tbuckley/cabot-search huggingface dataset:
Results of a phase II study of single-agent sunitinib in elderly non-small cell lung cancer patients.
Authors: C. Reynolds, A. I. Spira, W. L. Gluck, R. E. Pluenneke, K. A. Boehm, F. Zhan, L. Asmar
Journal: Journal of Clinical Oncology (2011)

7549 Background: Although chemotherapy doublets are standard therapy for stage III/IV non-small cell lung cancer (NSCLC), some elderly patients (pts) may have lower tolerance of therapy. Sunitinib (S) is an oral, multitargeted kinase inhibitor that has shown promising results as 2nd-line treatment (Tx) for NSCLC. This study was conducted to explore the safety and efficacy of S in an elderly NSCLC population. Methods: Primary objective: disease control rate (DCR) defined as complete response (CR) + partial response (PR) + stable disease (SD) at 6-weeks. Secondary objectives were overall response (OR, CR+PR), progression-free survival (PFS), time to progression (TTP), 1-yr survival, change in quality of life (QOL), and safety. Tx: S 37.5 mg/day Days 1-42 of each 42-day cycle until PD or intolerable toxicity. Key inclusion: previously chemo-naïve stage IIIB/IV NSCLC with nonsquamous histology; ECOG PS=0-1; pt age >70 yrs; normal renal, hepatic, and marrow function. Pts were excluded if they had hemoptysis, anticoagulation or clotting diathesis. Other standard S-specific criteria were applied. Results: 63 pts enrolled; 60 were treated. Baseline demographics: 51% male, 95% white, median age 78 yr (range, 70-88), 71% ECOG=1, 97% Stage IV, 82.5% adenocarcinoma, 46% had prior surgery, 19% prior radiation, 41% no prior Tx. Sites of metastasis: bone 32%, viscera 65%, and soft tissue 35%. Pts received a median of 2 cycles (range, 1-8). Efficacy: DCR=58%, OR=5% (0 CR, 3 PR). With a median follow-up of 5 mos (all patient; 6 mo surviving pts), median PFS was 3.0 mos (range, <1-12.9), median TTP was 4.2 mos (range, <1-12.9). 1-yr survival was 22.8% [95% CI: 11.2, 36.8]. QOL trended downwards in all categories throughout the study. Significant decreases were seen in physical and function well-being and total outcome index. The most frequent grade 3-4 treatment related adverse events were: fatigue (18%); thrombocytopenia, anorexia, and weakness (8%, each); and dehydration, diarrhea, and mucositis (5%, each). Conclusions: While S produced acceptable DCR in these elderly pts, OR was disappointing at 5%, as was the worsening of QOL. Supported, in part, by a grant from Pfizer, Inc., New York, NY.
Prognostic value of copy-number alterations of the Cohesin complex in intermediate-risk prostate cancer recurrence.
Authors: Jonathan So, Melvin Chua, Emilie Lalonde, Osman Mahamud, Alejandro Berlin, Alan Dal Pra, Michèle Orain, Helene Hovington, Alain Bergeron, Yves Fradet, Bernard Têtu, Alice Meng, Junyan Zhang, Gaetano Zafarana, Julie Livingstone, Melania Pintilie, Theodorus van der Kwast, Michael Fraser, Paul Boutros, Robert G. Bristow
Journal: Journal of Clinical Oncology (2016)

49 Background: The Cohesin complex plays a critical role in mitotic progression and post-replicative DNA damage repair. It serves to bring together sister chromatids both in metaphase and in homologous recombination repair following ionizing radiation. The complex has also been shown to be phosphorylated in the ATM/BRCA1 pathway. The expression of various proteins in the complex are dysregulated in many cancers: breast, prostate, etc. Interestingly, in breast cancer cell lines, Cohesin is required for MYC activation in response to estrogen. Our study sought to correlate copy number alterations in this pivotal complex with biochemical relapse in prostate cancer patients. Methods: Our cohort consists of 284 patients with D’ Amico-classified intermediate-risk prostate cancer, treated with image-guided radiotherapy (IGRT, N = 143) or radical prostatectomy (RadP, N = 141). Pre-treatment biopsies and prostatectomy samples were analyzed using the Affymetrix Oncoscan array. The Phoenix and AUA criteria was used to define biochemical relapse for RadP and IGRT patients respectively. Results: Copy number alterations of RAD21, SMC1B, and STAG1 were observed in 18% (n = 52), 6.3% (n = 18), and 12% (n = 35) of the cohort respectively. They were predominantly losses in SMC1B, but gains in RAD21 and STAG1. All three genes in the Cohesin complex were associated with increased risk of biochemical relapse: RAD21 on chromosome 8 (HR = 1.93, 95% CI 1.23, 3.02, Wald’s p = 0.004), SMC1B on chromosome 22 (HR = 3.37, 95% CI 1.91, 5.94, Wald’s p &lt; 10 -4 ), and STAG1 on chromosome 3 (HR = 1.74, 95% CI 1.04, 2.89, Wald’s p &lt; 0.05). However, when controlled for percent genome alteration and pre-treatment serum PSA levels, only copy number loss of SMC1B was a significant predictor of biochemical relapse (HR = 2.95, 95% CI 1.62, 5.38, Wald’s p &lt; 10 -3 ). Conclusions: We identified a novel association of copy-number alterations in members of the Cohesin complex with biochemical recurrence following radical prostatectomy or image-guided radiotherapy. This points to the central role of Cohesin in cell-cycle and DNA damage pathways promoting prostate cancer progression.
Impact of colonoscopically missed cancers on patient outcomes.
Authors: Anand Govindarajan, Linda Rabeneck, Jill Tinmouth, Lawrence Frank Paszat, Nancy Baxter
Journal: Journal of Clinical Oncology (2014)

404 Background: There is increasing recognition of the potential for cancers to be missed on colonoscopy, but little is known about their outcomes. The objective of this study was to evaluate the outcomes of missed cancers relative to those detected by colonoscopy. Methods: We conducted a retrospective population-based cohort study, including all patients diagnosed with colorectal cancer (CRC) in Ontario, Canada from 2003-2009, who had undergone a colonoscopy within 36 months prior to diagnosis. Using previously defined time windows, we defined detected cancers as those diagnosed within 6 months of index colonoscopy and missed cancers as those diagnosed between 6 and 36 months after index colonoscopy. Patient and tumor factors were recorded as covariates. The primary outcome was overall survival, with secondary outcomes of resection rate, emergency presentation, and surgical complication rate. Logistic regression was used to analyze binary outcomes and Kaplan-Meier and Cox regression analyses were used for survival outcomes. Results: Overall, 30,475 patients were included in the study, with 2,804 being classified as having a missed cancer. Factors associated with missed cancers included colonic location (vs. rectum), older age, female sex, rural residence, and Charlson comorbidity score. Absolute 5-year overall survival was significantly lower in missed compared to detected cancers (60.8% vs. 68.3%, difference: 7.5%, p &lt; 0.0001). In multivariable analysis, patients with missed cancers had a 22% higher hazard of death (HR: 1.22, 95% CI: 1.15 to 1.30, p &lt; 0.0001). Patients with missed cancers were significantly more likely to present emergently with obstruction, bleeding or perforation (OR: 2.86, 95% CI: 2.56 to 3.13, p &lt; 0.001) and were significantly less likely to have their tumors surgically resected (OR: 0.61, 95% CI: 0.55 to 0.67, p &lt; 0.001). Conclusions: CRCs that are missed on initial colonoscopy are associated with markedly inferior patient outcomes, with a higher risk of emergent presentation, a lower likelihood of surgical resection, and most notably a significantly worse overall survival. These findings reinforce the critical importance of studying and improving quality measures of CRC screening to improve patient outcomes.
Prediction of systemic spread independent of local extension or nodal disease by venous tumor thrombus in renal cell carcinoma.
Authors: Ahmed Aboumohamed, Lorenzo Digiorgio, Diana Mehedint, Kristopher Attwood, Thomas Schwaab
Journal: Journal of Clinical Oncology (2013)

435 Background: Renal cell carcinoma (RCC) venous extension is a challenging condition. Its prognostic significance is not well established. We investigated possible prognostic correlations between venous extension in RCC, with its various levels, and local extension, lymphatic spread and systemic metastasis; and its impact on progression free survival (PFS) and overall survival (OS). Methods: We analyzed an IRB-approved prospectively-maintained kidney cancer database at Roswell Park Cancer Institute. Patients with venous involvement were identified, classified according to the highest cephalic venous thrombus extension into 3 groups; group 1, renal vein; group 2, infrahepatic; group 3, subdiaphragmatic. Preoperative, postoperative, and pathologic factors were recorded. Patient characteristics were compared between groups using Kruskal-Wallis and Chi-Square tests for quantitative and categorical variables respectively. Results: 711 patients underwent nephrectomy for RCC between 2004 and 2011. Out of 63 patients with RCC and venous tumor thrombus, 55 patients were analyzed in this study who underwent radical nephrectomy and venous thrombectomy. Median age was 63 years and median follow-up was 18.7 months. 37 patients were group 1, 10 were group 2, and 8 were group 3. 1 and 3 year PFS were 66% and 38.5% respectively, and 1 and 3 year OS were 74.2% and 47.4% respectively. There were no statistically significant differences in OS or PFS between different groups. Among several factors examined, venous extension was associated with increased risk of distant metastasis, and that risk did not increase with higher cephalic venous extension (p = 0.011). When patients were categorized by local extension and nodal disease spread, there was no statistically significant association with venous tumor extension (p =0.24 and 0.35 respectively), though they were independently associated with distant spread (p = 0.002 and 0.013 respectively) and OS (p =0.005 and0.03 respectively). Conclusions: Venous tumor extension alone can serve as an independent predictor of distant metastasis in patients with RCC. Our analysis suggests that cephalic venous thrombus extension does not impact patient survival.
Patient versus clinician symptom reporting during chemoradiation for rectal cancer.
Authors: Libertad T. Flores, Antonia V Bennett, Ethel B Law, Carla Hajj, Mindy P Griffith, Karyn A. Goodman
Journal: Journal of Clinical Oncology (2012)

646 Background: Pelvic radiotherapy with concurrent 5-fluorouracil based chemotherapy (chemoradiation) is a component of standard therapy for patients with T3/T4 or node-positive rectal cancer. Chemoradiation can be associated with significant acute gastrointestinal toxicity. This study sought to retrospectively compare patient and clinician reports of acute symptoms experienced by rectal cancer patients receiving chemoradiation. Methods: The charts of 199 rectal cancer patients who received chemoradiation from 11/06 to 2/11 were reviewed. Clinicians assessed toxicity weekly using Common Terminology for Clinical Adverse Event (CTCAE) version 3.0. Patient-reported outcomes (PROs) were collected weekly, in clinic, beginning 9/09 using the 7-item Bowel Problems Scale. 197 patients had at least one clinician assessment or PRO and were eligible for this study. Patient and clinician assessments were compared among a subgroup of 65 patients (paired group) who had at least one patient and clinician assessment on the same date using descriptive statistics. Agreement between patient and clinician assessments was evaluated by Cohen’s kappa coefficient. Results: Characteristics were well-balanced between all rectal patients and the paired group, with the exception of the use of intensity modulated radiotherapy (IMRT). IMRT has been used increasingly over time, and IMRT was therefore used in a larger proportion of the paired group versus all patients (77% vs. 51%, respectively). Diarrhea and proctitis were reported more often by patients than clinicians throughout treatment. Uncorrected agreement for diarrhea and proctitis was 82% and 72%, respectively. Corrected for chance, Cohen’s kappa was .64 for diarrhea, indicating moderate agreement, and .22 for proctitis, indicating only slight agreement. Conclusions: Our findings suggest a discrepancy between clinician and patient symptom reports. Further study is warranted to discern potential benefits of including PROs in prospective studies, and to find whether PROs can help clinicians set patient expectations, and/or enhance communication for optimal symptom management.
Pretreatment rectal tumors quantitative dynamic contrast-enhanced MRI characterization and predictability of outcome: Pilot study.
Authors: Wael Shabana, Sameh Saif, Greg Cron, Rebecca Thornhill, Natalia Koudrina, Anna Koudrina, Derek J. Jonker
Journal: Journal of Clinical Oncology (2014)

416 Background: Treatment of rectal cancer is currently a one-size-fits-all approach. Unfortunately, some rectal tumors do not respond well to treatment and/or give rise to latent metastases. Therefore, a need exists for biomarkers which can better characterize tumor aggressiveness and help guide treatment decisions. We investigated the feasibility and performance of dynamic contrast-enhanced (DCE) MRI (performed pre-treatment) as a potential biomarker to predict rectal cancer response to treatment. Methods: 47 patients with rectal masses underwent DCE-MRI at 3T pre-treatment. DCE-MRI was performed with 3D FLASH (TR/TE/flip 6ms/1.6 ms/25 deg). Gadolinium concentration-versus-time in tissue was estimated with the aid of a variable-flip-angle T1 mapping procedure performed pre-DCE. The arterial input function was estimated by measuring phase-versus-time in major arteries. Tracer kinetic modeling was used to obtain maps of the quantitative perfusion parameters Ktrans and Kep. Treatment outcome was categorized as successful (regression) or unsuccessful (progression, stable, or recurrence). We also dichotomized latent metastases as absent or present. The pathology outcome of the lesions was categorized as cancerous or non-cancerous. A support vector machine classifier was constructed from the perfusion parameters, and the accuracy of each classifier was determined by 10-fold cross validation. Results: Clinical characteristics were 31 successful outcomes, 8 unsuccessful; 25 with latent metastases absent, 5 with latent metastases present; 40 cancerous, 7 non-cancerous. The accuracies of quantitative DCE-MRI parameters for predicting treatment outcome, latent metastases, and pathology outcome were 78%, 83%, and 84%, respectively. Conclusions: Pre-treatment DCE-MRI appears to be a useful predictor of rectal tumor malignancy, treatment outcome, and latent metastases. Perfusion parameters have very promising potential to predict rectal cancer outcome and may serve as an added tool for rectal cancer treatment planning.
The role, use, and nuances of clinical data systems in oncology quality improvement.
Authors: Thomas W. Belnap, William T. Sause, Braden D. Rowley, Cory Jones, John C. Ruckdeschel
Journal: Journal of Clinical Oncology (2012)

135 Background: Data is essential to achieve meaningful quality improvement. A variety of commercial products are currently available for sophisticated data collection. However, data systems alone are not sufficient to improve quality. Additional resources are required in order to leverage electronic clinical data for meaningful improvement. This abstract outlines the necessary requirements and available methods for data-based oncology quality improvement using the experience of Intermountain Healthcare. Methods: The organizational components required for quality improvement are complex. Successful quality improvement begins with project feasibility, data availability and clinical leadership. Clinical processes are reviewed, data accuracy and availability are confirmed and clinical goals are established. Data collection, validation, and analysis are standardized across multiple facilities and providers. Data must be analyzed and presented in a way that clearly illustrates differences in current performance compared to quality goals, should be tracked over time to ensure real and sustainable progress, and must be combined with other improvement strategies to maximize impact. Results: Once quality reports are generated, a physician champion presents them to clinical staff along with education materials, national guidelines and current evidence from peer-reviewed literature. Clinicians are presented with individualized data comparing their personal performance to de-identified performance of their peers, the facility and the system. Providers are given updated data on a regular basis, the data system is monitored for outliers and the need for subsequent interventions, and additional metrics are tracked to ensure process changes don’t negatively impact quality in other areas. Conclusions: Oncology quality improvement requires both clinical and data infrastructure. Electronic clinical data systems are essential for quality improvement, but are not sufficient by themselves. Additional resources are required to capture, extract, validate and analyze clinical data. Appropriate use of these resources transforms existing electronic data systems into a powerful quality improvement tool.
Docetaxel chemotherapy in metastatic castration-resistant prostate cancer (mCRPC): Cost of care for Medicare and commercially insured men.
Authors: Andrew J. Armstrong, Cat N Bui, Kate Fitch, Tia Sawhney, Bruce Brown, Scott C Flanders, Peter St. John Francis, Mark A. Balk, Julie Deangelis, James Chambers
Journal: Journal of Clinical Oncology (2016)

262 Background: Docetaxel (DTX) is commonly used to treat metastatic prostate cancer, yet little data is available about the cost of a DTX chemotherapy episode of care (DEC) for treating mCRPC. This study analyzes DEC cost and health service utilization for men with mCRPC. Methods: We performed a claims-based analysis using Truven MarketScan and Medicare 5% sample data sets. Eligibility was required in all months of 2010 and ≥ 1 month of 2011, along with ≥ 1 2011 claim coded with prostate cancer and ≥ 1 DTX claim. Initial 2011 DECs required no DTX claim in the prior 12 months while subsequent DECs required a 60-day gap between DTX claims. DEC costs included all paid claims, except prescription drugs, from the 1st DTX claim to 30 days after the last DTX claim with early termination for death, insurance disenrollment or the end of a 24-month look-forward period. DTX drug costs were adjusted for 2011 generic DTX introduction while all other DEC costs were adjusted to 2015 using national average unit cost increase. Results: 155 commercially insured patients (COMM) and 281 Medicare patients (MDCR) were identified with 172 and 325 DECs, respectively. The average number of DTX cycles per DEC was 6.3 for COMM and 6.9 for MDCR, with 105 and 102 average days between the 1st and last infusion, respectively. The average DEC cost was $63,788 for COMM and $28,742 for MDCR with DTX drug costs contributing $13,169 (21%) and $2,588 (9%) per DEC, respectively. The average cost per DEC contributed by DTX-infusion days was $27,900 (44%) for COMM and $8,577 (30%) for MDCR. Non-DTX-infusion day costs per DEC included $10,838 (17%) for infused/injectable drugs for COMM and $7,074 (25%) for MDCR, along with $9,324 (15%) and $6,875 (24%) for inpatient admissions, respectively. 29% of COMM-DECs and 40% of MDCR-DECs had ≥ 1 inpatient admissions while 22% and 25% had ≥ 1 emergency room (ER) visit, respectively. 22% of COMM and 28% of MDCR inpatient costs and 15% of COMM and 33% of MDCR ER costs were chemotherapy related. Conclusions: Non-DTX drug costs including infusion day services, infused/injectable drugs administered on non-DTX days and inpatient admissions contributed the majority of DEC costs in COMM and MDCR mCRPC populations.
Caregiver time burden in newly diagnosed glioblastoma: A prospective analysis.
Authors: Lauryn Hemminger, Christine Pittman, Nimish Mohile
Journal: Journal of Clinical Oncology (2016)

242 Background: Caregiver (CG) burden is particularly high in glioblastoma (GBM) because neurologic deficits lead to cognitive dysfunction and physical dependence. The amount of time that CGs devote to GBM pts is not well described. The extent to which time burden impacts CG quality of life and perceived burden is unknown. Methods: We performed an IRB-approved prospective analysis of 38 CGs of pts with newly diagnosed GBM enrolled over 8 mo. at a single academic institution. CGs were defined as individuals responsible for any aspect of pt support, and multiple CGs were allowed for each pt. CGs completed the Caregiver Quality of Life in Cancer (CQOLC) survey plus questions about CG role and time dedicated to pt care within 2 mo. of initial neuro-oncology visit. We described time burden and correlated this with 3 CQOLC questions addressing CG stress, emotional well-being, and perceived burden. Results: 30/38 CGs completed the surveys. The 30 CGs (21 female) included 16 spouses, 8 children, 3 parents, 2 siblings and 1 friend. 21 were primary CGs (13 female). 21 CG spent &gt; 40 hrs/wk with pt, 10 spent &gt; 40 hrs/wk on direct pt care, and 7 spent &gt; 40 work hrs/wk caring for the pt. Table 1 illustrates CG time burden stratified by primary vs non-primary CG. CG time spent on direct pt care positively correlated with CGs feeling overwhelmed by their responsibilities as assessed by the CQOLC (p &lt; 0.0001, spearman coefficient 0.66). Amount of work hrs spent on pt care also correlated with the CG feeling overwhelmed. (p = 0.0003, spearman coefficient 0.61). Conclusions: CG time burden in GBM is substantial even at the time of diagnosis, and is most notable in primary CGs. CG time burden correlates with signs of emotional distress as measured by the CQOLC. Assessing time burden for individual CGs may help identify early risk for distress and develop interventions to improve CG quality of life. [Table: see text]
Physician orders for scope of treatment (POST) forms in metastatic cancer patients: A 3-year single-university–institution retrospective review.
Authors: Brendan F. Curley, Farhad Khimani, Alvin Howard Moss
Journal: Journal of Clinical Oncology (2013)

133 Background: Physician orders for dcope of treatment (POST) forms are standardized forms for patient preferences for end-of-life care. These forms contain orders by a physician who has identified a patient who is seriously ill with life-limiting progressive, advanced illness. Utilization of the POST form in advanced and metastatic cancer patients has not yet been evaluated. Methods: At West Virginia University/Mary Babb Randolph Cancer Center, we performed an IRB approved retrospective chart review of all patients who died of metastatic or advanced malignancies from 2010-2012. Statistical analysis was performed with SPSS Version 20. Results: 139 patients were identified who were diagnosed with metastatic cancer and treated at West Virginia University who died from 2010-2012. Of those 139 patients, 26 (18.7%) completed POST forms. 51 (36.7%) patients received systemic oncologic treatment in their last thirty days of life. In the last ninety days of life, patients averaged 16.2 days hospitalized. 123 (88.4%) patients had at least one hospital stay in their last three months of life, with 82 (58.7%) having two or more stays. 65 (46.8%) patients had a hospital readmission within thirty days. 39 (28.1%) patients had an ICU stay with an average duration of 2.6 days. Almost half of all patients reviewed (67, 48.2%) died in the hospital. Patients averaged 2.9 CT scans and 5.2 X-rays over the last ninety days of their life. 116 (83.5%) patients had an end-of-life discussion, with an average time from discussion to date of death of 24.5 days. Only 60 (43.2%) were identified as having a palliative care consult completed. Conclusions: The American Society of Clinical Oncology (ASCO) recommends implementation of Palliative Care at the time of diagnosis of advanced cancer. POST forms appear to have a positive impact on end-of-life care in this population of advanced cancer patients. Increasing their implementation in metastatic oncology patients will likely improve end-of-life care. [Table: see text]