tbuckley/cabot-search huggingface dataset:
CTCs enumeration and profile in different cancer types in a group of patients from the United States.
Authors: Dimitrios-Athanasios Ntanovasilis, Panagiotis Apostolou, Ioannis Papasotiriou
Journal: Journal of Clinical Oncology (2018)

e24033 Background: Circulating tumor cells (CTCs) constitute a cell subpopulation with great importance for oncologists, because of their prognostic value. CTCs detach from the primary tumor, circulate through the blood stream, and can initiate metastatic spread to other organs. This study presents clinical data from cancer patients in United States, incorporating CTCs number and profiling. Methods: Blood samples from cancer patients were collected and CTCs were isolated using enrichment protocols. Cellular and molecular based assays were used to enumerate them and study their expression profile. Markers were categorized according to involvement in cell cycle, migration, angiogenesis, growth factors, signal transduction pathways and resistance to radiotherapy. Statistical comparison was performed among samples and groups. Results: This study includes data from 181 cancer patients, categorized in groups according to cancer type. In 57 breast cancer patients (mean age 60±1.37) CTCs were 6.34±0.2/7.5ml. In 10 colon patients (mean age 63.1±3.93) CTCs were 7.97±0.71/ml. In 21 lung patients (mean age 63.61±2.53) CTCs were 6.40±0.38/ml. In 21 prostate patients (mean age 69.57±1.86) CTCs were 5.55±0.45/ml. In 6 pancreatic patients (mean age 63.83±3.62) CTCs were 6.75±0.0.52/ml. In 5 ovarian patients (mean age 54.8±4.91) CTCs were 6.54±0.76/ml. In 5 sarcoma patients (mean age 49.2±9.91) CTCs were 8.1±0.73/ml. In the last group of 56 samples, including less common types of cancer such as myeloma, lymphoma etc, the mean age was 60.87±1.86 while the CTCs were 5.97±0.25. The majority of samples expressed markers correlated with high proliferation, migration and angiogenesis ability. Regarding the hormone sensitivity, only breast (65%) and prostate (80%) patients’ CTCs were hormone dependent, while only 8% of total samples were resistant to radiotherapy, mainly in breast and colon cancer. Conclusions: The study of CTCs is very important for the scientific community. Their profile might be the key for predicting response to therapy as well as for monitoring the progression of the disease. Analysis of a wide spectrum of genes and proteins correlated with crucial biological procedures could be useful at clinical level.
Gli promotes tumor progression and metastasis through regulating EMT in non–small-cell lung cancer
Authors: L. Jiang, S. Jiang, L. Wang
Journal: Annals of Oncology (2018)

Background: Lung cancer is the leading causes of cancer-related deaths globally. The most frequent histologic type of lung cancer is non–small-cell lung cancer (NSCLC), accounting for approximate 85%. NSCLC is notoriously aggressive, and tumors often undergo epithelial-mesenchymal transition (EMT), a process required for invasion and metastasis. The components that control this process are thus promising therapeutic targets. This study examines the role of Sonic Hedgehog (SHh)/Gli pathway signaling in the regulation of EMT in NSCLC. Methods: Gli/EMT protein expression levels were examined by western blot in paired NSCLC patient tissues and NSCLC cell lines. Functional analyses were performed to investigate SHh/Gli signaling and EMT in NSCLC cell lines. MTS cell viability, luciferase reporter, qRT-PCR, and western blot assays were performed to analyze pathway activity, while wound healing and transwell assays were executed to measure cell migration and invasion. All experiments were conducted in triplicate, and subjected to two-sided student t-tests, ANOVA, and Scheffe's tests to determine significance when applicable. Results: Higher Gli1 expressions were detected in tumor samples than in paired normal tissues. Differential expression of EMT biomarkers and activation of p-AKT were observed in tumor tissues. N-Shh stimulation of cells significantly increased reporter activity in NSCLC cell lines, while Gli-i treatment of transfected cells showed less relative reporter activity. When subjected to both Gli-i and N-Shh treatment, NSCLC cell lines continued to demonstrate decreased Gli transcriptional activity. Gli inhibition is associated with decreased expression level of p-AKT, N-cadherin and Vimentin. Knockdown of both Gli1 and Gli2 showed decreased EMT, migrative and invasive ability. Cells stimulated by N-Shh demonstrated greater mobility. In addition, AKT-i treated cells also demonstrated inhibited EMT activity. Conclusions: This study provides evidence for aberrant upregulation of the Gli signaling pathway and a strong association between expression of Gli versus AKT and EMT markers in NSCLC. Inhibition of Gli and AKT pathway activity may thus serve as a potential therapeutic strategy for the treatment of NSCLC patients. Legal entity responsible for the study: Shanghai Chest Hospital. Funding: National Natural Science Foundation. Disclosure: All authors have declared no conflicts of interest.
Impact of age on treatment outcomes of head and neck squamous cell carcinoma (HNSCC) patients.
Authors: Jitlada Juengsamarn, Poompis Pattaranutaporn, Chuleeporn Jiarpinitnun, Teeranuch Chureemas, Nuttapong Ngamphaiboon, Phichai Chansriwong
Journal: Journal of Clinical Oncology (2016)

6081 Background: Impact of age on treatment outcomes of head and neck squamous cell carcinoma (HNSSC) patients. Methods: We retrospectively HNSCC patients treat at Ramathibodi hospital between 1/2008 and 12/2013. Nasopharyngeal carcinoma was excluded. We evaluated the effect of age including other risk factors on treatment outcomes. Results: Total of 601HNSCC patients with median age of 66 years (range 25-95) was identified. At the time of diagnosis, 43% of patients were ≥ 65 years, while 26% and 16% were > 70 and > 75 years respectively. In elderly patients ( ≥ 65years), 58% presented with locally advanced stage (stage III-IV). Increase of age was a worse prognostic factor for OS with HR 2.93 (95%CI 2.3-3.7, P < 0.01). In multivariate analysis, hypoalbuminemia was a poor prognostic factor for overall survival (OS). In locally advanced HNSCC elderly patient, chemoradiotherapy (CRT) did not improve OS when comparing with radiotherapy alone, HR 0.87 (95% CI 0.58-1.30, P 0.37). Conclusions: Age was associated with poor OS. Hypoalbuminemia was a poor prognosis factor for OS. CRT in locally advanced HNSCC elderly patients did not improved OS when compared with radiotherapy alone. Median OS Hazard ratio 95% Confidence interval Overall (n = 601) 28.6 (0.03-93) Primary site Oral cavity (39%) Oropharynx (19%) Hypopharynx (14%) Larynx (22%) ≥ 65 years vs < 65 years (n = 339) 67.3 vs 20.2 2.93 (2.3-3.7) P < 0.01 BMI in elderly 0.66 (0.28-1.57) P 0.35 Charlson score in elderly 0.84 (0.73-0.97) P 0.02 Albumin in elderly 0.95 (0.92-0.97) P 0.01 Surgery in elderly 0.72 (0.55-0.93) P 0.01 CRT vs RTalone in elderly 0.87 (0.58-1.30) P 0.37 CRT Cisplatin vs non-cisplatin regimen 0.87 (0.53-1.43) P 0.80
Impact of ruxolitinib in myelofibrosis post allogeneic stem cell transplant: A pilot study.
Authors: Joyson Poulose, Jeffrey J. Pu, Jozef Malysz, Michael Bayerl, Julie Fanburg-Smith, Raymond J. Hohl, Shin Mineishi, Junjia Zhu
Journal: Journal of Clinical Oncology (2018)

7071 Background: Allogeneic stem cell transplant (SCT) is the only potentially curative treatment for intermediate and high-risk myelofibrosis (MF). The use of Ruxolitinib (Rux) in the pre-SCT setting has demonstrated significant improvements in constitutional symptoms and splenomegaly. However, the optimal time of starting Rux and the effects of post-SCT Rux maintenance are still unclear. Methods: We analyzed outcomes of patients diagnosed with MF at our center who never received Rux (Cohort A), received only pre-SCT Rux (Cohort B), and received post-SCT Rux (Cohort C) between 6/2012 and 6/2017. Results: This study analyzed 16 patients, 11 male and 5 female, with median age of 59 years (range 47-72) at the time of SCT. The MF scores ranged from 2 to 3 (WHO Grade) at diagnosis. All patients had constitutional symptoms and splenomegaly at diagnosis except 1 who had prior splenectomy. There were 3 patients in cohort A, 9 patients in cohort B, and 4 patients in cohort C (3 patients received both pre- and post-SCT Rux; 1 received only post-SCT Rux). The median duration of Rux pre-SCT was 8 months (5-20); the mean duration of Rux post-SCT was 20 months (4-32). A JAK2V617F mutation was detected in all patients in cohort A, 7 patients in cohort B, and 3 patients in cohort C. All patients received reduced intensity conditioning regimen. The median time (days) for neutrophil engraftment (ANC>500) was 17 (13-18) in group A, 15 (0-74) in group B, and 12.5 (12-16) in group C. The median time (days) to transfusion independence was 148 (118-1140), 72 (11-105), and 24.5 (13-101) for patients in cohorts A, B, and C respectively. CMV/EBV viremia was detected in 8 patients before day 100, 3 of them in cohort A. Grade II-III acute GVHD was seen in all patients in cohort A and 4 patients in cohort B, but none in cohort C. The median spleen size reduction post-SCT was 17% in cohort A, 11% in cohort B, and 32% in cohort C. At the time of last follow up, an overall response was seen in 4 patients in cohort B, 2 with CR. All patients in cohort C achieved a CR and are alive. No one in group A achieved a remission. Conclusions: In this pilot study, patients treated with Rux pre- and post-SCT showed better outcomes and fairly good tolerability. Further studies on a larger patient population are warranted.
Outcomes after taranscatheter arterial chemoembolization plus radiotherapy compared with chemoembolization lone for unresectable hepatocellular carcinoma.
Authors: Yong Xing Bao, Lei Xiao, Huijie Zhao, Ge Wu, Gulizila Baishan, Rui Mao, Hua Zhang
Journal: Journal of Clinical Oncology (2017)

e15617 Background: Hepatocellular carcinoma (HCC) is the third leading cause of death globally, and it is the sixth most common malignant tumor. Recent epidemiological data showed that HCC is the most common cancer with the highest mortality in men under age 60 years in China. For HCC, inoperable and intermediate to advanced cases account for approximately 70% to 80% of all HCC cases in china. Base the BCLC guideline, transarterial chemoemolization (TACE) was the first choice for these patients, and 3-years survival approximately 30%. Therefore, treatments other than TACE are urgently needed. Methods: In order to evaluate the efficacy and safety of TACE combined with Radiotherapy (RT) or TACE monotherapy in the treatment of HCC, patients with unresectable and intermediate HCC who received the treatment of TACE puls RT (25 cases) or TACE monotherapy (50 cases) in our single center during Jan.2012 to June. 2013 were retrospectively analyzed. Results: The results showed that for the TACE combined with RT group (25 cases), the median survival time was 13 months, and the TACE group (50 cases) was 7 month respectively, Kaplan Meier survival curve and the log-rank test shows TACE combined RT group compared with TACE group with overall survival time difference is statistically significant (chi-square = 28.72, P&lt;0.05). Conclusions: TACE combined with RT is superior to TACE with respect to the overall survival for unresectable HCC patients.
CLIA validation workflow of a novel tumor cell isolation platform.
Authors: Valeria Sero, Aditi Khurana, Marc Ting, Judy Webb, Suman Verma, Amanda Gerber, Chiara Bolognesi, Cynthe Sims, Shelly Gunn, Philip Cotter, Mathew Moore, Gianni Medoro, Nicolò Manaresi, Farideh Z. Bischoff
Journal: Journal of Clinical Oncology (2017)

e23161 Background: DEPArray™ technology is based on Dielectrophoresis (DEP). High quality image-based cell selection enables users to identify, isolate and recover intact specific individual rare cells of interest from complex, heterogeneous tissues such as live or fixed cell suspensions. Here we demonstrate a validation workflow for application of molecular sequencing technologies and FISH downstream of rare cell recovery. Methods: FFPE scrolls (n = 93) were dissociated and stained with markers to distinguish putative stromal and tumor populations. DNA integrity was tested using a qPCR technique to predict the amount of DNA required for a successful downstream sequencing metrics. DEPArray™ recovered stromal and tumor cells underwent NGS analysis on an Illumina platform based DEPArray™ OncoSeek Panel. Separately, recovered stromal and tumor cells were also utilized for targeted HER2 FISH. CellSearch® cartridges (19 Breast and 5 Bladder Cancers) were processed through the DEPArray to isolate WBCs (CK-/CD45+/DAPI+; n = 30), CTCs (CK+/CD45-/DAPI+; n = 33) and atypical (CK-/CD45-/DAPI+; n = 47) cells. Recovered cells underwent whole-genome amplification with Ampli1™ WGA and quality controlled by Ampli1 QC. Ampli1 LowPass kit was then used to prepare NGS libraries for absolute CNA profiling by low-pass WGS. Results: Reproducibility and reliability was reported as 100% for instrument performance. For FFPE, the OncoSeek panel simultaneously detected SNPs, indels and CNAs of 63actionable and oncology relevant genes. For FISH, 95% concordance with conventional HER2 results was observed. For CTCs, Ampli1 LowPass detected copy number gains/losses confirming tumor origin of the CK+ cells. A portion of non-conventional cells also demonstrated copy number alterations consistent with tumor origin. Conclusions: The isolation of pure single or pooled tumor cells with the DEPArray™ technology can be used as a method to improve downstream MDx analysis using different techniques, thus to inform treatment decisions and provide valuable prognostic information.
A universal high-throughput liquid biopsy technique for rare tumor cells recovery from various body fluids.
Authors: Yaoping Liu, Tingyu Li, Wei Zhang, Lianjun Lin, Xiaolong Rao, Kunlin Yang, Jixin Zhang, Yan Xiong, Ligong Nie, Xinmin Liu, Haichao Li, Wei Wang
Journal: Journal of Clinical Oncology (2018)

e24224 Background: Recently, micro/nanotechnology has been involved in developing highly sensitive liquid biopsy technique because of the manipulation capability at single tumor cell level. However, the reported technologies targeted for the blood suffer from low throughput ( < 2 mL/min), and insufficient to realize a fast detection of the exfoliative tumor cells from the other clinical body fluid, which usually has a large volume up to hundreds of milliliters. Therefore, developing a technique to recover rare tumor cells from a large volume of body fluid is in high demand. Methods: Based on the Parylene MEMS technique, we have developed a micropore-array with the diameter and space of the micropore precisely controllable. Filters with diameter of 10 μm and space of 4 μm, i.e. porosity of 46.79%, were tested to recover rare cancer cells(spiked as few as 10 pre-labeled A549 (lung cancer cell) and T24 (bladder cancer cell) )from various large volume of fluids as shown in the table. Results: For the PBS samples, the throughput is 132.67±1.43 mL/min and the recovery rates of 10 A549 and T24 cells are 71.33±0.05% and 87.39±15.04 %, respectively. Although consisting of complex cell compositions, operations of the clinical samples still present high throughputs and excellent rare cell recoveries as shown in the table. Conclusions: The proposed micropore-array is a universal liquid biopsy technique and can recover rare target cells from a large volume of various clinical body fluids with high recovery rates and high throughputs. It holds promise in wide cancer related clinical diagnosis and treatments. Clinical trial information: 2016[1257], 2017[1384], 2017[1385].Samples Throughputs (mL/min) Recovery rates (%) of 10/104 pre-labeled A549/T24 cells PBS (10 mL, 5 cases) 132.67±1.43 71.33±0.05 (10 A549 cells) PBS (10 mL, 5 cases) 87.39±15.04 (10 T24 cells) Undiluted whole blood (5 mL, 3 cases ) 10.37±5.72 75.00±7.07 (10 A549 cells) Broncho-alveolar lavage fluid (15 mL, 4 cases) 16.20±15.12 86.00±5.29 (10 A549 cells) Urine (10 mL, 3 cases) 8.89±1.92 56.00±14.40 (10 T24 cells) Pleural fluid (15mL, 3 cases) 5.67±4.04 72.76±22.18 (104 A549 cells)
Abstract 14462: The Same Level of Brachial Systolic Blood Pressure Causes Much Stronger Cardiac Load for Older Than Younger People
Authors: Masatake Kobayashi, Hiroshi Kobayashi, Kazutaka Oshima, Yoichi Iwasaki, Yuto Kumai, Yasuhiko Tsunoda, Mineko Kino, Kenji Takazawa, Akira Yamashina
Journal: Circulation (2012)

The Same Level Of Brachial Systolic Blood Pressure Causes Much Stronger Cardiac Load For Older Than Younger People. Background:Brachial systolic blood pressure (bSBP) has been used as the evaluatio...
Neoadjuvant versus adjuvant chemotherapy for resectable malignant pleural mesothelioma: An analysis of the National Cancer Database.
Authors: Fernando Espinoza-Mercado, David Berz, Jerald D Borgella, Taryne A Imai, Harmik J Soukiasian
Journal: Journal of Clinical Oncology (2018)

e20556 Background: The National Comprehensive Cancer Network guidelines for Malignant Pleural Mesothelioma (MPM) recommend a combination of surgery and chemotherapy (neoadjuvant or adjuvant) for patients with clinical stages I-III that can tolerate surgical resection. The role of neoadjuvant vs adjuvant chemotherapy continues to be debated. Methods: The National Cancer Database file for mesothelioma 2004-2014 was queried for patients with clinical stage I-III MPM that underwent either pleurectomy/decortication or extrapleural pneumonectomy. Delivery of chemotherapy was dichotomized for neoadjuvant or adjuvant. Univariable and multivariable analysis was conducted. Overall survival was compared by Kaplan-Meier method. Groups were adjusted for age, sex, histology, surgery type, use of radiation therapy and TNM stage with Cox proportional hazards regression. Subgroup analysis was done for histologic subtypes and patients that received trimodality therapy using stratified log-ranks. Results: A total of 5,064 patients with MPM from 2006-20014 met selection criteria; of these, 45% (n = 2,232) underwent chemotherapy and 3.7% (n = 232) surgery as their only therapeutic intervention; meanwhile 13.7% (676) patients had surgery with any combination of chemotherapy and surgery (neoadjuvant [n = 310, 35.1%], or adjuvant [572, 64.9%]). On univariate analysis overall survival was 20.7 months (95% CI 18.3-23.0) with neoadjuvant chemotherapy, and 17.2 months (95% CI 15.5-18.9) with adjuvant chemotherapy (Log-rank p< 0.148). After adjustment for confounding variables, neoadjuvant and adjuvant chemotherapy had equivalent risk of death (neoadjuvant - Hazard Ratio [HR] 0.75 (95% CI 0.61-0.94, p< 0.014; adjuvant - HR 0.75 (95% CI 0.63-0.92, p= 0.005). This finding was consistent in subgroup analysis of patients in patients that received trimodality therapy. Conclusions: Timing of chemotherapy did not influence survival, irrespective of age, race, histology, clinical stage, comorbidity index and use of radiation therapy.
The impact of cumulative toxicity on physical quality of life in patients with metastatic colorectal cancer receiving first line chemotherapy.
Authors: Claudia Schuurhuizen, Inge Konings, Annemarie Braamse, Laurien Buffart, Haiko Bloemendal, Joost Dekker, Henk M.W. Verheul
Journal: Journal of Clinical Oncology (2017)

3564 Background: We have previously suggested that treatment related toxicity has impact on physical quality of life (QOL) scores, as opposed to global QOL. Moreover, the cumulative effect of experienced toxicities, including low-grades AEs, may be of more importance. The purpose of this observational cohort study was to evaluate the association between cumulative toxicity and physical and global QOL in patients with metastatic colorectal cancer (mCRC) receiving chemotherapy. Methods: 105 patients with mCRC starting first line chemotherapy were evaluated. All patients completed the EORTC-QLQ-C30 questionnaire at baseline and after 10 weeks. Toxicity, clinical outcomes and demographics were retrieved from patient records. For each patient, we calculated cumulative toxicity in three different ways: i) total number of adverse events (AEs) (all grades), ii) total number of grade 3-4 AEs, and iii) total number of AEs multiplied by their grade. The relation between each cumulative toxicity score and QOL assessed at 10 weeks, was studied. Results: The mean age of patients was 64.8 ± 9.7 years, 70.5% were male, and 83.8% received first line oxaliplatin based combination chemotherapy. AEs occurred in 98.1% of patients, grade 3-4 AEs in 37.1%, and grade 1-2 AEs in 61.0%. The mean number of experienced AEs (all grades) was 5.3 ± 2.7. The most common toxicities included diarrhea, neuropathy and fatigue. None of the toxicity scores was related to global QOL outcome. A higher total number of all grades AEs (β = - 2.2, 95%CI = -3.7; -6.6) and total number of AEs multiplied by grade (β = -1.3, 95%CI = -2.2; -3.5) were significantly associated with worse physical QOL. Conclusions: Cumulative toxicity, defined as the total of all grades AEs, significantly affects physical QOL in patients with mCRC receiving first line chemotherapy. Improvement of treatment related toxicity management by reducing the total number of AEs, may result in relevant improvements in patients’ QOL. Our results emphasize that future RCTs should present physical QOL outcomes instead of global QOL, as well as all grades and total number of toxicities for individual patients.
Combination of a therapeutic cancer vaccine and immune checkpoint inhibitors in prostate cancer.
Authors: Ravi Amrit Madan, Marijo Bilusic, Julius Strauss, Fatima Karzai, Lisa M. Cordes, Philip M. Arlen, Marc Robert Theoret, Myrna Rauckhorst, Colin Pritchard, Houssein Abdul Sater, Anna Couvillon, Amy Hankin, Monique Williams, William L. Dahut, Jeffrey Schlom, James L. Gulley
Journal: Journal of Clinical Oncology (2018)

5084 Background: Immune checkpoint inhibitors (ICIs) have yet to demonstrated efficacy as monotherapy in non-MSI-HI prostate cancer. Vaccines may increase immune cells in the tumor microenvironment, potentiating ICIs. Methods: This study combines PROSTVAC(P), a pox-viral based vaccine targeting PSA, ipilimumab (Ipi; 1 mg/kg) and nivolumab (Nivo; 240 mg) in patients (pts) with castration resistant prostate cancer (CRPC). The initial regimen was P on Day 1, all 3 agents (PIN) 2 weeks(wks) later, and PIN every 3 wks thereafter. After Ipi was removed the regimen = P on Day 1, P+Nivo on wks 2,4 and then Nivo every 2 wks with P monthly. Results: 11 pts enrolled with median age = 75 and PSA = 16.1. 10 were metastatic CRPC, 6 pts had an ECOG PS = 0 (5 PS = 1). 3 pts had grade 3 immune-related adverse events (irAE; all responded to steroids and continued P once complete). Only the first 2 pts were treated with PIN but had cystitis and hepatitis, respectively, after which Ipi was removed from the regimen. Of 9 P+Nivo pts, 1 had transient myocarditis. 1 of 2 pts treated with PIN had an 88% PSA decline and a partial response (PR) for 10+ months. Of the P+Nivo pts, 6 are evaluable for response (on trial > 3 months). The 2 pts with the greatest PSA decline have been evaluated for MSI-HI status, 1 was positive. Some patients have had late PSA declines from intra-study peak PSA. Clinical trial information: NCT01875250. Conclusions: Ipi was removed from regimen after first 2 pts had≥Gr 3 irAEs, only 1 irAE from the 9 pts on P+Nivo. P+Nivo may have activity in CRPC, additional follow-up and further MSI-HI testing is warranted. Pt # PSA decline > 30% from baseline Time on study (+ still on study) Additional information 1 (PIN) 88% (PR) 10+ months irAE cystitis, treated with steroids MSI-HI negative CDK12 mutation (bi-allelic) 2 (PIN) n/a 7.2 months irAE hepatitis, treated with steroids delayed PSA decline of 23% lasting 4.25 months 3 (P+N) n/a 4.5 months Off study for 2nd cancer diagnosis, not treatment related 4 (P+N) 97% 7.5+ months Substantial reduction in bladder mass MSI-HI positive 5 (P+N) 36% 4.8+ months n/a 6 (P+N) n/a 4.6+ months irAE myocarditis, treated with steroids delayed PSA decline of 34% continuing at 2 months 7 (P+N) n/a 3.5 months Progressive disease 8 (P+N) n/a 3.8+ months delayed PSA decline of 20% lasting 2.5 months