tbuckley/cabot-search huggingface dataset:
Accelerated radiotherapy and temozolomide in adults with newly diagnosed glioblastoma multiforme: A pilot study
Authors: D. N. Korones, M. Milano, P. Okunieff
Journal: Journal of Clinical Oncology (2008)

13014 Background: Radiotherapy is the backbone of treatment for patients with newly diagnosed glioblastoma (GBM). Standard-of- care for this disease includes 6 weeks of once daily radiation to 60 Gy and temozolomide. We sought to improve upon this standard by intensifying the radiotherapy in conjunction with standard dosing of temozolomide. Methods: Patients were eligible for the study if they had newly-diagnosed GBM, were ≥ 18 years of age, and had a WHO performance score of 0–2. Radiation was delivered in 1.6 Gy fractions twice a day, 6 hr between doses (4 weeks; total 64 Gy). The initial target volume included the contrast enhancing lesion and post- operative defect demonstrated on CT/MRI plus a 2.0 cm margin. All patients received temozolomide, 75mg/m2/d×42 days during the 4 weeks of radiation and an addition 2 weeks beyond. A radiosurgery boost was allowed, but not required for patients with residual lesions < 4 cm. One month after completing the low dose temozolomide (6 weeks after radiation), patients received temozolomide, 200mg/m2/d×5 days every 28 days for 12 cycles. Results: 28 patients have been enrolled, all with glioblastoma. Two patients stopped therapy due to fatigue following cycle 1 of post-radiation temozolomide. Median age was 57 years (34–77), and 82% were male. Four had a gross total resection, 14 subtotal resection, and 10 had only a biopsy. Only one patient had a radiosurgery boost. Of the 24 patients evaluable for response, 3 had a partial response, 17 had stable disease, and 4 had progressive disease. The median progression-free survival (PFS) was 5 mo (0–21 mo), and the 6 mo PFS was 44%. Twelve of 25 (48%) evaluable patients were alive at 1 year, and only 2 of 25 (8%) at 2 years. Of the 26 MRI documented recurrences, 17 were local, 3 were outside the radiation field, 4 were satellite lesions, and one each was local + satellite lesion and local + an out-of-field recurrence. Study-related toxicity included one patient with prolonged cytopenia during low- dose temozolomide and one patient with varicella-zoster. Conclusions: We conclude that accelerated radiotherapy in conjunction with temozolomide does not result in a survival advantage for patients with newly diagnosed glioblastoma, and may be associated with an increased of out-of-field recurrences. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Schering-Plough
Prediction of survival in patients with metastatic colorectal cancer treated with third-line cetuximab and irinotecan through changes in microRNA expression in whole blood during treatment
Authors: J. V. Schou, K. K. Andersen, B. V. Jensen, D. L. Nielsen, P. Pfeiffer, E. V. Høgdall, M. Yilmaz, M. Kruhoffer, J. S. Johansen
Journal: Journal of Clinical Oncology (2011)

3532 Background: MicroRNAs (miRNAs) have shown potential as predictive markers for disease outcome in patients with cancer. MiRNA profiling in whole blood from patients with metastatic colorectal cancer (CRC) before and during treatment was performed to identify a panel of deregulated miRNAs and changes in miRNA expression over time that could predict overall survival (OS). Methods: A total of 144 patients with metastatic CRC included in a prospective phase II study of third-line treatment with cetuximab and irinotecan every second week were studied. MiRNAs before and during treatment were isolated from whole blood collected in PAXgene Blood RNA tubes (Qiagen), and miRNA profiling was performed using TaqMan MicroRNA Array v2.0 (Applied Biosystems). The Cox proportional hazard (CPH) model was applied to study the absolute effect of miRNA expression on OS. Each miRNA expression for every measurement was included as a time varying covariate and each miRNA effect on OS was tested. All miRNA that met the 0.001 significance level was then included in a multivariate CPH model. Second, we studied the effect of miRNA change over time by calculating relative changes in miRNA for patients with at least two miRNAs (n=105). Results: At time of follow-up 132 (92%) of the patients were dead. High expression of miR-361-5p and miR-597, and low expression of miR-31, miR324-3p, let-7e and miR-24 predicted OS after controlling for KRAS mutation status, performance status, age and gender. Hazard ratios (HR) and 95% confidence interval (CI) were miR-31 (0.72; 0.55-0.94), miR-361-5p (2.01; 1.33-3.03), miR-597 (1.70; 1.27-2.27), miR324-3p (0.47; 0.31-0.70), let-7e (0.63; 0.44-0.90) and miR-24 (0.66; 0.44-0.99). During treatment, relative changes in miRNA expression for miR-31 (0.77; 0.62-0.95), let-7g (0.62; 0.43-0.89) and miR-424 (1.38; 1.08-1.76) predicted OS. Conclusions: We identified 6 miRNAs that may be good biomarkers of value for OS in patients with metastatic CRC treated with cetuximab and irinotecan. MiR-31 was a predictor for OS at any time point during treatment, and relative change in miR-31 expression during treatment was a predictor for OS.
Telephonic assesment of consumer satisfaction of telephonic case management of cancer patients.
Authors: Arthur H. Rossof, Michael W. Rosen, Melissa Lindholm, Pam Schumacker, Diane Richards
Journal: Journal of Clinical Oncology (2016)

80 Background: Feedback provided by customers/consumers has become an established means of assessing the quality of goods and services. The Optum division of UnitedHealth Group maintains two telephonic case management programs for cancer patients to support quality and cost effective care: Cancer Resource Services (CRS) and the Cancer Support Program (CSP). In each case, the purpose of the telephonic intervention is to provide support, education, and, when appropriate, steerage to one of our contracted Centers of Excellence (COEs). Methods: In this report, we provide satisfaction data collected during 2014 from surviving patients whose cases were closed or reached their 1-year anniversary in these case management programs. These telephonic surveys were conducted by a contracted third party. Results: For CRS, 363 members were contacted and surveys were completed; for CSP, 400 were contacted and completed. Average age was 61 (CRS) and 57 years (CSP). 61% were women. Sixty-two % of the CRS patients were treated at a COE as were 59% of the CSP patients. For CRS members, 90% experienced a positive health care experience (satisfied or very satisfied); for CSP, 94%. Quality of life was improved in 51% for CRS and 65% for CSP. For all four of these measures, there was a statistically significant (p &lt; 0.05) improvement compared with the survey data from 2013. There was 96% overall satisfaction with the program for both CRS and CSP, while overall satisfaction with the nurse/case manager was 96% (CRS) and 98% (CSP). 96% (CRS) and 94% (CSP) are likely to recommend these services to others while 97% and 91% are likely to use these services again if needed. Positive comments outweighed suggestions for improvement. The most common suggestion for improvement was to expand the availability of these services. Conclusions: We conclude that our members with cancer are benefiting from the experience of telephonic case management by our experienced oncology nurse/case managers who are, in turn, assisted by our associated staff of social workers and medical directors.
Perioperative chemotherapy with ECX +/- panitumumab in locally advanced gastroesophageal adenocarcinomas (GEA): A randomized study of the Arbeitsgemeinschaft Internistische Onkologie and the Chirurgische Arbeitsgemeinschaft Onkologie of the German Cancer Society.
Authors: Michael Stahl, Andre L. Mihaljevic, Markus Moehler, Stephan Kanzler, Thomas Hoehler, Peter C. Thuss-Patience, Stefan Paul Moenig, Volker Kunzmann, Sebastian Schroll, Florian Lordick, Hans-Joachim Meyer, Andreas Sandermann, Christoph Schumacher, Hansjochen Wilke
Journal: Journal of Clinical Oncology (2015)

104 Background: Perioperative chemotherapy represents the European standard of care in locally advanced GEA. Efficacy may be improved by combining chemotherapy and molecular targeted drugs. Due to overexpression of epidermal growth factor receptor (EGFR) in most GEA EGFR-inhibitors may be candidates for such improvement. Methods: To evaluate the role of EGFR-antibodies in the perioperative treatment we performed a multicenter randomized phase II study. Patients with locally advanced (cT3-4 N0-3 M0) adenocarcinomas of the stomach or gastro-esophageal junction (GEJ) were eligible. Patients were treated with ECX with (arm 1 ) or without (arm 2) panitumumab (P, 9 mg/kg body weight iv, q 3 weeks). Three cycles were planned prior to and after surgery. The primary endpoint was to prove a reduction in ypT3-4 categories by adding P to ECX. Results: From 11/2010 to 7/2013 a total of 171 pts. were randomized, and 163 pts. (83 arm 1, 80 arm 2) were eligible. Prior to therapy 29% of the pts. in both arms had T4 tumors (CT scan and EUS) and 82% vs. 78% showed lymph node involvement. In 42% vs. 45% the primary tumour was located in the GEJ. 68 pts. (82%) vs. 68 pts. (85%) completed 3 preoperative cycles. The mean total dose of preoperative chemotherapy related to the planned dose reached 90% for panitumumab (arm 1 only), 91% vs. 92% for cisplatin, and 81% vs. 85% for capecitabine. R0-resection was achieved in 90% vs. 89% of the patients. The rate of pts. without downstaging (ypT3-4 at surgery) was statistically not significant higher in the experimental arm (73% vs. 66%, p=0.23), as was the overall treatment failure in the ITT analysis (odds ratio 1.37 (0.65-2.86)). The PCR-rate (ypT0N0) was comparable (3% vs. 5%, p=0.43). One toxic death was observed during chemotherapy (arm 2) and 1 pt. of both arms died due to complications after surgery. Conclusions: The study failed to reach its primary endpoint. The addition of P to ECX was not able to improve downstaging of locally advanced GEA. Survival data and results of translational research will be available during the course of 2015. Clinical trial information: NCT01234324.
Key drug development features in the design of early-phase oncology trials: An FDA perspective.
Authors: R. Charlab Orbach, G. M. Blumenthal, P. Cortazar, K. K. Filipski, C. Grimstein, L. Zhang, P. Mummaneni, B. Booth, I. Zineh
Journal: Journal of Clinical Oncology (2011)

2597 Background: FDA drug approval requires demonstrated efficacy in adequate, well-controlled trials. In oncology, two key questions should be asked prior to initiation of “pivotal” efficacy trials: 1) which patient subsets should be enrolled into efficacy trials; and 2) what dose(s) should be tested? Improved phase 1 (P1) trials may help answer these questions and maximize likelihood for success in later development. We developed a knowledge management (KM) tool to aid FDA scientists in amassing a database of P1 trial characteristics, with the intention of developing standardized regulatory advice for future oncology drug development. Methods: We evaluated medical literature and investigational new drug (IND) P1 protocols submitted to FDA to determine key elements for database development. We then convened a panel of FDA clinical oncologists, pharmacologists, and pharmacogeneticists to determine what data should be captured to 1) allow comparisons of early drug development features for successful and unsuccessful development programs; and 2) inform future regulatory policy. Results: The KM tool was devised to capture information that could signal whether enrichment strategies should be considered or differential drug responses could be expected in later trials. In addition, the searchable database captures key elements from early phase oncology trials such as: a) molecule type and mechanism of action for targeted or non-targeted agents; b) molecular alterations known to associate with disease or drug target; c) PD assessment in tumor and surrogate tissues; d) molecularly- or clinically-enriched dose escalation and expansion cohorts; e) availability of a molecular test to select patients most likely to benefit from therapy; f) dosing schedule; g) dose escalation method and protocol-defined escalation endpoint; h) dose-limiting toxicity; i) observed responses; and j) recommended vs. actual phase 2 doses. Conclusions: P1 trials are important in helping guide drug development. We developed the first regulatory database of P1 trial design features to serve as a source for comprehensive assessment of early oncology drug development programs, which may be used for future policy development.
Prevalence of self-reported cognitive dysfunction in breast cancer patients.
Authors: Heidi Skirbe, Gabriela Hohn, Paula Klein, Mary Ann Juliano, Jeremy Winell, Victoria Rosenwald, Joanne Festa
Journal: Journal of Clinical Oncology (2013)

e20701 Background: A series of four time-limited, psycho-educational workshops was piloted by a neuropsychologist at an urban academic medical center, providing information, coping strategies, and resources to women who had been treated for breast cancer (BrCa) and who then sought cognitive treatment. Based on positive evaluations of these workshops, we assessed the prevalence of self-reported cognitive dysfunction in BrCa patients with the goal of assessing the need for and interest in the expansion of cognitive services to affected patients. Methods: The study was IRB approved. A convenience sample of 50 BrCa patients in a medical oncology waiting area completed a 16 item questionnaire which assessed potential cognitive problems on a 4-point Likert scale, with responses ranging from 0 (no problem) to 3 (serious problem). Results: Fifty patients completed the survey, of whom 46% requested further information on cognitive services. Conclusions: An unexpectedly large proportion of BrCa patients perceived cognitive difficulties, possibly compounded by fatigue and emotional dysfunction, and expressed interest in cognitive supportive services. Others may have failed to report cognitive difficulties, unaware of their onset. Quality of life of cancer patients is diminished by cognitive decline. Our data indicate a need for and interest in formal assessment and intervention programs to identify patients with cognitive and emotional dysfunction and offer remediation via workshops and therapy. Formal neuropsychological assessment and treatment resourcestargeting cognitive changes associated with cancer should be expanded to meet documented need. Further research will optimize the scheduling and structure of interventions. [Table: see text]
Predictors of accrual to clinical trials in an integrated health care delivery system.
Authors: C. P. Somkin, L. M. Ackerson, G. Husson, T. Kolevska, D. Goldstein, L. Fehrenbacher
Journal: Journal of Clinical Oncology (2011)

6093 Background: While many studies have identified major barriers to physicians’ enrolling patients in clinical trials, few have examined the effect of these barriers on actual trial accrual. Methods: In 2008 we conducted a mail survey of 88 oncologists and combined the results with data on clinical trial accrual in the subsequent 2 years for each oncologist. The survey sample included all adult medical oncologists at Kaiser Permanente Northern California. The survey instrument assessed physicians’ views on (1) value of trials; (2) time and effort needed to enroll and follow trial patients; (3) availability of services to support trials; (4) importance of trials to themselves and (5) their organization; (6) patient opinions about trials; as well as physicians’ (7) awareness of, and experience with, trials generally and with specific trials; (8) preferences for specific elements of trial design; (9) experience communicating with patients about trial concepts. Primary outcome measure was the number of patients enrolled in a trial in the 2 years following the survey. A summary score was calculated for each of the domains above by averaging the responses to the questions in each domain. We calculated a Spearman correlation between each domain score and the number of patients enrolled in any cancer clinical trial in following 2 years. Results: Out of a survey sample of 88 medical oncologists, 74 (84%) responded. Out of 606 patients enrolled in oncology clinical trials, responders enrolled a median of 5 patients in 2 years. Despite the fact that 82% reported that “clinical trials were their first choice of therapy if available” the percent of total enrollment activity by the top, middle, and lowest third of oncologists was 75%, 20%, 5% respectively. Domains most highly correlated with a doctor’s enrollment rate were views on the value of trials (correlation: 0.29, 95% CI: 0.06 to 0.49); awareness of/experience with trials (correlation: 0.33, 95%CI: 0.11 to 0.52); and perceived unavailability of support services (correlation:-0.23, 95%CI: -0.44, to -0.002). Conclusions: Even among oncologists in an organization with similar access to trial support and resources, individual values and awareness of, and experience with, trials affect enrollment.
Does the multidisciplinary approach in prostate cancer improve patient outcome?
Authors: L. Nicacio, N. J. Combates, J. Beetsch
Journal: Journal of Clinical Oncology (2011)

e16556 Background: The benefits of the multidisciplinary approach (MDA), defined as the converging of multiple specialties or technologies to establish a diagnosis and develop a treatment plan // for optimal patient management, are well known in many clinical disciplines. In breast cancer, for example, it has led to significant strides in the reduction of disease incidence and mortality. We investigated whether the MDA affects clinical endpoints and patient care in prostate cancer (PCa) and if advanced PCa is a part of current MDA initiatives. Methods: To examine evidence supporting efficacy of the MDA in treating PCa, evidence-based PCa literature was searched from 2007-2010 using the search terms MDA, care coordination, medical home, and patient management for PCa. Also, source references of articles found and a special issue of the Journal of Oncology Practice (JOP) on multidisciplinary care were reviewed. Additionally, through Internet-based searches with standardized search terms, we identified and interviewed US PCa providers with clinical practices purporting to use the MDA. Results: Of the 270 articles identified from the search, plus 559 from source references, plus the JPO issue, 32 articles addressed MDA in PCa. Overall, the identified publications demonstrated lack of a uniform definition of MDA care and substantial methodological variability. No article reported increased survival using the MDA approach in PCa; the vast majority were descriptive and none presented clinical outcomes. Of the 14 MDA providers interviewed, only 7 offered true MDA. The other 7 retrospectively reviewed select cases via a tumor board. There was no uniformity about the definition of MDA, a focus only on early localized disease, and no consensus as to the opportune time to refer advanced patients to medical oncology. Late-stage PCa was viewed as noncontroversial with well-defined treatment regimens. Conclusions: There is strong support for clinical coordination in PCa. However, the association between MDA and clinical benefit has not been determined. There is much need for clinical decision points along the PCa treatment continuum to reduce variability and improve quality care.
Should lymph node retrieval be a surgical quality indicator in colon cancer?
Authors: Reilly Patrick Musselman, Mingyang Xie, Kelsey McLaughlin, Husein Moloo, Robin P Boushey, Rebecca Ann C Auer
Journal: Journal of Clinical Oncology (2012)

648 Background: Adequate lymph node harvest is easily obtained and is necessary for proper staging of colorectal cancer, making it an attractive measure of surgical quality for policy makers. However, achieving an adequate lymph node harvest requires a multidisciplinary effort. The purpose of this study was to determine if it is appropriate to use this measure as a surgical quality indicator for individual surgeons. Methods: The study was undertaken at a high volume center with standardized colon cancer specimen processes. The charts of 1,138 consecutive segmental colon cancer surgeries performed between 2002 and 2008 were retrospectively analyzed. The primary outcome was inadequate lymph node retrieval for colon cancer surgery defined by fewer than 12 lymph nodes on pathology. Predictor variables were based on patient, surgeon, pathology and tumor related factors. Univariate analysis was performed on all potential predictor variables, followed by multivariate logistic regression. Results: 841 cases (69.0%) achieved adequate lymph node harvest, while 377 (31.0%) were inadequate. Factors on univariate analysis associated with inadequate lymph node harvest were specimen length (p&lt;0.0001), tumor location (p&lt;0.0001), and T-stage (0.0015), all of which remained significant multivariate logistic regression. The average specimen length differed by 3.6 cm between non-adequate and adequate specimens. When broken down by procedure, resection length did not vary significantly between high and low volume surgeons or between colorectal and non-colorectal surgeons. Furthermore when surgeons were ranked according to their success rate of &gt;12 LN retrieval, there was no difference between surgeons in mean specimen length. Conclusions: In a high-volume, tertiary care centre that uses standardized practices for specimen processing, 31% of cases yielded fewer than 12 lymph nodes. Factors relating to the patient and tumor were the primary predictors of a successful outcome and there was no association between surgeon-related factor and adequate LN retrieval. Caution should be used when considering LN harvest as a surgical quality indicator for individual surgeons.