Recommendations for MRI-based contouring of gross tumor volume and organs at risk for radiation therapy of pancreatic cancer.

PURPOSE: Local recurrence is a common and morbid event in patients with unresectable pancreatic adenocarcinoma. A more conformal and targeted radiation dose to the macroscopic tumor in nonmetastatic pancreatic cancer is likely to reduce acute toxicity and improve local control. Optimal soft tissue contrast is required to facilitate delineation of a target and creation of a planning target volume with margin reduction and motion management. Magnetic resonance imaging (MRI) offers considerable advantages in optimizing soft tissue delineation and is an ideal modality for imaging and delineating a gross tumor volume (GTV) within the pancreas, particularly as it relates to conformal radiation planning. Currently, no guidelines have been defined for the delineation of pancreatic tumors for radiation therapy treatment planning. Moreover, abdominal MRI sequences are complex and the anatomy relevant to the radiation oncologist can be challenging. The purpose of this study is to provide recommendations for delineation of GTV and organs at risk (OARs) using MRI and incorporating multiple MRI sequences. METHODS AND MATERIALS: Five patients with pancreatic cancer and 1 healthy subject were imaged with MRI scans either on 1.5T or on 3T magnets in 2 separate institutes. The GTV and OARs were contoured for all patients in a consensus meeting. RESULTS: An overview of MRI-based anatomy of the GTV and OARs is provided. Practical contouring instructions for the GTV and the OARs with the aid of MRI were developed and included in these recommendations. In addition, practical suggestions for implementation of MRI in pancreatic radiation treatment planning are provided. CONCLUSIONS: With this report, we attempt to provide recommendations for MRI-based contouring of pancreatic tumors and OARs. This could lead to better uniformity in defining the GTV and OARs for clinical trials and in radiation therapy treatment planning, with the ultimate goal of improving local control while minimizing morbidity.

Using higher organisms in biological early warning systems for real-time toxicity detection.

Many biological early warning systems (BEWS) have been developed in recent years that evaluate the physiological and behavioral responses of whole organisms to water quality. Using a fish ventilatory monitoring system developed at the US Army Centre for Environmental Health Research as an example, we illustrate the operation of a BEWS at a groundwater treatment facility. During a recent 12-month period, the fish ventilatory system was operational for 99% of the time that the treatment facility was on-line. Effluent-exposed fish responded as a group about 2.8% of the time. While some events were due to equipment problems or non-toxic water quality variations, the fish system did indicate effluent anomalies that were subsequently identified and corrected. The fish monitoring BEWS increased treatment facility engineers' awareness of effluent quality and provided an extra measure of assurance to regulators and the public. Many operational and practical considerations for whole organism BEWS are similar to those for cell- or tissue-based biosensors. An effective biomonitoring system may need to integrate the responses of several biological and chemical sensors to achieve desired operational goals. Future development of an 'electronic canary', analogous to the original canary in the coal mine, could draw upon advances in signal processing and communication to establish a network of sensors in a watershed and to provide useful real-time information on water quality.

Military deployment toxicology: a program manager's perspective.

The Persian Gulf War drew attention to the potential hazards of chemicals that personnel may encounter during military operations and deployments overseas. During the War, the oil well fires of Kuwait highlighted the military threat of industrial chemicals in the area of operations. Following the War, the occurrence of Gulf War Illnesses brought home concerns and suspicions regarding "low level" and "mixed" exposures to chemicals. The public's concern and attention resulted in numerous institutional responses to the real and perceived problems of health risks during military deployments. These institutional responses ranged in scope from a Presidential Review Directive to the initiative known as the Deployment Toxicology Research, Development, Testing and Evaluation (RDT&E) Program. Most institutions, however, seem to agree that additional research is needed to assess the health risks from chemical exposures during military deployments. Establishing and managing an effective RDT&E program in risk assessment for deployed forces is a challenging enterprise. The Deployment Toxicology RDT&E Program was conceived utilizing the military's acquisition framework, an effective methodology with a proven record of fielding of new technologies. Based on a series of structured meetings with military representatives that would utilize new risk assessment tools, a hierarchical set of plans was developed to identify and prioritize end products. The challenge ahead for the Deployment Toxicology RDT&E Program is to execute these plans, provide the necessary oversight, and transition the results into successful product development.

Application of neurobehavioral toxicology methods to the military deployment toxicology assessment program.

The military Tri-Service (Army, Navy & Marines, Air Force) Deployment Toxicology Assessment Program (DTAP) represents a 30-year (1996-2026) planning effort to implement comprehensive systems for the protection of internationally deployed troops against toxicant exposures. A major objective of DTAP is the implementation of a global surveillance system to identify chemicals with the potential to reduce human performance capacity. Implementation requires prior development of complex human risk assessment models, known collectively as the Neurobehavioral Toxicity Evaluation Instrument (NTEI), based on mathematical interpolation of results from tissue-based and in vivo animal studies validated by human performance assessment research. The Neurobehavioral Toxicity Assessment Group (NTAG) at the Naval Health Research Center Detachment-Toxicology (NHRC-TD), Dayton, OH, and associated academic institutions are developing and cross-validating cellular-level (NTAS), laboratory small animal (NTAB), nonhuman primate (GASP), and human-based (GASH) toxicity assessment batteries. These batteries will be utilized to develop and evaluate mathematical predictors of human neurobehavioral toxicity, as a function of laboratory performance deficits predicted by quantitative structural analysis relationship (QSAR-like) properties of potential toxicants identified by international surveillance systems. Finally, physiologically-based pharmacokinetic (PBPK) and pharmacodynamic (PBPD) modeling of NTAS, NTAB, GASP, GASH data will support multi-organizational development and validation of the NTEI. The validated NTEI tool will represent a complex database management system, integrating global satellite surveillance input to provide real-time decision-making support for deployed military personnel.