tbuckley/cabot-search huggingface dataset:
Time trend and risk factor for treatment-related death (TRD) in patients with advanced non-small cell lung cancer (NSCLC) receiving systemic chemotherapy in phase III trials
Authors: Y. Fujiwara, K. Kiura, K. Hotta, N. Takigawa, M. Tabata, K. Shinagawa, M. Tanimoto
Journal: Journal of Clinical Oncology (2008)

19015 Background: Despite recent improvements in the supportive care, TRD remains a serious problem for lung cancer patients undergoing systemic chemotherapy. However, few studies have assessed formally whether the TRD rate has changed over the years. Moreover, factors affecting the TRD rate have not been fully understood. Here, we investigated these issues in patients with advanced NSCLC through the literature search. Methods: We searched phase III trials addressing the role of systemic chemotherapy in the treatment of advanced NSCLC. Time trend and factors affecting the TRD rate were assessed by multiple regression analysis. Results: In total, 100 trials were identified that involved 36,348 patients with 220 treatment arms, which were initiated between 1982 and 2002. Cisplatin-based regimens were the most frequently investigated (53.2%). There were 678 TRDs, and the median TRD rate per treatment arm was 1.1%. The TRD rate has been consistent over the years (the TRD rate = 0.02 × [year of trial initiation]-45.3) (p = 0.39). Of note, the TRD rate was significantly higher in cisplatin-based regimens than in other regimens (2.1% vs. 1.6%, p < 0.05). The multivariate analysis revealed that the use of cisplatin, but not the year of trial initiation, was a sole significant risk factor for the TRD rate (p < 0.05). Regarding to the causes of TRD in the assessable 150 treatment arms (68.2%), there were febrile neutropenia/sepsis (FN/S) (42.9%), cardiovascular events (13.0%), renal failure (9.8%), and others (34.3%). The use of cisplatin led to a higher rate of TRD due to renal failure but lower rate due to hemorrhage, as compared with the non-cisplatin regimens did (0.2% vs. 0.02%, and 0.09% vs. 0.11%, respectively). In addition, the rates of TRD due to FN/S and cardiovascular events were almost identical between the groups. Conclusions: The overall TRD rate was quite low, but not still negligible in phase III trials for advanced NSCLC, because it has been consistently observed over the years. Physicians should be careful about the occurrence of TRD, especially when patients receive cisplatin-based regimens, although some TRDs might be rather correlated to the use of other chemotherapeutic regimens. No significant financial relationships to disclose.
DNA methyltransferase-3B (DNMT3B) in oral cancer (OC) development.
Authors: P. Saintigny, J. Jelinek, C. R. Pickering, W. Lang, M. J. Frederick, L. Zhang, H. Ren, V. Papadimitrakopoulou, J. J. Lee, E. S. Kim, Y. H. Fan, A. K. El-Naggar, W. K. Hong, J. Myers, J. J. Issa, S. M. Lippman, L. Mao
Journal: Journal of Clinical Oncology (2011)

1506 Background: We have reported that a gene expression signature including DNMT3B canpredict OC development (dvlpt) in patients (pts) with oral preneoplasia (OPL). This led us to study OPL DNA methylation profiles. Methods: Gene expression profiles of 86 prospectively collected OPL with a median follow-up (fu) of 6.1 years (yrs), including 35 who developed OC, were used to compute a univariate Cox model for DNMT1, 3A and 3B. Methylated CpG island amplification method was used to study 12 OPL who developed (group A), and 12 OPL who did not develop (group B) OC, with a median fu of 2.2 yrs and 7.6 yrs respectively. DNA was SmaI/XmaI digested, amplified, labeled (each OPL of group A being compared to one OPL of group B), and hybridized on a chip covering 6,647 autosomal genes. Genes differentially methylated were defined by an absolute log2 ratio > 1, at least 2 probes showing the same effect, and an absolute minimal distance to the transcription starting site < 1kb. Their pattern of expression was analyzed using independent publicly available gene expression profiles from 37 OC and 20 matched normal (NM) mucosa. Results: DNMT3B gene expression, but not DNMT1 and DNMT3A, was associated with OC dvlpt (hazard ratio=7.7, 95% confidence interval: 3.3-18.6, P <0.0001), and did not correlate with proliferation markers. Hypermethylated genes in pts who developed OC had a significant overlap across the 12 comparisons, whereas hypomethylated genes were random. Log2 ratios were averaged across the 12 comparisons, and 55 autosomal genes hypermethylated in pts who developed OC were identified, consistent with a CpG island methylation phenotype (CIMP) occurring early during OC dvlpt. These genes participate in signal transduction, morphogenesis and dvlpt, and some were previously reported to be upregulated by demethylating agents. Using gene expression profiles from an independent study, the vast majority of the 55 genes were downregulated in OC vs. NM mucosa. Unsupervised hierarchical clustering using the 55 genes, allowed to separate OC and NM mucosa almost perfectly in two distinct groups. Conclusions: DNMT3B gene expression is a strong predictor of OC dvlpt. CIMP may occur early in OC dvlpt, and may be amenable to new chemoprevention strategies.
Severe Mucositis Adversely Affects Survival after Autologous Stem Cell Transplantation (ABMT) for Lymphoid Malignancies.
Authors: Brian Bolwell, Matt Kalaycio, Ronald Sobecks, Steven Andresen, Lisa Rybicki, Elizabeth Kuczkowski, Sherry Mendiola, Joe Kohuth, Kimberly Bell, Julie Curtis, Stacey Brown, Brad Pohlman
Journal: Blood (2005)
Feasibility of a breast health educational program to increase breast cancer awareness among adolescents and their female relatives in low-income communities.
Authors: Enrique Soto Perez De Celis, David D. Smith, Edgar Baltazar-Avalos, Arti Hurria, Martin A Reyes-Bautista, Rina Gitler-Weingarten, Alba M Pavas-Vivas, Patricia Rojo-Castillo, Max Sirota-Toporek, Alejandro Mohar, Mayte Ayala-Gonzalez, Viridiana Chaveste-Ramos, Brenda Cosme-Gonzalez, Sofia N Gallegos-Quintana, Ana FS Martinez-Aviles, Julia A Melendez-Rosas, Andrea Salazar-Moreno, Yanin Chavarri Guerra
Journal: Journal of Clinical Oncology (2015)

76 Background: Delays in the diagnosis of breast cancer in developing countries are partially related to a lack of knowledge on breast health (BH), particularly in rural communities with poor access to education. We implemented a BH educational program for adolescents from a rural community in Mexico, aimed at increasing knowledge and promoting intergenerational transmission of information from adolescents to their female relatives. Here, we report the results of our feasibility aims, as well as the change in knowledge in the students after the intervention. Methods: In this pilot study, adolescents enrolled in a public rural Mexican middle school were invited to participate in the program. They received age-appropriate, culturally sensitive sessions from expert educators focused on transmitting BH knowledge in their household. Our primary outcome was satisfaction with the content, with 75% approval needed for the program to be considered acceptable. Pre and post true/false tests to evaluate the students’ knowledge were applied. Paired t-test was used to detect changes in knowledge. A p value of &lt; 0.05 was considered significant. Acceptability of the program among the school teachers was assessed. Results: 238 students were invited to participate, of which 126 (53%) provided parental consent and completed the program. Median age was 13.5 years (12-16). 96% (n = 121) of the students considered the sessions very interesting and 99% (n = 124) thought they either learned “a lot” (66%; n = 83) or “some” (33%; n = 41). The pre- and post-test mean proportion of correct answers was 63% (12.5-100%, SD 0.2) and 89% (25-100%, SD 0.12) respectively. A statistically significant improvement in the proportion of correct answers was found for 5 out of 8 questions. 100% (n = 18) of the teachers thought the intervention was acceptable. Conclusions: Our results show that implementing a BH educational program for rural adolescents in low-income communities is feasible and acceptable, and that such a program can increase their knowledge on BH. Our next planned step is to assess intergenerational transmission of the information to the students’ female relatives.
Overall survival in randomized controlled trials of chemotherapy (CT) with or without GCSF support: A systematic review.
Authors: G. H. Lyman, D. C. Dale, E. Culakova, M. S. Poniewierski, D. A. Wolff, N. M. Kuderer, J. Crawford
Journal: Journal of Clinical Oncology (2010)

9141 Background: To evaluate the impact of G-CSF support on overall mortality in cancer patients receiving CT, a systematic review of randomized controlled trials (RCTs) was conducted. Methods: Electronic databases were searched through November 2009 identifying 60 RCTs of solid tumor or lymphoma in adult patients receiving CT with or without primary G-CSF and reporting overall mortality by study arm. Heterogeneity was assessed by Q-statistic and I2. Relative risk (RR) and absolute risk (AR) difference were estimated using the method of Mantel and Haenszel using a random effects model as described by DerSimonian and Laird. Results: Patients received CT with (n=11,337) or without (n=11,992) primary G-CSF support. Median follow-up of studies was 60 months. Deaths were reported in 4,250 patients randomized to G-CSF and in 4,618 controls. Heterogeneity was observed across studies for RR (Q=89.7, p=.006; I2=34%) but not for AR difference. Overall RR and AR decrease for mortality were 0.93 [0.90 – 0.96;P<.001] and 3.2% [2.1% - 4.2%;P<.001], respectively. In 24 studies of treatment with curative intent, the impact on mortality [RR=0.89; 0.85 – 0.95;P<.001] was greater than in 36 noncurative studies [RR=0.95; 0.92 – 0.98, p=.001]. Among 7 trials limited to elderly patients, the RR for mortality was 0.90 [0.84 – 0.97;p=.004]. RR and AR decrease with G-CSF support varied by disease site: breast (RR=0.95; AR=1.5%), lung (RR=0.93; AR=5.6%), lymphoma (RR=0.89; AR=4.8%), genitourinary (RR=0.95; AR=4.2%). RR reduction was greater among 12 studies of dose dense CT with G-CSF (RR=0.89 [0.85 – 0.94];P<.001) compared to other schedules (RR=0.95 [0.92 – 0.98];p=.001). RR for mortality when survival was the primary outcome was 0.91 [0.88 – 0.94] compared to 0.98 [0.94 – 1.01] if a secondary outcome. RR was 0.92 [0.89 – 0.95,P<.001] among international RCTs compared to 0.98 [0.95 – 1.02;p=.40] in US studies (p=.004). Greater RR reduction for mortality was observed among studies with longer follow-up (p=.02). Conclusions: Overall mortality is reduced in patients receiving CT with G-CSF support. Greatest impact on mortality was observed in studies in early-stage disease or malignant lymphoma and with dose dense schedules. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen Amgen
Association of metformin with reduced mortality in patients with colorectal cancer: A systematic review and meta-analysis of observational studies.
Authors: Preet Paul Singh, Siddharth Singh, Wilson I. Gonsalves, Axel Grothey
Journal: Journal of Clinical Oncology (2014)

522 Background: Metformin inhibits mTOR and downstream pathways involved in cell proliferation and survival by inducing AMPK activation. Although its use has been associated with decreased risk of colorectal cancer (CRC), the effect of metformin on cancer related mortality is unclear. We performed a meta-analysis of published observational studies evaluating metformin use in patients with CRC and its association with overall and CRC-specific survival. Methods: Through a systematic search of PubMed and conference presentations (cut-off: August 2013), we identified 8 observational studies (18,537 total patients with CRC; 6242 CRC patients with DM) reporting the association between metformin use and survival after diagnosis of CRC. Summary hazard ratio (HR) with 95% confidence intervals (CI) was estimated using the random effects model, and heterogeneity was measured using the inconsistency index (I 2 ). Results: On meta-analysis, metformin use was associated with a 34% reduction in mortality in CRC patients as compared to non-use (adjusted HR, 0.66; 95% CI, 0.54-0.81), albeit with high heterogeneity (I 2 =66.9%). After exclusion of one study, which contributed to considerable heterogeneity, a 28% reduction in mortality was considered a more conservative, consistent effect estimate (adjusted HR, 0.72; 95% CI, 0.64-0.81), with minimal heterogeneity (I 2 =16.2%). On restricting analysis only to patients with DM, use of metformin (vs non-use) was associated with decreased all-cause mortality (6 studies; adjusted HR, 0.63; 95% CI, 0.49-0.81) and CRC-specific mortality (3 studies; adjusted HR, 0.66; 95% CI, 0.50-0.87). Conclusions: Based on meta-analysis of observational studies, the use of metformin in diabetic patients with CRC appears to be associated with reduced all-cause mortality and CRC-specific mortality. Further prospective investigation of metformin’s effect on outcome in CRC patients is warranted.
The incidence and prognostic significance of bone metastases and skeletal-related events in lung cancer patients: A population-based cohort study in Denmark.
Authors: V. M. Chia, K. Cetin, J. B. Jacobsen, M. N∅rgaard, A. Ø. Jensen, C. F. Christiansen, H. T. S∅rensen
Journal: Journal of Clinical Oncology (2010)

e18074 Background: Lung cancer often presents at an advanced stage of disease and can give rise to bone metastases (BM). Metastatic bone disease is associated with painful and debilitating complications, but less is known about its effects on patient survival, particularly after the occurrence of skeletal-related events (SREs). Methods: Using data from the Danish Cancer Registry, we studied 11,940 patients diagnosed with lung cancer (1999-2003) with follow-up through December 31, 2008. We estimated the cumulative incidence of BM following cancer diagnosis and the subsequent occurrence of SREs (fractures, spinal cord compression, and surgery to the bone), treating death as a competing risk. We computed and compared survival for three lung cancer subgroups – no BM, BM but no SREs, and BM with SREs – using Kaplan-Meier and multivariate Cox models. Results: Overall, 6.4% (n = 760) were diagnosed with BM either at lung cancer diagnosis or during follow-up: 5.1% (n = 607) had BM but no SRE and 1.3% (n = 153) had both BM and at least one SRE (spinal cord compression was most frequent). Although the cumulative incidence of BM and the subsequent occurrence of SREs were similar according to histologic type, the incidence of BM appeared slightly elevated in those with adenocarcinomas (5-year cumulative incidence of 8.5% (95% confidence interval [CI]: 7.7-9.3) in adenocarcinoma versus 6.3% (95% CI: 5.9- 6.8) for all lung cancer patients combined). Less than 1% of lung cancer patients diagnosed with bone metastases survived beyond three years. One-year crude survival was lowest for those with both BM and SREs (4.4%) compared to the groups with no BM (35.3%) and with BM but no SREs (5.2%). Accordingly, the adjusted mortality rate was 2.1 times greater in those with BM alone (95% CI: 1.9-2.3) and 2.7 times higher for those with both BM and SREs (95% CI: 2.3-3.1) compared with lung cancer patients without BM and SREs. Conclusions: Survival was poorer for lung cancer patients with BM versus those without, but short-term mortality rates appear even higher among those with BM who also experience an SRE. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen Amgen
Concordance with best-practice guidelines for systemic treatment computerized prescriber order entry systems.
Authors: Sherrie Hertz, John Gilks, Leonard Kaizer, Marta Yurcan, Vishal Kukreti
Journal: Journal of Clinical Oncology (2013)

245 Background: In 2012, Cancer Care Ontario, released evidence-based guidance for the key features, functionalities, and components of a Systemic Treatment Computerized Prescriber Order Entry (ST CPOE) system to ensure safe, high-quality care. Concordance measurement indicators were developed alongside the guidelines and a survey was then conducted to understand the current state in a meaningful and practical manner in the province of Ontario. Methods: A self-assessment survey was distributed to 22 hospital groups, including cancer centres and both academic and community hospitals, using four different ST CPOE systems in Ontario. 52 items were assessed on a four-point Likert scale, and descriptive hospital data was collected. Composite scores were calculated by category (regimen and protocols, functionality, useful alerts, audit logs, system integration, usability) and overall. Local and provincial results were analyzed. Results: Twenty-one (21) responses were received, with the majority (17) of surveys being completed by pharmacists. 48% had been using a ST CPOE system for more than 5 years and 38% for less than one year. 81% responded that they did not, or did not know if, they had local/institutional indicators for monitoring their systems. The mean total concordance score overall was 79% (range 65% to 92%) of a potential 208 total points. The highest mean score was in the category of audit logs (92%) and the lowest in system integration (69%). Approximately half (48%) had a multidisciplinary ST CPOE advisory group. While 16 hospitals were using the same ST CPOE system, there was distinct variability in responses from these sites, indicating the effects of tailored implementations and/or discrepancy in level of knowledge of system functionalities. Conclusions: Current concordance with best practice guidelines for ST CPOE systems in Ontario is incomplete and variable. While ST CPOE systems have potential to improve safety in the chemotherapy delivery, differences in system functionalities and their implementation have been identified. This study will be used to inform specific areas of strength, set benchmarks and potential areas for improvement.
Proof-of-concept: A working demonstration of real-time patient tracking using time-driven activity-based costing.
Authors: Tiffany M. Jones, Yu-Ting Huang, Alexis B. Guzman, Monica DelValle-Garza, Christian C. Kolom, James Incalcaterra, Thomas W. Feeley
Journal: Journal of Clinical Oncology (2014)

28 Background: Historically, hospital costs are based on a cost-to-charge ratio. The current cost system determines when a charge is filed and a bill is created, which can be days following the patient visit. This time lag between the patient visit and the billed charges can be problematic. In preparation for episode-based payments, it is essential to know the true cost of care at the time of delivery. To accomplish this goal, the University of Texas MD Anderson Cancer Center (MDACC) leveraged existing time-driven activity-based costing (TDABC) process maps to track the true costs of the patient care cycle. Methods: The first steps were to understand the patient care cycle through process mapping. Next, data sources were identified to capture patient volumes. Process maps were adjusted to capture the data sources and provide a more accurate cost. Trigger logic models were created to link data sources and the TDABC process maps to the true cost for each patient appointment. Lastly, we developed a SAS software program to compute the real-time TDABC costs for 50 patients in the Head &amp; Neck Center. Results: Our existing data sources capture information relevant to TDABC on a regular basis. Patient appointment data provided the patient visit, and billing and time data provided approximations of the amount of time spent in the encounter and the number of resources involved in the patient visit. Out of 219 process maps, 148 (70%) were matched to existing patient appointment and charge data using the trigger logic. This allowed us to track 4,980 patient appointments for 50 patients in fifteen minutes. Conclusions: As data are collected throughout the institution, it is realized that multiple data sources are needed to reconcile the patient’s experience and to match the TDABC process maps to existing data sources. Since our data sources are updated daily and are based on a patient’s date of service, we can capture our costs of delivering care close to real-time. This process is continually refined as additional data sources are made available and as process maps are developed in other parts of MDACC.
A national strategy for quality and safety in radiotherapy: A comprehensive quality improvement approach.
Authors: Gunita Mitera, Eshwar Kumar, Matthew Parliament, Crystal Angers, Michael Donald Brundage, Suzanne Drodge, Caitlin Gillan, John French, Louise Bird, Jean-Pierre Bissonnette, Lianne Wilson, Erika Brown, Michael Milosevic
Journal: Journal of Clinical Oncology (2014)

148 Background: Canada utilizes a public payer, private health care delivery model, delegated sub-nationally. Effective coordination of uniform access to safe, high quality care can be challenging in this and similar international models. Quality improvement in radiotherapy (RT) involves approximately 50% of all cancer patients who will require RT during their illness. The Canadian Partnership for Quality Radiotherapy (CPQR) is a national quality improvement approach employing pan-Canadian engagement of a multi-disciplinary group of physicians, allied health professionals, administrators and patients. The objectives are to create a national culture of safe, high quality RT delivery for all patients; develop and implement a comprehensive sustainable national program for safe, high quality RT. Methods: All CPQR QA products/programs are processed using standard methodology of review and validation through community consultation, and endorsed by national stakeholders. QA products are incorporated into national QA guidelines and indicators for RT programs, technical equipment and patient experiences; integrating these into a national accreditation program; developing a national RT incident reporting and learning system. Active dissemination strategies use bottom-up and top-down approaches. Results: The national RT programmatic QA guidelines and key quality indicators were released in 2011 and 2013, with 3849 downloads. Approximately 50% of Canadian RT centres indicated implementing CPQR guidelines and changing local QA practices. 9 equipment QA guidelines were developed and validated, 6 are in development. National monitoring and learning structures are being developed through an accreditation program and incident reporting repository to be operated by national organizations for sustainability. Knowledge exchange activities included 26 presentations and 10 national/international invited discussions. A national systematic evaluation process will be executed shortly. Conclusions: CPQR’s national RT QA development and implementation approach is a successful model that can be adopted in other areas of healthcare considering system improvement.