The effect of laparoscopic guidance on gynecologic interstitial brachytherapy.

STUDY OBJECTIVE: To compare laparoscopic-assisted interstitial brachytherapy (LAIB) with traditional interstitial brachytherapy (TrIB) in the treatment of gynecologic malignancies. DESIGN: Retrospective review (Canadian Task Force classification II-3). SETTING: University hospital. PATIENTS: A total of 42 women undergoing interstitial brachytherapy for a gynecologic malignancy. INTERVENTIONS: Interstitial brachytherapy by traditional method versus laparoscopic guidance. MEASUREMENTS AND MAIN RESULTS: In all, 42 women underwent interstitial brachytherapy with a mean follow-up of 24 months. In all, 28 patients underwent TrIB and 14 underwent LAIB. The mean operating department time was 177 minutes for LAIB and 91 minutes for TrIB (p<.001). No intraoperative complications existed in either group. Of the 14 patients undergoing LAIB, 2 (14%) had carcinomatosis, and the brachytherapy was aborted. Of patients who proceeded with LAIB, 64% had clinically significant pelvic adhesions necessitating lysis of adhesions. Mean radiation doses were similar for both external beam (LAIB=54 Gy, TrIB=50 Gy; p=.12) and brachytherapy (LAIB=29 Gy, TrIB=30 Gy; p=.8). No difference existed in the mean follow-up between groups (p=.7). In regard to long-term grade 3/4 radiation toxicity, 1 (10%) patient undergoing LAIB had a rectovaginal fistula. Six (27%) patients (p=.39; 95% CI 9%-43%) undergoing TrIB experienced high-grade toxicity, including 2 rectovaginal fistulas, 1 rectal stricture, 1 necrotizing fasciitis, 1 urinary incontinence, and 1 soft-tissue necrosis. CONCLUSION: The LAIB procedure appears safe, but substantially increases operating department time. No significant decrease in late high-grade toxicities were detected in comparison with TrIB. The LAIB procedure allows for both lysis of adhesions and identification of unknown carcinomatosis.

Oral transmissibility of prion disease is enhanced by binding to soil particles.

Soil may serve as an environmental reservoir for prion infectivity and contribute to the horizontal transmission of prion diseases (transmissible spongiform encephalopathies [TSEs]) of sheep, deer, and elk. TSE infectivity can persist in soil for years, and we previously demonstrated that the disease-associated form of the prion protein binds to soil particles and prions adsorbed to the common soil mineral montmorillonite (Mte) retain infectivity following intracerebral inoculation. Here, we assess the oral infectivity of Mte- and soil-bound prions. We establish that prions bound to Mte are orally bioavailable, and that, unexpectedly, binding to Mte significantly enhances disease penetrance and reduces the incubation period relative to unbound agent. Cox proportional hazards modeling revealed that across the doses of TSE agent tested, Mte increased the effective infectious titer by a factor of 680 relative to unbound agent. Oral exposure to Mte-associated prions led to TSE development in experimental animals even at doses too low to produce clinical symptoms in the absence of the mineral. We tested the oral infectivity of prions bound to three whole soils differing in texture, mineralogy, and organic carbon content and found soil-bound prions to be orally infectious. Two of the three soils increased oral transmission of disease, and the infectivity of agent bound to the third organic carbon-rich soil was equivalent to that of unbound agent. Enhanced transmissibility of soil-bound prions may explain the environmental spread of some TSEs despite the presumably low levels shed into the environment. Association of prions with inorganic microparticles represents a novel means by which their oral transmission is enhanced relative to unbound agent.

What hypofractionated protocols should be tested for prostate cancer?

PURPOSE: Recent analyses of clinical results have suggested that the fractionation sensitivity of prostate tumors is remarkably high; corresponding point estimates of the alpha/beta ratio for prostate cancer are around 1.5 Gy, much lower than the typical value of 10 Gy for many other tumors. This low alpha/beta value is comparable to, and possibly even lower than, that of the surrounding late-responding normal tissue in rectal mucosa (alpha/beta nominally 3 Gy, but also likely to be in the 4-5 Gy range). This lower alpha/beta ratio for prostate cancer than for the surrounding late-responding normal tissue creates the potential for therapeutic gain. We analyze here possible high-gain/low-risk hypofractionated protocols for prostate cancer to test this suggestion. METHODS AND MATERIALS: Using standard linear-quadratic (LQ) modeling, a set of hypofractionated protocols can be designed in which a series of dose steps is given, each step of which keeps the late complications constant in rectal tissues. This is done by adjusting the dose per fraction and total dose to maintain a constant level of late effects. The effect on tumor control is then investigated. The resulting estimates are theoretical, although based on the best current modeling with alpha/beta parameters, which are discussed thoroughly. RESULTS: If the alpha/beta value for prostate is less than that for the surrounding late-responding normal tissue, the clinical gains can be rather large. Appropriately designed schedules using around ten large fractions can result in absolute increases of 15% to 20% in biochemical control with no evidence of disease (bNED), with no increase in late sequelae. Early sequelae are predicted to be decreased, provided that overall times are not shortened drastically because of a possible risk of acute or consequential late reactions in the rectum. An overall time not shorter than 5 weeks appears advisable for the hypofractionation schedules considered, pending further clinical trial results. Even if the prostate tumor alpha/beta ratio turns out to be the same (or even slightly larger than) the surrounding late-responding normal tissue, these hypofractionated regimens are estimated to be very unlikely to result in significantly increased late effects. CONCLUSIONS: The hypofractionated regimens that we suggest be tested for prostate-cancer radiotherapy show high potential therapeutic gain as well as economic and logistic advantages. They appear to have little potential risk as long as excessively short overall times (<5 weeks) and very small fraction numbers (<5) are avoided. The values of bNED and rectal complications presented are entirely theoretical, being related by LQ modeling to existing clinical data for approximately intermediate-risk prostate cancer patients as discussed in detail.