The Effect of Radiation on Complication Rates and Patient Satisfaction in Breast Reconstruction using Temporary Tissue Expanders and Permanent Implants.

The optimal method of reconstruction following mastectomy for breast cancer patients receiving radiation therapy (RT) is controversial. This study evaluated patient satisfaction and complication rates among patients who received implant-based breast reconstruction. The specific treatment algorithm analyzed included patients receiving mastectomy and immediate temporary tissue expander (TE), followed by placement of a permanent breast implant (PI). If indicated, RT was delivered to the fully expanded TE. Records of 218 consecutive patients with 222 invasive (85%) or in situ (15%) breast lesions from the Salt Lake City region treated between 1998 and 2009 were retrospectively reviewed, 28% of whom received RT. Median RT dose was 50.4 Gy, and 41% received a scar boost at a median dose of 10 Gy. Kaplan-Meier analyses were performed to evaluate the cumulative incidence of surgical complications, including permanent PI removal. Risk factors associated with surgical events were analyzed. To evaluate cosmetic results and patient satisfaction, an anonymous survey was administered. Mean follow-up was 44 months (range 6-144). Actuarial 5-year PI removal rates for non-RT and RT patients were 4% and 22%, respectively. On multivariate analysis (MVA), the only factor associated with PI removal was RT (p = 0.009). Surveys were returned describing the outcomes of 149 breasts. For the non-RT and RT groups, those who rated their breast appearance as good or better were 63% versus 62%, respectively. Under 1/3 of each group was dissatisfied with their reconstruction. RT did not significantly affect patient satisfaction scores, but on MVA RT was the only factor associated with increased PI removal. This reconstruction technique may be considered an acceptable option even if RT is needed, but the increased complication risk with RT must be recognized.

Toxicity after central versus peripheral lung stereotactic body radiation therapy: a propensity score matched-pair analysis.

PURPOSE: To compare toxicity after stereotactic body radiation therapy (SBRT) for "central" tumors-within 2 cm of the proximal bronchial tree or with planning tumor volume (PTV) touching mediastinum-versus noncentral ("peripheral") lung tumors. METHODS AND MATERIALS: From November 2005 to January 2011, 229 tumors (110 central, 119 peripheral; T1-3N0M0 non-small-cell lung cancer and limited lung metastases) in 196 consecutive patients followed prospectively at a single institution received moderate-dose SBRT (48-60 Gy in 4-5 fractions [biologic effective dose=100-132 Gy, α/ß=10]) using 4-dimensional planning, online image-guided radiation therapy, and institutional dose constraints. Clinical adverse events (AEs) were graded prospectively at clinical and radiographic follow-up using Common Terminology Criteria for Adverse Events version 3.0. Pulmonary function test (PFT) decline was graded as 2 (25%-49.9% decline), 3 (50.0%-74.9% decline), or 4 (≥75.0% decline). Central/peripheral location was assessed retrospectively on planning CT scans. Groups were compared after propensity score matching. Characteristics were compared with χ(2) and 2-tailed t tests, adverse events with χ(2) test-for-trend, and cumulative incidence using competing risks analysis (Gray's test). RESULTS: With 79 central and 79 peripheral tumors matched, no differences in AEs were observed after 17 months median follow-up. Two-year cumulative incidences of grade ≥2 pain, musculoskeletal, pulmonary, and skin AEs were 14%, 5%, 6%, and 10% (central) versus 19%, 10%, 10%, and 3% (peripheral), respectively (P=.31, .38, .70, and .09). Grade ≥2 cardiovascular, gastrointestinal, and central nervous system AEs were rare (<1%). Two-year incidences of grade ≥2 clinical AEs (28% vs 25%, P=.79), grade ≥2 PFT decline (36% vs 34%, P=.94), grade ≥3 clinical AEs (3% vs 7%, P=.48), and grade ≥3 PFT decline (0 vs 10%, P=.11) were similar for central versus peripheral tumors, respectively. Pooled 2-year incidences of grades 4 and 5 AEs were <1% and 0%, respectively, in both the prematched and matched groups. CONCLUSION: Moderate-dose SBRT with these techniques yields a similarly safe toxicity profile for both central and peripheral lung tumors.

Capric Acid Absorption in the Presence of Hydroxypropyl-ß-Cyclodextrin in the Rat Ileum using the In Situ Single-Pass Perfusion Technique.

The purpose of the present study was to gain quantitative mechanistic insight into the role cyclodextrin carriers may play in the intestinal absorption of highly lipophilic molecules. The physical model approach was employed to investigate capric acid absorption in the rat ileum using the in situ single-pass method with 2-hydroxypropyl-ß-cyclodextrin (HPB) present in the perfusate. Two physical models were examined: the flat surface model in which the intestinal wall was treated as a hollow, smooth, circular cylinder, and the villus model in which the intestinal surface allowed for the presence of villi. Capric acid absorption was found to be essentially 100% aqueous boundary layer controlled at low HPB concentrations and increasingly membrane controlled at the higher HPB concentrations. Theoretical calculations based on the experimental data and model parameters were found to be consistent with: at low HPB concentrations, capric acid was mainly absorbed at the villus tips and there was very little capric acid penetration into the intervillus space; in contrast, at 50 mM HPB, there was considerable capric acid penetration into the intervillus space, this corresponding to around a 4.5-fold increase in the accessible area for absorption when compared with 0 mM HPB.

Transport of a lipophilic ionizable permeant (capric acid) across a lipophilic membrane (silicone polymer membrane) from aqueous buffered solutions in the presence of hydroxypropyl-ß-cyclodextrin.

The present study describes a physical model approach applicable to understanding the transport of highly lipophilic, ionizable drugs across a lipophilic membrane between two aqueous compartments in the presence of a cyclodextrin in the aqueous phase. Model predictions were compared with experimental results of capric acid (HA) transport across a silicone polymer membrane in the presence and in the absence of 2-hydroxypropyl-ß-cyclodextrin (HPB) in the aqueous phase over wide ranges of conditions. Key parameters entering into the physical model calculations were the HA-HPB and the A(-)-HPB binding constants, the unionized and ionized free and the complexed HA species diffusion coefficients, the HA pKa, the HA intrinsic silicone polymer membrane permeability coefficient, and the aqueous boundary layer thickness. All of these key parameters were determined from independent or essentially independent experiments. The agreement between the model predictions and the experiments were generally quite good over the entire ranges of the studied independent variables. The results of this study provide an approach that is useful in the mechanistic understanding of how cyclodextrins may enhance the passive absorption of highly lipophilic, low solubility drug molecules in the intestinal tract.

Is short-interval mammography necessary after breast conservation surgery and radiation treatment in breast cancer patients?

PURPOSE: The optimum timing and frequency of mammography in breast cancer patients after breast-conserving therapy (BCT) are controversial. The American Society of Clinical Oncology recommends the first posttreatment mammogram 1 year after diagnosis but no earlier than 6 months after completion of radiotherapy. The National Comprehensive Cancer Network recommends annual mammography. Intermountain Healthcare currently follows a more frequent mammography schedule during the first 2 years in BCT patients. This retrospective study was undertaken to determine the cancer yield mammography during the first 2 years after BCT. METHODS AND MATERIALS: 1,435 patients received BCT at Intermountain Healthcare between 2003 and 2007, inclusive. Twenty-three patients had bilateral breast cancer (1,458 total breasts). Patients were followed up for 24 months after diagnosis. The 1- and 2-year mammography yields were determined and compared with those of the general screening population. RESULTS: 1,079 breasts had mammography at less than 1 year, and two ipsilateral recurrences (both noninvasive) were identified; 1,219 breasts had mammography during the second year, and nine recurrences (three invasive, six noninvasive) were identified. Of the 11 ipsilateral recurrences during the study, three presented with symptoms and eight were identified by mammography alone. The mammography yield was 1.9 cancers per 1,000 breasts the first year and 4.9 per 1,000 the second year. CONCLUSIONS: These data demonstrate that the mammography yield during the first 2 years after BCT is not greater than that in the general population, and they support the policy for initiating followup mammography at 1 year after BCT.

Stereotactic radiosurgery eligibility and selection bias in the treatment of glioblastoma multiforme.

Several single institution studies have shown a survival advantage when a stereotactic radiosurgery (SRS) boost followed fractionated external beam radiation (FracRT) in the treatment of glioblastoma (GBM). RTOG 93-05 employed SRS before FracRT and demonstrated no survival benefit. We examined the effect of SRS eligibility before and after FracRT on patient outcome in a group of patients treated with conventional therapy without SRS. From 1998 to 2008, 106 patients with GBM treated definitively at the University of Utah were divided into groups based on eligibility for SRS: ineligible ("Never"), eligible before FracRT ("All Pre"), eligible before FracRT only ("Pre Only"), or eligible before and after FracRT ("Always"). Overall (OS) and progression-free survival (PFS) based on SRS eligibility was assessed. Eleven patients were alive at the time of analysis with a median follow-up of 42.3 months. Median OS for groups "All Pre" (n = 29), "Always" (n = 17), "Pre Only" (n = 12), and "Never" (n = 77) were 13.6, 13.6, 12.4, and 9.2 months, respectively. Of the 29 patients in group "All Pre," 12 (41.4%) were ineligible for SRS following FracRT. PFS did not significantly differ between groups. SRS for GBM can only be of benefit to selected patients with minimal focal postoperative disease. Following FracRT, over a third of initially SRS-eligible patients demonstrated more extensive disease in our experience. It is possible inclusion of such patients in a series of SRS for GBM could mask a benefit in remaining patients. No significant difference in OS or PFS based on SRS-eligibility status was found.

Systematic studies on the paracellular permeation of model permeants and oligonucleotides in the rat small intestine with chenodeoxycholate as enhancer.

The objective of this study was to mechanistically and quantitatively analyze chenodeoxycholate-enhanced paracellular transport of polar permeants and oligonucleotides in the rat jejunum and ileum. Micellar chenodeoxycholate solutions were used to perturbate the tight junctions. Supporting studies included assessment of the aqueous boundary layer (ABL) with ABL-controlled permeants, measurements of the permeability coefficients and fluxes of the bile acid in dilute and micellar concentrations, and determinations of pore sizes with paracellular probes (urea, mannitol, and raffinose). The paracellular permeability coefficients, P(para), of two model oligonucleotides (ON3 and ON6; 12- and 24-mers with 11 and 23 negative charges, respectively) were determined. The enhanced permeabilities paralleled the increased fluxes of micellar bile salt solutions into mesenteric blood and the opening of the tight junctions as compared to controls. As the pore radius increased from 0.7 nm to a maximum of 2.4 nm in the jejunum and ileum, the absorption of ON3 was enhanced up to sixfold in the jejunum and about 14-fold in the ileum with P(para) values between 0.5 x 10(-6) and 6 x 10(-6) cm/s, whereas ON6 was enhanced up to twofold in the jejunum and fivefold in the ileum with permeabilities between 0.3 x 10(-6) and 2 x 10(-6) cm/s.