tbuckley/cabot-search huggingface dataset:
Operative morbidity and mortality in octogenarians and nonagenarians with ovarian cancer.
Authors: C. L. Walters, K. E. Schneider, J. M. Whitworth, J. M. Fauci, J. M. Straughn, M. N. Barnes
Journal: Journal of Clinical Oncology (2011)

5070 Background: The decision to choose aggressive cytoreduction versus neoadjuvant chemotherapy in patients with newly diagnosed ovarian cancer is often influenced by age and medical comorbidities. We sought to compare perioperative morbidity and mortality of patients age >/= 80 compared to younger patients. Methods: After IRB approval was obtained, a retrospective chart review was conducted evaluating patients that underwent surgical cytoreduction for ovarian or peritoneal cancer between 1/05 and 12/09. Patients were divided into two cohorts (<age 80, and >/= age 80). Patient demographics, surgical procedures, readmission rates, length of stay (LOS), 30 day mortality rates, and chemotherapy administration were examined. Student’s t test and chi square test were used to evaluate statistical significance. Results: 384 patients that underwent surgical debulking for ovarian cancer were identified. 352 (91.7%) patients were <80yo, while 32 (8.3%) patients were >/= 80yo. Amongst the younger cohort, 236 (67.0%) were optimally cytoreduced compared to 17 (53.1%) in the older cohort (p=0.12). Patients in the older cohort had more medical comorbidities (1.7 v 1.2, p=0.03). Thirty day readmission rates were similar between the two cohorts; 14.5% for the younger cohort versus 15.6% for the older cohort (p=0.80). Post-operative complication rates were also similar (45.2% v 53.1%, p=0.46). More patients in the older cohort required preoperative admission for medical clearance (50.0% v 18.7%, p<0.01). Mean LOS was significantly longer in the older cohort (10.0 days v 7.5 days, p=0.02). The number of patients that received adjuvant chemotherapy was significantly lower in the older cohort (71.9% v 93.8%, p<0.01). The 30 day mortality rate was significantly higher in the older cohort (18.8% v 4.0%, p<0.01). Older patients with two or more medical comorbidities had a 30 day mortality rate of 31.3%. Conclusions: Although octogenarians who undergo surgical debulking have similar complication rates as their younger counterparts, they will require more medical clearance and have a longer hospital stay. Older patients are less likely to undergo chemotherapy and have a higher 30 day mortality rate than younger patients.
Innovation or disparity? National trends in nonoperative management of rectal adenocarcinoma.
Authors: Clayton Tyler Ellis, Cleo A. Samuel, Karyn B. Stitzenberg
Journal: Journal of Clinical Oncology (2016)

688 Background: While surgical resection has always been the cornerstone of curative treatment for rectal cancer, preoperative chemoradiation for stage II/III rectal cancer results in up to 49% of patients with a clinical complete response. As a result, many have questioned whether surgery can be omitted for this group of patients. Currently, there is insufficient evidence on the safety and efficacy of chemoradiation-only, or non-operative management (NOM), to support the wholesale adoption of this treatment paradigm. Despite this, anecdotal evidence suggests there is a trend for increased use of NOM. Our objective was to examine trends in the use of NOM for rectal cancer over time as well as patient- and facility-level factors associated with its use. Methods: We included all incident cases of invasive, non-metastatic, rectal adenocarcinoma reported to the National Cancer Data Base (NCDB) from 1998–2010. We performed univariate and multivariate analyses to assess NOM use over time as well as patient- and facility-level predictors of NOM. Results: 146,135 patients met inclusion criteria: 5,741 had NOM and 140,394 had surgery +/- additional therapy. From 1998-2010, the use of NOM doubled from 2.4% to 5% of all cases annually. Patients who were Black (AOR=1.71, 95%CI=1.57-1.86), uninsured (AOR=2.35, 95%CI=2.08-2.65), Medicaid-enrolled (AOR=2.10, 95%CI=1.90-2.33), and those treated at low-volume facilities (AOR=1.53, 95%CI=1.42-1.64) were more likely to receive NOM than White, privately insured, and high-volume facility patients, respectively. Additionally, NOM was more common in the South (AOR=1.53, 95%CI=1.32-1.76) and Pacific (AOR=1.82, 95%CI=1.57-2.12) as compared with the Northeast. Conclusions: NOM is an innovative approach that demonstrate promise in the treatment of rectal cancer. Pursing this approach in the context of a clinical trial and with well-informed patients would be appropriate. We observed evidence of increasing NOM utilization; however, this increase is occurring more frequently in Black and uninsured/Medicaid patients, raising concern that increased NOM use may actually represent increasing disparities in rectal cancer care rather than innovation.
SAGE directory of cancer guidelines.
Authors: Melissa C. Brouwers, Ellen Rawski, Lavannya Bahirathan, Karen Spithoff, Caroline Zwaal
Journal: Journal of Clinical Oncology (2012)

306 Background: The Standards and Guidelines Evidence (SAGE) directory of cancer guidelines is a resource designed to facilitate evidence-based clinical practice, policy formation, and guideline adaptation, and reduce duplication in guideline development. Methods: Developed in 2008, SAGE is a publically available (www.cancerview.ca/sage), searchable database of English language cancer control guidelines and standards released since 2003. Qualifying guidelines in SAGE are rated using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. These ratings can be used to measure trends in guideline quality. SAGE also documents guideline development status, including current guidelines, guidelines in progress, those in need of an update and guidelines undergoing updates. Results: SAGE contains over 1,900 indexed records from 271 developer organizations spanning 27 countries and international jurisdictions. There is considerable variability in guideline quality both within and across guideline developers, and AGREE II quality domains of applicability and editorial independence are the poorest performing. SAGE has the ability to provide information on guideline topic gaps and overlap, demonstrating that the majority of guidelines target breast, lung, colorectal and prostate cancers, and focus on the treatment stage of the cancer control continuum. This provides a channel of communication amongst organizational groups and facilitates guideline development partnerships. Conclusions: The value-add of SAGE to mitigate inconsistencies in guideline quality is the appraisal component of its records. It is the ultimate goal that SAGE will continue to assist efforts to leverage positive change in the field of practice guidelines, patient care and system performance in cancer control.
Bridging community and academic cancer centers using nurse navigation.
Authors: Eleanor Miller
Journal: Journal of Clinical Oncology (2016)

102 Background: The Penn Cancer Network was formed in the early 1990’s to bridge a connection between the community oncology setting and The University of Pennsylvania, an academic medical center. Aspects of the network contracts include cancer program assessment and development, accreditation preparation, and most recently dedicated access to cancer care via the network nurse navigator. This poster emphasizes the impact of a network nurse navigator has as a highly sought link between health systems, providers and patients to streamline patient referrals, with a formal process evolving over time. Methods: The establishment, growth and success of the referral process can be attributed to multiple efforts on behalf of the nurse navigator and administration, including but not limited to strong relationship development among nurse navigators and administrators at the hospitals and a formalized process developed by the nurse navigators using an online portal for referrals directly to the nurse navigator. Metrics are also maintained to demonstrate clinical and financial outcomes. Results: Since the establishment of a dedicated nurse navigator in 2010, referrals have increased year over year and two hospitals have since joined Penn Medicine, in part due to these strong relationships. Systematic chart reviews and data analysis have been completed annually to present to administration, with hundreds of patients being referred annually for second opinions, complex surgeries or clinical trials. A comprehensive financial analysis has been done to demonstrate the impact of these patient referrals on the health system, increasing annually. Conclusions: Access to the network nurse navigator has been emphasized as a major advantage to being a network hospital. A nurse navigator is well positioned to triage to subspecialties, assess patient and provider needs, and be knowledgeable in the operations of both systems. Data analysis has been paramount in demonstrating the impact of this program, both clinically and financially. This process could be done for formal network relationships or informal, but it certainly builds a great pattern to improve patient’s access to care.
Direct measurement of calcium metabolism in patients with castration-resistant prostate cancer using a novel isotope tracing approach in urine.
Authors: A. P. Pai, P. Lara, C. Pan, D. Hillegonds
Journal: Journal of Clinical Oncology (2011)

e15083 Background: Recent cohort studies have shown that in patients with metastatic castration-resistant prostate cancer, the degree of perturbation from normal bone turnover provides a strong indication of risk for disease progression, skeletal complications and death. Biomarkers of bone cell function and bone collagen degradation provide an integrated index of the underlying disease for patients with bony metastases, but available bone markers are insufficiently precise and accurate. In this study, patients with castration-resistant prostate cancer with bony metastases will consume a single oral calcium-41 dose and the pharmacokinetics of this will be measured over an 18 month period. Participants will also be assessed clinically for time to progression, skeletal related events and death. Methods: Patients with metastatic castration-resistant prostate cancer and bony metastatses, as diagnosed via bone scintigraphy, who were on bisphosphonates were enrolled into the study. As part of this ongoing IRB-approved clinical trial, seven consenting research subjects consumed a single 1.2 microgram 41Ca tracer dose and provided 30-250mL urine specimens (single voids) after dose on day 1 (6h after dosing), days 7, 14, 28, 42, 60, and monthly thereafter. Isotope ratios were measured via accelerator mass spectrometry. Results: Urinary 41Ca/Ca was significantly and inversely associated with increasing skeletal tumor burdens suggesting that development of an isotopic urine test for bone metastasis extent is feasible, providing a non-invasive and quantitative measure of disease extent. Data is currently available to 5 months past 41Ca dosing in four of seven subjects, and we are currently assessing correlations between bone turnover and outcomes such as disease progression, skeletal related events and death. Conclusions: This work is the first direct measurement of long-term calcium metabolism in advanced prostate cancer, providing a basic scientific complement to cellular and collagen-based measures of bone formation and resorption rates as well as a correlation to clinically relevant outcomes. Trial accrual is ongoing and additional analyses are expected.
Risk of hyperglycemia attributable to everolimus in renal cell and non–renal cell carcinoma patients: A meta-analysis.
Authors: Kevin Y Xu, Raji Shameem, Shenhong Wu
Journal: Journal of Clinical Oncology (2016)

515 Background: Everolimus has been used widely in cancer patients and is associated with the development of hyperglycemia. Due to confounding factors, everolimus’ specific impact on hyperglycemia has not been well understood. We performed a meta-analysis to determine the risk of hyperglycemia attributable to everolimus in cancer patients of varying tumor types. Methods: PubMed and ASCO conference abstracts up to June 2015 were systematically searched. Eligible studies included randomized controlled trials (RCTs) in which everolimus was compared to placebo in cancer patients with or without additional cancer therapies. Heterogeneity tests were performed to examine between-study differences in hyperglycemia. The incidence and relative risk of all-grade and high-grade hyperglycemia attributable to everolimus were determined using random- or fixed-effects models. Results: A total of 7 phase III and 2 phase II RCTs with various tumors were included in our analysis. Everolimus significantly increased the risk of all-grade (RR = 2.60, 95% CI: 2.03-3.31, P &lt; 0.001) and high-grade (RR = 3.00, 95% CI: 1.72-5.23; P &lt; 0.001) hyperglycemia. The incidences of all-grade and high-grade hyperglycemia attributable to everolimus were 6.8% (95% CI: 3.4-13.2%) and 2.5% (95%: 1.2-4.9%) respectively. The everolimus-specific risk of all-grade hyperglycemia varied significantly with tumor types (P &lt; 0.001), with the highest incidence seen in renal cell carcinoma (27.2%, 95% CI: 22.2-32.8%) and the lowest in breast cancer (3.3%, 95% CI: 1.3-8.2%). No significant variation was found between everolimus alone or everolimus in combination with other agents. Similar results were also found for the risk of high-grade hyperglycemia attributable to everolimus. Conclusions: The specific contribution of everolimus to both all-grade and high-grade hyperglycemia may be modified significantly by tumor types. Close monitoring should be given to patients with renal cell carcinoma.
The impact of early thromboembolic event on prognosis in cancer patients: A single-center analysis of 1,838 patients.
Authors: M. Bozkurt, K. Okutur, K. Aydin, E. Namal, A. Öztürk, C. Tecimer, Z. Akcali, G. Demir
Journal: Journal of Clinical Oncology (2011)

e19694 Background: Thromboembolic events (TE) are common complication of cancer, may lead to mortality and detoriate quality of life. “Initial period”, (first 3 months) after the diagnosis of cancer holds the highest risk for development of cancer-associated TE. Methods: Between 2007 to 2010, we retrospectively evaluated the occurence of TE in patients with histologically confirmed solid tumors. The diagnosis of TE is confirmed by radiology and patients were treated accordingly. One hundred five of 1838 patients (5.7%) were diagnosed as TE. Twenty nine of 105 patients (28%) had TE at initial period and 76 (72%) had TE at delayed (later than three months) period. Results: There was no statistical significant relationship for age and gender between TE and non-TE groups. Forty three (41%) had distal lower extremity (DLE) deep venous thrombosis (DVT), 33 (31%) had PE and the rest includes 15 central/proximal DVT (14%), 8 PE with DLE DVT (8%), 4 central venous catheter-related DVT (4%) and 2 upper extremity DVT (2%). Frequencies for TE according to histopathology were; Non Hodgkin’s lymphoma (6/36=16.7%), pancreatic cancer (13/79=16.5%), gastric cancer (17/152=11.2%), NSCL (adenocarcinoma) (9/82=11%), GBM (4/53=7.5%) and colorectal cancer (21/312=6.7%). Median survival was 30.5 months for TE group and 127 months for non-TE group (log-rank, p=0.0001). Median time from diagnosis to TE was 7.25 months. Median overall survival was 15 months and 34.25 months for patients with TE at initial period and with delayed TE (log-rank, p=0.011), respectively.The diagnosis of TE were more frequent in advanced stage (stage I-II vs stage III-IV, 13/105=12% vs 92/105=88% respectively, p=0.0001) and with histology of adenocarcinoma (84/105=80% vs 21/105=20% respectively, p=0.016). Odds ratio (OR) for TE in patients with adenocarcinoma histology was 1.8 [ 95% confidence interval (CI):1.1-2.9], and with advanced stage, OR was 4.35 [95% CI:2.42-7.84]. OR for TE in patients with adenocarcinoma at advanced stage was 2.54 [95% CI:1.44-4.49] Conclusions: In our patient cohort, having TE at initial period, histology of adenocarcinoma and advanced stage emerged as independent prognostic factors for poor survival in cancer patients.
<i>In vitro</i> and <i>in vivo</i> analysis of synergistic antitumor effects of interferon-α and sorafenib in renal cell carcinoma
Authors: M. Eto, A. Takeuchi, T. Ohki, K. Tatsugami, S. Naito
Journal: Journal of Clinical Oncology (2008)

16143 Background: Sorafenib and sunitinib, a multi-kinase and tyrosine-kinase inhibitor, respectively, have demonstrated anti-tumor activity in patients with advanced renal cell carcinoma (RCC), which led to their approval by the FDA for this indication. Recent reports have shown the ability of these targeted agents to synergize with cytokines, such as Interferon (IFN)-α (JCO 25:3288, 2007), leading to a greater anti-tumor activity. In this study, we sought to understand the underlying mechanism for the synergism of sorafenib and IFN-α in RCC both in vitro and in -bearing mouse models. Methods: The murine (RENCA) and human (ACHN, 786-O) RCC cell lines were used for the in vitro cell proliferation assay. ACHN and RENCA were transplanted subcutaneously (s.c.) into NCr-nu/nu and syngeneic BALB/c mice, respectively. Mice were co-treated with sorafenib and IFN-α, and tumor growth was monitored. For the RENCA model, immunological assays, such as CTL, NK activities and FACS analysis, were also performed. Results: In ACHN and RENCA cell lines, synergistic antiproliferative effects of IFN-α and sorafenib was clearly demonstrated in vitro by combination index value analysis. In 786-O cell line, the additional effects of IFN-α on the in vitro growth inhibition by sorafenib was also detected. In both ACHN NCr-nu/nu and RENCA BALB/c models, synergistic antitumor effects of IFN-α and sorafenib was clearly demonstrated, indicating the synergistic direct effects of each drug on tumor growth. In the RENCA BALB/c model, FACS data did not show any changes in CD4/8 ratio, % NK cells, % memory CD8 cells, % regulatory T cells, irrespective of the treatments received. However, in that model model, while sorafenib alone did not induce NK or CTL activity, IFN-α alone or in combination with sorafenib did induce these activities. Conclusions: Our results demonstrate a synergistic activity of IFN-α and sorafenib and provide a rationale for a combination therapy with IFN-α and sorafenib for the treatment of patients with advanced RCC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Dainippon Sumitomo Pharma Co., Ltd.
Predicting progression in patients followed with active surveillance for low-risk prostate cancer.
Authors: Itay Aharon Sternberg, Changhong Yu, Gal Elimelech Keren Paz, Philip H. Kim, Melanie Bernstein, Paul Lakin, Michael W. Kattan, Behdar Ehdaie, Vincent Paul Laudone, Peter T. Scardino, James Andrew Eastham, Karim A. Touijer
Journal: Journal of Clinical Oncology (2014)

38 Background: Due to the inability to predict progression and need for treatment, patients with low-risk prostate cancer (LRPC) managed by active surveillance (AS) are subjected to repeated biopsies and their possible complications. We developed a nomogram predicting the risk of progression in patients on AS for LRPC. Methods: A retrospective review of all patients enrolled in an AS program at Memorial Sloan-Kettering Cancer Center (MSKCC) between 1993 and 2012 was conducted. Demographic, clinical, and pathologic data for patients who met the inclusion criteria for AS (cT1 or cT2a, prostate-specific antigen [PSA] less than 10, Gleason 6 or less, no more than three positive biopsy cores and no greater than 50% involvement of any single core) on the diagnostic and the confirmatory biopsies were collected and used to develop a nomogram for predicting progression-free probability. Multivariable logistic regression analysis was used to model the association between each risk variable (age, PSA levels, clinical stage, biopsy features) and disease progression. Progression was defined as failure to meet the inclusion criteria during follow up. Results: A total of 1,095 patients were enrolled in an AS program at MSKCC during the study period, of which 680 met the inclusion criteria for AS on both the diagnostic and the confirmatory biopsies and had available follow-up. At a median follow-up of 3 years 101 patients progressed. A nomogram predicting the progression-free probability was designed based on characteristics at diagnosis, result of a confirmatory biopsy and the number of negative and positive surveillance biopsies to date. A concordance index of 0.596 was calculated. Conclusions: Conditioned upon external validation, this nomogram can be used to counsel patients on their risk of progression and their surveillance protocol can be adjusted appropriately, possibly avoiding unnecessary biopsies and preventing biopsy-related complications.
Dendritic cell immunotherapy in non-small cell lung cancer
Authors: Y. Choi, J. Chung, H. Shin, G. Cho, C. Sohn
Journal: Journal of Clinical Oncology (2008)

14013 Background: Therapeutic outcomes of definitively treated non-small cell lung cancer (NSCLC) are very poor. In the past two decades, adoptive immunotherapy, based on tumor-infiltrating lymphocytes or lymphokine-activated killer cells, has been used in clinical trials. Dendritic cells (DCs) are highly specialized immune cells derived from bone marrow stem cells which are unique in their ability to initiate and maintain primary immune responses. The purpose of this trial is to decide dosage and to evaluate the clinical efficacy, immune responses, and safety by injecting dendritic cell vaccine in non-small cell lung cancer. Methods: In this clinical trial, maximum tolerated dose (MTD) was decided through the three step evaluations by initially injecting 3, 6, 12 X 106 autologous dendritic cells into the dermis for 3 times per 2 weeks and later 2 more times monthly in NSCLC. Enroll patients had completely standard therapy. Autologous dendritic cells were manipulated using GM-CSF and IL-4 for maturation and tumor lysate was loaded to DC by electroporation, pulse, or combination of both. Results: A total of 15 patients were enrolled from January 2004 to April 2006, and they were vaccinated with autologous tumor-lysate- pulsed monocyte-derived DCs. the maximum dosage of 12X106 cell decided in this trial was safe. At the end of the clinical trial, the tumor estimation was conducted for 8 patients with 1 case of SD (12.5%) and 7 cases of PD (87.8%). To assess the potential to generate a tumor-specific immune response, an assay developed to determine intracellular IFN-γ production before and after vaccination. IFN-γ was examined in 9 patients. Immune responses were increased after 4th vaccination in 5 patients, all were more than 100% response rate. this response was not correlated to clinical outcome. Conclusions: MTD, 12×106 cell in this trial proved to be safe and the possibility of new treatment is suggested considering the fact that the patients in this trial were the ones who failed in the standard therapy or were not eligible for the therapy. No significant financial relationships to disclose.