tbuckley/cabot-search huggingface dataset:
Statistical methods as a problem-solving strategy in health care.
Authors: Diane Schaub, James Terrell
Journal: Journal of Clinical Oncology (2012)

279 Background: Clinical personnel in healthcare are being challenged to improve quality and increase productivity in order to lower healthcare costs in the United States. With the effort to become more cost conscious, there is an ever increasing need to analyze processes and make them more efficient. The complexity of these processes and the data associated with them require more complex analysis and more sophisticated statistical tools. Unfortunately the statistical training of many health care employees is not adequate for the more complex tools and processes. Methods: At the University of Texas MD Anderson Cancer Center, we use Minitab software, widely used in the manufacturing sector, as our primary statistical analysis software. It is on this platform that the Office of Performance Improvement is creating training courses to assist in raising the statistical literacy level of clinical employees. This software is fairly easy to use, and contains tools for visualizing data such as control charts and box plots, as well as performing multivariable analysis such as regression or ANOVA (Analysis of Variance). Results: Early adopters of the methodology to utilize statistical tools in process improvement studies has been extremely positive. They enjoy being able to quantify their improvement results, document them, and share them with others. Conclusions: Process Improvement leaders need to improve their skills in several areas of statistical methodology. Specifically, they should be able to select the correct graphic to show the critical information in their data, they should be able to select the proper tools and perform analysis to interpret the data, and they should have a technical vocabulary to share and communicate their key learning with others. Minitab is a widely accepted software package for process improvement here at MD Anderson Cancer Center. There are many other very good software packages on the market but it is helpful for support, teaching, and consistency if an institution settles on a package as a basic standard.
Morbidity, mortality, and improvement (MM&amp;I) conference leading to change.
Authors: Andrew Jacob Moore, Tracy Coyne, Dana Backlund Cardin, Jill Gilbert
Journal: Journal of Clinical Oncology (2012)

94 Background: During quarterly MM&amp;I Conferences, a recurrent systems problem identified was the underreporting of chemotherapy infusion reactions. Attendees acknowledged difficulty in obtaining accurate data regarding adverse events and justifications for treatment cessation, which may lead to under dosing of effective therapies. Methods: MM&amp;I conference is an interactive multidisciplinary forum that emphasizes discussion to improve system-based problems. Attendees include faculty, fellows, residents, nursing staff, informatics and pharmacy representatives. Participants used the Ickwaka Fishbone Diagram to identify issues that led to underreporting of reactions. Through discussion of the issues and identification of potential improvement activities, participants recognized that improved nursing documentation could accurately capture data related to adverse drug events. Representatives from the informatics department identified a report that could be generated automatically when infusions are stopped that would require nursing staff to identify the type of reaction and give justification for not completing the infusion. Reports would also include actions taken and patient responses. Results: Implementation of electronic nursing documentation revealed that the prevalence of infusion reactions were much higher than previously identified. During the first 6 months of electronic documentation there were 71 identified reactions compared to 46 reactions documented during the 6 months prior to implementation. Paclitaxel (22%) and Rituximab (39%) were identified as the two most common agents associated with infusion reactions. Twenty (28%) infusion reactions resulted in cessation of that particular chemotherapy. Conclusions: The format of the MM&amp;I Conference engaged members of a multidisciplinary team to promote collaboration for system-based improvements in patient care and safety. Electronic nursing documentation has put a mechanism in place to capture data related to infusion reactions that will allow us to evaluate the effectiveness of future interventions to decrease the prevalence of infusion reactions, as well as the number of therapies that are stopped indefinitely due to these reactions.
Effect of novel growth hormone-releasing hormone antagonists on growth of experimental renal cell carcinomas.
Authors: Ferenc Rick, Luca Szalontay, Andrew Abi-Chaker, Norman L. Block, Gabor Halmos, Andrew V. Schally
Journal: Journal of Clinical Oncology (2013)

469 Background: Although targeted therapy has improved the clinical outcome for patients with metastatic renal cell carcinoma (RCC), a complete response is rare and therapy has adverse effects. Early antagonists of growth hormone-releasing hormone (GHRH) were shown to inhibit experimental RCC cell line, Caki-1, in vitro and in vivo. Herein, we investigate the effects of novel and highly potent antagonists of GHRH of MIA class on the growth of three RCC cell lines. Methods: The expression of GHRH receptor in all three cell lines was evaluated by ligand competition studies. The influence of GHRH antagonists MIA-602, MIA-604, MIA-606, and MIA-690 on cell viability was assessed by MTS assay in ACHN, A498, and 786-0 human RCC cells. GHRH antagonists were given at dose of 5µg daily in these three nude-mice xenograft models. Cell cycle parameters were analyzed by laser flow cytometry. Results: Ligand competition studies revealed specific, high affinity binding sites for GHRH receptor in all three RCC cell lines. GHRH antagonists inhibited the proliferation of all three RCC cells in a dose dependent manner. GHRH antagonists caused significant inhibition of tumor growth of ACHN, A498, and 786-0 RCCs ranged from 53-75% after 35 days of treatment (p&lt;0.001). Treatment of ACHN cells with MIA-690 (10µM) led to a significant increase in number of cells with subG 1 DNA content, suggesting apoptosis. Conclusions: The effectiveness of the novel GHRH antagonists in inhibiting growth of experimental RCC models in vitro and in vivo was demonstrated. The inhibitory effect of GHRH antagonists is mainly due to direct inhibitory effects exerted through GHRH receptors. Biochemical and histological evaluation is needed to explore the mechanisms of action of GHRH antagonists in RCC.
Prevalence of overweight and obesity in a population of childhood leukemia patients and survivors.
Authors: Jennifer Lyn Jordan, Robert Michael Cooper
Journal: Journal of Clinical Oncology (2012)

324 Background: Overweight and obesity (BMI&gt;95 percentile) in the pediatric population has become a prominent problem. The prevalence of pediatric obesity has increased from 5% in 1976-1980 to 17% among children and adolescents in 2007-2008. The presence of obesity in survivors of certain childhood cancers has been identified as a late effect of therapy, especially in survivors of ALL and brain tumors. Obesity prevalence following treatment for ALL ranges from 11-57%. The long-term health consequences of obesity include diabetes mellitus, hypertension, cardiovascular disease, metabolic syndrome and certain cancers. Kaiser Permanente (KP) tracks pediatric BMI as part of routine health maintenance. There is an initiative to promote Healthy Eating and Active Living (HEAL) and reduce childhood obesity. As part of this initiative the HEAL clinic provides a multi-disciplinary weight management program for the general adolescent population at KP Los Angeles Medical Center (LAMC). Methods: A chart review was conducted using the electronic medical record system at LAMC. 99 records, 22 current patients and 77 survivors of ALL, were identified and reviewed for Body Mass Index (BMI) and compared to the general pediatric population of KP in Southern California. Results: See Table. 57 leukemia patients and survivors were identified as overweight or obese, which is a 57.5% prevalence rate. This is significantly higher than the rate of pediatric overweight and obesity of 37.1% in the KP Southern California general population. Conclusions: The use of an electronic medical record system confirms a higher prevalence of overweight and obesity in the ALL patients and survivors at KP LAMC than the general pediatric population in Southern California. The intervention piloted by the HEAL clinic has been adapted to treat this group of overweight and obese cancer patients and survivors. [Table: see text]
Concurrent or sequential adjuvant hormonoradiotherapy after conservative surgery for early stage breast cancer: First results of the CO-HO-RT phase II randomized trial
Authors: D. Azria, Y. Belkacemi, G. Romieu, S. Gourgou-Bourgade, K. Zaman, M. Gutowski, B. S. Rosenstein, C. Llacer Moscardo, C. Lemanski, M. Ozsahin
Journal: Journal of Clinical Oncology (2008)

556 Background: We recently showed in an aromatase-gene transfected breast cancer cell line, a radiosensitizing effect of letrozole. We then conducted a multicentric phase II randomized trial evaluating adjuvant concomitant radiotherapy and letrozole with radiotherapy followed by letrozole in postmenopausal early breast cancer patients (CO-HO-RT trial). Methods: Postmenopausal pts with early stage breast cancer were randomized after conservative surgery to either: A) concurrent RT-LET (LET started 3 weeks before the first day of RT) or B) sequential RT-LET (LET started 3 weeks after the end of RT). Whole breast RT was delivered to a total dose of 50 Gy ± a 10–16 Gy boost. Pts were stratified by center, adjuvant chemotherapy (ACT), boost, CD8 radiation-induced apoptosis. Primary endpoint was radiation-induced acute and late skin toxicity. Skin toxicities were evaluated by two different clinicians at each medical visit (CTCAE v3.0). Lung CT-scan and functional pulmonary tests were performed regularly. Quality of life and cosmetic assessments were registered. DNA samples were screened for SNPs in the ATM genes. Results: A total of 150 pts were randomized between 01/05 and 02/07. Median follow-up was 17 months (range, 6–49). No statistical differences were identified between the two arms in terms of mean age; initial TNM; median surgical bed volume; postsurgical breast volume. ACT and RT boost were delivered in 19% and 38% of pts, respectively. Overall, 10 patients (6.7%) presented grade 3 acute skin dermatitis during RT without differences between both arms. Grade 2 acute skin dermatitis was observed in 36.5% and 32% in arm A and B, respectively, but symptoms rapidly settled in most patients by months 3, 6, and 12. Grade 2 radiation-induced subcutaneous fibrosis was found in 8 patients (5%) with a slight difference in disfavor of arm B (7%) vs 4% in arm A. Three patients (2%) presented a grade 2 pneumonitis (all in arm A). Overall, quality of life and cosmesis were good to excellent. Conclusions: Concurrent or sequential adjuvant radiohormonotherapy with letrozole is feasible in daily practice. Identifying hypersensitive patients with CD8 RIA or ATM screening will help tailoring treatments. No significant financial relationships to disclose.
Phase II study of trastuzumab in combination with capecitabine and oxaliplatin in patients with advanced gastric cancer.
Authors: Min-Hee Ryu, Baek-Yeol Ryoo, Young Soo Park, Sook Ryun Park, Jong Gwang Kim, Hye-Suk Han, Ik-Joo Chung, Eun-Kee Song, Kyung Hee Lee, Seok Yun Kang, Yoon-Koo Kang
Journal: Journal of Clinical Oncology (2014)

83 Background: Trastuzumab (Herceptin) in combination with capecitabine and cisplatin has been the standard first-line chemotherapy in patients with HER2-positive advanced gastric cancer (AGC). Oxaliplatin is generally less toxic and more convenient than cisplatin, and currently replacing cisplatin for the treatment of AGC. This study aims to investigate the efficacy and safety of trastuzumab in combination with capecitabine and oxaliplatin (HER-XELOX) in HER2-positive AGC. Methods: With Simon’s minimax two stage design (P 0 [response rate of historic control]=0.4, P 1 =0.55, two-sided alpha=0.1, beta=0.2, and 10% drop-out rate), a total of 55 patients with AGC positive for HER2 defined as either HER2 immunohistochemistry (IHC) 3+ or IHC 2+and FISH+ were enrolled from Aug 2011 to Feb 2013. HER-XELOX regimen consisted of trastuzumab 8 mg/kg i.v. on day 1 in cycle 1 and then 6 mg/kg in subsequent cycles, capectabine 2000 mg/m 2 /day p.o. on days 1-14, and oxaliplatin 130 mg/m 2 i.v. on day 1, every 3 weeks. HER-XELOX was administered as a first-line chemotherapy until disease progression, unacceptable toxicity, or consent withdrawal. Results: Among the 55 patients, 37 (66%) patients were male. Median age was 57 years (range, 29-74). ECOG performance status was 0-1 in 51 (93%) patients. Fifty three (96.4%) patients had metastatic disease, and 2 (3.6%) had locally advanced unresectable disease. With complete response in 2 patients and partial response in 35 patients, confirmed overall response rate was 67.3% (95% CI, 54-80%). With a median follow-up of 13.8 months (range, 6.1-23.9) in surviving patients, median progression-free survival was 9.8 months (95% CI, 7.0-12.6). Median overall survival was 21.0 months (95% CI, 6.4-35.7). Common grade 3 or 4 toxicities with frequency &gt; 10% included neutropenia (18.2%), anemia (10.9%), and neuropathy (10.9%). There was no febrile neutropenia. One patient died of treatment-related diarrhea and sepsis. Conclusions: HER-XELOX regimen is well tolerated and highly effective in patients with HER2-positive AGC. Clinical trial information: NCT01396707.
Effect of preoperative radiotherapy on local recurrences in rectal cancer patients with <i>PIK3CA</i> mutation.
Authors: Y. He, L. van 'tVeer, M. Lopez Yurda, I. Mikolajewska-Hanclich, I. D. Nagtegaal, C. J. Van De Velde, C. A. Marijnen
Journal: Journal of Clinical Oncology (2010)

3639 Background: Preoperative (chemo) radiation has a significant reducing effect on local recurrence rates in rectal cancer. Identifying rectal cancer patients who are at risk for local recurrence (LR) would allow for refinement in selection of patients who would benefit from preoperative radiotherapy (PRT). PIK3CA mutations have been demonstrated to correlate with poor prognosis among patients with resectable stage I to III colon cancer. In non-PRT stage I-III rectal cancer patients, we demonstrated a 5-year LR risk of 28% for mutated patients vs. 9% (p = 0.006) for nonmutated patients (He, CCR 2009). In this study, we evaluate whether PIK3CA mutant rectal cancer patients benefit from PRT in preventing LR. Methods: Patients were derived from the Total Mesorectal Excision (TME) trial, in which stage I-III rectal cancer patients were randomized for PRT (5x5 Gy) followed by TME surgery, or TME surgery only (median follow-up 7.2 years). A case-only design was used to evaluate the frequency of PIK3CA mutations in both irradiated and nonirradiated patients with a LR. Tumor-tissue of 24 out of 74 nonirradiated and 30 out of 32 irradiated patients with a LR was available. PIK3CA mutations in exon 9 and 20 were evaluated by PCR and sequencing. Results: We previously demonstrated a PIK3CA mutation frequency of 7.9% in 240 nonirradiated patients. In nonirradiated patients with a LR, the frequency of PIK3CA mutations was 20.8% (5/24), whereas in irradiated LR patients only 6.7% (2/30) PIK3CA mutations were found (OR = 0.27; 95% CI 0.05-1.56, p = 0.14). Due to the overall small number of mutations (∼8%), 29 cases (PIK3CA mutants) and 190 controls (wild-type patients) with a LR would be required to increase the power to a 90% level, which is 69 irradiated and 150 nonirradiated patients. Conclusions: PIK3CA mutations can be used as a prognosticator to identify rectal cancer patients with an increased risk for local recurrences. The odds ratio evaluating the beneficial effect of PRT on PIK3CA mutant patients suggests that PIK3CA mutations may also be used as a predictor for PRT benefit. This finding supports our suggestion that prospective evaluation of PIK3CA mutation status can reduce overtreatment for low-risk rectal cancer patients. No significant financial relationships to disclose.
Survival after Yttrium-90 radioembolization in elderly and nonelderly patients with hepatocellular carcinoma or colorectal cancer liver metastases.
Authors: Rebecca Ann Redman, Douglas Coldwell, Vivek R. Sharma
Journal: Journal of Clinical Oncology (2015)

449 Background: Systemic treatment of unresectable hepatocellular carcinoma (HCC) or colorectal cancer liver metastases (CLM) in the elderly can be complicated by increased toxicity. In addition, the increasing incidence of comorbidities with age may preclude surgical resection with curative intent. Hepatic arterial therapy is increasingly utilized in patients with HCC or CLM not amenable to surgical resection. Studies of transarterial chemoembolization in the elderly have generally shown similar safety and efficacy as compared to younger patients, although some studies suggest worse outcomes. The selective nature of radioembolization has the potential for improved tolerability in this patient population. Methods: We report the results of a retrospective review of patients with unresectable HCC or metastatic disease to the liver treated with Yttrium-90 radioembolization at a single institution. Results: Patients were referred for treatment after multidisciplinary evaluation, but were not treated as part of a clinical trial. A total of 94 patients treated were evaluable for follow up. There were approximately twice as many males as females (64% vs 36%). Elderly was defined as 70 years of age or older, representing 20 of the 94 patients. Average age of the elderly cohort was 76 (range 70-90), compared to 56 years of age (range 23-69) for the younger patients. Survival was measured from date of first radioembolization. Median survival was similar for elderly and younger patients when considering all tumor types (337 days vs 288 days). There was no difference in median survival between elderly and non-elderly patients with CLM (377 days vs 365 days) or with HCC (370 days vs 363 days). Conclusions: In our experience, survival after Yttrium-90 radioembolization in elderly and younger patients with primary HCC or CLM is similar. Age alone should not preclude consideration for liver-directed therapy.
Obstacles to evaluation of adverse drug events (ADEs) occurring during pharmaceutical sponsored clinical trials of new cancer drugs: Preliminary findings from the RADAR/IRB study
Authors: D. West, S. M. Belknap, S. A. Weitzman, P. Yarnold, L. Qualkenbush, T. Kuzel, A. Benson, C. L. Bennett
Journal: Journal of Clinical Oncology (2005)

6100 Background: More than 80% of all clinical trial deaths occur during cancer drug clinical trials. Given the substantial toxicity of cancer drugs and the high number of fatalities in cancer drug clinical trials, it is essential that ADE reporting be accurate and complete. We hypothesized that a modular drug-toxicity specific case report form would improve the completeness and quality of ADE reports to the IRB. As part of a collaboration among three NCI-designated comprehensive cancer centers, we developed a plan to evaluate the quality and completeness of ADE reports submitted to each IRB for four new cancer drugs. Methods: The study plan was to evaluate IRB adverse event reports for bevacizumab, oxaliplatin, gefitinib, and imatinib. For all clinical trials for each of these 4 cancer drugs, we requested formal approval to evaulate cancer drug-associated ADEs from the local IRB, the local cancer center, the local principal investigator (PI), the relevant cooperative oncology group (RCOG), and the pharmaceutical industry sponsor (pharma). Results: Thus, the study sample consists of all subjects in clinical trials of bevacizumab. There were 42 bevacizumab-associated adverse events among 110 subjects enrolled in 6 separate trials. Conclusions: Evaluation of drug safety in cancer clinical trials is constrained by barriers imposed by pharmaceutical sponsors. The scope of our work was substantially hampered by the unwillingness of some sponsors to participate. Future contracts with pharmaceutical sponsors should explicitly allow local investigators and their collaborators to evaluate and report their own ADE observations and to collate ADE data across multiple sites. Additional work is needed to further define the characteristics, frequency, and quality of cancer drug adverse event reports to the IRB and to sponsors. No significant financial relationships to disclose.
Pulmonary complications with the use of mTOR inhibitors in targeted cancer therapy: A systematic review and meta-analysis.
Authors: Benjamin Adam Gartrell, Jian Ying, Shanthi Sivendran, Neeraj Agarwal, Kenneth M. Boucher, Toni K. Choueiri, Guru Sonpavde, William K. Oh, Matt D. Galsky
Journal: Journal of Clinical Oncology (2013)

362 Background: mTOR inhibitors are approved in several malignancies including renal cell carcinoma (RCC). While pulmonary toxicities are a recognized adverse effect associated with this drug class, the frequency and risk of these side effects have not been well characterized. Methods: Clinical trials of mTOR inhibitors in solid tumors were identified through a search of PubMed and ASCO abstracts. Prospective studies of temsirolimus, everolimus, and ridaforolimus in solid tumors were evaluated for inclusion. 22 eligible phase II and phase III trials that included 4,242 patients were identified and included in a systematic review and meta-analysis. Adverse event data was extracted for pulmonary complications including pneumonitis, dyspnea, and cough. The incidence rate and the incidence rate ratios were determined for these pulmonary adverse events. Results: Based on our analysis of the 20 trials that reported pneumonitis, the incidence rate of any grade pneumonitis in patients with solid tumors treated with mTOR inhibitors is 0.11 (95% CI, 0.06-0.17). The incidence rate of grade 3 or 4 pneumonitis is 0.03 (95% CI, 0.01-0.04). The incidence rate ratio of any grade pneumonitis with mTOR inhibitors relative to controls is 18.9 (95% CI, 6.5-55.1), and the incidence rate ratio for the development of grade 3 or 4 pneumonitis is 7.9 (95% CI, 2.6-24.0). The incidence rates of any grade cough and dyspnea were found to be 0.23 (95% CI, 0.20-0.27) and 0.15 (95% CI, 0.10-0.21), respectively. The incidence rates of grade 3 or 4 cough and dyspnea are found to be 0.01 (95% CI, 0.00-0.01) and 0.03 (95% CI, 0.02-0.04), respectively. There was a statistically significant, but modest increase in risk of developing any grade cough (incidence rate ratio of 1.9 [95% CI, 1.6-2.4]) and grade 3 or 4 dyspnea (incidence rate ratio of 2.0 [95% CI, 1.2-3.3]) with mTOR inhibitors relative to controls. Conclusions: This study confirms that mTOR inhibitors are associated with pulmonary adverse events and provides a quantitative estimation of the risk of these adverse events in solid tumor patients treated with these drugs. The majority of pulmonary adverse events are low grade.