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The majority of patients with late stage castration-resistant prostate cancer (CRPC) develop bone metastases that often result in significant bone pain. Therapeutic palliation strategies can delay or prevent skeletal complications and may prolong survival. An alpha-particle based therapy, radium-223 dichloride (²²³RaCl₂), has been developed that delivers highly localized effects in target areas and likely reduces toxicity to adjacent healthy tissue, particularly bone marrow. Radiation safety aspects were evaluated for a single comprehensive cancer center clinical phase 1, open-label, single ascending-dose study for three cohorts at 50, 100, or 200 kBq kg⁻¹ body weight. Ten patients received administrations, and six patients completed the study with 1 y follow-up. Dose rates from patients administered ²²³Ra dichloride were typically less than 2 μSv h⁻¹ MBq⁻¹ on contact and averaged 0.02 μSv h⁻¹ MBq⁻¹ at 1 m immediately following administration. Removal was primarily by fecal excretion, and whole body effective half-lives were highly dependent upon fecal compartment transfer, ranging from 2.5-11.4 d. Radium-223 is safe and straightforward to administer using conventional nuclear medicine equipment. For this clinical study, few radiation protection limitations were recommended post-therapy based on facility evaluations. Specific precautions are dependent on local regulatory authority guidance. Subsequent studies have demonstrated significantly improved overall survival and very low toxicity, suggesting that ²²³Ra may provide a new standard of care for patients with CRPC and bone metastases.

Objective: 68Ga-1,4,7,10-Tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-F(ab')2-trastuzumab [68Ga-DOTA-F(ab')2-trastuzumab] has been developed at our institution as a positron imaging reagent for assessing human epidermal growth factor receptor 2 (HER2) expression status by in-vivo imaging. Initial studies on animals demonstrated promising results in the monitoring of treatment response to heat shock protein 90-targeted drugs that inhibit the client protein HER2. We report here our initial clinical experience in the assessment of the toxicity, pharmacokinetics, biodistribution, and dosimetry profile of 68Ga-DOTA-F(ab')2-trastuzumab with PET/computed tomography using a mean of 236 MBq/5 mg administered intravenously., Materials and Methods: A group of 16 women with breast cancer were enrolled in this study. The one patient who did not receive 68Ga-DOTA-F(ab')2-trastuzumab was excluded from analysis. Both HER2-negative (n=7) and HER2-positive (n=8) cases were studied. Among the latter, seven had undergone trastuzumab treatment previously and one had not., Results: It was determined that 68Ga-DOTA-F(ab')2-trastuzumab was well tolerated, with a T½ of ≈ 3.6 ± 0.9 h; the critical organ was the kidney, with a mean dose of 0.383 cGy/37 MBq; and tumor targeting was seen in 4/8 patients with HER2-positive disease., Conclusion: The reagent is safe, and assessments through additional studies in a better-defined group of patients, using larger administered masses of antibodies, with a better immunoreactive fraction are needed.

The long-term cosmetic outcome of breast implant reconstruction is unknown. The morbidity and cosmetic outcome of 360 patients who underwent immediate postmastectomy breast reconstruction with various types of implants have been analyzed prospectively over a 9-year period. Of these patients, 334 who completed their reconstruction were suitable for evaluation of their cosmetic outcome. The early complication rate (< 2 months) was 9.2 percent, with an explantation rate of 1.7 percent. The late complication rate (> 2 months) was 23 percent, with a pathological capsular contracture rate of 11 percent at 2 years and 15 percent at 5 years and an implant removal rate of 7 percent. The revisional surgery rate was 30.2 percent. The cosmetic results were assessed prospectively using an objective five-point global scale. Every patient was scored at each visit once surgery was completed. The overall cosmetic outcome deteriorated in a linear fashion, from an initial acceptable result of 86 percent 2 years after patients completed their reconstruction to only 54 percent at 5 years. This decline in cosmetic outcome was not associated with the type of implant used, the volume of the implant, the age of the patient, or the type of mastectomy incision employed. Radiotherapy was not a significant factor because only 28 patients were irradiated. Upon Cox model analysis, pathological capsular contracture was the only factor that contributed significantly to a poor cosmetic outcome in which p < 0.0001 (relative risk 6.3). Despite a high revisional surgery rate, deterioration still occurred, suggesting that other unaccounted for variables were responsible. On photographic retrospective review of the patients without capsular contracture who demonstrated deterioration in their cosmetic scores, it became clear that a possible reason for their poor results was late asymmetry produced by the failure of both breasts to undergo symmetrical ptosis with aging.

Although it is thought that transverse rectus abdominis muscle (TRAM) flap breast reconstruction produces excellent cosmetic results that are maintained over the long term, there is little objective evidence in the literature to support this. One hundred seventy-one consecutive patients who underwent TRAM flap reconstruction were prospectively analyzed over an 8-year period to assess their morbidity and late cosmetic outcome.The early patient complication rate (< 2 months) was 37.4 percent, the late hernia and fat necrosis rates (> 2 months) were 8.8 and 13.5 percent, respectively, and the contralateral symmetrization rate was 33.9 percent. The cosmetic results were evaluated prospectively using an objective five-point global scale. Each patient was scored at each visit once surgery was completed. Follow-up continued until a flap was lost, a patient died, or the point of last patient contact was reached. Six patients died during the study. The actuarial percentage cosmetic outcome remained stable during the study period, with an acceptable result in 96.4 percent of patients at 2 years and in 94.2 percent of patients at 5 years. Only five patients in this series obtained poor cosmetic outcomes, with three due to substantial flap necrosis and two because of poor flap design. Two free TRAM flaps were also lost. Log-rank analysis revealed that neither patient age nor timing of surgery significantly affected the cosmetic outcome. Single pedicle and supercharged (single pedicle) TRAM flaps produced slightly better results than bipedicle and free TRAM flaps. In this prospective longitudinal study, TRAM flap reconstructions were shown to produce aesthetically pleasing results. Moreover, with long-term follow-up, it was demonstrated that these reconstructions maintained their stability.