tbuckley/cabot-search huggingface dataset:
Interdisciplinary palliative care in metastatic non-small-cell lung cancer.
Authors: Marianna Koczywas, Mihaela C. Cristea, Karen L. Reckamp, Jay Thomas, Virginia Sun, Betty R. Ferrell
Journal: Journal of Clinical Oncology (2012)

9068 Background: Palliative cancer care is the integration into cancer care of therapies that address multiple issues that cause suffering for patients and their families and impact their life quality. Challenges and barriers continue to hinder the integration of palliative care into comprehensive, ambulatory oncology care. This paper aims to describe how symptoms, distress, and quality of life (QOL) data from the usual care phase of a NCI-supported Program Project (P01) informed the development of an interdisciplinary palliative care intervention for patients with metastatic non-small-cell lung cancer (NSCLC). Methods: Patients receiving usual care for metastatic NSCLC were recruited into this prospective longitudinal study. A total of 130 patients with stage IV NSCLC were accrued, and 114 patients had evaluable data. Upon informed consent, patients completed outcome measures that assessed physical function/cognitive status, social activities and support, symptom characteristics, psychological distress, and overall QOL. Patient-reported outcomes were completed at baseline, 6, 12, and 24 weeks post-accrual. Results: Subjects were primarily female (64%), ranged in age from 40-84 years, and 39% were ethnic minorities. The majority were former smokers (66%). KPS, IADL, and Cognitive scores deteriorated significantly over time (p=.001, .009, and .042, respectively). Patients reported higher severity scores with symptoms such as dyspnea, fatigue, insomnia, lack of appetite, peripheral neuropathy, pain, dry skin, nail changes, and problems with sexual interest in all four time periods. Global Symptom Distress Index and Total Symptom score both significantly worsened at 24 weeks (p=.003 and .017, respectively). Physical Well-Being worsened significantly (p=.036), while overall QOL, spiritual well-being, and psychological distress scores remained statistically stable over time. Conclusions: Patients with metastatic NSCLC continue to experience high symptom burden and diminished physical well-being over time while receiving treatments. An interdisciplinary palliative care intervention is currently being tested to improve symptom burden and overall QOL.
ITRAQ-based quantitative proteomics to reveal Apolipoprotein A-I and Transferrin as potential serum markers in CA19-9 negative pancreatic ductal adenocarcinoma.
Authors: Wenchuan Wu, Chao Lin, Guochao Zhao, Dansong WANG, Wenhui Lou, Xinyu Qin
Journal: Journal of Clinical Oncology (2015)

e15280 Background: Currently the diagnosis of pancreatic ductal adenocarcinoma (PDAC) relies on CA19-9 and radiological means, whereas some patients don't have elevated levels of CA19-9 secondary to pancreatic cancer. The purpose of this study was to identify potential serum biomarkers for CA19-9 negative PDAC. Methods: A total of 114 serum samples were collected from three groups: CA19-9 negative PDAC patients (n = 34), CA19-9 positive PDAC patients (n = 44), and healthy volunteers (n = 36), whereas the first 12 samples from each group were used for iTRAQ analysis. Thereafter, candidate biomarkers were selected for validation by ELISA with the rest specimens. Results: Using iTRAQ approach, a total of 5 proteins were identified as significantly different between CA19-9 negative PDAC patients and healthy subjects according to our defined criteria. Apolipoprotein A-I (APOA-I) and Transferrin (TF) were selected to validate the proteomic results by ELISA in a further 78 serum specimens. It revealed that TF significantly correlated with the degree of histological differentiation (P = 0.042), and univariate and multivariate analyses indicated that TF is an independent prognostic factor for survival (hazard ratio, 0.302; 95% confidence interval, 0.118- 0.774; P = 0.013) of patients with PDAC after curative surgery. Conclusions: ITRAQ-based quantitative proteomics revealed that APOA-I and TF may be potential CA19-9 negative PDAC serum markers.
Lung cancer screening in high-risk individuals with annual low-dose chest CT in a community setting.
Authors: Niraj K. Gupta, Richard K Freeman, Susan Storey, Dave Reeves, Anthony Ascioti, Chad Davis, Thomas Dugan, Vincent Flanders, Stanley Givens, Mohamed Heikal, Sunil Jhajria, Christopher Leagre, Robert Liebross, Raja Mahidhara, Brandon Martinez, Moyad Moallem, Anne Shaynak, Brent Toney
Journal: Journal of Clinical Oncology (2014)

e12529 Background: National Lung Screening Trial (NLST) establisehd the role of lung ca screening in high-risk individuals. Annual screening with a low dose CT-chest for 3 years resulted in a 20% relative reduction in mortality from lung cancer. Based on these results, lung ca screening is now recommended by the NCCN, ACCP, and ASCO. Despite the encouraging results observed in a large screening trial, information on a lung ca screening program in a community setting is lacking.Goal of this study is to share the interim results of a screening program at a large community cancer program. Methods: A lung cancer screening program was implemented at St Vincent Medical Center, Indianapolis, IN in the summer of 2011. High-risk individuals as defined by the NLST study were offered annual low-dose CT scans of the chest. A multidisciplinary team consisting of thoracic surgeons, medical-radiation oncologists, pulmonologists, social worker and navigator was part of the program. Results: Between 6/1/2011 and 5/30/2013, a total of 356 patients were screened. Sixty one were screened from 6/2011- 5/2012 and 295 from 6/2012 to 5/2013. A higher number of women, 206 (58%) were screened than men,150 (42%). Majority were Caucasians, 92% with 6% African Americans . Forty four (11%) of those with normal scan in 2012 returned for a second scan the next year.There were a total of 113 (32%) abnormal scans. More women, 69 (61%) had abnormal findings then men, 44 (39%) with a mean age of 62 yrs. (range:53-71). Fifty (45%) were recommended a follow-up CT scan with-in a year and 49 (45%) an annual CT. Out of 113 abnormal scans, 14 (12%) underwent diagnostic work-up to establish a diagnosis and of those two (17%) had lung ca. Hence, two out of 113 (1.7) % with abnormal scans were evntually diagnosed with lung ca. One male and one female aged, 71 and 68 respectively. Both had stage-1 NSCLC (adenoca). Conclusions: We provide the results of a lung ca screening in a community setting. Increasing awareness among primary care providers and the public would help in a wide-spread adoption of the screening process. Reminders for annual follow-up CTs can improve compliance. A multidisciplinary team is essential for evaluation and management of those with suspicious findings on the CT scans.
Serum pharmacoproteomics of erlotinib-treated advanced prostate cancer patients: A SELDI-TOF mass spectrometry analysis
Authors: A. Gonçalves, B. Taylor, Y. Toiron, B. Esterni, N. Salem, F. Bladou, P. Viens, G. Gravis
Journal: Journal of Clinical Oncology (2006)

14603 Background: EGFR (Epidermal Growth Factor Receptor) is a promising target in various epithelial cancers. Erlotinib is an orally active small molecule tyrosine kinase inhibitor (TKI) targeting EGFR, under evaluation in prostate cancer. To identify protein biomarkers associated with EGFR TKI treatment we performed serum protein profiling in advanced prostate cancer patients receiving erlotinib, using Surface Enhanced Laser Desorption/Ionization-Time of Flight Mass Spectrometry (SELDI-TOF MS). Method: Serums from 23 advanced or metastatic prostate cancer patients enrolled in a phase II study of erlotinib as single agent were collected before treatment, on D28 and D56 and kept frozen in liquid nitrogen until analysis. Serum samples from each patients and each time points were first urea treated and then incubated with 3 different ProteinChip arrays (Ciphergen Biosystems): IMAC-Cu, CM10 and H50 using a fully automated platform (Tecan). After adding SPA matrix, arrays were analysed using a PBSIIc ProteinChip reader (Ciphergen Biosystems). After noise reduction, baseline substraction, and data normalisation, protein peaks were detected using the Biomarker Wizard tool integrated to the ProteinChip Software 3.1. Numeric data were then exported to excel files that were used for further biostatistic processing. Results: Combining protein profiles resolved from each experimental condition, several hundreds of protein peaks were obtained. Protein profiles from untreated and D28 and D56-treated patients were compared using non-parametric statistical methods and several protein peaks appeared differentially expressed between pre and post-treatment samples. Supervised methods identified protein peaks correlating with specific erlotinib toxicity on day 28. Since only minimal activity was noted in this trial, no protein profile correlating with anti-tumor effect was identified. Purification and identification of proteins modulated by treatment and associated with toxicity are ongoing. Conclusion: Serum protein profiling using SELDI-TOF MS is a promising method to characterize pharmacoproteomics of innovative compounds under development and to identify protein biomarkers potentially associated with drug effects. No significant financial relationships to disclose.
Impact of age on genomic alterations associated with pancreatic ductal adenocarcinoma (PDAC).
Authors: Ben George, Mark Bailey, Alexa Betzig Schrock, Lauren Thorpe, Laurie M. Gay, Paul S. Ritch, James P. Thomas, Beth Erickson, Susan Tsai, Kathleen K. Christians, Douglas B. Evans, Philip J. Stephens, Vincent A. Miller, Jeffrey S. Ross, Aatur D. Singhi, Siraj Mahamed Ali
Journal: Journal of Clinical Oncology (2017)

282 Background: Large scale, retrospective, sequencing projects have identified well-defined subtypes of PDAC, but therapeutic paradigms remain unchanged. We hypothesized that genomic alterations associated with PDAC in young adults (YA, age &lt; 50) are distinctly different from that of older adults (OA, age &gt; 50) to identify an enrichment of targetable alterations. Methods: DNA was extracted from formalin fixed paraffin embedded (FFPE) PDAC clinical specimens and comprehensive genomic profiling (CGP) was performed on hybrid-capture, adaptor ligation based libraries to a mean coverage depth of &gt; 600 for up to 315 genes plus 47 introns from 19 genes frequently rearranged in cancer. Results: CGP was performed on 1533 FFPE PDAC specimens, 566 (36.9%) were from the primary tumor, 967 (63.1%) from metastatic sites. Median age at diagnosis was 63 years (yrs), 180 (11.7%) were YA. KRAS mutations were identified in 78.7 of YA and 87.7% of OA. The differentially altered genes between the two groups were KRAS (p = 0.004), TP53 (p = 0.04), BRCA2 (p = 0.02), AKT2 (p = 0.03), MAP2K4 (P = 0.003) and DNMT3A (p = 0.0002). The median tumor mutational burden (TMB) for the entire study set was 2.7 (YA – 2.5, OA –2.7). BRAF kinase domain deletion was observed in 1 patient (OA). ALK fusions were present in 2 patients (1 YA &amp; 1 OA) and these patients had durable responses to specific ALK inhibitors. Conclusions: The majority of the genomic alterations identified were not significantly different on the basis of age. However, identification of subpopulations, such as ALK kinase fusions and BRAF kinase domain deletions that can translate into sustained clinical benefit from matched targeted therapy is promising. This underscores the importance of CGP in PDAC to investigate other targetable genomic alterations.
Outcomes of locoregional therapy for metastatic gastric cancer.
Authors: Ravi Shridhar, Jamie Huston, Kenneth L Meredith
Journal: Journal of Clinical Oncology (2017)

143 Background: Patients with metastatic gastric cancer have poor survival. The purpose of this study was to compare outcomes of metastatic gastric cancer patients with or without surgery and radiation therapy (RT). Methods: The National Cancer Database (NCDB) was accessed to identify patients with stage IV gastric cancer between 2004 and 2013 and stratified by surgery. Propensity score matching was performed against age, metastatic site, radiation, and signet ring histology. Overall survival (OS) analysis was determined by Kaplan-Meier and log-rank analysis. Multivariate analysis (MVA) was analyzed by the Cox proportional hazard ratio model. Results: A total of 1808 patients were identified. Surgery was associated with an OS benefit. Median and 5-year OS for surgery and no surgery was 16 months and 16% and 10 months and 2%, respectively (p &lt; 0.001). Median and 5 year OS for patients treated with surgery and RT was 22.4 months and 26%. Median and 5 year OS for surgery patients treated with or without preoperative RT was 27.2 months and 28% and 15.2 months and 12%, respectively (p &lt; 0.001). There was no OS benefit with postoperative RT. MVA for all patients revealed that surgery and tumor location were associated with decreased mortality while peritoneal metastases were associated with increased mortality. In surgical patients, MVA showed that RT, partial esophagectomy, and tumor location were associated with decreased mortality, while positive margins, signet ring histology, and peritoneal metastases were associated with increased mortality. In nonsurgical patients, only carcinomatosis was prognostic on MVA. Conclusions: Surgery and radiation are associated with increased survival in a subset of patients with metastatic gastric cancer. Prospective trials will be needed to address the role and sequence of surgery and radiation in metastatic gastric cancer.
A combination of dual PI3K-mTOR inhibitor, GDC-0980, with PARP inhibitor plus carboplatin blocked tumor growth of BRCA-competent triple-negative breast cancer cells.
Authors: Nandini Dey, Yuliang Sun, Jennifer Carlson, Lori Friedman, Pradip De, Brian Leyland-Jones
Journal: Journal of Clinical Oncology (2013)

2613 Background: PARP is a promising target in the TNBC. The PI3K pathway, in addition to its pro-proliferative effects on tumor cells, also controls the repair of DSB (Kumar, 2010; Friedman, 2009; Juvekar, 2012; Ibrahim, 2012). We hypothesize that the growth of TNBC tumor will be blocked due to the inhibition of (1) HR / NHEJ, and (2) PI3K-mTOR pathway mediated survival signals following GDC-0980 (G), when combined with PARP inhibitor (impaired DNA-SSB-repair), and carboplatin (C) (increased DNA-DSB). Methods: We tested the in vivo efficacy of a combination of G with ABT888 (A) plus C in BRCA-competent TNBC cells, and compared the triple combination arm (A+C+G) with a combination arm of A+C+ pan PI3K inhibitor GDC-0941 in mice xenograft (MDA-MB231) model. Mechanistically, we tested, (1) cell survival/ proliferation (5-7 BRCA-wt and mutant cell lines) using MTT assay, CelltiterGLO, and cell cycle analyses, (2) anchorage independent and dependent clonogenic growth (3D ON-TOP and soft-agar assay), (3) apoptosis, and (4) cell signaling marker(s). Results: (1) G alone decreased the tumor growth by 40-50%. (2) The G + A + C combination blocked the growth of established tumors by 90% as compared to control(s). (3) Interestingly, G + A + C combination had markedly higher percentage of inhibition of tumor growth than the inhibition observed in the A+C+GDC-0941 arm (36%). (4) G treatment time-dependently increased cl-caspase 3, 9, and cl-PARP and increased AnnexinV positivity both time (24 and 48 hrs) and dose dependently (50 and 200 nM) in cells. (5) G when combined with A+C was most effective in inducing apoptosis in PIK3CA-mutated BT20 cells. (6) The triple combination (50 nM G+10 μM A + 10 μM C) inhibited clonogenic growth of MDA-MB231, MDA-MB468 and BT20 cells. (7)Treatment of G decreased downstream effectors of PI3K-mTOR pathway, pAKTS473, pP70S6K and pS6RP. Conclusions: Tumor growth of BRCA-competent TNBC cells is blocked by a combination treatment of G with A+C. The profound anti-tumor effect of this triple combination can be explained by the anti-proliferative and pro-apoptotic actions of the drugs. The combination of G with A+C merits further investigation in TNBC.
Adjuvant therapy (AT) following resection of pancreatic ductal adenocarcinoma (PDAC): Are patients from rural, remote areas disadvantaged?
Authors: Kimberly A Bertens, John Massman, Samuel Garbus, Margaret T Mandelson, Bruce Lin, Vincent J. Picozzi, Adnan Alseidi, Thomas Biehl, William Scott Helton, Flavio G Rocha
Journal: Journal of Clinical Oncology (2017)

373 Background: AT with chemotherapy (CT) + radiation (RT) has been shown to improve PDAC survival over surgery alone. Although race and socioeconomic status can affect outcomes in PDAC, the impact of rural or remote residence on the delivery and effect of AT has not been studied. Methods: Patients undergoing pancreatectomy for PDAC were identified from the National Cancer Data Base between 2006 and 2013. Individuals were classified as living in a metro area, urban/rural adjacent to metro area (URA), and urban/rural remote area (URR). Patients with less than 6 months follow-up were excluded. Logistic regression was performed to assess residence as a predictor of receiving AT. Overall survival (OS) as a function of inhabitance was estimated by the method of Kaplan and Meier and prognostic factors were identified by Cox regression. Results: A total of 32,521 individuals underwent pancreatectomy for PDAC. The majority of AT was delivered in academic research facilities in 56% of patients while only 29% of patients received both CT and RT. Univariate analysis demonstrated individuals in URR were less likely to receive CT (55% vs 58%, p &lt; 0.01) but not RT (30% vs 31%, p &lt; 0.261) and had a longer interval to AT (82 vs 75 days, p &lt; 0.009) than those in metro areas. However on multivariate analysis URR inhabitance was no longer predictive of any form of AT (OR = 0.892, 95% CI: 0.792-1.006, p = 0.062). Hispanic ethnicity, Medicaid insurance, uninsured status, and lower education were all predictive of decreased likelihood of receiving AT. Median OS was inferior for URR dwellers with pathologic T2 and T3 tumors compared to those in metro areas (19.8 vs. 24.4 months, p = 0.044 and 17.5 vs. 19.4 months, p &lt; 0.001). Cox regression revealed URR location remained independently associated with poorer OS (HR 1.076, 95% CI: 1.008-1.149, p &lt; 0.029). Conclusions: While living in a URR does not lead to reduced access to AT, it is associated with a worse OS in resected PDAC. This may be due to inadequate AT or other socioeconomic factors present in URR patients. Attention must be focused on improving oncologic care for groups susceptible to treatment disparities.
Initial results from the 21-gene breast cancer assay registry: A prospective observational study in patients (pts) with ER+, early-stage invasive breast cancer (EBC).
Authors: Jeffrey L. Vacirca, Michaela L. Tsai, Adam Brufsky, Richard Alan Michaelson, Frederick P. Smith, Lee Steven Schwartzberg, Steven M Butler, Farid Jamshidian, Amy Pratt Sing
Journal: Journal of Clinical Oncology (2013)

565 Background: Genomic assays such as the 21-gene breast cancer assay (Oncotype DX), have improved the ability to individualize pt treatment based on their individual tumor’s biology. Since 2004, when the 21-gene assay became commercially available, more than 300K assays have been ordered. While several studies have been conducted assessing the impact of having the Recurrence Score (Score) result on treatment decisions, most have been retrospective or evaluating the treatment recommendation. The Oncotype DX Breast Cancer Registry is a large prospective study conducted in clinical practices evaluating the types of pts having the assay ordered and the actual treatments delivered. We report here the first set of analyses. Methods: Pts with ER+ EBC were eligible to enroll. Data collected at baseline (BL) included age, size, grade, ER, PR and HER2 status. Data collected at the 6-month visit included Score and treatment given. Pt demographics, Score distribution, and associations with clinicopathologic (CP) factors are described. Results: A total of 890 pts were enrolled at 15 U.S. sites between 11/09-3/12. 803 eligible pts were included in the analyses. The Table shows BL characteristics, Score distribution and %CT given. Distribution of Score values across the CP factors was similar to the cohort overall. 30% of pts received CT. Among low Score patients, CT was given in 17% of pts &lt;50y, 9% of Grade 3 tumors and 11% of tumors &gt;2cm. Conclusions: A large, prospective registry for pts with EBC receiving the 21-gene breast cancer assay examined the application of the Score to treatment. The Score distribution is consistent with other retrospective cohorts. The association between the Score and the CP factors was modest. The CP factors did not predict the Score. In general, CT decisions followed the Score with the exception of younger pts; 17% received CT despite a low Score. These findings from a real-world cohort underscore the importance of understanding breast cancer biology in order to make more informed and individualized treatment decisions. [Table: see text]
Performance teamwork training in ambulatory oncology.
Authors: Anne Gross, Susan Mann, Michael Kalfin, Sharon Lane, Saul Weingart, Craig A. Bunnell
Journal: Journal of Clinical Oncology (2012)

e16559 Background: Increasingly complex diagnostic and multimodality treatment algorithms have yielded superior outcomes, but also magnified the risk for adverse events precipitated by failures of communication and coordination. We implemented team training principles in 14 outpatient oncology practices across 3 campuses (community and academic) to reduce the risk of errors and increase operational efficiency and quality. Methods: Over 950 physicians, nurses, pharmacists, and staff were trained in evidence-based concepts of teamwork. Intervention included 1) baseline data collection regarding key clinical processes, (e.g. non-communication of same-day chemotherapy order changes); 2) observations/interviews with care team members; 3) process meetings to identify vulnerabilities and develop agreements and tools to support them; 4) Train the Trainer methodology; 5) staff training; 6) post-training data collection. Results: Despite the infrequency of non-communicated same-day changes in chemotherapy orders at baseline (~2%), a trend toward improvement was seen (chi-square p=0.068). The incidence of missing chemotherapy orders for infusion visits not associated with an MD visit decreased significantly. Staff reported improved practice efficiencies and a more respectful, safer environment. Press Ganey patient-reported perceptions of teamwork improved significantly. Conclusions: Team training improved communication, task coordination, perceptions of efficiency, quality, safety and interactions among team members, as well as patient perception of teamwork in both community and academic environments of a comprehensive cancer center. [Table: see text]