tbuckley/cabot-search huggingface dataset:
Pregnancy outcomes in women with cancer.
Authors: Andrea Milbourne, Charlotte C. Sun, Michelle A. Fanale, Richard L. Theriault, Sue A Rimes, Jennifer Keating Litton, Mildred M. Ramirez
Journal: Journal of Clinical Oncology (2012)

6116 Background: Parenthood after cancer is a critical concern for many cancer patients (pts). Pregnancy (prg) during cancer is an emotional time for about 1/1000 pregnant women. No randomized controlled studies exist examining the impact of cancer treatment (tx) on the developing fetus nor on the woman with cancer. Methods: From 2002-2011, women presenting for cancer tx during prg were approached for this IRB-approved prospective database study. All pts provided written consent. Results: To date 143 pts are evaluable. The median age at diagnosis was 32.1 years and median gestational age (GA) at enrollment was 18.2 weeks. 95/143 (66.4%) are White, 19 (13.3%) are African American, 17 (11.9%) are Hispanic and 12 (8.4%) are Asian/Other. Primary cancers included breast (n=59, 41.3%), hematologic (n=29, 20.3%), melanoma (n=13, 9%), GYN (n=11, 8%), GI (n=8, 5.6%), head/neck (n=7, 6%) and other (n=16, 11%) (brain=4, GU=1, thyroid=3, head/neck=7, thoracic=1, sarcoma=6, unknown primary=1). 111/143 (77.6%) of prgs resulted in live births. Median birth weight was 6.5 lbs. Median follow-up time for pts was 32.3 months. To date, 3/19 pts who terminated prgs have died (1.6%). Most terminations occurred in the 1st trimester. To date, 79 pts (55.2%) are NED and 23 pts have died; of these 19 (1.7%) had live births. No major malformations were observed in the 74/143 (52%) of pts who received chemotherapy (CTx) during pregnancy. 57% received FAC/FEC; other regimens included ABVD (n=5), cytarabine (n=5), CHOP/R-CHOP, and platinum-based regimens. Median GA at the start of CTx was 19.7 wks. Median number of CTx cycles during prg was 4. Other pts underwent surgery (n=32), no tx (n=14), deferred tx until after delivery (n=17), radiation (2), transplant (3), other (1). Conclusions: Cancer diagnosis during prg is compatible with successful tx and prg outcome. Cancer tx during the 2nd and 3rd trimester can be safely given and in our pts did not result in adverse prg outcomes. Tx during the 1st trimester is usually not recommended. Thus cancer pts in their 1st trimester need to be extensively counseled about their disease as well as about the risks to the prg. In our pts continuation or termination of prg were not associated with an increased risk of death.
The DETECT Study Program: Personalized treatment in advanced breast cancer based on circulating tumor cells (CTCs).
Authors: Amelie Schramm, Thomas W. P. Friedl, Susanne Albrecht, Jens Bodo Huober, Brigitte Kathrin Rack, Elisabeth Katharina Trapp, Peter A. Fasching, Florin-Andrei Taran, Andreas D. Hartkopf, Andreas Schneeweiss, Volkmar Mueller, Bahriye Aktas, Klaus Pantel, Franziska Meier-Stiegen, Wolfgang Janni, Tanja N. Fehm
Journal: Journal of Clinical Oncology (2015)

TPS11109 Background: The prognostic value of circulating tumor cells (CTC) in metastatic breast cancer (MBC) has been repeatedly shown, but potential implications of CTC presence and CTC phenotypes for treatment decisions are still not well understood. The main aims of the DETECT study program are to evaluate efficacy of individualized breast cancer treatments based on presence and phenotype of CTCs, and to investigate the role of CTCs in predicting specific treatment responses. Methods: In the phase III study DETECT III women with HER2-negative MBC but HER2-positive CTCs are randomized to physician´s choice therapy (single-agent endocrine or single-agent chemotherapy) with or without HER2-targeted therapy with lapatinib. The phase II study DETECT IV offers two treatment options for women with HER2-negative MBC and only HER2-negative CTCs. Patients with hormone-receptor positive MBC receive endocrine therapy plus everolimus, and patients with triple-negative MBC or hormone-receptor positive MBC plus indication for chemotherapy receive cytostatic treatment with eribulin. In the phase IIIa study DETECT V, women with HER2-positive and hormone-receptor positive MBC are treated with either endocrine therapy or chemotherapy added to a dual HER2-targeted backbone treatment with trastuzumab and pertuzumab. Clinical efficacy will be estimated by CTC clearance and progression-free survival in DETECT III and DETECT IV. As the focus of DETECT V is on the comparison of safety and quality of life between the two treatment arms, primary and main secondary endpoints are rate of adverse events and quality-adjusted survival (Q-TWiST method). Translational research projects try to identify additional predictive markers of therapy response by molecular characterization of CTCs. Therefore, prevalence of CTCs using the FDA-cleared CellSearch System (Janssen Diagnostics, LLC) and their HER2 status is determined. As of January 2015, more than 1100 patients have been screened for CTCs, making the DETECT study program the worldwide largest trial for MBC. The results will provide crucial information regarding suitability of CTCs as liquid biopsy to guide more individualized therapy decisions. Clinical trial information: NCT01619111/NCT02035813/NCT02344472.
Geriatric high-grade soft tissue sarcoma (G-HG STS): An analysis of 116 patients (pts) evaluating prognostic factors and clinical outcomes stratified by histology.
Authors: Richard Hong Hui Quek, Mohamad Farid Rin Harunal Rashid, Summer Pan, Mann Hong Tan, Leon Siang Shen Foo, Kesavan Sittampalam, Alisa Sairi, Kiraely Adam, Widayana Hanafi, Soon Thye Lim, Kevin Tay, Lay-Tin Soh, Francis Chin, Melissa Teo, Donald Poon
Journal: Journal of Clinical Oncology (2012)

10051 Background: STS in geriatric pts is not well studied. We evaluated prognostic factors and clinical outcomes in elderly pts with HG STS. Methods: Single centre retrospective study. G-HG STS pts defined as age &gt; 65 yrs seen in our centre from 2002 - 2011 with complete medical records were identified. Charlson age-comorbidity score was assessed for each pt. Results: 116 pts from 4 most common HG STS histo-types representing 69% of pts in the geriatric STS cohort were analysed; leiomyosarcoma (LMS, 14%), non well-differentiated liposarcoma (nWD-LPS, 9%), angiosarcoma (AS, 30%), and undifferentiated pleomorphic sarcoma (UPS, 47%). Median age was 72 yrs, 81% presented with localised disease; of 78% of these localised pts who had curative surgery, 49% received adjuvant therapy, of whom 92% had radiotherapy (RT) only. AS arises more commonly from the head/neck region (p&lt;0.001) and fewer receive curative surgery (p=0.006). In 43 pts who had metastases either at diagnosis or relapse, 33% received first-line palliative chemotherapy with a response rate of 27% in evaluable pts. At a median follow-up of 15.8 mths, overall survival (OS) for the entire cohort was 25.1 mths, 30.5 vs 3.9 mths in pts presenting with localised vs metastatic disease respectively (p&lt;0.0001). In pts who had curative surgery for localised disease, overall relapse-free survival (RFS) was 17.7mths; 26.8 mths vs 16.0 mths vs 7.3 mths vs 12.5 mths in LMS, nWD-LPS, AS and UPS respectively. In univariate analysis, adjuvant RT, non-head/neck primary and sarcoma subtype were associated with improved RFS. In multivariate analysis, adjuvant RT (p&lt;0.001), sarcoma subtypes AS (p=0.011) and UPS (0.012) vs LMS remained significant. In pts with metastatic HG STS either at diagnosis or relapse, overall median OS was 5.9 mths; 5.9 mths (LMS), 30.5 mths (nWD-LPS), 6.4 mths (AS) and 4.3 mths (UPS). In univariate analysis, presence of bone metastases was significantly associated with inferior OS (p=0.0029). Charlson score did not correlate with RFS or OS. Conclusions: Prognosis of G-HG STS appears poor particularly in AS and UPS. Adjuvant RT improves outcomes in this group of pts and should not be omitted based on age alone.
Oncology providers' perspectives on endocrine therapy prescribing and management.
Authors: Stephanie B. Wheeler, Megan Roberts, Diane Bloom, Katherine Elizabeth Reeder-Hayes, Jeffrey M. Peppercorn, Carol Golin, Jo Anne Earp
Journal: Journal of Clinical Oncology (2015)

e20645 Background: Adjuvant endocrine therapy (ET) plays an important role in reducing risk of recurrence among women with hormone receptor positive breast cancer. Although the literature suggests initiation and adherence to ET is suboptimal, the reasons for this finding are not well documented. The goal of our study was to better understand issues around ET prescribing and patient management from oncology providers’ perspectives. Methods: Using purposive sampling aided by key stakeholders and web searches, we recruited oncology providers (oncologists, surgeons, oncology nurses) who treated breast cancer patients. We conducted 30-45 minute, in-depth, telephone interviews with 20 providers, using a semi-structured guide to explore in-depth their perspectives on barriers and facilitators to ET use. We used thematic content analysis to identify categories of meaning and double-coded all transcripts using Atlas.ti. Results: Providers recommend ET to all eligible patients except those with medical contraindications or other risk factors. They believe it is an integral part of treatment--even more beneficial than chemotherapy in most cases. Providers based their ET prescribing decisions on patients’ menopausal status, estrogen positivity, side effects, and co-morbidities (e.g., blood clots, osteoporosis). Oncologists typically discussed ET multiple times, introducing the idea at the onset of breast cancer treatment and again in more detail after other treatments were completed. They expressed that the most compelling argument to clearly communicate to patients is the amount of reduction in recurrence risk associated with taking ET. Providers reported that non-initiation was a rare occurrence, but that non-adherence was much more of a problem, often due to unresolvable side effects. Conclusions: From the perspective of clinicians managing ET for breast cancer, side effects from these treatments represent the dominant factor in non-adherence. Efforts to improve adherence should focus on strategies to minimize side effects and optimize side effect management. This finding has important implications for novel endocrine regimens that offer improved outcomes through longer duration or more intensive therapy.
Panitumumab antitumor activity in patients (pts) with metastatic colorectal cancer (mCRC) expressing low (1–9%) or negative (&lt;1%) levels of epidermal growth factor receptor (EGFr)
Authors: J. Hecht, E. Mitchell, J. Baranda, I. Malik, D. Richards, L. Navale, P. D’Avirro, R. Amado
Journal: Journal of Clinical Oncology (2006)

3547 Background: Panitumumab is a fully human monoclonal antibody directed against EGFr. We investigated the antitumor activity of panitumumab in pts with mCRC who failed prior therapy and had low or negative EGFr tumor expression. Methods: In this multicenter, phase 2 study of 150 planned pts, pts had documentation of disease progression (PD) during or after adequate doses of fluoropyrimidine, irinotecan, and oxaliplatin (centrally confirmed refractory disease [CCRD]), 2–3 prior regimens, ECOG score 0–2, and low or negative EGFr staining (by IHC) in evaluable tumor cells. Pts received panitumumab at 6 mg/kg Q2W until PD or drug intolerability. Tumor assessments (modified WHO, blinded central review) were taken periodically from wk 8 until PD. Endpoints were objective response (OR) through wk 16 (+ ≥ 4 wk confirmation; primary) and OR throughout study, response duration, progression-free survival (PFS) time, survival time, and safety (secondary). Results: In this interim analysis (6/05), 88 pts were enrolled and had ≥ 1 dose of panitumumab (safety set); 23 pts had ≥ 20 wks before the cutoff and CCRD (efficacy set). The efficacy set consisted of 16M/7W, median age of 65 (range: 46, 85) yrs, 83% white, 100% with ECOG ≤ 1, 74% colon cancer and 26% rectal cancer; all received ≥ 2 prior regimens (equivalent characteristics for safety set). 2/11 (18%) pts with EGFr-negative tumors and 1/12 (8%) with low EGFr staining had a partial response. Duration was up to 16 wks. 7/23 (30%) of all pts had SD. Median (95% CI) PFS was 7.9 (7.0, 23.0) wks. In the safety set, all pts had a treatment-related adverse event; 19% grade (gr) 3; 2% gr 4. Integument and eye toxicities were: 92% skin, 17% eye, 28% nail, 8% hair, and 2% chelitis. 20 (23%) had diarrhea (1 gr 3); 7 (8%) had hypomagnesemia (2 gr 3/4). Three pts had an infusion reaction-1 gr 3 (led to panitumumab discontinuation) and 2 gr 1/2. In 65 pts with both a baseline and post-baseline sample, no human anti-human antibodies to panitumumab were detected. Updated data will be presented. Conclusions: Responses to panitumumab were seen in pts with mCRC with both low and negative EGFr levels. Efficacy appears similar to that in other studies with panitumumab in pts with higher EGFr tumor levels. [Table: see text]
MIRACLE study (CBCSG016): A randomized phase II study of letrozole versus letrozole plus everolimus for hormone receptor positive premenopausal women with recurrent or metastatic breast cancer on goserelin treatment after progession on tamoxifen.
Authors: Binghe Xu, Donggeng Liu, Jinsong Lu, Tao Ouyang, Xiang Li, Ying Fan
Journal: Journal of Clinical Oncology (2015)

TPS623 Background: In premenopausal women with HR-positive advanced breast cancer, ovarian function suppression combined with aromatase inhibitors is a standard first-line choice of hormone treatment, especially patients progressed after tamoxifen. An emerging mechanism of endocrine resistance arose from aberrant signaling through the phosphatidylinositol 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) signaling pathway. The BOLERO-2 study showed that the addition of everolimus, an mTOR inhibitor, to exemestane significantly improved PFS in postmenopausal HR+/HER2- advanced breast cancer patients progressed on NSAIs. However, different from western countries, the majority (50-55%) of patients are premenopausal women in Asia, including China. The benefits of everolimus plus endocrine therapy in premenopausal women have not yet been well delineated. In addition, the feasibility of patients progressed on the endocrine continue to receive the same endocrine agent plus everolimus is unclear. Methods: ...
A prospective evaluation of the attitudes of patients, physicians and nurses using a computer-assisted quality of life instrument (LCSS-QL) in a multicenter clinical trial in non-small cell lung cancer (NSCLC)
Authors: R. J. Gralla, P. J. Hollen, N. Leighl, J. M. Meharchand, H. Krieger, H. Solow
Journal: Journal of Clinical Oncology (2006)

6123 Background: The LCSS has been computerized (LCSS-QL) for inexpensive hand-held devices (pocket-pc) to enhance feasibility, provide immediate results, and automatically record data. Correlation coefficient between paper form and electronic version is excellent (r=0.93). This analysis determines the acceptability and value of LCSS-QL assessed by patients and health care professionals. Methods: NSCLC patients utilized LCSS-QL in a clinical trial and also completed a form evaluating their experiences after their first and third treatment cycles. All received docetaxel and platinum. Eleven physicians and nurses administered LCSS-QL and completed an evaluation form. The evaluation included: time required, satisfaction with the process, value of assessment, impact on communication, resource utilization. Results: The evaluation form was completed by 126 patients (cycle 1) and 94 (75%) completing cycle 3. Baseline characteristics: Stage III/IV 29/71%; median KPS 80%; 56% male; median age 69 yrs. Results are in the table : All physicians considered their time per patient was not lengthened and 80% felt that QL evaluation could save time. 67% of nurses felt the instrument could save time, while 83% felt that their time with patients was lengthened. Utilization: 67% of professionals reported QL evaluation would identify earlier patients not benefiting from chemo; 91% were more aware of pain issues. Conclusions: Patients and health-care professionals found using a validated QL instrument in a computerized form via a hand-held device was easy, added value and satisfaction while enhancing communication and awareness of PRO issues. This electronic format added no physician time. These results indicate that this QL evaluation method should be used more frequently in clinical trials and patient management. Supported in part by a grant from Sanofi-Aventis Canada, Laval, QC. [Table: see text] [Table: see text]
Demographic and clinical characteristics of patients with metastatic colorectal cancer (mCRC) associated with <i>RAS</i> testing from 129 million covered lives.
Authors: Bruce A. Bach, Alexandra Christodoulopoulou, Andrew Klink, Guy Hechmati, Urvi Mujumdar, Bruce A. Feinberg, Marwan Fakih
Journal: Journal of Clinical Oncology (2017)

739 Background: Guidelines for the treatment of patients with metastatic colorectal cancer (mCRC) recommend that all tumors be tested for RAS mutations to identify patients who will most benefit from chemotherapy regimens with biologic agents. The aim of this study was to describe characteristics of patients captured by a large national health claims database who were tested vs those who were not tested for RAS mutations and to identify potential predictors of RAS testing. Methods: Patients with mCRC diagnosed from 2012–2014 (ICD-9 codes 153.x, 154.0x, or 154.1x and 197.x–198.x) were identified from a US healthcare claims database consisting of 129 million unique covered patient lives. Patient demographics and baseline clinical characteristics were compared between patients who were and were not tested for RAS mutations (identified by CPT codes) using chi-square and t-tests. Odds ratios (ORs) were estimated for potential predictors by fitting multivariate logistic regressions to adjust for patient characteristics. Results: Of the 4,527 mCRC patients identified (mean age at diagnosis, 61.2 years; 54% male); 39% (n = 1,787) had a claim for RAS testing during the study period. Patients tested had similar mean age and comorbidity index at diagnosis compared to those not tested (60.8 vs 61.5 years, P = 0.06; 3.98 vs 3.90, P = 0.47). A greater proportion of RAS-tested patients were commercially insured compared to those not tested (37% vs 26%, P &lt; 0.01). Adjusted for other patient characteristics, patients with commercial insurance (OR: 1.62 [95% confidence interval–CI: 1.41–1.87]), metastases to viscera (OR: 1.61 [95% CI: 1.42–1.84]), or diagnosis of colon primary site compared to rectum (OR: 1.32 [95% CI: 1.16–1.51]) had increased odds of receiving RAS testing; all P &lt; 0.01. Conclusions: These observational data show that mCRC patients with commercial insurance, metastases to viscera, and colon cancer have a higher probability of being tested for RAS mutations. Overall, the data suggest that RAS status is underdetermined, with certain subgroups appearing to be more likely to be tested than others.
VEGF-A 165 family of isoforms as predictive biomarkers in patients with nonsquamous non-small cell lung cancer (NSCLC) treated with bevacizumab.
Authors: Jesus Garcia-Foncillas, Manuel Domine, Federico Rojo, Tatiana Hernandez, Sandra Zazo, Gloria Serrano, Cristina Chamizo, Cristina Carames, Nerea Carvajal, Irene Moreno, Nuria Perez-Gonzalez, Ana Leon, Carmen Laura Auz, Jose Ignacio Martin-Valades, Juan Madoz, Francisco Lobo
Journal: Journal of Clinical Oncology (2013)

e19109 Background: Bevacizumab is a recombinant monoclonal humanized antibody to vascular endothelial growth factor (VEGF) that improves Time to Progression (TTP) in patients with advanced non-squamous NSCLC in combination with a doublet of platins, but currently no proven predictive markers exist. The VEGF-A 165 splice variant has been described as the most abundant and active isoform in cancer. Exon 8 splice modifications of VEGF 165 generates the VEGF-A 165 a family of isoforms, which has a pro-angiogenic effect, and VEGF-A 165 b family, with an anti-angiogenic activity. This study is aimed to explore the role of VEGF 165 a and VEGF 165 b expression in tumors as predictive biomarkers of efficacy in patients with NSCLC treated with platins plus bevacizumab. Methods: 22 patients were included (20 adenocarcinomas and 2 large cell carcinomas): 5 received carboplatin-taxol-bevacizumab, 14 carboplatin-taxotere-bevacizumab and 3 cisplatin-gemcitabine-bevacizumab. Total RNA was isolated by RNeasy FFPE procedure. VEGF 165 a and VEGF 165 b expression was analyzed by RT-qPCR using appropriate specific primers and probes. Individual VEGF 165 a and VEGF 165 b family of isoforms expression was calibrated to normal tissue and the ratio between both isoforms was calculated. Results: VEGF 165 a overexpression was detected in 14 (63.6%) cases and VEGF 165 b overexpression in 15 (68.2%). Individual overexpression for each family of isoforms was not predictive of benefit to bevacizumab therapy (p=0.933 and 0.166). However, the ratio between VEGF 165 a and VEGF 165 b was associated with TTP, correlating a predominant expression of pro-angiogenic VEGF 165 a with a significant benefit compared with cases with predominant VEGF 165 b expression (median TTP, 15 vs. 8 months respectively, p=0.005). The expression of both isoforms did not impact on OS (p=0.477). Conclusions: The overexpression of VEGF 165 a and low expression of VEGF 165 b family of isoforms correlated with benefit to anti-angiogenic therapy in NSCLC patients, supporting a potential use as predictive biomarkers for bevacizumab treatment in stage IV non-squamous NSCLC.
Erratum: Epidermal growth factor receptor promotes glomerular injury and renal failure in rapidly progressive crescentic glomerulonephritis
Authors: Guillaume Bollée, Martin Flamant, Sandra Schordan, Cécile Fligny, Elisabeth Rumpel, Marine Milon, Eric Schordan, Nathalie Sabaa, Sophie Vandermeersch, Ariane Galaup, Anita Rodenas, Ibrahim Casal, Susan W Sunnarborg, David J Salant, Jeffrey B Kopp, David W Threadgill, Susan E Quaggin, Jean-Claude Dussaule, Stéphane Germain, Laurent Mesnard, Karlhans Endlich, Claude Boucheix, Xavier Belenfant, Patrice Callard, Nicole Endlich, Pierre-Louis Tharaux
Journal: Nature Medicine (2011)