tbuckley/cabot-search huggingface dataset:
Influence of demographics on patient refusal to enroll into clinical trials
Authors: M. V. Midathada, T. Spencer, K. Mack, L. Erkman, R. Govindarajan
Journal: Journal of Clinical Oncology (2005)

6038 Background: Elderly and minority patients are known to be underrepresented in clinical trials. Patient refusal to participate in clinical trials is an important factor. We conducted a retrospective analysis of a data base established at our institution to explore the demographic patterns of patients who declined to participate in clinical trials and to identify whether the distance from cancer centers is a factor for poor accrual. Methods: Between 1994 and 2004, 1303 patients were considered for clinical trials at our institution. The distance of patient’s residence from the cancer center was divided into 25 mile segments based on zip codes. Multivariate logistic regression was used to assess the influence of age, sex, race and distance on refusal for enrollment. Results: There were 594 (45%) males, 709 (54%) females, 1098 (84%) Caucasians (C), 204 (15%) African Americans (AA) and one of other race. 247 (19%) did not meet eligibility criteria, 190 (14%) refused to participate, 764 (58%) were eligible and participated in a trial and 98 (7%) were not enrolled for other reasons. 30% lived within 25 miles, 30% were more than 100 miles away and 40% were from suburban location (25 - 100 miles). For those who refused, the median age was 57.2 years (range 17–89); the median distance was 60.3 miles (range 0–1255). There was no significant influence of age, sex, or distance on refusal in univariate analysis. A multivariate logistic regression model adjusted for age, race, sex and distance found evidence of a gender by age interaction when males and females were modeled separately. The model for females found that elderly females (>65 years) declined more than younger females (OR 1.01, p=0.07), and AA females refused more than C females (OR 1.71, p=0.03). Distance was not a significant factor (p=0.831). There were no significant factors associated with refusal in the model for males. Conclusion: Elderly female and AA female patients are more likely to refuse participation in clinical trials compared to the other subgroups and may have to be targeted for further analysis to look at the contributing reasons. Distance did not impact the patient decision to participate. No significant financial relationships to disclose.
Prediction of lung cancer using volatile biomarkers in breath
Authors: M. Phillips, N. Altorki, J. H. M. Austin, R. B. Cameron, R. N. Cataneo, J. Greenberg, R. Kloss, R. A. Maxfield, H. I. Pass, W. N. Rom, O. Tietje
Journal: Journal of Clinical Oncology (2005)

9510 Background: In patients with lung cancer, induction of high risk cytochrome p450 genotypes may also accelerate catabolism of volatile organic compounds (VOCs) produced by normal metabolism (e.g. alkanes and alkane derivatives). A breath test for these VOCs can detect alterations in their abundance, and potentially identify a set of biomarkers of lung cancer. Methods: VOCs in 1.0 L alveolar breath collected over 2.0 min were analyzed in 195 patients with untreated primary lung cancer and 212 control subjects without lesions at chest CT. 268 subjects were randomly assigned to a training set to construct a fuzzy logic model of breath VOC markers of lung cancer, and 139 to a prediction set, where the model was tested as a predictor of lung cancer. Results: A fuzzy logic model employing 29 VOCs predicted primary lung cancer with 90.6% sensitivity, 82.7% specificity, and 0.91 area under curve (AUC) of the receiver operating characteristic (ROC). When all 407 subjects were combined in a leave-one-out analysis employing 29 VOCs, the model predicted primary lung cancer with 81.5% sensitivity, 87.3% specificity, 0.91 AUC, negative predictive value=99.6% and positive predictive value=11.6%. ROC curves were similar in TNM stages 1 through 4. The breath test predicted lung cancer in post-operative primary lung cancer patients (77/80), and in pre-operative and post-operative cases of cancer metastatic to lung from another site (12/13), mesothelioma (6/6), and suspicious chest imaging without biopsy evidence of cancer (40/41). Conclusions: Lung cancer, including early stage, can be predicted with a two-minute breath test for VOCs. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Menssana Research, SystAim GmbH Menssana Research Menssana Research Menssana Research
Non-small cell lung cancer biomarkers: Discovery using mab proteomics.
Authors: L. Takacs, M. Guergova-Kuras, I. Kurucz, N. Tardieu, J. Kadas, C. Malderez-Bloes, A. Jullien, Y. Kieffer, B. Dezso, B. Karger
Journal: Journal of Clinical Oncology (2011)

10561 Background: A challenge in the treatment of lung cancer is the lack of early, pre-symptomatic diagnosis. Here, we describe the application of monoclonal antibody proteomics approach to profile the natural plasma proteome for the discovery of lung cancer biomarkers. Methods: We produced large monoclonal antibody (mAb) libraries directed against the natural form of complex mixtures of protein antigens present in the plasma of non-small cell lung cancer (NSCLC) patients. Lung cancer specific biomarkers in the plasma were detected via high throughput ELISA with mAbs. Antigen identification and specificity of the selected antibodies was determined using immunoprecipitation followed by mass spectrometric analysis. The presence of the biomarkers in non-small cell lung cancer tissues was validated by immunohistochemistry. Results: Differential profiling of plasma proteomes of four clinical collections, totalling 301 patients with lung cancer and 235 healthy controls, identified twenty four monoclonal antibodies recognizing protein biomarkers specific for NSCLC. The majority of the selected mAbs detect antigens present in non-small cell lung cancer cells in-situ. Our study confirms previously reported circumstantial evidences for the association with lung cancer for four of the identified biomarkers and provides an independent validation in larger multi-centric clinical collection for the association of their plasma concentrations to the presence of lung cancer. Multivariate analysis of the biomarker results generated with one of these collections (214 NSCLC cases of which 128 in stage I and 169 healthy controls) yielded a five biomarkers classifier that could discriminate NSCLC cases from healthy controls with 77% sensitivity and 87% specificity. The performance of the classifier was validated in an independent collection and combination with well known a NSCLC biomarkers showed additive effect and combined performance of 84 % sensitivity at 95 % specificity. Conclusions: Using the mAb proteomics approach we have identified a panel of monoclonal antibodies associated with specific protein biomarkers that could be readily transferred to a simple screening test for the early detection of non-small cell lung cancer.
Psychological state and trait correlates of quality of life prior to radiotherapy for prostate cancer.
Authors: Sara J Walker, Yiyi Chen, Kyungjeen Paik, Brandy Mirly, Alexis K Fields, Charles R. Thomas, Arthur Hung
Journal: Journal of Clinical Oncology (2016)

129 Background: Improvement in cancer treatment has increased need to focus on survivors’ quality of life (QOL). Survivors often experience psychological stress, with impact on QOL and disease-related mortality. Better understanding the heterogeneity in individuals’ psychological adjustment to cancer diagnosis and treatment may help identify the most valid screening practices and patients most in need of psychosocial support. The specific aim of the current study investigates correlates of psychological state and trait with QOL prior to radiotherapy for localized non-metastatic prostate cancer. We hypothesized 1) positive correlations with QOL and trait Extraversion, Openness, and Conscientiousness, and 2) negative correlations between QOL and state depression/anxiety and trait Neuroticism. Methods: The PHQ-9, GAD-7, and NEO-FFI-3 assessed depressive state, anxiety state, and personality traits, respectively. The FACT-P assessed physical, social, emotional, and functional well-being. Our sample (n=29) had median age of 68 (range 52-79) and education of 16 years (range 10-20). Race/ethnicity: 89% European-American, 4% African-American, 7% Other. Association between constructs was assessed by Pearson’s correlation coefficient. Results: Higher depression, anxiety, and Neuroticism were negatively associated with physical (p &lt; 0.04), emotional (p &lt; 0.01), and functional (p &lt; 0.02) well-being, and well-being related to prostate cancer-specific concerns (p &lt; 0.01). Trait Agreeableness was associated with emotional (p &lt; 0.01) and functional (p &lt; 0.01) well-being. Extraversion was associated with social (p &lt; 0.05) and functional (p &lt; 0.02) well-being. Openness was associated with functional well-being only (p &lt; 0.03). Contrary to hypothesis, Conscientiousness did not significantly correlate with any measured aspect of QOL. Conclusions: Assessing psychological risk and protective factors prior to radiotherapy may help identify patients in most need of psychosocial supports, informing effective screening protocols and individualized treatment planning. Future directions include prospectively measuring predictive value of baseline risk and protective factors on post-treatment QOL.
Liposomal Nanoparticles Carrying anti-IL6R Antibody to the Tumour Microenvironment Inhibit Metastasis in Two Molecular Subtypes of Breast Cancer Mouse Models
Authors: Chunlei Guo, Yanan Chen, Wenjuan Gao, Antao Chang, Yujie Ye, Wenzhi Shen, Yunping Luo, Shengyong Yang, Peiqing Sun, Rong Xiang, Na Li
Journal: Theranostics (2017)

Tumour microenvironment (TME) contributes significantly towards potentiating the stemness and metastasis properties of cancer cells.IL6-Stat3 is one of the important cell signaling pathways in mediating the communication between tumour and immune cells.Here, we have systematically developed a novel anti-CD44 antibody-mediated liposomal nanoparticle delivery system loaded with anti-IL6R antibody, which could specifically target the TME of CD44 + breast cancer cells in different mouse models for triple negative and luminal breast cancer.This nanoparticle had an enhanced and specific tumour targeting efficacy with dramatic anti-tumour metastasis effects in syngeneic BALB/c mice bearing 4T1 cells as was in the syngeneic MMTV-PyMT mice.It inhibited IL6R-Stat3 signaling and moderated the TME, characterized by the reduced expression of genes encoding Stat3, Sox2, VEGFA, MMP-9 and CD206 in the breast tissues.Furthermore, this nanoparticle reduced the subgroups of Sox2 + and CD206 + cells in the lung metastatic foci, demonstrating its inhibitory effect on the lung metastatic niche for breast cancer stem cells.Taken together, the CD44 targeted liposomal nanoparticles encapsulating anti-IL6R antibody achieved a significant effect to inhibit the metastasis of breast cancer in different molecular subtypes of breast cancer mouse models.Our results shed light on the application of nanoparticle mediated cancer immune-therapy through targeting TME.
Proteomic Pattern-Based Risk Stratification of Outcome Shows Significant Higher Accuracy Compared to HCT-CI in Patients with AML and MDS,
Authors: Christiane E Dobbelstein, Jochen Metzger, Elke Dammann, Uwe Borchert, Stefanie Buchholz, Michael Stadler, Matthias Eder, Juergen Krauter, Arnold Ganser, Eva Mischak-Weissinger
Journal: Blood (2011)
Efficacy of subcutaneous testosterone on menopausal symptoms in breast cancer survivors.
Authors: Rebecca L. Glaser, Anne E. York, Constantine Dimitrakakis
Journal: Journal of Clinical Oncology (2014)

109 Background: Menopausal symptoms can be severe in breast cancer survivors in whom estrogen therapy is contraindicated. Our previous pilot trial demonstrated that testosterone (T) combined with anastrozole (A) in subcutaneous implants provided therapeutic T levels without elevating estradiol. Our current goal was to document the clinical effect of T+A combination implants (no estrogen) on menopausal symptoms. Methods: This IRB approved study was designed to prospectively follow breast cancer survivors (stage 0-4) treated with subcutaneous T+A, for breast cancer recurrence. The therapeutic effectiveness of T on the relief of psychological, somatic and urogenital symptoms was documented using the validated, self administered, 11 item Menopause Rating Scale. Patients completed the survey prior to and following therapy. Results: Over 950 T/T+A pellet insertions have been performed in breast cancer survivors since 2006. Since 4/2013, 72 patients have been enrolled in the study. T dosing is weight based. Implants are inserted at 3-month intervals on average. Therapeutic T levels were confirmed without elevation of estradiol in any postmenopausal survivor. There have been no cancer recurrences in up to 8 years of therapy. A single patient with active metastatic disease at enrollment developed ascites. There was statistically significant improvement (P &lt; 0.0001) in psychological symptoms (depression, irritability/aggression, anxiety), somatic symptoms (hot flashes/sweating, heart discomfort, sleep problems/insomnia, physical exhaustion, impaired memory, joint/muscular pain) and urogenital symptoms (vaginal dryness, bladder problems/incontinence, sexual problems). Conclusions: Testosterone in combination with an aromatase inhibitor, delivered by subcutaneous implant, was extremely effective for the relief of hormone deficiency symptoms in breast cancer survivors. Furthermore, this supports testosterone’s therapeutic effect via the androgen receptor. [Table: see text]
Process mapping and time study to improve efficiency of HDR prostate brachytherapy.
Authors: Laura A. Doyle, Virginia L. Lockamy, Cheng Peng, Adam Dicker, Yan Yu, Robert Benjamin Den, Amy S. Harrison
Journal: Journal of Clinical Oncology (2014)

103 Background: New technologies and procedures have the potential to improve outcomes; however, initial implementation is often associated with a steep learning curve, decreased efficiency, and patient safety implications. Since process mapping, checklists and external benchmarks have been proven to be useful quality improvement (QI) tools in health care, we sought to use these QI tools in a novel setting to decrease new procedure times without sacrificing the quality of care. Methods: Implementation of a real-time, ultrasound based prostate high-dose-rate brachytherapy procedure involved a multidisciplinary team composed of approximately 6-8 team members and numerous complex tasks. To characterize time spent on various aspects of the procedure and improve efficiency, our team developed a detailed process map including checklists and team debriefings. A benchmark was created based on an experienced institution which has performed &gt;100 procedures annually. Times for key events, such as induction of general anesthesia, acquisition of first image, catheter insertion and completion of planning were recorded during each case. The process map was analyzed based on clinical tasks and treatment planning tasks. Results: The expert institution completed a procedure in 65 minutes. Over the course of ten cases at our institution, total procedure time ranged from 222-107 minutes. Implementation of the process map resulted in a reduction of total time by 52% (51% for clinical tasks and 65% for planning). Process improvements included changes to room layout, availability of supplies and identification of parallel processes. Improvement in efficiency was done without compromising quality as defined by dosimetric parameters. Conclusions: The implementation of a new procedure benefits from the integration and utilization of a process map. We were able to reduce procedure time significantly, which resulted in decreased time under general anesthesia, reduced risk of deep vein thrombosis and improved overall patient safety.
Prospective evaluation of quality of life (QOL) during a phase I/II study of adjuvant chemotherapy with image-guided high-precision radiotherapy for completely resected gastric cancer.
Authors: Rebecca Barbara Goody, Helen Mackay, Bethany Pitcher, Amit M. Oza, James D. Brierley, Joon-Hyung J. Kim, Rebecca Wong, Zahra Kassam, Carol Jane Swallow, Bernard Cummings, Robert Edward Dinniwell, Jennifer J. Knox, Anthony M. Brade, Laura A. Dawson, Melania Pintilie, Jolie Ringash
Journal: Journal of Clinical Oncology (2016)

164 Background: Adjuvant chemoradiotherapy improves overall and relapse free survival in patients with completely resected gastric cancer, but confers toxicity. This prospective phase I/II clinical trial assessed the toxicity, efficacy and QOL when adding bi-weekly cisplatin to adjuvant chemoradiotherapy with infusional 5-fluorouracil (5-FU). Phase I data showed promising outcomes with acceptable toxicity. Methods: Treatment comprised 45 Gy in 25 fractions of image-guided 3D-CRT or IMRT concurrently with weeks 3-7 of 12 weeks of infusional 5-FU. Cisplatin (up to bi-weekly) was added in a standard dose-escalation protocol. Patients completed the EORTC QLQ-C30 at baseline, end of radiotherapy, 4 weeks post chemotherapy and at 1 and 2 years. Results: Among 55 participants (mean age 54, range 28 to 77; 55% male; median follow-up 3.03 years), QOL compliance ranged from 93% at baseline to 70% at 4 weeks post-treatment. Maximal tolerable dose of cisplatin was 40 mg/m 2 bi-weekly for 4 cycles. OS and DFS rates are 85% and 74% respectively at 2 years. Mean scores for global QOL (median difference = -25, p &lt; 0.0001), role and social functioning, fatigue, nausea and vomiting, and appetite declined at completion of radiation; physical functioning showed a statistically significant decline of borderline clinical importance (median difference = -6.7, p &lt;.0001). All scales recovered by 4 weeks after chemotherapy except fatigue, which returned to baseline by one year. Conclusions: Adjuvant gastric chemoradiotherapy incorporating cisplatin worsened global QOL, fatigue, nausea and vomiting and appetite. Most scales recovered by 4 weeks post-chemotherapy. This regimen is tolerable not only by observer rated toxicity, but also by patient reported QOL measures. Clinical trial information: NCT00188266.
A program to increase use of chemoprevention for women with high-risk breast lesions.
Authors: Constance A. Roche, Kevin S. Hughes
Journal: Journal of Clinical Oncology (2012)

46 Background: Tamoxifen, raloxifene, and exemestane have been demonstrated to reduce risk of breast cancer in high-risk women, bututilization is very low.Among the reasons cited are lack of awareness and reluctance of physicians to prescribe. Women with high-risk breast lesions are generally candidates for chemoprevention and can be evaluated and counseled in a high-risk breast clinic. Knowledge about drugs that can prevent breast cancer may increase uptake among high-risk women. Methods: In a single practice, women with a diagnosis of atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), lobular carcinoma in situ (LCIS), or severe atypical ductal hyperplasia/borderline ductal carcinoma in situ are offered an extended visit with a nurse practitioner in the Breast and Ovarian Cancer Risk and Prevention Clinic. The visit includes data collection, patient interview about relevant history and personal preferences, risk assessment, including use of relevant models (via HughesRiskApps.com), and recommendations for surveillance and prevention. Emphasis is placed on understanding of individual risk as well as risks and benefits and appropriateness of chemoprevention and surveillance modalities. Based on personal and family history, women are advised if chemoprevention is appropriate to consider, their choice is made, and they are encouraged to have surveillance in the Breast Clinic. Results: Since January 2001, 487 women with a diagnosis of ADH, ALH or LCIS, or severe ADH have been evaluated and counseled in the Breast and Ovarian Cancer Risk and Prevention Clinic. 132/487 (27%) were advised against taking chemoprevention and 355/487 (73%) were appropriate for chemoprevention. Of those for whom chemoprevention was clinically appropriate, 188/355 (53%) took one of the medications, or participated in a chemoprevention trial. 53/188 (28%) did not complete therapy (discontinued at 2 weeks to 54 months) due to preference or side effects. 75 women have completed five years of therapy and 60 are currently on therapy. Conclusions: When provided with personalized information about breast cancer risk and the pros and cons of chemoprevention, many women will choose to take medication to reduce breast cancer risk.
A prospective paired survey of oncologist and patient attitudes toward therapeutic cancer clinical trial (CT) enrollment in a diverse academic health center patient population.
Authors: M. Ray, D. M. Smith, O. I. Olopade, B. N. Polite
Journal: Journal of Clinical Oncology (2010)

6120 Background: Cancer clinical trial (CT) enrollment is low, particularly for minorities. Few prospective studies simultaneously survey both the oncologists (MDs) and patients (pts) to identify barriers. Methods: New breast, colon, and lung cancer pts and their MDs completed a self-administered survey. Pts provided self ID race, comorbidities, social support, CT knowledge, health literacy, locus of control, health system trust, and basic sociodemographics. After the appointment, pts and MDs were asked about the CT discussion and reasons for nonenrollment. Results: 324 pts approached but 50 pts (16%) were not eligible, declined to participate, or withdrew consent. Of the remaining 274 pts, 246 pts (90%) and 201 MDs (73%) responses were obtained. Race: W-152 (62%), AA- 66 (27%), Hispanic-9 (4%), Asian-10 (4%), Other-5 (2%), Missing-4 (2%). AA had lower income (p<0.001), education (p<0.001), and health literacy (p=0.03). AA and W had similar comorbidities after controlling for income. AA were less likely to have heard of a CT (52%AA vs. 83%W, p<0.001). CT was available 59% overall and was marginally higher for W (49%AA vs. 63%W, p=0.1). For this subset, MDs offered CT to W at slightly higher, but not statistically significant rates (16%AA vs. 32%W, p=0.1) If CT available, AA were more likely to sign consent (35%AA vs. 12%W, p=0.006) and MDs reasons for not offering CT differed by race. MDs more likely did not offer to AA because of noncompliance (10%AA vs. 0%W, p=0.001) but more likely did not offer to W because of travel distance (15%W vs. 0%AA, p=0.03). No other barriers were seen by race if CT available. Regardless of race, a high rate of discordance was observed between MDs and pts regarding the CT discussion (Table). Conclusions: Improved MDs communication about treatment and CT discussion is required for all patients. If available, MDs offer CT similarly by race, but reasons for not offering differ by race. AA are more likely than W to sign consent even though AA are less familiar with CT overall. Was a CT discussed? Oncologists Yes No Patients Yes 33 (92%) 32 (38%) No 3 (8%) 54 (62%) Total 36 (100%) 86 (100%) No significant financial relationships to disclose.