tbuckley/cabot-search huggingface dataset:
Spirituality, symptom distress and quality of life of Latin American patients with advanced cancer (LAAdCa): A multicenter study.
Authors: Marvin Omar Delgado-Guay, Alejandra Palma, Eva Rosina Duarte, Monica Grez, Laura Tupper, Diane D Liu, Andrea Octavia Ferguson, Hilda Cantu, Jewel Ochoa, Janet L. Williams, Eduardo Bruera
Journal: Journal of Clinical Oncology (2016)

e21656 Background: The association between Spirituality(S), religiosity(R), spiritual pain(SP), symptom expression, coping strategies and Quality of life(QOL) have not been well characterized. The main purpose of this Multicenter study was to analyze these associations among LAAdCa. Methods: We interviewed 325 LAAdCa receiving outpatient Palliative Care in Chile, Guatemala, and USA. Patients completed FICA(S/R assessment), Edmonton Symptom Assessment Scale–FS(symptoms including SP), PSWQ(Worry), CESD(Psychological distress) B-COPE; B-R-COPE(coping strategies), and FACIT-sp-Ex(QOL). Results: Median age 58(range:19-85), 60% women, 62% Catholic, 30% Christian not-Catholics, and 2% with no religion. 97% of LAAdCa considered themselves spiritual and 89% religious, median:7(IQR:5-10) and 7(5-9) respectively. Median Importance of S in life(score 0-10) was 10(IQR:8-10). LAAdCa reported that S/R: helped them to cope with their illness(98%, p < 0.0001), was a source of strength and comfort (99%, p < 0.0001), and had a positive effect in physical symptoms (81%, p < 0.0001), emotional symptoms(84%, p < 0.0001), and helped to their caregivers to cope with their illnesses(100%, p < 0.0001). 60% of LAAdCa reported that their S/R needs had not been supported by the medical team. 24% had received pastoral attention inside the hospital. 162/311(52%) of LAAdCa reported SP(median 6; IQR:5-8). SP significantly correlated with worse pain(p = 0.02), fatigue(p = 0.0002), depression(p < 0.0001), anxiety(p < 0.0001), worry(p < 0.001), behavioral disengagement(p = 0.01), FACIT-sp-Ex(p = 0.0002), negative religious coping strategies(p < 0.0001). A multicovariate analysis showed SP correlated with anxiety(p < 0.0001), FACIT-sp-Ex(p = 0.02), and negative religious coping strategies(p = 0.002). Conclusions: The majority of LAAdCa considered themselves Spiritual and Religious. LAAdCa assigned a highly important role to S/R and correlates with less emotional distress, positive coping strategies and QOL. Despite these findings, 52% LAAdCa reported SP and that their S/R needs were not totally supported by the medical team. More research is needed.
Angiogenesis characteristics in benign and malignant melanocytic skin tumors.
Authors: Viktoria V. Pozdnyakova, Maria I. Maksimova, Liubov Yu Vladimirova, Natalia A. Maksimova, Yury Valentinovich Przhedetskiy
Journal: Journal of Clinical Oncology (2018)

e21529 Background: To compare the level of microvascular density and vasculoendothelial growth factor (VEGF) in tissues of benign and malignant melanocytic skin tumors. Methods: 60 pts (21-49 years old) with melanocytic skin tumors were studied. 30 pts had melanoma (T1-3N0-1M0) and 30 pts had nevus, including 9 pts with dysplastic nevus. The microvascular density marker – CD31 and VEGF were studied by IHC method. Results: CD31 level in melanoma pts was found as following: 70% of pts (21 of 30) had 12-18 vessels in sight, 30% (9 of 30 pts) had 8-12 vessels in sight; in pts with benign melanocytic tumors: 80% (24 of 30) had no more than 3 vessels in sight and in 20% (6 of 30) the level varied from 4 to 8 vessels in sight mostly in pts with dysplastic nevus. CD31 level in average was 14.0±1.3 in melanoma, 4.7±0.4 in dysplastic nevus and 2.8±0.3 in nevus correspondingly (p < 0.05); 3.8±0.9 in total in benign melanocytic skin tumors (p < 0.05). VEGF expression was found in 63.3% of pts (19 of 30) with melanoma, 50% (15 of 30) of pts with benign melanocytic tumors, among them 78.8% (7 of 9 pts) had dysplastic nevus and 38.1% (8 of 21 pts) had nevus. There was no VEGF expression in 36.7% (11 of 30) pts with melanoma and in 50% (15 of 30) pts with benign melanocytic tumors: 62% (13 of 21 pts) in nevus and 22.2% (2 of 9 pts) with dysplastic nevus. VEGF expression was 26.5±2.9% in total benign tumors group: 29.3±2.9 in dysplastic nevus and 23.6±2.1% in nevus while in melanoma group it was the highest 32.5±2.9%. The difference was statistically significant in melanoma and nevus group only (p < 0.05). Conclusions: The increase of CD31 was 3 times higher comparing to dysplastic nevus and 5 times higher to nevus (p < 0.05). VEGF expression was increased 1.4 times higher comparing to nevus (p < 0.05). These data could be used for diagnostic and treatment approaches for benign and malignant skin tumors as well as possible application of anti-VEGF agents in treatment of melanocytic tumors.
CD56 Expression Marks Human Group 2 Innate Lymphoid Cell Divergence from a Shared NK Cell and Group 3 Innate Lymphoid Cell Developmental Pathway
Authors: Luxi Chen, Youssef Youssef, Cameron Robinson, Gabrielle F. Ernst, Mary Y. Carson, Karen A. Young, Steven D. Scoville, Xiaoli Zhang, Regine Harris, Palak Sekhri, Anthony G. Mansour, Wing K. Chan, Ansel P. Nalin, Hsiaoyin C. Mao, Tiffany Hughes, Emily M. Mace, Yinghong Pan, Navin Rustagi, Sujash S. Chatterjee, Preethi H. Gunaratne, Gregory K. Behbehani, Bethany L. Mundy-Bosse, Michael A. Caligiuri, Aharon G. Freud
Journal: Immunity (2018)
TCT-775 A Systematic Review of Randomized and Non-randomized Studies Comparing Dual Therapy with Triple Therapy in Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention
Authors: Alexander Sullivan, Michael Nanna, Sunil Rao, Sarah Cantrell, C. Michael Gibson, Freek Verheugt, Eric Peterson, Megan Yee, David Kong
Journal: Journal of the American College of Cardiology (2018)
E3311 trial of transoral surgery for oropharynx cancer: Implementation of a novel surgeon credentialing and quality assurance process.
Authors: Shuli Li, Robert L. Ferris, F. Christopher Holsinger, Gregory S. Weinstein, Harry Quon, Ranee Mehra, Joaquin J. Garcia, Christine H. Chung, Maura L. Gillison, Lynne I. Wagner, Jolie Ringash, Jan S. Lewin, Eduardo Mendez, John A. Ridge, Jeremy Richmon, Scott Magnuson, Richard Bryan Bell, Russel B. Smith, Giovana Thomas, Barbara Burtness
Journal: Journal of Clinical Oncology (2016)

6054 Background: ECOG-ACRIN (E3311) examines the role of transoral head and neck surgery in treatment deintensification for stage III/IV p16+ oropharyngeal cancer (OPC). Patients with lateralized, resectable T1-T2 OPC and N1-N2b with no matted nodes undergo transoral resection and neck dissection, followed by risk-based adjuvant therapy. Intermediate risk patients [negative margins, N2 ± extranodal extension (ENE) ≤ 1mm] are randomized to 50Gy vs. 60Gy radiation. We established credentialing criteria and ongoing quality assurance (QA) for transoral surgeons wishing to accrue to E3311. Methods: Each surgeon attests to experience of > 20 cases of transoral resection of OPC, using either transoral robotic or laser microsurgery. Surgeons then submit paired surgical pathology and operative reports for 10 transoral resections within the past 24 months. Nine experienced head and neck surgeons established criteria for approval, review case submissions, on-hold status and ongoing QA. Positive margin(s) were permitted on only 1 of 10 cases during initial credentialing or while accruing to E3311. Results: Since 2013, 107 surgeons applied for credentialing. After peer-review, 71 surgeons were credentialed for E3311 at 51 different centers, with 49 surgeons having accrued > 1 and 31 having accrued ≥ 3 patients (accrual per surgeon 1-24, median = 4). Twelve surgeons were asked to provide additional, replacement cases, where histology or margin status was unclear or deemed insufficient during review. Of these, 10 were approved upon re-review. Two surgeons withdrew their applications, and 22 have not submitted cases for credentialing review. Ongoing QA has led to review of two surgeons with positive margin(s) in their first 5 cases. The composite QA stopping rule of 22% combining grade III/IV bleeding and positive margins was not met during planned DSMC review (August 2015), with 8% grade III/IV bleed rate and 3% positive margins. Conclusions: Initial surgeon credentialing and ongoing QA results in low rates of positive margins and grade III/IV oral bleeding rates in a multicenter trial of transoral surgery. Clinical trial information: NCT01898494.
Cell-free circulating tumour DNA (ctDNA) in the management of patients (pts) with non-biopsiable (Bx) advanced non-small cell lung cancer (NSCLC).
Authors: MArina Kushnir, Carmen Murias, Helen Winter, Param Bain, Christopher Abbosh, Dionysis Papadatos, Thomas Newsom-Davis, Tanya Ahmad, Charles Swanton, Martin David Forster, David Allan Moore, Philip Bennett, Iris Faull, Richard B. Lanman, Hendrik-Tobias Arkenau
Journal: Journal of Clinical Oncology (2018)

e24044 Background: Genomic profiling of cell-free ctDNA is a non-invasive method to guide personalised medicine. We assessed the utility of ctDNA in routine clinical practice where tumor Bx were impossible to obtain, tissue insufficient or clinically contraindicated. Methods: A 73-gene panel using ctDNA NGS (Guardant360®) was offered to consecutive stage 4 NSCLC pts - results were discussed in our Genomics Review Board to assess potential actionable alterations and enrolment into clinical trials. Results: 50 pts (37F:13M; median 64 yrs) participated. ctDNA was obtained in 6 treatment (Tx) naïve pts, in 22pts post 1st-line, in 7pts post 2nd-line, in 5 pts post 3rd-line and in 5 pts with > 4 Tx – in 5 pts prior Tx was unknown. EGFR status at Dx was known in 40 (23mt/17wt) and unknown in 10 pts. Of the pts with known EGFRmt, 6 pts progressed on gefitinib, 7 pts on afatinib, 8 pts on erlotinib, and 2 pts did not receive prior anti-EGFR Tx. ctDNA testing confirmed EGFRmt in 14 pts. In 9 pts with previously Bx-proven EGFRmt ctDNA did not detect an EGFRmt - the lag time between Bx and ctDNA was a median of 18 months (range 1-94 months). New EGFRmt were found in 3 pts with unknown EGFR status allowing access to anti-EGFR Tx. Acquired T790M were found in 4 pts progressing on prior anti-EGFR Tx, those pts received osimertinib. In 1 pt with ctDNA T790M+, a concomitant solid Bx was T790M -. Other alterations were, TP53 (n = 23), KRAS (n = 7), , ERBB2 (n = 1) NTRK1 (n = 2), NF1 (n = 12), MET (n = 7), BRAF (n = 5), PIK3CA (n = 5), ALK (n = 2), BRCA1 (n = 1), BRCA2 (n = 2), PDGFRA (n = 3), AR (n = 4), TERT (n = 3), CDK4 (n = 3), CDK6 (n = 3), FGFR2 (n = 2), STK11 (n = 2), KIT (n = 2), SMAD4 (n = 3), CDH1 (n = 1), NOTCH1 (n = 2), RB1 (n = 3), TSC1 (n = 1), ERBB1(n = 1), MTOR (n = 3), MYC (n = 3), ARAF (n = 1), GNAS (n = 1), AKT1(n = 1), CDKN2A (n = 2), ARID1A (n = 2), CTNNB1 (n = 1), CCNE1 (n = 1). Critical review in the GRB meeting was fundamental in interpreting the genetic alterations of significance. Conclusions: We confirm the feasibility/utility of ctDNA testing in NSCLC pts where tumor Bx were insufficient, impossible or contraindicated and identified 7 pts (14%) who based on their ctDNA results received 1st/2nd-line anti-EGFR Tx, several more were recommended for clinical trials.
ctDNA sequencing for early detection of colorectal cancers: Comparative analysis of colon cancer and rectal cancer data.
Authors: Xiaoni Zhang, Ligang Xia, Mingyan Xu, Hongyue Qu, Mingxin Wen, Charles E. Melançon, Jeremy Edwards, Shifu Chen
Journal: Journal of Clinical Oncology (2018)

e15653 Background: ctDNA has recently been recognized as a promising biomarker for colorectal cancer (CRC) screening and early diagnosis. However, we hypothesized that the clinical value of ctDNA sequencing for early detection of colon cancer (CC) and rectal cancer (RC) may be different. We therefore carried out experiments to identify potential differences. Methods: Twenty-nine patients with primary CRC were prospectively enrolled between September 2016 and April 2017, including 19 patients with CC and 10 patients with RC. For each patient, a freshly frozen tissue sample was collected during surgery and immediately stored at -80°C until DNA extraction; and its paired plasma sample was obtained before surgery. These samples were target captured using an 85-gene panel that covers most CRC related mutations, and sequenced to > 10,000× coverage using the Illumina platform. Mutations in each sample were identified; and the results compared. Results: CC patients were found to have higher median plasma cfDNA concentrations than RC patients (14.2 ng/ml vs. 8.94 ng/ml). The concordance rate of mutations detected in ctDNA and tissues were also found to be different in CC patients (18/19, 94.7%) compared to RC patients (5/10, 50%). For the 20 Stage I and Stage II patients, the mutation concordance rate between ctDNA and tissues was found to be 70% (14/20), indicating that ctDNA is a viable method for early detection of CRC. Conclusions: Liquid biopsy via ctDNA sequencing has great potential for early detection of CRC. Furthermore, we suggest that DNA from CC tissue is more likely to be released into blood than DNA from RC tissue.
Can lay health workers achieve the triple aim? Results from the Engagement of Patients with Advanced Cancer (EPAC) trial.
Authors: Manali I. Patel, VJ Periyakoil, Kate Bundorf, David Thom, Arnold Milstein, Steven M Asch, James Kahn
Journal: Journal of Clinical Oncology (2016)

6507 Background: Rising cancer costs demand innovative approaches to improve patient satisfaction and outcomes while reducing expenditures. We developed a novel model that integrates lay health workers (LHWs) into care to assist with documentation of patients’ goals and symptoms. We partnered with the VA to implement the approach and to study its efficacy on satisfaction, utilization, and costs. Methods: Newly diagnosed patients with stage 3 and 4 and recurrent cancer were randomly assigned to receive either the LHW intervention or usual care alone. Analyses were performed using intent-to-treat. χ², t-tests, or Wilcoxon Rank Sum were used to compare baseline characteristics and outcomes (satisfaction, utilization, and costs) between the intervention and usual care groups. Mean differences in total costs of care were compared using Wilcoxon Rank Sum. We used regression analysis to estimate differences in satisfaction between baseline and six months between the study arms. Results: Between August 15, 2013 and February 2, 2015, 213 patients were randomized, with 108 in the intervention and 105 in usual care. Median age was 69; 99% were male. The majority (78%) were non-Hispanic white with 6% non-Hispanic black, 2% Hispanic, and 2% Asian Pacific Islander. The majority (54%) were unmarried. The average travel distance was 92 miles. Lung cancer was the most common diagnosis (36%). The majority had stage 4 disease (54%). Six months after enrollment, 45% of patients had died in both study arms. More patients in the intervention had a documented goals of care (93% versus 29%; p<0.001) and advance directive (78% versus 38%; p<0.001) and received hospice services (40% versus 23%; p=0.008). Satisfaction was also higher among patients in the intervention group (p<0.001) compared to patients in usual care alone. Patients in the intervention had lower mean total healthcare costs as compared to patients in usual care alone, although not statistically significant ($134,901 versus $116,123; p=0.2). Conclusions: Incorporating timely documentation of patients’ goals of care and provision of ongoing patient support via LHWs improved patient satisfaction and reduced total healthcare expenditures.
Identifying predictive SNPs in patients with metastatic colorectal cancer (mCRC) using Random Survival Forests.
Authors: Shu Cao, Dongyun Yang, Sebastian Stintzing, Fotios Loupakis, Wu Zhang, Yan Ning, Marta Schirripa, Mitsukuni Suenaga, Satoshi Okazaki, Yuji Miyamoto, Afsaneh Barzi, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2016)

3606 Background: We have investigated many candidate genes in a pathway approach and showed significant association with response, PFS and OS, without understanding their clinical importance when comparing the different pathways. In this study, we used random survival forests (RSF), an ensemble tree method for analysis of survival data, to identify the most predictive genes. Methods: In this study, we analyzed 27 single nucleotide polymorphisms (SNPs) of 24 genes in 745 patients with mCRC receiving first-line FOLFIRI plus bevacizumab in three randomized phase III trials: PROVETTA (n = 220, male/female 129/91, median age 63 years), TRIBE arm A (n = 228, male/female 138/90, median age 60 years) and FIRE3 arm B (n = 297, male/female 195/102, median age 65 years). The SNPs were involved in the following pathways: tumor budding, angiogenesis, HIPPO, macrophage and autophagy. In RSF procedure, 1000 trees were constructed, with each tree constructed on a bootstrap sample from the original cohort. The variables were selected by Variable Importance and Minimal Depth. Results: Patient characteristics and outcomes are shown in the table below. In overall patients, CBP (rs129963) in Wnt pathway was identified to be the important predictor for PFS, ß-catenin (rs3864004) in tumor budding/Wnt pathway and DSCR1 (rs6517239) in HIPPO pathway were identified to be predictive for OS. In male, DSCR1 (rs6517239) was important for both PFS and OS. In female, PDGFRB (rs2302273) and HRG (rs2228243) from macrophage pathway were found predictive for PFS. HRG (rs2228243) was also predictive for OS. In patients with tumor on right-sided colon, EPS15 (rs17567) was predictive in PFS. In patients with tumor on left-sided colon, CBP (rs9392) and CBP (rs129963) were identified for PFS and OS, respectively. Conclusions: Our study identified ß-catenin, DSCR1, CBP, PDGFRB, HRG and EPS15 may serve as prognostic markers in mCRC patients treated with bev based chemotherapy. Total patients (n = 745) Male (n = 462) Female (n = 283) Right-sided (n = 178) Left-sided (n = 492) Median age, years 62 64 61 62 62 Median follow-up, months 49.6 50.4 49.6 44.9 49.3 Median PFS 10.3 10.3 10.3 9.4 10.9 Median OS 26.1 25.4 27.3 21.5 30.3
Efficacy and safety of liposome-paclitaxel and carboplatin based concurrent chemoradiotherapy for locally advanced lung squamous cell carcinoma.
Authors: Liming Sheng, Xianghui Du
Journal: Journal of Clinical Oncology (2018)

e20516 Background: The aim of this study was to evaluate the efficacy and toxicities of liposome-paclitaxel and carboplatin concurrent with radiotherapy for locally advanced lung squamous cell carcinoma (LSCC). Methods: The clinical data of 38 patients with locally advanced LSCC treated with liposome-paclitaxel based concurrent chemoradiotherapy were collected and reviewed. The overall response, toxicities, progression-free survival and overall survival were analyzed with SPSS 13.0 software. Results: The efficacy of treatment was classified as complete remission in 4 cases (10.5%), partial remission in 22 cases (57.9%) and stable disease in 12 cases (31.6%). The objective response rate was 68.4% (26/38). The most common types of hematological toxicities were anemia (65.7%) and leukopenia (57.9%), but all the events were transient. No paclitaxel-induced allergic reactions occurred during the treatment. The median PFS and OS time were 17.0 months and 29.0 months. Conclusions: Liposome-paclitaxel and carboplatin concurrent with radiotherapy showed a significant antitumor effect to LSCC with manageable toxicities. Further clinical investigation are warranted to evaluate the efficacy of this regimen.
Knee pain in an athletic young man
Authors: Charlotte Marriott, Christopher George
Journal: BMJ (2018)

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Dendritic cell vaccine transduced with ubiquitin-mesothelin fusion gene for pancreatic cancer.
Authors: Motoki Miyazawa, Toshiyasu Ojima, Masahiro Katsuda, Masaki Nakamura, Keiji Hayata, Mikihito Nakamori, Manabu Kawai, Seiko Hirono, Ken-Ichi Okada, Atsushi Shimizu, Yuji Kitahata, Hiroki Yamaue
Journal: Journal of Clinical Oncology (2016)

e14586 Background: We previously reported that the potential of developing future clinical applications of the vaccines using genetically modified dendritic cells (DCs) expressing human mesothelin (MSLN) which is potential target of immunotherapy for pancreatic cancer (Miyazawa et al. Cancer lett. 2011). Ubiquitinated antigens are processed to antigenic peptides by the ubiquitin (Ub)-proteasome system and presented by HLA class I. We investigated whether DCs transduced with Ub gene fused with MSLN gene could induce enhanced anti-tumor immune response. Methods: Adenoviral vector encoding MSLN gene (AdMSLN) and Ub-fused MSLN gene (AdUbMSLN) were generated. MSLN specific cytotoxic T lymphocytes (CTLs) were induced from autologous peripheral blood mononuclear cells (PBMCs) from healthy donors by in vitro stimulations with DC-AdMSLN or DC-AdUbMSLN. The cytotoxic activity was tested using a 4-hour 51Cr-release assay. PK1 which is a pancreatic adenocarcinoma cell line endogenously expressing MSLN and lymphoblastoid cell lines (LCLs) transduced with the MSLN gene were used as target cells. The interferon-gamma production in the culture supernatants were assessed by ELISA. Results: CTLs induced by DC-AdUbMSLN killed both PK1 and MSLN transduced LCLs more effectively than CTLs induced by DC-AdMSLN. The rate of intracellular MSLN expression in DC-AdMSLN was 56% compared with 2% in DC-AdUbMSLN by flow cytometry. The inhibition of MSLN degradation by using a proteasome inhibitor (MG132) increased the rate of MSLN expression to 46% in DC-AdUbMSLN. In addition, the interferon-gamma production by MSLN-specific CTLs incubated with DC-AdUbMSLN was much higher than MSLN-specific CTLs incubated with DC-AdMSLN under the same condition. Conclusions: These results indicated that DC-AdUbMSLN could induce CTLs more efficiently because ubquitinated MSLN promoted to be processed to peptides by the Ub-proteasome system and presented by DCs as peptide-HLA class I complexes.