tbuckley/cabot-search huggingface dataset:
The effectiveness of a structured exercise and education program on clinical and quality-of-life outcomes in patients with cancer who are actively undergoing therapy compared with patients not currently receiving therapy.
Authors: L. M. Leach, A. Kleski, K. Spencer, J. Anthony, M. LaLonde, T. J. Sweeney, T. Caulin-Glaser
Journal: Journal of Clinical Oncology (2011)

9140 Background: While studies have demonstrated the impact of exercise on cancer patients, there is limited research available on the effect of a structured exercise and education program on clinical and quality of life outcomes in cancer patients actively undergoing treatment. Methods: Cancer survivors (n = 118, female = 108, males = 10) completed an 8-week exercise program meeting two days per week as a group (94 = breast cancer, 24 = other cancers). Twenty-nine participants (25%) were actively undergoing chemotherapy or radiation. Anthropometrics, functional capacity (6-minute walk), muscular endurance, symptoms of depression (Beck Depression Inventory-II), fatigue (Revised Piper Fatigue Scale), and QOL (SF-36) were assessed upon program entry and exit. Those who attended ≥70% of the exercise and education sessions were included in this analysis. For each outcome measure, paired t-tests were performed using SAS software. Results: Statistically significant improvements in functional capacity (p=<.0001), muscular endurance (p=0.0062 for lower body) and (p=0.0007 for upper body), flexibility (p=0.0123), QOL scores (mental (p=0.0012) and physical (p=0.0059) component summary scores) and fatigue (p=0.0097) were seen in patients actively undergoing treatment. Those patients actively undergoing treatment did not show a significant reduction in symptoms of depression compared to cancer patients not undergoing treatment. Conclusions: A structured, group-based exercise and education program significantly improved cancer patients’ functional capacity, QOL, and fatigue levels in cancer patients, especially those actively undergoing treatment. This type of program can serve as a unique setting to help improve the functional and psychological outcomes of cancer patients, especially those actively undergoing chemotherapy or radiation.
Multidisciplinary process improvement to optimize oral chemotherapy safety.
Authors: Stephanie Buia Amport, Kerin B. Adelson, Monica Fradkin, Renee Havriliak, Michelle Renee Harrison, Osama Abdelghany, Stephanie Kregling, Jessica Wright, Bret Morrow, Roberta Sterling, Mandeep Smith, Frank Esposito, Martha Stutsky, LeeAnn Miller, Rogerio Lilenbaum, Catherine A. Lyons, Anne C. Chiang, Howard Cohen
Journal: Journal of Clinical Oncology (2016)

134 Background: The rapid development of oral chemotherapy agents brings unique challenges. These drugs must be treated with the same vigilance as parenteral chemotherapy. The oral chemotherapy system is not optimized or integrated across our hospital. A quality assessment survey identified the need for a better means to monitor and improve oral chemotherapy patient outcomes. Methods: Patient and staff satisfaction with the current process was measured. A chartered multidisciplinary task force reviewed existing practice and developed a program to identify patients, ensure drug access, standardize prescription and consent, ensure on-going clinical support including patient education, regimen specific adherence monitoring, toxicity assessment and address patient concerns. Current state process mapping and gap analysis identified eighty-seven points where care could break down. A risk mitigating model was developed to include clinically reviewed electronic orders, nursing and pharmacist order review, specialty pharmacy, Medication Assistance Program (MAP) to assist with access and co-payment, patient education, day 5 and 21 pharmacist to patient phone calls, multidisciplinary flow sheet documentation, EMR report to track patients and outcomes and standardized patient education and provider training. The implementation team addresses process challenges identified via clinical team feedback e.g. therapy delays and implements fixes. Results: See table below. Specialty pharmacy revenue is directed to supporting non-profit clinical care at a time when revenue sources are being cut. MAP co-pay support exceeds $2.3 million. Conclusions: A patient-centered multidisciplinary care model integrating clinical, operational, financial and technology resources optimized care. Our improvement approach created opportunities for collaboration between pharmacists, physicians and nurses and can be adapted for many settings. [Table: see text]
The natural history of preoperative indeterminate pulmonary nodules in patients with resectable pancreatic adenocarcinoma.
Authors: Dennis C. Nguyen, Stephanie Chang, Zhou Gongfu, Andrea Wang-Gillam, David Linehan, William G Hawkins, Steven M Strasberg, Christine Menias, Constantine Raptis, Ryan C. Fields
Journal: Journal of Clinical Oncology (2013)

161 Background: Preoperative abdominal imaging often detects indeterminate pulmonary nodules (IPN) in patients with resectable pancreatic adenocarcinoma. The natural history of IPN in this setting is not well characterized. Methods: Patients with adenocarcinoma of the head of the pancreas who underwent pancreaticoduodenectomy (PD) were queried from a prospectively maintained database. Pre- and postoperative imaging was reviewed and IPN characterized and analyzed for associations with nodule progression and overall survival (OS). Results: 463 patients underwent PD for adenocarcinoma of the head of the pancreas from 2000-2010. Of these, 329 (71%) had reviewable pre-operative imaging. 48 patients (15%) had pre-operative IPN (non-calcified) identified with follow-up imaging available for review. The only pre-operative factor associated with the presence of IPN was increasing age (68 v. 64 years; p=0.003). 8 patients (12%) had new or enlarging nodules, of whom 5 (7%) had confirmed pulmonary metastatic adenocarcinoma. There was no difference in OS between patients with or without pre-operative IPN (2-year OS 41% v. 38%, respectively; p=0.37). Further, no radiographic criteria of IPN (including # of, size of, bilateral, calcified, solid, spiculated, smooth, lobular, or ground-glass nodules) was associated with OS. On follow-up, new or enlarging nodules were not associated with OS. Conclusions: IPN are often found in patients undergoing PD for pancreatic adenocarcinoma. The majority of IPN remain stable on post-operative imaging. Neither the presence of IPN nor nodule characteristics was associated with OS. These data do not support the routine additional workup of pre-operative IPN in patients with resectable adenocarcinoma of the head of the pancreas; however, larger studies are needed to further characterize the significance of IPN in the preoperative evaluation of patients with pancreatic adenocarcinoma.
Establishment and characterization of patient-derived tumor xenograft using gastroscopic biopsies in gastric cancer.
Authors: Lin Shen, Jing Gao, Yan Zhu, Tiantian Tian, Yan Yan Li, Na Li, Jianling Zou
Journal: Journal of Clinical Oncology (2015)

68 Background: The patient-derived tumor xenograft (PDTX) model has become the most realistic model for preclinical studies. PDTX models of gastric cancer using surgical tissues are reported occasionally; however, the PDTX model using gastroscopic biopsy, which is presented in this study, is very rare. Methods: A total of 185 fresh gastroscopic biopsies of gastric cancer were subcutaneously transplanted into NOD/SCID (Nonobese Diabetic/Severe Combined Immunodeficiency) mice. The characteristics of PDTX were identified by hematoxylin and eosin (H&amp;E) staining, immunohistochemistry (IHC), dual-color in-situ hybridization (DISH), and targeted next-generation sequencing. Chemosensitivity of PDTX model was tested using chemotherapy regimens based on patients. Results: Sixty-three PDTX models were successfully established (34.1%, 63/185) and passaged to maintain tumors in vivo, and the mean latency period of xenografts was 65.86±32.84 days (11-160 days). Biopsies of prior chemotherapy had a higher transplantation rate (52.1%, 37/71) than biopsies after chemotherapy (21.9%, 25/114; P&lt;0.01). No differences were found between the latency period of xenografts and characteristics of patients. The pathological and molecular features of PDTX as well as chemosensitivity were highly consistent with those of primary tumors of patients. The genetic characteristics were stable during passaging of PDTX models. Conclusions: PDTX models using gastroscopic biopsies in gastric cancer were demonstrated for the first time, and the biological characteristics of the PDTX models were highly consistent with patients, which provided the best preclinical study platform for gastric cancer. [Table: see text]
Preclinical antitumor activity and mechanisms of action of apricoxib, a clinical COX-2 inhibitor.
Authors: F. Burrows
Journal: Journal of Clinical Oncology (2011)

543 Background: Apricoxib, a selective COX-2 inhibitor, is currently in phase II trials, but its anticancer mechanisms of action could be better defined. Apricoxib inhibits COX-2 enzymatic activity and suppresses production of PGE 2 and VEGF at low nanomolar concentrations but also directly inhibits tumor cell proliferation and survival with 10-20μM potency. In this study we characterized the in vivo activity of apricoxib in xenograft models of lung, breast and colorectal carcinoma. Also, we examined the relationship between the PK, PD and antitumor activity and the effect of the drug on both tumor cell-autonomous functions and aspects of the tumor-host relationship in the HT29 model. Methods: Human tumor xenografts were grown in nude mice and apricoxib was given daily PO. Drug levels were quantified by LC-MS and VEGF levels by ELISA. Vessel density, apoptosis, proliferation and EMT were assessed by immunohistochemistry. Results: Apricoxib significantly retarded tumor growth in NSCLC models and also enhanced the efficacy of SOC drugs in breast and lung tumors. In the HT29 model, the drug was active at both doses tested. Drug concentrations in plasma and tumors peaked at 2-10 μM within an hour and decreased rapidly to submicromolar levels but concentrations persisted above the active concentration for inhibition of PGE 2 production for &gt;24h. This strongly indicates that apricoxib exerts its in vivo activity via blockade of COX-2-dependent PGE 2 production. Plasma VEGF levels decreased to zero for 6h post-dose, but returned to baseline by 24h. CD31 and Endomucin staining revealed no drug effect on microvessel density, although the percentage of immature vessels was reduced, as determined by pericyte coverage/NG2 expression. Apoptosis was significantly increased by TUNEL in apricoxib-treated tumors. PCNA analysis revealed a decrease in proliferating cells. ECAD expression was significantly increased in treated animals, whereas ZEB1 expression was lower, suggesting that COX-2 activity also plays an important role in EMT. Conclusions: Apricoxib possesses antitumor activity as a single agent and in combination. In the HT29 model, apricoxib inhibits tumor proliferation and survival, normalizes tumor vasculature and reverses EMT. [Table: see text]
Phase 1/2 dose escalation trial of the prostate-specific membrane antigen (PSMA)-targeted immunoconjugate MLN2704 in patients with progressive metastatic castration-resistant prostate cancer (CRPC)
Authors: M. I. Milowsky, M. Galsky, J. Lewin, C. P. Rozario, L. Owens, T. Marshall, D. Nanus, I. J. Webb, H. I. Scher
Journal: Journal of Clinical Oncology (2005)

4615
Is the International Germ Cell Consensus Classification (IGCCC) sufficiently predictive in 2015?
Authors: Craig R. Nichols, Claudio Jeldres, Christian K. Kollmannsberger
Journal: Journal of Clinical Oncology (2015)

387 Background: The IGCCC has been an invaluable tool to guide clinical trial development in disseminated germ cell tumors. This classification was developed in the early 1990s. The data were abstracted from records of pts treated between 1975 and 1990 and &gt; 100 institutions submitted data. This analysis resulted in the development and validation of a simple system based on clinically derived parameters. Three risk groups were identified for disseminated nonseminoma.; “good risk” group with a predicted 5 year overall survival (OS) &gt; 90%, ‘intermediate risk” with a 5 yr OS of 75% and “poor risk” with a predicted 48% 5 yr OS. Recently, a number of clinical trials and large institutions have reported outcomes in intermediate and poor risk disseminated germ cell tumors. Outcomes reported exceed IGCCC predictions. We hypothesize that the IGCCC substantially underestimates outcomes in the modern era. Further we speculate that a re-analysis of existing clinical trial data would be fruitful in predicting outcomes for disseminated germ cell tumors in the 21st century. Methods: Reports from large randomized clinical trials reporting outcomes in intermediate and poor risk disseminated germ cell tumors were reviewed and estimates of Progression Free and Overall survival made. Results: See Table. Conclusions: Compared to the IGCCC predictions based on data from 25-40 years ago, there appears to be improved overall survival in disseminated germ cell tumors in the modern era. Intermediate risk and poor risk disease appears to have OS exceeding 80-85% and 75% respectively. A more accurate prediction of outcomes with standard treatments should inform clinical trial design going forward. [Table: see text]
PSA doubling time of ≤6 months as the optimal cutoff for predicting clinically relevant outcomes for men receiving salvage radiation therapy post radical prostatectomy.
Authors: William C. Jackson, Skyler B. Johnson, Benjamin Foster, Corey Foster, Yeohan Song, Darren Li, Howard Mark Sandler, Ganesh S. Palapattu, Daniel A. Hamstra, Felix Yi-Chung Feng
Journal: Journal of Clinical Oncology (2013)

167 Background: Short PSA doubling time (PSADT) after biochemical recurrence (BR) post radical prostatectomy (RP) is known to predict worse outcomes following salvage external beam radiation therapy (SRT). The ideal PSADT cut-off, however, in this context remains uncertain. In this study, we sought to identify the best PSADT cut-off for predicting clinical outcomes following SRT for BR after RP. Methods: 575 patients who received SRT at a single institution for BR after RP were retrospectively reviewed in an IRB approved analysis. The impact of PSADT on biochemical failure (BF), distant metastasis (DM), prostate cancer-specific mortality (PCSM), and overall survival (OS) was assessed using Kaplan-Meier and Cox Proportional Hazards models. Results: Median follow up was 56.7 months post SRT. PSADTs could be calculated for 277 patients. PSADT strongly predicted BF, DM, PCSM, and OS on univariate analysis regardless of cut-off point. There was no statistical difference in BF, DM, PCSM, or OS between patients with PSADT &lt;3 (n=40) and 3-6 months (n=61) or between 6-10 (n=62) and &gt;10 months (n=114). A difference existed in BF (p&lt;0.01 HR: 2.2 [95%CI: 1.4-3.5]) and DM (p=0.02 HR: 2.2 [95%CI: 1.2-4.3]) between PSADT of 3-6 and 6-10 months. PSADT ≤6 had the largest positive predictive value (PPV) for BF (70%), DM (36%), and PCSM (13%) at 5 years. There was no difference in negative predictive value between a PSADT &gt;10 vs. &gt;6 months for BF, DM, PCSM, and OS with 5 year rates of (60% vs. 60%, 86% vs. 86%, 99% vs. 98%, and 95 vs. 94% respectively). On multivariate analysis PSADT ≤6 was a strong predictor of BF (p&lt;0.01 HR: 2.1 [95%CI: 1.5-3.0]), DM (p=0.01 HR: 2.0 [95%CI: 1.2-3.4]), and PCSM (p=0.04 HR: 2.3 [95%CI: 1.1-5.2]), with a trend towards predicting OS (p=0.12 HR: 1.5 [95%CI: 0.9-2.6]). Conclusions: A PSADT ≤6 months was the best predictor of outcomes in our data set, particularly for DM and PCSM. Currently, the most common predictive nomogram for SRT uses PSADT &lt;10 months as the cut-off point for BF. These results suggest that using a PSADT of ≤6 months may improve the ability to predict clinically significant outcomes and hence identify men who may benefit from additional therapy.
hFlt3 Expression Marks Long-Term Hematopoietic Stem Cells, but Not the Pathway Common to Granulocyte/Monocyte and Lymphoid Lineages in Human Hematopoiesis.
Authors: Yoshikane Kikushige, Goichi Yoshimoto, Toshihiro Miyamoto, Fumihiko Ishikawa, Hiromi Iwasaki, Mine Harada, Koichi Akashi
Journal: Blood (2006)
Toxicities of the anti-PD-1 immune checkpoint antibody nivolumab in the acute inpatient setting.
Authors: Norman Brito-Dellan
Journal: Journal of Clinical Oncology (2016)

227 Background: Knowledge of immune-system regulation led to the discovery of immune checkpoints molecules, which have demonstrated anti-tumor activity across various malignancies. These advances represent a new set of challenges for clinicians, including non-oncologists treating the cancer patient, who must develop a working knowledge of the mode of action of these agents, their unique response kinetics, and how to diagnose and effectively manage their toxicities. Nivolumab is a monoclonal immune checkpoint antibody that binds to the PD-1 receptor on T-cells, blocking PD-1 pathway-mediated anti-tumor immune response inhibition. Methods: Review of current literature and analysis of 3 cases of patients with Nivolumab-related toxicities at a major cancer center. Results: Case #1: 74 years-old female with NSCLC who was started on nivolumab after developing disease progression with various regimens. Nivolumab was held 4 months later due to development of erythematous, edematous papules and plaques, with overlying ulcerations and crust in forearms, thighs and trunk. Also, paronychias and loss of nail beds in both great toes. She developed no new lesions after discontinuation of immunotherapy. Case #2: 71 years-old male with right lung NSCLC, started on Nivolumab after evidence of disease progression after completion of carboplatin/paclitaxel. Four months later developed grade 2 Nivolumab-induced pneumonitis; this was withheld and ultimately discontinued due to persistent pneumotoxicity in spite of corticosteroids. Case #3: 41 years-old male with synchronous right lung ALK-positive adenocarcinoma, on crizotinib, and left lung squamous cell carcinoma, on nivolumab. He developed nivolumab-induced ANCA-negative glomerulonephritis, which was discontinued while continuing the crizotinib. His renal function normalized 3 months later, with GFR going from 14 to 122. Conclusions: Most adverse events with the anti-PD-1 agent Nivolumab are generally reversible after discontinuation of therapy, yet some high-grade immune-related adverse events require management with corticosteroids and other immune modulating agents. Further research is needed.
Impact of the endoscopic ultrasound on the management of the lung carcinoma: A single center experience
Authors: P. Singh, P. Mukhopadhyay, Y. Jadhav, R. M. Reddy, B. Camazine, J. C. Lasiter, C. Jinadatha, R. A. Erickson
Journal: Journal of Clinical Oncology (2005)

7187 Background: Recent studies have shown that EUS-FNA is an accurate test for the cytological diagnosis & staging (D&S) of the lung carcinoma (LC). In our center, EUS was introduced for a prospective study on LC. The purpose of this study was to determine the impact of EUS-FNA on management of the lung cancer. Method: Data were collected from Jan. 2002 to Nov. 2004 on subjects with suspected LC. CT-guided FNA, bronchoscopy, mediastinoscopy/surgery and PET scan were commonly used tests for the D&S. EUS-FNA was introduced as an alternative test for the D&S in Nov. 2003. The three years (2002, 2003, 2004) were compared for the total number of patients with LC, the test that established the tissue diagnosis, complication rate due to diagnostic procedures, proportion of patients that required the invasive procedures (mediastinoscopy) for the staging of the NSCLC. ANOVA & Chi-square test were used to compare the three years for continuous & dichotomous variables, respectively. Result: There was positive trend in the use of EUS for establishing the cytological diagnosis and histological type of LC. In 2004, EUS was the commonest procedure to establish the tissue diagnosis of the LC. Overall complication rate due to diagnostic procedures for suspected LC were significantly low in 2004 as compared to that in 2002 and 2003. EUS-FNA detected metastases to mediastinum in 40% of cases in 2004. There was significant reduction in the proportion of patients undergoing mediastinoscopy for the staging of Non-small cell lung carcinoma (NSCLC) in 2004 as compared to 2002 and 2003. Conclusion: There is a positive trend in the usage of the EUS for the diagnosis & staging of the lung cancer, which is associated with significant lowering of the overall complication rate due to other diagnostic procedures and negative trend in use of invasive procedure (mediastinoscopy) for staging of the NSCLC. We recommend that EUS should be incorporated in the routine diagnostic work up of the lung carcinoma. No significant financial relationships to disclose.
Overall and abdominal adiposity in a prospective colorectal cancer patient cohort: The COPE study.
Authors: Erin M. Siegel, Kristen Maddox, Bridget Riggs, Ione G. Townsend, Jazmin Calzada, Domenico Coppola, David Shibata
Journal: Journal of Clinical Oncology (2014)

467 Background: Obesity is an important risk factor for colorectal cancer (CRC); however, the exact role of adiposity on CRC remains unknown. Our overarching hypothesis is that abdominal fat, specifically visceral fat, through alterations in pro-inflammatory and tumor-promoting factors (e.g., IGF-1 or insulin) promotes aggressive tumor behavior and proliferation. To address this hypothesis, we have established an ongoing cohort of CRC patients [Colorectal Outcomes, Prognosis and Epidemiology (COPE) Study] with repeated adiposity and blood measures during the first year post-diagnosis. The objective of this study is to begin examining differences in diagnostic overall and abdominal adiposity by clinicopathological factors. Methods: Newly diagnosed patients with invasive adenocarcinoma of the colon or rectum were enrolled from 2010 to 2013 (N=213). Baseline overall adiposity by body mass index (BMI) and abdominal adiposity by waist circumference (WC) were collected. In a pilot study in 30 cases, baseline levels of IGF, IGFBP3, insulin and glucose to examine if serum markers were associated with obesity among CRC patients. The differences were evaluated by gender and clinical factors using ANOVA. Results: This study included 126 male and 87 female CRC patients with a median age of 64 years (range: 29-93). A majority of the patients were Caucasian (94%), married (68%), and never smokers (59%). The mean BMI and WC were 27.6±5.2 kg/m 2 and 96.5±15.8 cm, respectively. WC, but not BMI, was significantly higher among men (p=0.02), among patients with colon cancer (p=0.01), with higher stage (stage I/II vs. III/IV; p=0.02) and in high grade tumors (p=0.03). Serum IGFBP3 was significantly elevated in patients with abdominal adiposity (p=0.004) and colon cancer (p=0.004). Conclusions: Excess abdominal adiposity (WC) was related to advanced stage and high grade, whereas overall adiposity (BMI) was not. This study highlights the prevalence of abdominal adiposity and its potential biological importance among CRC patients. The development of more refined techniques (e.g. CT-based) of further defining the visceral and subcutaneous components of abdominal adiposity in cancer patients may prove to be informative.