A Practical Guide to Intensity-Modulated Radiation Therapy  Price Reduced!

Author:  Memorial Sloan-Kettering Cancer Center
ISBN:  9781930524132      ISBN10:  1930524137
Published:  2003 | 450 pp. | Softcover

Price:   $ 62.95      was 125.00





Sample Chapter [pdf format]

Index: 553 references: Illustrated with more than 200 figures, 40 in full color


According to a Collaborative Working Group sponsored by the National Cancer Institute, "Intensity modulated radiotherapy (IMRT)…represents one of the most important technical advances in radiation therapy since the advent of the medical linear accelerators". In the last ten years, the clinicians and scientists at Memorial Sloan-Kettering Cancer Center have been fortunate to be involved in the development and implementation of this advanced form of radiotherapy. Indeed, it was in part serendipity that several key components of the IMRT process became available at MSKCC that permitted us to implement IMRT treatment with the use of dynamic multileaf collimation (DMLC) in 1995. Since then, we have amassed a body of technical and clinical experience in the use of this modality.

This book is an attempt to provide an account of our perspective, methodology, and experience in the physical and medical aspects of IMRT. For the medical physicists, there are detailed discussions on the inverse method, the commissioning and acceptance testing of DMLC, dose calculation and independent monitor unit (MU) check. For the radiation oncologists and clinical physicists, the relevant material includes treatment planning, quality assurance protocols, disease-specific treatment procedures, and emerging clinical outcome data. In addition, advanced topics relevant to IMRT are addressed such as the estimation of tumor control and normal tissue complication probabilities, the quantification and minimization of treatment uncertainties, the use of respiration-controlled techniques, and the emerging importance of biological imaging. Given the enthusiasm for the potential benefits of this modality, we hope this book will be useful for our colleagues in the radiation oncology community interested in applying IMRT.

Lastly, we wish to acknowledge colleagues who in the past have contributed to our IMRT program. These include John Laughlin, Jerry Kutcher, Radhe Mohan, Thomas Bortfeld, among others.

C Clifton Ling
New York, New York
January 2003


The adoption of intensity-modulated radiation therapy (IMRT) is a major shift in the practice of radiation oncology, perhaps the most important one since the development of gantry-mounted linear accelerators. Supervoltage energy combined with gantry mounting providing the ability to use both fixed and moving radiation sources was a quantum leap over the previously available fixed source to skin treatment from limited directions. These advances were due to both the more penetrating nature of supervoltage radiation and its skin sparing as compared to fixed mounted orthovoltage machines. This technology made rotational and arc therapy available and allowed the patient to be treated from many directions while in a single position. It was these improvements that ushered in current radiotherapy practices.

A longstanding goal of radiation therapy has been to make the radiation dose conform as closely as possible to the target volume while minimizing the dose to transited normal tissues. IMRT is the next major saltation in the quest for such a treatment. This method has come about because of advances in radiation physics, collimators, computers, software, and the armamentaria available for delivering radiation treatment. Perhaps not so clearly realized is the expanding revolution in medical imaging. It is cross-sectional tomographic and three-dimensional imaging using X-ray and magnetic resonance imaging (MRI) that allow much improved delineation of the tumor and the dose limiting normal tissues. Positron emission tomography (PET) and magnetic resonance spectroscopy (MRS) provide additional information important to tumor identification, localization, and, most intriguingly, the ability to anatomically evaluate tumor physiology. The increased diagnostic imaging ability coupled with IMRT has allowed conforming of radiation dose to the target volume to become a reality. Further, rather than continue pursuing homogeneity of dose within the target volume, radiation dose can now be made to conform to localized tumor using physiology as a guide: for example, raising the dose administered to regions of hypoxia or varying it consistent with tumor cell concentration. It can be modified during a course of multifraction radiation therapy in response of these variables to treatment.

There is an old adage cautioning one to be careful of what one wishes for, because the wish might be granted. Such may be the case with IMRT. We now are able to conform the radiation to the target volume: we are even able to sculpt the dose within the target volume consistent with our desires while minimizing unwanted radiation--or at least--placing it in the least damaging anatomic locations. But in order to do so we must be much more confident of the tumor location. The target definition needs to be accurately arrived at since we are now able to reduce dose at the edges of the tumor quite abruptly with this technique. Since it is characteristic of cancer to have subclinical disease beyond the gross tumor margins, we must either improve our diagnostic imaging techniques to visualize such subclinical disease or at least give us an estimate of tumor cell concentration and the rate at which this diminishes at the tumor periphery. With such information the shape of the dose distribution surrounding the high dose volume can be appropriately configured. The optimal shape of the dose fall-off could then be made to conform to the tumor cell concentration. As with previous methods, it is also determined by the proximity of dose-limiting normal tissues as well as by knowledge of the natural history of the tumor.

Radiation dose delivered to transited normal tissues is inherent in all radiation therapy for internal cancers. This unwanted radiation must be deposited consistent with the nature of the toxicity associated with irradiating the specific tissue. This is dependent on the dose, dose rate, the beam arrangement, and the resulting volume of the specific tissue irradiated to high doses. For the same beam arrangement, the integral dose of IMRT is no different from that of non-intensity-modulated 3DCRT plans, or that of simpler plans with similar radiation path-lengths. However, the ability to place and shape the unwanted radiation is far greater with IMRT and may result in dose deposition in normal tissues different from that of past practices. Addressing unfamiliar dose distributions encountered in IMRT may become important in treatment planning, and organ response to large volume moderate dose radiation needs to be carefully quantified.

In order to use IMRT properly not only must we have confidence as to the tumor location but we must also be confident of the position of the patient as well as the target volume during treatment. Immobilization of the patient, the use of fiducial-markers, real-time monitoring of the tumor location as well as gating of the treatment to breathing or other physiologic functions such a bowel gas movement are important if we are to successfully use intensity-modulated radiation therapy. There is far less margin for error in patient setup and tumor or organ motion with this method. Ideally, the technique should have imaging feedback at regular intervals during the treatment with the hope that eventually one might have real-time feedback and control of patient and tumor position, i.e., cybernetic radiation therapy.

Dose sculpting within the target volume requires that PET scanning and MRS be anatomically fused with computed tomography (CT) and MRI. Despite data being presented and evaluated as two-dimensional images, treatment is three-dimensional, requiring that the target volume be visualized this way. Once a three-dimensional presentation of the target volume and adjacent normal tissues is realized, then a vast increase in therapeutic alternatives might be achieved with non-coplanar field arrangements.

IMRT offers the opportunity to reconsider radiation fractionation since individual fraction sizes can be greatly increased using this technique. It may well be true that different types of tumors require very different fractionation schemes to achieve optimal benefit. The devices for delivering the radiation dose also need to be reevaluated. Gantry-mounted linear accelerators with dynamic multileaf collimators currently are the most commonly used technique, but there are others, either presently in use or in development. It will be important to determine what the appropriate armamentaria should be for an effective radiation oncology practice. These considerations will depend upon opportunities provided for off-axis treatment, reduced treatment time, increased flexibility, and the facility to use images in both treatment planning and treatment monitoring in real or close to real time.

Considerations of radiation dose have conventionally been arrived at more often by the tolerance of the normal tissues than by determining a dose consistent with the high probability of curing the tumor. The proper dose to maximize tumor control is now being reconsidered. Dose escalation is now possible with IMRT. While this offers opportunities for improved tumor cure, it also increases the considerable risks of damage to the matrix normal tissue in which the tumor resides. Damage to these normal tissues rather than those outside the target volume becomes the major limitation on the dose delivered.

Even the current cancer paradigms must be revisited. It is the accepted premise that it is not possible to visualize all of the cancer. Should this concept continue to underlie therapeutic planning as we greatly reduce the uncertainties of tumor extension with evolving imaging methods? Perhaps most important is reconsideration of the notion that metastases are always in great number and widely scattered throughout the body. With early diagnosis and current imaging techniques, it may well be that there are circumstances where the number of metastases are relatively limited and such oligometastases are restricted to one of the major sites of metastases: the brain, bone, lung, or liver. If we can identify such patients then perhaps these oligometastases can be individually treated with the goal of cure, or at least, long-term control. With the increasing effectiveness of systemic treatment, the oligometastatic state may also be achieved by the success of systemic treatment destroying small tumor volumes, leaving only a limited number of anatomically definable larger metastases. These residual tumors could be eradicated by targeted radiation delivery, perhaps delivered with carefully limited IMRT using hypofractionation with very precise immobilization and tumor conformality.

So what we have been wishing for is becoming a reality: one may be able to offer real improvement in cancer care if precise and accurate radiation therapy is combined with improved knowledge of tumor location and extent or conversely such treatment may result in increased marginal recurrences because of improper assessment of the target volume. In order for this approach to be successful we must extract all we can from diagnostic imaging methods both before and during a course of radiation therapy. Despite the clear decrease in the acute toxicity of IMRT because of the improved sparing of transited normal tissues it is not yet clear that there may not be increased toxicity due to increased dose administered to normal structures within the target volume. Nor is it clear what the effects of different dose distributions on normal tissue function will be or whether the increase in normal tissue volume receiving moderate radiation dose due to dose-escalation will increase the development of second tumors. These opportunities and uncertainties require that IMRT be used with care and based on a carefully documented experience.

Memorial Sloan-Kettering Cancer Center has been one of the pioneers of conformal radiation therapy and intensity-modulated radiation therapy. This book offers the reader an opportunity to consider how IMRT is currently used in clinical practice at that institution. While the IMRT technique is evolving, it is important for radiation oncologists to learn from the experience of these investigators so as to be most effective in bringing this new technique to practice. Consider this "A User's Guide to Intensity-Modulated Radiation Therapy."

Samuel Hellman, M.D.
University of Chicago
Chicago, Illinois
January 2003