tbuckley/cabot-search huggingface dataset:
Utilizing an A3 project to improve assessment of oral chemotherapy adherence across a five-site enterprise.
Authors: Marjorie Hepler, Kathleen Dunn, Debra Kay Allen, Diane Denny, Maurie Markman
Journal: Journal of Clinical Oncology (2016)

136 Background: Cancer Treatment Centers of America, Inc. (CTCA) is a national network of five hospitals that specialize in treating patients fighting complex or advanced-stage cancer. During the fall of 2013, two of the five centers began the pursuit of Quality Oncology Practice Initiative (QOPI) certification. A third site began QOPI certification the spring of 2014 and the remaining two sites followed suit the spring of 2015. This process brought attention to the patient population receiving oral chemotherapy and the importance of careful monitoring of those self-administering their cancer treatment regimens. In July of 2014, before the remaining two sites began the QOPI certification process, an A3 project was introduced to the enterprise, focusing on the assessment of patients’ toxicity and adherence to their oral chemotherapy regimen. The initial data suggested either a lack of documentation or missed opportunity for patient education with baseline performance data at 7.8% across the sites. Methods: Using A3 problem solving and education of care management teams at each site, a policy was composed and processes put in place to engage nursing in conducting follow up via telephone for those patients newly prescribed oral chemotherapy. This also included use of an acronym featured in the EHR to ensure appropriate documentation. Random chart reviews occurred monthly to monitor progress and to provide feedback to the nurses on proper documentation of assessment of adherence and toxicity. The goal was to attain a 60% composite score across the five centers with a score of 62% achieved, signifying a 694% improvement. Results: Once the patient received the oral chemotherapy, the care manager placed weekly calls to assess adherence and toxicities. Composite scores for fiscal year 2015 show a marked increase in the documentation of assessment of adherence in patients receiving oral chemotherapy. Conclusions: Involvement in problem solving and ongoing education of nursing regarding importance of assessment of adherence and toxicities of patients receiving oral chemotherapy significantly improves documentation ensuring high quality safe care. [Table: see text]
Comparison of native and adaptive immunity profiles of healthy volunteers and patients with well-differentiated thyroid cancer.
Authors: S. Hossain, C. Bhimani, Z. Chen, S. S. Ramalingam, D. M. Shin, C. Cohen, F. R. Khuri, E. Waller, T. K. Owonikoko
Journal: Journal of Clinical Oncology (2011)

5585 Background: Clinical studies indicate a strong association between the clinical outcomes of thyroid cancer and patients’ immunologic function. Modulation of negative regulators of immunity such as T regulatory cells (Tregs), CTLA-4 and PD-1 are promising strategies for the treatment of solid malignancies. We performed a prospective analysis of the immunologic profiles of thyroid cancer patients and compared frequencies of immune cells in the blood with those of healthy controls. Methods: We enrolled 23 patients (8 patients with active disease/15 patients in remission) and 15 healthy volunteers under an IRB-approved protocol. Multiparameter flow cytometry was performed on peripheral blood samples using 200-300 µL of RBC-lyzed samples. Cells were stained with antibodies against CD3, CD4, CD94, NKG2A, CD16, CD56, CD25, and Foxp3 (with appropriate isotype controls) and the numbers of NK, NK-T-cell, conventional T-cell and T-reg subsets/µL was determined. Differences in specific cell counts between patients and healthy control was assessed by F-test statistics and p value <0.05 was considered significant. Results: Blood samples from thyroid cancer patients had higher absolute numbers of Tregs and immune-regulatory CD94+ NK cells. There was no significant difference between patients and controls in total T-cell counts but total numbers of NK cells were higher in thyroid cancer patients than controls. Conclusions: Thyroid cancer patients have significantly more immune regulatory Tregs and functionally suppressed NK cells compared with healthy controls. This data suggests that increased numbers of negative regulatory immune cells may impact the clinical course of this disease. Modulating immune function may be a potential therapeutic strategy in thyroid cancer. Cell type Control (15) cells/µL Patients (23) cells/µL P value Total CD3+, CD4+ T cells 8,957 ± 641 9,211 ± 957 0.84 CD3+, CD4+, CD25+, [Foxp3+] Tregs 57 ± 11 295 ± 43 <0.0001 Total NK cells 1,318 ± 169 2,330 ± 315 0.008 Total NK+ CD94+ 673 ± 115 1,244 ± 209 0.02
6-Mercaptopurine (6MP) Intake during Maintenance for Childhood Acute Lymphoblastic Leukemia (ALL) - a Comparison of Self-Report and Electronic Monitoring: A Report from the Children's Oncology Group (COG) Study AALL03N1
Authors: Wendy Landier, Yanjun Chen, Lindsey Hageman, Heeyoung Kim, Bruce C. Bostrom, Jacqueline Casillas, David Dickens, William E. Evans, Kelly W. Maloney, Leo Mascarenhas, Arthur K. Ritchey, Amanda M. Termuhlen, William L. Carroll, F. Lennie Wong, Mary V. Relling, Smita Bhatia
Journal: Blood (2015)
FOLFOX4 regimen administered through combined hepatic arterial and systemic infusion for treatment of colorectal cancer with unresectable liver metastases.
Authors: M. Guan, C. Bai, S. Chen, H. Ying, X. Li, J. Zhou, Y. Shao, Y. Lin, X. Yang
Journal: Journal of Clinical Oncology (2011)

e14138 Background: Liver metastasis is the most common type of metastasis of colorectal cancer (CRC), and was found in 60-70% at autopsy. Only about 10% patients are amenable to hepatectomy, which is currently the only curative treatment. Hepatic arterial chemotherapy is an attractive alternative treatment to systemic chemotherapy, since 90% of blood supply to liver metastases is through hepatic artery, and that a higher drug concentration can be delivered to the metastatic tumor. Methods: Inclusion criteria: CRC patients with unresectable hepatic metastases and no prior chemotherapy during 2006-2009 in Peking Union Medical College Hospital were included. Treatment regimen: first day: HAI of oxaliplatin over 2h and L-folinic acid over 2h, followed by a bolus HAI of 5-fluorouracil (5-FU) then continuous HAI of 5-FU over 20 h; second day: Intravenous infusion of L-folinic acid over 2h followed by 5-FU bolus then continuous infusion of 5-FU over 22 h. The patients received HAI and systemic venous administration during the odd cycles, and the intravenous administration of the same regimen during the even cycles. Results: 27 colorectal cancer patients with unresectable hepatic metastases and no prior chemotherapy were enrolled in the study. A total of 236 treatment cycles were given with a median of 10 cycles. The therapy generated the following results after 6 cycles: CR 1/27 (3.7%), PR 16/27 (63.0%), SD 6/27 (22.2%) and PD 3/27 (11.1%). Four patients had hepatectomy. A median time to progression of 11 months and a median overall survival period of 24 months were documented. The major adverse events include grade±-II nausea/vomiting, upper abdominal pain, peripheral neuropathy, neutropenia/ thrombocytopenia. Conclusions: The FOLFOX4-like chemotherapy regimen was efficacious and safe for the treatment of metastatic CRC lesions in the liver, and facilitated the control of local lesions.
Strategies for protecting patients from anthracyline-induced cardiac dysfunction.
Authors: A. K. Dickey, C. Geisberg, Y. R. Su, I. A. Mayer, J. A. Means-Powell, C. Silverstein, X. Peng, D. Freehardt, B. White, D. J. Lenihan, D. Sawyer
Journal: Journal of Clinical Oncology (2011)

591 Background: Breast cancer affects 1 in 8 women in the US. Anthracyclines (AC) are highly effective chemotherapy agents for breast cancer; however, a subset of patients develop cardiotoxicity, with significant morbidity and mortality. Currently, physicians are unable to predict who may develop cardiotoxicity, and they have few strategies for protecting the heart during treatment. The role of exercise in modulating the effects of AC on the heart remains incompletely understood. We have found that mice who were allowed to exercise during AC exposure developed accelerated cardiac dysfunction as measured by echo. This led us to conduct a prospective study examining the effect of voluntary exercise on AC-associated cardiac dysfunction. Methods: In a prospective observational study, 32 newly-diagnosed breast cancer patients receiving AC were enrolled over 2 years. Baseline and post-AC echocardiograms and exercise questionnaires were completed. Subclinical cardiac dysfunction was defined as >5% decrease in ejection fraction from baseline or development of diastolic dysfunction. Results: Subclinical cardiac dysfunction was observed in 11 out of 32 patients (34.3%). None the 13 patients who were taking ACE inhibitors or beta blockers developed subclinical cardiac dysfunction, a statistically significant difference (p=0.001). Furthermore, those with higher self-reported physical activity prior to chemotherapy were 3.4 times less likely to develop subclinical decline in cardiac function (p=0.01). Conversely, patients with greater levels of physical activity during the weeks coinciding with chemotherapy experienced a 1.75 times higher incidence of subclinical cardiac decline, although not statistically significant (p=0.23). Conclusions: Patients on ACE inhibitors and beta blockers appear to be protected from subclinical cardiac dysfunction during AC. High physical activity prior to AC treatment was shown to protect against subclinical cardiac dysfunction; however, restriction of physical activity while on AC may protect against cardiac decline. Further work with a larger cohort of subjects is warranted to definitively address the interaction between physical activity and AC associated cardiac dysfunction.
Universal screening for depression in cancer patients and its impact on management patterns.
Authors: Amanda Shreders, Shehzad Niazi, David Hodge, Nicolette Chimato, Ankit Agarwal, Elaine Gustetic, William Adam Hammond, Bhagirathbhai R. Dholaria, Sikander Ailawadhi
Journal: Journal of Clinical Oncology (2016)

232 Background: Screening for distress in cancer patients (pts) is recommended by several national guidelines. High distress scores are associated with increased depression. We established universal depression screening and investigated its impact on cancer patient management. Methods: Patient Health Questionnaire (PHQ9) was administered to newly diagnosed cancer patients prior to receiving their first non-oral antineoplastic agent. Patient demographics, disease characteristics, chronic medication load, antidepressant use, treatment interruptions, weight change, referral and adherence to psychiatry were recorded. Pts with high (&gt; 9) and low (&lt; 4) PHQ9 scores were compared using Chi-square and Wilcoxon rank-sum tests. Results: Screening was performed in 1,190 consecutive pts over an 18 month period at Mayo Clinic. Responses were received from 1055 (89%) pts, of which 144 had high score (PHQ-H). These were compared with 99 randomly selected low score (PHQ-L) pts. The 243 pts (median age 65; range 18-92 years) in the final analysis included: 53.5% females, 90% Caucasians, 74% married and 77% living with others. Diagnosis was solid organ cancer in 81% and metastatic disease in 54% patients, and 13% were on antidepressants for preexisting depression. PHQ-H were more likely to be on antidepressants than PHQ-L (19% vs. 3%; p = 0.0002), be referred to psychiatry (69% vs. 12%; p &lt; 0.0001), attend psychiatry appointment (45% vs. 12%; p &lt; 0.0001) and require behavioral therapy (50% vs 8%; p = 0.0065). PHQ-H did not have a significantly increased antidepressant use, treatment interruptions (p = 0.5) or weight change (p = 0.4). Race, gender, chronic medication load, marital status, living situation, metastatic disease and type of cancer were not significantly different between PHQ-H and PHQ-L. Conclusions: We implemented a universal depression screening and management plan for cancer pts and noted that previously being on antidepressants was associated with higher patient distress. Higher score led to more frequent behavioral therapy, possibly preventing non-compliance or need for increased psychotropic medications. Our model identifies cancer pts with depression and implements an effective management plan for their care.
The Size of the Dendritic Cell Population At Diagnosis Worsens Prognosis in Acute Myeloid Leukemia – Bigger Is Not Better
Authors: Marta I Pereira, Ana I Espadana, Emília Cortesão, Gilberto P Marques, Catarina Geraldes, Adriana C Teixeira, Artur Paiva
Journal: Blood (2011)
Primary care physicians' endorsement of the importance of shared decision making in diverse cancer screening contexts.
Authors: Jennifer Elston Lafata, Richard F. Brown, Michael P. Pignone, Scott Ratliff, Laura Aubree Shay
Journal: Journal of Clinical Oncology (2016)

179 Background: Despite widespread advocacy, shared decision making (SDM) is not routinely used in office-based cancer screening discussions. We describe primary care physicians’ (PCPs) endorsement of the importance of SDM in different cancer screening contexts. Methods: Between 3/15-5/15 we administered a mailed survey to PCPs randomly selected from the American Medical Association’s Master File. Using 5-point Likert scales, we report PCP’s ratings of the importance of SDM for 11 specific screening scenarios graded by the US Preventive Service Task Force (USPSTF), four specific to not screening elderly patients. Multivariable logistic regression, accounting for repeated observations, was used to estimate the association of physicians’ endorsement of SDM as ‘very important’ with (1) USPSTF grade A [highest endorsement] vs. others, and (2) if scenario pertained to not screening among the elderly. The model controlled for physician age, gender, race, specialty, medical school affiliation, practice size, and PCP’s internal/external motivation for SDM. Results: PCPs were on average 52 years of age, 38% female, and 69% white (N = 288). They were most likely to rate SDM as ‘very important’ for colorectal cancer (CRC) screening in adults aged 50-75 (69%), and least likely for CRC screening in adults aged &gt; 85 (34%). Model results indicated PCPs were significantly (p &lt; 0.01) more likely to endorse SDM as ‘very important’ for A-grade services compared to others, particularly D-grade services (OR = 0.63), and less likely to do so when decision was not to screen among elderly (OR = 0.45). PCPs with more internal motivation for SDM were more likely to endorse its importance (OR = 2.29), but no other physician characteristic was associated with SDM endorsement. Conclusions: The more PCPs internally value SDM, the more likely they are to endorse it as very important regardless of screening scenario. Yet, PCPs’ endorsement varied by USPSTF grade, being particularly low when screening was not recommended, especially when the decision pertained to screening not recommended among elderly patients.
A phase I and pharmacokinetic single agent study of pazopanib (P) in patients (Pts) with advanced malignancies and varying degrees of liver dysfunction (LD).
Authors: S. Shibata, J. Longmate, V. M. Chung, H. Lenz, S. Kummar, J. Sarantopoulos, M. L. Harrison, T. W. Synold, S. P. Ivy, E. M. Newman
Journal: Journal of Clinical Oncology (2010)

2571 Background: P, an oral small molecule inhibitor of VEGFR-1,2,3, PDGFR-α, β, and c-Kit is FDA approved for advanced renal cancer. However the maximum tolerated dose (MTD) in Pts with varying degrees of LD has not yet been determined. Because P is primarily eliminated through the hepatic route, we sought to determine the MTD in Pts with advanced malignancies and LD. Methods: Pts with advanced malignancies, KPS ≥ 60%, adequate renal function, and hematologic values were enrolled in cohorts defined by degree of LD: none (N), mild (M) (bilirubin < 1.5x ULN or ALT > ULN), moderate (Md) (bilirubin > 1.5 – 3× ULN), and severe (S) (bilirubin > 3× ULN). Pts in the N cohort received P at the approved 800mg/d, while Pts in the other cohorts received doses according to a 2/6 phase I dose escalation schema. Dose-limiting toxicity (DLT) was defined as grade 4 hematologic toxicity, grade 3 nausea, diarrhea, or bleeding; any other grade 4 nonhematologic toxicity. Bilirubin increases leading to cohort changes of M or Md to S, or increases in S levels > 1.5x baseline for > 1-2 weeks were also DLTs. PK analysis was performed using a validated HPLC/MS/MS method. Results: 69 Pts are enrolled thus far (N-20, M-20, Md-17, S-12). 82.2% were white and 10.1% were Asian. 40.4% had colorectal cancer. Among evaluable Pts, the M cohort MTD was 800 mg/d with 1/6 Pts having an increased AST at 400 mg/d and 1/10 Pts with grade 5 bleeding at 800 mg/d. The Md cohort MTD was 200 mg/d with 2/6 Pts at 400 mg/d having DLT level increases in AST/ALT. 10 Pts have been treated at 200 mg/d without a DLT. Dose escalation in the S cohort is ongoing with the current dose at 100 mg/d. Conclusions: The MTD of P in M, Md, and S LD is 800mg/d, 200 mg/d, and not yet established respectively. Based on these data, a dose reduction in P is recommended for Pts with moderate or higher LD. Supported by U01 CA 62505. Preliminary steady-state P PK at week 3, normalized to a dose of 800 mg/day (medians andranges) Normal dose 800 mg(n=12) Mild dose 400 mg (n=5) Moderate dose 200 mg (n=7) Cmax (mg/ml) 48.6 (17.1–85.7) 45.4 (29.2–97.6) 95.6 (25.6–131.6) tmax (hr) 2.7 (1.0–24.1) 3.0 (2.0–4.1) 2.0 (1.0–4.0) AUC0-6 (mg × hr/ml) 249.1 (92.0–475.9) 250.2 (156.6–411.6) 507.6 (138.4–731.6) Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Wyeth
Comparative effectiveness of first-line chemotherapies in advanced non-small cell lung cancer.
Authors: Jennifer T. Chang, Michele M. Spence, Rita L. Hui, Joanne E. Schottinger, Nazia Rashid, Mirta Millares
Journal: Journal of Clinical Oncology (2014)

293 Background: There is a variety of chemotherapy regimens used as first-line treatment in advanced non-small cell lung cancer (NSCLC). Few studies have used real-world data to compare the clinical outcomes associated with different chemotherapy combinations. The study objective was to compare overall survival between chemotherapy regimens used for patients with advanced NSCLC in an integrated healthcare system. Methods: This retrospective cohort analysis included patients age 18 or older from Northern and Southern California Kaiser Permanente with a diagnosis of Stage IIIB/IV NSCLC identified in the cancer registry. First chemotherapy date occurred from January 2008 through September 2012 with at least 6 months of follow up to March 31, 2013. Overall survival was measured as the number of months from initial chemotherapy until death, end of enrollment or March 31, 2013. Chemotherapy regimens were categorized into five mutually exclusive groups: pemetrexed-based, pemetrexed + bevacizumab, bevacizumab-based, platinum doublets and singlets. Survival was compared between the five groups using Cox proportional hazard models, adjusting for age, gender, race, region, stage, histology, days from diagnosis to initial chemotherapy and Diagnostic Cost Group (DxCG) risk score. The analysis was performed for all age groups and by age over and under 65. Results: Among 1,989 adults, those that received singlet chemotherapy were at significantly increased risk of mortality compared to doublets (HR 1.23; 95% CI 1.02-1.49). Patients younger than 65 who had received pemetrexed + bevacizumab regimens were at significantly reduced risk of mortality (HR 0.58; 95% CI 0.35-0.95) when compared to platinum doublets. Among patients over 65, there were no significant differences in survival between the chemotherapy regimens. Conclusions: Adult patients with advanced NSCLC who are younger than 65 years old have improved survival after receiving pemetrexed + bevacizumab chemotherapy regimens compared to platinum doublet regimens. No survival differences were found between regimens in patients over the age of 65.
The effect of selective inhibition of HDAC6 with ACY1215 on bortezomib activity in multiple myeloma (MM).
Authors: L. Santo, T. Hideshima, A. L. Kung, M. Yang, D. Tamang, M. Jarpe, J. H. van Duzer, R. Mazitschek, D. Cirstea, K. Patel, J. Tseng, S. Rodig, S. Pozzi, J. Bradner, K. C. Anderson, S. S. Jones, N. S. Raje
Journal: Journal of Clinical Oncology (2011)

e18569 Background: HDACs are being studied as novel therapeutic targets in MM. Here, we investigated the preclinical activity of an HDAC6 selective inhibitor ACY1215 in MM, alone and in combination with bortezomib (BZ). Methods: In vitro enzyme assays were used to evaluate the selectivity of ACY1215. The cytotoxicity of ACY1215 versus pan-HDAC inhibitor (e.g. SAHA) were compared in MM cell lines, MM patient cells, MM osteoblasts (OB) and osteoclasts (OC), as well as peripheral blood mononuclear cells (PBMCs) from healthy donors. Western blotting and RT-PCR were used to identify the mechanisms of cell death. The activity of ACY1215 and BZ was confirmed in vivo using two different murine xenograft models of human MM, plasmacytoma model and disseminated MM model. Results: ACY1215 showed more potent inhibitory activity against HDAC6 (EC50 0.0054 µM) than SAHA. Like SAHA, ACY1215 triggered potent MM cytotoxicity but showed less toxicity than SAHA against PBMCs and activated T-cells. Low doses of ACY1215 with BZ showed synergistic anti MM activity, resulting in apoptosis via caspase-8,-9,-3 and PARP activation. Moreover, ACY1215 increased BZ-induced ER stress in MM cells, evidenced by induction of UPR components including PERK, CHOP and p-IRE1α. ACY1215, alone and with BZ, enhanced OB differentiation (increased alkaline phosphatase enzyme activity) and increased mRNA expression of β-catenin, osteocalcin, and Runx2 (OB markers). Importantly, both treatments inhibited OC differentiation (reduced number of multinucleated cells staining for TRAP). In vivo studies confirmed decreased human MM cell growth and prolonged host survival after combination ACY1215 and BZ therapy versus controls (34 vs 22 days, n=7, p<0.0011, in plasmacytoma model and 40 vs 17 days, n=12, p<0.0001, in disseminated model), without significant adverse effects. PK/PD studies showed ACY1215 plasma levels (2133 ng/ml) at 1 hr following treatment. Immunohistochemistry on excised human MM demonstrated increased in acetylated-α tubulin, a biomarker of HDAC6 inhibition, stained cells 4 hrs after ACY1215 treatment. Conclusions: These results provide the rationale for clinical evaluation of ACY1215, alone and together with BZ, in the treatment of MM.
131I-MIBG Therapy in a Metastatic Small Bowel Neuroendocrine Tumor Patient Undergoing Hemodialysis
Authors: Behruz Rahimi, William Makis, Terence A. Riauka, Alexander J.B. McEwan, Don Morrish
Journal: Clinical Nuclear Medicine (2017)

Systemic radioisotope therapy with 131I-metaiodobenzylguanidine (131I-MIBG) is an effective form of targeted therapy for neuroendocrine tumors. One of the absolute contraindications to administering 131I-MIBG therapy listed in the 2008 European Association of Nuclear Medicine guidelines is renal insufficiency requiring dialysis, although this contraindication is not evidence based. We describe a 68-year-old woman with a metastatic small bowel neuroendocrine tumor who developed renal insufficiency requiring hemodialysis. Imaging and dosimetry with 131I-MIBG were performed and showed that the radiation doses to the whole body and lungs were within safe limits. She was treated with 1820 MBq of 131I-MIBG with no short-term adverse reactions.