for death is less amongst those 60–69 years and &gt;79 years old, but there is no difference in survival for patients overall. [Table: see text] No significant financial relationships to disclose.
How are quality of life and work productivity associated with living longer with HER2+ metastatic breast cancer?
Authors: Preeti S. Bajaj, Matthew Sussman, Jeffrey Yu, Carolina M. Reyes, Alisha Stein, Catherine Lai, Musa Mayer, Sara A. Hurvitz, Debu Tripathy
Journal: Journal of Clinical Oncology (2017)

215 Background: Advances in therapy have led to an increase in survival in women with HER2+ metastatic breast cancer (MBC). However, changes in health-related quality of life (HRQoL) and productivity related to longer survival have not been well studied. Methods: A one-time survey was administered to women recruited through select clinics and advocacy organizations. Inclusion criteria were female sex, age 18+, US residence, and having HER2+ MBC. HRQoL and impact on productivity were assessed using several validated instruments: EQ Visual Analogue Scale (EQ VAS), Functional Assessment of Cancer Therapy-Breast (FACT-B), Rotterdam Symptom Checklist (RSCL), Distress Thermometer (DT), PROMIS Applied Cognition-Abilities-8a, and Work Productivity &amp; Activity Impairment Questionnaire-Specific Health Problem (WPAI-SHP). Regression analyses were conducted to compare differences in measures by years since diagnosis (&lt; 6 vs. ≥ 6 years), adjusting for age. Results: A total of 404 women participated in the survey. Mean age was 54.2 years, 91.6% were white, and 27.5% reported it had been ≥ 6 years since their HER2+ MBC diagnosis. In unadjusted analyses, women living with MBC ≥ 6 years reported significantly greater HRQoL (FACT-B, p=0.01) and emotional well-being (FACT-B EWB, p&lt;0.01), lower distress (DT, p = 0.02; RSCL Physical &amp; Psychological Symptom Distress, p = 0.01 &amp; p = 0.03), and lower impairment due to MBC (WPAI-SHP, p&lt;0.05). No differences were seen in EQ VAS or PROMIS scores. In age-adjusted analyses, women living with MBC ≥ 6 years had significantly greater emotional well-being (FACT-B EWB, p&lt;0.01), lower distress (DT, p&lt;0.05; RSCL Physical Symptom Distress, p = 0.03), and lower activity impairment due to breast cancer (WPAI-SHP, p&lt;0.01). There were no major differences in findings between women recruited online versus in clinics. Conclusions: Women living with HER2+ MBC for ≥ 6 years may experience improvements in HRQoL compared to women diagnosed more recently. This may suggest that women adjust to the disease over time; however, potential selection biases in the recruitment of survey respondents may limit generalizability of these findings. Further investigation of temporal changes in HRQoL is warranted.
Efficacy of HSV-TK<sup>+</sup> suicide gene donor lymphocytes after haploidentical transplantation (haplo-HSCT): Preliminary results of randomized TK008 study.
Authors: Fabio Ciceri, Chiara Bonini, Arnon Nagler, Evangelia Yannaki, Maria Teresa Lupo Stanghellini, Attilio Bondanza, Giacomo Oliveira, Raffaella Greco, Eduardo Olavarria, Eva M Weissinger, Michael Stadler, Donald Bunjes, Dietger Niederwieser, Lutz Uharek, Wolfgang Bethge, John DiPersio, Michele Donato, Andrew Pecora, Antonio Lambiase, Claudio Bordignon
Journal: Journal of Clinical Oncology (2014)

7003 Background: Haploidentical family donors represent the ideal solution to offer for every patient with high risk leukemia the potential cure of hematopoietic stem cell transplantation. Extensive application of haplo-HSCT is limited by high rate of late transplant related mortality (TRM) and relapse associated with the inadequate immune reconstitution (IR) due to ex vivo T cell depletion or in vivo post-transplant cyclophosphamide administration for severe graft-vs-host disease (GvHD) prevention. Methods: In a haplo-HSCT phase III trial (TK008, NCT00914628), we infuse donor lymphocytes genetically engineered to express the suicide gene herpes simplex thymidine kinase (TK cells) to induce early IR after a T cell depleted graft. Key inclusion criteria are acute leukemia at high risk in patients lacking an HLA-matched donor. Control arms include T cell depleted or post HSCT cyclophosphamide haplo-HSCT. We enrolled 25 patients in 8 centres in Europe and US; 17 were assigned to experimental arm, 15/17 were in complete remission at HSCT. Hypothesis testing: 1-year disease free survival (DFS) 30% (control) vs 52% (TK arm). Results: Results are presented only for patients enrolled in the experimental arm at November 2013 last follow-up. TK cells were given to 13 patients; IR was obtained in 9/13 patients after a median of 2 TK cell monthly infusions; median time from last infusion to IR (CD3+>100/µL) was 28 days (95% CI 24-41). Six pts developed GvHD (2 grade I, 2 grade II and 2 grade III) that was always abrogated by suicide gene induction; no progression from acute to chronic GvHD and no GvHD-related death occurred. IR obtained with TK cell infusion correlated with rapid development of a wide T cell repertoire and detection of high frequencies of T-cells specific for opportunistic pathogens. At a median follow-up of 473 days, by ITT analysis, 1-year overall survival is 89% (+ 10), DFS and immunosuppression-free survival is 80% (+ 10), 1-year TRM is 11% and relapse incidence is 8%. Conclusions: Preliminary results of this ongoing phase III trial confirm safety and potential benefit in improving survival of the T-cell gene transfer technology integrated with T cell depleted haplo-HSCT. Clinical trial information: NCT00914628.
Association between triglyceride (TG) levels, other clinical characteristics, and outcomes in patients with advanced non-small cell lung cancer (NSCLC) treated with erlotinib and bexarotene
Authors: K. H. Dragnev, J. C. Cyrus, J. R. Rigas, W. M. DiSalvo, E. Dmitrovsky
Journal: Journal of Clinical Oncology (2009)

8101 Background: Studies of the nonclassical retinoid bexarotene (B) alone or in combination with chemotherapy have revealed improved survival for a subset of NSCLC patients (pts) who developed hypertrigyceridemia despite treatment with antilipid agents. It is not known if a similar association exists when B is combined with a targeted agent. We have completed 2 trials of erlotinib (E), and B, in pts with advanced NSCLC showing minimal toxicities and evidence of clinical activity. In both trials atorvastatin was begun only after elevated TG were detected. This approach differed from other studies where statin therapy was initiated concurrently with B. Methods: E 150 mg and B 400 mg/m2 were administered daily orally to pts with stage IV NSCLC, mostly as third line or higher. Atorvastatin 20 mg was started for elevated fasting TG. The dose was increased to 40 mg if hypertriglyceridemia persisted, followed by the addition of fenofibrate and/or dose reductions of B to 300 mg/m2. TG levels assessed in the first 4 weeks were correlated with overall survival. The appearance of skin rash was documented. Results: Sixty-one pts with stage IV NSCLC were enrolled, 54% women and 72% with adenocarcinoma, 15% never smokers, 20% current smokers, 15% had prior anti-EGFR therapy. Median survival time (MST) was 22 (1–274) wks (intent-to-treat). For pts with elevated TG, the MST was 24 (1–274) wks, while for pts with normal TG the MST was 21 (4–72). There was a statistically significant correlation between TG levels and survival, Spearman's correlation coefficient 0.48, p=0.0003. We will present the analysis of the association between outcomes and other clinical characteristics. Conclusions: Development of hypertriglyceridemia in the first 4 weeks of therapy with E and B in the absence of antilipid treatment is associated with increased overall survival. These findings implicate clinical benefit of dual targeting of EGFR and cyclin D1 especially in a subset of NSCLC pts with elevated TG early in therapy. Further work to identify the molecular basis for this association is needed to allow selection of pts more likely to benefit from this combined therapy. [Table: see text]
Utilization of low-cost and high-cost imaging in cancer care.
Authors: Thomas C. Soong, An-Chen Feng, Chung-Jen Huang, Yong Alison Wang, Yu-Yi Huang
Journal: Journal of Clinical Oncology (2014)

e17518 Background: Medical advances have pushed up the cost of cancer care. We examine the utilization patterns of low-cost and high-cost imaging by cancer types and cancer care phases Methods: We identified 9029 stage 0-III breast, colorectal, liver or lung cancer patients who were diagnosed and treated with curative intent between Jan 2003 and Dec. 2010. The proportion of these patients imaged and yearly imaging rate per patient, of low-cost imaging (X-ray, ultrasound), and high-cost imaging (computed tomography, magnetic resonance imaging, positron emission tomography - computed tomography, and bone scan) were calculated by cancer types and by cancer care phases (diagnosis-to-treatment phase, continuing care phase, and long-term follow-up phase). Results: The proportion of patients using low-cost imaging remained high at 99.1% in the diagnosis-to-treatment phase, 95.5% in the continuing care phase, and 92.8% in the long-term follow-up phase. The proportion of patients using high-cost imaging decreased from 64.5% to 62.6, then to 44.3% across the three care phases. In the breast cancer group, the imaging use rate peaked in the long-term follow-up phase and ultrasound was mostly used. In the colorectal, liver, and lung cancer groups, images were most frequently used in the diagnosis-to-treatment phase and CT scan was the mostly used high-cost imaging. Conclusions: Deviation from guidelines is observed in the use of low-cost and high-cost imaging, with more than recommended use of ultrasound in breast cancer group, and fewer than recommended use of CT in colorectal, liver and lung cancer groups.