tbuckley/cabot-search huggingface dataset:
Adjuvant therapy for early gastric cancer patients: A retrospective study.
Authors: Shen Hong, Hou Honglun, Wu Minghui, Chen Tianzhou
Journal: Journal of Clinical Oncology (2014)

e15072 Background: Early gastric cancer (EGC) has an excellent prognosis, but some patients with lymph node-positive disease will develop recurrence. In this study we investigated whether adjuvant chemotherapy may benefit some early gastric cancer. Methods: We retrospective analysis 36 patients who underwent gastrectomy and primary D2 lymph node dissection for solitary EGC between 2006 and 2010 at the second affiliated hospital, zhejiang university. 2 patients were pathologically diagnosed with Stage IA disease (T1N0 with lymphatic-vascular positive), 14 patients with IB (T1N1), 14 patients with IIA (T1N2), 6 patients with IIB (T1N3). The 36 patients were received chemotherapy with capecitabine and oxaliplatin. Results: Two (5.6%) of the 36 patients developed recurrence. One patient with T1N2 was found of peritoneal metastasis 3 years after operation and died 13 months later. Another patient with T1N3 was found of pelvic metastasis 3 months after operation and died 7months later. No relapse or metastasis of the rest. The patients with T1N0, T1N1, T1N2 and T1N3 have a 5-year disease-specific survival of 100%, 100%, 92.9% and 83.3% separately. Conclusions: The patients with stage IIA and IIB may obtain additional survival benefit if targeted with adjuvant chemotherapy.
Harmonization of patient-reported outcomes into EHRs at four cancer hospital outpatient clinics for patient care and quality assessment.
Authors: Arlene Chung, Angela M. Stover, Lynne I. Wagner, Thomas William LeBlanc, Umit Topalaglu, Yousuf Zafar, Leah L. Zullig, Phil Smeltzer, Ethan M. Basch
Journal: Journal of Clinical Oncology (2017)

129 Background: Patient-reported outcome (PRO) measures are well established in oncology trials but are not collected systematically during clinical care, to guide symptom management, or to assess quality. A growing body of evidence shows that collecting PROs during cancer care yields better clinical outcomes. Yet, little is known about best practices for PRO integration into electronic health record (EHR) workflows. We report on the first cross-institutional effort for PRO data harmonization across four CTSA-funded institutions (University of North Carolina at Chapel Hill, Wake Forest University, Duke University, Medical University of South Carolina). Methods: Through surveys, systematic stakeholder qualitative focus groups, a landscape analysis, and technical/workflow assessment, our cross-institutional team sought to: 1) determine a set of common PRO measures to be collected via patient portals tethered to EHRs across the 4 sites; 2) develop an implementation strategy for the collection of PROs via patient portal within clinical workflows; and 3) collect a common set of PROs in cancer clinical care. We also sought to develop the methodological steps to harmonize extracted PRO data across each site to each other and then to the PCORnet Common Data Model Common Measures for PROs across each site. Results: Across the four sites, each institution uses Epic Systems (EHR and patient portal) and had available a library of PRO questionnaires which included the PROMIS profile (29 items) and short forms, SF-20, RAND, PHQ-2, and PHQ-9. The study team developed a list of domains and the tools available within each domain for stakeholders to prioritize at each site. The proposed workflows take into consideration the use of these data within the clinical encounter. Pilots at each site to collect PROs are underway along with the methodological work for data extraction and harmonization and will be reported at the meeting. Conclusions: The collection of a common set of PROs across EHRs has important implications for improving individual patient’s symptoms and for enhancing the quality of cancer care. Complex workflows and technical barriers must be considered successful implementation.
Screening for Endocrine Hypertension: An Endocrine Society Scientific Statement
Authors: William F. Young, David A. Calhoun, Jacques W.M. Lenders, Michael Stowasser, Stephen C. Textor
Journal: Endocrine Reviews (2017)

Hypertension may be the initial clinical presentation for at least 15 endocrine disorders. An accurate diagnosis of endocrine hypertension provides clinicians with the opportunity to render a surgical cure or to achieve an optimal clinical response with specific pharmacologic therapy. It is challenging for the clinician to know when and how to perform case-detection testing for all the endocrine disorders in which hypertension may be the presenting symptom. Herein, we review the different forms of endocrine hypertension, with a focus on prevalence, clinical presentation, guidance on when to perform case detection testing, and currently available case-detection tests.
International multicenter phase II study of the HDAC inhibitor (HDACi) depsipeptide (FK228) in cutaneous T-cell lymphoma (CTCL): Interim report
Authors: S. Whittaker, W. McCulloch, T. Robak, E. Baran
Journal: Journal of Clinical Oncology (2006)

3063 Background: Depsipeptide, a unique bicyclic peptide histone deacetylase inhibitor (HDACi), has shown activity in a range of in vitro and in vivo tumor models and clinical activity in T-cell lymphomas and prostate cancer. This study seeks to confirm the CTCL activity previously reported by the NCI (Piekarz, et al., ASCO, 2004). Methods: Single-arm, open label study, in 25 centers in the UK, Germany, Poland and the US. Patients aged ≥18 years with biopsy-confirmed CTCL (centrally reviewed) who have failed at least one prior systemic treatment receive up to 6 cycles of depsipeptide as a 4-hour IV infusion on Days 1, 8 and 15 q 28 days. Eligibility criteria include: mycosis fungoides and Sézary syndrome plus variants, Stages IB - IVA, adequate organ function, ECOG PS ≤ 1. Patients with significant cardiovascular abnormalities are excluded in addition to those taking QTc-prolonging or CYP3A4-inhibiting drugs. The primary endpoint is overall reponse rate measured by a combination of imaging, circulating cell counts and a weighted skin average instrument, confirmed by standardized photography. A subset undergoes pharmacokinetic assessments. Correlative studies include acetylation status, apoptotic markers and proteomic analyses where possible. Target accrual is 76 to yield 64 evaluable patients. Results: 30 patients have received treatment with 17 evaluable for efficacy. Responses seen are 1 cCR, 4 PRs (duration 2+ to 6 months) 9 SD and 3 PD. 3 patients withdrew early for PD and 2 for other reasons. The remaining patients on study are too early to assess. Most frequent toxicities are: nausea/vomiting, fatigue, myelosuppression and asymptomatic ECG changes. No patient has withdrawn for toxicity and there have been no treatment-related deaths. Conclusions: The previously reported efficacy of depsipeptide in CTCL has also been seen in the present study. Duration of response is encouraging. Toxicity is manageable and the study continues to accrue. [Table: see text]
Long-term effects of severe acute malnutrition on lung function in Malawian children: a cohort study
Authors: Natasha Lelijveld, Marko Kerac, Andrew Seal, Emmanuel Chimwezi, Jonathan C. Wells, Robert S. Heyderman, Moffat J. Nyirenda, Janet Stocks, Jane Kirkby
Journal: European Respiratory Journal (2017)

Early nutritional insults may increase risk of adult lung disease. We aimed to quantify the impact of severe acute malnutrition (SAM) on spirometric outcomes 7 years post-treatment and explore predictors of impaired lung function. Spirometry and pulse oximetry were assessed in 237 Malawian children (median age: 9.3 years) who had been treated for SAM and compared with sibling and age/sex-matched community controls. Spirometry results were expressed as z-scores based on Global Lung Function Initiative reference data for the African–American population. Forced expiratory volume in 1 s (FEV 1 ) and forced vital capacity (FVC) were low in all groups (mean FEV 1 z-score: −0.47 for cases, −0.48 for siblings, −0.34 for community controls; mean FVC z-score: −0.32, −0.38, and −0.15 respectively). There were no differences in spirometric or oximetry outcomes between SAM survivors and controls. Leg length was shorter in SAM survivors but inter-group sitting heights were similar. HIV positive status or female sex was associated with poorer FEV 1 , by 0.55 and 0.31 z-scores, respectively. SAM in early childhood was not associated with subsequent reduced lung function compared to local controls. Preservation of sitting height and compromised leg length suggest “thrifty” or “lung-sparing” growth. Female sex and HIV positive status were identified as potentially high-risk groups.
Phase I/II trial of induction chemotherapy in locally advanced head and neck carcinoma (LAHNC) and recurrent disease (RD) after surgery/radiotherapy with weekly docetaxel (D), tomudex (T) and cisplatin (P)—DTP
Authors: E. J. Johnson-Buarque
Journal: Journal of Clinical Oncology (2006)

15536 Background: The role of neoadjuvant chemotherapy in LAHNC and treatment for RD have not been established yet. Infusional 5-FU combination with DP is one of the most active regimens for patients (pts) with LAHNC, at the same time is very toxic (hematological, gastrointestinal (GI) and cardiovascular). In order to reduce its toxicity we designed a novel weekly triple-drug scheme trying to reduce toxicity and mantain the high response rate. Methods: LAHNC and RD pts received D 35/mg/m 2 , T 1 mg/m 2 and P 25 mg/m 2 on days 1, 8 and 15. with one week rest. Some pts received only days 1 and 8 due to hematological toxicity (grade 2, 3 or 4). Planned treatment included 3 through 6 cycles (50% pts received 3 cycles). After neoadjuvant chemotherapy, pts with LAHNC were sent to their doctors to continue the treatment according to their own preference (surgery, RXT or RXT/QT). Results: Between november 2001 and may 2004, 24 pts (M = 17 F = 7) median age 61 (range 45–72) have been enrolled. 17 was LAHNC and 7 RD; tumor sites were: oral cavity 18 and oropharinx/larinx 6 pts. Response rate (RECIST) and toxicity (NCI) were avaible to all pts. 37.5% pts had grade 3/4 toxicity (hematological or GI) and these pts had a dose reduction. There was one febrile neutropenia and no deaths. The overall rate response was 91.6% (3 CR and 19 PR) in all sites of disease including lymphonodes. Conclusions: This scheme DTP has a high respose rate with low and manageable toxicity. It will be necessary to compare it with concurrent radiotherapy + dose reduction chemotherapy with or without cetuximab. No significant financial relationships to disclose.
Enhancing treatment planning workflow in radiation oncology.
Authors: Arpine Khudanyan, Jerry Jeff Jaboin, Barb Agrimson, Simon Brown, Wolfram Laub, Jo Price, Stephanie Junell, Jeff Hanson, Dorothy Ryan, Jennifer Ruocco, Charles R. Thomas
Journal: Journal of Clinical Oncology (2017)

84 Background: The treatment planning process is the most impactful and complex aspect of radiation oncology care. In order to provide short turn around times from patient CT simulation to treatment plan QA, requires a level of strain and haste for multiple members of the treatment team. We evaluated 18 months of data to determine the percentage of Quality Assurance (QA) approvals of nonemergent complex plans (including 3D/IMRT/Arc/SBRT/SRS) that are not completed by 8:00a the day prior to a patient's first treatment appointment, and found that this occcurred on time 62% of the time. We utilized the ASCO Quality Training Process (QTP) process to brainstorm methods to enhance workflow, and create an action plan that would allow for small Plan-Do-Study-Act cycles to reach our ideal state of &gt; 90% On Time Treatment Plan Delivery. Methods: We utilized LEAN tools from the ASCO QTP progam (June 2016 cycle). We created an Ishikawa diagram to determine the areas of greatest potential. We subsequently developed a highly detailed flow chart of our work processes. Then we utilized Mosaiq scripts to establish baselines for our process measures. Results: From our Ishikawa diagram, the initial most impact was in generate target volume contours after the CT simulation. Our first measure was to visually manage the CT simulation process. We established a computer based quality control list (QCL) to enhance the communication process, and provided a "reminder" at the time of simulation of the target contour delivery date. After collection of data points, there was a significant improvement in on time delivery (now 89%, and approaching the ideal state), as illustrated by our Run Chart, and a coincident decrease in variability between providers and cases was noted in this cohort. Conclusions: Our preliminary change effort is promising, but further data will enhance our findings. Our next steps are to collect an additional two weeks of data, and initiate another PDSA cycle with a new measure of automated reminders from the QCL system. In achieving our project goals and making it sustainable, we believe that we will be providing high quality, high value patient care, while enhancing the healthiness of the work environment for our staff.
Maternal Cancer During Pregnancy and Risks of Stillbirth and Infant Mortality
Authors: Donghao Lu, Jonas F. Ludvigsson, Karin E. Smedby, Katja Fall, Unnur Valdimarsdóttir, Sven Cnattingius, Fang Fang
Journal: Journal of Clinical Oncology (2017)

Purpose To examine whether maternal cancer during pregnancy is associated with increased risks of stillbirth and infant mortality. Methods On the basis of nationwide health registers, we conducted a study of 3,947,215 singleton births in Sweden from 1973 through 2012. Exposure was defined as maternal cancer diagnosed during pregnancy (number of births = 984) or during the year after pregnancy (number of births = 2,723). We calculated incidence rate ratios (IRRs) for stillbirth and infant mortality, comparing exposed births to unexposed births. Small-for-gestational-age (SGA) and preterm births were examined as secondary outcomes. Results Maternal cancer diagnosed during pregnancy was positively associated with stillbirth (IRR, 2.5; 95% CI, 1.2 to 5.0), mainly stillbirths assessed as SGA (IRR, 4.9; 95% CI, 2.2 to 11.0), and with preterm SGA births (relative risk 3.0; 95% CI, 2.1 to 4.4). Positive associations of maternal cancer diagnosed during pregnancy or the year after pregnancy were noted for both neonatal mortality (deaths within 0 to 27 days; IRR, 2.7; 95% CI, 1.3 to 5.6 and IRR, 2.0; 95% CI, 1.2 to 3.2, respectively) and preterm birth (IRR, 5.8; 95% CI, 5.3 to 6.5 and IRR, 1.6; 95% CI, 1.4 to 1.8, respectively). The positive association with preterm birth was due to iatrogenic instead of spontaneous preterm birth. Preterm birth explained 89% of the association of maternal cancer during pregnancy with neonatal mortality. Conclusion Maternal cancer during pregnancy is associated with increased risks of rare but fatal outcomes, including stillbirth and neonatal mortality. This may be due to conditions associated with fetal growth restriction and iatrogenic preterm birth. Careful monitoring of fetal growth and cautious decision making on preterm delivery should therefore be reinforced.
Peter Gordon Watson
Authors: Andrew Watson
Journal: BMJ (2017)

Peter Gordon Watson was born in Newport, Monmouth, where his parents were running a free mobile medical clinic during the great depression. After national service as a subaltern in the Royal Horse Artillery, he read natural sciences at Queens’ College, Cambridge, before his clinical studies at University College Hospital, London.

He trained in ophthalmology at University College Hospital, Moorfields Eye Hospital, and the Institute of Ophthalmology, and he eventually became senior lecturer to Professor Barrie Jones at Moorfields. He was encouraged to set up a scleritis clinic there, which he ran as an honorary consultant from 1970 to 1995. At the time there was effectively no treatment for scleral inflammation, and no one knew how the disease developed, which varieties were dangerous and sight threatening, and which were benign and needed no treatment at all. The clinic soon attracted patients from around the world. The …
Type I collagen–targeted PET probe for pulmonary fibrosis detection and staging in preclinical models
Authors: Pauline Désogère, Luis F. Tapias, Lida P. Hariri, Nicholas J. Rotile, Tyson A. Rietz, Clemens K. Probst, Francesco Blasi, Helen Day, Mari Mino-Kenudson, Paul Weinreb, Shelia M. Violette, Bryan C. Fuchs, Andrew M. Tager, Michael Lanuti, Peter Caravan
Journal: Science Translational Medicine (2017)

Pulmonary fibrosis is scarring of the lungs that can arise from radiation injury, drug toxicity, environmental or genetic causes, and for unknown reasons [idiopathic pulmonary fibrosis (IPF)]. Overexpression of collagen is a hallmark of organ fibrosis. We describe a peptide-based positron emission tomography (PET) probe (
Patterns of failure in advanced-stage diffuse large B-cell lymphoma (DLBCL) patients treated with R-CHOP chemotherapy and the emerging role of consolidative radiotherapy.
Authors: Zheng Jane Shi, Satya Das, Derick Okwan-Duodu, Natia Esiashvili, Christopher Flowers, Kun Jiang, Zhengjia Chen, Xiaojing Wang, Walter J. Curran, Mohammad K. Khan
Journal: Journal of Clinical Oncology (2013)

8546 Background: The role of consolidative radiotherapy (RT) after a complete response (CR) to R-CHOP for stage III-IV DLBCL patients is unclear. The goal of our study is to evaluate the Emory experience when consolidative RT is delivered to initial presenting nodal and extranodal sites or bulky sites in these patients. Methods: From 01/2000 to 05/2012, 211 histologically confirmed DLBCL patients with stage III-IV disease who received R-CHOP were identified at Emory University. Patterns of failure for patients who achieved CR to R-CHOP were analyzed. Local control (LC), distant control (DC), progression free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier method and compared between patients who received R-CHOP alone versus R-CHOP plus consolidative RT using Log-rank test. Multivariate analyses were also performed using Cox proportional hazards model. Results: 163 patients had detailed treatment records. After a median 6 cycles of R-CHOP, 110 patients (67.5%) achieved CR and were entered for analysis. Fourteen patients (12.7%) received consolidative RT to a median dose of 30.6 Gy as part of initial management. With a median follow up time of 32.9 months, 43.8% of patients who received R-CHOP alone failed at the initial presenting sites with or without distant recurrence (DR), whereas isolated DR only occurred in 3.2% of these patients. Consolidative RT was associated with significantly improved LC (91.7% vs 48.8%, p&lt;0.0001), DC (92.9% vs 71.9%, p&lt;0.0001), PFS (85.1% vs 44.2%, p&lt;0.0001) and OS (92.3% vs 68.5%, p&lt;0.0001) at 5-years when compared to patients with R-CHOP alone. In addition, the in-field control rate was 100% within irradiated sites for patients who received consolidative RT. On multivariate analysis, consolidative RT and non-bulky disease were predictive of increased LC and PFS, whereas bone marrow involvement was associated with increased risk of DR and worse OS. Conclusions: 44% of patients with advanced stage DLBCL failed at initial presenting sites despite achieving a CR to R-CHOP. Incorporation of consolidative RT as part of upfront treatment in these patients was associated with improved LC and PFS.
A phase I and pharmacokinetic (PK) study of intravenous (IV) calcitriol and gefitinib assessing EGFR pharmacodynamic (PD) interactions through serial skin biopsies
Authors: Marwan G. Fakih, Candace S. Johnson, Josephia R. Muindi, Jennifer D. Black, Patrick J. Creaven, Michael G. Brattain, James L. Kepner, Renee A. French, Donald L. Trump
Journal: Cancer Research (2005)

3995   Introduction: Calcitriol has antitumor activity in a variety of pre-clinical models. We have recently shown that calcitriol, at a concentration of 10nM (not achievable with oral administration), potentiates the antitumor activity of gefitinib  in vitro  and  in vivo . Calcitriol treatment was associated with down-regulation of pAKT and upregulation of pEGFR expression. We have initiated a phase I clinical trial of IV calcitriol and fixed dose gefitinib to determine the maximum tolerated dose of this combination and the PK and PD interaction between these two agents. Methods: Patients with refractory solid tumors are eligible for study treatment provided they have normal organ function, ECOG performance status 0-2, and no history of hypercalcemia. IV calcitriol is infused over 1 hour weekly except Day 8. Gefitinib 250 mg is given orally once a day starting Day 8. Calcitriol is escalated in 3 + 3 design (dose levels (DL): 10, 15, 20, 26, 34, 44, 57, 74, 96, and 125 mcg). No intrapatient escalation is allowed. Calcitriol PKs are obtained on D1 and 15. Punch skin biopsies are obtained pre-study, Day 1 (8 hrs after calcitriol: calcitriol effect), Day 14 (pre-calcitriol: gefitinib effect), and Day 15 (post-calcitriol: calcitriol + gefitinib effect). Results: To date, 24 patients (median age 67; 18/6 M/F) have been treated without a dose-limiting toxicity. Toxicity has been limited to rash (4 patients with grade 2). No hypercalcemia or hyperphosphatemia was noted in cohorts 1-8. Accrual on study is ongoing. No responses have been documented. Stable disease was noted in 1 patient each with NSCLC, penile cancer, GIST, and prostate cancer. Immunohistochemical analysis of EGFR signaling in serial skin biopsies has been performed on cohorts 1-5. Single agent calcitriol (day 1 biopsy) slightly induced EGFR activity (pEGFR, pERK). Gefitinib (day 14 biospy) was associated with marked down-regulation of EGFR signaling in the skin (pEGFR, pERK, pAKT). The addition of calcitriol (day 15 biopsy) attenuated the gefitinib-mediated inhibition of EGFR, ERK, and AKT activity. The relationship between calcitriol dose and AUC was linear over the dose range studied (DL 1-6). At DL 6 (57mcg), the AUC and C max  were 30 ng.hr/ml and 8.8 nM. Gefitinib administration had no effect on calcitriol PK profile. Conclusion: At DL ≤ 5, calcitriol attenuates gefitinib-mediated EGFR inhibition. Weekly IV calcitriol can be escalated safely to doses ≥ 57mcg /week (≥ DL7). AUCs achieved at these levels have been associated with antitumor activity in pre-clinical models. These findings support further the investigation of IV calcitriol as an antitumor agent in future clinical studies. Supported by NCI grants CA67267, CA95045 and CA85142