tbuckley/cabot-search huggingface dataset:
Effect of race on completion of chemotherapy in early stage breast cancer: A systematic review and meta-analysis.
Authors: Angela K Green, Emeline Aviki, Sujata Patil, Victoria Susana Blinder
Journal: Journal of Clinical Oncology (2018)

e18749 Background: Black women have a higher risk of death from breast cancer (BC) compared to whites. Survival in early stage BC is influenced by the relative dose intensity (RDI) of adjuvant chemotx and completion of recommended tx. Individual studies have indicated that black women more commonly receive dose-reduced or incomplete chemotx, thereby increasing their risk of BC-related mortality. Methods: We performed a systematic review of all articles published from January 1987 to June 2017. Eligible studies were in English and examined the influence of race or socioeconomic status on dose delays or dose reductions among women with stage I, II, and/or III breast cancer. We extracted data regarding RDI and incomplete treatment from each study and, if necessary, contacted study authors to obtain missing data. We used Review Manager 5.3.5 to test for heterogeneity and conduct pooled analyses using a random effects model. Results: Of 2116 titles, twelve met criteria for inclusion. Measures of chemotherapy dosing varied across studies: 2 studies measured RDI; 3 measured first-cycle dose reductions (an established proxy for RDI); 4 measured completion of recommended number of cycles; and 7 studies measured delay in initiation of tx after diagnosis or surgery. All 12 studies included comparisons by race; only 2 studies directly examined the association between socioeconomic status and chemotx dosing. We performed a meta-analysis evaluating the relationship between race and completion of recommended tx. (complete vs. incomplete). There was significant heterogeneity between studies (X2= 8.15, p = 0.04, I2= 63%). Thus a random effects model was used to pool outcomes. There was no significant association between race and completion of recommended chemotherapy, OR = 1.53 (95% CI: 0.97, 2.40). Conclusions: Outcome measures used to characterize the chemotx dosing in breast cancer treatment are varied. In a pooled analysis, the odds of not completing recommended adjuvant chemotx was not associated with race. The extent to which inadequate dosing of chemotx contributes to increased mortality among black BC patients remains unclear due to limited research and warrants future analysis.
Diverse Functions of Macrophages in Different Tumor Microenvironments
Authors: Ming Yang, Daniel McKay, Jeffrey W. Pollard, Claire E. Lewis
Journal: Cancer Research (2018)

Tumor-associated macrophages are a major constituent of malignant tumors and are known to stimulate key steps in tumor progression. In our review in this journal in 2006, we postulated that functionally distinct subsets of these cells exist in different areas within solid tumors. Here, we review the many experimental and clinical studies conducted since then to investigate the function(s), regulation, and clinical significance of macrophages in these sites. The latter include three sites of cancer cell invasion, tumor nests, the tumor stroma, and areas close to, or distant from, the tumor vasculature. A more complete understanding of macrophage diversity in tumors could lead to the development of more selective therapies to restore the formidable, anticancer functions of these cells. Cancer Res; 78(19); 5492-503. ©2018 AACR.
Phase II study of adjuvant chemotherapy with paclitaxel and nedaplatin for FIGO stage IB-IIA uterine cervical cancer with lymph node metastasis following radical hysterectomy: A Kansai Clinical Oncology Group study (KCOG-G1101).
Authors: Munetaka Takekuma, Yuka Kasamatsu, Shin Nishio, Hideo Omi, Tsutomu Tabata, Yuji Takei, Kaei Nasu, Yoshiyuki Takahashi, Shinji Toyoda, Yoshikazu Ichikawa, Atsushi Arakawa, Fuminori Ito, Hiroshi Tsubamoto, Taisuke Mori, Kimihiko Ito
Journal: Journal of Clinical Oncology (2017)

e17024 Background: A multicenter phase II trial was conducted to assess the efficacy and toxicity of paclitaxel and nedaplatin as the initial postoperative adjuvant chemotherapy for high-risk uterine cervical cancer. Methods: The patients with FIGO stages IB1-IIA2 squamous cell carcinoma of the uterine cervix were enrolled. Histologic confirmation of lymph node metastasis was mandatory. Intravenous paclitaxel 175 mg/m(2) over 3hours and nedaplatin 80 mg/m(2) over 1 hour were administered on day 1 of a every 28 day cycle, of which there were 5 cycles after radical hysterectomy. Results: 62 patients were enrolled into the study protocol from November 2011 to July 2015. The median age of patients was 48.5 years (range; 28-64). Median tumor diameter was 37 mm (0-34). 10 patients (16.1%) had parametrial invasion, 44 (71.0%) had deep stromal invasion, and 53 (85.5%) had lymph-vascular invasion. 30 patients (48.4%) had one metastatic lymph node, 11 (17.7%) had two, 3 (4.8%) had three, 5 (8.1%) had four and 13 (21.0%) had five or more. With a median follow-up of 36.9 months (range: 17.2-61.5), the 2-year progression-free survival rate and pelvic disease progression-free rate were 78.9% (95% CI, 68.5% to 89.3%) and 85.0% (95% CI, 75.8% to 94.3%), respectively. The 2-year overall survival rate was 93.3% (95% CI, 86.8% to 99.8%). Adverse events were almost acceptable. Grade 3-4 adverse events (NCI-CTC ver4.0) that occurred in 5% or more patients were neutropenia (60.7%) and infection (6.6%). The proportion of patients who completed 5 cycles of treatment was 90.3%. Conclusions: Adjuvant chemotherapy with paclitaxel and nedaplatin for patients with high-risk cervical cancer after radical hysterectomy was demonstrated to be an effective and feasible treatment. Phase III trial should compare this with concurrent chemoradiotherapy. Clinical trial information: 000005605.
Oncogenic microRNAs to predict relapse in early breast cancer patients.
Authors: Marek Sochor, Petra Basova, Michal Pesta, Jiri Bartos, Tomas Stopka
Journal: Journal of Clinical Oncology (2017)

e23021 Background: Early breast cancer is a frequent female disease with different outcomes. New approaches are needed in order to improve its prognosis. MicroRNAs (miRs) are modulators of gene expression and act as oncogenes and function to inhibit tumor suppressors and to promote metastasizing. Monitoring of miRs could be of benefit to the prognosis of EBC patients. Methods: We prospectively collected sera from 133 EBC patients (follow-up 53,25 months) in 3 time points (before I and after surgery II, after therapy III). Patients were stratified into high and low-risk groups according to HR, HER2, Ki-67, grade, LN. For RNA isolation serum was used followed by RT-qPCR and was applied longitudinal multivariate data analysis. Aim of the project was to determine serum expression of miR-155, miR-19a, miR-181b, miR-24 in 3 time points, to find difference in expressions between high and low-risk groups, to find association between miRs and clinical/pathological risk factors and associations in miRs expression and prognosis of EBC. Results: EBC patients significantly over-express miRs in time point I. In time point II the levels of miR-155, miR-181b, miR-24 significantly decreased ( p&lt; 0.05). miR-19a decreased in time point III ( p= 0.00869). Levels of miR-155, miR-19a, miR-181b, miR-24 are significantly more abundant in high-risk in comparison to low-risk patients ( p&lt; 0.05) and decrease upon therapy. The multivariate GEE model revealed that miR-155, miR-24 were predictive of the relapse ( p= 0.025 and 0.041). miR-19a, miR-181b are insignificant with respect to the relapse ( p&gt; 0.05). Triple-negativity, HER2+, grade III, LN+ have no effect on the probability of relapse ( p&gt; 0.05) when miRs are simultaneously taken into an account. The only risk factor that makes the prediction of relapse more precise is Ki-67 &gt; 20% ( p= 0.013 in case of miR-155 and p= 0.023 in case of miR-24). Conclusions: OncomiRs are significantly more abundant in EBC patients at diagnosis and decline after therapy. Differences in miR levels reflect EBC risk groups. The data shows that miR-155 and miR-24 enable monitoring of EBC and predict relapse independently of clinical/pathological risk factors. Combining the miR levels with Ki-67 expression further specifies the relapse probability.
Whole exome sequencing (WES) of metastatic leiomyosarcoma (LMS) and liposarcoma (LPS) and correlation of genomic aberrations with clinical outcomes in the phase III randomized trial of trabectedin (T) vs. dacarbazine (D).
Authors: Gurpreet Kapoor, Weimin Li, Dong Shen, Roland Elmar Knoblauch, Michael Gormley, George C. Wang, Deborah S. Ricci, Michael P. Smith, Clifford Motley, Sigrid Malbrain, Robert G. Maki, Margaret vonMehren, Shreyaskumar Patel, George D. Demetri
Journal: Journal of Clinical Oncology (2018)

11513 Background: This phase 3 study (NCT01343277) showed statistically significant improvement in disease control by T vs. D in patients (pts) with metastatic LMS and LPS (Demetri et al., JCO, 2016). WES was done to explore associations between genomic alterations and clinical outcomes in this prospective database. Methods: Of 518 pts enrolled on study, archival tumor samples were collected from 456 (88%) pts: 180 uterine LMS (uLMS), 149 non-uterine LMS (non-uLMS), 66 de-differentiated LPS (ddLPS), 46 myxoid LPS (mLPS) and 15 pleomorphic LPS (pLPS). Peripheral blood samples from a subset of 346 patients were also analyzed as matched normal to filter noise from nonpathogenic variants in WES. Results: Consistent with sarcoma TCGA data, these LMS and LPS samples had frequent homozygous gene deletions with relatively low mutational load. TP53 & RB1 alterations were frequent in LMS compared to LPS, and showed no association with clinical outcomes. Analyses of 103 DNA damage response (DDR) genes showed frequent ( > 20%) somatic alterations across subtypes, correlating with improved PFS only in uLMS tumors (HR: 0.63, p = 0.03). Genomic alterations in PI3K pathway genes were noted in 30% of mLPS and associated with worse PFS (HR: 3.0, p = 0.045). A trend towards better OS was noted in ddLPS tumors with MDM2 amplification (90%) compared to normal MDM2 copy number. Certain subtype-specific genomic aberrations in immune modulation pathways (uLMS and ddLPS) were associated with worse clinical outcomes, whereas alterations in immune suppressors (non-uLMS) and lipid metabolism (ddLPS) were associated with improved clinical outcomes. Conclusions: This detailed genomic analysis of a large cohort of metastatic LMS and LPS pts matched with prospective data on treatment outcomes suggests that aberrations in oncogenic pathways (DDR, PI3K, MDM2-p53) and immune modulation may contribute to response or resistance to treatment with T or D. Further analyses should inform our understanding of sarcomas and may aid clinical decision making for LMS and LPS.
Circulating tumour cells and survival in abiraterone- and enzalutamide-treated patients with castration-resistant prostate cancer.
Authors: Bram De Laere, Peter Van Oyen, Christophe Ghysel, Piet Ost, Wim Demey, Lucien Hoekx, Dirk L. Schrijvers, Barbara Anna Henk Brouwers, Willem Lybaert, Els Grieta Everaert, Jozef Ampe, Piet Van Kerckhove, Daan Joost De Maeseneer, Michiel Hendrik Strijbos, Alain Bols, Karen Fransis, Gert Van den Eynden, Jean Vandebroek, Steven J Van Laere, Luc Yves Dirix
Journal: Journal of Clinical Oncology (2017)

5049 Background: A heterogeneous landscape of patients with metastatic castration-resistant prostate cancer (mCRPC) exists in current clinical practice. We investigated the prognostic value of CTC enumeration and dynamics, in the context of second-line endocrine therapies (i.e. abiraterone or enzalutamide). Methods: In a prospective, multicentre study blood samples were collected from patients with mCRPC at baseline (n = 147) and follow-up (n = 95/147(64.6%)). At baseline, patients were stratified in favourable ( &lt; 5 CTCs/7.5mL) and unfavourable (≥5 CTCs/7.5mL) groups, whereas at follow-up, in those demonstrating a stable, in- or decreasing CTC count. PFS and OS were compared between groups. PSA changes at 10-12 weeks were evaluable in 83 patients. Results: Patients with ≥5 CTCs/7.5 mL (n = 59) at baseline had a shorter PFS (3.9 vs. 11.3 months, p&lt; 0.0001) and OS (9.34 months vs. not reached, p&lt; 0.0001). Patients demonstrating increasing CTCs (n = 21) on therapy had a shorter PFS (4.03 vs. 10.36 vs. 13.08 months, p &lt; 0.0001) and OS (11.2 months vs. not reached, p &lt; 0.0001), compared to patients with decreasing (n = 41) and stable (n = 33) CTCs, respectively. Multivariate Cox regression showed that the number of CTCs (HR (95%CI): 1.0054 (1.0006–1.010), p= 0.0260) and an increasing follow-up CTC count (HR (95%CI): 2.8987 (1.2856–6.536), p= 0.0103) were independent predictors of PFS. CTC increase was the sole independent predictor for OS (HR (95%CI): 7.3512 (1.7953–30.101), p= 0.0055). At 10-12 weeks, a PSA response of ≥30% and ≥50% was achieved in 46/83 (55.4%) and 33/83 (39.8%) patients, respectively, which was statistically different between chemo-naive or -pretreated patients (≥30%: p= 0.0395), patients with increasing, stable or decreasing CTC counts (≥30%: p= 0.0019; ≥50%: p= 0.0032), and patients with increasing or stable/decreasing CTC counts (≥30%: p= 0.0006; ≥50%: p= 0.0014). Conclusions: CTC levels are associated with PFS and OS in mCRPC patients, starting a new line of endocrine therapy. Follow-up CTC enumeration is associated with PSA response and its dynamics is an independent predictor of PFS and OS, thereby demonstrating the pharmacodynamic properties of CTCs.
Predicting long-term prognosis using targeted cell free DNA sequencing in resectable pancreatic cancer patients.
Authors: Bo Song, Ling Fung Paul Tang, Grace Q. Zhao, Shengrong Lin, Kang Ying, Gang Jin
Journal: Journal of Clinical Oncology (2016)

e23026 Background: Surgical excision of tumors provides the best long-term clinical outcome for pancreatic cancer patients. In this study, we evaluate the value of a novel assay utilizing plasma cell free DNA (cfDNA) in assessing the long-term prognosis of patients with resectable pancreatic cancer. Methods: To validate the accuracy and detection sensitivity of our novel NGS based cfDNA analysis, the allele frequency of KRAS mutations were compared to the result of ddPCR on cfDNA. Targeted cfDNA sequencing using a panel of 50 high-occurrence pancreatic cancer genes was performed on 84 plasma samples collected preoperatively from patients with resectable pancreatic cancer (stage I- II). The resulting somatic mutation profiles were then correlated with their corresponding clinical outcomes. Results: The validation experiments demonstrated that the allele frequency of KRAS between NGS highly correlate with ddPCR on cfDNA when the allele frequency was greater than 0.1%. 3 major KRAS variants and other known pancreatic driver genes including TP53, SMAD4, and CDKN2A were detected. Though somatic mutations were detected in only 1/3 of our sample set, all detected mutations were validated by tumor gDNA sequencing. Patients with matching mutation in cfDNA and tumor gDNA exhibited worse overall survival (os), especially those with the KRAS G12V mutation. Among patients with detectable levels of cfDNA, those receiving adjuvant chemotherapy demonstrated an improved progression free survival (PFS) compared to those not receiving chemotherapy. Conclusions: We have generated cfDNA-derived somatic mutation profiles for patients with resectable pancreatic cancer using our novel technology Nebula – Firefly, a high precision sequencing technology equipped with a unique error correction mechanism. Comparative analysis of the relationship between somatic mutation profiles from patient cfDNA and tumor gDNA with patient outcomes suggests the detection of somatic mutations in cfDNA may have prognostic value. In addition, our preliminary results reveal ctDNA somatic mutation profiles may help identify strong candidates for postoperative adjuvant chemotherapy for improved clinical outcomes.
Abstract 15366: Brain Emboli After Left Ventricular Ablation
Authors: Isaac R Whitman, Rachel A Gladstone, Nitish Badhwar, Henry H Hsia, Byron K Lee, S. A Josephson, Karl M Meisel, William P Dillon, Christopher P Hess, Edward P Gerstenfeld, Gregory M Marcus
Journal: Circulation (2016)

Introduction: Ablation for ventricular tachycardia (VT) or premature ventricular complexes (PVCs) is common. Ablation for atrial fibrillation (AF) has been shown to impose risk of subclinical cereb...
Impact of adrenergic and prostanoid inhibitors used chronobiologically on outcomes in patients with metastatic renal cell carcinoma.
Authors: Gouri Shankar Bhattacharyya, Hemant Malhotra, Amish Vora, Ghanashyam Biswas
Journal: Journal of Clinical Oncology (2018)

e16581 Background: Increasing evidence from pre-clinical from pre-clinical studies and retrospective studies, suggest that adrenergic and prostaglandin signalling pathways are important in the control of tumorigenesis. Data presented to-date in humans have predominantly been from retrospective studies. The data presented here will include the first data on the use of Sorafenib (S) with (Arm A) or without Propranolol (P) and Etodolac (E) (Arm B) in the pre-treatment of metastatic renal cell carcinoma. Methods: Patients with inoperable metastatic renal cell carcinoma, post first line (Sunitinib or Pazopanib) MSKCC Risk Stage II and III, ECOG Status 0 – 1 were eligible for this. This was a matched cohort study, P was administered chronobiologically at 9 am and 3 pm to reach a heart rate between 60 to 70 bpm (mean 40 mg/day), E was administered at 400 mg after dinner and was increased up to 600 mg to drop CRP below 50. After 1 week, S was administered at 400 mg/day and was increased to 800 mg/day after an additional week. The primary end point was Overall Survival. Results: From 2010 to 2015 – 48 patients were enrolled. Median age 64.6 years; 74% were male, BMI – 21, CRP – 69.3. Renal insufficiency Grade II in 8 patients (17%), Clear Cell RCC – 40 patients (83%). Characteristics were well balanced in both arms. Median duration and dose intensity of S with P + E was higher than in S Arm alone. Main severe Grade (4) Toxicity (Arm A/B) consists of hand foot syndrome - Grade 4 – 33% vs 0% and Grade 2 & 3 was seen in 67% vs 17%. For evaluable patients’ median overall survival was 4.9 months vs 12 months for Arm A vs Arm B respectively. The magnitude of change in select bio-markers (albumin, ferritin, CRP, VEGF, IL-6, Heart Rate), was significantly different in Arm A and in Arm B, but none were found to be predictive for this small study. Conclusions: S with P + E was well tolerated and feasible in metastatic renal cell carcinoma. The data shows significant improvement in it’s primary end points of over all survival with substantial reduction in the primary toxicity (HFSR). Further study of this is warranted.
Outcomes of concurrent radiation with cisplatin versus cetuximab in locally-advanced head and neck squamous cell carcinoma (LAHNSCC).
Authors: Ly Viet Do, Morteza Dowlatshahi, Zayd Parekh, Richard Trevino, Richard Eng, Karen Fann, Ngon Dinh, Raymond W. Lee, Charlene Sen-Yee Lee, Tin T. Hla
Journal: Journal of Clinical Oncology (2018)

e18007 Background: LAHNSCC can be treated with concurrent chemoradiation or concurrent radiation with cetuximab. Previous studies have suggested superior outcomes for LAHNSCC treated with radiation and cisplatin versus radiation and cetuximab. We compared outcomes amongst our cohort of patients who were treated with concurrent radiation therapy (RT) and cisplatin versus concurrent RT and cetuximab in a multi-institutional setting. Methods: Retrospective analysis was performed on stage III and IV LAHNSCC patients treated at Cancer Care Institute from 01/97 to 08/17 with cisplatin (n = 37) or cetuximab (n = 11) with concurrent RT to 7000 cGy using 3DCRT or IMRT with image guidance. Patients included in this study had LAHNSCC of the oropharynx, hypopharynx, larynx, and oral cavity. Patients with metastatic disease at presentation were excluded. Loco-regional control (LRC), overall survival (OS), and distant metastasis-free survival survival were then analyzed using the Kaplan Meier Method and Cox analysis tools. Results: 3-year LRC for concurrent chemoradiation was 100% vs. 42% for cetuximab and radiation (P < 0.0001). 5-year OS of concurrent chemoradiation was at 56% vs. 48%; for cetuximab and radiation (P = 0.6). 3 patients in the cetuximab treated group had successful salvage treatment with surgical resection. 2/3 of these patients required total laryngectomies. None of the patients treated with chemoradiation required salvage therapy. 2-year organ preservation rate for concurrent chemoradiation was 100% vs. 87.5% for cetuximab and radiation (P = 0.0047). Conclusions: The data obtained from this retrospective analysis adds to a growing body of literature that suggests that RT with concurrent cisplatin may yield superior outcomes in comparison to concurrent cetuximab. In addition, our data suggests a higher quality of life with improved organ preservation rates associated with chemoradiation. Randomized phase III trials should be performed to validate these findings.
TCT-171 Time Course of The Survival Advantage of Transcatheter Over Surgical Aortic Valve Replacement: Interplay between Sex and Patient Risk Profile
Authors: Daisuke Ueshima, Giulia Masiero, Alessandro Schiavo, Mostafa Rabea Abdelhaleem Badawy, Sorin Brener, Giuseppe Tarantini
Journal: Journal of the American College of Cardiology (2018)
Differences in presentation and management patterns in patients with hepatocellular carcinoma (HCC) between China and Singapore: Initial data from the HCC Registry in Asia.
Authors: Pierce K. H. Chow, Lequn Li, Jiangtao Li, Poh-Seng Tan, Fan Jia, Shukui Qin, Yvanka Marie Gilliam, Joanna Zhi Jie Ling, Mihir Gandhi
Journal: Journal of Clinical Oncology (2018)

e18587 Background: HCC is the 6th most common cancer in the world with > 70% of cases in Asia. There is limited real world data on how HCC is diagnosed, preferred treatment modalities, outcomes, and costs associated with treatments. Methods: The HCC Registry in Asia (AHCC08) is an investigator-initiated multi-country longitudinal cohort study of patients newly diagnosed with HCC between 2013 and 2018 in Asia-Pacific (ClinicalTrials.gov identifier: NCT03233360). Planned sample size is 2500 patients from 9 countries. We present initial data on diagnosis, etiology, stage at presentation, and treatment modalities of HCC from China [CN] (4 centers) and Singapore [SG] (2 centers). Results: 174 patients (132 CN; 42 SG) were enrolled till December, 2017. Patients from China were younger (mean age 52 years CN; 67 years SG), with a higher proportion of regular alcohol drinkers (46% CN; 21% SG). 93% and 41% of patients had hepatitis B in China and Singapore, respectively. Most Singapore patients were diagnosed by imaging criteria [AASLD/APASL] (98% SG; 14% CN). Patients in China present at later Barcelona clinic liver cancer [BCLC] stages (stage A: 32% CN, 48% SG; stage B: 11% CN, 21% SG). Few radiofrequency ablation [RFA] were carried out as the first-line therapy in China ( < 2% CN; 12% SG). Liver resection was preferred first-line HCC treatment in China (61% CN; 17% SG), followed by loco-regional therapy (TACE/TAE/TAI 30% CN; TACE/TAE/Y90 38% SG) and systemic therapy (10% CN; 19% SG). Conclusions: There is considerable variation in presentation and management patterns between China and Singapore. These data on real world practice will be useful to health policymakers, pharmaceutical companies and clinicians in improving public health policies and developing treatment strategies for HCC. Pierce K. H. Chow, Lequn Li, Jiangtao Li, Poh-Seng Tan, Fan Jia, Shukui Qin, Yvanka Marie Gilliam, Joanna Zhi Jie Ling, Mihir Gandhi on behalf of Asia-Pacific Hepatocellular Carcinoma (AHCC) Trials Group