tbuckley/cabot-search huggingface dataset:
Patients of Asian descent with gastric cancer treated in the United States: Comparative characteristics and survival outcomes.
Authors: Ryan Rhome, Erin Moshier, Michael Buckstein
Journal: Journal of Clinical Oncology (2017)

10 Background: Asian gastric cancer trials often show better outcomes than similar Western trials suggesting a possible difference in disease characteristics or biology. Large databases can be used to assess whether ethnic differences persist in the United States. Methods: The National Cancer Database was queried to examine disease characteristics, treatment utilization, and outcomes for gastric cancer from 2004-2013 for Asian vs. non-Asian patients. Patients were excluded with inadequate follow-up, unknown staging or race. Cox proportional hazards model was used to assess hazard ratio (HR) of death. Results: 101,426 patients were analyzed (6,994 Asians, 94,432 non-Asians). Asian patients were more likely to be female, younger, treated at academic centers, early stage, lower co-morbidity score, and high grade vs. non-Asian (Chi-square, all p&lt;0.001). Asian patients were less likely to receive chemotherapy or radiation or have a positive margin. HRs of death (adjusted for age, sex, facility, histology, insurance, co-morbidity score, margin, grade, surgery, radiation, and chemotherapy) for Asian patients are shown in the table. Further dividing by most represented Asian sub-groups showed differences between countries of origin. Conclusions: Imbalances exist in clinical features and treatment utilization in Asian patients compared to non-Asians. After adjustment, Asian race is associated with higher overall survival. Adjusted sub-group analyses show survival differences by country of origin, suggesting biological variability. [Table: see text]
Variation in health-related quality of life (HRQOL) by line of therapy, age, and gender among patients with chronic lymphocytic leukemia.
Authors: Christopher Flowers, Charles Michael Farber, Ian Flinn, David L. Grinblatt, Neil E. Kay, Thomas J. Kipps, Mark Kozloff, Nicole Lamanna, Susan Lerner, Jeff Porter Sharman, Mark Adam Weiss, Arlene S. Swern, Zeba M. Khan, Thomas K. Street, Kristen A. Sullivan, Ren Yu, Chris L. Pashos
Journal: Journal of Clinical Oncology (2013)

7086 Background: The HRQOL of patients (pts) with chronic lymphocytic leukemia (CLL) has not been adequately delineated across patient, disease and treatment characteristics. We evaluated HRQOL of CLL pts undergoing treatment in the United States (US) by age, gender and line of therapy. Methods: Data were collected in Connect CLL, a prospective observational US registry. Physicians provided data on demographics, clinical characteristics and line of therapy at enrollment. HRQOL was self-reported by pts at enrollment using the Functional Assessment of Cancer Therapy-Leukemia, an instrument that yields a leukemia-specific total HRQOL score (FACT-Leu) and a cancer-specific total HRQOL score (FACT-G). Mean total scores were analyzed by line of therapy, age and gender. Statistical significance was ascertained by ANOVA using SAS 9.2. Multivariate analyses were conducted to assess the relative association of line of therapy, age and gender with HRQOL. Results: Among 1,252 pts enrolled from 161 geographically diverse centers (90% community, 8% academic, 2% veterans/military), pts were predominantly male (63%), white (89%) with mean age 69 yrs. Pts were categorized by line of therapy at enrollment: First 61%, Second 18%, Third 11%, Higher 9%; and by age group: &lt;65 33%, 65-74 35%, 75+ 32%. Univariate analyses suggested that the total FACT-Leu score was significantly better in men than women (P=0.004); in pts aged 65-74 vs younger or older pts (P=0.033); and in pts initiating first-line treatment vs pts receiving subsequent treatments (P=0.0002). Similar results were found with the FACT-G score except that gender differences were not statistically significant. Multivariate analysis confirmed that line of therapy (P=0.007), gender (P&lt;0.0001), and age group (P=0.039) were each associated with significant differences in the FACT-Leu total score. Conclusions: Results from the Connect CLL Registry indicate that HRQOL is better among pts initiating first-line therapy compared to pts initiating subsequent treatments, and that this remains true when age and gender are considered. Future analyses should determine how HRQOL may change over time relative to treatment and treatment response.
VEGF and VEGFR1 gene expression levels and tumor recurrence in adjuvant colon cancer
Authors: Y. Ning, G. Lurje, K. Danenberg, J. Cooc, D. Yang, A. Pohl, W. Zhang, H. Lenz
Journal: Journal of Clinical Oncology (2009)

4040 Background: Tumor recurrence after curative resection is still a major problem in the management of adjuvant colon cancer, with recurrence rate approximately 30–40%. Identifying molecular markers for tumor recurrence is critical for successfully selecting patients who are more likely to benefit from adjuvant chemotherapy. Our group previously showed that angiogenesis gene polymorphisms (VEGF and IL-8) may associated with tumor recurrence in adjuvant colon cancer (Lurje Ann Oncol, 2008). Here we tested the hypothesis whether gene expression levels of angiogenesis pathway (COX-2, EGFR, VEGF, VEGFR1, VEGFR2 and IL-8) could also predict the risk of tumor recurrence in stage II and III colon cancer patients treated with adjuvant chemotherapy. Methods: Tissue samples from 140 adjuvant colon cancer patients (69 females and 71 males with a median age of 59 years; range=28–86) were available for gene expression assays. These tissue samples were obtained at the University of Southern California/Norris Comprehensive Cancer Center (USC/NCCC) and LAC+USC medical center between 1999 and 2006. Sixty-three patients had stage II and 77 had stage III colon cancer. The median follow-up was 5.4 years (range=2.0–16.8). 51 of 140 patients (36.4%) developed tumor recurrence with a 5-year probability of 0.28 ± 0.06 for stage II and 0.40 ± 0.06 for stage III colon cancer patients. mRNA was extracted from laser-capture-microdissected tumor tissue. After cDNA was prepared by reverse transcription, quantitation of the candidate genes and an internal reference gene (ß-actin) was performed using a fluorescence-based real-time detection method (TaqMan). Results: We found VEGF and VEGFR1 gene expression levels independently significantly associated with time to tumor recurrence in adjuvant colon cancer patients. Patients with lower VEGF gene expression and lower VEGFR1 gene expression levels had significantly longer time to tumor recurrence compared to those with higher VEGF and higher VEGFR1 gene expression levels (p&lt;0.05, log-rank test). Conclusions: VEGF and VEGFR1 gene expression levels may predict tumor recurrence risk in adjuvant colon cancer patients. Our exploratory data warrant future confirmatory trial. [Table: see text]
Phase II study of gefitinib and inserted cisplatin plus docetaxel as a first-line treatment for advanced non-small cell lung cancer haboring an epidermal growth factor receptor activating mutation.
Authors: Shintaro Kanda, Yuichiro Ohe, Hidehito Horinouchi, Yutaka Fujiwara, Hiroshi Nokihara, Noboru Yamamoto, Ikuo Sekine, Hideo Kunitoh, Kaoru Kubota, Tomohide Tamura
Journal: Journal of Clinical Oncology (2013)

8064 Background: Gefitinib yields a longer progression-free survival (PFS) period than platinum–doublet chemotherapy as a first–line treatment for patients with advanced non–small–cell lung cancer (NSCLC) harboring an epidermal growth factor receptor (EGFR) activating mutation, but most patients develop resistance against gefitinib after the initial response. We hypothesized that the insertion of platinum–doublet chemotherapy during the initial response could prevent the emergence of acquired resistance and prolong survival, compared with gefitinib alone. Methods: We performed a phase ΙΙ study of the following first–line treatment for patients with advanced NSCLC with EGFR mutation. Gefitinib (250 mg) was administrated on days 1–56. After a two–week rest, three cycles of cisplatin (80 mg/m 2 ) and docetaxel (60 mg/m 2 ) were administered on days 71, 92, and 113. Gefitinib was re–started on day 134 and was continued until progression. The primary endpoint was the two–year PFS rate. The sample size was estimated at 33, and this treatment was considered worthy for further development if more than 11 of the 33 patients who started treatment had a 2–year PFS. Results: Thirty–three Japanese patients were enrolled. Twenty–five patients could re–start gefitinib, 12 achieved a PFS period of over 2 years, and 9 continued to receive the protocol treatment without experiencing progression. The 1–, 2–, and 3–year estimated PFS rates were 59.4%, 37.5%, and 33.8%, respectively, and the median PFS time was 19.2 months. The 1–, 2–, and 3–year estimated survival rates were 90.0%, 82.9%, and 62.4%, respectively, and the median survival time had not been reached at the time of analysis. Treatment–related deaths and unexpected severe toxicities were not seen. Conclusions: Our results indicated that first–line treatment consisting of gefitinib and inserted cisplatin plus docetaxel is promising for patients with advanced NSCLC with EGFR mutation. A phase ΙΙΙ study of this treatment compared with gefitinib alone is warranted. Clinical trial information: 000001738.
Molecular characterization of early vs. late onset gastroesophageal cancers.
Authors: Sadaf Qureshi, Joanne Xiu, Maryam Sarraf Yazdy, Anthony Frank Shields, Philip Agop Philip, John Marshall, Heinz-Josef Lenz, Mohamed E. Salem
Journal: Journal of Clinical Oncology (2017)

46 Background: Gastric and esophageal adenocarcinomas (GA and EA) in young patients (pts) are more likely driven by genetic factors than environmental carcinogens. Tumor molecular variations defining individual differences in age of onset have not been well elucidated. Methods: Protein expression (IHC), gene amplification (ISH), and next generation sequencing (NGS) were tested on GA and EA tumors. Tumor mutational load (TML) was calculated using only somatic nonsynonymous missense mutations sequenced with a 592-gene panel. Chi-square and t-tests were used for comparative analyses. Results: In total, 1670 tumors were examined; older (age &gt;60) vs. younger (&lt;45)comparisons were made in 599 GA and 491 EA (Table). In GA, significantly higher TOPO2A and TOPO1 expression was seen in older vs. younger pts, while higher mutation rates of FGFR2, IDH1, and NRAS were seen in younger pts. In EA, EGFR expression was higher in the older pts, while ATM and BRCA1 mutations were higher in the younger pts. When only primary tumors were studied, younger GA had a higher NRAS mutation rate (4.5% vs. 0, p=0.02) than older GA, and younger EA had higher cMET amplification (10% vs. 0, p=0.002) and ATM mutations (25% vs. 0, p=0.01) than older EA. In metastatic EA, higher BRCA1mutations (1/2 [50%] vs. 0/12 [0%], p=0.01) and lower EGFR overexpression (81% vs. 29%, p = 0.004) were seen in younger vs. older pts. No differences were seen in the PD-1 or PD-L1 expression rates between the two groups. Mean TML was lower in young GA than old GA (6.2 mutation/megabase vs. 10.4, p=0.005) but was not different between young EA and old EA (5.3 vs. 6.9, p=0.1). Conclusions: Younger GA/EA has a molecular profile unique from older pts, suggesting molecular aberrations play a different part in early-onset disease. Prevalence of aberrations in the young, such as cMET amplification and FGFR2, IDH1, BRCA1mutations may indicate important therapeutic targets. [Table: see text]
Modified FOLFIRINOX for metastatic pancreatic adenocarcinoma after failure of nab-paclitaxel plus gemcitabine.
Authors: Masato Ozaka, Takashi Sasaki, Seita Kataoka, Ryo Kanata, Kazunaga Ishigaki, Ikuhiro Yamada, Masato Matsuyama, Koichi Takano, Naoki Sasahira
Journal: Journal of Clinical Oncology (2017)

467 Background: Both FOLFIRINOX and Nab-paclitaxel plus Gemcitabine standard treatment in first-line treatment of metastatic pancreatic adenocarcinoma (MPA). It could be of interest to use them consecutively, knowing that there is currently no standard for 2nd line treatments for MPA. The aim of this study was to evaluate the efficacy and tolerability of modified FOLFIRINOX after gemcitabine plus Nab-paclitaxel failure in MPA. Methods: From January 2015 to March 2016, medical records were retrospectively reviewed for consecutive patients receiving modified FOLFIRINOX for a histologically proven MPA after failure of Nab-paclitaxel plus Gemcitabine. Patients were treated with modified FOLFIRINOX every 2 weeks as follows: intravenous oxaliplatin 85 mg/m2, irinotecan 150 mg/m2, 5-FU infusion 2,400 mg/m2 over 46 h, no bolus 5-FU, until disease progression, patient refusal or unacceptable toxicity. Results: Modified FOLFIRINOX was administered to 23 pts. Among these patients, median age was 64 years (range 42.4 - 74.2). 83% of the patients had a PS 0, the primary site of the tumor was the head of the pancreas in 39% of patients, and 26% of patients experienced recurrence after resection. Disease control rate was 66.7% (n = 17) with a 23.8 % (n = 17) objective response rate (RECIST). Within the whole cohort, median PFS was 4.3 months (95% CI: 3.1-5.3) and median overall survival (OS) was 9.3 months (95% CI: 3.8-14.8). Since the start date of first line chemotherapy with Nab-paclitaxel plus Gemcitabine, median OS was 18.8 months (95% CI: 9.6-27.9). No toxic death occured. Grade 3-4 toxicities were reported in 30% of patients and were neutropenia (17%), anemia (8%), cholangitis (8%) and acute kidney injury (4%). Conclusions: Modified FOLFIRINOX seems promising with a manageable toxicity profile after Nab-paclitaxel plus Gemcitabine failure, in selected patients able to receive second line treatment for a MPA. These promising results have now to be confirmed in a phase III randomized trial.
Cranberry Capsules for bacteriuria Plus Pyuria in Nursing Home Residents—Reply
Authors: Manisha Juthani-Mehta, Peter H. Van Ness, Peter Peduzzi
Journal: JAMA (2017)

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Dynamic Cellular Interactions with Extracellular Matrix Triggered by Biomechanical Tuning of Low‐Rigidity, Supported Lipid Membranes
Authors: Setareh Vafaei, Seyed R. Tabaei, Kabir H. Biswas, Jay T. Groves, Nam‐Joon Cho
Journal: Advanced Healthcare Materials (2017)

The behavior of cells in a tissue is regulated by chemical as well as physical signals arising from their microenvironment. While gel‐based substrates have been widely used for mimicking a range of substrate rigidities, there is a need for the development of low rigidity substrates for mimicking the physical properties of soft tissues. In this study, the authors report the development of a supported lipid bilayer (SLB)‐based low rigidity substrate for cell adhesion studies. SLBs are functionalized with either collagen I or fibronectin via covalent, amine coupling to a carboxyl group‐modified lipid molecule. While the lipid molecules in the bilayer show long‐range lateral mobility, the covalently functionalized extracellular matrix (ECM) proteins are immobile on the bilayer surface. Specific adhesion of cells results in an enrichment of the protein on the bilayer and the appearance of a zone of depletion around the cells. Further, the lateral reorganization of the ECM proteins is controlled by altering the fluidity of lipid molecules in the substrate. Thus, the experimental platform developed in this study can be utilized for addressing basic questions related to cell adhesion on low rigidity substrates as well as biomedical applications requiring adhesion of cells to low rigidity substrates.
Pertuzumab plus trastuzumab for HER2-positive metastatic urothelial cancer (mUC): Preliminary data from MyPathway.
Authors: Alan Haruo Bryce, Razelle Kurzrock, Funda Meric-Bernstam, Herbert Hurwitz, John D. Hainsworth, David R. Spigel, Ron Bose, Charles Swanton, Howard A. Burris, Shuangli Guo, Bongin Yoo, Mary Stanley Beattie, Darren Tayama, Christopher Sweeney
Journal: Journal of Clinical Oncology (2017)

348 Background: Patients (pts) with mUC have few treatment options beyond the second-line setting. HER2 gene amplification has been reported in a minority of pts with UC, but there have been anecdotal reports of the activity of HER2-targeted agents. MyPathway is a multi-basket study evaluating the efficacy and safety of targeted therapies in non-indicated tumor types harboring relevant molecular alterations. We present preliminary data for pts with HER2-positive mUC receiving HER2-targeted treatment with pertuzumab + trastuzumab. Methods: MyPathway (NCT02091141) is an open-label, multicenter, phase IIA study. Pts in this subset analysis had refractory mUC with HER2 amplification or putative activating mutations by gene sequencing, FISH, or IHC. Pts received standard doses of pertuzumab + trastuzumab without chemotherapy until disease progression or unacceptable toxicity. The primary endpoint is investigator-assessed overall response rate (RECIST v1.1). Results: As of July 31, 2016, 12 pts with platinum-resistant HER2-positive mUC (HER2-amplified, n=9; HER2-mutated, n=3) have been enrolled. At a median follow-up of 5.4 (range 0.9–14.5) mos, 1 pt had complete response (CR, ongoing at 12.5 mos), 2 had partial responses (PR; duration of response, 3.7 and 5.5 mos), and 2 had stable disease (SD) for &gt;4 mos (Table). Safety was consistent with the product labels. Conclusions: Preliminary results indicate that the combination of pertuzumab + trastuzumab has activity in previously treated HER2-amplified mUC, including a durable CR in a pt with peritoneal metastases. Accrual to MyPathway is ongoing. Clinical trial information: NCT02091141. [Table: see text]
Genomic heterogeneity of lung cancers and its potential clinical implications.
Authors: Jianjun Zhang, Yu Liu, Jianhua Zhang, Daniel Richard Gomez, Junya Fujimoto, Carmen Behrens, Jiexin Zhang, Arlene M. Correa, Curtis Gumbs, Xizeng Mao, Sahil Seth, Xingzhi Song, John Heymach, J. Jack Lee, Stephen Swisher, William Nassib William, Waun Ki Hong, Yanning Gao, Ignacio Ivan Wistuba, Andrew Futreal
Journal: Journal of Clinical Oncology (2015)

7530 Background: Substantial genomic heterogeneity of lung cancers between different patients, reflecting distinct genetic background and potentially different carcinogen exposures in different patients, has been well documented, particularly under the Cancer Genome Atlas (TCGA) efforts. On the other hand, our recent study (Zhang, et al, Science, 2014, 346:256-9) and others (de Bruin, et al, Science, 2014, 346:251-6) have revealed limited intra-tumor heterogeneity (ITH) in localized lung adenocarcinomas (LUAD). Our more recent work on synchronous multifocal lung cancers (MSLC) has demonstrated distinct genomic profiles in different tumors within the same patients in spite of identical genetic background and exposure history (Liu and Zhang et al, submitted). Methods: We analyzed data from the two studies on ITH of LUAD (Zhang, et al, Science, 2014, 346:256-9 and de Bruin, et al, Science, 2014, 346:251-6), our MSLC study and data from TCGA LUAD study to assess the genomic heterogeneity of lung cancers under different clinical scenarios. We are currently conducting studies to assess the genomic heterogeneity of primary lung cancers versus distant metastases, versus relapsed diseases, and versus secondary primary lung cancers. Results: The percent mutations in a tumor sample that are identical to mutations from another tumor sample under different clinical scenarios are: 91% between different regions within the same tumors (n = 16); 80% between primary lung cancers and metastatic lymph nodes (n = 4); 0.12% between different independent tumors within the same patients (n = 6) and 0.05% from unrelated patients (n = 519). The data from primary lung cancers versus distant metastases, versus relapsed diseases and versus second primary cancers is pending. Conclusions: With the caveat of small sample size, our data suggests that in localized LUADs, metastases resemble matched primary tumor closely while multifocal primary cancers within the same patients have distinct genomic profiles in spite of identical genetic background and exposure history. Genomic profiling may be useful for identification of both synchronous and metachronous multifocal lung cancers.
Translating Prostate Cancer Working Group 2 (PCWG2) progression criteria into a quantitative response biomarker in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Aseem Anand, Anders Bjartell, Daniel Costin Danila, Danny Francisco Martinez, Lars Edenbrandt, Steven M. Larson, Howard I. Scher, Michael J. Morris
Journal: Journal of Clinical Oncology (2017)

170 Background: PCWG2 radiographic progression criteria, which are associated with survival, rely on lesion counting. There is a need for a fully quantitative assessment of tumor burden as a component of a true response biomarker for mCRPC. Here, we used the bone scan index (BSI) to fully quantitate the increase in skeletal disease burden at each radiographic milestone that constitutes the PCWG2 criteria. Methods: mCRPC patients (pts) from clinical trials using PCWG2 criteria to determine progression (PD) were assessed. Pts were required to have baseline (BL) and at least two follow-up (FU) bone scans. The EXINI automated platform was used to generate BSI at key PCWG2 landmarks: 2+2 criteria for early PD and post flare PD criteria with the appearance of 1 and ≥2 new lesions. Median (M) and Interquartile range (IQR) of the relative change in BSI were calculated to quantify the increase in total tumor burden. Results: A total of 257 pts were assessed, of whom 169 had two or more FU bone scans at 8 or 12 week intervals. Of the total 169 pts, 86 (51%, 95%CI 43-58) met PD by PCWG criteria. 35 (41%, 95%CI 31-51) of 86 pts met the early PD criteria, the remaining 51 (59%, 95%CI 49-69) met PD at subsequent time points after flare period. The ability of the automated platform to reproduce a BSI value, retrieved from the same scan, was highly consistent (100%). The relative BSI increase during the course of meeting PD by PCWG2 is shown in the Table. Conclusions: This is the first quantitative assessment of changes in total tumor burden in pts meeting PCWG2 criteria. Relative changes in BSI can be substantial in meeting the criteria. These data build on the PCWG2 criteria by quantitating the increase both of existing lesions and the contribution of new lesions. We are now assessing the associations with survival that these incremental increases represent. [Table: see text]