tbuckley/cabot-search huggingface dataset:
Characterization of therapies and timelines for men with prostate cancer-specific mortality.
Authors: Allie E. Steinberger, Elisa M. Ledet, Eric Luk, Patrick Cotogno, Michael Stolten, Daniel Desmond, Jonathan L. Silberstein, Oliver Sartor
Journal: Journal of Clinical Oncology (2015)

239 Background: Careful study of treatments in men with prostate cancer (PCa)-specific mortality is scant in non-trial settings. We sought to examine the characteristics and use of selected therapies in men dying from PCa, beginning from the time of diagnosis. Unique herein is the unequivocal attribution of PCa death by a single experienced clinician. Methods: Patients dying from PCa at Tulane Cancer Center from 2008 to 2014 (n=96) were studied through retrospective chart reviews. All patients died of metastatic, castrate-resistant disease (mCRPC). Results: The median age at diagnosis for the deceased cohort was 66 years (95% CI: 64-68 years); 29% of patients initially presented with metastatic PCa. 59% of patients had definitive primary therapy (radical prostatectomy or radiation). Though most men died prior to availability of the newer FDA-approved agents, patients received a median of 7 (range: 1-14) therapies. Median survival was 60 months (95% CI: 45.8-74.2 mo) after diagnosis with a median PSA pre-death of 171 (range: 0-3530) and median age at death of 73 years (95% CI: 71-75 years). At death, 4% of men had a PSA &lt; 4 and 20% of men had a normal LDH (&lt; 241 U/L). Distant metastatic disease at diagnosis was a significant predictor of death (HR=4.33, p&lt;0.001) while definitive primary therapy was a significant predictor of survival (p&lt;0.001). Median survival for patients presenting with metastases was 39 months (range: 5-213) compared to 82.5 months (range: 6-269) for localized disease (p &lt; 0.001). Definitive therapy, vs. none, was associated with a median survival of 81.5 months vs. 47 months (p&lt;0.001). Of the cohort, 48% received docetaxel before death; 49% received abiraterone, 10.4% received enzalutamide, 13.5% radium-223 and 15.6% sipuleucel-T. The only significant difference between docetaxel and non-docetaxel groups was median age of diagnosis at 62 and 71, respectively (p=0.002). Conclusions: This retrospective analysis provides initial views that clarify characteristics of men dying from PCa as well as the therapies they received before death. More data is needed in multi-institutional settings to confirm these findings. Given the evolving landscape for mCRPC treatments, therapeutic choices will change over time.
Amplification of chromosome 3q21-25 in urothelial carcinoma with squamous differentiation.
Authors: Thomas Sanford, Maxwell V. Meng, Sima P. Porten
Journal: Journal of Clinical Oncology (2016)

457 Background: Squamous differentiation is found in up to 60% of patients with urothelial carcinoma of the bladder. There is conflicting evidence regarding clinical relevance of aberrant urothelial differentiation as both population-based and retrospective studies have supported and refuted its correlation with poor prognosis and advanced stage in multivariate models. The biology of these tumors is poorly understood but some suggest that extensive squamous differentiation may resemble pure squamous tumors with similar responses to chemotherapy, radiation, and higher rate of local recurrence. Our aim was to compare tumors with squamous differentiation with those of pure urothelial histology at the genomic level to better elucidate targetable differences. Methods: We reviewed pathology reports for 412 patients with urothelial carcinoma from TCGA to identify patients with any amount squamous differentiation. Copy number alteration data obtained via the GISTC algorithm was downloaded from cbioportal.com. Chi square analysis was used to compare chromosomal amplifications in samples with squamous differentiation compared with samples that had no amount of variant histology. Results: 50 patients (12%) had some squamous differentiation, of which 15 commented on the percent of involvement – on average, 17% of the sample had squamous differentiation. A total of 257 (62%) of patients had no variant histology. Multiple specific sites in the 3q21-26 chromosomal region were noted to be amplified in squamous histology compared with pure urothelial carcinoma. Specific genes found to be amplified included SOX2 and PIK3. Conclusions: Amplifications of chromosome 3q21-25 were enriched in patients with squamous differentiation compared to those with pure urothelial carcinoma of the bladder. Amplification of this region has been reported in squamous transformation in multiple sites, including lung cancer. This study shows that, similar to other cancers, SOX2 may be necessary for squamous transformation. Furthermore, squamous cancer, which has traditionally though to be chemo-resistant, may respond to agents that target amplifications of genes found on the long arm of chromosome 3 including the PIK3-Akt pathway.
UK guideline on transition of adolescent and young persons with chronic digestive diseases from paediatric to adult care
Authors: Alenka J Brooks, Philip J Smith, Richard Cohen, Paul Collins, Andrew Douds, Valda Forbes, Daniel R Gaya, Brian T Johnston, Patrick J McKiernan, Charles D Murray, Shaji Sebastian, Monica Smith, Lisa Whitley, Lesley Williams, Richard K Russell, Sara A McCartney, James O Lindsay
Journal: Gut (2017)

The risks of poor transition include delayed and inappropriate transfer that can result in disengagement with healthcare. Structured transition care can improve control of chronic digestive diseases and long-term health-related outcomes. These are the first nationally developed guidelines on the transition of adolescent and young persons (AYP) with chronic digestive diseases from paediatric to adult care. They were commissioned by the Clinical Services and Standards Committee of the British Society of Gastroenterology under the auspices of the Adolescent and Young Persons (A&amp;YP) Section. Electronic searches for English-language articles were performed with keywords relating to digestive system diseases and transition to adult care in the Medline (via Ovid), PsycInfo (via Ovid), Web of Science and CINAHL databases for studies published from 1980 to September 2014. The quality of evidence and grading of recommendations was appraised using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The limited number of studies in gastroenterology and hepatology required the addition of relevant studies from other chronic diseases to be included. These guidelines deal specifically with the transition of AYP living with a diagnosis of chronic digestive disease and/or liver disease from paediatric to adult healthcare under the following headings; 1.&nbsp;Patient populations involved in AYP transition 2.&nbsp;Risks of failing transition or poor transition 3.&nbsp;Models of AYP transition 4.&nbsp;Patient and carer/parent perspective in AYP transition 5.&nbsp;Surgical perspective
Lapatinib impact on pulmonary hypertension.
Authors: Yaser Alkhatib, Derar Albashaireh, Tameem Abdul Hamid Al-Aqtash, Rana Awdish, Amr S. Hanbali
Journal: Journal of Clinical Oncology (2013)

160 Background: Pulmonary Arterial Hypertension (PAH) and cancer share growth factor and protein kinase signaling pathways that result in smooth muscle cell proliferation and vasculopathy. A number of tyrosine kinase inhibitors (TKI) have been developed for the treatment of cancer, and some of these like Imatinib have been investigated in PAH. There is little known about the impact of other TKI on the pulmonary vasculature. After reporting a case of lapatinib-induced PAH that reversed after withdrawal of the drug, we investigated the association of lapatinib with the development of PAH in our institution. Methods: A retrospective chart review was conducted, in accordance with IRB protocol, of all patients treated with lapatinib over the past five years at our institution. Patients who had undergone 2-D echocardiogram both prior to and after treatment were included in the analysis. Systolic Pulmonary Artery Pressures (PASP), right-sided chamber dilation and function, TAPSE were each evaluated. Through chart review, patients were evaluated in terms of risk factors for non-Group 1 PAH. A Wilcoxon signed-rank sum test was used to compare the changes in PASP before and after the initiation of lapatinib. Results: A total of 27 patients were found to have 2-D echo done before and after starting treatment with lapatinib. All patients had normal PASP before starting treatment. Eight patients developed elevated PASP following treatment. Two patients had evidence of left-sided heart disease felt to contribute to their elevated pressures, while the remaining 6 patients had no evidence for Group 2 (associated with left heart disease), 3 (associated with lung disease or hypoxemia) or chronic thromboembolic PAH. Right heart catheterization was available in one patient, confirming the diagnosis of PAH. The median pre-treatment and post treatment PASP in those 6 patients was 29.5 mmHg and 65.5 mmHg respectively (N=6; p = 0.03). Conclusions: Lapatinib is a TKI with a selective inhibition to EGFR and HER2, approved by FDA in 2007 as a second line agent in advanced breast cancer. Given the potential of TKIs as anti-proliferative agents in PAH, a number are currently under study, but little is yet known. This is the first study in the literature to show that PAH is a potential side effect of lapatinib.
Data-driven transformation to an oncology patient-centered medical home.
Authors: John David Sprandio, Brian Flounders, Maureen R. Lowry, Susan Higman Tofani
Journal: Journal of Clinical Oncology (2012)

285 Background: Consultants in Medical Oncology and Hematology (CMOH) implemented an EMR in 2003. It fell short in the compilation and presentation of meaningful data upon which to base clinical decisions. CMOH created a new workflow and effectively integrated the EMR with a practice-developed clinical decision support software (CDSS) called Iris. Methods: A project team outlined the data sources required in making a clinical decision and reviewed staff workflow. Within six months, they developed a system for displaying data from internal and external sources into a single scrollable screen for use by the physician at the point of care. Results: Iris promotes a rapid-learning cycle that results in 1) improved adherence to NCCN guidelines; 2) enhanced access and continuity of symptom management; 3) enhanced communication, tracking, and coordination of care; 4) reduction in ER utilization/hospital admissions; 5) a performance status driven approach to end of life care; 6) a systematic measurement of physician performance. This approach enabled CMOH to meet the NCQA’s criteria for level III Patient-Centered Medical Home in 2010. Conclusions: Implementation of EMRs alone does not improve health care delivery. Rather, it is the merger of clinical operations workflow and technology infrastructure delivering consumable data to providers that drives quality improvements and enhancements to the value of cancer care. [Table: see text]
High preoperative monocyte-lymphocyte ratio (MLR) as a prognostic factor in nonmetastatic clear cell renal cell carcinoma.
Authors: Georg C. Hutterer, Caroline Stoeckigt, Tatjana Stojakovic, Jessica M. Martin Hernandez, Katharina Eberhard, Sebastian Mannweiler, Armin Gerger, Karl Pummer, Martin Pichler, Richard Zigeuner
Journal: Journal of Clinical Oncology (2014)

534 Background: The ratio of peripheral blood absolute monocyte count to absolute lymphocyte count (MLR) has been proposed as a negative impact for patient’s survival in haematological cancers. However, findings about MLR’s potential prognostic significance in non-metastatic renal cell carcinoma (RCC) patients have not been reported yet. Methods: We retrospectively evaluated the prognostic significance of the MLR in a cohort comprising of 678 consecutive non-metastatic clear cell RCC patients, operated between 2000 and 2010 with curative radical or partial nephrectomy at a single tertiary academic centre. Pre-treatment MLR was calculated one day before surgical intervention. Patients were categorised using an MLR cut-off of 0.35. Cancer-specific- (CSS), metastasis-free- (MFS), as well as overall survival (OS) were assessed using the Kaplan-Meier method. To evaluate the independent prognostic significance of the MLR, multivariate Cox regression models were applied for all three endpoints. Additionally, the influence of the MLR on the predictive accuracy of the Leibovich prognosis score was determined by Harrell’s concordance index (c-index) and decision curve analysis (DCA). Results: An increased MLR was statistically significantly associated with poor outcomes for all three endpoints in univariable analyses (all p≤0.006). Multivariable analyses identified an increased MLR as an independent prognostic factor for patients’ CSS [HR=2.33, 95%CI=1.10-4.94, p=0.027], but not for MFS [HR=1.59, 95%CI=0.94-2.69, p=0.087], nor for OS [HR=1.37, 95%CI=0.93-2.03, p=0.112]. The estimated c-index was 0.83 using the Leibovich prognosis score and 0.86 when MLR was added. Conclusions: Regarding RCC patients’ CSS, an increased MLR represented an independent prognostic factor. Adding the MLR to well-established prognostic models such as the Leibovich prognosis score might improve their predictive ability.
Effect of intensity-modulated radiation therapy with SIB technique on local control and toxicity for neoadjuvant pelvic radiation with concurrent 5-fluorouracil based chemotherapy for rectal cancer compared with three-dimensional conformal radiation therapies.
Authors: Nitika Thawani, Vyas Shilpa, Shaakir Hasan, Gabriel Axelrud, Deb Niloyjyoti, Subhakar Mutyala
Journal: Journal of Clinical Oncology (2014)

632 Background: To compare the areas of residual disease after neoadjuvant pelvic radiation with 5-FU based chemotherapy for rectal cancer using Intensity Modulated Radiation Therapy (IMRT) with simultaneous integrated boost (SIB) technique compared to 3D Conformal Radiation Therapy (3DCRT) Methods: Fourty nine (49) consecutive rectal cancer patients treated with pelvic radiation and concurrent 5-FU based chemotherapy were analyzed. We compared twenty-eight (28) patients treated on an institutional IMRT protocol versus twenty-one (21) patients treated with 3DCRT. All patients received 45-50.4 Gy to the pelvis in 3DCRT group. All patients with IMRT received 45 Gy in 25 fractions to the pelvic no des. The primary rectal tumor recieved a simultaneous integrated boost to a dose of 50 Gy in 25 fractions. IMRT planning was done with dose constraints for bladder, rectum, and small bowel and bone marrow. All patients in both groups received 5-FU based chemotherapy during radiation. Evaluation of toxicity was based on RTOG criteria. 2 patients in the 3DCRT group and 2 in IMRT group received either growth factors or blood-products transfusion and needed hospitalization during treatment secondary to acute toxicities. Results: All patients completed their prescribed course of radiation. CR rates were 5/21(23%) in 3DCRT and 4/28(25%) in the IMRT-SIB (p-value 0.74). 9/21(42%) in 3D and 19/29(65%) in the IMRT group underwent Low anterior resection according to the location of the tumor. There was no grade 4 toxicity in the IMRT-SIB group. Overall grade 2 toxicity in 3D Vs IMRT-SIB group was - GI -52% Vs 19%, GU- 8% Vs 8%, skin 42 Vs 4%, hematologic 33 Vs 47%. Overall Grade 1 toxicity in 3DCRT Vs IMRT group was- GI- 33% Vs 52%, GU 23% vs 28%, Skin 52% Vs 38%, hematologic 4% Vs 33%. Conclusions: Neoadjuvant pelvic radiation with 5 FU for rectal cancer has similar local control rates. There is less GI, skin and hematologic toxicity when delivered via IMRT-SIB versus 3DCRT. IMRT is safe and may allow dose escalation with potential probability of increased tumor response.
Systems engineering in health care: Overview and examples from The University of Texas MD Anderson Cancer Center.
Authors: Victoria S. Jordan
Journal: Journal of Clinical Oncology (2012)

140 Background: The University of Texas has six health institutions and Industrial and Systems Engineering faculty throughout university locations across the state. These academic medical centers, including MD Anderson Cancer Center, and schools of engineering, business, and medicine are partnering to implement Systems Engineering in healthcare throughout the UT system. The “systems approach to implementing Systems Engineering” is an opportunity to serve as a world-class model for collaboration across academic institutions for engineering, business, medicine, and healthcare organizations to implement Systems Engineering and systems thinking in healthcare. The objective of the collaboration is not just to produce successful projects, but to achieve transformational change. Methods: This presentation will provide an overview of Systems Engineering and provide examples of the different tools and strategies from the discipline including lean, six sigma, mathematical simulation, optimization and operations research, human factors, facility design layout, statistical process control, design of experiments, scheduling, supply chain and inventory management, staffing models, etc. Funding, leadership, training, and communication efforts associated with the effort will be reviewed including the grant application process for transformational efforts. (The implementation follows the PDSA process.) Results: Currently nine grants have been awarded in the UT system for implementing Systems Engineering. Results will be shared (in terms of cost savings and/or avoidance and patient satisfaction) from specific projects such as a lean effort in the Diagnostic Center and simulation models to schedule nurses in the OR and to determine resource requirements in the ICU. Conclusions: Systems Engineering is a valuable discipline that is relatively new to healthcare. Practicing clinical oncologists can increase efficiency, patient flow, and patient and physician satisfaction by applying Systems Engineering tools and strategies.
DART Study: A phase II randomized trial of dalantercept plus axitinib versus placebo plus axitinib in advanced clear cell renal cell carcinoma (RCC): Results from Part 1.
Authors: Martin Henner Voss, Elizabeth R. Plimack, Brian I. Rini, Michael B. Atkins, Robert Alter, Rupal Satish Bhatt, J. Thaddeus Beck, Kristen M. Pappas, Dawn Wilson, Xiaosha Zhang, Matthew L. Sherman, Shuchi Sumant Pandya
Journal: Journal of Clinical Oncology (2015)

407 Background: Activin receptor-like kinase 1 (ALK1) is a novel target in angiogenesis involved in blood vessel maturation and stabilization. Concurrent targeting of ALK1 and vascular endothelial growth factor (VEGF) signaling results in dual angiogenic blockade and augmented inhibition of tumor growth in RCC xenograft models. Dalantercept (Dal) is an ALK1 receptor-fusion protein that acts as a ligand trap and has demonstrated monotherapy activity with an acceptable safety profile in a completed phase I study. Methods: Part 1 of this study evaluated the safety, tolerability, and preliminary activity of escalating dose levels of Dal plus fixed dose axitinib in pts with advanced RCC. 3-6 pts each received Dal (0.6, 0.9, or 1.2 mg/kg) SC Q3W and axitinib 5 mg PO BID. Key eligibility: predominantly clear cell RCC, 1 prior VEGFR TKI, ≤3 prior tx. Results: As of September 12, 2014, 29 pts were enrolled in three cohorts (n=6, 9, 14) at dose levels of 0.6, 0.9 and 1.2 mg/kg, respectively. At the 1.2 mg/kg dose level, 1 DLT of grade 3 abdominal and back pain occurred (n=1) in addition to more Dal associated edema events including peripheral edema (n=6), fluid overload (n=1), ascites (n=1), and pleural effusion (n=1). The 0.9 mg/kg dose level was well tolerated (3 pts with low grade edema; no pleural effusions or ascites) and selected for Part 2. Frequent AEs regardless of attribution: fatigue, diarrhea, dysphonia, nausea, peripheral edema, creatinine rise, epistaxis, hypertension, arthralgia, hand-foot rash, and cough. 28 pts were evaluable for response by RECIST 1.1. The ORR was 25% (n=7) and 31.3% (n=5) among pts who received ≥ 2 prior txs (n=16), including VEGF targeted tx, mTOR inhibitors, and immune tx. Of those evaluable for disease control at 6 mos. (n=25, 3 active pts have not reached 6 mos.), 52% (n=13) remained progression free. PFS data are maturing and will be presented. Conclusions: The combination of dalantercept and axitinib is well tolerated and associated with encouraging activity in pts with prior VEGF, mTOR, and immune therapies. Part 2 of this study randomizes pts to dalantercept + axitinib vs. placebo + axitinib and is actively accruing patients. Clinical trial information: NCT01727336.
Sarcopenia as a marker for prediction of long-term survival following radical cystectomy.
Authors: Mario Kramer, Bennet Hensen, Max Clemens Jansen, Martin JP Hennig, Marie C Hupe, Hossein Tezval, Frank Wacker, Markus A. Kuczyk, Axel S. Merseburger
Journal: Journal of Clinical Oncology (2016)

435 Background: Patients undergoing radical cystectomy (RC) face a relevant risk of tumor relapse and mortality based on variable factors. Risk stratification may be enhanced by objective measures such as sarcopenia (loss of skeletal muscle mass) which has been described as a potential biomarker associated with survival after radical cystectomy. However, data on this highly interesting biomarker in conjunction with urothelial carcinoma of the bladder are sparse. Methods: A retrospective study including patients that were treated with RC at Hannover Medical School between 2005 and 2011 were included. The lumbar skeletal muscle index (SMI) was measured on preoperative computed tomography (CT) which was performed within 60 days prior to surgery. MeVisLab 2.7 was used to perform calculations. The fat mass index (FMI) was calculated based on the same CT slides. The body mass index (BMI) was used as a comparative value. Cut off points were developed for men and women separately. Results: Indices were measured on 103 patients (79 men, 24 women, mean age: 67.5 yrs). 72 (70%) pts. had muscle-invasive disease, 21 (20%) pts. were lymph node positive and 6 (6%) pts. had synchronous metastasis. Median follow-up time was 39 months. SMI (cm 2 /m 2 ), FMI (kg/m 2 ) and BMI (kg/m 2 ) for men were calculated with mean scores of 51.2, 9.6 and 27.0, respectively. The corresponding calculated means for women were 38.7, 10.0 and 25.3. None of the stratification markers correlated with overall survival (OS) using Kaplan-Meier plots. However when applied on patients that survived at least 12 months, the sarcopenia index (SMI) became statistically significant (p &lt; 0.05). Conclusions: The presence of sarcopenia may be predictor of poor overall survival later than 12 months after radical cystectomy. BMI and FMI may not be used in risk stratification models. Further research is needed to validate the current findings.