tbuckley/cabot-search huggingface dataset:
Statistical evaluation of a molecular classification tool for discriminating cancer recurrence versus new primary cancer formation.
Authors: E. M. Ellsworth, W. E. Gooding, D. M. Smith, W. Spence, S. D. Finkelstein
Journal: Journal of Clinical Oncology (2010)

e21059 Background: Second cancer formation is an increasingly important problem because of longer survival of cancer patients and improved imaging and sampling technologies. Traditional microscopic criteria (morphologic similarity, immunostain patterns) are not reliable or may not be applicable (eg, fine needle aspirates that disrupt morphology; multiple cancer sites in same organ) when determining the relatedness of 2 cancers. We created a classification rule to discriminate metastasis from new primary based on comparing the mutational profiles of both cancers. Methods: Archival specimen pairs from 2 cohorts consisted of 63 pts with breast, colorectal and lung cancer and known metastasis and 21 pts with known independent second primary cancers in which one tumor involved breast, colon or lung. Classification into either cohort was independent of molecular results. Extracted DNA from microdissected targets of pure tumor cells taken from routine histology slides were evaluated for 17 oncogene or tumor suppressor gene mutations. We created a distance metric to evaluate the degree of difference in each mutational marker for each pair of tumors in each patient. Low distance implies similar mutations (metastasis); high distance, dissimilar mutations (new primary). Using a training set representing subsets of each cohort, we evaluated reference levels and classification rules. Results: We found that a difference in 4 markers indicated a new primary. This rule achieved 100% accuracy in evaluating the training set. Further evaluation with a test set will be completed shortly. Conclusions: Microscopic analysis has many limitations for determining the relatedness of 2 separate cancers. This classification rule for interpreting the results of comparative mutational profiles may provide a robust way to definitively determine if 2 cancers represent 1 primary with metastasis or 2 separate primaries. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration RedPath Integrated Pathology RedPath Integrated Pathology RedPath Integrated Pathology
Patient experience with survivorship care plans: Findings from an online registry of breast cancer survivors.
Authors: J. S. Buzaglo, K. R. Dougherty, M. Amsellem, M. Golant
Journal: Journal of Clinical Oncology (2011)

9136 Background: The IOM (2005) recognized that survivorship care plans (SCP) and treatment summaries (TS) are critical to the delivery of comprehensive survivorship care. The plans are intended to integrate primary and follow-up cancer care, understanding patients are mobile across healthcare systems. These recommendations present a significant challenge to oncology practices; yet, little is known about their use and value to patients. The Cancer Support Community, the largest provider of psychosocial support to cancer patients in the US, surveyed breast cancer survivors about their experience with SCPs to identify areas of unmet need. Methods: To date nearly 3,000 breast cancer survivors have joined the Breast Cancer M.A.P. (Mind Affects the Physical) Project, an online registry designed to examine the psychosocial impact of breast cancer. In November 2010,844 consecutive registrants were provided study-specific questions: 1) receipt of a SCP or TS, 2) if received, satisfaction with SCPs, and 3) queries about information desired but not provided. This sample was 99% female, 88% Caucasian, and the mean age was 55. 72% had at least a college degree. The majority (58%) was initially diagnosed with at least Stage II disease; 14% reported having had a recurrence. Results: Of the respondents, only 12% of breast cancer survivors had received a treatment summary (n=101) and 10.5% had received a survivorship care plan (n=90). Of those who received a SCP, 53% found it to be useful or very useful. Among registrants who received a SCP, 25% reported that information about test results, dates of treatment, and information about future tests were missing from their SCP. Registrants would have also liked their SCP to include information about: 1) general survivorship resources, 2) complementary and alternative treatments, 3) recurrence, 4) late effects, and a summary of the diagnosis and prognosis. Conclusions: The data from the MAP Project indicate that the majority of breast cancer survivors did not receive a survivorship care plan and of those who did receive a plan, a substantial proportion did not find it useful. There continues to be gaps in the adoption, delivery, and utility of cancer survivorship plans.
Utilization of laparoscopy for resections of stomach and esophagus cancers: Is hospital the deciding factor?
Authors: Lindsay A. Bliss, Zeling Chau, Catherine J. Yang, Jillian K. Smith, Elan R. Witkowski, Elizaveta Ragulin-Coyne, Sing Chau Ng, Jonathan F. Critchlow, Arthur J. Moser, Jennifer F. Tseng
Journal: Journal of Clinical Oncology (2014)

86 Background: Foregut surgery is technically complex. Outcomes for such high-stakes operations receive increasing scrutiny and the use of minimally invasive approaches has been further adopted. This study aims to determine national trends in laparoscopy utilization and patient outcomes for potentially curative cancer resections of the esophagus and stomach. Methods: Retrospective review of all esophageal and gastric cancer resections in the Nationwide Inpatient Sample during 1998 to 2011. Univariate analyses of sex, race, admission status, Elixhauser comorbidity score, year, insurance, hospital characteristics, procedure, and center volume were performed by chi-square. Cochran-Armitage test was used for trends. Logistic regressions were used to model inpatient mortality, complications and laparoscopy. Results: From 1998 to 2011, 120,527 and 25,540 patients (nationally-weighted records) underwent gastrectomies and esophagectomies for cancer. From early (1998-2002) to late (2008-2011) study years, inpatient mortality decreased from 6.69% to 3.88% (&lt;0.0001) and complications increased from 27.41% to 31.63% (&lt;0.0001) for gastrectomy. Similarly, inpatient mortality decreased from 9.75% to 5.53% (&lt;0.0001) and complications increased from 37.69% to 43.07% (&lt;0.0001) for esophagectomy. Use of laparoscopy in gastrectomy increased from 1.64% to 5.89% (p &lt;0.0001) and in esophagectomy from 0.80% to 5.74% (&lt;0.0001). Patients undergoing laparoscopy had lower inpatient mortality (3.13% vs. 5.96%, p=0.0010) and were less likely to experience complications (26.20% vs. 31.47%, p=0.0121). After adjustment, independent predictors of the use of laparoscopy included elective admission, female sex, resection after 2003 and resection at a large (vs. medium), urban, teaching high volume center (vs. low volume center) in the Northeast (vs. Midwest and South). Conclusions: Inpatient mortality and complications for gastrectomy and esophagectomy have improved over the past decade. Use of minimally invasive techniques is expanding with associated superior patient outcomes. Resection hospital characteristics drive which patients undergo laparoscopy for esophagus and stomach cancers.
ASCO PRO workgroup update: Patient-reported outcome measures as a quality indicator.
Authors: Angela M. Stover, Anne C. Chiang, Ethan M. Basch
Journal: Journal of Clinical Oncology (2016)

276 Background: Although patient questionnaires are commonly used to assess healthcare experiences (e.g., satisfaction with care), patient-reported outcome (PRO) measures assessing symptoms and physical functioning have not conventionally been used for quality assessment. More typically, quality of care is measured with administrative data, such as hospital readmission rates. There is an opportunity to advance the science of quality measurement by integrating a patient-centered approach. Methods: ASCO established a multi-stakeholder PRO Workgroup (including extensive patient input) to develop and test PRO-based performance measures (PRO-PMs). The ASCO PRO Workgroup outlined three initial PRO-PMs to test for patients receiving moderately/highly emetogenic chemotherapy: 1) process: proportion self-reporting symptoms at, or within 2 weeks, of last visit; 2) outcome: proportion experiencing moderate/high levels of nausea; and 3) outcome: proportion reporting moderate/high pain. We will give an update on progress of the ASCO PRO Workgroup and outline next steps needed to implement PRO measures as a quality metric. Results: Three key methodological advancements are needed before PRO measures can be used as a quality metric. First, areas of cancer care delivery need to be identified that are important to patients when considering quality of care and are amenable to performance evaluation with PRO measures (e.g., symptom control). Second, existing PRO questionnaires need to be systematically identified and evaluated for potential quality use. The review should evaluate psychometric properties, validity and reliability, and feasibility for clinical use. Third, testing is needed in representative practice settings to iteratively refine: 1) logistical strategy for systematically collecting this information at the practice level; 2) approaches for minimizing missing data, particularly from underserved populations; and 3) adjustments for patient characteristics (case-mix). Conclusions: Methodological advancements are necessary before PRO measures can be implemented as a quality metric. PRO measures have the potential to provide quality assessments that are useful to patients making health care decisions.
An analysis of the role of paulinia cupana (Guaraná) in blood IL-1b and brain IL-6 levels as well as brain IL-6 and TNF-a mRNA expression in mice.
Authors: R. Marcon, A. Del Giglio, L. F. Pianowski, J. B. Calixto
Journal: Journal of Clinical Oncology (2011)

e21002 Background: Paulinia cupana also known as Guaraná is an amazonic plant which has been used for centuries as a tonic by indigenous populations. We have recently demonstrated that the dry crude extract of Guaraná is effective in preventing the treatment of cancer related fatigue (CRF) in breast cancer patients undergoing adjuvant chemotherapy. Of note, CRF patients have been associated with high blood levels of IL-1beta and IL-6. Methods: female Balb/c mice were divided in 8 groups each with 6 to 8 animals each and treated as follows: 1) Normal Saline PO; 2) Excipient PO; 3) Dexamethasone 1mg/kg subcutaneously (SC) (positive control group; 4-6) Guaraná purified Extract (PC18) at 30, 100 and 300 mg/kg PO; 7-8) Gurana dry crude extract at 100 and 300 mg/kg PO. All animals, except those from Group 1 received 100 ml (2.5 µg/mice) of intraperitoneal Escherichia coli Lipopolyssacaride (LPS). Animals were evaluated for social and exploratory interaction (Fishkin and Winslow, 1997) and motor activity (Dunn e Swiergiel, 2005) before (0) and at 2, 4, 8 and 24 hours after the LPS treatment. Levels of IL-1 beta and IL-6 were measured in the blood by ELISA 2 hours after LPS injection (N=5 animals per group) and the mRNA expression of IL-6, IL-12, TNF-alpha and INF-gama in the brain by quantitative real time RT-PCR 2 hours after LPS injection (N=5 animals per group). Results: We observed a statistically significant improvement in social interaction in animals treated with Guaraná extract. We observed no significant change in the IL-6 levels in the blood from animals that received Guarana extract, whereas plasma IL1-beta levels were significantly lower in the animals treated with Guaraná. Interestingly, Guaraná significantly suppressed the increase in brain IL-6 and TNF-alpha mRNA levels induced by LPS. Conclusions: Guaraná extract is effective to improve social behavior in animals treated with LPS which is associated with suppression of blood IL-1beta as well as IL-6 and TNF-alpha mRNA expression in the brain. Therefore, guarana extract may exhibit orally anti-inflammatory effects that might explain its anti-fatigue activity observed clinically in cancer patients.
Operational improvements to clinic flow.
Authors: Katherine Gross, Kelli Jacobs, Michael Romano
Journal: Journal of Clinical Oncology (2014)

253 Background: With expanding clinic volume and future growth potential, we face an issue of limited physical clinic capacity. This has resulted in extended patient wait times, physician idle time, and longer clinics days. Each of these issues adds to both provider and patient dissatisfaction and operational inefficiencies. Methods: Key operational metrics and through put data was analyzed with the oncology team. Agreements and goals for the process improvement were: no provider would be told they could not see a sick patient, patient’s time would be respected and maximize provider productivity. Data demonstrated that the current state would not accommodate future growth. Several operational changes were agreed upon by physician and administrative leadership: level load the days of the week, require several providers to move their clinic days; place structure and real-time discussion into how we manage same day and future “add-on” patients though setting clear expectations around clinician template times; assign a full time staff member to function as a “clinic flow coordinator" to triage same day add-ons, and facilitate provider room assignments, communicate with providers, and identify system or people barriers to clinic flow; provide each of the patients a “restaurant style” pager that will light up when they are ready to be taken to a room, allowing them the freedom to leave the waiting room without fear of missing their appointment time; implement a room-utilization manager software program allowing staff to see and collectively manage real time clinic flow and room utilization. Results: Provider feedback was very positive related to the flow and utilization of clinic rooms. The check-in staff described a less full waiting room even though volumes remained constant. We will monitor patient perception by patient satisfaction scores. Conclusions: To date, much of the results have been anecdotal. In order for these changes to become practice there is a clear need to tie in satisfaction and operational efficiency metrics. There will be ongoing coaching and feedback with providers and staff related to adherence to the new processes. As new providers are added to the practice, we will be very purposeful when adding their creating their templates and adding their clinic days.
A multicenter population-based experience with abiraterone acetate (AA) in patients with metastatic castration resistant prostate cancer (mCRPC).
Authors: Ravinder Clayton, Daniel Yick Chin Heng, Jackson S.Y. Wu, Rob Zielinski, Scott A. North, Urban Emmenegger, Sebastien J. Hotte, Humaid Obaid Al-Shamsi, Leo Chen, Bernhard J. Eigl
Journal: Journal of Clinical Oncology (2013)

113 Background: The COU-AA-301 trial showed that abiraterone (AA), an oral cytochrome p450 CYP17 inhibitor, improved survival for men with mCRPC progressing after docetaxel. AA is now a standard treatment in this setting. In order to better understand the non-clinical trial experience with AA, we undertook a multicenter retrospective analysis of patients (pts) treated with AA. Methods: Consecutive pts with mCRPC from 5 tertiary cancer centers in Canada who had received AA post-docetaxel were identified using centralized pharmacy records for each center. Pts who received AA for approved indications or within expanded access programs were included. Demographics, prognostic factors, treatment outcomes and toxicity profiles were collected. Results: One hundred and eighty seven pts, who initiated AA between Jan-2011 and Jun-2012, were included. Median age at diagnosis and AA start was 65 and 73 years. 73 (39%) pts had M1 disease at diagnosis. ECOG 0/1/2/3 was noted in 17/96/39/8 pts. Median PSA at AA start was 132 with a median PSAdt of 2.8 months. 54 (29%) pts received more than 1 prior course of chemotherapy. Median follow up was 20.5 months. Median survival from start of AA was 9.3 months (95% CI, 7.9-12.6). Regional results were: Alberta 14 months (95% CI, 13-18); BC 8.2 months (95% CI, 5.4-9.6); and Ontario 7.3 months (95% CI, 5.7-8.1). Median overall survival from date of mCRPC was 36 months (95% CI, 29-40); in Alberta this was 39 months (95% CI, 29-47); BC 26 months (95% CI, 18-41); and Ontario 33 months (95% CI, 25-41). AA was well tolerated with toxicities comparable to those seen in the trial population, with anemia and fatigue being the most common reported toxicity. Conclusions: This is one of the largest cohorts of men with mCRPC treated with AA in the non-clinical trial setting. Treatment outcomes corroborate with results reported in clinical trials, supporting the effectiveness of AA in an unselected population. A difference in survival outcomes between the different cancer regions can be attributed to differences in time to AA start. Future analyses to evaluate potential prognostic/predictive factors will be undertaken.
Medico-pharmaceutical approach to reduce costs of infusion-related reactions (IRR) associated with cetuximab at Paul Brousse hospital
Authors: V. Castagné, E. Goldschmidt, F. Lévi, N. Brahimi, W. Almohamad, D. Machover, A. Karaboué, H. Habert, L. Bonhomme-Faivre, M. Bouchahda
Journal: Journal of Clinical Oncology (2008)

20748 Background: Cetuximab (Cetux) is an anti-EGFR monoclonal IgG1 antibody with proven activity both as a single agent or in combination with chemotherapy against metastatic colorectal cancer (MCC). Approximately 3% of severe IRR occur, especially during the first minutes of the first infusion, despite the only recommended antihistamine premedication, preventing further administration. We sought 1/ to reduce the occurrence of severe IRR through improved premedication and 2/ to decrease drug wasting costs through an original pharmaceutical preparation. Methods: 344 patients (pts) entered consecutively in our institution, 134 women and 210 men, with a median age of 60 y (range, 19–88) and a Karnovsky PS >70% treated for advanced gastrointestinal malignancies received a first Cetux infusion (400 or 500 mg/m2 over 2 h) from March 2004 to November 2007. Premedication consisted of dexchlorpheniramine (5 mg) for the first 44 pts (group A) and dexchlorpheniramine (5 mg), methylprednisolone (60 mg) and ranitidine (50 mg) for the subsequent 300 pts (group B). Cetux (2 mg/ml) was prepared in 2 bags, a test one (100 mg) and a second one containing the remaining dose. In case of severe IRR, this second bag kept in the pharmacy ward at 4–8°C was reused within the next 24 h. Results: Grade 3–4 IRRs occurred in 3/44 pts of group A (6.8%) and 4/300 pts of group B (1.7%) (Exact Fisher test, p=0.047). As a result, the hospital costs related to the management of severe IRR were markedly reduced. The second Cetux bag, that was not infused in these 7 pts and 2 patients with Grade 1–2 IRR, was administered to subsequent pts. This pharmaceutical preparation further allowed to avoid the waste of 63 100-mg vials of Cetux, and a subsequent economy of 14 600 euros. Conclusions: This overall medico-pharmaceutical approach minimized Cetux costs through improved prevention of severe IRR at our institution. Its widespread application could contribute both to a better quality of patient care and a better control of cancer treatment-related costs. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Merck Serono France
Screening and Triage Test for Early Detection of Gastric Cancer (STEAD-GC): A noninvasive trial for early detection of gastric cancer.
Authors: Alejandro Corvalan, Maria Jose Maturana, Marianela Sanchez, Alfonso Calvo, Catterina Ferreccio
Journal: Journal of Clinical Oncology (2012)

17 Background: Gastric cancer (GC) is the second leading cause of cancer-related deaths worldwide. Previously, we identified a potential biomarker for non-invasive detection of GC, the DNA methylation of the promoter region of Reprimo, a p53-dependent G2 arrest mediator candidate (Clin Cancer Res 2008;14:6264-9). Furthermore, we developed a quantitative assay (MethyLight) for a mass screening of GC (DDW2011-1029128). Here we reported the preliminary findings of our ongoing prospective trial STEAD-GC (Screening and Triage test for Early Detection of Gastric Cancer) which is being conducted in Chile, a country with a high mortality rate for GC. Methods: Twenty GC cases (tumor, non-tumor tissues and plasma samples) and 41 symptomatic chronic gastritis cases (29 tissues and 12 pairs of tissue and plasma samples) were evaluated for Reprimo levels by MethyLight after DNA extraction and bisulfite conversion. Results: Concentrations of DNA were similar in both groups (Avg 32.2 ng/ml [range: 8.9-70.8 ng/ml]). The average DNA levels of Reprimo were higher in GC [964,215 copies/ml, 539,593 copies/ml and 80,113 copies/ml in tumor, non-tumor and plasma, respectively] but lower in symptomatic chronic gastritis [137,721 copies/ml and 8,387 copies/ml, tissue and plasma, respectively]. Methods: Twenty GC cases (tumor, non-tumor tissues, and plasma samples) and 41 symptomatic chronic gastritis cases (29 tissues and 12 pairs of tissue and plasma samples) were evaluated for Reprimo levels by MethyLight after DNA extraction and bisulfite conversion. Conclusions: By using our previous cut-off of 15,125 copies/ml, our method correctly identified 10 out of 12 gastritis cases and 16 out of 20 GC cases (p value &lt;0.001). Our data confirms our non-invasive method for early detection of GC may be suitable for a mass screening of GC.
Identification of Highly Divergent Diatom-Derived Chloroplasts in Dinoflagellates, Including a Description of Durinskia kwazulunatalensis sp. nov. (Peridiniales, Dinophyceae)
Authors: Norico Yamada, Stuart D. Sym, Takeo Horiguchi
Journal: Molecular Biology and Evolution (2017)

Dinoflagellates are known to possess chloroplasts of multiple origins derived from a red alga, a green alga, haptophytes, or diatoms. The monophyletic "dinotoms" harbor a chloroplast of diatom origin, but their chloroplasts are polyphyletic belonging to one of four genera: Chaetoceros, Cyclotella, Discostella, or Nitzschia. It has been speculated that serial replacement of diatom-derived chloroplasts by other diatoms has caused this diversity of chloroplasts. Although previous work suggested that the endosymbionts of Nitzschia origin might not be monophyletic, this has not been seriously investigated. To infer the number of replacements of diatom-derived chloroplasts in dinotoms, we analyzed the phylogenetic affinities of 14 species of dinotoms based on the endosymbiotic rbcL gene and SSU rDNA, and the host SSU rDNA. Resultant phylogenetic trees revealed that six species of Nitzschia were taken up by eight marine dinoflagellate species. Our phylogenies also indicate that four separate diatom species belonging to three genera were incorporated into the five freshwater dinotoms. Particular attention was paid to two crucially closely related species, Durinskia capensis and a novel species, D. kwazulunatalensis, because they possess distantly related Nitzschia species. This study clarified that any of a total of at least 11 diatom species in five genera are employed as an endosymbiont by 14 dinotoms, which infers a more frequent replacement of endosymbionts in the world of dinotoms than previously envisaged.