RESUMO
PURPOSE: It is essential for radiation oncology departments to have comprehensive patient safety and quality programs. Two years ago we undertook a systematic review of our safety/QA program. Existing policies were updated and new policies created where necessary. One crucial component of any safety/QA program is continually updating it based on current information, the 'check' and 'act' portions of the Deming Cycle. We accomplished this with a transparent variance reporting system and a safety/QA committee reviewing and acting on reported variances. METHODS: With 5 radiation oncology centers in our institution, we needed to devise a system that would allow anyone to report a variance and provide our QA committee the ability to review variances system-wide. We developed the system using web-based tools. The system allows individuals to report variances, anonymously or named, specify the nature of the variance and indicate the tools used to identify the variance. RESULTS: In 2011, 285 variances were reported, 102 were reported by physicists, 86 anonymously, 71 by therapists and 26 by dosimetrists. We realized the need to develop clear classifications for variances. We added a high priority category, defined as variances which resulted in or had the potential to result in harm to a patient or when a policy is purposely overridden. Of the 285 variances reported, 5 were high priority. We created a process variance category, defined as variances where a specific clinical process is not followed. Of the 285 reported variances 155 were process variances. CONCLUSIONS: Reporting of variances through a centralized database is central toward developing a robust patient safety/quality assurance program. Anonymous reporting fosters a non-punitive environment, and promotes the 'safety culture'. The goal of such a system is to review trends in clinical processes and ultimately to improve safety/quality by reducing variances associated with these processes.
RESUMO
PURPOSE: Gemcitabine (2'2'-difluoro-2'-deoxycytidine, dFdCyd) is a potent radiosensitizer of rodent and human tumor cells. Our Phase I clinical trial using once-weekly dFdCyd as a radiosensitizer in the treatment of patients with Stage IV squamous cell head and neck cancer has produced a high rate of tumor response and significant normal mucosal toxicity. These findings raised the question of whether we are using dFdCyd in the optimal dose and schedule. In vitro studies suggest that twice-weekly dFdCyd has the potential to be more effective than once-weekly dFdCyd when administered in combination with radiation (RT) given 5 days per week. Therefore, we have used a mouse model to assess whether the therapeutic ratio of combined modality therapy may be improved by using a twice-weekly drug regimen. We asked two questions: 1) Does a once-weekly or twice-weekly dFdCyd regimen cause more normal tissue radiosensitization? 2) Does a once-weekly or twice-weekly dFdCyd + RT regimen produce a better therapeutic index? METHODS AND MATERIALS: To assess normal tissue toxicity, C3H mice underwent mouth (60)Co RT (27.5 Gy in 5 daily fractions) +/- dFdCyd delivered intraperitoneally (IP) either once or twice weekly 6 hours prior to irradiation. Acute lip reactions were quantified according to a standard scoring system, and weight loss was measured. We measured tumor control using squamous cell carcinoma (SCC) VII murine squamous cell flank tumors (50-125 mm(3)) treated with the same regimens used in the mouth irradiation model. RESULTS: We found that dFdCyd delivered 800 mg/kg once weekly or 150 mg/kg twice weekly caused similar (and maximal tolerable) weight loss; therefore these regimens were chosen to test which schedule produced more acute lip radiosensitization. Twice-weekly dFdCyd + RT was somewhat more toxic by weight loss (800 mg/kg once weekly: 11.9%; 150 mg/kg twice weekly: 17.7%; p = 0.09). To assess therapeutic index, we treated SCC VII flank tumors with RT combined with isotoxic drug/RT regimens (dFdCyd 800 mg/kg once weekly or 100 mg/kg twice weekly). Tumors treated with twice-weekly dFdCyd + RT were significantly smaller than tumors treated with once-weekly drug + RT at 28 days from the start of treatment (p < 0.03). CONCLUSIONS: These findings demonstrate that equitoxic once- versus twice-weekly dFdCyd regimens cause differing levels of oral mucosal radiosensitization. This would suggest that each radiation-dFdCyd schedule will require its own dFdCyd dose escalation trial (which cannot be determined by the maximum tolerated dose (MTD) for dFdCyd alone using that schedule). In addition, our findings suggest that for head and neck cancers twice-weekly dFdCyd may have a higher therapeutic index compared with once-weekly dFdCyd when combined with daily RT.
