Does prone positioning reduce small bowel dose in pelvic radiation with intensity-modulated radiotherapy for gynecologic cancer?

PURPOSE: Intensity-modulated radiotherapy (IMRT) has been shown to reduce the radiation dose to small bowel in pelvic RT in gynecology patients. Prone positioning has also been used to decrease small bowel dose by displacement of small bowel from the RT field in these patients. The purpose of this study was to determine whether the combination of both IMRT and prone positioning on a belly board can reduce small bowel dose further in gynecologic cancer patients undergoing pelvic RT. METHODS AND MATERIALS: IMRT plans for pelvic RT were computed in 16 patients with gynecologic cancer who had undergone planning CT scans in both the supine and the prone positions on a belly board. For the gross tumor volume, the uterus, cervix, and tumor (or postoperative region) were traced. The clinical target volume was defined as the vessels and lymph nodes from the obturator level to the aortic bifurcation, presacral region, and upper 4 cm of the vagina, in addition to gross tumor volume. The planning target volume was defined as a 2-cm margin in addition to the gross tumor volume and upper 4 cm of the vagina, and 1.5 cm for lymph nodes and vessels. Normal tissue regions of interest included small bowel, large bowel, and bladder. IMRT plans using (1) the limited arc technique (180 degrees arc length) and (2) the extended arc technique (340 degrees arc length) were computed. Dose-volume histograms for normal tissue structures and target were compared between the supine and prone IMRT plans using the paired t test. RESULTS: Prone positioning on a belly board decreased the small bowel dose in gynecologic pelvic IMRT, and the magnitude of improvement depended on the specific IMRT technique used. With the limited arc technique, prone positioning significantly decreased the irradiated small bowel volume at the 25-50-Gy dose levels compared with supine positioning. Small bowel volumes receiving > or =45 Gy decreased from 19% to 12.5% (p = 0.005) with prone positioning. With the extended arc technique, the decrease in irradiated small bowel volume was less marked, but remained detectable in the 35-45-Gy dose levels. Small bowel volumes receiving > or =45 Gy decreased from 13.6% to 10.1% (p = 0.03) with prone positioning. The effect of prone positioning on large bowel and bladder was variable. Large bowel volumes receiving > or =45 Gy increased with prone positioning from 16.5% to 20.6% (p = 0.02) in the limited arc technique and was unaffected in the extended arc technique. CONCLUSION: These preliminary data suggest that prone positioning on a belly board can reduce the small bowel dose further in gynecology patients treated with pelvic RT, and that the dose reduction depends on the IMRT technique used.

Disruption of DAG1 in differentiated skeletal muscle reveals a role for dystroglycan in muscle regeneration.

Striated muscle-specific disruption of the dystroglycan (DAG1) gene results in loss of the dystrophin-glycoprotein complex in differentiated muscle and a remarkably mild muscular dystrophy with hypertrophy and without tissue fibrosis. We find that satellite cells, expressing dystroglycan, support continued efficient regeneration of skeletal muscle along with transient expression of dystroglycan in regenerating muscle fibers. We demonstrate a similar phenomenon of reexpression of functional dystroglycan in regenerating muscle fibers in a mild form of human muscular dystrophy caused by disruption of posttranslational dystroglycan processing. Thus, maintenance of regenerative capacity by satellite cells expressing dystroglycan is likely responsible for mild disease progression in mice and possibly humans. Therefore, inadequate repair of skeletal muscle by satellite cells represents an important mechanism affecting the pathogenesis of muscular dystrophy.

In vivo determination of extra-target doses received from serial tomotherapy.

BACKGROUND AND PURPOSE: The purpose of this study was to perform in-vivo measurements of extracranial doses received by patients undergoing serial tomotherapy of the head and neck. MATERIAL AND METHODS: Intensity modulated radiotherapy treatment (IMRT) plans were designed for nine patients using the CORVUS treatment planning system (NOMOS Corp.). These plans were delivered using a tertiary collimator dedicated for serial tomotherapy attached to a 10-MV linear accelerator. For each patient, one optically stimulated luminescence dosimeter (OSLD) was placed on the sternum and one on the lower abdomen. The OSLDs were then processed, thereby estimating the in vivo absorbed doses to the sternum and gonads as a function of distance from the treatment site. RESULTS: The OSLDs were shown to measure known doses to within 5%, thereby validating their accuracy for this dose and energy range. In the patient studies, the dose received by the OSLDs varied in direct proportion to the number of monitor units delivered and inversely with the distance from the target volume; the patient dose at a distance of 15 cm from the target is approximately 0.4% of the total monitor units delivered, and drops to below 0.1% of the total MUs at approximately 40 cm from the center of the target. The average sternal dose was 1353 mSv and the average abdominal dose was 327 mSv for an average prescribed dose of 60.1 Gy. This can be attributed, at least partially, to the inefficient treatment delivery that on average required 9.9 MU/0.01 Gy. CONCLUSIONS: While IMRT reduces the normal tissue volume in the high-dose region, it also increases the overall monitor units delivered, and hence the whole-body dose, when compared with conventional treatment delivery. As has been noted in existing literature, these increases in whole-body dose from radiotherapy delivery may increase the likelihood of a radiation-induced secondary malignancy. Therefore, it is important to assess the risk of secondary malignancies from IMRT delivery, and compare this relative risk against the potential benefits of decreased normal tissue complication probabilities.

Risk group dependence of dose-response for biopsy outcome after three-dimensional conformal radiation therapy of prostate cancer.

BACKGROUND AND PURPOSE: We fit phenomenological tumor control probability (TCP) models to biopsy outcome after three-dimensional conformal radiation therapy (3D-CRT) of prostate cancer patients to quantify the local dose-response of prostate cancer. MATERIALS AND METHODS: We analyzed the outcome after photon beam 3D-CRT of 103 patients with stage T1c-T3 prostate cancer treated at Memorial Sloan-Kettering Cancer Center (MSKCC) (prescribed target doses between 64.8 and 81Gy) who had a prostate biopsy performed >or=2.5 years after end of treatment. A univariate logistic regression model based on D(mean) (mean dose in the planning target volume of each patient) was fit to the whole data set and separately to subgroups characterized by low and high values of tumor-related prognostic factors T-stage (or=T2c), Gleason score (6), and pre-treatment prostate-specific antigen (PSA) (10 ng/ml). In addition, we evaluated five different classifications of the patients into three risk groups, based on all possible combinations of two or three prognostic factors, and fit bivariate logistic regression models with D(mean) and the risk group category to all patients. Dose-response curves were characterized by TCD(50), the dose to control 50% of the tumors, and gamma(50), the normalized slope of the dose-response curve at TCD(50). RESULTS: D(mean) correlates significantly with biopsy outcome in all patient subgroups and larger values of TCD(50) are observed for patients with unfavorable compared to favorable prognostic factors. For example, TCD(50) for high T-stage patients is 7Gy higher than for low T-stage patients. For all evaluated risk group definitions, D(mean) and the risk group category are independent predictors of biopsy outcome in bivariate analysis. The fit values of TCD(50) show a clear separation of 9-10.6Gy between low and high risk patients. The corresponding dose-response curves are steeper (gamma(50)=3.4-5.2) than those obtained when all patients are analyzed together (gamma(50)=2.9). CONCLUSIONS: Dose-response of prostate cancer, quantified by TCD(50) and gamma(50), varies by prognostic subgroup. Our observations are consistent with the hypothesis that the shallow nature of clinically observed dose-response curves for local control result from a patient population that is a heterogeneous mixture of sub-populations with steeper dose-response curves and varying values of TCD(50). Such results may eventually help to identify patients, based on their individual pre-treatment prognostic factors, that would benefit most from dose-escalation, and to guide dose prescription.