tbuckley/cabot-search huggingface dataset:
What about the guys? An assessment of gender differences in hereditary colorectal cancer testing.
Authors: Carin Espenschied, Jonathan Pepper, Rachel E. McFarland
Journal: Journal of Clinical Oncology (2017)

537 Background: Approximately 5-10% of colorectal cancer (CRC) is due to hereditary causes. Identification of an inherited cause may impact surgical and treatment decisions for CRC patients and may identify increased risks for other cancers that warrant increased screening and/or risk reduction measures. Men have testing for hereditary breast and ovarian cancer less often than women, even though these genes may also cause increased risk for cancer in men and men are as likely as women to carry mutations in these genes and pass them onto their children. We aimed to explore whether similar gender differences exist related to testing for hereditary CRC. Methods: We retrospectively reviewed clinical data and test results from consecutive CRC cases, who had a multi-gene panel with 13-49 genes at our laboratory, between March 2012 and June 2016. Statistical comparisons between males and females were conducted using Fisher’s exact test. Results: Of CRC cases (n = 7142), 61.1% were female and 12.8% were positive for mutation or likely pathogenic variant. Average age of CRC onset for men was 47.2, and for women was 49.5. Women with CRC before age 20 had the highest mutation rate (31.8%), but men were more likely to test positive than women overall (14.1% vs 12.0%, p = 1.1e-2). Mutations were most frequent in the same three genes for both men and women, but in different orders: MLH1, CHEK2, and MSH2 for males and CHEK2, MSH2, and MLH1 for females. The only genes with significant differences in mutation rates between men and women were MLH1 (3.2% vs 1.5%, p = 2.0e-6) and MSH6(1.7% vs 0.8%, p = 3.0e-3). Conclusions: Hereditary CRC is expected to affect men and women equally. In our cohort, however, the majority of individuals tested were women, while men were more likely to test positive. Possible explanations include smaller sample size and earlier age of onset in men, perceptions of referring clinicians, and different levels of interest in genetic counseling and testing between male and female patients. These data highlight an important opportunity for educating and identifying more men with hereditary CRC who may benefit from genetic information. Further studies are needed to confirm these results and explore reasons for the differences.
Initial gemcitabine/nab-paclitaxel (GA) followed by sequential (S) mFOLFIRINOX or alternating (A) mFOLFIRI in metastatic pancreatic cancer (mPC): The SEENA-1 study.
Authors: Vincent J. Picozzi, Joseph W. Leach, John E. Seng, Stephen Patrick Anthony, Raul Mena, Tim Larson, Erkut Hasan Borazanci, Glen J. Weiss, Shih-Li Bruce Lin, Gayle S. Jameson, Vanessa Bolejack, Amy C. Stoll, Daniel D. Von Hoff, Ramesh K. Ramanathan
Journal: Journal of Clinical Oncology (2017)

359 Background: GA, FOLFIRINOX and FOLFIRI are standard chemotherapy (CTX) regimens for mPC.The optimal introduction of these regimens following GA is not known. This phase II study evaluated 2 different approaches to this question. Methods: Eligibility criteria included 1) untreated mPC, 2) ECOG PS 0/1, 3) organ function adequate for Rx. Patients (pts) were treated according to one of 2 methods following GA given per standard dose/schedule: FOLFIRINOX (bolus 5-FU omitted) for up to 12 cycles at 24 weeks or at time of disease progression (S); or GA alternating with FOLFIRI q8 weeks up to 48 weeks total Rx (A). Results: 54 evaluable pts (28S, 26A) were enrolled . Pt characteristics included median age 65, M/F 48/52% , liver involvement 89%. 17/53 pts (31%) did not achieve disease control at 8 weeks (8 toxicity/complications , 6 disease progression, 3 declined further protocol therapy). Of the remaining 37 pts, 24/13 were treated with S/A regimens, respectively. Grade ≥ 3 treatment toxicities reported while on study with frequency ≥ 10% included anemia 21%, neutropenia 43%, thrombocytopenia 15%, and fatigue 22%. Grade ≥ 3 neuropathy occurred in 8% of pts. For all 54 pts using RECIST 1.0, CR/PR/SD/DC was 2 (4%)/20 (37%)/19 (35%)/41(76%). Ca19.9 response ≥ 90% was seen in 20/37 (54%). For all pts, median OS was 12.3 months ( 95% CI 8.6-14.5 mo); 12 and 24 mo OS was 51% and 11%, respectively. For the 37 pts with DC on GA at 8 weeks (calculated from start Rx) median OS was 13.5 mo (95% CI 10.7-15.4 mo); 12 and 24 mo OS was 55% and 16% , respectively. No statistically significant differences were seen between S and A with respect to toxicity, response or survival. Conclusions: 1) As opposed to introduction of 5FU-based CTX at the time of disease progression/prohibitive toxicity, introduction prior to that time may be at least comparable regarding both toxicity and OS. 2) This approach may further enhance OS in pts who achieve DC on GA at 8 weeks. 3) Neither S nor A method of 5FU-based CTX introduction following GA was clearly superior in this study. 4) How best to combine 5FU-based combination CTX following GA in mPC merits further study. Supported by the Seena Magowitz Foundation.
Safety and tolerability of veliparib combined with capecitabine plus radiotherapy in patients with locally advanced rectal cancer: a phase 1b study
Authors: Brian G Czito, Dustin A Deming, Gayle S Jameson, Mary F Mulcahy, Houman Vaghefi, Matthew W Dudley, Kyle D Holen, Angela DeLuca, Rajendar K Mittapalli, Wijith Munasinghe, Lei He, John R Zalcberg, Samuel Y Ngan, Philip Komarnitsky, Michael Michael
Journal: The Lancet. Gastroenterology & hepatology (2017)
Tumor location, pathology, and patient ethnicity in the predictive accuracy of EUS in gastric and gastroesophageal junction cancers.
Authors: Andy Z. Huang, Vimbai Nyemba, Than Than Aye, Na Liu, Peter Homel, Yiwu Huang, Yiqing Xu
Journal: Journal of Clinical Oncology (2015)

e15043 Background: Endoscopic ultrasound (EUS) is a common test performed in patients diagnosed with gastric and gastroesophageal junction (GEJ) cancers for T and N staging; its result is highly valuable in treatment planning. The reported accuracy varies from 50% to 90%. We hypothesized that EUS accuracy could be influenced by the location, histology and ethnicity and evaluated those factors in EUS performed in the community Methods: This is a retrospective analysis of all patients diagnosed with gastric and GEJ cancers who had EUS followed by surgery without neoadjuvant chemotherapy between 1/2006 and 12/2013. EUS and surgical T and N staging were scored for accuracy, understaging or upstaging by EUS. The following variables were evaluated; Tumor location: GEJ, cardia, body or antrum; Tumor histology: intestinal versus diffuse (signet ring) type; and Ethnicity: Asian versus non-Asian. Results: 28 patients (20 M, 8F) were identified; mean ± SD age was 67 ± 11years (range 40 to 93). 20 were Asians and 8 were non-Asians. The overall rates of agreement between EUS and surgical staging for T and N were 53.1% and 61.3% respectively. EUS was most accurate for T when the tumor was located in the body (83.3%, n = 6), 50% in GEJ (n = 10), 50% in the cardia (n = 3), and least accurate in the antrum (33.3%, n = 9; p = .037). EUS tended to upstage the T when it is located in the body or GEJ, and downstage the T when a tumor is located in the cardia or antrum. EUS had a 100% accurate prediction in T1, but predicted only 16.7% in T2, and 50% each in T3 and T4 tumors (T by surgical staging). When EUS showed T2 (n = 12), the true T by surgery varied from T1 to T4. When EUS showed T3 or T4, the true T varied from T2-T3. For N staging, EUS showed a trend of best accuracy in the body (83.3%) and least accuracy in the GEJ (40%). The EUS accuracy rate does not differ based on patient ethnicity or tumor histology for T or N staging. Conclusions: There is a relatively high inaccuracy rate in using EUS prediction for T and N staging. EUS appears to show best accuracy when the tumor is located in the body and has a T1 staging. Its accuracy does not change due to tumor histology or patient ethnicity. A larger sample size and prospective study is needed to confirm those findings.
Sarcopenia as a useful predictor of postoperative complications following radical cystectomy: An assessment of preoperative CT scans.
Authors: Martin Jp Hennig, Marie C Hupe, Bennet Hensen, Max Clemens Jansen, Mario W Kramer, Markus A Kuczyk, Axel Stuart Merseburger
Journal: Journal of Clinical Oncology (2017)

351 Background: Muscle-invasive urothelial carcinoma is usually treated with radical cystectomy (RC). However, patients face a relevant risk of postoperative complications on variable factors. Recent reports described that sarcopenia, which is defined by a loss of sceletal muscle body composition, may enhance risk stratification. Methods: Our retrospective study includes 200 patients (154 men, 46 women, mean age: 67.9 years) which were treated with RC between 2005 and 2014. Median follow-up time was 26 months. Computed tomography (CT) scans were performed within 60 days prior to surgery. Lumbar skeletal muscle index (SMI) were measured with MeVisLab 2.7 by manually segmentation of preoperative CTs. The fat mass index (FMI) was calculated based on the same CT slides. Cut off points were developed for men and women separately. Additionally, short-, mid- and long-term complications were assessed using the Clavien-Dindo classification. Results: SMI (cm 2 /m 2 ), FMI (kg/m 2 ) and BMI (kg/m 2 ) for men were calculated with mean scores of 52.8, 9.6 and 26.7, respectively. The corresponding calculated means for women were 38.9, 10.0 and 26.1. The SMI for short- and mid-term complications was statistically significant (p &lt; 0.01) when applied on patients with a BMI over 25 kg/m 2 . Using Kaplan-Meier plots none of the other markers (BMI and FMI) correlated with complications or overall survival (OS). Conclusions: The presence of sarcopenia assessed by CT may improve risk stratification in patients undergoing radical cystectomy. BMI and FMI may not be used in risk stratification models, even though further validation for subgroups is needed. Future research is needed to validate the current findings. Noninvasive and semiautomatic calculation of SMI in preoperative CT scans may improve risk stratification in patients undergoing radical cystectomy and thus could reduce morbidity and mortality.
A blood-based epigenetic test for early detection of nasopharyngeal carcinoma (NPC).
Authors: Yew-Oo Tan, Eduard M. Alfanta, Ramon Antonio B. Lopa, Elaine Hsuen Lim, Hwee Yong Whang, Karmen Wong, Philip Jordan, Emily Corfield, Matthew Salter, Megan Field, Alexandre Akoulitchev, Thomas Kwok Seng Loh, Boon C. Goh, Wen Son Hsieh
Journal: Journal of Clinical Oncology (2013)

6063 Background: NPC is highly curable in early stages but 70% of NPC patients are diagnosed with advanced disease due to lack of effective screening. Genetic and epigenetic alterations involved in the pathogenesis of NPC are known. The higher order chromosomal structures reflecting aberrant transcriptional states of these genes can be measured via techniques such as chromosome conformation capture. Detection of these changes in peripheral blood may provide an accurate test for the early cancer detection. Methods: Blood samples have been collected from 84 patients with histologically confirmed NPC and 100 matched controls. Samples from 45 NPC patients and 68 controls have been analyzed. Fourteen genes known to be dysregulated in NPC were investigated. Potential higher order juxtaposition sites in the candidate genes were predicted using pattern recognition software. PCR primer sets were designed around the chosen sites to screen potential markers. Twenty-two markers showing predictability between NPC and control samples were analysed for optimal reproducibility using alternative primer sets. The optimal sets of markers were then tested amongst the complete set of samples. The dataset was processed by re-sampling using the synthetic minority oversampling technique. The overall sample was split into two groups (66% training set and 34% test set) in the classification. Results: Sixteen markers from 7 candidate genes were found to be optimal in differentiating between NPC and control samples in the first 103 samples. Using the multilayer perceptron (MLP) classification, the following results were obtained: Sensitivity 88.9%, 95% CI (79.2% - 98.6%); Specificity 72.7%, 95% CI (58.9% - 86.5%); PPV 72.7%, 95% CI (58.9% - 86.5%); NPV 88.9%, 95% CI (79.2% - 98.6%). The accuracy of the test was similar in detection of stage I and II NPC versus that of stage III or IV NPC. Conclusions: Using a PCR-based method to detect alterations in the cancer epigenome, the feasibility of developing a blood test of potential utility in early diagnosis of NPC was demonstrated. Analysis of larger numbers of patient samples and optimization of markers are ongoing. The performance characteristics of the test in the total population of 184 samples will be presented.
EZH2 expression and clinical outcome in African-American men with prostate cancer.
Authors: Vivek Narayan, Priti Lal, Charnita Zeigler-Johnson, S. Bruce Malkowicz, Timothy Rebbeck
Journal: Journal of Clinical Oncology (2017)

81 Background: Despite increasing recognition of molecular differences in prostate cancers from African-American men (AAM) and European-American men (EAM), the prognostic utility of novel tissue biomarkers in AAM remains poorly defined. Overexpression of the oncogenic transcriptional regulator EZH2 has been associated with clinical outcome in localized prostate cancer, but it has not been adequately evaluated in AAM. We sought to define the prognostic significance of EZH2 overexpression in a racially-balanced cohort of men with localized prostate cancer and to explore potential race-specific differences. Methods: This was a retrospective analysis of men who underwent radical prostatectomy at the University of Pennsylvania between 1991 and 2010. Subjects with formalin fixed paraffin embedded tissue available for EZH2 immunohistochemistry were included. Slides were graded in a semi-quantitative manner for both the volume and the intensity of EZH2 staining. Multivariate Cox regression models were used to evaluate the independent association of clinicopathologic parameters, including EZH2 staining index, and biochemical recurrence (BCR)-free survival. Results: 121 patients (62 AAM, 59 EAM) were eligible for analysis. 56 patients (46.3%) demonstrated EZH2 overexpression, which was balanced between AAM and EAM subgroups (43.6% vs 49.2%, respectively). Extracapsular extension, positive surgical margins, and EZH2 overexpression were independently associated with BCR-free survival (HR of 2.02 for EZH2 overexpression, 95% CI 1.05 – 3.86, p = 0.035). Potential effect modification by race was identified (p for interaction = 0.056). While EZH2 overexpression was independently associated with BCR-free survival in AAM (HR 2.78, 95% CI 1.06 – 7.32, p = 0.038), no significant association was identified in the EAM subset (HR 0.89, 95% CI 0.35 – 2.29, p = 0.812). Conclusions: EZH2 overexpression is a valid prognostic marker in AAM treated with prostatectomy. The potential for enhanced prognostic significance of EZH2 overexpression in AAM may lend insight into observed racial disparities. These results highlight the need for adequate representation of AAM in clinical trials evaluating novel EZH2-directed therapies.
Deciding to withhold or withdraw (WH/WD) anticancer therapy (ACT) in advanced cancer patients: Physicians and patients points of view and interactions.
Authors: Yvan Beaussant, Christophe Tournigand, Lionel Pazart, Florence Mathieu-Nicot, Elodie Cretin, Eric Deconinck, Carole Bouleuc, Aurelie Godard, Frederique Maindrault-Goebel, Patrice Cuynet, Regis Aubry
Journal: Journal of Clinical Oncology (2012)

e19623 Background: ASCO highlighted the need to improve communication with and decision making for pts with advanced cancer. This study explores the decision-making process for pts with advanced cancer when the question to WH/WD ACT is raised, with a cross-analysis of physicians and pts points of view. Methods: Multi-center qualitative study in 5 oncology and hematology units, based on semi-structured single interviews with referent oncologists and their pts. An epidemiological survey was performed to identify the prevalence of such decisions. Results: Of the 839 pts hospitalized during a given week, the question to WH/WD ACT was raised in 3.4% of cases (n=29) and in 12,8% when excluding ambulatory pts (n=26 of 202). All 29 referent physicians and 21 pts were interviewed. Futility and poor general condition were the most frequently cited reasons to WH/WD ACT. Subjective determinants related to the physician/patient relationship and their respective experiences were also predominant in all interviews. Although most physicians reported attempting to fully inform pts about their poor prognosis and treatment options, only a minority were able to anticipate the option to WH/WD ACT in these discussions. The fear to remove pts’ hope and to increase anxiety, and a feeling of capitulation and abandonment were the main obstacles they pointed out. For pts, hope and struggle attitudes were predominant, as well as anxiety about their situation and confidence in the physicians’ decisions. More than 80% of pts declared leaving the physician to decide alone. Most of them expected to be involved in the decisions, but only 1/3 reported being actually aware of this questioning. Conclusions: In this study, oncologists faced the difficult decision whether to continue, WH/WD ACT for 1/7 hospitalized patient. The uncertainty of the benefit/risk assessment seemed to strengthen the subjective determinants of the questioning. Pts and physicians mutual willingness to maintain hope reinforced an attitude of “not giving up”. Communication training of health professionals and integrative palliative care could favor the ethical questioning and improve care through the respect of pts’ preferences.
FATE: the new partnership to Fight Against TB in Central and Eastern Europe
Authors: Tomasz Jagielski, Alena Aleksa, Elizabeta Bachiyska, Ágnes Bakos, Valeriu Crudu, Jaroslaw Dziadek, Jirí Homolka, Daniela Homorodean, Inta Jansone, Vera Katalinic-Jankovic, Rafal Krenke, Uroš Kuzmic, Igor Mokrousov, Vlad Nikolayevskyy, Alena Nikolenka, Gjyle Mulliqi Osmani, Dimitrios Papaventsis, Ilva Pole, Igor Porvazník, Branislava Savic, Natalia Shubladze, Ivan Solovic, Nóra Szabó, Silva Tafaj, Aida Ustamujic, Jakko van Ingen, Edita Vasiliauskiene, Peter K. Yablonsky, Ilona Zemanova, Viacheslav Zhuravlev, Manca Žolnir-Dovc
Journal: The Lancet Infectious Diseases (2017)
Epigenetically induced expression of CD30 in T-PLL: A rationale for the use of brentuximab vedotin.
Authors: Zainul Hasanali, Kamal Sharma, Sara Shimko, August Stuart, Xin Liu, Elliot E Epner, Thomas P. Loughran
Journal: Journal of Clinical Oncology (2012)

6616 Background: T-cell prolymphocytic leukemia (T-PLL) is characterized by high lymphocyte counts, skin involvement and enlarged organs. Treatment with alemtuzumab (alem) induces complete remission (CR) in &gt;50% of patients, duration is short (median: 6 mos). Therapy with the histone deacetylase inhibitors (HDACi) vorinostat (SAHA) or romidepsin (romi) and cladribine (2-CdA), may augment mAb activity. Methods: Five T-PLL patients were studied (Table). Diagnosis was made by pathology, flow cytometry and TCR studies. Alem (30 mg sq d1,3,5) and 2-CdA (5mg/m2 d1-5), followed by alem, 2-CdA and SAHA (400mg q d X 5 days) or romi (14mg/m 2 d 1,8,15) was given. One patient with skin lesions expressed CD30 and received brentuximab vedotin (SGN-35). Results: All patients achieved CR (mean: 10; median: 8 mos). Relapsed patients responded with repeat dosing. Genes assayed indicate involvement of the MAPK pathway (p53, DUSP2, TRIB1, C/EBP). mRNA expression of the membrane receptor CD30 (TNFRSF8) increased following therapy in 4/5 patients (mean: 14; Range: 1.3-69 fold). CD30 protein was confirmed by IHC and Western blotting. One patient with relapsed T-PLL involving skin had a dramatic clearing of lesions and blood counts after one dose of SGN35. Conclusions: Therapy with HDACi and 2-CdA overcomes resistance and augments clinical activity of alem and SGN-35, as evidenced by derepression of CD30 and response to treatment. We present a rationale for epigenetic resensitization to mAbs and their drug conjugates (ADC) in T-PLL. A prospective multicenter clinical trial is warranted. [Table: see text]
The estimation of sarcoma incidence and prevalence utilizing routine public health insurance data.
Authors: Markus Kajo Schuler, Freya Trautmann, Jochen Schmitt
Journal: Journal of Clinical Oncology (2014)

e17597 Background: Sarcomas are a heterogeneous group of rare malignant tumors. Cancer registries are not suitable to determine the burden of sarcoma because of the difficulty in classifying and identifying sarcomas in the original tissue. Therefore, other sources need to be utilized to estimate the burden of sarcoma. We aimed to estimate the incidence and prevalence of sarcomas based on routine public health insurance data. Methods: This secondary data based cohort study utilized the AOK-database Saxony, Germany, a pseudonymized population-based administrative healthcare database with complete information on outpatient health care (diagnoses, procedures, treatments) and sociodemographic characteristics of 2.4 million individuals from 2005 until 2011 that is widely representative for the German population. For means of internal case validation, the ICD-10-code for sarcoma had to be documented at least twice to classify patients as prevalent cases. Incident cases were defined as confirmed cases of sarcoma with no sarcoma diagnosis in the previous three years. Results: Within the 7 year observation period a total of 2,328 patients were classified as cases of prevalent sarcoma. The prevalence of confirmed sarcoma was 112.6/100,000 persons. In 2011, the raw and age-standardized (WHO standard) incidence rates were 10.2/100,000 and 6.9/100,000 persons, respectively. Conclusions: This study suggests that the burden of sarcoma can be estimated from population-based administrative healthcare data. The observed prevalence and incidence are in good accordance with other estimations from Europe suggesting validity of the methods used. Although overestimation or underestimation of the burden of sarcoma cannot be excluded as our estimations could not be validated against primary clinical data, we believe that secondary health insurance data constitute a valuable source to investigate the quality of sarcoma care and the effectiveness of interventions for sarcoma in routine care.
Improving Public Health by Making Cities Friendly to Walking and Biking
Authors: Janette Sadik-Khan, Seth Solomonow
Journal: JAMA Internal Medicine (2017)

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