Rectal spacing, prostate coverage, and periprocedural outcomes after hydrogel spacer injection during low-dose-rate brachytherapy implantation.

PURPOSE: To analyze the dosimetric impact and periprocedural outcomes with a bioabsorbable hydrogel rectal spacer injected during low-dose-rate (LDR) prostate brachytherapy implants. METHODS AND MATERIALS: A consecutive series of 80 patients implanted with stranded I-125 LDR brachytherapy seeds were evaluated, of which 40 underwent a transperineal injection of polyethylene glycol (5 cc) in between the prostate and rectum. Same day CT-based dosimetry was compared between patients with and without hydrogel spacer to evaluate for differences in rectal and prostate dosimetry. Physician-reported toxicities were coded with Common Terminology Criteria for Adverse Events (CTCAE) v4. RESULTS: Baseline patient and implant characteristics were similar. There were no acute genitourinary or rectal toxicities attributed to the hydrogel spacer. Comparing patients with and without hydrogel, the mean separation between the prostate and rectum was 13.9 ± 5.2 mm vs. 6.5 ± 5.0 mm (p < 0.0001), respectively. The adjusted mean dose to 1 cc, 2 cc, and 5 cc of the rectum relative to prescription dose was decreased by 32% (p < 0.01), 26% (p < 0.01), and 17% (p < 0.01), respectively. There were no statistically significant differences in prostate coverage: mean V100 (92% vs. 91%), V150 (45% vs. 48%), and D90 (106% vs. 106%), respectively. At 1 month followup, grade 1 rectal toxicity was 12.5% vs. 17.5% (p = 0.35). No patients developed Grade ≥2 rectal toxicity with hydrogel, although one did without. CONCLUSION: Hydrogel rectal spacers significantly reduced rectal exposure to LDR brachytherapy seeds without an observable impact on prostate coverage or periprocedural side effects. These outcomes reflect only LDR implants that used stranded seeds.

Neoadjuvant cryotherapy improves dysphagia and may impact remission rates in advanced esophageal cancer.

Background and study aims Liquid nitrogen spray cryotherapy (LNSC) can provide rapid dysphagia relief, and is postulated to stimulate a local antitumor immune response. The aim of this prospective pilot clinical trial was to evaluate the safety and efficacy of LNSC when administered prior to chemoradiotherapy. Patients and methods Treatment-naïve adult patients with dysphagia at the time of biopsy-proven squamous carcinoma or adenocarcinoma of the esophagus were prospectively enrolled at two tertiary medical centers. Patients underwent a single session of LNSC. The primary outcome measure was change in dysphagia at 1 and 2 weeks post-cryotherapy. A secondary outcome measure was clinical complete response rate (CR) following chemoradiotherapy. Results Twenty-five patients were screened, of whom 21 patients were eligible and enrolled. There were seven with metastatic and 14 with locally advanced cancer. The primary outcome of dysphagia improvement of ≥ 1 point occurred in 15/21 patients (71 %) at 1 week, and 10/20 patients (50 %) at 2 weeks. The median dysphagia score improved by 1 at 1 week ( P  = 0.0003), and 0.5 at 2 weeks ( P  = 0.02). Six of nine patients (67 %) with locally advanced cancer who completed chemoradiation did not have residual tumor cells on mucosal biopsy, and five of nine patients (56 %) had a clinical CR. There were no serious cryotherapy-related complications. Conclusions LNSC provided safe and effective palliation for esophageal cancer patients who presented with dysphagia at index diagnosis. Its combination with chemoradiotherapy did not lead to any serious toxicity. Our study provides a scientific rationale for pursuing larger clinical trials addressing synergistic effects of combining LNSC with chemoradiation.

Variabilities of Magnetic Resonance Imaging-, Computed Tomography-, and Positron Emission Tomography-Computed Tomography-Based Tumor and Lymph Node Delineations for Lung Cancer Radiation Therapy Planning.

PURPOSE: To investigate interobserver delineation variability for gross tumor volumes of primary lung tumors and associated pathologic lymph nodes using magnetic resonance imaging (MRI), and to compare the results with computed tomography (CT) alone- and positron emission tomography (PET)-CT-based delineations. METHODS AND MATERIALS: Seven physicians delineated the tumor volumes of 10 patients for the following scenarios: (1) CT only, (2) PET-CT fusion images registered to CT ("clinical standard"), and (3) postcontrast T1-weighted MRI registered with diffusion-weighted MRI. To compute interobserver variability, the median surface was generated from all observers' contours and used as the reference surface. A physician labeled the interface types (tumor to lung, atelectasis (collapsed lung), hilum, mediastinum, or chest wall) on the median surface. Contoured volumes and bidirectional local distances between individual observers' contours and the reference contour were analyzed. RESULTS: Computed tomography- and MRI-based tumor volumes normalized relative to PET-CT-based volumes were 1.62 ± 0.76 (mean ± standard deviation) and 1.38 ± 0.44, respectively. Volume differences between the imaging modalities were not significant. Between observers, the mean normalized volumes per patient averaged over all patients varied significantly by a factor of 1.6 (MRI) and 2.0 (CT and PET-CT) (P=4.10 × 10-5 to 3.82 × 10-9). The tumor-atelectasis interface had a significantly higher variability than other interfaces for all modalities combined (P=.0006). The interfaces with the smallest uncertainties were tumor-lung (on CT) and tumor-mediastinum (on PET-CT and MRI). CONCLUSIONS: Although MRI-based contouring showed overall larger variability than PET-CT, contouring variability depended on the interface type and was not significantly different between modalities, despite the limited observer experience with MRI. Multimodality imaging and combining different imaging characteristics might be the best approach to define the tumor volume most accurately.

Comparative study of late rectal toxicity in prostate cancer patients treated with low-dose-rate brachytherapy: With or without supplemental external beam radiotherapy.

PURPOSE: Supplemental external beam radiation therapy (sEBRT) is often prescribed in men undergoing low-dose-rate (LDR) brachytherapy. A population of patients was analyzed to assess the effect of sEBRT on late rectal toxicity. It was hypothesized that sEBRT + LDR would be associated with a higher risk of late rectal toxicity. METHODS AND MATERIALS: This retrospective cohort study examined LDR brachytherapy patients, treated with or without sEBRT, with a minimum of 5-year followup. Longitudinal assessments were evaluated using the computerized patient record system. The Kaplan-Meier method was used for analysis. RESULTS: Median followup was 7.5 years for 245 patients from 2004 to 2007. sEBRT was administered to 33.5%. Followup beyond 5 years was available for 89%. Overall rates of Grade ≥2 and ≥3 rectal toxicities were 6.9% and 2.9%, respectively. The risk of Grade ≥2 rectal toxicity was 2.8-fold higher for patients receiving sEBRT (95% confidence interval: 1.1-7.2; p = 0.02). The risk of Grade ≥3 rectal toxicity was 11.9-fold higher for patients who received sEBRT (1.5-97.4, 95% confidence interval; p = 0.003). Six of seven patients with a Grade ≥3 rectal toxicity received sEBRT, including one who required an abdominoperineal resection. Median post-LDR D90, V150, V200, and R100 values were 103.3%, 59.4%, 30.1%, and 0.5 cc. CONCLUSIONS: In a cohort of LDR brachytherapy patients with high rates of followup, sEBRT + LDR was associated with significantly higher risk of Grade ≥2 and ≥3 late rectal toxicity. This analysis supports previous findings and maintains concern about the supplemental use of external beam radiation therapy with LDR brachytherapy while its benefit for tumor control has yet to be prospectively validated.

Time-Driven Activity-Based Costing: A Comparative Cost Analysis of Whole-Breast Radiotherapy Versus Balloon-Based Brachytherapy in the Management of Early-Stage Breast Cancer.

PURPOSE: Value in health care is defined as outcomes achieved per dollar spent, and understanding cost is critical to delivering high-value care. Traditional costing methods reflect charges rather than fundamental costs to provide a service. The more rigorous method of time-driven activity-based costing was used to compare cost between whole-breast radiotherapy (WBRT) and accelerated partial-breast irradiation (APBI) using balloon-based brachytherapy. MATERIALS AND METHODS: For WBRT (25 fractions with five-fraction boost) and APBI (10 fractions twice daily), process maps were created outlining each activity from consultation to post-treatment follow up. Through staff interviews, time estimates were obtained for each activity. The capacity cost rates (CCR), defined as cost per minute, were calculated for personnel, equipment, and physical space. Total cost was calculated by multiplying the time required of each resource by its CCR. This was then summed and combined with cost of consumable materials. RESULTS: The total cost for WBRT was $5,333 and comprised 56% personnel costs and 44% space/equipment costs. For APBI, the total cost was $6,941 (30% higher than WBRT) and comprised 51% personnel costs, 6% space/equipment costs, and 43% consumable materials costs. The attending physician had the highest CCR of all personnel ($4.28/min), and APBI required 24% more attending time than WBRT. The most expensive activity for APBI was balloon placement and for WBRT was computed tomography simulation. CONCLUSION: APBI cost more than WBRT when using the dose/fractionation schemes analyzed. Future research should use time-driven activity-based costing to better understand cost with the aim of reducing expenditure and defining bundled payments.

Locally advanced vulvar cancer in elderly women: is chemoradiation beneficial?

OBJECTIVES: There is a higher incidence of invasive vulvar cancer in the elderly population. With multiple medical comorbidities, radiation with sensitizing chemotherapy in the elderly can be complicated, yet the risks and benefits of chemoradiation have not been studied in this population. We investigate whether elderly patients are more likely to die of intercurrent disease (ICD) or of treatment complications. METHODS: A meta-analysis was performed to compare remission rates, death from ICD or treatment complications, and rates of surgery in elderly and nonelderly patients with vulvar cancer treated with chemoradiation. Data were searched in the Cochrane Review. Eligibility criteria included: woman with advanced primary squamous cell carcinoma of the vulva, women receiving preoperative or primary chemoradiation treatment with curative intent, and prospective studies that reported the necessary data of interest. Data collected included: age (elderly, defined as 65 years and above), stage, treatment, and mortality. RESULTS: Seventy subjects were identified from 7 studies that met eligibility criteria. Seventy-eight percent (25/32) of patients younger than 65 years were without evidence of disease after treatment versus 66% (25/38) of patients aged 65 years and above (P=0.30). Three percent (1/32) of patients younger than 65 years of age died of ICD or treatment complications versus 11% (4/38) of patients 65 years and above (P=0.37). CONCLUSIONS: We noticed a trend demonstrating death from ICD or treatment complications was higher for elderly patients. Future research should focus on treatment with chemoradiation in the elderly population with regard to survival benefit, toxicity, and death from ICD or treatment complications.

Altruistic kidney donation to a stranger: psychosocial and functional outcomes at two US transplant centers.

BACKGROUND: The number of living kidney donors with no preexisting relationship to the recipient has increased sharply. This study compared the psychosocial and functional outcomes of these altruistic donors to a stranger (ADs) with donors with a longstanding relationship with the recipient (traditional donors [TDs]). METHODS: ADs (n=39) and TDs (n=52), who were similar on age, sex, and year of donation, were recruited from two transplant programs in the United States. Participants completed validated measures of psychosocial and functional outcomes a median of 5 years after donation (range, 1-12 years). RESULTS: ADs and TDs did not differ significantly in the total number of donation motives. Both were motivated by a desire to help, the benefits to the recipient outweighing the risks to the donor, a sense of moral duty, and imagining oneself in the position of the recipient. Psychological benefits were endorsed equally by both types of donors, although TDs reported higher Quid Pro Quo scores relative to ADs (P=0.04). ADs and TDs did not differ significantly on any of the Short Form-36, Version 2 scales (P values ranged from 0.19 to 0.85). Few donors (3 ADs and 1 TD) regretted their donation decision. CONCLUSION: Overall, findings indicate that carefully screened ADs experience psychosocial and functional outcomes comparable with those of TDs and should not be systematically excluded from the opportunity to donate.

Advance care planning decisions of women with cancer: provider recognition and stability of choices.

Our prior research found that 43% of women with cancer relied on more than one person for advance care planning (ACP) and support. We conducted this follow-up study to address the stability of patient choices around ACP and providers' knowledge of patients' named supports. Living participants from the original survey were recontacted and asked to participate in this study. Of the original 215 participants, 113 (66%) participated. The median time between surveys was 23 months. At resurvey, 33 (26%) patients did not name the same person to all three roles. Controlling for age, race, partner status, tumor type, and remission status, naming one person for all three roles was associated with higher concordance at follow-up for primary support (PS) and health care proxy (HCP). Comparing patients' and providers' responses (N = 162), concordance was 71% for emergency contact (EC), 60% for PS, but only 51% for HCP. In this follow-up study, a smaller percentage of women named more than one person to the roles of EC, PS, and HCP compared to the original survey. Of concern, concordance between patient and provider was low, particularly for HCP. This was notable especially when responses changed over the interval time, and when ACP and PS roles were split between multiple people. Understanding the network of people who serve ACP and support roles may be important as we seek to improve the process of ACP and surrogate decision making.

High-resolution mapping of phase behavior in a ternary lipid mixture: do lipid-raft phase boundaries depend on the sample preparation procedure?

For some time now, we have been using a fluorescence resonance energy transfer (FRET)-based strategy to conduct high-resolution studies of phase behavior in ternary lipid-raft membrane mixtures. Our FRET experiments can be carried out on ordinary, polydisperse multilamellar vesicle suspensions, so we are able to prepare our samples according to a procedure that was designed specifically to guard against artifactual phase separation. In some respects (i.e., the number and nature of two-phase regions observed), our phase diagrams are consistent with those in previously published reports. However, in other respects (i.e., overall size of miscibility gaps, phase boundary locations and their dependence on temperature), there are clear differences. Here, we present FRET data taken in dioleoylphosphatidylcholine/dipalmitoylphosphatidylcholine/cholesterol (DOPC/DPPC/Chol) mixtures at 25.0, 35.0, and 45.0 degrees C. Comparisons between our results and previously reported phase boundaries suggest that lipid-raft mixtures may be particularly susceptible to demixing effects during sample preparation.

The cartilage thickness distribution in the tibiofemoral joint and its correlation with cartilage-to-cartilage contact.

OBJECTIVE: The objective of this study was to investigate whether regions of cartilage in the tibiofemoral joint where cartilage-to-cartilage contact occurred was thicker than other regions. DESIGN: In vivo human subjects. BACKGROUND: The thickness of the cartilage in the knee has been investigated in various studies. However, the factors that influence the thickness distribution within the joint remain unclear. METHODS: Six healthy living knees (5 male, 1 female, average age = 27) were scanned using magnetic resonance imaging. Three-dimensional models of the tibial and femoral cartilage layers were created. The cartilage thickness distribution was compared between regions where cartilage-to-cartilage contact was observed during in vivo weightbearing flexion and regions with no contact. RESULTS: The regions with cartilage-to-cartilage contact were significantly thicker than the regions without cartilage-to-cartilage contact (P < 0.05). On the medial condyle, the cartilage-to-cartilage contact regions were up to 40% thicker than regions with no contact. On the lateral femoral condyle, the maximum difference between these regions was 20%. On the tibial plateau, the maximal differences between regions with and without cartilage-to-cartilage contact were found to be 40% on the medial side and 50% on the lateral side. CONCLUSIONS: The data suggested that in normal knees, the cartilage was thicker in regions where cartilage-to-cartilage contact was present. Future studies should investigate the effects of in vivo loading on cartilage maintenance and growth. Relevance Injuries that alter knee kinematics might load regions of the joint where the cartilage is thinner. This might alter the stress distributions within the cartilage.