tbuckley/cabot-search huggingface dataset:
Sepsis in adult leukemia patients.
Authors: Jan Garza
Journal: Journal of Clinical Oncology (2012)

133 Background: Sepsis is estimated to affect 16.8% of the cancer population with hematologic malignancies leading to significant mortality. The incidence may be higher in elderly leukemia patients with concurrent comorbidities. Results of case scenario questionnaires presented to leukemia nurses during a quality improvement project revealed a potential to increase recognition of systemic inflammatory response syndrome, commonly used to identify patients who are at high risk for sepsis, severe sepsis, and septic shock, by 20% among leukemia nurses. Earlier recognition of the systemic inflammatory response syndrome by clinicians is thought to possibly reduce the mortality among those with leukemia. The purpose of this poster is to present the pre-test/post-test results of an educational intervention aimed at increasing earlier recognition of SIRS and consequent sepsis, severe sepsis, and septic shock by 20% among 65 nurses on the leukemia units at a major cancer center. Methods: A multidisciplinary team Pharmacists from ICU and Leukemia and ICU MERIT Team-Leader, led by 2 APNs from ICU and Leukemia, developed and presented an educational program to nurses on the leukemia units to support proposed changes in practice. Pre-test and post-tests were used to determine nurses’ knowledge prior to and after the educational intervention. Results: Analysis of pre- and post-test scores revealed 61% increase in recognition of SIRS, sepsis, severe sepsis, and septic shock. There were no cases of systemic inflammatory response syndrome identified among the 29 leukemia patients by nurses prior to the intervention compared to 9 out of 16 post intervention. Conclusions: Education of nurses on leukemia units revealed an increase in their knowledge base and improvement in recognition of SIRS, sepsis, severe sepsis and septic shock. Implications for nursing include a need to incorporate this education to all nurses who are assigned to units caring for hematologic malignancies to include lymphoma, stem-cell transplant, and myeloma. Our quality improvement project showed the need for on-going healthcare provider education to recognize the symptoms early which may save lives and reduce costs of healthcare.
Characteristics and outcome of octogenarian versus young patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC) treated with ketoconazole.
Authors: Victoria J. Sinibaldi, Michal Dadon-Nachum, Maya Gottfried, Natalie Maimon, Zamir Dovrish, Avivit Peer, Avivit Neumann, Avishay Sella, Svetlana Kovel, Michael Anthony Carducci, Mario A. Eisenberger, Daniel Kejzman
Journal: Journal of Clinical Oncology (2014)

256 Background: Standard treatment options for patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC) include docetaxel based chemotherapy, abiraterone, and radium 223. Octogenarian pts (age 80 and older) are often considered to be unfit for chemotherapy. However, recommendations for their management is limited by the paucity of clinical trials data in this population. In countries where abiraterone in the pre-chemotherapy setting has not been approved yet, or for pts who can’t afford it, the CYP 17 inhibitor ketoconazole is used as an alternative advanced hormonal tx. We aimed to study baseline characteristics and outcome of octogenarian versus young (age 60 or younger) pts with mCRPC treated with ketoconazole. Methods: We performed an international multicenter retrospective study of pts with mCRPC, who were treated with ketoconazole at four centers across two different countries. We compared baseline characteristics and outcome of octogenarian versus young pts. The effect of very old age on prostate-specific antigen (PSA) response, progression free survival (PFS), and overall survival (OS), was tested with adjustment of other known confounding risk factors using a chi-square test and partial likelihood test from Cox model. Results: Between 2004 and 2013, 35 octogenarians (median age 83) and 33 young pts with (median age 57) mCRPC were treated with ketoconazole. The groups were balanced regarding the following baseline clinicopathologic characteristics: extent of disease (limited-axial skeleton and/or nodal versus extensive-appendicular skeleton and/or visceral), combined gleason score, pre-treatment risk category (Keizman, Oncologist 2012; based on pre-tx neutrophil to lymphocyte ratio/prostate-specific antigen doubling time, and prior response to ADT), pain intensity, ECOG performance status, alkaline phosphatase level, hemoglobin level, PSA level. In octogenarian versus young pts, PSA response (greater than or equal to 50% decline from baseline) was 40% versus 61% (OR 3.5, p=0.04), median PFS 7 versus 8 months (HR 0.91, p=0.44), and median OS 31 versus 36 months (HR 0.66, p=0.31). Conclusions: In very old vs young mCRPC patients treated with ketoconazole, PSA response was lower. Baseline clinicopathologic characteristics, PFS, and OS were not significantly different between the groups.
Are the numbers of retrieved lymph nodes (LNs) within and outside the radiation field significant prognostic factors in patients who received chemoradiotherapy (CRT)?
Authors: Kazutake Okada, Sotaro Sadahiro, Toshiyuki Suzuki, Akira Tanaka, Akemi Kamijo
Journal: Journal of Clinical Oncology (2013)

510 Background: We had presented last year that the number of lymph nodes (LNs) significantly decreased within the radiation field, but not outside the radiation field in rectal cancer patients who received preoperative chemoradiotherapy (CRT) as compared with patients who underwent surgery alone. In the present study, we examined the relation between survival and the number of LNs within and outside the radiation field, separately. Methods: The study group comprised 210 patients who underwent radical surgery for clinical stage II or III rectal cancer from 1991 through 2010. A total of 108 patients underwent surgery alone (S group), and 102 patients received preoperative CRT, 40 or 45 Gy with concurrent oral UFT or S-1, (CRT group). LNs were divided into two groups according to their distribution; within the radiation field (within the mesorectum) or outside the radiation field. Results: Patient demographics did not differ between the groups. The number of LNs examined was 2617, of which 290 (11%) were metastatic. The mean total number of LNs was significantly higher in the S group (16 ± 11) than in the CRT group (9 ± 7; p&lt;0.01). The number of LNs within the radiation field was significantly higher in the S group (6 ± 6) than in the CRT group (4 ± 4; p&lt;0.01), but the number of LNs outside the radiation field did not differ. The total number and the number of metastatic LNs outside the radiation field did not differ between the groups, however, the number of metastatic LNs within the radiation field was significantly higher in the CRT group (S group, 2 ± 2; CRT group, 3 ± 4; p&lt;0.01). In the S group, the total number of LNs and the number of LNs within the mesorectum were both prognostic factors in pStage II disease. A total number of ≥18 LNs and ≥5 LNs within the mesorectum were associated significantly with better outcomes. The number of metastatic LNs within the mesorectum was a prognostic factor in pStage III disease. In the CRT group, however, the total number of LNs and the number of LNs within the mesorectum were not related to survival. Conclusions: The number of LNs within the mesorectum might be a prognostic factor in patients who receive surgery alone, but not in patients who receive CRT.
MicroRNAs as Master Regulators of Glomerular Function in Health and Disease
Authors: Piera Trionfini, Ariela Benigni
Journal: Journal of the American Society of Nephrology (2017)

MicroRNAs (miRNAs) are important regulators of gene expression, and the dysregulation of miRNAs is a common feature of several diseases. More miRNAs are identified almost daily, revealing the complexity of these transcripts in eukaryotic cellular networks. The study of renal miRNAs, using genetically modified mice or by perturbing endogenous miRNA levels, has revealed the important biologic roles miRNAs have in the major cell lineages that compose the glomerulus. Here, we provide an overview of miRNA biogenesis and function in regulating key genes and cellular pathways in glomerular cells during development and homeostasis. Moreover, we focus on the emerging mechanisms through which miRNAs contribute to different diseases affecting the glomerulus, such as FSGS, IgA nephropathy, lupus nephritis, and diabetic nephropathy. In-depth knowledge of miRNA-based gene regulation has made it possible to unravel pathomechanisms, enabling the design of new therapeutic strategies for glomerular diseases for which available therapies are not fully efficacious.
Colorectal carcinoma (CRC) management approach in octogenarians and over a single institute experience.
Authors: Emmet Jordan, Amy Murphy, Seamus Coyle, Miriam O Connor, Paula Calvert, Anne M Horgan
Journal: Journal of Clinical Oncology (2013)

575 Background: The incidence of CRC increases with age. Future numbers are projected to rise due to an ageing population. Little data exists on chemotherapy in those ≥80 years (yrs) with CRC, a subgroup rarely included in clinical trials. The purpose of this study was to evaluate chemotherapy use, feasibility and tolerability in patients ≥80 yrs with CRC in a single institution. Methods: CRC diagnosed in those ≥80 yrs in a single institution in Ireland , from 2004 -2009, was determined. Clinicopathological data collected included age, gender, morphology, stage, and treatment including surgery, radiation or chemotherapy. In those receiving chemotherapy tolerance was determined by dose delays, reductions and number of completed cycles. Results: 83 cases of CRC were identified; 80-89 yrs (n=78), 90-100 yrs (n=5). Median age was 84 yrs (range 80-102), 38/83 (45.8%) were female. 59 cases of colon and 24 cases of rectal cancer were seen. Stage at diagnosis included IV (n=18), III (n=21), II (n=38) and I (n=6). For stage IV disease 4/18 (22%) received chemotherapy. Median overall survival for those with stage IV disease who received chemotherapy was 317 days (range 64-487) versus 169 days (range 30-473) for supportive care. 3/21(14%) stage III patients received chemotherapy. Median survival for stage III disease who received chemotherapy was 1193 days (range 432-1640) compared to 641 days who did not (range 0-1640). All patients with stage IV disease received single agent (SA) treatment (capecitabine n=3, cetuximab n=1). Treatment of stage III disease included: XELOX n=1, 5Fluorouracil/Leucovorin n=1, capecitabine n=1). 3/6 (50%) had dose reductions (n=4) and delays (n=7) in treatment. 1 patient completed scheduled adjuvant treatment. 1 patient with metastatic disease received second and third line treatment (SA irinotecan, cetuximab). Data including performance status, co morbidity will be presented. Conclusions: The uptake of chemotherapy in this cohort is low. Although the rates of treatment modifications are high, those treated appear to benefit. Better clinical tools are needed to differentiate those older patients likely to benefit from systemic therapy and those better served by supportive measures alone.
Analysis of morbidity and clinical implications of laparoscopic para-aortic lymphadenectomy in a continuous series of 98 patients with advanced-stage cervical cancer and negative PET CT imaging in para-aortic area.
Authors: C. Uzan, A. Souadka, S. Gouy, T. Debaere, J. Duclos, J. Lumbroso, C. Haie Meder, P. Morice
Journal: Journal of Clinical Oncology (2011)

e15574 Background: Laparoscopic para-aortic lymphadenectomy (PAL) is being used increasingly to stage patients with locally advanced cervical cancer (LACC) and to define radiation fields limits before chemoradiation therapy (CRT). The aim of this study was to review complications and to determine whether surgical complications delayed the beginning of CRT. Methods: We retrospectively reviewed a continuous series of patients with LACC, no positive PA nodes at PET CT and who had undergone a primary laparoscopic PAL. Results: From 11/2007 to 06/2010, 98 patients with LACC had undergone pretherapeutic PAL. One patient missed her scheduled PET CT before surgery. Two other patients had not undergone PAL: extensive carcinosis had been discovered in one case and a technical problem had arisen in the other. No major peroperative complications had occurred. Seven patients had lymphocyst needing an imaging-guided (or laparoscopic) puncture. Eight patients (8.4% - which corresponds to the rate of PET CT false negatives) had metastatic disease within para-aortic lymph nodes. In case of suspicious pelvic nodes at PET CT, risk of PA disease was greater (24.0% vs 2.9%, p=0.004, OR= 10.7 [2.3; 50.1]) (Table).When patients with and without surgical morbidity were compared, the median delay to the start of treatment was not significantly different (15 days[3-49] vs. 18 [3-42] days, NS). Conclusions: The morbidity of laparoscopic PAL was limited and the completion of treatment had not been delayed when complications had occurred. Nevertheless, the results of the table raise the question of the interest of PAL in patients with negative PET CT in the pelvic area because, in that case, risk of PA disease is very low. Distribution of patients according to suspicious pelvic nodes (pelvic PET N+) and histological PA disease (n=95 patients with PET and PAL performed). Histological PA+ Histological PA - Total Pelvic PET N+ 6 19 25 Pelvic PET N- 2 68 70 Total 8 87 95
Primary colorectal tumors and their metastasis are genetically not the same: Implications for choice of targeted treatment?
Authors: J. S. P. Vermaat, I. J. Nijman, M. J. Koudijs, W. M. Roessingh, F. L. Gerritse, M. Mokry, R. H. Giles, P. J. van Diest, E. Cuppen, E. E. Voest
Journal: Journal of Clinical Oncology (2011)

3535 Background: In the era of personalized cancer treatment, patient selection to enrich for specific targets is key to improve treatment outcome. Given the genomic instability of tumors in time we addressed whether analysis of the primary tumor or the metastasis is most suitable for patient selection for targeted treatment. Methods: With next generation (SOLiD 3+ system, Life Technologies) and targeted sequencing (DNA capture-arrays, Agilent) we have analyzed the genetic environment of a cancer mini-genome–the exons of 1,265 cancer-associated genes- of the primary tumor and its sequential liver metastasis in 21 colorectal cancer (CRC) patients (pts). Using laser microdissection >80% tumor cell-enriched DNA was isolated from in total 47 samples, including healthy tissue of 5 pts. Sequence data was aligned and mapped against the human reference genome (GRCh37/hg19) using BWA. To limit the influence of SNV (Single Nucleotide Variation) caller artifacts we applied 3 different published methods (our PERL script, VarScan and GATK toolkit) and considered the overlapping variants as reliable. To predict the possible impact of identified SNV's on protein function polymorphism phenotyping version2 was used. Results: All 47 samples were successfully sequenced (median coverage=87x, range: 52-217). In total 6,696 known (84%) and 1,305 novel (16%) SNV’s were identified. These included 1,460 non-synonymous and 29 gained/lost stop-codons, potentially altering protein function. On average 83 potentially relevant SNV's were gained in the metastasis and 70 SNVs present in the primary tumor were lost. Interestingly, these genetic variations affected several essential pathways. This demonstrated that tumor evolution caused losses and gains of critical genes in time. In this sample set genetic selection pressure concerning the amount of gained/ lost SNV's on the metastasis due to chemotherapy could not be shown. Conclusions: These results indicate that metastatic disease significantly differs from its primary origin in CRC pts. This suggests that for the selection of the appropriate patient population for targeted therapy the metastasis better reflects the actual disease status.
Predictive value of transcriptional changes in peripheral blood for future clinical onset of lung cancer in asymptomatic smokers
Authors: T. Zander, S. Debey-Pascher, D. Eggle, A. Staratschek-Jox, E. Stoelben, J. Linseisen, G. Nagel, P. Boffetta, J. Schultze, J. Wolf
Journal: Journal of Clinical Oncology (2008)

1509 Background: The disastrous 2-year survival rate of only about 15% in lung cancer is mainly due to diagnosis of the disease in advanced stages. Early detection thus may be a promising strategy to improve survival rates. We aimed at the identification of lung cancer specific expression profiles in blood samples prior to clinical manifestation of the disease. Methods: A lung cancer associated RNA-fingerprint was generated in peripheral blood samples of a cohort of smokers with prevalent lung cancer (13 cases, 11 controls). This fingerprint was validated in a second cohort of smokers with prevalent lung cancer (22 cases, 15 controls). Next, from 25.000 healthy individuals recruited in the area of Heidelberg, Germany, into the European Prospective Investigation on Cancer and Nutrition (EPIC) all smokers (12) developing lung cancer within 2 years after study inclusion (incident cases) and respective matched controls were identified. The RNA-fingerprint established in the two prevalent cohorts was used to predict future onset of lung cancer in the incident cohort. The results were validated on two different array platform. Results: Using the human WG-6 array (Illumina) in the cohort of smokers with prevalent lung cancer sensitivity and specificity of the test were estimated to be 86% and 86%, respectively. Class prediction was highly significant using KNN based algorithms or hierarchical clustering (p<0.0001 Fisher´s exact test). When further applying the test in the cohort with incident lung cancer we significantly predicted the clinical manifestation of lung cancer (p<0.05). Using identical test criteria on data generated on a different technical platform (Illumina human WG-6 V2) similar results were obtained (odds ratio of 17 [95% CI: 2.2 to 121] p<0.05). Permutation analysis further supports the validity of the data (p<0.01). Conclusions: The blood-based lung cancer RNA-fingerprint is suitable to identify lung cancer patients and to predict the occurrence of clinical manifest lung cancer within 2 years. Remarkable most of the relevant transcripts are derived from immune response related genes. These results may form the basis for the further development of a blood-based lung cancer early detection test. No significant financial relationships to disclose.
Use of surgery and chemoradiation in stage II and III rectal cancer: A retrospective comparison of treatment modalities in major insurance types using the NCDB.
Authors: Mary Warlaumont, Lauren Brin, Timothy Fuller, Naomi Whittaker, Peter T. Silberstein
Journal: Journal of Clinical Oncology (2013)

e14641 Background: The preferred method of care for stage II/III rectal cancer is trimodal therapy: neoadjuvant chemoradiation plus surgical resection. We aim to compare the treatment practices for patients with stage II/III rectal cancer in major insurance types. Methods: Using data from the National Cancer Database (NCDB), we analyzed the treatment patterns of 91,782 patients diagnosed with stage II/III rectal cancer from 2000-2009. The NCDB includes data from 70% of all U.S. cancer patients. This is the largest study of this kind to date. Results: In stage II/III rectal cancer, patients with private insurance received more trimodal therapy (70.3%) than patients with VA Insurance (56.6%), Medicare (46.9%), Medicaid (66.5%), or no insurance (61.7%) (p&lt;.0001). VA patients received less trimodal therapy than Medicaid or non-insured patients (p&lt;.0001). Medicare patients (26.9%) were treated with surgery alone more often than patients with private insurance (9.8%), Medicaid (10.4%), VAH (12.2%) or no insurance (9.4%) (p&lt;.0001). VA (4.8%) and Medicare (4.3%) patients were more likely to not receive any “First Course Treatment” than patients with private insurance (1.3%) (p&lt;.0001). Patients over 70yo received less trimodal therapy (42.2%) than patients under 70yo (68.9%) (p&lt;.0001) and received more surgery without chemotherapy or radiation (29.3%) than patients less than 70yo (9.2%) (p&lt;.0001). Conclusions: Stage II/III rectal cancer patients with private insurance received more trimodal therapy than VA, Medicare, Medicaid, or uninsured patients. VA patients received less trimodal therapy than Medicaid or uninsured patients. [Table: see text]
Actigraphy as an objective measure of performance status in patients with advanced cancer.
Authors: William F. Pirl, Daisuke Fujisawa, Jamie Stagl, Justin Eusebio, Lara Traeger, Areej El-Jawahri, Joseph A. Greer, Jennifer S. Temel
Journal: Journal of Clinical Oncology (2015)

62 Background: Treatment decisions are often based on performance status (PS), a subjective rating of patient functioning derived from observation and patient-report. Devices that monitor physical activity, such as wrist actigraphs, can accurately measure the percent of time a person is immobile while awake (awake immobile). Thus, actigraphy may have potential to better estimate true PS. We compared actigraphy to both Eastern Cooperative Oncology Group PS (ECOG PS) and patient-reported physical activity as predictors of survival in patients with stage IV non-small cell lung cancer (NSCLC). Methods: Participants (n = 41) were ambulatory patients with stage IV NSCLC receiving care at MGH. Participants wore a watch-sized accelerometer device (ACTIWATCH 2) for three consecutive 24-hour periods (72 hours) and completed a self-report questionnaire about physical activity, scored as METS (metabolic equivalents) per week. Patients’ oncologists rated their ECOG PS (0-5) at the end of the 72-hour actigraphy period. Relationships among ECOG PS, awake immobile, and METs per week were tested with Pearson correlations. A ROC curve for 6-month survival was used to determine a meaningful cut-off for awake immobile. Unadjusted Cox regression models tested associations with survival from assessment times. Results: Participants’ ECOG PS ratings were: 0 (22%), 1 (63%), 2 (12%), and 3 (2%). ECOG PS and awake immobile were correlated (r = .42, p &lt; .01). METS per week was correlated only with ECOG PS (r = -.35, p = .03). At time of analysis, 15 patients had died with a minimum follow up of 9 months. Among all patients, survival was predicted by ECOG PS, HR = 3.77 (95% CI 1.70-8.35), p &lt; .01; awake immobile as both as a continuous (percentage points) and categorical ( &gt; 23%) variable, HR = 1.04 (95% CI 1.00-1.09), p = .05 and HR = 4.12 (95% CI 1.37-12.39), p = .01, respectively; but not METS per week. Among patients with good EGOC PS (0-1), only awake immobile ( &gt; 23%) predicted survival, HR = 5.80 (95% CI 1.39-24.12), p = .02. Moreover, within the largest ECOG group (PS1), awake immobile ( &gt; 23%) still predicted survival, HR = 5.53 (95% CI 1.18-25.94), p = .03. Conclusions: Actigraphy, an objective measure of patient activity, may have utility in determining patient PS.