tbuckley/cabot-search huggingface dataset:
Service delivery supporting quality cancer care: A national multidisciplinary care project for breast cancer
Authors: K. A. Luxford, A. Evans, H. Zorbas, C. Ewan, S. Redman, K. Rainbird, N. Price
Journal: Journal of Clinical Oncology (2004)

6063 Background: Multidisciplinary care (MDC) has been found to improve outcomes for women with breast cancer and clinical practice guidelines recommend management in an MDC setting. Key reports about cancer control highlight the need for reform of cancer service delivery. A national demonstration project was conducted in Australia to examine approaches to fostering MDC for women with breast cancer. The project investigated the process, impact, cost and acceptability of implementing MDC. Three multi-facility collaborations were funded to implement local strategies to improve care in accord with a set of Principles of MDC. The principle-based approach focuses on: team approach; communication among team members; access to full therapeutic range; compliance with care standards; and involvement of the woman.Methods: Strategy implementation was evaluated using a pre-post design over 21-months using a clinical audit (n=250), survey of women treated (n=250), clinician survey (n=44), meeting activity logs and independent cost analysis. A process evaluation was conducted using reports and interviews with key collaboration representatives. Results: Outcomes included the establishment of weekly treatment planning meetings attended by all core disciplines. Significant improvements were found in diagnostic practice (p=0.011) and the provision of routine psychosocial support (p<0.0001). Clinicians reported improved care coordination, increased input from allied disciplines, flow-on effects and decreased personal stress. Women reported an increased perception of ‘team’ care. Average meeting costs per case presented ranged between AU$180-$550 (currently US$126-$387). Conclusions: The project outcomes demonstrate benefits of MDC for both clinicians and women with breast cancer. Recommendations have been made to the federal government advocating a need for national and state level support as well as local service level resourcing of MDC. Potential benefits for other cancers have also been highlighted. No significant financial relationships to disclose.
Assessment of Burden of COPD (ABC) tool: perception<i>versus</i>evidence
Authors: Sarah Houben-Wilke, Frits M.E. Franssen, Ineke Kok, Henk J. Otten, Johan P. Wempe, Jan H. Vercoulen
Journal: European Respiratory Journal (2017)

It is not disputable that chronic obstructive pulmonary disease (COPD) is a multifaceted disease affecting patients' health beyond the lungs with immense variability between individuals [1–3]. Given that complexity and variability, multidimensional assessment and treatment integrating concepts of complex adaptive systems are needed [4]. Agusti and MacNee [5] stated that physicians need a "control panel" including at least three dimensions (severity, activity and impact) to assess different elements of the disease. This "control panel" might be useful for routine clinical practice and to move COPD management towards personalised medicine [5]. However, can one "control panel" reflect the complexity and heterogeneity of this complex, multisystem disease? Can one tool guarantee a personalised approach? Multidimensionality should be assessed by studying multi-dimensions, not by using a multidimensional assessment tool <http://ow.ly/ht1c3091F29>
Beta-tubulin III isotype expression and response to anti-tubulin therapy in metastatic breast cancer (MBC)
Authors: S. Tam, P. Gumerlock, I. Galvin, T. Kimura, R. Livingston, T. Thompson, J. Gralow
Journal: Journal of Clinical Oncology (2004)

2138 Background: Abnormal tubulin expression could potentially influence response to taxanes and vinca alkaloids. Tubb-III is a brain- and nerve-specific isotype, although abnormal expression has been found in breast and other cancers. Hasegawa et al have shown high expression of class I and III mRNA in MBC to be associated with docetaxel resistance. Bernard-Marty et al have shown docetaxel resistance in MBC expressing class II isotypes but not class III or IV. In Southwest Oncology Group (SWOG) 9509, a study of antitubulin agents in lung cancer, we found that abnormal expression of Tubb-III was associated with poorer survival. We hypothesized that the expression of Tubb-III would correlate with poorer response and survival in a retrospective study of MBC patients (pts) who received combination anti-tubulin therapy. Methods: A total of 43 pts with MBC were treated on a University of Washington protocol with docetaxel and vinorelbine. As previously reported (Gralow et al, ASCO 2000), overall response rate was 64%, median time to progression was 287 days, and median survival was 927 days. Tumor blocks were obtained where available, and immunohistochemistry (IHC) was performed with antibodies to Tubb-III. Specimens were evaluated for % of tumor cells staining positive for Tubb-III and intensity of IHC staining. A total score was established by multiplying the % of cells by intensity. Results: Tumor blocks are potentially available on 30 pts, and to date Tubb-III IHC staining has been performed on 15. Conclusion: Our preliminary data do not show Tubb-III expression to be correlated with resistance to anti-tubulin therapy or decreased survival in MBC. This is discordant with our findings in lung cancer, and reports of others in breast cancer. We plan to complete Tubb-III IHC analysis on all pts with available tumor blocks for ASCO 2004, and explore other tubulin isotypes. No significant financial relationships to disclose.
Use of magnetic resonance imaging to plan breast conserving surgery following neoadjuvant chemotherapy for early breast cancer
Authors: M. Bhattacharyya, S. Vinnicombe, D. Ryan, R. Al-Mufti, R. Carpenter, C. Gallagher
Journal: Journal of Clinical Oncology (2004)

658 Background: The selection of patients (pts) for breast conserving surgery (BCS) following neoadjuvant chemotherapy (NAC) is dependant upon accurate assessment of the extent of residual disease within the breast such that up to 60 % patients fail primary surgery and require re-excision or mastectomy. Methods: All pts seen over a 3-year period with histologically confirmed invasive breast cancer on core biopsy, stage cT2 –T3, who were not suitable for, but desired BCS, were considered for NAC. T4 tumours were excluded. Pre and post NAC mammography (MM), breast ultrasound (U/S), and MRI were independently reported and compared with clinical and pathological assessment and whether BCS achieved by segmental mastectomy and sentinel node guided axillary sampling. Results: 32 pts median age 42 years (range 24–60) were treated; 22 (69%) pre-menopausal; stage I (6%), II (62%), III (31%) Median tumour size pre-NAC was 4.75cm (range 2–8cm) on physical examination. All received 6 cycles of anthracycline based chemotherapy. Clinical response: CR 12.5%, PR 81.3% SD 6.2%. MM in this young population was uninformative in 62.5% following NAC. U/S and MRI correlation with pathological response was r= 0.65 and r=0.71 respectively. In 4 pts, MRI tumour size was > 1cm larger than pathological size because of associated DCIS in 3 and post treatment hyaline fibrosis in 1 patient. In 2 pts, MRI size was > 1cm smaller because of delayed surgery. MRI but not U/S was able to differentiate between residual invasive tumour and DCIS or fibrosis from the gadolinium enhancement curves. Following NAC 25 (72%) were suitable for BCS (unsuitable- proximity to nipple 5, multifocal 1, skin tethered 1) of whom 20 proceeded (3 chose mastectomy, 2 radiotherapy only). 17 (85%) pts had successful initial surgery, 3 (15%)had positive margins requiring re-operation because of difficulty locating very small residual masses. Conclusions: MRI aided the selection of pts for BCS after NAC due to the high correlation with pathological findings. 72% pts achieved BCS, 85% of them with single operation. No significant financial relationships to disclose.
Phase I dose-escalation study of the highly potent VEGF receptor kinase inhibitor, AZD2171, in patients with advanced cancers with liver metastases
Authors: M. Medinger, K. Mross, U. Zirrgiebel, R. Strecker, C. Wheeler, G. Clack, J. Lewis, T. A. Puchalski, C. Unger, J. Drevs
Journal: Journal of Clinical Oncology (2004)

3055 Background: Antiangiogenic therapy is a promising strategy to inhibit tumor growth and the formation of metastases. Vascular endothelial growth factor (VEGF) is a key proangiogenic factor essential for the development of new tumor blood vessels. AZD2171 is an orally available, highly potent inhibitor of VEGF receptor tyrosine kinase that has been assessed in a Phase I study of patients with advanced cancer and liver metastases. This study was designed to evaluate the safety and tolerability of ascending doses of AZD2171. Additional assessment of pharmacokinetics (PK), surrogate markers of activity and antitumor effects was also made. Methods: Cohorts of three patients received a single oral dose of AZD2171 (0.5, 1, 2.5, 5 or 10 mg p.o.) followed by a 7-day washout period and then received daily dosing at the same dose for a total of 28 days. Further 28-day treatment cycles were administered until a withdrawal criterion was met. Results: To date, 16 patients with advanced cancers and liver metastases (9 female, 7 male, median age 57 years) have been treated with AZD2171. Preliminary PK data indicate that AZD2171 is rapidly absorbed with a median time to maximal plasma concentration of 3.0 hours and a grand arithmetic mean terminal phase half-life of 20 hours. The exposure observed following continuous once-daily dosing for 28 days was entirely consistent with the terminal phase half-life obtained after a single oral dose. The PK profile appears to be linear following single and multiple doses. Treatment was well tolerated at the dose levels evaluated and the MTD has not been established. In the 10 mg cohort, one patient developed CTC grade 2 dizziness. No other drug-related toxicities have been observed. Conclusion: Continuous, once-daily, oral treatment with the highly potent VEGF receptor tyrosine kinase inhibitor, AZD2171, was well tolerated in this ongoing Phase I study. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca; ProQinase AstraZeneca
Epidermal growth factor receptor tyrosine kinase inhibitor in treatment of brain metastasis from non-small cell lung cancer.
Authors: Lan-jun Zhang, Ling Cai, Jian-fei Zhu, Tie-hua Rong, Shao-xiong Wu, Zhong-pin Chen, Meng-zhong Liu
Journal: Journal of Clinical Oncology (2012)

e18121 Background: Brain metastasis (BM) presents 20-25% of patients with non-small cell lung cancer (NSCLC). Whole brain radiation therapy (WBRT) along with stereotactic radiosurgery (SRS), or surgical resection (SR) or chemotherapy (CXT) were usually used alone or in a combination modality for the treatment. In this study, we purposed to determine the outcome of patients with BM from non-small cell lung cancer treated with EGFR-TKI in combination with conventional therapy. Methods: A total of 201 BM patients with NSCLC were treated sequentially using EGFR-TKI combined with WBRT, or SRS, or SR, or CXT between Jan, 1999 and Nov, 2011 according to our institutional protocol. The median age was 56 yrs (range: 25-80). The histopathological type was predominantly adenocarcinoma (88%) and squamouscell carcinoma (9%), adenosquamous carcinoma (3%). Median follow-up was 28 months (range: 5-80). In addition to the treatment regimen, twelve potential prognostic factors were evaluated including age, gender, smoking status, primary tumor type, tumor size, expression of carcinoembryonic antigen (CEA), intracranial symptoms, lymph nodes metastasis (LNM), number of intracranial metastases, extracerebral metastases, time of taking EGFR-TKI, and TKI-related rash. Results: Median overall survival (OS) for the entire cohort was 29 months (95% CI: 25-34). The OS rate at 1, 2, 3 year were 61%, 38%, and 29%, respectively. On univariate analyses, improved OS was found to be significantly associated with age &lt; 56 yrs (P=0.027), non-expression of CEA (P=0.016), absence of intracranial symptoms (P=0.018), no lymph nodes metastases (P=0.000), number of intracranial metastases &lt; 3 (P=0.003), absence of extracerebral metastases (P=0.000), time of taking medicine ≥ 5 months (P=0.000), and appearance of acneiform rash (P=0.001). On multivariate analysis, time of taking medicine (P=0.000), age (P=0.046), absence of intracranial symptoms (P=0.002) and absence of extracerebral metastases (P=0.000) retained statistical significance. Conclusions: Patients with NSCLC and brain metastasis might benefit from treatment of EGFR-TKI in combination with conventional treatment.
The prophylactic use of lamivudine can maintain dose-intensity of doxorubicin in hepatitis-B surface antigen (HBs Ag)-positive patients with non-Hodgkin's lymphoma who received cytotoxic chemotherapy
Authors: G.-W. Lee
Journal: Journal of Clinical Oncology (2004)

6607 Background: We investigated the effectiveness of lamivudine to prevent hepatitis flare up due to reactivation of hepatitis-B virus (HBV) in hepatitis-B surface antigen (HBs Ag)-positive patients with Non-Hodgkin's lymphoma (NHL) during cytotoxic chemotherapy. Methods: HBsAg-positive patients with NHL were identified from the lymphoma database of the Asan Medical Center from January 1995 to August 2002, and their medical records were reviewed. We found that 31 patients were received cytotoxic chemotherapy among 41 NHL patients with HBsAg-positive during same period. We divided them into 2 groups of HBs Ag patients with NHL as follows: Group A who received cytotoxic chemotherapy with lamivudine 100mg daily; Group B without any prophylactic antiviral therapy. Results: There were no significant differences between Group A and B in several clinical variables. Seventeen patients (85%) in group B and one patient (9%) in Group A had hepatitis due to reactivation of HBV (p<0.001), with one hepatic failure related death in Group B and none in group A. The mean dose intensity of doxorubicin (Adriamycin) actually delivered was 13.3mg/m2/week (80% Relative Dose intensity [RDI]) in Group A and 9.1mg/m2/week (55% RDI) in Groups B (p<0.001). Conclusions: Our data suggest that the frequency of chemotherapy-related HBV reactivation may be significantly decreased by lamivudine prophylaxis with maintenance of the dosage of adriamycin. No significant financial relationships to disclose.
Addressing risk of financial toxicity in an ambulatory oncology practice: Our institutional experience with the ASCO Quality Training Program.
Authors: Thomas A. Hensing, Tyler Bauer, Anna Palafox, Margaret Whalen, George W. Carro
Journal: Journal of Clinical Oncology (2017)

114 Background: Due to escalating cost of cancer care, patients (PTs) with cancer are at increased risk for financial toxicity (FTOX) that can exacerbate disparities in care and lead to clinically relevant adverse PT outcomes; including quality of life; symptom burden; adherence; and survival. A review of our informed consent (IC) process demonstrated that PTs were not routinely informed of financial risks of high-cost (HC) cancer therapies at the time of IC. Methods: A multidisciplinary team was formed to conduct a rapid-cycle quality improvement project with the aim of reducing FTOX through improvement in patient education at the time of IC. Because of HC and increased utilization, the initial pilot focused on treatment with immune checkpoint inhibitors (ICI). A cause and effect diagram identified the potential causes that FTOX was not addressed during the IC process. Diagnostic data were obtained through staff surveys and querying our EMR from June to August, 2016. A Pareto chart identified lack of educational (ED) tools at the time of IC and a poorly understood prior authorization (PA) process as the most common causes for not addressing risk of FTOX during IC. Plan-do-study-act (PDSA) #1 began with development of a PT ED tool to be used during IC. The tool was approved by the Patient Advisory Board. Staff from clinical teams utilizing ICI for approved indication completed training on its use and a pilot study was initiated. PDSA#2 focused on optimizing the PA process and PDSA#3 focused on PT distress and FTOX monitoring through the NCCN distress and a validated patient-reported-outcome tools (COST), respectively. Results: The utilization of the PT ED tool reached the project aim (administer to &gt; 65% of pts during IC) during initial phase of PDSA#1, although accrual is ongoing. A revised PA process (PDSA#2) was developed, staff were educated and the updated PA process was initiated. Work on PDSA#3 is ongoing. Conclusions: This QI project suggests that it is feasible to address FTOX through PT ED during IC for HC cancer therapies. However, the impact of this intervention on PT distress, overall FTOX and treatment disparities will need to be monitored closely.
Developing a CAncer genomics Digital Educational Tool to assess the knowledge and expectations of patients with advanced solid tumors (CADET).
Authors: Herbert H. F. Loong, Anna Spreafico, Natalie Cook, Kelvin K. Chan, Geeta D Krishna, Helen Chow, Celeste Yu, Steve Kang, Phillip Stanley Blanchette, Philippe L. Bedard, Albiruni R. A. Razak, Lillian L. Siu
Journal: Journal of Clinical Oncology (2015)

6524 Background: Genomic testing in cancer (GTC) is increasingly important to guide therapy for patients (pts) with advanced cancers, as eligibility for many early-phase clinical trials is restricted to patients with specific actionable mutation(s). Using a prospectively administered GTC questionnaire, we previously found that only 48% of pts with advanced solid tumors felt that they had sufficient knowledge to make an informed decision to pursue GTC (Blanchette et al, Cancer, 2014). Objective: To develop a digital education tool (DET) to improve pts’ knowledge of GTC, and to assess whether such tool can change pts’ attitudes and expectations toward GTC. Methods: A 5-min video was developed highlighting background information, logistics and rationale for GTC. Pts referred for phase 1 trials and molecular profiling were recruited to view the DET and to complete an identical GTC questionnaire as used in our previous study. These were returned by mail on a voluntary basis. Questionnaire comprised of 12 knowledge of cancer & genomics and 17 attitudes & expectations questions. Results from this cohort (B) were compared with the previously reported cohort (A). Results: Between Aug 2013 and Feb 2014, 118 pts consented to the study with 98 pts completing the questionnaire, representing 83% of pts surveyed. Demographics were similar between the cohorts. In terms of knowledge, as an aggregate, more correct answers were identified from questionnaires administered in B vs. A (72% vs. 67%, OR 1.26; 95%CI 1.06 – 1.51, p=0.01). Multivariate analysis adjusting demographics, prior work experience in healthcare or having close family members with cancer confirmed better knowledge score in cohort B vs. A (OR 1.22, 95% CI 1.01 – 1.47; p=0.04). More pts in cohort B felt they had adequate knowledge regarding potential benefits & risks of DNA testing to make an informed decision to purse GTC (66% vs. 48%, p=0.013) and agree that DNA testing may improve cancer treatment (79% vs. 64%, p=0.037). Conclusions: This DET helps fulfill the support pts need, enhancing knowledge and affecting attitudes towards GTC. Evaluation of long-term effect of this DET is warranted.
A Phase 2/3 Multicenter, Randomized, Open-Label Study to Compare the Efficacy and Safety of Lenalidomide Versus Investigator's Choice in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Authors: Myron S. Czuczman, Marek Trněný, Andrew Davies, Simon Rule, Kim M. Linton, Nina Wagner-Johnston, Randy D. Gascoyne, Graham W. Slack, Pierre Brousset, David A. Eberhard, Francisco J. Hernandez-Ilizaliturri, Gilles Salles, Thomas E. Witzig, Pier Luigi Zinzani, George W. Wright, Louis M. Staudt, Yandan Yang, P. Mickey Williams, Chih-Jian Lih, Jacqueline Russo, Anjan Thakurta, Patrick Hagner, Pierre Fustier, Dale Song, Ian D. Lewis
Journal: Clinical Cancer Research (2017)

Purpose: Randomized, multicenter, open-label, phase 2/3 trial investigating lenalidomide versus investigator's choice (IC) in relapsed/refractory diffuse large B-cell lymphoma (DLBCL).Experimental Design: Patients with DLBCL who received ≥2 prior therapies were stratified by DLBCL subtype [germinal center B-cell (GCB) vs. non-GCB; determined by immunohistochemistry (IHC)] and then randomized 1:1 to lenalidomide (25 mg/day, 21 days of 28-day cycle) or IC (gemcitabine, rituximab, etoposide, or oxaliplatin). Crossover to lenalidomide was permitted for IC-treated patients with radiologically confirmed progressive disease. The primary endpoint was overall response rate (ORR). Progression-free survival (PFS), overall survival, and subtype analysis [GCB vs. activated B-cell (ABC)] using gene expression profiling (GEP) were exploratory endpoints.Results: Stage 1: 102 DLBCL patients (by IHC: non-GCB, n = 54; GCB, n = 48) received ≥1 dose of lenalidomide or IC. Hematologic treatment-emergent adverse events with lenalidomide versus IC included neutropenia (42.6%; 36.4%), anemia (33.3%; 47.3%), thrombocytopenia (24.1%; 43.6%), and leukopenia (5.6%; 12.7%), respectively. Overall, lenalidomide-treated patients had an ORR of 27.5% versus 11.8% in IC (ORRs were similar regardless of IHC-defined DLBCL subtype). Median PFS was increased in patients receiving lenalidomide (13.6 weeks) versus IC (7.9 weeks; P = 0.041), with greater improvements in non-GCB patients (15.1 vs. 7.1 weeks, respectively; P = 0.021) compared with GCB (10.1 vs. 9.0 weeks, respectively; P = 0.550).Conclusions: The clinical benefit of lenalidomide monotherapy in DLBCL patients was more evident in the non-GCB subtype. Exploratory analyses suggest that this preferential benefit was more pronounced in the GEP-defined ABC population, demonstrating a need for additional studies of lenalidomide in DLBCL using GEP subtyping. Clin Cancer Res; 23(15); 4127-37. ©2017 AACR.