Cancer Science & Therapy

The use of nanocarriers as drug delivery systems for chemotherapeutic agents can improve the overall pharmacological properties of commonly used drugs in chemotherapy. The clinical success, as well as the ease with which surface modifi cations can be made to both liposomes and micelles to accommodate targeting ligands have made these nanocarriers in particular attractive candidates for future work involving targeted drug delivery. Although not targeted, there are clinically approved liposomal-based drugs that are currently used to treat various types of cancers. Furthermore, there are several other formulations involving both of these nanocarriers which are now in various stages of clinical trials. This review discusses the use of liposomes and micelles in cancer therapy and attempts to provide some current information regarding the clinical status of several of these nanocarrier-based drugs. In addition, recent work involving the incorporation of targeting ligands to systems such as these in order to improve colocalization between the drug and cancer cells is also addressed. Furthermore, while the use of these nanocarriers in particular is the primary focus here, this review also contains a discussion on other commonly used nanocarriers in cancer therapy to include various polymer-based and polymer-protein conjugates. Finally, the possibility of using combinatorial approaches involving multiple surface modifi cations made to both liposomes and micelles in order to further improve their drug delivery capabilities is also discussed.

Intensity Modulated Radiation Therapy (IMRT) has the potential to deliver a highly conformal dose distribution to the target volume compared to conventional radiotherapy. However, the use of IMRT introduces complexities in dose delivery and veri fi cation. Routine IMRT QA is typically performed in a homogeneous solid water phantom and does not verify the accuracy of a treatment planning system’s handling of the heterogeneity correction algorithm, which is particularly important in a low density lung medium. The purpose of this work is to evaluate common IMRT QA point measurement processes that take advantage of a commercial heterogeneous phantom [CIRS IMRT thorax phantom (CIRS, Inc., Norfolk, Virginia, USA)]. Dose calculated with Monte Carlo (MC) methods and pencil beam (PB) methods are used. IMRT QA using the CIRS phantom with the MC and PB algorithms was retrospectively analyzed using control charts and a capability index. Fifteen actual IMRT treatment plans of lung cancer patients were used for this study. The dose was measured in the phantom at points located in lung, bone, and tissue with an ion chamber (IC) for 15 cases and thermoluminescent dosimeters (TLDs) for 5 cases. Measurements and calculations in each heterogeneity (e.g., TLD/MC in bone) were considered as separate processes. Control charts and the capability index Cpm were used to evaluate the following processes using the CIRS phantom: IC/MC, PB/MC, TLD/MC for measurements in the lung, tissue and bone. The processes PB/IC and MC/IC using conventional homogeneous water-equivalent slab geometry were also evaluated. In total, 11 IMRT QA processes were considered. Comparison of the data showed that the dose inside the lung calculated with PB was overestimated by 6% on average relative to the MC calculations. On average, MC calculations in bone and tissue agree within 3% with PB calculations and IC measurements. Process capability values (Cpm) greater than 1.33 indicate a well performing process. Using the CIRS phantom, Cpm ranged from 0.25 for the PB/ MC process in lung to 1.41 for the TLD/MC process in tissue. By comparison, the process using the conventional water- equivalent slab phantom showed the PB/IC and MC/IC Cpm values of 1.36 and 1.21, respectively. Nine of the 11 IMRT QA processes studied were not able to meet the clinical speci fi cations of 5%. However, we found the CIRS phantom is versatile to compare both homogeneous and heterogeneous IMRT QA measurements to calculations. Our results indicate that additional re fi nements of the IMRT QA processes are required. This is especially true for calculations and measurements in lung-equivalent media. The capability index is a simple and useful quantitative tool for comparing different approaches to lung IMRT QA.

Background: Recursive partitioning analysis classes is the prognostic score that has been found by several groups to predict survival in patients with brain metastases from primary breast cancer. Recent data suggests that primary tumour characteristics might provide further important information. Methods: The impact of primary tumour size, histological grade, hormone receptor status, number of lymph node metastases and Nottingham prognostic index (NPI) was evaluated together with established factors such as performance status by uni- and multivariate analyses in 90 patients. All patients had been treated with whole-brain radiotherapy with or without radiosurgery or surgical resection. Results: In multivariate analysis, only performance status, age and interval from primary tumour diagnosis to brain metastases were significant. Patients with favourable NPI survived longer. However, this finding is based on a small group of patients and needs to be confirmed in larger studies. Higher histological grade and NPI were associated with significantly shorter interval to development of brain metastases. Conclusions: The standard brain metastases scores might not fully appreciate the unique biology and time course of breast cancer. Emerging prognostic factors such as NPI or triple-negative status might improve the models currently used by clinicians.

Intensity Modulated Radiation Therapy (IMRT) is widely accepted as an appropriate method to treat tumors at many different anatomic locations including lung. Dose calculation algorithms that have different degrees of accuracy are used to produce clinical IMRT treatment plans. In this study, Monte Carlo (MC) dose calculation was used to evaluate the reliability of plan evaluation parameters compared to a pencil beam (PB) dose calculation for IMRT of the lung.Twenty fi ve lung IMRT cases were randomly selected for analysis. Plan evaluation parameters were calculated using PB and MC methods for the targets and organs at risk (OARs). Comparisons were made using dose-volume histograms, mean dose, and equivalent uniform dose. The following doses-volume histogram points were compared: D98, D95 of the GTV and PTV, V20 and V30 for the lungs, D33 for the heart and esophagus and Dmax for the spinal cord. Mean dose differences were 3.6 ± 2.3% and 4.3 ± 2.8% for the GTV and PTV, respectively. The average EUD differences were 4.1 ± 2.4% for the GTV and 5.7 ± 4.9% for the PTV. Less than 2% differences were observed between the MC and PB algorithms for all OAR plan evaluation parameters. However, minimum and maximum differences for some plan evaluation parameters ranged from about ±20%.There are appreciable differences in plan evaluation parameters between the PB and MC calculations for the targets. The mean dose and EUD have a weak but statistically signifi cant inverse dependence on the number of fi elds, total MU, GTV volume and PTV volume for the targets. There can be large case-to-case differences between PB and MC for both the targets and OARs. Accurate MC calculations can remove those remaining systematic errors from treatment plans compared to PB calculations.