Faculty Bibliography

PURPOSE/OBJECTIVE:To use radiation exposure rate measurements to determine patient-specific radiation safety instructions with the aim of reducing unnecessary precaution times and to evaluate potential doses to members of the public. METHODS AND MATERIALS/METHODS:Radiation exposure rate measurements were obtained from 1279 patients with Stage T1-2 prostate cancer who underwent transperineal (125)I or (103)Pd seed implantation from January 1995 through July 2008. An algorithm was developed from these measurements to determine the required precaution times to maintain public effective doses below 50% of the limits for specific exposure situations. RESULTS:The median air kerma rates at 30 cm from the anterior skin surface were 4.9 microGy/h (range: 0.1-31.5) for (125)I and 1.5 microGy/h (range: 0.02-14.9) for (103)Pd. The derived algorithms depended primarily on the half-life T(p), the measured exposure rate at 30 cm, and specific exposure situation factors. For the typical (103)Pd patient, no radiation safety precautions are required. For the typical (125)I patient, no precautions are required for coworkers, nonpregnant adults who do not sleep with the patient, or nonpregnant adults who sleep with the patient. Typical (125)I patients should only avoid sleeping in the "spoon" position (i.e., in contact) with pregnant adults and avoid holding a child for long periods of time in the lap for about 2 months. CONCLUSIONS:The large number of cases available for this study permitted the development of an algorithm to simply determine patient-specific radiation safety instructions. The resulting precaution times are significantly less restrictive than those generally prescribed currently.

PURPOSE/OBJECTIVE:To report the influence of posttreatment prostate-specific antigen (PSA) nadir response at 2 years after external beam radiotherapy (RT) on distant metastases (DM) and cause-specific mortality (CSM). METHODS AND MATERIALS/METHODS:Eight hundred forty-four patients with localized prostate cancer were treated with conformal RT. The median duration of follow-up was 9.1 years. A fixed landmark time point at 2 years was used to assess the influence of nadir PSA value as a time-dependent variable on long-term outcomes. RESULTS:Multivariate analysis demonstrated that nadir PSA <or=1.5 ng/mL at the landmark was an independent predictor of progression-free survival after adjusting for T stage, Gleason score, pre-RT PSA value, and RT dose (p = 0.03). The 5- and 10-year cumulative incidences of DM were 2.4% and 7.9%, respectively, in those with nadir PSA levels <or=1.5 ng/mL at the 2-year landmark, and were 10.3% and 17.5%, respectively, in patients with higher nadir values. Multivariate analysis showed that the higher nadir PSA value at the 2-year landmark (p = 0.002), higher Gleason scores (p < 0.001), and increasing T stage (p = 0.03) were predictors of DM after adjusting for pre-RT PSA values and RT dose. Multivariate analysis also showed that higher Gleason scores (p = 0.002), and higher nadir PSA values at the 2-year landmark (p = 0.03) were risk factors associated with CSM after adjusting for T stage and pre-RT PSA value. CONCLUSIONS:Nadir PSA values of <or=1.5 ng/mL at 2 years after RT for prostate cancer predict for long-term DM and CSM outcomes. Patients with higher absolute nadir levels at 2 years after treatment should be evaluated for the presence of nonresponding disease, and earlier salvage treatment interventions should be considered.

BACKGROUND:There has been an increase in the utilization of single-fraction stereotactic body radiation therapy (SBRT) to treat thoracic structures, but there have been few reports describing toxicity outcomes with this treatment. METHODS:We evaluated 119 sites (114 patients) with no prior history of thoracic radiation were treated from 10/1/2003 to 10/27/2008 with single-fraction SBRT to thoracic structures. The median dose to the gross tumor volume was 2400 cGy (range 1800-2400 cGy), as was the median dose to the planning target volume (range 1600-2400 cGy). A detailed review of thoracic toxicities was performed to include pneumonitis or Grade 2 or higher esophageal and bronchial toxicity. In addition, we retrospectively contoured the esophagus and bronchus of 48 patients treated in 2004-2005, prior to the establishment of dose constraints to determine the range of doses that these structures received. RESULTS:Of the contoured patients, the median dose to the hottest 1cc (D1cc) of the esophagus was 1250 cGy (range 158-2572 cGy). The median bronchial D1cc was 1101 cGy (range 260-2211 cGy). At a median follow-up of 11.6 months, there were seven Grade 2 or higher esophageal toxicities, including one Grade 3 and one Grade 4 toxicities. There were two bronchial toxicities, one Grade 2 and one Grade 3. There were no cases of pneumonitis. CONCLUSIONS:High-dose single-fraction SBRT is well tolerated to the thoracic region, with most patients tolerating high doses to central structures without significant toxicity.

Strategic planning for the Radiation Therapy Committee of the Southwest Oncology Group (SWOG) is comprehensively evaluated every six years in an effort to maintain a current and relevant scientific focus, and to provide a standard platform for future development of protocol concepts. Participants in the 2008 Strategic Planning Workshop included clinical trial experts from multiple specialties, industry representatives from both pharmaceuticals and equipment manufacturers, and basic scientists. High-priority research areas such as image-guided radiation therapy for control of limited metastatic disease, analysis of biomarkers for treatment response and late toxicity, assessment of novel agents in combination with radiation, standardization of radiation target delineation, and the assessment of new imaging techniques to individualize cancer therapy, were discussed. Research priorities included clinical study designs featuring translational end points that identify patients most likely to benefit from combined modality therapy; intervention including combination radiation with standard chemotherapy; radiation with radiosensitizing molecular-targeted therapies; and stereotactic radiation for treatment of patients with regard to asymptomatic metastasis and radiation-induced tumor autoimmunity. The Committee concluded that the future research opportunities are among the most exciting to have developed in the last decade, and work is in progress to embark on these plans.

For men diagnosed with clinically localized prostate cancer, definitive therapy with radical prostatectomy, external beam radiation therapy, or brachytherapy offers a high chance of cure. Currently, there are insufficient data to recommend 1 treatment approach over another, leaving physicians and patients to decide based on their own biases and preferences. Prediction tools, such as nomograms and probability tables, have been created as decision aids to facilitate patient counseling and decision making. Nomograms in particular can assess the therapeutic efficacy of a given therapy by providing individualized estimates of the risk of failure after treatment. The authors performed a comprehensive literature review to identify nomograms assessing the efficacy of brachytherapy in patients with clinically localized prostate cancer, and found a paucity of such models. Analysis of currently available brachytherapy nomograms reveals suboptimal predictive power compared with models based on other treatment modalities. The purpose of this review is to spur development of new and more accurate prediction tools for predicting outcomes after brachytherapy, offering physicians and patients the opportunity to equally assess the efficacy of all available treatment modalities for clinically localized prostate cancer. Cancer 2009;115(13 suppl):3121-7. (c) 2009 American Cancer Society.

PURPOSE/OBJECTIVE:Quality Research in Radiation Oncology (QRRO) has embarked on a new national process survey to provide benchmark data that will allow radiation oncologists to assess the quality of care in their own practices by measuring quality indicators (QIs) and comparing individual with national practice. METHODS:Investigators at QRRO developed QIs on the basis of nationally recognized, evidence-based guidelines such as those of the National Comprehensive Cancer Network, as well as additional emerging QIs for processes involving rapidly emerging technology. They specifically defined the QIs as clinical performance measures. Published results of the national survey database for patients treated in 1998 and 1999 were reviewed and additional analyses conducted to assess data adequacy to measure compliance with these clinical performance measures. RESULTS:Examples of workup QIs for breast cancer patients showed that 97% underwent diagnostic bilateral mammography, 96% underwent pathology reviews, 83% underwent the determination of estrogen receptor status, 81% underwent the determination of progesterone receptor status, and 31% underwent the determination of human epidermal growth factor receptor 2 status. Compliance with treatment QIs for field recommendations on the basis of nodal findings can be measured. Of patients with prostate cancer, 90% underwent digital rectal examinations, 99% underwent prostate-specific antigen tests, and 99% had their Gleason scores determined. Compliance with QIs on the basis of prognostic group can also be measured. CONCLUSIONS:Benchmarking utilization patterns provides a foundation for assessing the appropriateness of cancer care in the future. The QRRO database is a rich data source, and the new survey will provide contemporary benchmark data for these measures.

BACKGROUND:To the authors' knowledge, the indications for adjuvant treatment in acinic cell carcinoma (AciCC) of the parotid gland have not been elucidated to date. The aim of the current study was to determine patterns of failure and adverse prognostic features. METHODS:Between March of 1989 and August of 2006, 35 patients underwent surgery at Memorial Sloan-Kettering Cancer Center for AciCC of the parotid gland and had their clinical and pathologic features retrospectively analyzed at the primary site. All cases were reviewed by 2 head and neck pathologists. Five-year estimates of survival outcomes were performed, followed by univariate analysis of potential prognostic features. RESULTS:The T classifications were as follows: T1 in 46% of patients, T2 in 23% of patients, T3 in 18% of patients, and T4 in 9% of patients. Three patients had cervical lymph node involvement. All patients underwent surgery as their primary treatment. Approximately 63% of patients (n = 22) received radiation treatment. The median follow-up time for surviving patients was 59.9 months. Five-year estimates of disease-free survival (DFS), overall survival (OS), and local control were 85%, 90%, and 90%, respectively. Of the clinical variables tested, clinical extracapsular extension (ECE), facial nerve sacrifice, and lymph node involvement were found to be significantly associated with a detriment in DFS and OS (P < .05). Positive surgical margins, histologic ECE, >2 mitoses per 10 high-power fields (HPF), atypical mitosis, vascular invasion, perineural invasion, pleomorphism, and necrosis were associated with adverse DFS (P < .05). All of these variables except for vascular invasion (P = .377) and perineural invasion (P = .07) were associated with OS. If high-grade tumors were defined on the basis of high mitotic activity (>2 mitoses/10 HPF) and/or tumor necrosis, high-grade carcinomas had a significantly lower DFS and OS (P = .001). CONCLUSIONS:AciCC had a low treatment failure rate, and a large number of patients could be considered candidates for surgery only. A histologic grading system was devised to help stratify patients for adjuvant treatment.

PURPOSE/OBJECTIVE:To quantify, as a function of average magnetic resonance spectroscopy (MRS) score and tumor volume, the probability that a cancer-suspected lesion has an elevated Gleason grade. METHODS AND MATERIALS/METHODS:The data consist of MRS imaging ratios R stratified by patient, lesion (contiguous abnormal voxels), voxels, biopsy and pathologic Gleason grade, and lesion volume. The data were analyzed using a logistic model. RESULTS:For both low and high Gleason score biopsy lesions, the probability of pathologic Gleason score >/=4+3 increases with lesion volume. At low values of R a lesion volume of at least 15-20 voxels is needed to reach a probability of success of 80%; the biopsy result helps reduce the prediction uncertainty. At larger MRS ratios (R > 6) the biopsy result becomes essentially uninformative once the lesion volume is >12 voxels. With the exception of low values of R, for lesions with low Gleason score at biopsy, the MRS ratios serve primarily as a selection tool for assessing lesion volumes. CONCLUSIONS:In patients with biopsy Gleason score >/=4+3, high MRS imaging tumor volume and (creatine + choline)/citrate ratio may justify the initiation of voxel-specific dose escalation. This is an example of biologically motivated focal treatment for which intensity-modulated radiotherapy and especially brachytherapy are ideally suited.