Image-Guided Radiation Therapy in Lymphoma Management: The Increasing Role of Functional Imaging PDF

Preface

Image-Guided Radiation Th erapy (IGRT) can be seen as the latest step in the evolution of radiation therapy from a loosely focused directional therapeutic to a more tightly focused highly targeted biologically active form of treatment for cancer. As the degree of targeting increases, there is concomitant reduction of non-target or "innocent bystander" damage to normal tissue within the treatment site. Refi ning the target and diff erentiating it from nearby normal structures are key factors in driving current interest in IGRT and its potential for reducing normal tissue damage.

An important component of risk minimization involves developing algorithms to guide the direction of delivered dose to the location of clonogenically viable target cells. Th is location will usually include areas of visible tumor and radiographically detectable marginal cancer masses but usually also involves a more poorly defi ned region in which tumor cell density may be too low to detect with conventional radiographic studies. Advanced anatomic imaging procedures, such as CT, MRI, and ultrasound, have been readily incorporated into the armamentarium of the radiation oncologist and the treatment planning team. For some tumor types, volumetric imaging obtained from these modalities provides suffi cient information for successful treatment, while in other cases, more sophisticated approaches, such as use of conebeam CT, are necessary.

For malignant lymphoma, the task of precision targeting can be more elusive, as tumor boundaries are not always well demarcated anatomically. In the case of lymphoma, PET (positron emission tomography) imaging with the radiotracer18F-Fluorodeoxyglucose (18FDG) to image tumor glucose utilization has proven particularly rewarding in staging as well as monitor the eff ects of treatment. PET essentially allows real-time in vivo observation of clinically relevant biological processes taking place within normal and transformed tissue. While compounds such as 18FDG have been shown to be useful as tumor markers and staging indicators, new families of radiotracers are now being evaluated as potential indicators of tumor responsiveness and surrogate clinical tumor control endpoints in management of malignant lymphoma. Serial changes in the pattern observed with 18FDG-PET studies of patients undergoing chemotherapy or radiation appear capable of predicting ultimate responses aft er a "trial" course of initial therapy. This serial imaging should in theory allow ineff ective agents and treatments to be terminated and replaced with alternative treatment before serious toxicity or gross disease progression becomes manifest.

The application of these principles to clinical cancer medicine is now being formalized via comprehensive clinical trials and expert consensus reviews. This area remains very much a work in progress. In this manual, we have attempted to provide current highlights of the way that many diff erent teams of experienced radiation oncologists and nuclear medicine physicians are using

the new technologies of radiotherapy image guidance and correlated functional imaging. Each chapter is meant to be a summary of relevant clinical data and approaches to tumor control. An introductory chapter summarizes the way that image guidance and functional imaging are being applied to the problems of tumor control. These technologies are expanding very rapidly and it is likely that subsequent editions will require major rewriting as these technologies become more standardized. The manual is not meant to be encyclopedic in its coverage and will not take the place of more standard textbooks of radiation medicine. It should, however, serve as a starting point for students and practitioners interested in understanding the direction of this field.

At present true image guidance is still used in a minority of clinical radiation medicine protocols but the proportion is growing rapidly. Many expert radiation oncologists believe that ultimately nearly all therapeutic radiation exposures will be delivered using some form of image guidance. However we must avoid the tendency to use high technology for worthless levels of precision. IGRT will have to show its merits through comparative eff ectiveness studies conducted and graded by fi nancially disinterested parties. The demonstration of the power of functional imaging in lymphoma management is already fulfi lling this mandate and its application to highly conformal beam targeting will have to meet these same hurdles in order to convince skeptics of its ultimate worth.

The teams of authors responsible for writing and editing these chapters include nuclear medicine physicians, medical oncologists, and physicists, in addition to radiation oncologists. It is only through the recruitment and organization of such multidisciplinary teams that the optimal use of these technologies will ever be elucidated and brought to bear on clinical oncology. The use of IGRT and functional imaging are ideally suited for the management of some clinical situations, and it will be incumbent on current and future teams of multi-specialty physicians to identify exactly which groups of patients may be best served through this technologic application of carefully targeted treatment. One size will not fit all, and our decision to publish this introductory manual was meant to mark the beginning of an exciting technologic and medical journey that will lead to personalized care for patients suff ering from this disease.

A century ago, radiation therapy was one of the only clinical treatments capable of producing true cure in malignant lymphoma patients. As cytotoxic chemotherapy became more widely available the dependence on radiotherapy diminished and it is currently much more rarely used in defi nitive therapy. It is possible that some of the principles and practices outlined in this volume will help build on a techno-biologic paradigm shift that may once again lead to a renaissance in the use of radiation medicine as a component of multimodality lymphoma management.