tbuckley/cabot-search huggingface dataset:
Tumor-associated macrophages: CD206 and CD68 expression and patient outcomes in locally advanced breast cancer.
Authors: Chelsea Nicole Williams, David Blake Hodges, Jana Marie Reynolds, Ashwini Bhat
Journal: Journal of Clinical Oncology (2018)

e24130 Background: Research has shown that recurrence of cancer following initial therapy is related to the complex biology of tumor cells and their surrounding microenvironment. Tumor associated macrophages can compose up to half of the cell mass within a breast tumor.1 M2 macrophages have numerous functions that can promote the proliferation of tumor cells and metastasis.1 This study investigated CD206 and CD68 expression (macrophage markers) in the tumor stroma as a prognostic factor for overall survival and risk of recurrence in patients with locally advanced breast cancer that is estrogen and/or progesterone receptor positive (ER/PR+) and human epidermal growth factor receptor 2/neu negative (HER2-). Methods: A retrospective review of cases of women diagnosed with stage III, ER/PR+, Her2- breast cancer was performed by querying the Scott & White Medical Center tumor registry. Sixty-five patients met the inclusion criteria. Tumor samples were obtained from the initial biopsy. Expression was evaluated using a
Information Transparency in the Drug Approval Process—Reply
Authors: Bishal Gyawali, Daniel A. Goldstein
Journal: JAMA Oncology (2018)

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Locus-specific loss of heterozygosity (LOH) in <i>BRCA1/2</i> mutated (mBRCA) ovarian tumors from the SOLO2 (NCT01874353) and Study 19 (NCT00753545) clinical trials.
Authors: Kirsten Timms, Jessica S Brown, Darren R. Hodgson, J Carl Barrett, Tsveta Milenkova, Jonathan A. Ledermann, Charlie Gourley, Eric Pujade-Lauraine, Michael Perry, Alexander Gutin, Victor Abkevich, Jerry S Lanchbury
Journal: Journal of Clinical Oncology (2018)

5563 Background: The PARP inhibitor olaparib is approved in the US for patients with mBRCA (germline) advanced ovarian cancer, and in the EU for platinum-sensitive relapsed mBRCA (germline or somatic) ovarian cancer. A recent study reported retention of a normal allele in 7% of germline BRCA1 mutant ovarian tumors and 16% of germline BRCA2 ovarian tumors, and suggested that absence of locus-specific LOH may be a biomarker of primary resistance to DNA damaging agents (Maxwell KN et al, Nature Commun. 2017;22:319). Methods: mBRCA tumors were identified from two trials with patients with platinum sensitive relapsed ovarian cancer: SOLO2 (NCT01874353), Study 19 (NCT00753545). Analysis was performed on tissue obtained at the time of diagnosis. LOH status was assigned using a genomic instability algorithm, and confirmed via human review. Both processes evaluated relative read count and allele dosage data from 54,000 independent SNPs. Results: 210 mBRCA tumors (144 BRCA1, 66 BRCA2) were identified in the SOLO2 cohort. 103 mBRCA (70 BRCA1, 33 BRCA2) were identified in the study 19 cohort. There was lack of locus-specific LOH observed in 1 BRCA2 mutant in each trial. There was no statistically significant difference in the frequency of locus-specific LOH between the two cohorts. The frequencies of locus-specific LOH in the combined SOLO2 and Study 19 cohort were statistically significantly different to that reported by Maxwell et al (Table) for BRCA1, BRCA2, and combined BRCA1/2 mutants (p = 0.001, 0.01, 0.00002, respectively). Conclusions: Locus-specific LOH in mBRCA tumors from the SOLO2 and Study19 cohorts was almost universal; however it is possible that selection for platinum sensitivity enriched for tumors with loss of both alleles. These data support the use of germline or tumor BRCA1/2 testing as a means of identifying patients likely to respond to olaparib treatment in platinum-sensitive ovarian cancer. Further analysis of this phenomenon in additional cohorts will be presented. Clinical trial information: SOLO2 (NCT01874353), Study 19 (NCT00753545).LOH Status Maxwell et al SOLO2+Study 19 BRCA1 BRCA2 BRCA1/2 BRCA1 BRCA2 BRCA1/2 Yes 48 27 75 214 97 311 No 4 5 9 0 2 2 Total 52 32 84 214 99 313 % non-LOH 7.7 15.6 10.7 0 2 0.6
Second primary maligancies in acute promyelocytic leukemia.
Authors: Nibash Budhathoki, Binay Kumar Shah
Journal: Journal of Clinical Oncology (2016)

e18511 Background: Use of all trans-retinoic acid (ATRA), Arsenic trioxide and anthracycline based chemotherapy has significantly improved long term survival in acute promyelocytic leukemia(APL). There is limited data on second primary malignancy in APL survivors. This study was conducted to study the second primary malignancies (SPM) in APL in United States. Methods: We included adult acute promyelocytic leukemia patients aged 18 years and older from National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) 13 database in the study. We calculated the risk of second primary malignancies in the APL patients using multiple primary standardized incidence ratio (MP-SIR) session of SEER*stat software. Results: There were total of 1177 patients diagnosed with acute promyelocytic leukemia from January 1992 to December 2011. Their median follow up period was 38 months (0 - 127 months). Median age at the time of diagnosis of SPM was 65 years (20 years - 87 years). Median latency period for development of SPM was 75 months (6 - 178 months). Among APL survivors, forty two patients (3.47%) developed 47 second primary malignancies with O/E ratio of 1.09 and excess risk of 5.52 (p value = 1.15, 95% CI = (0.8-1.46).Overall there was no increased risk of cancer among APL survivors. However, among patients of 18-59 years age group, there was significant increase in salivary gland tumor (N = 3) with O/E ratio of 60.42 and excess risk of 5.51 (p value = < 0.05, 95% CI = 12.46 - 176.58). Among patients aged 60 years and above, urinary bladder carcinoma was the most common second primary malignancy. Five cases (17.85%) were reported during the study period with O/E ratio of 3.36 and excess risk of 22.49 ( p value = 0.03, 95% CI = 1.03 - 7.85). Both salivary gland tumor and urinary bladder cancers had latency of 5 years or more. Conclusions: Risk of salivary gland tumors and urinary bladder cancer is increased among APL survivors after 5 years of latency period compared to the general population.
Adjuvant chemotherapy and radiation options and their associated outcomes in surgically-resected non-small cell carcinoma.
Authors: Lisa Huang, Nengliang Yao, Geoffrey Graeber, Jianying Zhang, Debra Maddox, John Charles Flickinger, Malcolm M. DeCamp, John M. Varlotto, James Liebmann, William Vincent Walsh, Syed Quadri, Kerri McKie, Cameron Stock, Karl Uy
Journal: Journal of Clinical Oncology (2016)

e20001 Background: Adjuvant chemotherapy has been recommended for Stage IB(node negative tumors > 4CM) and II/III NSCLC and Radiation Therapy has been recommended for N2 disease. We assessed whether outcomes are affected by the type of chemotherapy used for adjuvant treatment or by the timing of radiation in relation to chemotherapy for patients with N2 disease. Methods: The SEER-MEDICARE database was retrospectively reviewed from years 2004-2011. Propensity score matching was used to balance characteristics based upon age, stage, sex and co-morbidities. Patients included in the study underwent a definitive surgical procedure and were not diagnosed with another primary cancer within one year of diagnosis. Cox proportional hazard models were used to measure overall survival(OS) and lung-cancer specific survival(LCSS) after adjusting for sociodemographic and tumor characteristics. Results: 17,361 patients were available after inclusion criteria. Approximately 29% and 12% received chemotherapy and radiation. Of the patients receiving known platin-based chemotherapy combinations, 73.4% and 26.6% received carboplatin or cisplatin doublets. The receipt of carboplatin regimens was related to Charlson co-morbidity score 4 or greater, p < 0.001 and renal failure, p < 0.001. As compared to cisplatin combinations, carboplatin combinations were associated with decreased OS (HR = 1.13, p = 0.03) and LCSS (HR = 1.15, p = 0.03). The timing of radiation(before, during, or following chemotherapy) and the type of radiation (IMRT vs others) were not related to the OS, LCSS, or cardiovascular mortality. In the subset of squamous cell carcinoma patients, gemcitabine use was associated with better OS (HR = 0.72, p = 0.001) but not LCSS. In the subset of patients with adenocarinoma, use of pemetrexed was not associated with an OS and LCSS as compared to other regimens. Conclusions: Although cisplatin doublets are associated with a LCSS and OS benefit, most patients receive carboplatin doublets. Neither timing or type of radiation was related to outcomes. Gemcitabine chemotherapy may have a survival benefit in patients with resected squamous cell carcinoma.
Global hunger grows amid conflict and climate change
Authors: Melanie Newman
Journal: BMJ (2018)

Global hunger continued to grow in 2017, ending hopes that its increase in recent years would prove to be short term.

The United Nations’ annual report on world food security in nutrition found that 821 million people—one in nine of the world’s population—were affected by hunger in 2017.1

The rise, from 804 million in 2016, represents the third consecutive year of increase in global hunger after more than a decade of steady decline. The situation is worsening in South America and most African regions.

“The big news is not good news,” said Jose Graziano da Silva, director general of the UN’s Food and Agriculture Organization, announcing the …
Phase 1/2 study investigating safety, tolerability, pharmacokinetics, and preliminary antitumor activity of anti-PD-L1 monoclonal antibody bgb-A333 alone and in combination with anti-PD-1 monoclonal antibody tislelizumab in patients with advanced solid tumors.
Authors: Jayesh Desai, Mark Voskoboynik, Ben Markman, Jeannie Hou, Dewan Zeng, Tarek Meniawy
Journal: Journal of Clinical Oncology (2018)

TPS3113 Background: Programmed cell death-1 (PD-1) and its ligand, programmed death-ligand 1 (PD-L1), play critical roles in the immune modulation of tumor progression. Tislelizumab is a humanized IgG4 monoclonal antibody against PD-1. A first-in-human, phase 1A/1B study (NCT02407990) demonstrated that single-agent tislelizumab was generally well tolerated and showed evidence of antitumor activity in patients with advanced solid tumors at the recommended dose of 200 mg administered every 3 weeks (Q3W). BGB-A333 is a humanized IgG1 monoclonal antibody against PD-L1 which increased functional activities of human T cells in in vitro studies, and showed antitumor activity in various cancer xenograft models. BGB-A333 blocks the interaction between PD-L1 and CD80 (B7-1), which in turn release the inhibitory signals to T-cells, enhances T-cell expansion, and prevents T-cell energy induction. Therefore, a combination of anti-PD-1 and anti-PD-L1 can potentially elicit stronger antitumor immunity through blockade of multiple complementary immune-suppressive signals in tumor microenvironments. Methods: This open-label study (NCT03379259) consists of two phases, each phase consisting of two parts. Phase 1 is designed to investigate the safety and tolerability of the BGB-A333 RP2D alone and in combination with tislelizumab. Phase 1A (BGB-A333 dose escalation) will follow a 3+3 design to establish the RP2D of BGB-A333. Phase 1B (combination dose confirmation) explores safety and tolerability of IV BGB-A333 (determined from dose escalation) in combination with IV tislelizumab (200 mg Q3W). Phase 2 is designed to evaluate the antitumor activity of BGB-A333 alone and in combination with tislelizumab. Phase 2A (BGB-A333 dose expansion) will enroll patients into two cohorts: non-small cell lung cancer and urothelial carcinoma. Phase 2B (combination dose expansion) will enroll patients with specific tumor types, which will be chosen based on data from phase 2A and other studies. The primary endpoint of the phase 2 study is overall response rate. Clinical trial information: NCT03379259.
Pretreatment neutrophilto lynphocyte ratio in ewing sarcoma family of tumors: An analysis of 570 patients.
Authors: Bivas Biswas, Akash Jha, Atul Batra, Moushumi Sengupta, Sameer Bakhshi
Journal: Journal of Clinical Oncology (2017)

e22504 Background: Ewing sarcoma family tumor (ESFT) is a systemic disease and inflammatory in nature. Inflammatory biomarkers have been identified as prognostic marker in various malignancies including sarcoma. Here we have evaluated the prognostic implication of pretreatment neutrophil to lymphocyte ratio (NLR) in ESFT. Methods: We have calculated baseline NLR from peripheral blood parameters in 570 patients of ESFT treated with uniform chemotherapy protocol in our institution from June’2003 to Feb’2015. Treatment protocol consists of neoadjuvant chemotherapy followed by surgery and/or radiotherapy as local treatment modality and adjuvant chemotherapy. NLR was dichotomized as high and low with high NLR defined as value over the median. Data was censored on 30 th Jan’2016. Results: Median age was 15 years (range: 0.1-55) with male: female ratio of 40:17 and 41% (n = 236) patients had metastasis at presentation. Most common sites of tumor were long bones in 209 (37%), thorax in 108 (19%) and pelvis in 90 (16%) patients. Hundred-one (18%) had a soft tissue primary. Twenty-five percent (n = 144) patients had systemic symptoms at presentation. Median symptom duration was 4 months (range: 0.5-36) with median tumor size 8.8 cm (range: 1.6-26). Median NLR was 1.55 (range: 0.08-12.87). High NLR was associated with older age (p = 0.002), female sex (p = 0.02), low serum albumin (p = 0.003) and high lactate dehydrogenase level (p = 0.03). After median follow-up of 32 months (range: 0.8-152), 5-year event-free survival (EFS) was 25.3% &amp; 35.8% and overall survival (OS) was 38% &amp; 48.7%, respectively in whole cohort and in those with localized disease. In the whole cohort, high NLR ( &gt; 1.55) emerged as independent prognostic factor predicting inferior EFS (Hazard ratio-1.36, p = 0.03) along with metastasis at presentation (p &lt; 0.001) and tumor diameter &gt; 8 cm (p = 0.005), in multivariate analysis. NLR couldn’t predict OS. Conclusions: High pretreatment NLR emerged as independent prognostic factor predicting inferior EFS in patients with ESFT. It is an easily available and cost effective biomarker. Prognostic nature of NLR should be evaluated in a prospective study and if proven, should be included in prognostic model to tailor therapy.
Obesity-related reduction in NT-proBNP levels in healthy individuals is greater in women compared to men
Authors: N. Navin Suthahar, W. C. Meijers, J. E. Ho, R. T. Gansevoort, A. A. Voors, P. Van der Meer, S. J. Bakker, S. Heymans, V. Van Empel, P. Van der Harst, D. J. Van Veldhuisen, R. A. De Boer
Journal: European Journal of Heart Failure (2018)
Outcomes with adjuvant chemo-radiation (ACRT) in patients (pts) with localized gastric cancer (GC): Analysis of National Cancer Data Base (NCDB).
Authors: Afsaneh Barzi, Dongyun Yang, Heinz-Josef Lenz, Sarmad Sadeghi
Journal: Journal of Clinical Oncology (2016)

4044 Background: The choice of adjunctive therapy (AT) in localized GC varies by tumor location (TL): cardia (cGC) and non-cardia (nGC). We assessed the effectiveness of 3 commonly used ATs: ACRT, Neoadjuvant Chemo-radiation (NACRT), and Perioperative Chemotherapy (PCh). Methods: 3 cohorts were defined corresponding to AT modality. Pts with GC and known TL who underwent definitive surgery and AT were eligible. 21477 pts were included in the AT cohorts. Overall survival (OS) was used as primary outcome. TL, TNM Stage, demographics, and facility type (FT), were included in the Cox model. Results: Median OS for ACRT was 42.1 months (95% CI 40.2-44.1) which was significantly higher vs. NACRT 35.9 (34.2-37.9: HR 1.17) and PCh 34.2 (32.7-35.8: HR 1.12) p < .0001. Stratifying cohorts for cGC, ACRT remained superior with median OS of 36.4 (34.5-39.0) vs. NACRT 34.0 (32.5-35.6: HR 1.13) and PCh 33.3 (31.2-35.6: HR 1.11) p < .0001. These number for nGC were 48.3 (45.6-52.0), 35.1 (31.0-40.9: HR 1.18), and 35.9 (33.5-38.3: HR 1.20) p < .0001. PCh downstaged average tumor size of 4.5 to 4cm in cGC (p < 0.001) but this effect was not present in nGC. In 10796 pts with cGC treatment distribution was 24%, 55%, and 21% for ACRT, NACRT, and PCh. These numbers for nGC were 10681, 55%, 7%, and 38%. Conclusions: Sequence and type of AT makes a significant difference in the outcome of GC. Within the limitations of a registry analysis, ACRT appears to be the best AT for both cGC and nGC. The distribution of patients among AT modalities reflects a difference based on cGC and nGC. This choice is not supported by these results and should be re-evaluated. Summary of results. ACRT NACRT PCh N (%) (cGC, nGC) 8517 (40) (2618, 5899) 6630 (31) (5892, 738) 6330 (29) (2286, 4044) Age 63 62 64 Male/Female (%) 66/34 82/18 66/34 Race: White/Black/East-Asia/Hispanic/others (%) 58/18/7/3/12/1/1 87/5/1/1/4/1/1 63/15/5/3/12/1/1 Differentiation: well-moderate/poor/unknown (%) 70/26/4 51/36/13 67/27/6 FT: Academic/non-academic 35/64 50/50 48/52 Insurance: Private/Medicare/Medicaid/Others (%) 43/41/9/7 51/38/5/6 43/43/7/7 Pathological Stage 0, I, II, III, IV (%) 0/13/32/48/7 3/23/34/37/2 1/17/30/43/8
Abstract 20453: Clinical Utility of Japan-CTO and PROGRESS CTO Scores in Predicting Long-Term Outcomes of Coronary Chronic Total Occlusion Recanalization
Authors: Jon Suh, Hyun Woo Park, Hyung Oh Choi, Ho-Jun Jang, Tae-Hoon Kim, Sung Woo Kwon, Sang-Don Park, Pyung Chun Oh, Jeonggeun Moon, Woong Chol Kang, Yoon Haeng Cho, Hee Yeol Kim, Nae Hee Lee
Journal: Circulation (2017)

Introduction: Patient selection and predicting clinical outcomes of percutaneous coronary intervention (PCI) of chronic total occlusion (CTO) remain challenging. Hypothesis: We hypothesized that bo...
Multi-site implementation of patient-reported outcome measures for personalized care and patient activation in symptom management.
Authors: Doris Howell, Madeline Li, Zeev Rosberger, Nicole Montgomery, Carole Mayer, Anne Snider, Denise Bryant-Lukosius, Marc Hamel, Rosanna Faria, Lorraine Martelli, Alyssa Macedo, Adriana Krasteva, Lisa Catherine Barbera
Journal: Journal of Clinical Oncology (2016)

e21665 Background: The Improving Patient Experience and Health Outcomes Collaborative (iPEHOC) is a multi-site quality improvement initiative in six cancer programs across Quebec, Ontario and remote Aboriginal clinics. The goal of iPEHOC is to facilitate the uptake of a standardized core set of patient-reported outcome measures (PROMs) for personalized treatment planning and patient activation in routine cancer care. Methods: The iPEHOC computerized system includes a tailored patient assessment of PROMs for symptoms of pain (BPI), fatigue (CFS), depression (PHQ-9) and anxiety (GAD-7), with a graphic output for customizing care in the clinical encounter. These symptoms were selected as a priority for PROMs implementation given their prevalence and impact on patients. Data is collected from electronic tracking systems to evaluate the implementation of PROMs and symptom severity in each area. The iPEHOC intervention includes standardized case-based education to enhance integration of PROMs for use in collaborative treatment planning and patient activation to improve symptom outcomes. Sites tracked clinician participation and knowledge translation activities through a standardized reporting tool. This system was implemented in sites with different stages of readiness, models of care and patient population complexity. Results: Preliminary results reveal screening rates across sites ranging from 56% - 100%, with 38% – 70% of patients triggering at least one additional PROM. Averaged across the pilot sites 42%, 32%, 59% and 95% of patients scored between moderate to severe on PROMs for depression, anxiety, pain interference and fatigue, respectively. Clinical teams from all participating sites attended education and ongoing case-based learning sessions on the use of PRO data. Conclusions: Routine collection and uptake of PROM data in clinical care is feasible with attention paid to organizational alignment as well as the use of integrated knowledge translation that engages key stakeholders and case-based training. The use of best practices in change management can transcend differing organizational context and cancer care delivery systems to improve patient experience.
Population pharmacokinetics of CAP7.1 and the effect on total target lesion size in adult patients with biliary tract cancer.
Authors: Matthias Machacek, Ulrich-Frank Pape, Ulrich Keilholz, Marianne Sinn, Stefan Kasper, Johannes Meiler, Arndt Vogel, Lothar Mueller, Karel Caca, Jan Kuhlmann, Oswald Burkhard, Victor Rodriguez Laval, Glyn Steventon, Nalan Utku, Holger Jansen
Journal: Journal of Clinical Oncology (2016)

e15602 Background: The aim of this study was to describe the population pharmacokinietics (PK) of CAP7.1, the prodrug of etoposide, and to describe how changes in total target lesion (TTL) size in biliary tract cancer (BTC) patients depend on treatment with CAP7.1. Methods: Non linear mixed effects modeling with Monolix was used to develop a population PK model. Data for the population PK model was from an open label, dose escalation phase I study and the ongoing randomized, multicenter phase II trial in BTC patients. Data from a total of 39 patients with 434 observations was available for PK modeling. Variability in CAP7.1 plasma concentrations exeeded those of etoposide; for this reason a dose-etoposide PK model was developed without taking into account CAP7.1 concentrations. The individual a posteriori PK model parameter estimates were then used with Simulx to simulate etoposide AUC0-24h , cmax and cmin for each BTC patient and compared with the individual changes in TTL size. Results: Etoposide PK was best described with a two compartmental model with a first order metabolic conversion rate and with linear clearance from the central compartment. The metabolic rate was 0.39 1/h (CV 44%), the clearance 3.2 L/h (CV 56%), the first volume 6.2 L (CV 37%), and the two exchange rates between the two compartments were k12 = 0.53 and k21 = 0.2 1/h. The calculated terminal half life of etoposide was 7.9 h. Linear regression analysis between the simulated AUC0-24h and change in TTL size showed that a higher AUC0-24h was associated with a lower increase in TTL size (R2= 0.172). For an AUC0-24h larger than 100 h ug/mL six out of eight BTC patients had an increase in TTL size of less than 20%. Similarly, a higher cmax (R2= 0.177) or cmin (R2= 0.11) were associated with a larger effect on TTL size although less pronounced for cmin . Conclusions: While the PK of CAP7.1 was variable the dose-etoposide population PK could be well described. The emerging pattern from the data analysis showed that for a higher etoposide AUC0-24h a larger fraction of patients could maintain the increase in TTL size below 20% for the observational period in the phase II study in BTC Clinical trial information: NCT02094560.