tbuckley/cabot-search huggingface dataset:
Thoughts and experience 10 years post surgery from a cancer researcher and survivor: The burdens of a prostate cancer survivor.
Authors: Raymond W. Jurgens
Journal: Journal of Clinical Oncology (2016)

e290 Background: There are a myriad of experiences reported from various cancer survivors, but few individuals have been involved with cancer drug development, speaking publicly to prostate cancer groups, working privately with prostate cancer survivors and studying the psychosocial aspects of post treatment patients. Methods: N/A Results: The postsurgical and post treatment issues , particularly ED are either not discussed by the patient due to embarrassment or lack of knowledgeable of the type of questions to ask, or not addressed directly by the HCP. Unlike other oncological disciplines, the prostate cancer patient is confronted with major decisions on which treatment approach to choose from which therapeutic discipline. The clinicians they are meeting are explaining their expertise on radiation, surgery, chemo, or other interventions leading the patient to become overwehlemed at these choices. There are few “neutral” voices talking to the patient on which procedure or treatment would suit him best. In addition to the treatment decisions the patient is also told about watch and wait approach. Besides the tough decision for the patient to choose the right approach for himself, he is shown data by each treatment specialty from postsurgical &amp; other treatments relative to the percentage success rates for ED and continence that the patient may expect. These numbers through data from the participating surgical centers etc are typically very inflated. Many patients leave thinking they will return to normal function in x amount of months, only to find that they are quite dysfunctional for much longer or in some cases never gaining functionality. The last part of the discussion is what is available for these men with continuing dysfunction. Potential options exist but for many men they are met with mixed results. The treatments for ED are quite expensive to most men, and in many cases do not work. When the diesterase inhibitors fail to work for the patient, options for ED remain vary greatly-from mechanical interventions to various chemical and pharmacological approaches, and the patient has no voice to turn to get non biased information needed to help with the next steps. Conclusions: Suggestions for the HCP.
Phase II study of oral panobinostat (LBH589), a potent pan-deacetylase inhibitor, in patients with refractory Cutaneous T-cell Lymphoma (CTCL)
Authors: M. Duvic, F. Vanaclocha, M. G. Bernengo, C. Okada, D. Breneman, P. L. Zinzani, L. Zhang, K. Bopp, G. Laird, S. Hirawat, M. Prince
Journal: Journal of Clinical Oncology (2008)

8555 Background: Panobinostat (LBH589) is a potent pan-deacetylase inhibitor (DACi) which has demonstrated activity in patients (pts) with CTCL in a phase I study (Prince et al, ASCO 2007). This phase II study aims to confirm that activity. Methods: This open-label study enrolled pts with CTCL (stage IB-IVA), including Mycosis fungoides (MF) and Sezary syndrome (SS), who have failed ≥2 prior systemic therapies, have adequate organ function and ECOG PS ≤2. Pts with significant cardiovascular abnormalities or QTcF >450 msec on screening ECG were excluded. Pts were accrued to Group 1 (Grp 1, previously treated with oral bexarotene) or Group 2 (Grp 2, bexarotene naïve); both following a Simon 2-stage design. Panobinostat (20 mg) was administered orally on days 1, 3, and 5 weekly until disease progression or intolerance. Primary endpoint is the response rate measured using a composite score derived from assessment of skin disease using modified Severity-Weighted Assessment Tool [mSWAT], evaluation of visceral and lymph nodes, and circulating Sezary Cell count. Intensive ECG monitoring for QTcF prolongation was performed. Results: 40 pts (Grp 1=25; Grp 2=15) have been treated to date (median age 57 yrs [range 30-83]; 24 male, 16 female; 28 MF, 12 SS). Median numbers of prior treatment regimens are 5 (Grp 1) and 3 (Grp 2). For Grp 1, best overall response is PR for 3 pts, SD for 4 pts, PD for 3 pts. Other pts in Grp 1 and most pts in Grp 2 have had ≤2 months of follow-up. Of evaluable pts, 5 achieved a confirmed skin response including 1 complete skin response. Also, 1 pt with PD improved to PR after initial flaring of disease. Most common (>15%) AEs (all grades) include diarrhea, thrombocytopenia, fatigue, asthenia, hypertriglyceridaemia, dysgeusia, nausea and pruritus. Among 1578 ECGs analyzed, there has been no QTcF >500ms, one QTcF >480ms, and one QTcF >60ms increased from baseline. Conclusions: Based on activity as documented by improvement in composite score and skin responses, enrollment to Stage 2 for Grp 1 and Stage 1 for Grp 2 is ongoing. Preliminary safety data suggest panobinostat is generally well tolerated with no major safety concerns. Available efficacy and safety data will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Merck, Novartis Oncology Novartis Pharmaceuticals
Improving code status documentation as a marker of advanced care planning at an outpatient academic cancer center: A pilot project.
Authors: Anjana Ranganathan, James J. Sauerbaum, Katie Green, Heather Sheaffer, Mary Coniglio, Tracey L. Evans
Journal: Journal of Clinical Oncology (2013)

38 Background: Advanced care planning can significantly impact the quality of end of life care. Readily accessible documentation of goals of care for patients (pts) known to have a high morbidity and mortality provides a concrete means for practitioners to discuss and guide advanced care planning. We previously reported a surprisingly small proportion of established pts in our oncology clinic with a documented code status (CS), and undertook a pilot project aimed at improving this rate. Methods: Query of the outpatient electronic medical record (EMR) at the Abramson Cancer Center for established pts revealed an average of 2% with a documented CS. Our pilot study focused on 8 providers in thoracic and gastrointestinal oncology. We established provider agreement on the importance of CS documentation, and analyzed the mechanisms in place for documentation. We educated providers on the method of documentation, raised visibility and importance of advanced directives, implemented a system of normalizing conversations for all new pts, reported weekly to providers on upcoming established pts without documentation and provided monthly report cards, indicating provider rates within the pilot group. Results: Prior to intervention, a median of 499-established pts per month were seen by our pilot group. A median of 50 pts (10%) had a documented CS with documentation rates by provider ranging from 0 – 91%. 5 of 8 providers had no established pts with a documented CS. After intervention, a median of 494-established pts per month were seen by the same group. A median of 197 pts (40%) (p &lt; 0.05) had a documented CS with provider rates ranging from 26 – 94%. All providers had documented a CS on at least some of their established pts; improvements ranged from an increase of 0 to 26%, to an increase of 1 to 43%. Conclusions: Previously, at our institution, only a small minority of established patients with an oncologic diagnosis had documentation of CS in the readily available EMR. Our pilot study resulted in a statistically significant increase in the documentation rates for all providers over a 2-month period. We have yet to analyze the clinical significance of this, with attention to quality and cost of end of life care.
Family members’ perspectives of caring for patients with terminal hepatocellular carcinoma.
Authors: Lissi Hansen, Susan J. Rosenkranz, Kathleen Wherity, Anna Sasaki
Journal: Journal of Clinical Oncology (2015)

323 Background: Hepatocellular carcinoma (HCC) is a growing problem worldwide and accounts for more than 700,000 deaths annually. There is no curative treatment for those diagnosed with terminal HCC. This group of patients differs from other populations with liver disease or cancer due to the combined disease processes of cancer and liver failure. Although family members often play an integral role in providing care, no study was found specifically examining family member experiences of caring for patients with terminal HCC. The aim of this study was to describe family members’ experiences and perceptions of providing care for patients with HCC as they near the end of life. Methods: This longitudinal, prospective pilot study described here presents the qualitative results of semi-structured in-person interviews with a convenience sub-sample of 13 family members conducted once a month for up to a 6-month period. The interview guide included questions about family member experiences of providing care for patients living with HCC and any current concerns of significance. Interview data were analyzed using conventional content analysis. Results: Analysis included a total of 39 family member interviews. Ten family members were female and three were male (mean age = 56 years, range = 22-68 years). Family members’ relationships to patients varied and included: spouses, siblings, adult children, parents, and ex-spouses. The analysis resulted in four major themes: perception of and response to terminal HCC diagnosis, HCC progression, symptom assessment and interpretation, and challenges of providing care. Findings were colored by complex relationships between family members and patients that changed or did not change as the disease progressed. Conclusions: This study contributes new knowledge to begin developing interventions that address family members’ need for support, help, and information as the disease progresses and at the end of life. Future research should include a larger sample size that is more ethnically and racially diverse, includes more male family members, and focuses on how care provided by family members may vary based on kinship, and relationship dynamics.
Microarray analysis of gene expression in gastric cancer cells from ascitic fluids before and after capecitabine and oxaliplatin (CapeOX).
Authors: Osamu Maeda, Kazuhiro Ishiguro, Kohei Funasaka, Ryoji Miyahara, Yoshiki Hirooka, Hidemi Goto, Yuichi Ando
Journal: Journal of Clinical Oncology (2016)

60 Background: Resistance to anti-cancer drugs is a critical issue in treatment of cancer. Alteration of gene expression profile accompanied with acquisition of drug-resistance is considered to be related with resistance mechanisms. Methods: 1. Ascitic fluids were collected before the beginning of CapeOX, during the treatment was effective, and after the disease was progressed. They were cultured for ten days and passed to new flasks, and were cultured in additional two weeks to remove normal cells including white blood cells and mesothelial cells. 2. AGS cells were cultured in medium with either fluorouracil or oxaliplatin, and fluorouracil- or oxaliplatin-resistant cells were established. AGS cells were also treated with a demethylating agent decitabine. 3. Expression of 25,147 genes was analyzed with microarray, and was compared among ascitic fluid cells before and after CapeOX, drug-resistant AGS cells, and decitabine-treated AGS cells. Results: Genes with alteration in expression due to CapeOX-resistance were classified into genes commonly changed with fluorouracil-resistant cells, those with oxaliplatin-resistant cells, and others. Among 873 genes with decreased expression after CapeOX, some genes including PCDH20 and DEFB4A have been reported as potential tumor suppressor genes. Expression of PCHD20 in AGS increased after treatment with decitabine. Conclusions: Drug-resistance in gastric cancer may be related with expression of genes including tumor suppressors regulated by epigenetic mechanisms. Repetitive collection of gastric cancer cells in ascitic fluids before and after chemotherapy is useful to understand drug-resistance mechanisms.
Experience with artificial urinary sphincter implantation in men who underwent prior pelvic radiation therapy for prostate cancer.
Authors: Sameer G. Jhavar, Erin Bird, Gregory P. Swanson
Journal: Journal of Clinical Oncology (2014)

236 Background: To assess outcomes after artificial urinary sphincter implantation in men who received prior pelvic radiation therapy. Methods: Between 1997 and 2012, 107 patients were identified from the Scott and White Hospital database who underwent artificial urinary sphincter implantation for urinary incontinence after prostate cancer treatment. Of these 17 were excluded for lack of follow-up data. Of the remaining 90 patients, 59 patients underwent prior surgery alone (group 1), 25 underwent prior surgery followed by pelvic radiation therapy (group 2); and 6 patients underwent prior radiation therapy alone. Results: Average ages at sphincter implantation were 69 yrs. (range 54 - 82), 73 yrs. (range 63 - 81), and 70 yrs. (range 60 - 80) respectively for groups 1, 2 and 3. Social continence rates were 80% (47/59) for group 1, 72% (18/25) for Group 2 and 50% (3/6) for group 3 at an average follow-up of 6 yrs. (range 0 - 17), 4 yrs. (range 1 - 12) and 3 yrs. (range 0 - 6) respectively. Average time between surgery and sphincter implantation was 5 yrs. (range 1-27) in group 1. Average time between radiation and sphincter implantation was 7 yrs. (range 1 - 18) and 6 yrs. (range 1 - 17) in Groups 2 and 3. Re-operation rates were 42% (25/59); 48% (12/25); and 50% (3/6) in groups 1, 2, and 3, respectively. In men who were incontinent at last follow-up, the average time between pelvic radiation and sphincter placement was relatively shorter as compared to those who were continent [5 yrs. (range 1 -11) vs. 7 yrs. (range 1 - 18) in Group 2; and 4 yrs. (range 1 -5) vs.10 yrs. (range 4 - 17) in group 3]. The rates of erosions were 10/59 (17%); 4/25 (16%); and 0/6 (0%) in groups 1, 2, and 3, respectively. The rates of infection were 5/59 (8%), 0/25 (0%), and 2/6 (33%) in groups 1, 2, and 3, respectively. Conclusions: Our experience with artificial urinary sphincter in men who underwent prior pelvic radiation therapy is comparable to that reported in the literature. Our results identify factors associated with worse continence after artificial urinary sphincter in men who underwent prior pelvic radiation therapy.
Consensus development: Within general oncology practice, what constitutes high-quality palliative care delivery?
Authors: Kathleen Elizabeth Bickel, Kristen McNiff, Jennifer Malin, Amy Pickar Abernethy, Anupama Kurup Acheson, Charles L. Shapiro, Tracey L. Evans, Arif Kamal, Mary K. Buss, Dale Lupu, Michael S. Broder, Monika K. Krzyzanowska
Journal: Journal of Clinical Oncology (2013)

280 Background: Multiple studies illustrate the benefits of combined palliative and standard cancer care, but oncology practices need guidance to fill existing gaps in delivering high quality palliative care (PC) to cancer patients. As a first step, ASCO and the American Academy of Hospice and Palliative Medicine (AAHPM) sought to develop a consensus definition of which PC aspects are within the purview of general adult oncology practice in the United States. Methods: An ASCO and AAHPM steering group used existing publications to define 9 domains of PC in oncology: Symptom Assessment and Management (A&amp;M), Psychosocial A&amp;M, Spiritual and Cultural A&amp;M, Communication and Shared Decision-Making, Care Planning, Appropriate Palliative Care and Hospice Referral, Coordination and Continuity of Care, Carer Support, and End-of-Life Care. Within each domain, key PC activities were itemized and described (e.g. pain assessment using a standardized scale at every clinical encounter), totaling 966 activities. A 31-member multidisciplinary panel participated in a modified RAND Delphi process, rating each activity on a 9-point scale according to 3 constructs: importance, feasibility, and scope of practice. Composite scoring categorized activities as either reasonably within scope of oncology practice, uncertain, or typically not in scope. Results: The response rate for each round was 94%. Notable panelist concerns included the breadth of palliative care practice, the varied access that oncology practices have to PC resources, and the varied individual knowledge and comfort with specific activities. Despite multiple small ranking changes between surveys, only 41 activities changed in scope of practice category. Of 966 activities, 62% were ranked as reasonably within scope of oncology practice, 36% were uncertain, and 2% were typically not in scope. Conclusions: Despite the diverse range of PC activities, panelists strongly agreed that more than half were reasonably within the scope of adult medical oncology practice. These items provide a foundation for improving palliative care delivery within an oncology practice, with suggestions for future performance measures and quality improvement activities.
Clinical activity of the oral MEK1/MEK2 inhibitor GSK1120212 in pancreatic and colorectal cancer.
Authors: W. A. Messersmith, G. S. Falchook, L. A. Fecher, M. S. Gordon, N. J. Vogelzang, D. J. DeMarini, V. G. Peddareddigari, Y. Xu, J. C. Bendell, J. R. Infante
Journal: Journal of Clinical Oncology (2011)

246 Background: GSK1120212 is a reversible, highly selective allosteric inhibitor of MEK1/MEK2. The objectives of this phase I study are to define the maximum tolerated dose (MTD), and to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and response rate of GSK1120212 in advanced solid tumors. Cohorts of advanced chemoresistant pancreas (PC) and colorectal cancer (CRC) patients have been enrolled. Methods: GSK1120212 is given orally, once daily (QD). In this three-part study GSK1120212 was escalated to an MTD, was administered in selected tumor types to evaluate recommended phase II doses (RP2D), and was evaluated for minimum biological activity using PD assessments. Results: 202 patients (pts) have received ≥ 1 dose of GSK1120212, including 26 PC and 27 CRC pts. The MTD is 3 mg QD and the RP2D is 2 mg QD. Dose limiting toxicities are rash (N=2), diarrhea (N=1), central serous retinopathy (N=2) and are reversible. At 2 mg QD (N=68), the most common adverse events are rash (47% G1, 37% G2, 4% G3) and diarrhea (41% G1, 12% G2, 1% G3). There has been one event of retinal vein occlusion. GSK1120212 has a small peak:trough ratio of ∼ 2 and an effective half life of ∼ 4.5 days. Steady state is reached by ∼ day 15. In the 26 evaluable PC pts, 2 partial responses (PR) and 11 stable diseases (SD) have been observed. 1 PR is KRAS mutation positive and is ongoing at 28 weeks. Among the SD pts, 2 achieved ≥ 20% tumor reduction and at least 3 were on study for 16 weeks or longer. CA19-9 reduction ≥ 55% was observed in both PR and 3 SD pts, 1 of which remained on study for 40 weeks. Among the KRAS mutation positive CRC pts (n=12), 4 SD were observed. These pts were on study for 31, 28, 16, and 16 weeks. Among the KRAS mutation negative or status unknown pts (n=12), 2 SD were observed; no pt was on study for &gt; 19 weeks. Among the B-RAF mutation positive pts (n=3), 2 SD were observed; both are still ongoing at &gt;16 weeks. Conclusions: The RP2D is well tolerated. The long effective half life and small peak:trough ratio of GSK1120212 allow constant target inhibition within a narrow range of exposure. GSK1120212 demonstrates durable clinical activity in a subset of pts with PC or CRC. [Table: see text]
Developing and implementing EMR functionality to improve oral chemotherapy outcomes.
Authors: Thomas A. Hensing, Bruce Brockstein, George W. Carro, Ashton Marie Hullett, Brad Hughes, Wayne Spath, Sharon Huginnie
Journal: Journal of Clinical Oncology (2016)

159 Background: Approval of new oral anticancer agents (OAA) continues to rise, accounting for 75% of new oncology drugs approved so far in 2015. OAA prescriptions generated at our institution demonstrate similar growth, as the prescription volume for OAA is approximately 200% greater than it was 8 years ago. Challenges of OAA, including safe prescribing, monitoring toxicities, and assessing adherence, continue to be an obstacle to providing quality care. In recognition of these challenges, our institution employed the electronic medical record (EMR) to develop tools to enhance safe prescribing, monitoring, and follow up for patients receiving OAA. Methods: Comprehensive, regimen-specific, OAA protocols were built in the EMR using the American Society of Clinical Oncology’s Quality Oncology Practice Initiative criteria as a guide. Protocols included OAA prescriptions, laboratory tests, monitoring communications, supportive care medications, plan for follow up, and a monitoring order. The monitoring order, dated 7 to 10 days after the start of each cycle, was utilized to identify patients for follow up, and as a documentation tool. During follow up calls, pharmacists provided education, addressed adherence and toxicities, and communicated findings to team members. The initial analysis focused on six of the most commonly prescribed OAA agents at our institution. Results: Cycle 1 follow up calls were placed for 115 new start OAA patients. Over half of the patients (56.5%) required an intervention (ex: symptom management, alerting the medical team, counseling). Eleven patients had barriers to adherence (ex: confusion, incorrect technique, cost, obtaining insurance coverage, and toxicity). Overall, 98% of patients verbalized appropriate adherence. There were 191 subsequent follow up efforts, after the cycle 1 follow up call, which resulted in 39 interventions (20%). Conclusions: OAA requires the same intensive monitoring and follow up as IV chemotherapy, but is more difficult to provide given the nature of administration of these medications. Utilizing the EMR to develop prescribing and monitoring tools can help address these challenges by providing a means for enhanced documentation and follow up.
Paucity of core palliative care elements available to children with cancer at end-of-life: Perspectives of bereaved parents and clinicians.
Authors: Alisha Kassam, Sharifa Habib, Julia Skiadaresis, Sarah Alexander, Joanne Wolfe
Journal: Journal of Clinical Oncology (2012)

9076 Background: Recognition of serious deficits in palliative care for children has prompted hospitals to develop specialized pediatric palliative care programs. However, only a minority of children who die from advanced cancer receive services from these dedicated programs. We aimed to determine which elements of palliative care are considered important according to bereaved parents and pediatric oncology clinicians and to determine availability of these elements. Methods: We administered questionnaires to 75 bereaved parents (response rate 53%) and 48 pediatric oncology clinicians (response rate 91%) at the Hospital for Sick Children in Toronto, Canada. The main outcome measures were importance ratings and availability of core elements of palliative care delivery based on the National Quality Forum clinical practice guidelines for quality palliative care. Results: Fifteen of the twenty-one core elements were highly valued by both parents and clinicians (defined as &gt; 60% of parents and clinicians reporting the item as important). When compared to clinicians, parents gave higher importance ratings to receiving cancer-directed therapy during the last month of life (p = 0.007) and involvement of a religious or spiritual mentor (p = 0.03). Clinicians gave higher importance ratings to involvement of a social worker (p &lt; 0.0001). Notably, of the valued elements, only three of them were available greater than 60% of the time according to clinicians and parents. Valued elements least likely to be available included a direct admission policy to hospital, involvement of a religious or spiritual mentor, sibling support and parent preparation for medical aspects surrounding death. Conclusions: Children with advanced cancer are not receiving key elements of palliative care despite both parents and clinicians recognizing them as important. Evaluation of barriers to provision of quality palliative care and strategies for overcoming them is critical.