The effect of dose escalation on gastric toxicity when treating lower oesophageal tumours: a radiobiological investigation

Purpose Using radiobiological modelling to estimate normal tissue toxicity, this study investigates the effects of dose escalation for concurrent chemoradiation therapy (CRT) in lower third oesophageal tumours on the stomach. Methods and materials 10 patients with lower third oesophageal cancer were selected from the SCOPE 1 database (ISCRT47718479) with a mean planning target volume (PTV) of 348 cm3. The original 3D conformal plans (50Gy3D) were compared to newly created RapidArc plans of 50GyRA and 60GyRA, the latter using a simultaneous integrated boost (SIB) technique using a boost volume, PTV2. Dose-volume metrics and estimates of normal tissue complication probability (NTCP) were compared. Results There was a significant increase in NTCP of the stomach wall when moving from the 50GyRA to the 60GyRA plans (11–17 %, Wilcoxon signed rank test, p = 0.01). There was a strong correlation between the NTCP values of the stomach wall and the volume of the stomach wall/PTV 1 and stomach wall/PTV2 overlap structures (R = 0.80 and R = 0.82 respectively) for the 60GyRA plans. Conclusion Radiobiological modelling suggests that increasing the prescribed dose to 60Gy may be associated with a significantly increased risk of toxicity to the stomach. It is recommended that stomach toxicity be closely monitored when treating patients with lower third oesophageal tumours with 60Gy

Syntheses, Structures, and Characterization of Metal Carbonyl Complexes as Photoactive CO Releasing Molecules and their Biological Utility Towards Eradication of Cancer

Carbon monoxide (CO) has recently been shown to elicit various salutary effects in mammalian physiology. This small molecule has shown to exert a multitude of actions, which includes, vasoregulation, inflammation reduction and anti-apoptotic actions in normal cells. Interestingly, in hyperproliferative cells, CO has shown to induce significant pro-apoptotic effects, which can be exploited therapeutically towards cancer eradication. However, the ability to deliver CO in a target-specific manner has been a tantalizingly challenging task. In order to tackle this issue, CO releasing pro-drugs have been developed in order to deliver CO in a more controlled fashion to cellular targets. However, a large number of such pro-drug molecules systemically release CO, a process that can hardly be controlled. We have employed metal carbonyl complexes (MCCs) to deliver CO upon light illumination, which are otherwise stable under dark conditions. The requirement of light of a particular wavelength to trigger CO photorelease from such MCCs is strictly dependent on complex design. The important goal is to develop an ideal MCC where CO release can be initiated upon illumination of lights of biocompatible wavelength range. The series of complexes in Chapter 2 bearing manganese(I), ruthenium(II), and rhenium(I) metal centers elucidates the design principles necessary to enable CO photorelease under certain ranges of light illumination. In such endeavor, the choice of organic ligand frame and co-ligand along with their geometrical placement are critical. The choice of metal also plays an important role in dictating the photo behavior of such complexes. Chapter 3 utilizes the design principles established in chapter 2 and further explores the ligand design and steric features associated with organic ligand frame towards CO photorelease. These characteristics facilitated exceptionally rapid CO release under the control of visible light, thus affording a system ideal for application in certain therapeutic procedure that requires high local concentration of CO. The subject matter of chapter 4 deals with developing a trackable CO delivery system without attenuation of the drug (CO) within the cellular matrices. The design principles for such trackable CO releasing MCC involved rigid ring ligand frames bound to manganese(I) metal center which resulted a “turn on” luminescence, and with a rhenium(I) metal center afforded a “two-tone” theranostic system upon CO delivery. In part 1, such Mn(I) carbonyl complex aided the tracking of CO release event within MDA-MB-231 cancer cells under the control of visible light, while in part 2 the internalization of a luminescent Re(I) complex pro-drug can be followed within biological matrices and a distinct second fluorescence signal is observed when the drug (CO) is released upon illumination. The eventual obstacle towards developing a truly biocompatible CO releasing pro-drug (both sensitivity to visible light and aqueous solubility) is achieved in chapter 5. Two manganese carbonyl complexes incorporating rigid fluorescent α-diimine ligands are reported in this chapter. The inclusion of 1,3,5-triaza-7-phosphaadmantane (PTA) as ancillary ligand confers remarkable water solubility to such complexes. Both of these MCCs exhibit CO release upon low power visible light illumination. Taken together these features, it reasonable to assume that these CO releasing pro drugs have huge potential to find their place in clinic settings as phototherapeutics in near future

Implementing a cognitive-behavioral pain self-management program in home health care, part 1: Program adaptation

Background and Purpose: Pain is highly prevalent among older adults receiving home care, contributing to disability, increased health care utilization, nursing home placement, and diminished quality of life. Pain is a particular problem in the home care setting, where current approaches are often inadequate, resulting in persistent high levels of pain and disability in this vulnerable population. Cognitive-behavioral approaches to pain management have demonstrated effectiveness in reducing pain intensity and associated disability but have not been systematically implemented in home health care. The purpose of this project was to adapt a communitybased, cognitive-behavioral pain self-management program designed for patients with persistent back pain for implementation by physical therapists (PTs) to use with patients with activity-limiting pain in the home care setting. Methods: In this observational study, 2 groups of PTs practicing in home care were trained in the community-based program and completed surveys and participated in discussions during the training workshops to gather input on the program components perceived to be most helpful for their patients with pain; modifications to the program and the patient education materials for use in home care; and recommendations concerning program training and support required for successful implementation. Data collected during the workshops were summarized and presented to 2 expert panels for additional input and final decisions regarding program adaptations. Results: Seventeen PTs with an average of 16.6 years of practice as a PT received the training and provided input on the community-based program. Program modifications based upon PT and expert panel review included reduction in the number of sessions, deletion of content, modification of the exercise component of the program, revision of patient materials, and modification of therapist training. Discussion/Conclusions: This study successfully adapted a group-based pain management program for implementation by health care providers in a home care setting. The process described here may be useful for other groups planning to implement evidence-based programs in new settings. Part 2 of this study, a companion article in this issue, describes the field-testing of this home-care adapted program. Copyright © 2013 The Section on Geriatrics of the American Physical Therapy Association