tbuckley/cabot-search huggingface dataset:
An international patient-centered outcome measurement set for colorectal cancer.
Authors: Harvey J. Mamon, Jessica A. Zerillo, Maartje Gisele Schouwenburg, Annelotte van Bommel, Caleb Stowell, Cornelis J. H. Van De Velde, Rob A.E.M. Tollenaar
Journal: Journal of Clinical Oncology (2017)

753 Background: While there are tools to measure outcomes relevant to patients with colorectal cancer, none is universally accepted and none incorporates components of long-term clinical outcomes, acute complications, and patient-reported outcomes (PROs). Methods: The International Consortium for Health Outcomes Measurement convened an international multidisciplinary working group to develop a comprehensive patient-centered outcome measurement set for patients with all stages of colorectal cancer. The working group utilized a literature review, patient focus group and their own clinical expertise to reach consensus on outcomes and case mix factors through a modified Delphi process. Measurement tools were selected by International Society of Quality of Life Research standards. The final list of PROs was validated through a patient survey. Results: The 29 members of the working group included patient representatives and palliative care, nursing, pathology, medical oncology, colorectal surgery and radiation oncology specialists from academic and nonacademic practices in Europe, Australia, Asia and the USA. The international focus group included 11 patients with colorectal cancer treated with palliative and curative intents. The working group defined four clinical outcomes applicable to all and eight specific to subgroups, such as presence of ostomy for patients with rectal cancer and hospital admission in the last 30 days of life for patients with advanced disease. An algorithm for documenting acute complications was developed. The working group defined 11 PROs applicable to all and eight specific to subgroups, such as erectile dysfunction for patients who received radiotherapy/surgery and neuropathy for those who received chemotherapy. 276 colorectal cancer patients completed the validation survey. Conclusions: Through use of extensive patient input, the international multidisciplinary group developed a patient-centered outcome measurement set incorporating clinical outcomes, acute complications and PROs for patients with colorectal cancer. This comprehensive measurement set allows for standardized international comparison on quality of care outcomes and will be revised annually.
Identification of ductal atypia with MR galactography
Authors: A.-R. Hartman, M. A. Mills, A. W. Kurian, J. M. Ford, D. N. Smith, B. L. Daniel
Journal: Journal of Clinical Oncology (2004)

1035 Background: Atypical breast duct cells in patients at increased risk of breast cancer have been predictive of a 5-fold increased breast cancer incidence. While ductal lavage is an FDA approved procedure, very little is known about the anatomy of the ductal system and when atypia is identified, how to localize the lesion when imaging tests are normal. The management of an atypical result is controversial and can include further evaluation in an attempt to localize a lesion with ductoscopy and breast MRI and risk reduction measures including tamoxifen or prophylactic surgery. We report on the use of a combination of breast MRI and ductal lavage; MR-Galactography to help define the normal anatomy of the breast ductal system and to localize atypia not identified by mammography and MRI. Methods: Women who carry a BRCA1/2 mutation and have been undergoing annual screening with mammography, breast MRI, and ductal lavage in our centers were invited to participate. Ten microliters of a 5-mmol/L Gd-DTPA solution was injected intraductally through a catheter and MR images were obtained on a 1.5T imager Signa LX using a dedicated 4-coil phased array breast coil. Ductal mapping was performed. Results: Two MR-galactography exams have been performed in a patient with a BRCA1 mutation. Successful cannulation and visualization of 3 ducts compromising 30% of the breast estimated by volumetric calculations was observed. Limitations to cannulation of more than 3 ducts were the small surface area of the nipple and the bulky catheter size. Conclusions: MR-galactography is a safe, feasible procedure that allows clear visualization of ductal anatomy. The cannulation of 2–3 ducts per breast as part of the standard ductal lavage protocol may only sample 30% of the breast ductal system, thereby missing a large portion of breast parenchyma. This protocol will be further developed to 1) allow easier cannulation of more ducts using magnification tools and smaller catheters 2) aid in localization of atypia identified on ductal lavage in the context of a normal contrast-enhanced MRI and 3) to detemine if atypia has a characteristic appearance on MRI that predicts for the clinical development of breast cancer. No significant financial relationships to disclose.
A first-in-human phase 1 study of a hepcidin monoclonal antibody, LY2787106, in cancer-associated anemia
Authors: Saroj Vadhan-Raj, Rafat Abonour, Jonathan W. Goldman, David A. Smith, Christopher A. Slapak, Robert L. Ilaria, Ramon V. Tiu, Xuejing Wang, Sophie Callies, Joanne Cox, Jay L. Tuttle, Yiu-Keung Lau, Eric J. Roeland
Journal: Journal of Hematology & Oncology (2017)

Hepcidin plays a central role in iron homeostasis and erythropoiesis. Neutralizing hepcidin with a monoclonal antibody (mAb) may prevent ferroportin internalization, restore iron efflux from cells, and allow transferrin-mediated iron transport to the bone marrow. This multicenter, phase 1 study evaluated the safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of a fully humanized mAb (LY2787106) with high affinity for hepcidin in cancer patients with anemia.Thirty-three patients with hepcidin levels ≥5 ng/mL received LY2787106 either every 3 weeks (19 patients, dose range 0.3-10 mg/kg) (part A) or weekly (14 patients, dose 10 mg/kg) (part B). LY2787106 PK/PD markers of iron and hematology biology were measured.LY2787106 clearance (32 mL/h) and volume of distribution (7.7 L) were independent of dose and time, leading to a dose-proportional increase in concentration with dose. Consistent dose-dependent increases in serum iron, and transferrin saturation were seen at the 3 and 10 mg/kg dose levels, typically peaking within 24 h after LY2787106 administration and returning to baseline by day 8.Our findings indicate that LY2787106 was well tolerated in cancer patients with anemia and that targeting the hepcidin-ferroportin pathway by neutralizing hepcidin resulted in transient iron mobilization, thus supporting the role of hepcidin in iron regulation.ClinicalTrial.gov, NCT01340976.
Quantitative Ki-67 score as predictive of response to neoadjuvant chemotherapy in breast cancer.
Authors: Jason R. Brown, Donald R. Lannin, Brigid K. Killelea, Michael DiGiovanna, David Rimm
Journal: Journal of Clinical Oncology (2013)

1085 Background: Neoadjuvant chemotherapy is administered prior to surgery for locally advanced tumors but does not confer any additional survival benefit. Measurement of Ki-67, a marker of cell proliferation, has been associated with response to therapy, but methods of measurement are controversial. There is no universal cut-point for association due to subjectivity in threshold for positivity and selection of the field of view. Here we propose that quantitative objective measurement for Ki-67 will provide a reproducible assay for likelihood of response to chemotherapy. Methods: A cohort of 115 consecutive (between 2002 and 2010) invasive breast cancer patients that received neoadjuvant therapy were included if pre-surgical biopsies were obtainable. Ki-67 expression was measured using quantitative immunofluorescence (AQUA) technology using the MIB-1 antibody. Images for each specimen were collected in 5 to 100 fields of view (FOV), and summary scores were obtained corresponding to the average and maximum of all the FOVs. Results: AQUA scoring was comparable to automated calculation of percent positive nuclei for prediction of response to chemotherapy (OR: 2.832 vs. 2.712). Both average and maximum AQUA scores showed Ki-67 expression was directly correlated to pathological complete response (pCR) (Ave p = 0.0002; Max p = 0.0011). Although examining the maximum field of view was more predictive of response to therapy (OR: 3.546 vs. 2.832), averaging all fields provided more sensitivity and specificity (AUC 0.769 vs. 0.732). Ki-67 average (p = 0.0025) and maximum (p = 0.0239) AQUA scores were also significant predictors of pCR in multivariable analysis with tumor size, nuclear grade, nodal status, ER status, and HER2 status considered. Conclusions: Measurement of Ki-67 expression by objective quantitative methods shows increased Ki-67 levels are an independent predictor of response to neoadjuvant chemotherapy. This assay is most sensitive and specific when the average Ki-67 expression from all fields of view is used.
Confirmation of C9741 intergroup results in a prospectively randomized trial comparing dose-intense chemotherapy with G-CSF support to 3-weekly chemotherapy for adjuvant therapy of nodal-positive (1–3 LN) breast cancer: Longitudinal CA 27.29 results indicate higher decay of minimal residual disease in the dose-dense arm
Authors: F. Ghani, S. Schildhauer, H. Eggemann, R. Geppert, K. Wernecke, M. Weigand, K. Possinger, D. Elling, D. Lüftner
Journal: Journal of Clinical Oncology (2004)

805 Background: In 2003, Citron et al. published the results of the C9741 trial showing an improvement of outcome for dose-dense adjuvant chemotherapy of breast cancer (Citron et al., JCO 2003, 21). The German Adjuvant Study Group is finishing recruitment (n = 884) into a trial in which patients either receive conventional ECP (arm A; epirubicin (E): 90 mg/m2 with cyclophosphamide (C) 600 mg/m2 x4 q3w, followed by paclitaxel (P) 175 mg/m2 x4 q3w) or dose-dense EP plus G-CSF on days 5–13 (arm B; E: 120 mg/m2 x4 q2w, followed by P: 175 mg/m2 x4 q2w). Methods: HER-2/neu (normal <15 ng/ml) and CA 27.29 (normal <30 U/ml) are measured using ELISA assays. The nonparametric analysis of variance for repeated measurements is used to detect significant influences of treatment arm, menopausal status, time effects and interactions. Results: Plasma results (baseline and end of chemotherapy) are available from 250 patients of whom 44% are premenopausal, a total of 30.3% is HER-2/neu positive in tissue. HER-2/neu concentrations increased from 9.3 ng/ml to 11.3 ng/ml irrespective of the arm (p=0,20) and menopausal status (p=0,85), but with a relevant time effect (p<0,00001). In contrast to HER-2/neu, CA 27.29 levels increased much more over time (p<0.00001) in the dose-dense arm B irrespective of menopausal status as compared to arm A (p=0.007).Conclusions: Plasma HER-2/neu increases significantly and irrespective of menopausal status during adjuvant chemotherapy as result of regulatory mechanisms at the HER-2/neu gene. Identical results were recently published for premenopausal patients (Lüftner et al., Breast Cancer Res Treat 2003, 80). The increase of HER-2/neu derives from HER-2/neu expression in epithelial organs and does not reflect minimal residual disease or relapse of breast cancer. The pronounced increase of CA 27.29 in the dose-dense arm can be explained by cell kill of minimal residual disease during intensified chemotherapy. No significant financial relationships to disclose.
Realism and constructivism in social perception
Authors: John F. Kihlstrom
Journal: Behavioral and Brain Sciences (2017)

Abstract Jussim's critique of social psychology's embrace of error and bias is needed and often persuasive. In opting for perceptual realism over social constructivism, however, he seems to ignore a third choice – a cognitive constructivism which has a long and distinguished history in the study of nonsocial perception, and which enables us to understand both accuracy and error.
Lifetime traumas and their influence on advanced cancer patients’ illness understanding and likelihood of end-of-life discussions.
Authors: Elizabeth L Kacel, Paul K Maciejewski, Holly Gwen Prigerson
Journal: Journal of Clinical Oncology (2012)

9146 Background: Research on posttraumatic stress in cancer patients has focused on patient reactions to their cancer diagnosis. Few studies have examined the impact of lifetime traumatic events prior to diagnosis on how advanced cancer patients understand the life-threatening nature of their illness and how likely they are to discuss their end-of-life (EOL) wishes with their oncology providers. Methods: The Coping with Cancer (CwC) is an NCI-funded prospective, multi-institutional cohort study of advanced cancer patients and their caregivers. Participants were recruited from September 2002 to February 2008 from six comprehensive cancer centers across the United States. Lifetime traumas were captured by the number of events reported in response to the Structured Clinical Interview for the DSM-IV (SCID) Lifetime Posttraumatic Stress Disorder question that probed for “extremely upsetting” life events. Associations between patient characteristics and number of lifetime traumas were estimated as odds ratios using ordinal logistic regression. Associations between number of lifetime traumatic exposures, controlling for confounding patient characteristics, and patient Terminal Illness Acknowledgement (TIA) and reports of EOL discussions were estimated as odds ratios using multiple logistic regression. Results: After adjusting for race, education, and recruitment site, the number of lifetime traumas patients reported remained significantly associated with TIA (OR = 1.25, p = .034) and discussion of EOL wishes (OR = 1.29, p = .013). Conclusions: The greater the number of traumatic experiences reported by cancer patients the more likely they are to acknowledge that they are terminally ill and discuss their end-of-life wishes with their oncology providers. The impact of witnessing or experiencing serious or life-threatening events in the past appears to improve advanced cancer patients’ abilities to understand the seriousness of their condition and increases the likelihood that they will discuss their preferences for care at the end of life with their doctors.
Shortened telomere length to predict initiation of carcinogenesis in Lynch syndrome.
Authors: Grainne O'Kane, Sarah A. McGarrigle, Simon Hooper, M. P. Farrell, Jacinta O'Sullivan, C. Muldoon, Padraic M. Mac Mathuna, Desmond Carney, David James Gallagher
Journal: Journal of Clinical Oncology (2014)

1554 Background: Lynch Syndrome (LS) is an autosomal dominant cancer predisposition syndrome conferring a 60-80% lifetime risk of developing colorectal cancer in addition to a spectrum of other malignancies. This occurs as a consequence of germline mutations in DNA mismatch repair (MMR) genes. Significant phenotypic heterogeneity exists among LS families. Anticipation has also been reported but remains poorly understood. We investigated an association between age of tumour onset and telomere length in Irish LS families. Methods: Family pedigrees were reviewed and parent-child pairs (PCPs) with LS-associated malignancy identified. Patients with genetically confirmed LS were invited to participate in the study. Peripheral blood mononuclear cells were isolated from affected mutation carriers (AC) and unaffected mutation carriers (UAC). DNA was extracted and relative telomere length (RTL) measured by quantitative polymerase chain reaction. Pearson’s correlation was used to compare age-adjusted RTL and age at tumour diagnosis. Results: Forty-four LS families were identified containing fifty-four PCPs with LS-associated malignancies. Anticipation was present in 90%; the median age of cancer diagnosis occurred 14.5 years earlier in mutation carriers (range 1-45 yrs). Telomere length has been analysed in fifty-one mutation carriers to date. (Table) As expected increasing age at blood withdrawal correlated with shorter telomere length (p<0.05). In AC the mean age-adjusted RTL was 1.281 and in UAC 0.980. In AC there was a strong correlation between earlier onset malignancy and shorter age-adjusted RTL (p=0.004). Conclusions: Anticipation is evident in Irish LS families and patients who develop earlier onset malignancy have shorter telomere lengths. We plan to validate our findings in a larger cohort and compare telomere length in an age and sex matched control cohort. AC (N=25) UAC (N=26) Male (N) 13 11 Female (N) 12 15 Median age cancer diagnosis (yrs.) 39 (22-77) ------- Median age blood withdrawal (yrs.) 52.5 (30-88) 40 (23-63) Mutation (N) MLH1 14 11 MSH 2 9 10 MSH 6 2 3 PSM 2 0 2 EPCAM 0 0
Transition from active treatment to survivorship care for childhood cancer patients.
Authors: Madhu S Gowda, Anne G.C Mauck, Matthew Bitsko, Alma Morgan, Robyn Dillon, Kamar Godder
Journal: Journal of Clinical Oncology (2017)

34 Background: It has been described that the transition at the end of treatment is a time for relief that the treatment is over but also for fear of recurrence, dealing with the physical sequelae of treatment, reintegration back with friends and with school. To address these concerns we developed a transition program with a goal to provide information, offer educational support and also assess the needs of this group by individual interviews and by measuring stress/anxiety/depression among patients and parents. Methods: Patients who were between 3 months pre and 1 year post end of treatment were enrolled. We conducted 4 educational ‘Forums’, worked with them to develop education plans by individual testing and school meetings were held to implement educational plans. Emotional status was assessed with Questionnaires such as the Revised Anxiety and Depression Scale (RCADS-P), Impact of Events Scale-Revised (IES-R), Brief Symptom Inventory (BSI), and the State Trait Anxiety Scale (STAI-C). Results: We had 7 patients attending the first 2 forums. When it was opened up to those beyond 1 year from the end of treatment, we had about 17 patient/parents that attended each of the subsequent forums. Compared to the numbers attending the forums, there was a higher request for one-to-one testing, individual school meeting, and requests for educational resources (53 school meetings held during that period). We had 38 parents and 21 children that completed the psychological screeners in total. On the RCADS-P, parents most often reported elevated symptoms of depression in their children. Findings showed that very few transition patients endorsed significant anxiety on the STAI-C. On the IES-R and BSI, the parents reported a higher level of anxiety, depression and post-traumatic stress. Conclusions: Patients in the transition phase were less involved in educational forums compared to Long Term survivors, the majority of them seeking one-on-one educational help. We hypothesize that problems become more evident as more time passes from the end of treatment. Also, between the RCAD-S and the BSI in adult survivors, depression seems to be the primary construct rather than anxiety.
Clinical characteristics and outcomes of atypical carcinoid (AC) tumor of the lung: A Surveillance, Epidemiology, and End Results database analysis.
Authors: Conor Ernst Steuer, Madhusmita Behera, Sungjin Kim, Zhengjia Chen, Rathi Narayana Pillai, Taofeek Kunle Owonikoko, Fadlo Raja Khuri, Suresh S. Ramalingam
Journal: Journal of Clinical Oncology (2014)

7554 Background: AC is a rare form of thoracic malignancy. The limited knowledge of the presentation and treatment of this tumor comes largely from small, single institution experiences. We analyzed the Surveillance, Epidemiology, and End Results database (SEER) to better understand the clinic characteristics of this disease. Methods: Demographic, treatment and outcome data on all patients with pulmonary AC was obtained from the SEER database with 18 reporting sites from 1973-2010 using SEER*Stat 8.1.2. All analyses were performed using SAS 9.3. Results: Out of 947,463 patients diagnosed with lung and bronchus tumors from 1985 to 2010, 441 patients with AC were identified. Demographic data and median overall survival (OS) for patient subgroups are presented in the table below. The median OS for all patients is 26 months. The 3-year survival rate (N=254) is 67%. The 3-year survival rate for distant (M1), regional (lymph node involvement), and localized (lung only) disease is 26%(13/50), 69%(50/72), and 85%(99/116) respectively. Older age, black race, and advanced disease are associated with a worse overall prognosis. Univariate analyses showed patients treated with surgery had reduced risk of death OS (HR .19, p <0.001) while radiation treatment was associated with increased risk of death (HR 2.45, p <0.001). Conclusions: Atypical carcinoid tumors are more frequent in women and present with early stage disease in nearly 80% of the patients. Patients who were able to undergo surgical resection had superior outcomes. Variable Level N (%) Median OS (months) Age Median (range) 65 (21 - 90) Race White 381 (87.19) 28 Black 37 (8.47) 14 Other 19 (4.35) Sex Male 138 (31.29) 27.5 Female 303 (68.71) 26 Summary stage Distant 83 (19.9) 13 Regional 131 (31.41) 28 Localized 203 (48.68) 35 Radiation Yes 54 (12.5) 19 No 378 (87.5) 28 Surgery of primary site Yes 341 (77.5) 32 No 99 (22.5) 13 Total N=441. Data are presented as number of patients (%) or median (range).
Novel biomarker of specific castration-resistant prostate cancer (CRPC) by exploring the proteome analysis.
Authors: Hiroji Uemura, Noriaki Arakawa, Yusuke Itoh, Takashi Kawahara, Yasuhide Miyoshi, Shouhei Akiba, Norihisa Ohtake
Journal: Journal of Clinical Oncology (2017)

247 Background: It is well known that prostate specific antigen (PSA) level has no reliable correlation with pathological malignancy of prostate cancer and is not a predictor for the development of castration resistant prostate cancer (CRPC). The aim of this study is to explore novel biomarkers to predict the development of CRPC by using proteomics from secreted proteins from human prostate cancer cells. Methods: The proteins secreted from 6 prostate cancers in culture medium were analyzed and compared with 8 other cancer cells including renal and urothelial cancers using LTQ Orbitrap mass spectrometer. With the focus on high tissue specificity, the candidate biomarker proteins were then identified through analysis of gene expressions in proteins common to human prostate cancers by real time qPCR. Next, a system to measure the identified mouse monoclonal antibodies against the focused proteins was established. Finally, serum levels of these proteins from 33 patients with benign prostate hyperplasia (BPH), 31 with untreated prostate cancer (PCa) and 35 with CRPC, were measured. Results: The proteome analysis identified 12 candidates of secreted cell membrane proteins as new biomarkers. The proteome analysis indicated that not only matured GDF15, but pro-peptide as well as fragments (GDDP) are released from prostate cancer cells. Patients’ serum was analyzed for matured and pro-peptide GDF15 using ELISA and immunoprecipitation-MRM mass spectrometry. The results showed that the serum level of GDDP-1, one of the processing forms of GDDP, was significantly higher in CRPC than those in BPH and untreated PCa (P &lt; 0.01). ROC analysis also showed that the AUC of GDDP-1(0.86) was higher than that of matured GDF15 (0.76). When the cutoff value of GDDP-1 was set at 4.0 ng/mL, there was a significant difference of overall survival (OS) in CRPC patients between those with more than 4.0 ng/mL compared to less than 4.0 ng/mL of GDDP-1, whereas there was no significant difference of OS measurable by PSA in CRPC patients. These data suggest that GDDP-1 may be a novel biomarker for CRPC. Conclusions: GDDP-1 shows potential as a novel biomarker for CRPC.