Estimated radiation pneumonitis risk after photon versus proton therapy alone or combined with chemotherapy for lung cancer.

BACKGROUND: Traditionally, radiation therapy plans are optimized without consideration of chemotherapy. Here, we model the risk of radiation pneumonitis (RP) in the presence of a possible interaction between chemotherapy and radiation dose distribution. MATERIAL AND METHODS: Three alternative treatment plans are compared in 18 non-small cell lung cancer patients previously treated with helical tomotherapy; the tomotherapy plan, an intensity modulated proton therapy plan (IMPT) and a three dimensional conformal radiotherapy (3D-CRT) plan. All plans are optimized without consideration of the chemotherapy effect. The effect of chemotherapy is modeled as an independent cell killing process using a uniform chemotherapy equivalent radiation dose (CERD) added to the entire organ at risk. We estimate the risk of grade 3 or higher RP (G3RP) using the critical volume model. RESULTS: The mean risk of clinical G3RP at zero CERD is 5% for tomotherapy (range: 1-18 %) and 14% for 3D-CRT (range 2-49%). When the CERD exceeds 9 Gy, however, the risk of RP with the tomotherapy plans become higher than the 3D-CRT plans. The IMPT plans are less toxic both at zero CERD (mean 2%, range 1-5%) and at CERD = 10 Gy (mean 7%, range 1-28%). Tomotherapy yields a lower risk of RP than 3D-CRT for 17/18 patients at zero CERD, but only for 7/18 patients at CERD = 10 Gy. IMPT gives the lowest risk of all plans for 17/18 patients at zero CERD and for all patients with CERD = 10 Gy. CONCLUSIONS: The low dose bath from highly conformal photon techniques may become relevant for lung toxicity when radiation is combined with cytotoxic chemotherapy as shown here. Proton therapy allows highly conformal delivery while minimizing the low dose bath potentially interacting with chemotherapy. Thus, intensive drug-radiation combinations could be an interesting indication for selecting patients for proton therapy. It is likely that the IMRT plans would perform better if the CERD was accounted for during optimization, but more clinical data is required to facilitate evidence-based plan optimization in the multi-modality setting.

RapidArc treatment verification in 3D using polymer gel dosimetry and Monte Carlo simulation.

The aim of this study was to verify the advanced inhomogeneous dose distribution produced by a volumetric arc therapy technique (RapidArc) using 3D gel measurements and Monte Carlo (MC) simulations. The TPS (treatment planning system)-calculated dose distribution was compared with gel measurements and MC simulations, thus investigating any discrepancy between the planned dose delivery and the actual delivery. Additionally, the reproducibility of the delivery was investigated using repeated gel measurements. A prostate treatment plan was delivered to a 1.3 liter nPAG gel phantom using one single arc rotation and a target dose of 3.3 Gy. Magnetic resonance imaging of the gel was carried out using a 1.5 T scanner. The MC dose distributions were calculated using the VIMC-Arc code. The relative absorbed dose differences were calculated voxel-by-voxel, within the volume enclosed by the 90% isodose surface (VOI(90)), for the TPS versus gel and TPS versus MC. The differences between the verification methods, MC versus gel, and between two repeated gel measurements were investigated in the same way. For all volume comparisons, the mean value was within 1% and the standard deviation of the differences was within 2.5% (1SD). A 3D gamma analysis between the dose matrices were carried out using gamma criteria 3%/3 mm and 5%/5 mm (% dose difference and mm distance to agreement) within the volume enclosed by the 50% isodose surface (VOI(50)) and the 90% isodose surface (VOI(90)), respectively. All comparisons resulted in very high pass rates. More than 95% of the TPS points were within 3%/3 mm of both the gel measurement and MC simulation, both inside VOI(50) and VOI(90). Additionally, the repeated gel measurements showed excellent consistency, indicating reproducible delivery. Using MC simulations and gel measurements, this verification study successfully demonstrated that the RapidArc plan was both accurately calculated and delivered as planned.

The effect of different lung densities on the accuracy of various radiotherapy dose calculation methods: implications for tumour coverage.

PURPOSE: To evaluate against Monte-Carlo the performance of various dose calculations algorithms regarding lung tumour coverage in stereotactic body radiotherapy (SBRT) conditions. MATERIALS AND METHODS: Dose distributions in virtual lung phantoms have been calculated using four commercial Treatment Planning System (TPS) algorithms and one Monte Carlo (MC) system (EGSnrc). We compared the performance of the algorithms in calculating the target dose for different degrees of lung inflation. The phantoms had a cubic 'body' and 'lung' and a central 2-cm diameter spherical 'tumour' (the body and tumour have unit density). The lung tissue was assigned five densities (rho(lung)): 0.01, 0.1, 0.2, 0.4 and 1g/cm(3). Four-field treatment plans were calculated with 6- and 18 MV narrow beams for each value of rho(lung). We considered the Pencil Beam Convolution (PBC(Ecl)) and the Analytical Anisotropic Algorithm (AAA(Ecl)) from Varian Eclipse and the Pencil Beam Convolution (PBC(OMP)) and the Collapsed Cone Convolution (CCC(OMP)) algorithms from Oncentra MasterPlan. RESULTS: When changing rho(lung) from 0.4 to 0.1g/cm(3), the MC median target dose decreased from 89.2% to 74.9% for 6 MV and from 83.3% to 61.6% for 18 MV (of dose maximum in the homogenous case at both energies), while for both PB algorithms the median target dose was virtually independent of lung density. CONCLUSIONS: Both PB algorithms overestimated the target dose, the overestimation increasing as rho(lung) decreased. Concerning target dose, the AAA(Ecl) and CCC(OMP) algorithms appear to be adequate alternatives to MC.

Day treatment versus enhanced standard methadone services for opioid-dependent patients: a comparison of clinical efficacy and cost.

OBJECTIVE: This study examined the differential efficacy and relative costs of two intensities of adjunctive psychosocial services--a day treatment program and enhanced standard care--for the treatment of opioid-dependent patients maintained on methadone hydrochloride. METHOD: A 12-week randomized clinical trial with 6-month follow-up was conducted in a community-based methadone maintenance program. Of the 308 patients who met inclusion criteria, 291 began treatment (day treatment program: N=145; enhanced standard care: N=146), and 237 completed treatment (82% of those assigned to the day treatment program and 81% of those receiving enhanced standard care). Two hundred twenty of the patients participated in the 6-month follow-up (75% of those in the day treatment program and 73% of those in enhanced standard care provided a follow-up urine sample for screening). Both interventions were 12 weeks in duration, manual-guided, and provided by master's-level clinicians. The day treatment was an intensive, 25-hour-per-week program. The enhanced standard care was standard methadone maintenance plus a weekly skills training group and referral to on- and off-site services. Outcome measures included twice weekly urine toxicology screens, severity of addiction-related problems, prevalence of HIV risk behaviors, and program costs. RESULTS: Although the cost of the day treatment program was significantly higher, there was no significant difference in the two groups' use of either opiates or cocaine. Over the course of treatment, drug use, drug-related problems, and HIV risk behaviors decreased significantly for patients assigned to both treatment intensities. Improvements were maintained at follow-up. CONCLUSIONS: Providing an intensive day treatment program to unemployed, inner-city methadone patients was not cost-effective relative to a program of enhanced methadone maintenance services, which produced comparable outcomes at less than half the cost.

Generics: what's in a name?

Historically, the most common intervention performed by physicians has been the writing of a prescription. Often the prescription was a combination of active agents and an inactive base. This art is no longer practiced in the United States. Currently, most prescriptions are written for specific "drugs." As the prescription is being written, the physician must decide to administer a brand-name or a generic equivalent. Generics are a class of medications prescribed for reasons of economy, and the physician and the patient expect that the therapeutic effect will be exactly the same as for the brand-name. Bioequivalence of specific agents can be assessed using the FDA's Orange Book. In addition to bioequivalence, many other scientific, ethical, and economic issues should be considered before a decision is made. Prescribing vigilance is necessary, because in many instances available information is often controlling or insufficient to support rational decisions. Brand-names, rather than generics, should be selected when the therapeutic index is narrow or if the likelihood of generic switching is high. The paper will discuss all aspects of the subject.