Radiotherapy Treatment Planning PDF

Preface

There are currently several textbooks of radiobiology available for teaching the subject to medical physicists, radiation oncology residents and graduate students. Some of these have been updated on a regular basis and attempt to cover the breadth of the sciences (radiation physics, radiation chemistry, cell biology, tissue pathology, physiology and patient management) involved in the process of tumor cell killing, which has become an integral part of current cancer treatments. And, of late, a strong emphasis has been placed on genetic and molecular biology characterizations that might inform about these radiation processes and lead to an improved diagnosis and treatment of cancers. So why another textbook on this subject at this time?

The field of radiation oncology has experienced an immense boost in recent years in its ability to identify gross tumor volumes (GTVs) and planned treatment volumes (PTVs) with advanced techniques of tumor imaging, including computerized tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) in addition to conventional radiology and ultrasound. Also, novel systems for delivering radiation dose to PTVs have been developed and are operational. These include higher energy linear accelerators for electron and photon beams, systems for tomotherapy, gamma-knives for focal irradiation and systems that deliver beams of neutrons, protons and carbon ions. These improved technologies allow for a much better conformation of the prescription dose to tumor volumes with significant reductions in exposures to normal tissues. The standard practice of ~2 Gy fractions delivered 5 days a week uniformly to PTVs up to the dose that might negatively impact normal tissue function was empirically arrived at over several decades of clinical experience using inferior technologies. Of current interest is whether or not these technology advances will allow for modifications to current radiation prescriptions that prove to be more efficacious, more acceptable to patients (fewer fractions) and possibly less costly. Planning altered fractionation schemes for patient treatment requires reliable quantitative knowledge of the expected radiobiology responses of various tumors and normal tissues.

Over the past 40 years, radiation biophysicists have quantified the killing of tumor cells by radiation in mathematical terms that could be useful for treatment planning. At first the single-hit multitarget (SHMT) formulation was the choice to describe the cell response to radiations administered by different sources in various laboratories. But currently, there is general agreement that the linear-quadratic (LQ) equation defines radiation-induced cell killing more precisely and has now become the standard. The coefficients for single-hit (alpha) and double-hit (beta) inactivation can precisely define the radiation response of cultured human tumor cells when rigorous laboratory standards are employed.

In this book, we will describe tumor cell inactivation from a radiation physics perspective and suggest appropriate LQ parameters for modeling tumor and normal tissue responses. Consequently, the majority of data cited will be from those reports that describe cell killing in terms of the two independent processes of the LQ model. Much of that information has come from our laboratories with the intent of extending it to tumor control probability (TCP) and normal tissue complication probability (NTCP) modeling. The compilation of radiation mechanism information from over 40 different publications into a coherent understanding of how ionizing radiations produce the killing of stem cells in human tumors will read somewhat like a monograph. Several physical and chemical parameters that can modulate the radiation response of clonogenic cells in tumors will be described according to their impact on the two mechanisms of cell killing.

The use of the LQ model in basic radiation mechanism studies with cells of relatively homogeneous radiation response is presented and will be extended to the fitting of survival data generated with heterogeneous cell populations (tumors) where the inactivation parameters are some combination of those for the various cells that make up the whole. The use of the LQ model for predicting normal tissue complication responses (where mechanisms other than stem cell killing could be active) will be briefly addressed. These mechanisms will be discussed more fully in the planned Volume II. No comprehensive review of all the molecular mechanisms that could impact the radiation treatment of human cancers will be attempted since, in most cases, these studies do not distinguish between the two mechanisms of cell killing by radiation. The potential molecular targets related to alpha- and beta-inactivation will be described along with suggestions for further molecular characterizations of these two independent processes. This textbook should read as an advanced "target theory."

While radiobiology research over the past three or four decades has produced meaningful parameters for medical physicists to initiate TCP and NTCP modeling that predicts for altered cancer treatment prescriptions, the efforts to define clinical assays that inform about clonogen radiosensitivity, tumor oxygenation and tumor growth fraction, in general, were not successful. Although predictive assay research was informative, no standard assays are currently utilized to obtain this information from individual patients. Consequently, several important parameters that must be input into the models are best estimates or "guestimates" obtained from various published studies. In spite of these shortcomings, the time has come to investigate in clinical trials all the potential benefits that might arise from the recent advances in cancer imaging and dose delivery. It is our hope that this book, focused on quantitative radiobiology in the LQ formulation, will assist both medical physicists and radiation oncologists to identify improved cancer treatments. And if it inspires current investigators to translate potentially improved radiotherapy schedules based upon TCP and NTCP modeling to actual patient benefit, our efforts in assembling this volume will not have been in vain.

The cover of this book is a reworking of a figure that was presented in a poster at the International Congress of Radiation Research in Dublin, Ireland, in 1999. It obviously says that the understanding of cell killing by radiation and its use in radiotherapy is like a jigsaw puzzle where different specialties are merged together to relate the underlying physics, chemistry, biophysics, biochemistry, pathology and clinical outcome data that are available. Reece Walsh, an 11th grader who is skilled in computer graphics, created its final version. Through this experience, he learned some of the university-level sciences involved in cancer radiotherapy and could proceed to a career in medical physics, since he is truly gifted in mathematics and the physical sciences.