A dosimetric comparison of MammoSite and ClearPath high-dose-rate breast brachytherapy devices.

PURPOSE: A new form of partial breast irradiation (PBI), ClearPath (CP) breast brachytherapy, has been introduced. We present our results of a dosimetric comparison of MammoSite (MS) and CP PBI. METHODS AND MATERIALS: The dimensions of the CP device were reconstructed onto the MS planning CT scans for 15 previously treated patients. The mean %V(100), %V(150), %V(200) (percent of the PTV that received 100%, 150%, and 200% of the prescription dose, respectively), ipsilateral breast %V(50) (percent of the ipsilateral normal breast that received 50% of the prescription dose), ipsilateral lung %V(30) (percent of the ipsilateral lung that received 30% of the prescription dose), the heart %V(5) (percent of the heart that received 5% of the prescription dose), and the maximum skin point dose per fraction were then determined for each patient using the two methods of balloon-based PBI. RESULTS: The mean %V(100) was 96.5% vs. 96.5%, the mean %V(150) was 42.1% vs. 42.9% (p=ns), and the mean V(200) was 11.4% vs. 15.2% (p<.05) for the MS and CP methods, respectively. The mean ipsilateral breast %V(50) was 19.8% vs.18.0% (p<.05), the mean ipsilateral lung %V(30) was 3.7% vs. 2.8% (p<.05), the mean heart %V(5) was 57.0% vs. 54.3% (p<.05), and the maximum skin point dose per fraction was 312.2 and 273.6cGy (p<.05) for the MS and CP methods, respectively. CONCLUSIONS: The MS and CP methods of PBI offer comparable target volume coverage; however, the CP device achieves increased normal tissue sparing.

Cost of radiotherapy versus NSAID administration for prevention of heterotopic ossification after total hip arthroplasty.

PURPOSE: Heterotopic ossification (HO), or abnormal bone formation, is a common sequela of total hip arthroplasty. This abnormal bone can impair joint function and must be surgically removed to restore mobility. HO can be prevented by postoperative nonsteroidal anti-inflammatory drug (NSAID) use or radiotherapy (RT). NSAIDs are associated with multiple toxicities, including gastrointestinal bleeding. Although RT has been shown to be more efficacious than NSAIDs at preventing HO, its cost-effectiveness has been questioned. METHODS AND MATERIALS: We performed an analysis of the cost of postoperative RT to the hip compared with NSAID administration, taking into account the costs of surgery for HO formation, treatment-induced morbidity, and productivity loss from missed work. The costs of RT, surgical revision, and treatment of gastrointestinal bleeding were estimated using the 2007 Medicare Fee Schedule and inpatient diagnosis-related group codes. The cost of lost wages was estimated using the 2006 median salary data from the U.S. Census Bureau. RESULTS: The cost of administering RT was estimated at $899 vs. $20 for NSAID use. After accounting for the additional costs associated with revision total hip arthroplasty and gastrointestinal bleeding, the corresponding estimated costs were $1,208 vs. $930. CONCLUSION: If the costs associated with treatment failure and treatment-induced morbidity are considered, the cost of NSAIDs approaches that of RT. Other NSAID morbidities and quality-of-life differences that are difficult to quantify add to the cost of NSAIDs. These considerations have led us to recommend RT as the preferred modality for use in prophylaxis against HO after total hip arthroplasty, even when the cost is considered.

A dosimetric comparison of Xoft Axxent Electronic Brachytherapy and iridium-192 high-dose-rate brachytherapy in the treatment of endometrial cancer.

PURPOSE: This analysis was undertaken to dosimetrically compare iridium-192 high-dose-rate brachytherapy (IB) and Xoft Axxent Electronic Brachytherapy (XB; Xoft Inc., Sunnyvale, CA) in the treatment of endometrial cancer. METHODS AND MATERIALS: The planning CT scans from 11 patients previously treated with IB were used to construct hypothetical treatment plans using the source characteristics of the XB device. The mean V95, V100, and V150 (percent of the planning target volume that received 95%, 100%, and 150% of the prescription dose) were calculated. For both the bladder and rectum, the V35 (percent of the organ that received 35% of the prescription dose) and V50 (percent of the organ that received 50% of the prescription dose) were calculated for each patient using both methods of vaginal brachytherapy. RESULTS: The mean %V95 was 99.7% vs. 99.6% (p = ns) and the mean %V100 was 99.0% vs. 99.1% (p = ns) for the IB and XB methods, respectively. The mean %V150 was 35.8% vs. 58.9% (p < 0.05) for the IB and XB methods, respectively. The mean bladder %V35 was 47.7% vs. 27.4% (p < 0.05) and the mean bladder %V50 was 26.5% vs. 15.9% (p < 0.05) for the IB and XB methods, respectively. The mean rectal %V35 was 48.3% vs. 28.3% (p < 0.05) and the mean rectal %V50 was 27.8% vs. 17.0% (p < 0.05) for the IB and XB methods, respectively. CONCLUSIONS: The IB and XB methods of vaginal brachytherapy offer equivalent target volume coverage; however, the XB method allows increased sparing of the bladder and rectum.

Triglycerides induce leptin resistance at the blood-brain barrier.

Obesity is associated with leptin resistance as evidenced by hyperleptinemia. Resistance arises from impaired leptin transport across the blood-brain barrier (BBB), defects in leptin receptor signaling, and blockades in downstream neuronal circuitries. The mediator of this resistance is unknown. Here, we show that milk, for which fats are 98% triglycerides, immediately inhibited leptin transport as assessed with in vivo, in vitro, and in situ models of the BBB. Fat-free milk and intralipid, a source of vegetable triglycerides, were without effect. Both starvation and diet-induced obesity elevated triglycerides and decreased the transport of leptin across the BBB, whereas short-term fasting decreased triglycerides and increased transport. Three of four triglycerides tested intravenously inhibited transport of leptin across the BBB, but their free fatty acid constituents were without effect. Treatment with gemfibrozil, a drug that specifically reduces triglyceride levels, reversed both hypertriglyceridemia and impaired leptin transport. We conclude that triglycerides are an important cause of leptin resistance as mediated by impaired transport across the BBB and suggest that triglyceride-mediated leptin resistance may have evolved as an anti-anorectic mechanism during starvation. Decreasing triglycerides may potentiate the anorectic effect of leptin by enhancing leptin transport across the BBB.

Thermal effusivity changes as a precursor to moist desquamation.

Skin toxicity is a ubiquitous side effect in radiotherapy and can be difficult to predict. Moist desquamation in cancer patients can decrease quality of life and occasionally demand unplanned treatment breaks thus worsening outcome. In breast cancer patients, moist desquamation occurs approximately one-third of the time, and while avenues such as intensity-modulated radiation therapy exist to decrease skin side effects, they may be prohibitively expensive to distribute widely. To selectively target patients who are at risk for high skin toxicity, toxicity prediction beyond heuristics is required. This study presents 3D thermal tomography, a translation technology that employs active thermal imaging to map the thermal effusivity of skin. Irradiated mice were imaged throughout reaction development to establish a correlation between effusivity changes and eventual toxicity severity. Female hairless mice (n = 11) were anesthetized and irradiated to 40 Gy in one fraction using a 1 cm Leipzig brachytherapy applicator with an Ir-192 source. After irradiation, thermal imaging was conducted daily with a flash lamp and infrared camera. Effusivity was calculated using custom software and tracked within irradiated and contralateral control regions. Mice were retrospectively grouped into high-grade (moist desquamation present, n = 6) and low-grade (n = 5). All mice showed an increase in the relative average effusivity difference among the treated and control regions between irradiation and peak reaction between 12 and 15 days after irradiation. The high-grade group showed an earlier increase in relative average effusivity difference (mean 1.7 days after irradiation versus 4.4 days after irradiation) than the low-grade group, and had a significantly greater relative average effusivity difference between 2-5 days after irradiation. We concluded that 3D thermal tomography is quick, non-invasive, non-ionizing and exhibited a correlative difference between mice that eventually developed moist desquamation and those that only presented dry desquamation. With further development, it may prove to be a useful tool in the clinic for differentiating patients who require preventative measures to reduce skin toxicity.

Tomotherapy and multifield intensity-modulated radiotherapy planning reduce cardiac doses in left-sided breast cancer patients with unfavorable cardiac anatomy.

PURPOSE: For patients with left-sided breast cancers, radiation treatment to the intact breast results in high doses to significant volumes of the heart, increasing the risk of cardiac morbidity, particularly in women with unfavorable cardiac anatomy. We compare helical tomotherapy (TOMO) and inverse planned intensity modulated radiation therapy (IMRT) with three-dimensional conformal radiotherapy using opposed tangents (3D-CRT) for reductions in cardiac volumes receiving high doses. METHODS AND MATERIALS: Fifteen patients with left-sided breast cancers and unfavorable cardiac anatomy, determined by a maximum heart depth (MHD) of >or=1.0 cm within the tangent fields, were planned for TOMO and IMRT with five to seven beam angles, in addition to 3D-CRT. The volumes of heart and left ventricle receiving >or=35 Gy (V35) were compared for the plans, as were the mean doses to the contralateral breast and the volume receiving >or=20 Gy (V20) for the ipsilateral lung. RESULTS: The mean MHD was 1.7 cm, and a significant correlation was observed between MHD and both heart and left ventricle V35. The V35s for IMRT (0.7%) and TOMO (0.5%) were significantly lower than for 3D-CRT (3.6%). The V20 for IMRT (22%) was significantly higher than for 3D-CRT (15%) or TOMO (18%), but the contralateral breast mean dose for TOMO (2.48 Gy) was significantly higher than for 3D-CRT (0.93 Gy) or IMRT (1.38 Gy). CONCLUSIONS: Both TOMO and IMRT can significantly reduce cardiac doses, with modest increases in dose to other tissues in left-sided breast cancer patients with unfavorable cardiac anatomy.

A dosimetric analysis comparing treatment of low-risk prostate cancer with TomoTherapy versus static field intensity modulated radiation therapy.

OBJECTIVES: Static field intensity modulated radiation therapy (IMRT) has demonstrated dosimetric and clinical benefits over 3-dimensional conformal radiation therapy. TomoTherapy is a unique form of IMRT that may offer further improvements. METHODS: The study population consisted of 15 patients with low-risk prostate cancer treated at Rush University with TomoTherapy (n = 7) or IMRT (n = 8). For each patient, both a TomoTherapy plan and an IMRT plan were generated using identical planning objectives. The planning target volume (PTV) was defined as the prostate and proximal seminal vesicles plus a margin. The prescription dose was 7740 cGy in 43 fractions. Radiation Therapy Oncology Group (RTOG) normal tissue guidelines were used as constraints, and the PTV coverage was made equivalent for the paired plans by equalizing the PTV V100. RTOG benchmark DVH values for the rectum and bladder and mean dose to the penile bulb were recorded. The volume of PTV receiving ≥ 105% of the prescription dose was measured. RESULTS: The mean DVH values for each of the RTOG constraints for rectum and bladder were significantly improved using TomoTherapy. The volume of the PTV that received at least 105% of the dose was higher with IMRT (11.7% vs. 0.2%, <0.001). The mean dose to the penile bulb was higher with TomoTherapy (40.4 Gy vs. 27.4 Gy, P = 0.005). CONCLUSIONS: TomoTherapy offers a more favorable dose distribution to the bladder and rectum, as well as improved target homogeneity in comparison with IMRT.

Case report and dosimetric analysis of an axillary recurrence after partial breast irradiation with mammosite catheter.

Partial breast irradiation (PBI) was designed in part to decrease overall treatment times associated with whole breast radiation therapy (WBRT). WBRT treats the entire breast and usually portions of the axilla. The goal of PBI is to treat a smaller volume of breast tissue in less time, focusing the dose around the lumpectomy cavity. The following is a case of a 64-year-old woman with early-stage breast cancer treated with PBI who failed regionally in the ipsilateral axilla. With our dosimetric analysis, we found that the entire area of this axillary failure would have likely received at least 45 Gy if WBRT had been used, enough to sterilize microscopic disease. With PBI, this area received a mean dose of only 2.8 Gy, which raises the possibility that this regional failure may have been prevented had WBRT been used instead of PBI.