tbuckley/cabot-search huggingface dataset:
Demographic trends in clinical trial withdrawal rate within the Bubble Study: Updated analysis.
Authors: Elizabeth Carloss Riley, Anthony E. Dragun, Kelly McMasters, Amy R. Quillo, Charles Raben Scoggins, Xiaoyong Wu, Shesh Rai, Dharamvir Jain
Journal: Journal of Clinical Oncology (2014)

71 Background: There are well described barriers to clinical trial participation among varied racial/ethnic and demographic groups. Little is known about clinical trial drop-out rate among these groups. This is an updated analysis of the demographic and clinical characteristics of patients who originally enrolled in the “Bubble Study” clinical trial but then withdrew at a later date. Bubble Study is a non-blinded, prospective observational cohort study designed to assess the adherence rate of adjuvant endocrine therapy among women with early stage breast cancer. Methods: From Aug 2012 to April of 2014, 88 women were enrolled. Demographic data (age, race. insurance status) and treatment factors (stage, surgery type, therapy duration, co-morbidites) were collected. Comorbidities were defined as none, moderate (1-3) or significant (&gt;3.) Descriptive statistics were produced for the entire cohort and the subjects of cohort. Frequencies were compared using a Chi-square test (Fisher’s exact test when expected cell frequencies are small). Results were declared significant at significance level of 5% and all analyses are performed using SAS (2003, 2005). Results: At the time of analysis, 86 patients enrolled (E), 41 of which withdrew (W.) Blacks represented 21% of the total E. Private insurance represented the majority (60.4% of those E and Medicare, Medicaid and Uninsured followed in that order (24.4%, 14% and 1.2% respectively.) There was no significant difference with regards to race and insurance between the E and W group although there was a trend toward a higher rate of W among Blacks (p=0.21). Stage, surgery type or age did not predict for W. Comorbidites had a marginal effect on W (p=0.02) The most common reasons reported for W were financial and/or insurance reasons (22%) and inconvenience of pharmacy pick up (15%.) Conclusions: Demographic characteristics that traditionally predict for under-representation in clinical trial enrollment did not predict for W from the Bubble Study. Although this sample size is small this data may suggest disparities in clinical trial participation are largely due to enrollement rather than withdrawal. Continued analysis of this trial and others will help confirm these findings. Clinical trial information: NCT01694225.
Tumor size as a prognostic factor for patients with colon cancer undergoing sentinel lymph node mapping and conventional surgery.
Authors: Sukamal Saha, Mohammed Nawaf Kanaan, Mohammed Shaik, Benjamin Abadeer, Alpesh Korant, Madhumitha Krishnamoorthy, Sunil Kaushal, T. Trevor Singh, Madan L. Arora, David Wiese
Journal: Journal of Clinical Oncology (2013)

546 Background: Unlike other solid tumors, tumor size (TS) is not a part of the TNM staging for colon cancer (CC). Our goal is to correlate TS with TNM staging, nodal positivity(NP), and 5-year overall survival (OS) for patients (pts) with invasive CC undergoing sentinel lymph node mapping (SLNM) vs. conventional surgery (CS). Methods: A retrospective review of 681 pts with invasive CC were reviewed and divided into two groups of pts (SLNM and CS). The pts in these two groups were subdivided according to the TS in four groups (0-2, 2-4, 4-6 and more than 6 cm). 461 pts underwent SLNM between 1996-2010 compared to 220 pts who underwent CS between 1996-2006. The pathology reports reviewed for TS (the maximum diameter of the primary tumor), T staging, and NP. The OS was calculated from the social security database and our hospital cancer registry. Then all data was compared between both groups. Results: Pts with TS &lt;2cm were mainly T1+T2 (72%, 70%), whereas tumors &gt;6 cm, majority of pts wereT3+T4 (94%, 85%). T1+T2 percentage consistently decreased as TS increased, and T3+T4 percentage was increasing consistently with increased TS (Table 1A). NP according to TS for SLNM pts were (16%, 53%, 56%, 48%) NP and for CS pts were (15%, 32%, 34%, 39%). In both groups, NP increased as TS increased compared to 0-2 cm group. The overall NP in both groups was 47% and 31% (Table 1B). OS for SLNM and CS pts were calculated in each group according to TS. Overall SLNM pts had better OS when compared to CS pts (65 %, 54%). Conclusions: Increasing TS was consistent with increasing T staging for both SLNM and CS pts. NP and OS were worse with increased TS for SLNM and CS pts. SLNM pts had higher NP and better outcome in OS when compared to CS pts, hence TS should be considered as a prognostic factor in pts with adenocarcinoma of the colon. [Table: see text]
Do high symptom scores trigger clinical actions by providers? Assessing the effect of standardized symptom screening.
Authors: J. Sussman, H. Seow, D. Bainbridge, G. R. Pond, L. Martelli-Reid
Journal: Journal of Clinical Oncology (2011)

9127 Background: Standardized cancer symptom screening is being used increasingly in cancer care systems. It is assumed that by using a standardized approach to symptom screening, the quality of care will be improved. Since 2007, Ontario cancer centres have implemented an electronic version of the Edmonton Symptom Assessment Scale (ESAS) at every patient visit. To date, there is little research documenting the relationship between screening and resultant clinical actions. This study examines how ESAS scores are associated with rates of symptom documentation in the patient chart and clinical actions taken. Methods: Retrospective chart reviews on a random stratified sample of visits by ambulatory lung and breast cancer patients at a large regional cancer centre. The dependent variable was ESAS symptom scores for pain and shortness of breath, categorized by severity: 0=none, 1-3, 4-6, and 7-10=severe. Outcomes included symptom documentation in the chart on the visit date and symptom-related action(s) taken within a week. Chart reviewers were blinded to ESAS scores. Results: 912 unique visits were reviewed, 25% from each score category. Pain and shortness of breath were documented in 51.8% and 29.7% of charts and a related action occurred in 16.9% and 3.9% of charts respectively. The proportion of visits that had pain documented increased significantly (36.9%, 49.2%, 55.2%, and 71.4%; p<0.001) as ESAS score category increased. Likewise, from low to high ESAS score category, the proportion of visits that had a pain-related action increased significantly (4.2%, 10.6%, 21.3%, and 37.0%; p<0.001). Similar trends were found for shortness of breath but at much lower rates with overall only 11.1% having evidence of actions taken when the symptom was documented in the chart. Conclusions: Our results illustrate the link between standardized symptom screening and clinical actions. However, substantial opportunities for improvement remain as symptom-related actions were documented infrequently, even when symptoms were reported as severe. Future research that addresses this apparant gap between screening and actions is important to support the concept of routine screening to improve quality of care.
Neoadjuvant treatment of clearly resectable colorectal liver metastases.
Authors: D. A. McCain
Journal: Journal of Clinical Oncology (2011)

e14154 Background: Neoadjuvant chemotherapy for clearly resectable colorectal metastases has not been evaluated since these patients have been traditionally refered to surgery first. However, at the authors institution with a high referal pattern to Medical oncology first, several patients with resectable colorectal metastases were treated with upfront chemotherapy then refered to surgery. Methods: From january 05, 2005 to December 02, 2010 a total of 257 patients underwent a liver resection and 78 were identified as having been treated with 3 to 6 cycles of FOLFOX/FOLFOX Avastin prior to hepatectomy. The aim of this study was to assess the overall survival of these patients. The patient population comprised patients whose primary lesion was less than 5cm and those whose lesion was greater than 5cm at the time of original diagnosis.The continous data were sumarized using mean (SD) after ascertaining that the data followed the normal distribution using Shapiro-Wilk test. Time to death was measured fom date of surgery to date of death. Time to death was assessed using Kaplan Meier product limit estimate. This evaluation was presented as median (95% CI) of overall survival. Each Kaplan Meier curve included the number of patients alive (at risk of death) at every time point used in the axis of the plot.Kaplan Meier curves for each lesion size class were compared using a two sided log-rank test. Any P<0.05 was considered statistically significant. Results: For the patients under study, the median survival with lesion size< 5cm (n=55) was 40.0 months and the median survival of patients with lesion size> 5cm (n=23) was51.0 months. The log rank test revealed a statistically significant difference (p=0.0448).This result indicates patients with lesions < 5cm were more likely to die than patients with lesions grater than 5cm. Conclusions: Neoadjuvant chemotherapy in resectable colorectal metastases reduces survival possibly by a compromise of surgical resection margins with significant volume reduction in smaller lesions (noted on follow up imaging and inra-operative ultrasonography) versus larger lesions.
Early detection of colorectal neoplasia: Combination of eight cancer-associated blood-based protein biomarkers.
Authors: Ib J. Christensen, Michael Wilhelmsen, Susan Gawel, Xiaoqing Yang, Nils Brunner, Frans Martens, Annike Heijboer, Gerard Davis, Hans J. Nielsen
Journal: Journal of Clinical Oncology (2016)

488 Background: Assessment of 8 blood based protein markers for identifying colorectal neoplasia. Methods: 4,698 subjects scheduled for first time ever colonoscopy with symptoms potentially attributable to colorectal neoplasia were accrued. Plasma levels of AFP, CA19-9, CEA, hs-CRP, CyFra21-1, Ferritin, Galectin-3, and TIMP-1 were determined by using the Abbott ARCHITECT i2000 automated immunoassay platform. Three clinical endpoints were chosen for this presentation: 1. CRC, 2. CRC and high risk adenoma, 3. CRC and other cancers. Logistic regression was used for statistical analysis of each endpoint. A final reduced model was selected choosing the best combination of 4 markers with the highest likelihood score statistic. Results: 512 CRC’s were identified, 323 CC and 189 RC. Malignancies other than CRC were detected in 177 subjects, 699 adenomas were identified including 298 with high risk, 1342 subjects had non-invasive bowell disease, and 1978 had a “clean” colon. Univariate analysis of each endpoint demonstrated that all markers were statistically significant. Multivariable logistic regression showed that the blood based markers in combination significantly predicted the 3 endpoints. The reduced model resulted in the selection of CEA, hs-CRP, CyFra21-1 and Ferritin for the 3 endpoints. The area under the receiver operating characteristic curves were 0.83, 0.74 and 0.82 respectively. The postive predictive value (PPV) at 90% sensitivity was 18% for endpoint 1 and the negative predictive value (NPV) was 97%. For endpoints 2 and 3, the PPV’s were 25% and 20% and the NPV’s were 93% and 96%. Conclusions: A subset of 4 biomarker in combination identify subjects with a high risk of CRC.
Response to cabazitaxel in CRPC patients previously treated with docetaxel and abiraterone acetate.
Authors: Carmel Jo Pezaro, Sylvestre Le Moulec, Laurence Albiges, Aurelius Gabriel Omlin, Yohann Loriot, Diletta Bianchini, Marine Gross-Goupil, David Lorente, Thibault de la Motte Rouge, Philippe Beuzeboc, Gerhardt Attard, Aline Guillot, Karim Fizazi, Johann Sebastian De Bono, Christophe Massard
Journal: Journal of Clinical Oncology (2013)

155 Background: Cabazitaxel, which is a tubulin-binding chemotherapy, and the CYP-17 androgen biosynthesis inhibitor abiraterone acetate (AA) are both approved for patients with metastatic castration resistant prostate cancer (CRPC) following docetaxel chemotherapy. Recent preclinical data suggest that taxanes impact AR signalling and could imply cross-resistance between new AR targeting treatments and taxane chemotherapy. The aim of this study is to evaluate the antitumor activity of cabazitaxel after AA. Methods: We retrospectively evaluated antitumor activity of cabazitaxel in patients (pts) with metastatic CRPC and progressive disease after docetaxel and AA. Radiological response by RECIST, PSA response by PCWG2 criteria and symptomatic benefit were examined. Results: 89 pts were treated with third-line cabazitaxel, after docetaxel (median 8 cycles; range: 4-12), and AA (median duration of treatment 4.8 months, range: 1-55 months). At cabazitaxel initiation median age was 68 years (range: 53-83), ECOG performance status was 0 or 1 in 70% of pts, and median PSA was 309 ng/ml (range: 3.75-9150). Bone, lymph node and visceral metastases were present in 80 pts (89%), 37 pts (41%), and 12 pts (13%) respectively. An average of 6 cycles of cabazitaxel (range 1-15) were administered. All pts had PSA data available and 44 (49%; 95% CI 39-60%) had a 50% or greater PSA decline. In the 35 pts with RECIST evaluable disease, 7 (20%; 95% CI 8-37%) had a partial response. Conclusions: In men with metastatic CRPC cabazitaxel appears to retain activity in the third-line setting following docetaxel and AA.
Usage of Oregon’s Death With Dignity Act (DWDA).
Authors: Charles David Blanke, Michael Leo LeBlanc, Dawn L. Hershman, Lee M. Ellis, Frank L. Meyskens
Journal: Journal of Clinical Oncology (2016)

44 Background: In 1997, OR enacted a voter initiative allowing terminally ill residents to self-administer physician-prescribed medication to end their lives. Statute requires prescriptions written for lethal medications be reported; the state also collects demographic and intended use data. We wished to to evaluate and report participation trends. Methods: OR's Public Health Division gathers compliance forms from prescribing/consulting physicians, pharmacists, and psychiatrists, prescribing physician follow-up forms, and death certificates. Data from 1998-early 2016 were reviewed, collated, and interpreted. Results: 1,545 prescriptions were written; 991 pts died from legally-prescribed lethal medication. The % of prescription recipients dying from drug use per yr ranged from 48-82, with no significant trend (logistic regression 2-sided p = .90) The prescribing rate increased 12%/yr on average through 2013, with a 28% increase in 2014 and 40% in 2015, not explainable by growth in population. Characteristics of 991 pts dying from drug: Most recipients had cancer (77%); 8% had ALS, 4.5% lung disease, 2.6% heart disease, and 0.9% HIV. 5.3% were sent for psychiatric evaluation. M/F (%) 51.4/48.6; median age (years) 71 (range 25-102); race white/black/asian/hispanic (%) 97/0.1/1.3/1; hospice Y/N (%) 90.5/9/5. 94% died at home. Estimated median time between intake and coma (min): 5 (range 1-38); to death (min): 25 (range 1-6240). 3.3% had known complications. Reasons for DWD (%): ADL not enjoyable 90; loss of autonomy 92, dignity 79, or bodily functions 48; inadequate pain control 25; financial 3. Conclusions: The number of prescriptions written for ORDWDA medications increased annually since enactment. The % of recipients self-administering drugs has varied. Very few pts are referred for psychiatric consultation prior to DWD. Most pts dying from lethal medications have cancer, and the overwhelming majority expire at home. Medications used are effective and rapidly acting. Little evidence exists disadvantaged pts are disproportionally using DWD. Pts use DWD for reasons related to QOL, autonomy, and dignity, and relatively rarely because of inadequate pain palliation. Future studies should evaluate why many pts prescribed lethal drugs choose not to take them.
Evaluation of a genomic-based prognostic test for metastasis in high-risk post-prostatectomy patients: Does it impact physician decision making?
Authors: Ketan K. Badani, Darby J. S. Thompson, Anirban Pradip Mitra, Mercedeh Ghadessi, Christine Buerki, Elai Davicioni, Penelope J. Wood
Journal: Journal of Clinical Oncology (2013)

196 Background: Currently, identification of individual patients who are truly at risk of developing lethal prostate cancer after radical prostatectomy (RP) is based on clinical nomograms. A prospectively validated genomic classifier (Decipher) has been shown to more accurately predict metastatic disease post RP than established clinical predictors and can identify patients with adverse pathology who may be cured by RP alone and may therefore not require additional treatment. Methods: An IRB-approved study assessed the impact of a genomic classifier (GC) test in 240 pathologically high-risk post RP case reviews. Twenty (20) urologic oncologists from 18 institutions reviewed 12 cases presented in a randomized, de-identified fashion via a secure online platform to provide treatment recommendations pre- and post- patient GC test results. Possible recommendations included referral to radiation oncologist and/or initiation of adjuvant hormones, close observation, or other. The primary endpoint was any change in treatment recommendation after unblinding of GC test results. Confidence in treatment recommendations was assessed using a 5-point Likert scale. Results: Following unblinding of GC test results, treatment recommendations changed in 43% (95% CI: 37-49) of all cases. Specifically, among cases with a pre-GC recommendation involving treatment, 31% (95% CI: 23-41) of respondents changed their recommendation to observation post-GC.Respondents considered the GC result to have influenced their recommendation in 63% (95% CI: 56-68) of cases. The addition of information provided by the GC result increased decision making confidence in 39% (95% CI: 30-49) of cases where a change of treatment recommendation was made. Following unblinding, physicians reported that the GC result was clinically relevant in 84% (95% CI: 79-84) of cases. Conclusions: GC appears to influence treatment recommendations and decision making confidence for high-risk prostatectomy patients. This study suggests that clinical implementation of GC may potentially impact treatment recommendations.
Overexpression of CTLA-4 in the Bone Marrow of Patients with Multiple Myeloma As a Sign of Local Accumulation of Immunosuppressive Tregs – Perspectives for Novel Treatment Strategies
Authors: Walter Moises Tobias Braga, Andre Luiz Vettore, Ana Carolina Carvalho, Djordje Atanackovic, Gisele W.B. Colleoni
Journal: Blood (2011)
Prospective study of paresthetic neurotoxicity from oxaliplatin-based regimens in the treatment of colorectal cancer.
Authors: X. S. Wang, D. R. Fogelman, C. Eng, M. Malekifar, R. J. Reynolds, N. A. Shah, T. R. Mendoza, K. Y. Glover, P. M. Dougherty, C. S. Cleeland
Journal: Journal of Clinical Oncology (2010)

3585 Background: Paresthetic neurotoxicity attributed to oxaliplatin-based chemotherapy is a treatment limiting factor in the administration of chemotherapy. The term neuropathy is often associated with pain, but many distressing components of neuropathy may emerge at different timing of therapy, and measurable by patient reported outcomes. Longitudinal studies could establish the development pattern of neuropathy-related symptoms during chemotherapy trajectories. Methods: Patients undergoing oxaliplatin-based chemotherapy (FOLFOX) for colorectal cancer (n = 59) rated symptoms weekly during chemotherapy via the M. D. Anderson Symptom Inventory (MDASI). Symptom responses were analyzed by mixed-effect modeling controlled for age, sex, diabetics, and cancer staging. Results: A third of the sample was female; 17% were older than 65 years. Controlling for covariance, the severity of patient-reported numbness/tingling increased steadily each week in following 12 weeks after started therapy (p < 0.001). The numbness/tingling increased significantly from the fifth week compared to baseline (about third cycle of therapy) (mean diff = 0.9 on the MDASI's 0-10 scale, p = 0.004). In contrast, pain severity remained very low during the first 13 week (about 6 cycles) of chemotherapy, but increased significantly thereafter (p < 0.001). Female gender seemed related to an increase in the severity of numbness (p < 0.01) but not with pain. Previously diagnosed diabetes related to higher severity of numbness (p < 0.01). The five most severe symptoms were numbness, fatigue, sleep disturbance, drowsiness, and distress on MDASI symptom items. Conclusions: To our knowledge, this prospective study is the first to use longitudinal analysis of patient-reported symptom burden in the early development of paresthetic neurotoxicity and other major symptom burden from oxaliplatin-based chemotherapy in colorectal cancer patients. Considering about 40% of colon cancer patients did not complete planned adjuvant FOLFOX due to dose limiting toxicity (Romanus et al, NCCN ASCO 2009 Abstract), our results indicate the importance of early intervention for managing paresthetic neurotoxicity and other major symptom burdens. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Bristol-Myers Squibb, Daiichi Sankyo, Genentech, sanofi-aventis
Possible role of autophagy inhibition in hypoxia-induced chemoresistance of pancreatic cancer cells.
Authors: Yoon Ho Ko, Young-Seok Cho, Hye Sung Won, Eun Kyoung Jeon, Young Seon Hong
Journal: Journal of Clinical Oncology (2012)

224 Background: Autophagy is a catabolic process and provides metabolic support for the cell by degradation of intracellular macromolecules. Various types of stress, including hypoxia, activate autophagy. Recent studies have suggested that hypoxia has been shown to associate with resistance to chemotherapy and radiation therapy and hence poor prognosis in pancreatic cancer. This study investigated the role of autophagy in the treatment of pancreatic cancer with gemcitabine under hypoxic condition. Methods: To evaluate the role of autophagy inhibition in hypoxia-induced chemoresistance, BxPC-3 human pancreatic cancer cell line was used under normoxic and hypoxic conditions.We evaluated the extent of LC3-II, as an autophagosome marker, induced by gemcitabine, by western blotting to measure the hypoxia- or chemotherapy- induced autophagy. We then examined the effects of gemcitabine on induction of apoptosis under normoxic and hypoxic conditions. Next, to determine the effect of 3-MA, a known inhibitor of autophagy, on overcoming hypoxia-induced chemoresistance, the MTS assay and flow cytometry were performed. Results: Compared with normoxia, gemcitabine-induced cell death under hypoxia was significantly decreased, as a result of the reduced apoptosis. Western blotting analysis demonstrated that LC3-II was increased under hypoxia, compared with normoxia.However, we found that 3-MA can enhance the growth inhibition and apoptotic effect of gemcitabine, even under hypoxia. These findings mean that autophagy mediates the chemoresistance under hypoxia. Conclusions: Activated autophagy plays a role in hypoxia-induced chemoresistance of pancreatic cancer cells. These findings may have important implications for future therapeutic strategies using gemcitabine against pancreatic cancer.