Determining Combined Modality Dosimetric Constraints by Integration of IMRT and LDR Prostate Brachytherapy Dosimetry and Correlation with Toxicity.

Purpose: Intermediate- and high-risk prostate cancer patients undergoing combination external beam radiation therapy (EBRT) and low dose rate (LDR) brachytherapy have demonstrated increased genitourinary (GU) toxicity. We have previously demonstrated a method to combine EBRT and LDR dosimetry. In this work, we use this technique for a sample of patients with intermediate- and high-risk prostate cancer, correlate with clinical toxicity, and suggest preliminary summed organ-at-risk constraints for future investigation. Methods and Materials: Intensity modulated EBRT and 103Pd-based LDR treatment plans were combined for 138 patients using biological effective dose (BED) and deformable image registration. GU and gastrointestinal (GI) toxicity were compared with combined dosimetry for the urethra, bladder, and rectum. Differences between doses in each toxicity grade were assessed by analysis of variance (α = 0.05). Combined dosimetric constraints are proposed using the mean organ-at-risk dose, subtracting 1 standard deviation for a conservative recommendation. Results: The majority of our 138-patient cohort experienced grade 0 to 2 GU or GI toxicity. Six grade 3 toxicities were noted. Mean prostate BED D90 (± 1 standard deviation) was 165.5±11.1 Gy. Mean urethra BED D10 was 230.3±33.9 Gy. Mean bladder BED was 35.2±11.0 Gy. Mean rectum BED D2cc was 85.6±24.3 Gy. Significant dosimetric differences between toxicity grades were found for mean bladder BED, bladder D15, and rectum D50, but differences between individual means were not statistically significant. Given the low incidence of grade 3 GU and GI toxicity, we propose urethra D10 <200 Gy, rectum D2cc <60 Gy, and bladder D15 <45 Gy as preliminary dose constraints for combined modality therapy. Conclusions: We successfully applied our dose integration technique to a sample of patients with intermediate- and high-risk prostate cancer. Incidence of grade 3 toxicity was low, suggesting that combined doses observed in this study were safe. We suggest preliminary dose constraints as a conservative starting point to investigate and escalate prospectively in a future study.

Integrating external beam and prostate seed implant dosimetry for intermediate and high-risk prostate cancer using biologically effective dose: Impact of image registration technique.

PURPOSE: Combining external beam radiation therapy (EBRT) and prostate seed implant (PSI) is efficacious in treating intermediate- and high-risk prostate cancer at the cost of increased genitourinary toxicity. Accurate combined dosimetry remains elusive due to lack of registration between treatment plans and different biological effect. The current work proposes a method to convert physical dose to biological effective dose (BED) and spatially register the dose distributions for more accurate combined dosimetry. METHODS AND MATERIALS: A PSI phantom was CT scanned with and without seeds under rigid and deformed transformations. The resulting CTs were registered using image-based rigid registration (RI), fiducial-based rigid registration (RF), or b-spline deformable image registration (DIR) to determine which was most accurate. Physical EBRT and PSI dose distributions from a sample of 91 previously-treated combined-modality prostate cancer patients were converted to BED and registered using RI, RF, and DIR. Forty-eight (48) previously-treated patients whose PSI occurred before EBRT were included as a "control" group due to inherent registration. Dose-volume histogram (DVH) parameters were compared for RI, RF, DIR, DICOM, and scalar addition of DVH parameters using ANOVA or independent Student's t tests (α = 0.05). RESULTS: In the phantom study, DIR was the most accurate registration algorithm, especially in the case of deformation. In the patient study, dosimetry from RI was significantly different than the other registration algorithms, including the control group. Dosimetry from RF and DIR were not significantly different from the control group or each other. CONCLUSIONS: Combined dosimetry with BED and image registration is feasible. Future work will utilize this method to correlate dosimetry with clinical outcomes.

Psychosocial factors related to nausea, vomiting, and fatigue in early pregnancy.

PURPOSE: To test whether nausea and vomiting or fatigue correlated with psychosocial variables. DESIGN: Descriptive, using secondary data from a prenatal database of 113 women in prenatal care in Texas. Mean gestational duration was 59 days at the time of data collection. METHODS: Psychosocial factors, frequency of nausea and vomiting and of fatigue were determined by use of questionnaires. Psychosocial measures had reliability and validity and included the Personal Resources Questionnaire and Center for Epidemiologic Studies Depression Scale. A checklist was used for measuring nausea and vomiting and fatigue. FINDINGS: Of 113 participants, 30 (26.5%) reported no, 43 (38.1%) occasional, and 40 (35.4%) frequent nausea and vomiting. Depressive symptoms had the highest correlation with nausea and vomiting. Social support was negatively related to nausea and vomiting. Four (3.5%) women reported no fatigue, 49 (43.4%) reported occasional fatigue, and 60 (53.1%) reported frequent fatigue in the past month. Depressive symptoms had the highest correlation with fatigue. The chi-square statistic showed that fatigue was significantly related to employment. Fatigue was not significantly associated with work hours or stressfulness of jobs. CONCLUSIONS: Only a limited number of psychosocial factors were associated with nausea and vomiting and fatigue in early pregnancy. Depression was related to physical symptoms, but unclear was whether depression preceded or resulted from the symptoms. Many women experienced symptoms, and better understanding of causality is needed to ameliorate the effects on women's well-being.