tbuckley/cabot-search huggingface dataset:
Management and outcomes of patients with recurrent intrahepatic cholangiocarcinoma following previous curative intent surgical resection.
Authors: Gaya Spolverato, Yuhree Kim, Sorin Alexandrescu, Hugo Marques, Luca Aldrighetti, T. Clark Gamblin, Carlo Pulitano, Todd W. Bauer, Feng Shen, Charbel Sandroussi, George A. Poultsides, Shishir Kumar Maithel, Timothy M. Pawlik
Journal: Journal of Clinical Oncology (2015)

349 Background: Many patients develop recurrence following resection of intrahepatic cholangiocarcinoma(ICC). Management and outcomes of patients with recurrent ICC following previous curative-intent surgery are not well documented. We sought to characterize the treatment of patients with recurrent ICC and define therapy-specific outcomes. Methods: Between 1990-2013, 542 patients who underwent surgery for ICC were identified from an international database. Data on clinicopathological characteristics, operative details, recurrence and recurrence-related management were recorded and analyzed. Results: At initial surgery, treatment was resection only(96.1%) or resection+RFA(3.9%). Overall 5-year survival was 25.9%; 376(69.4%) patients recurred with a median disease-free survival of 11.0 months. Vascular invasion(hazard ratio [HR]=1.43), nodal metastasis(HR=1.40) and poor differentiation(HR=1.30) were predictive of recurrence(all P&lt;0.05). First recurrence site was intrahepatic only (62.0%), extrahepatic only (14.1%), or intra- and extrahepatic(23.9%). Overall 259(68.9%) patients received treatment for recurrent ICC, while 117(31.1%) received best supportive care(BSC). Among patients who received treatment for recurrent disease, therapy consisted of systemic chemotherapy only(49.4%), repeat liver-directed therapy (25.9%), or systemic chemotherapy+liver-directed therapy(24.7%). Repeat liver-directed therapy consisted of repeat hepatic resection±ablation(30.5%), ablation alone (21.4%), and intra-arterial therapy(IAT)(48.1%). Among patients who recurred, median survival from the time of the recurrence was 11.0 months(BSC-7.7 months, systemic chemotherapy only-10.0 months, liver-directed therapy-18.0 months). The median survival of patients undergoing resection of recurrent ICC was 26.7 months versus 7.6 months for patients who had IAT(P&lt;0.001). Conclusions: Recurrence following resection of ICC is common, occurring in up to two-thirds of patients. When recurrence occurs, prognosis is poor. In well-selected patients with liver only recurrence, resection+chemotherapy may offer a modest survival benefit.
Lymph node ratio as prognostic after neoadjuvant therapy in breast cancer.
Authors: Danielle Marie Bertoni, Tina Hernandez-Boussard, Irene Wapnir
Journal: Journal of Clinical Oncology (2015)

123 Background: Lymph node ratio (LNR) is defined as the proportion of involved nodes over total number of nodes. The latter may be superior to TNM staging as a prognostic indicator in breast cancer treated surgically first. Pathological staging after neoadjuvant therapy (NAT) is based on the residual cancer burden (RCB) in breast and nodes. We hypothesized that LNR after NAT offers additional useful prognostic information. Methods: Patients receiving NAT were identified through the Stanford Tumor Registry. Based on previously published classifications LNRs in node positive disease was classified as low (L) 0.01-0.2, intermediate (I) 0.21-0.65, and high (H) &gt; 0.65. Other discriminant cut-off points were sought. Kaplan-Meier log-rank test was used for survival analysis. Results: 105 node-negative and 92 node-positive cases were identified (2003 -2010). Median number of nodes examined was 13, range 2-40. LNR among the node-positive cohort varied from 0.03 to 1.0. The distribution of positive nodes for L was 1-4, for I 1-13, and for H 2-25. The 3-year DFS and OS were 94% and 98%, for node-negative cases, and 66% and 77% for node-positive cancers. Survival for L = 79% (median 55%); I = 56.2% (median 52%); and H = 55.6% (median 49%). Using 0.5 as a new discriminant, the 3 and 5-year OS for LNR &lt; 0.5 was 78.1% and 69.9%, and for LNR &gt; 0.5 was 52.2% and 39.8%, respectively (p = 0.02). Conclusions: LNR of 0.5 was found to discriminatefor survivalin patients after NAT. This differs from the LNR categories defined for patients who had surgery first. Further validation in larger dataset is warranted.
White Paper AGA: An Episode-of-Care Framework for the Management of Obesity—Moving Toward High Value, High Quality Care: A Report From the American Gastroenterological Association Institute Obesity Episode of Care and Bundle Initiative Work Group
Authors: Joel V. Brill, Jamile A. Ashmore, Matthew L. Brengman, Daniel E. Buffington, S. David Feldshon, Kelli E. Friedman, Peter S. Margolis, Danielle Markus, Leslie Narramore, Amita Rastogi, Anthony A. Starpoli, Kenneth Strople, Jane V. White, Sarah E. Streett
Journal: Clinical Gastroenterology and Hepatology (2017)
Peptide vaccines with low-dose dexamethasone versus dexamethasone alone for chemotherapy-naive castration resistant prostate cancer: A randomized phase II study.
Authors: Hirotsugu Uemura, Takahiro Kimura, Takafumi Minami, Kazuhiro Yoshimura, Masahiro Nozawa, Shin Egawa, Hiroyuki Fujimoto, Akira Yamada, Kyogo Itoh
Journal: Journal of Clinical Oncology (2014)

3 Background: We previously developed MHC class I restricted peptide vaccines for prostate cancer and carried out a phase 1 trial for castration resistant prostate cancer (CRPC) patients to assess safety and immunological evaluation. In the present study, we conducted a randomized phase 2 trial to evaluate the efficacy of peptide vaccination therapy for chemotherapy-naive CRPC patients. Methods: Early-stage CRPC (PSA&lt;10ng/ml) patients positive for HLA-A02 or A24 or A3 super family were randomized into two treatment groups; peptide vaccine with low dose (1mg/day) dexamethasone (Dx) versus low dose Dx alone. Patients were vaccinated subcutaneously with 3 mg of selected peptides (max. 4 kinds) 6 times at two weeks interval. Dx 1mg/day p.o. was started on the first day of peptide vaccination. Toxicity was assessed monthly, and immunological responses such as cytotoxic T lymphocyte activity and clinical responses were evaluated every 3 months. The primary endpoint of this study is progression-free survival including serum PSA. Secondary endpoints are overall survival and safety. Results: A total of 83 chemotherapy-naive CRPC patients were selected for this trial. Of these 10 patients were excluded due to HLA type mismatch and exclusion criteria. 73 patients were enrolled and randomized; 37 in the vaccine treatment group and 36 in the Dx group. One patient in the Dx group self-withdrew from the study immediate after the randomization. Median time to PSA failure in the vaccine group was significant longer than the Dx group; 602 days vs 210 days, p&lt;0.001 (Table). Conclusions: These findings suggest that combination therapy of peptide vaccines and low dose dexamethasone may be a promising tool for chemotherapy-naive CRPC patients. Clinical trial information: UMIN000000959.[Table: see text]
Discordance in pathology report after central pathology review in early breast cancer and its impact on treatment choice.
Authors: L. Orlando, G. Viale, P. Schiavone, P. Fedele, A. Nacci, P. Rizzo, N. Calvani, F. Sponziello, C. Chetri, E. Mazzoni, M. D' Amico, A. Marino, M. Cinefra, S. Cinieri
Journal: Journal of Clinical Oncology (2011)

585 Background: Systemic therapies in early breast cancer are chosen on the basis of predictive factors defined by immunohistochemistry. In large clinical trials the rate of discordance between local and central pathologic report is noteworthy. In this retrospective analysis we evaluated the discordance rate in histological report and the clinical impact on treatment decision, after central pathologic review of early breast cancer. Methods: A retrospective pathology review was performed on formalin-fixed and paraffin-embedded tissue from primary breast tumors collected from different Italian Cancer Centers from 2008 to 2010, by the Central Pathology Laboratory at the European Institute of Oncology in Milan. Central review included assessment of histologic subtype, grade, Ki-67, hormone receptors (ER/PgR) and HER2. HER2 status was also confirmed by FISH. Primary end-point was the discordance rate (DR) in ER, PgR, HER2 between local and central pathology. Results: 112 specimens from 10 cancer centers were reviewed. Ten locally ER positive (≥1 % ER and PgR) tumors were ER negative at the central review (DR 12.3 %). Ten ER negative tumors at the local evaluation changed in ER positive after central review (DR 32.3%). The overall DR for ER was 17.8% (95% CI, 10.7%-24.8%). Ten PgR positive tumors became PgR negative, 5 PgR negative tumors resulted PgR positive at central review (DR 14.3% and 12.2% respectively; overall DR 13.6% (95% CI, 7.2%-19.9%). Regarding HER2, 20 positive samples resulted negative (DR 54%), while 9 HER2 negative were positive at central report (DR: 13.3%) with an overall DR of 26.6% (95% CI, 18.1%-35%). These findings resulted in therapy change in 64 (57%) patients, mainly with avoidance of chemotherapy and trastuzumab prescription. Changes in percentage of ER and/or PgR from < 50% to > 50% immunoreactive cells or vice versa were found in 23 cases and resulted in different treatment choice (mainly exclusive endocrine therapy). Conclusions:In our retrospective analysis, the central pathologic review had a significant impact on the treatment choise in early breast cancers, as previously shown in clinical trials. Further studies are warranted in to confirm these provocative results.
Circulating endothelial cell (CEC), a surrogate of tumor angiogenesis, as a diagnostic and prognostic marker in malignant pleural mesothelioma (MPM).
Authors: K. Yoneda, F. Tanaka, N. Kondo, H. Orui, M. Hashimoto, T. Takuwa, S. Matsumoto, Y. Okumura, A. Sato, T. Tsujimura, N. Tsubota, K. Kuribayashi, K. Fukuoka, T. Nakano, S. Hasegawa
Journal: Journal of Clinical Oncology (2011)

10577 Background: Circulating endothelial cell (CEC) is a potential surrogate of tumor angiogenesis, but the clinical value in malignant pleural mesothelioma (MPM) remains unknown. Methods: Patients who presented with suspicion or diagnosis of MPM were prospectively evaluated. CECs in 4.0mL of the peripheral blood were captured and quantitatively evaluated with the CellSearch system. Tumor angiogenesis was evaluated by immunohistochemical staining with an anti-CD34 antibody and represented as microvessel density (MVD). Results: Among 109 patients included in this study, 79 were finally diagnosed as having MPM and 30 as non-malignant diseases (NM). A significant positive correlation was observed between CEC-count and MVD (Spearman r=0.44, p<0.01). CEC-count was significantly higher in MPM than NM (131 and 40, p<0.01), which provided a significant diagnostic performance in discrimination between MPM and NM with the AUC-ROC of 0.689 (95%CI, 0.581-0.798; p<0.01). Stage IV MPM cases tend to show a higher mean CEC-count than stage I-III MPM cases (151 vs. 106; p=0.10). Higher-CEC (≥50) was a significant prognostic factor to predict a poor prognosis. Conclusions: CEC proved to be a surrogate of tumor angiogenesis in MPM. In addition, CEC was a promising clinical marker not only in discrimination between MPM and non-malignant diseases but also in predicting prognosis in MPM. This study was supported by “The Special Coordination Funds for Promoting Science and Technology from the Japanese Ministry of Education, Culture, Sports, Science, and Technology.” Nonmalignant MPM P value No. of pts 30 79 CEC-count (mean) 40 131 P<0.01 Overall survival (median, months) 11.4 m (CEC≥50) vs 20.0 m (CEC<50) P=0.03 Overall survival rate (%, at 1/2 yrs) 49%/15% (CEC≥50) vs 69%/33% (CEC<50)
Obesity and insulin resistance in pediatric acute lymphoblastic leukemia worsens during maintenance therapy.
Authors: A. J. Esbenshade, J. H. Simmons, T. Koyama, E. Koehler, R. B. Lindell, D. L. Friedman
Journal: Journal of Clinical Oncology (2011)

e19611 Background: Pediatric acute lymphoblastic leukemia (ALL) survivors are at increased risk for the metabolic syndrome. We examined the trajectory of development over the first year of maintenance therapy. Methods: In a prospective cohort of pediatric ALL patients over the first year of maintenance therapy, we examined obesity, insulin resistance and associated biomarkers, testing the hypothesis that they would worsen over that time period. Endpoints included change in body mass index (BMI), fasting insulin and glucose, calculated Homeostatic metabolic assessment (HOMA), leptin and adiponectin. Paired t-tests and Wilcoxin-signed rank were used to compare continuous variables and Spearman (ρ) for correlations. Results: At the start of maintenance, 29% of patients were overweight and 16% were obese, rising to 48% and 29%, respectively, at the end of the first year of maintenance. The mean BMI z-score was 0.53 at maintenance start and increased over the next year to 0.93 (change (Δ) 0.4 95% confidence interval [CI] (0.1, 0.7) p=0.004). Mean fasting insulin levels increased over the first year of maintenance from 4.1µU/ml to 11.5 µU/ml (Δ 7.4 95% CI (1.3, 13.5) p=0.019), and mean HOMA increased from 0.9 to 2.6 (Δ 1.7 95% CI (0.3, 3.2) p=0.019). At the start of maintenance, 1/31 (3%) had insulin resistance by HOMA (>3.15) compared with 8/31 (26%) at one year (McNamer test p=0.016). BMI z-score at one year correlated with HOMA (p= 0.483 p=0.007). Mean leptin increased over year one of maintenance from 6.6 ng/ml to 12.8ng/ml (Δ 6.2 95% CI (1.5, 10.9) p=0.012). Leptin at one year correlated with BMI z-score (p= 0.635 p<0.001) and with HOMA (p= 0.741 p<0.001). Mean adiponectin levels decreased over one year of maintenance from 19.8µg/ml to 15.4 µg/ml (Δ -5.4 95% CI (-7.5,-1, 1) p=0.01) and were inversely correlated to BMI z-score (p= -0.483 p=0.011) but not to HOMA (p= 0.001 p=0.997). Conclusions: Obesity and insulin resistance worsen over the first year of maintenance therapy and are correlated with changes in leptin and adinopectin, suggesting that this time period may be an ideal time for a preventive intervention to limit increases in BMI/insulin resistance, which are known to extend to the long-term survivorship period.
Late onset of bone metastases as a prognostic parameter in metastatic renal cell cancer (mRCC): A single-center experience in 82 mRCC patients treated with sunitinib.
Authors: Philipp Ivanyi, Jasper Koenig, Arne Trummer, Christoph W. Reuter, Arnold Ganser, Viktor Grünwald
Journal: Journal of Clinical Oncology (2014)

523 Background: Bone metastasis (BM) is considered a negative prognostic marker in metastatic renal cell carcinoma (mRCC). Here, we address the impact of BM onset on overall survival (OS) in mRCC patients during targeted therapy. Methods: Patients with BM who received sunitinib (SU) as 1st targeted treatment at our center between May 2005 and December 2012 were included in this retrospective analyzes. Treatment was performed according to local standard and patients were followed for survival. Spine surgery, fracture or irradiation were considered skeletal related events (SRE). Results: Out of 128 mRCC patients with BM, 82 patients had SU as 1st line targeted agent. 57 (69.5%) patients suffered from BM at initial diagnosis of mRCC (=synchronous BM [sBM]), while 25 (30.5%) patients developed BM during treatment course (=metachronous BM [mBM]). Baseline characteristics showed different histological gradings for sBM compared to mBM patients (p=0.029) and higher frequency of ≥3 metastatic organ sites prior to SU for sBM patients (sBM: n=40 [70.2%] vs. mBM: n=10 [40%], p=0.016). In Kaplan-Meier analysis, sBM patients showed a reduced mean OS from SU start (sBM 23.5 [95%CI:18.6-28.3] vs. mBM 41.3 [95%CI:31.7-50.9] month, p=0.001), whereas PFS during SU treatment was similar (sBM: 8.1 [95%CI:3.9-12.3] vs. mBM: 8.7 [95CI:2.7-14.8] months, p=0.93). Bisphosphonate treatment and SRE revealed no differences between subgroups (p=0.62), while spinal compression occurred in 6 patients with sBM, but none with mBM (p=0.153). 2nd-line targeted agents were less frequently administered in sBM patients (sBM n=17 vs. mBM: n=10). Multivariate Cox-regression confirmed MSKCC score (OR: 2.6 [95%CI:0.99-7.28], p=0.052), liver metastases (OR: 2.66 [95%CI:1.28-5.51], p=0.009], and sBM [OR: 2.45 [95%CI:1.19-5.08], p=0.016) as independent prognostic parameters for reduced OS after SU start. Conclusions: In our cohort, OS in patients with sBM was significantly reduced compared to mBM patients, despite similar PFS with SU and SRE rate. Despite the lower incidence of subsequent therapies in sBM, a more aggressive biology is likely to be the cause of these findings.
<i>Notes from the Field: </i>Francisella tularensis Type B Infection from a Fish Hook Injury — Minnesota, 2016
Authors: Tory Whitten, Jenna Bjork, Dave Neitzel, Kirk Smith, Maureen Sullivan, Joni Scheftel
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

On June 27, 2016, the Minnesota Department of Health (MDH) Public Health Laboratory (PHL) was notified of a suspected Francisella tularensis isolate cultured at a hospital laboratory.The isolate was confirmed as F. tularensis type B at MDH PHL by reverse transcription-polymerase chain reaction, culture, and direct fluorescent antibody testing.Francisella tularensis subspecies tularensis (type A) and holarctica (type B) bacteria are the causative agents of tularemia.MDH initiated an epidemiologic investigation to identify potential exposure sources and risks to additional persons.The case occurred in an immunocompetent white, non-Hispanic woman aged 67 years from Sherburne County, Minnesota.On June 18, she was fishing on a freshwater lake in northeastern South Dakota.While removing a hook from a fish, the hook penetrated the pulp of the patient's left middle finger.On June 21, she developed pain and swelling at the site of the puncture and was seen at an urgent care center where she received an injection of ceftriaxone and was prescribed oral cephalexin.The pain and swelling did not improve, and she was seen by her primary care provider the next day.Because of concern about a possible joint infection, the patient was referred to an orthopedic specialist, who saw her on June 23, at which time an enlarged, tender left axillary lymph node was noted.The orthopedist drained the finger wound, collected a swab of cloudy, nonpurulent fluid for culture, and changed the patient's antibiotic to ciprofloxacin.After MDH PHL confirmed tularemia on June 28, the patient was seen again by the orthopedist; by this time she had developed an escharlike ulcer.An infectious disease consultation was obtained, ciprofloxacin was discontinued, and a treatment course of doxycycline was initiated and ultimately continued for 5 weeks.As of July 8, the lymphadenopathy had resolved and the ulcerated wound was improving.MDH epidemiologists shared exposure information with the South Dakota Department of Health; no other cases of tularemia were reported from this area of South Dakota in 2016 (South Dakota Department of Health, personal communication, January 4, 2017).Tularemia can cause a wide range of symptoms in humans, depending upon the route of inoculation.The infection is often characterized by fever, lymphadenopathy, and an ulcer at the site of cutaneous inoculation.Type A is frequently associated with lagomorphs (hares, rabbits, and pikas), and type B is
epiG: statistical inference and profiling of DNA methylation from whole-genome bisulfite sequencing data
Authors: Martin Vincent, Kamilla Mundbjerg, Jakob Skou Pedersen, Gangning Liang, Peter A. Jones, Torben Falck Ørntoft, Karina Dalsgaard Sørensen, Carsten Wiuf
Journal: Genome biology (2017)

The study of epigenetic heterogeneity at the level of individual cells and in whole populations is the key to understanding cellular differentiation, organismal development, and the evolution of cancer. We develop a statistical method, epiG, to infer and differentiate between different epi-allelic haplotypes, annotated with CpG methylation status and DNA polymorphisms, from whole-genome bisulfite sequencing data, and nucleosome occupancy from NOMe-seq data. We demonstrate the capabilities of the method by inferring allele-specific methylation and nucleosome occupancy in cell lines, and colon and tumor samples, and by benchmarking the method against independent experimental data.
Applying value stream mapping to improve patient flow and satisfaction.
Authors: Chad W Cummings, Rob Kenney, Katherine Glass, Emily Elizabeth Monteleone, Brian James Bolwell
Journal: Journal of Clinical Oncology (2016)

244 Background: Value Stream Mapping (VSM) is a tool commonly used in manufacturing environments to analyze the current state process and to design an improved future state. VSM is a dynamic visual management tool that can be applied in the context of clinical activities to identify value-added (VA) and non-value added (NVA) activities along the spectrum of patient care. A VSM was created for the Breast Cancer Program to identify improvement opportunities in patient quality, flow, and communication across disciplines. Methods: A multidisciplinary team of physicians and clinical specialists were assembled to detail patient flows and coordination of care. Data for each process step was identified, and included, but not limited to: (1) lead times and (2) cycle times for each process. Clinical huddles were established to collect “real-time” patient information (n = 101 patients), and used to populate and validate the VSM. Additionally, retrospective analysis was performed using information from the tumor registry (n = 566 patients). Results: Visual representation of a patient’s journey revealed distinct opportunities to improve the coordination of care and communication. The Breast VSM identified 53 discrete steps, and illuminated 3 focus areas for action: (1) coordination and navigation of patients at multiple points of entry, (2) communication of diagnosis, and (3) reduction of time between major clinical activity (diagnosis to surgery or first treatment). NVA identified opportunities to reduce the number of steps (13) between diagnosis and first treatment, whereby up to 15% of these steps are financial clearance that can delay care. Process differences were discovered between external and internally referred patients, leading to delays in first consult, and a need for better patient navigation. Conclusions: VSM is an effective way to collaborate and drive improvements with multi-disciplinary teams. The non-value added activity highlighted on the maps provides an opportunity for improvements and reducing waste and delay in patient care. Providing timely communication and care will drive patient satisfaction around value-added steps.