tbuckley/cabot-search huggingface dataset:
Dissecting the effect of age on immune response in melanoma patients.
Authors: Nathaniel H. Fleming, Kevin P. Lui, Richard L. Shapiro, Russell S. Berman, Anna C. Pavlick, Judy Zhong, Michelle Krogsgaard, Ines Esteves Domingues Pires Da Silva, Iman Osman
Journal: Journal of Clinical Oncology (2014)

9058 Background: Older ageat diagnosis has been shown to be an independent negative prognostic factor in melanoma. Nevertheless, no biological basis for the impact of age on melanoma has been defined. In this study, we examined the impact of patient age on cellular immune response as well as response to immunotherapy treatment in the adjuvant setting in a well-studied cohort of melanoma patients. Methods: A prospectively-enrolled cohort of patients presenting with stage III melanoma at NYU was studied. Associations between age at diagnosis and presence of tumor-infiltrating lymphocytes (TILs), response to immunotherapy, and stage IV progression-free survival (PFS) and overall survival (OS) were tested by log rank test. In addition, checkpoint PD-L1 expression was tested in pre-treatment tumor specimens in a subset of patients. Results: 316 patients (median follow-up for survivors: 45 months) were studied and categorized into two groups by age at diagnosis: ≤60 years (n=163) and >60 years (n=153). The two groups were well matched by clinical substage at presentation. Patients in the older group had significantly shorter OS compared to the younger group (P=0.039). TILs were absent in a significantly larger proportion of the older compared to younger group (35% versus 21%, respectively; P=0.017). Among patients who received adjuvant immunotherapies (n=86), patients in the older group had significantly shorter OS (P=0.048), with a similar trend for PFS (P=0.059). No significant survival differences were observed among patients who received non-immunotherapy treatments (n=57) or no adjuvant treatment (n=165). We reasoned that PD-L1 expression could explain the difference in response to immunotherapy treatment by age; however, no significant difference was observed in PD-L1 expression by age among 66 cases tested at the time of submission. Conclusions: Data suggest that decreased immune response and a consequent lack of response to immunotherapy might be contributing, at least in part, to the worse prognosis of older melanoma patients. PD-L1, a key inhibitory receptor, does not seem to be responsible for the observed impaired immune response. Treatment strategies for melanoma patients may need to account for biological differences by patient age.
Barriers to creating the next-generation cancer registry.
Authors: David M. Dilts, Steven Kunyuan Cheng, Allison Stover Fiscalini, Carlie Kennedy Thompson, Mike Hogarth, Laura Esserman
Journal: Journal of Clinical Oncology (2014)

e17682 Background: The IOM report Delivering High-Quality Cancer Care highlights the need to improve the cancer care system. One idea is to convert current, passive, retrospective cancer registries into active, point-of-care, prospective data. This study identifies barriers to such a conversion. Methods: This multi-center study across the Athena Breast Health Network (UC-system) investigated the interface between providers’ workflow, patient flow, and information dataflow to identify barriers. Multiple interviews were completed at 4 UC-sites including at least 1 surgical, medical, and radiation oncologist, plus pathologist and registry expert at each site. Process maps were created and validated for accuracy and consistency. Barriers to such a registry were collected during 45 interviews. Results: The patient-oriented flow map yielded fairly standard flows across sites. The dataflow map used 35 breast cancer data elements, identified from the ASCO/HL7 Breast TPS (draft). Each element was mapped to the patient flow to identify: when the data could be captured, when data could be available for patient care, and which provider could be responsible for capturing data. There are 74 potential locations in the process where data could be captured. Of these, 40 (54.1%) have more than 1 provider responsible for data. Duplicate responsibilities were greater at interface points, such as at patient referrals. > 350 barriers were identified and classified into 7 categories: information discovery challenges, interface & functionality hurdles, process burdens, collaboration issues, data variability, clinical trials visibility, and training complexity. 3 overarching challenges were discovered: identifying if data exist somewhere in the EHR, if so where do they resides, and with multiple data sources in the EHR, where is the most accurate source of data. Details on each of these barriers, coupled with potential solutions were identified. Conclusions: This study documented patient-, data-, and work-flows, plus barriers to transforming cancer registries from passive, retrospective data sources to active, point-of-care decision-making support systems. To achieve the IOM recommendations and to achieve the future of oncology care, such a conversion is required.
Early tumor shrinkage versus early response as a predictor for overall survival (OS) in patients with metastatic colorectal cancer (mCRC) treated with triplet chemotherapy regimens (TCR).
Authors: Shouki Bazarbashi, Ali Husain Aljubran, Ahmad Al Zahrani, Wael Edesa, Mohamed Nabil-Ahmed, Mohammed Shoukri
Journal: Journal of Clinical Oncology (2014)

e14580 Background: TCR with fluoropyrimidines, oxaliplatin(O) and Irinotecan (I) have shown better efficacy in term of response and survival in mCRC. Early tumor shrinkage (ETS), defined as ≥ 20% shrinkage in tumor size per RECIST criteria, have shown to be a predictive for progression free survival and overall survival in mCRC in patients treated with anti-EGFR therapy. We report here the predictive potential of ETS in patients with mCRC treated on our prospective phase I-II trial of the combination of Capecitabine (C), O, I, and bevacizumab (B). Methods: Eligible patient had locally advanced unresectable or mCRC. Patients received 5-8 cycles of the combination of C: 1,000 mg/m2 bid day1-14, O: 130 mg/m2 IV day 1, I: 150 mg/m2IV day 1 and B: 7.5 mg/kg bodyweight IV on day 1. Cycles repeated every 21 days. Patients with response or stable disease were then maintained on the combination of C and B till progression. Patients on the TCR had radiological assessment for response after cycles 2, 5, and 8 and then every 3 cycles. Tumor measurement according to RECIST criteria and at each CT evaluation was recorded for every patient. Results: 54 patients enrolled. Median age 52 years (range 23-74). 28 (52%) were males. Performance status 0/1/2 were 11.3%/66%/19%. 9.4% received prior adjuvant chemotherapy. 54.7% had multi-organ involvement. Median follow up was 23 months. 45 patients evaluable for response. Response evaluation: CR: 4.4%, PR: 60%, SD 31% for a clinical benefit of 95.4%. 33% qualified for early response (CR or PR at 1stevaluation), 40% qualified for ETS. Median PFS and OS for the whole group was 16 (95% CI: 15.6-25.3) and 28 months (95% CI: 23.9-33.63) respectively. PFS and OS for patients achieving early tumor shrinkage vs no was 25 months and not reached vs. 9 and 22 months respectively(p=0.006 for both), and for early responders was 28 and 28 months vs. 9 and 28 months (p=0.02 and 0.5 respectively). Conclusions: Both ETS and response evaluation by RECIST criteria at 1st evaluation are predictor of PFS while only ETS predict OS in mCRC patients treated with TCR.
Comparison of outcomes of locoregionally advanced oropharyngeal and non-oropharyngeal SCC over two decades.
Authors: Lauren C. Herman, Theodore Karrison, Mary Ellyn Witt, Charles Muller, Kerstin Stenson, Elizabeth A. Blair, Ezra E.W. Cohen, Tanguy Y. Seiwert, Daniel J. Haraf, Everett E. Vokes
Journal: Journal of Clinical Oncology (2014)

6048 Background: Human papillomavirus (HPV) has emerged as a causative agent and positive prognostic factor for oropharyngeal (OP) head and neck squamous cell cancer (HNSCC). This prompts inquiry into whether recent improvements in HNSCC outcomes are due to therapy improvements or the increasing incidence of HPV-related HNSCC. Methods: We performed a review of all patients treated for locoregionally advanced HNSCC with chemotherapy and radiation at the University of Chicago on a series of prospective institutional trials. Patients were divided into three groups according to the time period during which they were treated. Groups one, two, and three were treated between 1993-1998, 1999-2003 and 2004-2010 respectively. Trends were compared for OP and non-OP. Results: 422 patients were identified with OP (55.7%) and non-OP (44.3%) cancers. All patients had ECOG 0-2. Median age was 57 yrs. OP overall survival (OS) improved over time with 5 yr OS of 42.3% (group 1), 72.5% (group 2), and 78.4% (group 3), p<0.001. There was a trend towards improved 5 yr OS for non-OP patients with 51.0% (group 1), 58.8% (group 2), and 66.3% (group 3), p=0.16. Similarly 5 yr progression free survival (PFS) improved for OP groups from 42.3% to 68.4% to 75.8% (p<0.001). The respective increase in non-OP was from 42.9% to 53.6% to 61.7% (p=0.094). Five year distant failure free survival (DFFS) was 42.3%, 71.1%, and 77.8% (p<0.001) for OP and 46.9%, 57.1%, and 66.0% (p=0.13) for non-OP. Trends remained statistically significant for OP groups after adjusting for baseline covariates but were diminished in the non-OP group (p=0.51, p=0.30, and p=0.38 for OS, PFS, and DFFS respectively). Conclusions: Over the past two decades, OP HNSCC outcomes (OS, PFS, DFFS) have significantly improved while non-OP HNSCC outcomes have trended toward improvement. Although our patients are not specifically stratified by HPV, it is likely that improving OP outcomes are due to the increasing incidence of HPV-related HNSCC in the OP. These data further justify trial stratification for HPV status, investigations of novel approaches for patients with carcinogen-related HNSCC, and current de-intensification approaches for HPV-related HNSCC.
Estimation of renal function in patients with liver cirrhosis: Impact of muscle mass and sex
Authors: Jeong-Ju Yoo, Sang Gyune Kim, Young Seok Kim, Bora Lee, Min Hee Lee, Soung Won Jeong, Jae Young Jang, Sae Hwan Lee, Hong Soo Kim, Young Don Kim, Gab Jin Cheon
Journal: Journal of Hepatology (2019)
Oxidative DNA damage repair products as molecular markers of cancer.
Authors: Krzysztof Roszkowski, Piotr Blaszczyk, Anna Mucha-Malecka, Anna Bak, Gabriela Karczewska, Paulina Makowska
Journal: Journal of Clinical Oncology (2014)

e13525 Background: The broad spectrum of oxidative damage DNA biomarkers: urinary excretion of 8-oxodG (8-oxo-7,8-dihydro-20-deoxyguanosine), 8-oxoGua (8-oxo-7,8-dihydroguanine) as well as the level of oxidative damage DNA in leukocytes, was analyzed in cancer patients and healthy subjects. Methods: 222 cancer patients and 134 healthy volunteers were subjected the analysis, using methodologies which involve HPLC (high-performance liquid chromatography) prepurification followed by gas chromatography with isotope dilution mass spectrometry detection and HPLC/EC. Results: For whole patient population (n=222) the median values of 8-oxoGua and 8-oxodG in urine samples were 12.44 (interquartile range: 8.14-20.33) [nmol/24 hr] and 6.05 (3.12-15.38) [nmol/24 hr], respectively. The median values of 8-oxoGua and 8-oxodG in urine samples of control group (n=85) were 7.7 (4.65-10.15) [nmol/ 24 hr] and 2.2 (1.7-2.8) [nmol/24 hr], respectively. The level of 8-oxodG in DNA isolated from leukocytes of patient population (n=179) and of control group (n=134) was 4.93 (3.46-9.27) per 10'6 dG and 4.46 (3.82-5.31) per 10'6 dG, respectively. Conclusions: The results suggest that oxidative stress in cancer patients demonstrated by augmented amounts of these modifications in urine could be typical not only for affected tissue but also for other tissues and even the whole organism. Assay that enables to determine levels of basic markers of oxidative stress might be applied in clinical practice as additional, helpful marker to diagnose cancer disease.
Therapeutic Candidate Alpn-101, a Dual ICOS/CD28 Antagonist, Potently Suppresses Human/NSG Mouse Xenograft Graft Vs. Host Disease (GvHD) in a Dose Ranging Study and Reduces Disease Activity in a Mouse Model of Hemophagocytic Lymphohistiocytosis (HLH)
Authors: Stacey R. Dillon, Katherine E. Lewis, Katherine Verbist, Paige Tedrick, Sabrin Albeituni, Ryan Swanson, Lawrence S. Evans, Steven D Levin, Mark W. Rixon, Stanford L. Peng, Kim E. Nichols, Kristine M. Swiderek
Journal: Blood (2018)
Abstract A25: Intragroup genomic, transcriptional, and epigenomic variability is higher in sporadic than in BRCA1-associated hereditary triple-negative breast tumors
Authors: Kivvi Duarte de Mello Nakamura, Rodrigo Fernandes Ramalho, Rafael Canfield Brianese, Ana Krepischi, Bruna D. F. Barros, Dirce Maria Carraro
Journal: Clinical Cancer Research (2018)

Abstract Intra-tumor genetic heterogeneity is a possible cause of therapy resistance and has consequences in the disease progression and patient survival. Triple-negative breast cancer (TNBC) is associated with rapid growth, early metastasis, and worse prognosis than other breast cancer subtypes. Close association has been identified between TNBC and germline loss-of-function mutations in BRCA1 gene which trigger the tumorigenic process in hereditary TNBC. Although at genomic level, TNBC was previously characterized as more heterogeneous than other breast cancer subtypes, the difference in genomic, epigenomic, and transcriptional variability between two groups of TNBC—sporadic (BRCA1-proficent) and hereditary (BRCA1-associated)—remains unclear. Here, we investigated both sporadic and hereditary TNBC, by using data from copy-number alterations (CNAs) array, methylation array, and RNA-Seq. A total of 80 samples, 40 TNBC BRCA1-proficient (classified as sporadic), 18 TNBC with BRCA1 germline mutation (classifed as hereditary) and 22 normal breast tissues used as controls, were used. Data from methylation and CNA arrays were analyzed with the RnBeads and snapCGH softwares, respectively. RNA-seq data was analyzed mainly with the STAR aligner, Bioconductor-GenomicFeatures and DESeq2 softwares. To assess the intragroup genomic, transcriptional, and epigenomic variability we used the inter-quantile difference between patients of the same group. Our results clearly demonstrated that the TNBC BRCA1-proficient group has a higher intragroup heterogeneity than the BRCA1-mutated group regarding (i) global pattern of gene expression, (ii) number and intensity of CNAs (copy number alterations), and (iii) level of promoter methylation. Moreover, normal breast samples showed the lowest intra-group heterogeneity for the last two features. Then, our results show higher genomic, transcriptional, and epigenomic variability in sporadic than hereditary TNBC and motivates further molecular subtyping of the sporadic TNBCs, which may reveal new targets to improve TNBC treatment. Citation Format: Kivvi Duarte de Mello Nakamura, Rodrigo Fernandes Ramalho, Rafael Canfield Brianese, Ana Krepischi, Bruna D. F. Barros, Dirce Maria Carraro. Intragroup genomic, transcriptional, and epigenomic variability is higher in sporadic than in BRCA1-associated hereditary triple-negative breast tumors [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr A25.
奥马珠单抗在抗组胺药物耐药 CSU 患者中的使用
Authors: F. Bérard, M.C. Ferrier Bouedec, L. Bouillet, Z. Reguiai, A. Barbaud, F. Cambazard, B. Milpied, B. Pelvet, I. Kasujee, H. Gharbi, J.P. Lacour
Journal: British Journal of Dermatology (2019)

这项来自法国的研究本身关注生物药奥玛朱单抗作为慢性自发性荨麻疹 (CSU) 的治疗。CSU 导致棘手(甚至致人衰弱)的瘙痒性鞭痕样荨麻刺伤(荨麻疹)以及通常影响口唇、舌和眼睑等较深部组织的肿胀(血管性水肿)。奥马珠单抗被批准用于对高剂量抗组胺药无效的重度 CSU。入组了 136名 CSU 患者,124 名完成了研究。向他们给予 3 剂标准剂量奥马珠单抗,每 4 周一次,共 12 周。半数患者还使用了其他药物(通常为抗组胺药物)来治疗他们的 CSU。研究者和参与者们知道所有参与者正在使用奥马珠单抗,且没有安慰剂组。发现两种评估改善的评分方法 (现有的 7 -天荨麻疹活动评分 UAS7 和较新的荨麻疹控制试验 UCT)存在相关性,即它们的评分相似。根据 UAS7 评分测量结果,奥马珠单抗在 2/3 患者中有效,根据 UCT 评分,在 3/4 患者中有效。这些结果不受患者有无血管性水肿影响。生活质量评分显著改善。血液中名为 D-二聚体的蛋白的平均水平在研究开始时增高,通过治疗下降,但与 UAS7 或 UCT 评分改善无关联。8/9 患者治疗后的 D-二聚体水平极高,因此测量 D-二聚体可能能够预测对奥马珠单抗的反应。除此以外,主要结论是:奥马珠单抗对 CSU 有效,副作用很少,且 UCT 是可靠的。
Are 12 systematic reviews on exercise in pregnancy too many? Not for 125 million women who are pregnant every year: Kudos Society of Obstetricians and Gynaecologists of Canada (SOGC) and Canadian Society for Exercise Physiology (CSEP)
Authors: Karim M Khan
Journal: British Journal of Sports Medicine (2019)

There are about 125 million pregnancies a year. Exercise may be one of the most important health-promoting behaviours a woman can undertake before and during pregnancy, yet there are many questions around exercise and pregnancy. Can exercise early in a pregnancy lead to miscarriage? Does exercise lead to a tight pelvic floor and thus obstruct the baby’s passage in vaginal delivery? When can I return to being physically active? Is it normal to be incontinent after childbirth and do I need to take steps to address it or will I regain normal micturition without help? When can I have sex? …
Liquid chromatography-multiple reaction monitoring mass spectrometry biomarker quantification for breast cancer patient assessment.
Authors: Yi Chen, David J. Britton, Elizabeth R. Wood, Hyo S. Han, Anthony M. Magliocco, Ian Pike, John M Koomen
Journal: Journal of Clinical Oncology (2014)

e22219 Background: Quantitative mass spectrometry assays have been developed for protein expression and phosphorylation biomarkers for breast cancer patient assessment, specifically estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2). The integration of these assays with tissue quality control (QC) as well as quantification of Ki67 for proliferation and vimentin for EMT, could open novel avenues for breast cancer patient classification and selection of therapy. Methods: Cell lines were used to develop peptide-based quantitative assays (n = 31) for protein expression and phosphorylation using liquid chromatography-multiple reaction monitoring mass spectrometry (LC-MRM). Analysis of digested lysates and immunoprecipitated proteins can examine biomarkers across a wide dynamic range of expression. High abundance biomarkers, including tissue QC biomarkers and levels of Ki67, vimentin, and HER2 are measured in whole cell lysate or tissue homogenate (0.01 mg protein). Then, parallel IP is used to enrich HER2 (0.1 mg protein) and ER/PR (1 mg protein) before SDS-PAGE, in-gel digestion, and LC-MRM. Assays were characterized in terms of sensitivity, accuracy, precision, and linearity and then applied to frozen tissue specimens and compared with other techniques. Results: LC-MRM assays for both unmodified and phosphorylated peptides have been developed and characterized for each protein using cell line models. Assays have been implemented to study Estradiol/EGF stimulation in MCF7 cells and lapatinib inhibition of HER2 in BT474 cells. These biomarkers were quantified in pre-treatment frozen tissue specimens from ER+, ER-, Her2+, and Her2- patients (n = 5 per group). LC-MRM measurements correlate well with ELISA measurements and can be compared against immunohistochemistry and FISH results. Conclusions: The ability to examine protein expression as well as phosphorylation status in these biomarkers with quantitative mass spectrometry has the potential to improve the selection of targeted therapeutics. Analysis of larger patient groups will establish clinical utility.
A retrospective cohort study evaluating the safety and efficacy of TAS-102 in patients with metastatic colorectal cancer (HGCSG1503): Analysis of tumor location.
Authors: Kohei Ogawa, Satoshi Yuki, Yasuyuki Kawamoto, Masataka Yagisawa, Kazuaki Harada, Hiroyuki Okuda, Kouichi Furukawa, Takuya Honda, Masayoshi Dazai, Takashi Kato, Takahide Sasaki, Yoshiaki Shindo, Sakae Ota, Atsushi Sato, Akira Ueda, Sosuke Kato, Akira Fukunaga, Hikari Nagai, Yuh Sakata, Yoshito Komatsu
Journal: Journal of Clinical Oncology (2018)

802 Background: Recent analysis from some clinical trials showed that primary tumor location in patients with metastatic colorectal cancer (mCRC) correlates with different outcome. The J003 trial and RECOURSE trial revealed the safety and efficacy of TAS-102 for patients with metastatic colorectal cancer (mCRC). In March 2014, TAS-102 was approved in Japan. However, the impact of primary tumor location in mCRC treated TAS-102 is unclear. Methods: We retrospectively analyzed the clinical data of 411 patients who received TAS-102 in the multi-institutional retrospective study (HGCSG1503). This study was analyzed by CTCAE v4.0 for adverse events (AEs), RECIST v1.1 for response rate (RR)/disease control rate (DCR). To compare with right-sided tumor (RT : Cecum to Transverse colon) and left-sided tumor (LT : Descending colon to Rectum), Fisher’s exact test was used in terms of patient characteristics, AE, RR/DCR, and Log-rank test was used in terms of TTF, PFS and OS. Results: Patients with RT and LT were 137 and 274, respectively. The patient’ characteristics between RT and LT were generally balanced except for Gender (Male ; 45.3% in RT, 56.9% in LT ; p = 0.028), Age (Median ; 68.0y in RT, 66.0y in LT ; p = 0.007), Liver metastasis (70.8% in RT, 57.7% in LT ; p = 0.010), Peritoneal metastasis (47.4% in RT, 24.5% in LT ; p &lt; 0.001), and KRAS exon2 status (wild ; 40.5% in RT, 59.0% in LT ; p = 0.001). The AEs between RT and LT were also generally balanced except for Platelet count decreased (≥Grade 3 ; 8.8% in RT, 2.9% in LT ; p = 0.014). RR/DCR were 0/30.9% in the RT and 0.8/40.3% in the LT (p = 1.000/0.088). Median TTF was 2.2 months in the RT and 2.1 months in the LT (HR 0.962, p = 0.712). Median PFS was 2.2 months in the RT and 2.2 months in the LT (HR 1.024, p = 0.826). Median OS was 7.3 months in the RT and 7.3 months in the LT (HR 1.114, p = 0.327). Conclusions: As a result of this analysis, efficacy was no significant difference between RT and LT for patients who were administered TAS-102 in the real-world clinical practice. This analysis suggested TAS-102 benefits mCRC patients regardless of primary tumor location. Clinical trial information: 000020551.