The identification of new targets in cancer biology has changed the traditional approach to cancer diagnosis and treatment and therefore also to drug development. The classical 'one size fits all' approach needed to be modified into a tailored approach that took into account the patient-to-patient variation. Innovative trials are warranted, based on the integration of new types of design and integrating the knowledge coming from new disciplines like bioinformatics, biostatistics, epidemiology and health economics. Several initiatives have started at national levels but also in large pan-European academic organizations [like the European Organization for Research and Treatment of Cancer (EORTC)] in the scope of generating a harmonized healthcare landscape across Europe.
Reliable evaluation of treatment benefit in early phase clinical trials is necessary. The time to progression ratio (TTPr), which compares successive TTP in a single patient, is a powerful criteria for determining targeted or immune therapies efficacy.
EORTC 24971 was a phase III trial demonstrating superiority of induction regimen TPF (docetaxel, cisplatin, 5-fluorouracil) over PF (cisplatin/5-fluorouracil), in terms of progression-free (PFS) and overall survival (OS) in locoregionally advanced unresectable head and neck squamous cell carcinomas. We conducted a retrospective analysis of prospectively collected data aiming to evaluate whether only HPV(-) patients (pts) benefit from adding docetaxel to PF, in which case deintensifying induction treatment in HPV(+) pts could be considered.Pretherapy tumor biopsies (blocks or slides) were assessed for high-risk HPV by p16 immunohistochemistry, PCR and quantitative PCR. HPV-DNA+ and/or p16+ tumors were subjected to in situ hybridization (ISH) and HPV E6 oncogene expression qRT-PCR analysis. Primary and secondary objectives were to evaluate the value of HPV/p16 status as predictive factor of treatment benefit in terms of PFS and OS. The predictive effect was analyzed based on the model used in the primary analysis of the study with the addition of a treatment by marker interaction term and tested at two-sided 5% significance level.Of 358, 119 pts had available tumor samples and 58 of them had oropharyngeal cancer. Median follow-up was 8.7 years. Sixteen of 119 (14%) evaluable samples were p16+ and 20 of 79 (25%) evaluable tumors were HPV-DNA+. 13 of 40 pts (33%) assessed with HPV-DNA ISH and 12 of 28 pts (43%) assessed for HPV E6 mRNA were positive. The preplanned analysis showed no statistical evidence of predictive value of HPV/p16 status for PFS (P = 0.287) or OS (P = 0.118).The incidence of HPV positivity was low in the subset of EORTC 24971 pts analyzed. In this analysis only powered to detect a large treatment by marker interaction, there was no statistical evidence that treatment effect found overall was different in magnitude in HPV(+) or HPV(-) pts. These results do not justify selection of TPF versus PF according to HPV status.
e17527 Background: Physicians are reluctant partners in error reporting. Insufficient evidence exists on what may affect IR in a specific cultural and organizational context. The primary endpoint of our study was to offer a critical perspective on the dominant attitudes toward IR systems among health operators of Friuli-Venezia Giulia cancer network. The survey was part of a Health Department patient safety project. Methods: A preliminary PubMed and ASCO database search was performed (keywords: incident/error reporting, attitudes, barriers, blame/safety culture, cancer, oncology, chemotherapy). Two web-based questionnaires were administered to health personnel of Oncology Units (OU) with developing and existing IR systems, respectively. Data were collected in a MySQL database and managed by PhpMyAdmin. SAS 9.1 was used for the analysis of frequency distributions. Results: Target population: 14 OU; 2 University Hospitals, 1 Scientific Institute for Research, Hospitalization, and Health Care (SIRHHC) (2 OU), 10 Hospital Centers; 262 operators (83 physicians, 172 nurses, 2 pharmacists, 5 technicians). Overall response rate: 44.6%; physician/nurse 59/36%; University Hospital (n = 99)/SIRHHC (n = 55)/Hospital Center (n = 101) 73%/9%/38%. Knowledge of risk management issues: 86% (90% of untrained operators from IR-free centers). Eighty-six percent of all operators showed a favourable attitude toward voluntary IR systems. Main reasons: patient safety improvement (65%); organizational growth (38%); professional duty (20.5%). A 78.5% preference for computerized forms was recorded. On a five-point scale, IR features rating 5 in >50% of the answers were: simplicity (85%); getting a feed-back (76%); exhaustivity (66%); adoption of organization more than individual recommendations (59%). Specific training, feedback guarantee and plainness of reporting forms were suggested by 90, 64, and 51% of all operators as essential measures for system acceptance and user satisfaction. Conclusions: Logistic and organizational factors (i.e., time constraints, work overload, resource allocation to incident reporting more than investigation and learning back) should be taken in account by county health directors aiming for successful reporting systems. No significant financial relationships to disclose.
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