tbuckley/cabot-search huggingface dataset:
Visceral fat content, clinical features, and prognosis in a database of 507 upper gastrointestinal cancers.
Authors: Kazuto Harada, Keisuke Kosumi, Yoshifumi Baba, Ryuichi Karashima, Satoshi Ida, Yu Imamura, Shiro Iwagami, Yuji Miyamoto, Yasuo Sakamoto, Naoya Yoshida, Hideo Baba
Journal: Journal of Clinical Oncology (2014)

4054 Background: Excess visceral adipose tissue may promote cancer development and progression through obesity-related metabolic disturbances, such as adipocytokine-related Inflammation, insulin resistance, and hypoxia. Although the relationship between visceral fat content and patient prognosis has been reported in some cancer types, the clinical, pathological and prognostic value of visceral fat volume in upper gastrointestinal cancers has yet to be investigated. We therefore examined the relationship between visceral fat status and clinical outcome in patients with the upper gastrointestinal cancers (esophageal cancer and gastric cancer) treated by surgical resection. Methods: Preoperative visceral fat content in 507 upper gastrointestinal cancer patients was retrospectively quantified by radiologic measures using standard computed tomography scans. The Cox proportional hazards model was used to compute mortality hazard ratio, adjusting for clinical and tumoral features. Throughout this study, the term “prognostic marker” is used in the context of the REMARK Guidelines. Results: Higher visceral fat content was correlated with male sex (p = 0.0012), presence of preoperative comorbidity (p = 0.0009), absence of preoperative therapy (p < 0.0001), low tumor stage (p = 0.029), low tumor depth (p = 0.0032) and gastric cancer (p = 0.0053). Subjects with low visceral fat experienced a higher overall mortality rate than their high visceral fat counterparts [log-rank p=0.0050; univariate HR= 1.73, 95% confidence interval (CI) 1.16–2.54; p=0.0075; multivariate HR 1.57; 95% CI, 1.02–2.37; p=0.031]. Interestingly, the influence of low visceral fat on patient outcome was modified by age at surgery (p for interaction = 0.036); low visceral fat was associated with a poor prognosis, especially in elderly patients (log rank p<0.0001). Conclusions: We identified a correlation between low visceral fat in upper gastrointestinal cancer patients and poor prognosis, suggesting that low visceral fat may provide a biomarker for identifying patients likely to experience an inferior outcome
Sexual dysfunction in women with lymphoma: Prevalence and etiologies.
Authors: Shari Beth Goldfarb, Talicia Jackson, Jeanne Carter, Maura N. Dickler, Ariela Noy
Journal: Journal of Clinical Oncology (2014)

e20594 Background: Sexual dysfunction is reported during and after treatment for lymphoma and causes a substantial burden on women. However, the prevalence and severity of sexual dysfunction in this population is not well defined.This study was performed to understand the impact of contemporary lymphoma therapy on female sexual function. Improved understanding of sexual health will facilitate the development of interventions for women with lymphoma undergoing treatment and for survivors of this disease. Methods: We developed a survey that includes the validated female sexual function index (FSFI), an established measure of health-related quality of life (the EuroQol EQ-5D) and disease-specific items to characterize sexual dysfunction and its causes based on literature review and expert consultations. Anonymous administration of the surveys was conducted in outpatient lymphoma clinic waiting areas at Memorial Sloan Kettering Cancer Center (MSKCC), under an IRB approved protocol. Results: We queried 50 women with lymphoma. The mean age was 38.5 (range 19-77). 37 women were premenopausal and 13 were postmenopausal. 94% (47/50) reported current or past chemotherapy. Sexual dysfunction attributed to lymphoma or its treatment, defined as an FSFI score <26.55, was reported by 50% (25/50) of respondents, with a mean score of 20. Among these women, 64% of patients were bothered by their sexual dysfunction, which impaired their quality of life. Patients attributed their sexual dysfunction to chemotherapy, fatigue and anxiety. Sexual dysfunction was reported in the following domains: desire, lubrication, arousal, orgasm, and pain. Conclusions: Sexual dysfunction is prevalent in women treated for lymphoma. Practitioners should recognize this as a potential adverse effect of therapy. Assessment of sexual symptoms throughout treatment and beyond may facilitate the use of interventions such as lubricants, vaginal moisturizers, dilators, treatment modification, hormonal therapy and counseling. Future work includes a longitudinal prospective trial to further characterize the etiologies of these symptoms and a randomized controlled trial to evaluate interventions for sexual dysfunction. This study was funded by Gabrielle’s Angel Foundation.
A mechanism for hereditary angioedema with normal C1 inhibitor: an inhibitory regulatory role for the factor XII heavy chain
Authors: Ivan Ivanov, Anton Matafonov, Mao-fu Sun, Bassem M. Mohammed, Qiufang Cheng, S. Kent Dickeson, Suman Kundu, Ingrid M. Verhamme, Andras Gruber, Keith McCrae, David Gailani
Journal: Blood (2018)
Is self-rated health a potential confounder of the relationship between patient satisfaction with service quality and survival in non-small cell lung cancer?
Authors: Digant Gupta, Kamal Patel, Mark Rodeghier, Christopher G. Lis
Journal: Journal of Clinical Oncology (2014)

e17577 Background: Previously we reported that higher satisfaction with service quality is associated with favorable survival outcomes in a variety of cancers. However, we cautioned the readers that patients with greater satisfaction with service quality might be the ones with better self-rated health (SRH), a well-established prognosticator of cancer survival. In other words, SRH could potentially confound the patient satisfaction and survival relationship. We investigated this hypothesis in non-small cell lung cancer (NSCLC). Methods: 778 NSCLC patients (327 males and 451 females; mean age 58.8 years) treated at 4 Cancer Treatment Centers of America hospitals between July 2011 and March 2013. Patient satisfaction was measured on a 7-point scale ranging from “completely dissatisfied” to “completely satisfied”. SRH was measured on a 7-point scale ranging from “very poor” to “excellent”. Both were dichotomized into 2 categories: top box response (7) versus all others (1-6). Patient survival was the primary end point. Cox regression was used to evaluate the association between patient satisfaction and survival. Results: 74, 70, 232, and 393 patients had stage I, II, III and IV disease respectively. 631 (81%) patients were “completely satisfied”. 184 (23.7%) patients had “excellent” SRH. There was a weak but significant correlation between satisfaction and SRH (Spearman rho = 0.19; p<0.01). On univariate analysis, “completely satisfied” patients had a significantly lower risk of mortality (HR=0.75; 95% CI: 0.57-0.99; p=0.04). Similarly, patients with “excellent” SRH had a significantly lower risk of mortality (HR=0.61; 95% CI: 0.46-0.81; p=0.001). On multivariate analysis controlling for stage at diagnosis, treatment history, age, gender and hospital location, SRH was found to be a significant predictor of survival (HR=0.61; 95% CI: 0.46-0.83; p=0.001) while patient satisfaction was not (HR=0.85; 95% CI: 0.63-0.1.1; p=0.29). Conclusions: SRH appears to confound the patient satisfaction-survival relationship in NSCLC. SRH should be used as a control variable in analyses involving patient satisfaction as a predictor of clinical cancer outcomes.
Imatinib Treatment for Locally Advanced or Metastatic Dermatofibrosarcoma Protuberans
Authors: Cristian Navarrete-Dechent, Shoko Mori, Christopher A. Barker, Mark A. Dickson, Kishwer S. Nehal
Journal: JAMA Dermatology (2019)

Dermatofibrosarcoma protuberans (DFSP) has the potential for local destruction and recurrence, although it carries a low risk of metastasis. Complete surgical resection with negative margins is considered the gold standard for treatment; however, there are cases that are unresectable owing to tumor extension or size or owing to risk of cosmetic and/or functional impairment. Imatinib treatment has been used for locally advanced or metastatic DFSP.
Age Subgroup Analysis of Health-Related Quality of Life of Blinatumomab Versus Standard-of-Care Chemotherapy in Patients with Relapsed or Refractory Philadelphia Chromosome-Negative B-Cell Precursor Acute Lymphoblastic Leukemia in a Randomized, Open-Label, Phase 3 Study (TOWER)
Authors: Max S. Topp, Zachary F. Zimmerman, Paul Cannell, Hervé Dombret, Johan Maertens, Anthony S. Stein, Janet L. Franklin, Ze Cong, Xinke Zhang, Andre Schuh
Journal: Blood (2018)
Landscape of genomic alterations (GA) detected by next-generation sequencing (NGS) in non-small cell lung cancer (NSCLC) adenocarcinoma in Israel.
Authors: Nir Peled, Hovav Nechushtan, Mira Wollner, Amir Onn, Dov Flex, Jair Bar, Maya Gottfried, Abed Agbarya, Alona Zer, Moshe Mishaeli, Amiel Segal, Julia Dudnik, Rivka Katzenelson, Addie Dvir, Lior Soussan-Gutman, Phil Stephens, Kai Wang, Vincent A. Miller, Jeffrey S. Ross
Journal: Journal of Clinical Oncology (2014)

e19111 Background: Profiling lung cancer tumors for targetable GAs is the cornerstone for individualizing treatment for this disease. We hypothesized that NSCLC samples would be enriched in actionable GAs in targetable genes. Methods: The analysis included all Israeli patients (pts) with NSCLC adenocarcinoma who underwent comprehensive NGS testing (FoundationOne) between 10/2011 and 12/2013. NGS was performed on hybridization-captured adapter-ligated libraries using DNA extracted from NSCLC specimens. It covered 3,769 exons from 236 cancer-related genes and 47 introns from 19 genes commonly rearranged in cancer. GAs including base substitutions, small indels, copy number alterations, and select gene fusions were characterized for each pt sample. Actionable GAs were defined as those identifying anti-cancer targeted therapies (commercially available or in registered clinical trials). NGS was performed as a commercially available service; the analysis was approved by the IRBs of all participating centers. Results: The analysis included 58 pts. Median (range) age was 60 (20-82) yrs and 33 (57%) were lifelong non-smokers. At the time of NGS testing, ≥74% of pts were pre-tested for EGFR and ALK, and 3 and 1 pts were positive, respectively. Samples used for NGS originated from the primary tumor in 34 pts (59%) and from metastatic lesions in 24 pts (41%). All 58 samples harbored ≥ 1 GA (mean: 3.2 GAs/tumor). The most frequent currently non-actionable GAs were identified in TP53 (53%) and RB1 (14 %). Fifty four pts (93%) harbored ≥ 1 actionable GA (mean: 1.7 actionable GAs/tumor). The most common actionable GAs were KRAS (29 %), EGFR (26 %), and CDKN2A (14 %). Gene fusions included ALK and RET both at 7%, and a rare TACC3-FGFR3 fusion (2%). Notably, NGS identified GAs in EGFR and ALK in pts whose prior EGFR/ALK testing was negative (6/43 [14%] and 2/42 [5%], respectively). GAs in the ERBB2 gene were observed in 4 samples (7%); all had insertion mutations with no amplifications. Conclusions: NGS of NSCLC samples revealed a high rate of actionable GAs in well-known anti-cancer targets, which were all mutually exclusive. Further analysis of this enhanced targetable GA rate appears warranted.
Sensitivity and specificity of an oral uracil-loading test dose for screening for DPD deficiency.
Authors: M C van Staveren, André B. P. van Kuilenburg, Henk-jan Guchelaar, Robert De Jong, Cornelis J. A. Punt, Hans Gelderblom, Jan Gerard Maring
Journal: Journal of Clinical Oncology (2014)

11101 Background: 5-fluorouracil (5FU) and capecitabine (CAP) are extensively metabolised by dihydropyrimidine dehydrogenase (DPD). DPD deficiency can lead to severe toxicity after 5FU or CAP. Uracil (U) can be used as a probe to determine the systemic DPD activity by measuring uracil and its metabolite dihydrouracil (DHU) in plasma. This study was performed to assess the sensitivity and specificity of an uracil loading dose for detecting DPD deficiency. Methods: All cancer patients who suffered from CTC grade III or IV toxicity after the first or second cycle of 5-FU or CAP-based treatment were asked to participate. Uracil 500 mg/m2 was administered orally followed by multiple blood sampling, plasma concentrations of U and DHU in plasma were determined. DPD activity in PBMCs was determined and patients were divided in 2 groups: DPD activity in PBMCs < 5 nmol/mg/hour (deficient group) and with activity ≥ 5 (normal group, controls: 9.9 ± 2.8 nmol/mg/hour). In the deficient group, PCR amplification of all 23 coding exons and flanking intronic regions of DPYD was performed. Plasma concentrations of U and DHU were determined by HPLC. A one-compartment uracil pharmacokinetics model was developed and used to determine Vmax of the DPD enzyme of each patient. Sensitivity and specificity of Vmax, U concentration and the U/DHU concentration ratio were determined using ROC analysis. Results: 47 patients were included (19 DPD deficient, 28 DPD normal). Sensitivity and specificity of the estimated pharmacokinetic parameters are displayed in the Table. PCR amplification in the DPD deficient group revealed the following pathogenic mutations: c.1129-5923C>G (n=4), c.2579delA (n=2), c.2846A>T (n=3), c.1905+1G>A (n=10), c.1679T>G (n=1). Conclusions: The sensitivity of 80% and specificity of 98% of the U/DHU ratio at t=120 min show that the oral uracil loading dose can effectively monitor DPD activity and can be used as a pre-emptive tool to identify patients with reduced DPD activity. Sensitivity, specificity, and cut-off levels for Vmax, U/DHU, and uracil concentration. Test parameter Cut-off level Sensitivity (%) Specificity (%) Vmax (mg/h/1,85m2) 665 79 79 U/DHU120min ratio 2.4 80 98 U120 min (mg/l) 6.4 80 96
Trends in small cell lung cancer (SCLC) survival: Predictors and impact of systemic therapy.
Authors: Madhusmita Behera, Camille Ragin, Sungjin Kim, Zhengjia Chen, Conor Ernst Steuer, Nabil F. Saba, Rathi Narayana Pillai, Chandra Prakash Belani, Suresh S. Ramalingam, Fadlo Raja Khuri, Taofeek Kunle Owonikoko
Journal: Journal of Clinical Oncology (2014)

7599 Background: The last 2 decades witnessed limited therapeutic advances in SCLC management. We evaluated trends in the use of systemic therapies and the impact on outcome in the US. Methods: We employed data from the SEER-MEDICARE database for SCLC patients diagnosed between 1985 and 2005. The 1985-1990 period served as a baseline for a temporal survival analysis conducted at 5-year intervals (1985-1990, 1991-1995, 1996-2000 & 2001-2005). Predictors of chemotherapy use were identified by logistic regression model with a backward variable selection method. Cox proportional hazards models were employed to estimate the effect of chemotherapy on survival by time of diagnosis with adjustment for significant predictors of chemotherapy use. Results: There were 47,351 eligible patients; M/F (52%/48%); median age (71 years); ethnicity (Whites-87%; Blacks- 7%; Hispanic: <0.4%; Asians: 1.4%; Others-2.8%); median OS overall, with and without chemotherapy (7.2, 9.6 and 3.6 months). Rate of chemotherapy use was very low but showed a significant increase over time (38, 55, 50, 53%, p<0.001). Females (51%), Asians (53%) and rural residents (60%) were more likely to receive chemotherapy. Race, comorbidity, year, age and location at diagnosis significantly predicted chemotherapy use. Linear trend analyses across the defined 5-year intervals showed improved survival in patients treated with chemotherapy over untreated patients (HR: 0.70; 0.66, 0.67, 0.64; p<0.001) after adjusting for significant predictors of chemotherapy use. While survival did not significantly change over time among patients treated with chemotherapy (HR: 1.0, 1.014, 1.035,1.033; p=0.337) it became worse in untreated patients (HR: 1.0, 1.047, 1.057, 1.071; p=0.002). Treatment with >1 type of chemotherapy was associated with improved survival (HR: 1.315; 0.941; 0.858; 0.827; p<0.001). Analysis in propensity score matched patients showed no survival difference between carboplatin and cisplatin (HR: 0.906 (0.761-1.078); p=0.267) or platinum doublet and CAV regimen (HR: 0.929 (0.847-1.019); p=0.118). Conclusions: Chemotherapy use was associated with an incremental survival benefit in MEDICARE-eligible SCLC patients treated in the real-world setting.
Phase I clinical trials in refractory colorectal cancer (CRC): Do older adult patients benefit?
Authors: Sukeshi Patel Arora, Norma S. Ketchum, Jonathan Gelfond, Joel Michalek, Devalingam Mahalingam
Journal: Journal of Clinical Oncology (2018)

784 Background: Current clinical trial data are largely driven by younger participants, yet half the population diagnosed with CRC are 70+. Upon progression, many CRC patients (pts) with refractory cancer are referred to phase 1 clinical trials; however, tolerability and clinical benefit is unclear in the elderly. Given our robust phase 1 program, we assessed the efficacy and safety of early therapeutics in the elderly CRC pts. Methods: A historical cohort analysis included mCRC pts enrolled amongst 44 phase I trials from 3/2004 - 9/2012. Median Progression free survival (mPFS) and overall survival (mOS) were estimated from Kaplan-Meier curves and groups were statistically compared with the log rank test. The magnitude of association between dichotomous factors and survival was estimated with the hazard ratio (HR). Results: 139 pts, median age 59 (33-81), 70+ 16.5% (n = 23); KRAS mut 39.4 %. ≥3 prior lines of therapy 73.9 %; Prior EGFR-I 75.5% (100% of KRAS wt). Location: Right 20.9 %, Left 61.9 %, Transverse 4.3 %, Unknown 12.9 %. Phase I agents: VEGF I 19.4%, EGFR/Growth Factor I 9.3%. mOS for &lt; 70 (n = 108) vs 70+ (n = 22): 6.5 vs 4.2 months (HR 1.88, p 0.007). mPFS for &lt; 70 (n = 116) vs 70+ (n = 23): 2.0 months vs x 1.5 months (HR 1.73, P 0.03). There was not a statistical difference between &lt; 70 versus 70+ in regards to dose cohort, number of cycles completed, or adverse events. Survival analysis in terms of risk factors in pts 70+ are in the Table below. Conclusions: Elderly CRC pts are underrepresented (16.5%) in phase 1 clinical trials and have worse survivals than non-elderly pts. Elderly CRC pts with liver and hematologic toxicities had a trend toward worse PFS but no OS. Phase I studies should incorporate prospective assessments to identify risk factors of morbidity and mortality in elderly CRC pts. [Table: see text]
Ex Vivo Assessment of Tnb-383B, a Bcma-Bispecific Antibody, Against Primary Tumor and Endogenous T Cells from Relapsing Multiple Myeloma Patients
Authors: David M. Foureau, Manisha Bhutani, Myra Robinson, Fei Guo, Duy Pham, Shelley Force Aldred, Ben Buelow, Katherine Rigby, Elise Tjaden, Marina Leonidas, Shebli Atrash, Ami P Ndiaye, James Symanowski, Peter M. Voorhees, Saad Z. Usmani
Journal: Blood (2018)
Corrigendum to “Caspase recruitment domain 6 protects against hepatic ischemia/reperfusion injury by suppressing ASK1” [J Hepatol 69 (2018) 1110–1122]
Authors: Juan-Juan Qin, Wenzhe Mao, Xiaozhan Wang, Peng Sun, Daqing Cheng, Song Tian, Xue-Yong Zhu, Ling Yang, Zan Huang, Hongliang Li
Journal: Journal of Hepatology (2019)
Adjuvant therapy use and outcomes of stage II and III colorectal cancer (CRC): Comparison of young and elderly patients (pts) in a large, contemporary, population-based Canadian database.
Authors: Haider Samawi, Derek Tilley, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2018)

807 Background: The incidence of CRC increases significantly with age. Despite the benefits associated with adjuvant therapy, older pts are frequently treated less aggressively due to perceived poor tolerance to treatment, comorbidity, or limited life expectancy. We aim to examine the impact of chronological age on use of perioperative therapies in a contemporary cohort of pts and determine differences in outcomes based on age. Methods: Adult pts who underwent surgical resection for stage II or III CRC in Alberta, Canada from 2004 to 2015 were analyzed. Pts were stratified based on pre-specified age sub-groups. Overall survival (OS) and cancer specific survival (CSS) were assessed using the Kaplan-Meier method and compared with the log-rank test. A Cox proportional hazards model was constructed to evaluate the impact of age on outcomes. Results: We identified 8,538 pts of whom 56% were men, 53% had stage III disease, and 26% had rectal cancer. Older pts were more likely diagnosed with right-sided tumors, earlier stage, and higher Charlson comorbidity index (CCI) (all p &lt;.01). Chemotherapy (CT) use decreased significantly with advancing age, even in recent years (Table). Older rectal cancer pts were also less likely to receive radiation (p &lt;.01). Elderly age was the strongest predictor for not using CT, after adjusting for sex, stage, tumor location, and CCI. On multivariate Cox regression, older age was associated with inferior OS and CSS, but CT improved outcomes. Conclusions: Despite evidence of benefit and prior studies recommending treatment of elderly, the current cohort of older pts with resected stage II and III CRC continue to undergo perioperative therapy less commonly than their younger counterparts. [Table: see text]
Efficacy and Safety of Prothrombin Complex Concentrate in Patients Treated with Rivaroxaban or Apixaban Compared to Warfarin Presenting with Major Bleeding
Authors: Deepa Jayakody Arachchillage, Sharon Alavian, Jessica Griffin, Kamala Gurung, Richard Syzdlo, Nilanthi Karawitage, Michael Laffan
Journal: Blood (2018)
Hypodiploidy in Childhood Acute Myeloid Leukemia: A Retrospective Cohort Study within the International Berlin-Frankfurt-Münster Study Group
Authors: Anne Sofie Borg Hammer, Kristian Juul-Dam, Julie Damgaard Sandahl, Jonas Abrahamsson, Walentyna Balwierz, Audrey Guilmatre, Iren Haltrich, Kirsi Jahnukainen, E. Anders Kolb, Gábor Kovács, Guy Leverger, Franco Locatelli, Riccardo Masetti, Ulrika Noren-Nyström, Susana C. Raimondi, Mareike Rasche, Dirk Reinhardt, Tomohiko Taki, Daisuke Tomizawa, Bernward Zeller, Henrik Hasle, Eigil Kjeldsen
Journal: Blood (2018)
Safety, Tolerability and Response Rates of Daratumumab in Patients with Relapsed Light Chain (AL) Amyloidosis: Results of a Phase II Study
Authors: Vaishali Sanchorawala, Shayna Sarosiek, John Mark Sloan, Dina Brauneis, Mary Ellen Migre, Meredith Mistark, Stephanie Santos, Ramon Cruz, Salli Fennessey, Anthony C Shelton
Journal: Blood (2018)