IMRT should not be administered at photon energies greater than

Arguing against the Proposition is Professor Fridtjof Nüsslin. Dr. Nüsslin received his Diploma in Physics in 1966 and his Dr.rer.nat. in Physics and Physiology both from the University of Heidelberg, Germany. He spent another two years for postdoctoral training in the Max-Planck-Institute for Nuclear Physics in Heidelberg before joining the Department of Radiology at the Medical School in Hannover, Germany for training in radiotherapy and radiology physics. In 1987 he was appointed Chair and Director of the Medical Physics Section of the Department for Radiology at the University of Tübingen, Germany. In 2004 he became Professor Emeritus and joined the Department of Radiation Therapy and Radiological Oncology of the University Hospital of the Technical University, Munich, as Visiting Professor. There he continues to be involved in research and training activities, mainly in radiation therapy, molecular imaging, radiobiology, and radiation protection. Dr. Nüsslin continues to be active in many scientific and professional organizations and, in 2006, he was elected Vice-President of the IOMP. Clearly there is a great deal of data to support the statement that radiation can cause cancer. Whenever radiation is delivered for beneficial reasons, the patient will still receive small doses of scatter and leakage radiation to organs distant from the primary treatment site. For each organ, the dose, no matter how small, comes with an associated risk of development of a secondary cancer. The basis of this statement comes from the linear relationship between risk and radiation dose derived from the A-bomb survivors.1,2 Some may argue that the risk is small and many of our cancer patients may never live long enough to develop a second malignancy but, in reality, more and more patients are living longer and survival rates for pediatric patients,3 where the risk values may be 5 to 10 times that of an adult, are increasing.4 Prior to the use of IMRT, the radiation oncology community considered the associated risks of secondary cancers to be negligible when compared to the benefits of the radiation treatment. However, with the implementation of IMRT where the number of monitor units has increased 3–9 fold over that for conventional treatments, depending on the dose delivery technique and planning system, the secondary doses and risks may no longer be considered negligible.5,6 The first IMRT treatments were performed using low x-ray energies that did not include any neutron contribution. Now, with the use of higher x-ray energies for IMRT treatments, the secondary neutron dose, although small, becomes an important contributor to the total secondary equivalent dose because of the neutron RBE. The risks and benefits of each patient's radiotherapy treatment should be considered prior to delivering the treatment. Any non-therapeutic dose of radiation that the patient receives represents a potential risk. Data from Kry et al. has shown that IMRT treatments with energies of or less from a specific make of accelerator, i.e. Siemens or Varian, result in less secondary dose to the patient than treatments with higher energies.6 This is mainly due to the neutrons produced at the higher energies. The larger secondary doses reported at the higher x-ray energies depended on the actual accelerator's photon energy spectrum, neutron RBE used, number of segments, and total number of monitor units. Depending on the energy, accelerator, and number of monitor units used, the risk of secondary fatal cancers can range from 2.2% to 5.1% for 15 and energies, respectively.7 Taking into consideration the uncertainty in the risk coefficients, the resulting risk from an IMRT treatment with has been shown to be statistically lower than for an IMRT treatment with .8 IMRT treatments administered with energies greater than produce higher secondary doses and the higher the dose, the greater the risk to our patients. Therefore, if one wants to use a higher energy for IMRT, the benefit of the resulting treatment plan should have to clearly outweigh the increased risk of radiation-induced cancer associated with the extra secondary radiation. In order to debate the pros and cons of high energy (i.e., about ) photon IMRT, one needs to remember some essentials of radiotherapy physics found in old textbooks: higher penetrative quality, more pronounced build-up, lower skin dose, steeper dose gradients at the PTV margin, better dose conformation to the PTV, and more effective dose sparing of normal tissue make high energies the superior beam quality in many clinical situations. Even for head and neck tumors, is preferred when the PTV is close to adjacent organs at risk. One disadvantage, however, is the increased neutron leakage at higher energies, but this is small compared to scatter from the useful beam. From a comparison of IMRT plans for head and neck treatments, it turns out that for 10 and the dose distributions are nearly identical. In a few cases, however, about a 20% lower skin dose at higher energies will prevent the loss of patients' hair. In a recent clinical study of IMRT lung treatment with 6 and x-ray beams, Madani et al.9 demonstrated the minor role of energy selection in IMRT. However, what has not been evaluated is the larger volume of normal tissues irradiated at lower doses, i.e., below . There are data emphasizing low-dose radiation induced long-term risks of secondary malignancies10 and cardio-vascular diseases.11 These kinds of long-term risks may strengthen the case for high energy IMRT. Pirzkall et al.12 studied the effect of beam energy and number of fields on IMRT for patients with prostate carcinoma. They found a significant impact of energy selection on the dose distribution in the region beyond a margin around the target volume. Even when applying nine fields, higher energies are to be preferred to achieve dose reduction in normal tissues and, hence, to lower the risks for late effects. In conclusion, as in conventional radiotherapy, there are good reasons to select higher energies in IMRT techniques when treating thoracic and pelvic tumors, mainly in order to prevent late low dose effects in normal tissues. In the head and neck region it may be prudent to apply lower energies, except in a few situations where steep dose gradients at the PTV margin are essential, or where skin dose reduction is expected to be clinically relevant. Finally, I would like to emphasize the need for Monte-Carlo dose calculation models to achieve valid results when doing this type of intercomparison study in IMRT treatment planning. Although the impact of energy selection is rather small, I would prefer high energy IMRT when dose reduction in normal tissue is an issue. The treatment decision for every patient is based on an analysis of the benefits versus the risks for the particular treatment. Although a clinician may not rigorously document such an analysis, the process still occurs as the patient's plan and prescription are approved. Clearly the energy to be used to achieve an effective treatment is one of the most important decisions. Will the energy selected achieve proper coverage of the PTV, reduce the dose to the surrounding normal tissues, reduce the integral secondary dose near the target and, finally, leave the patient with an "acceptable" risk of developing a secondary malignancy in distant organs away from the treatment field? The patient's age, overall health, and life expectancy, are also important factors to be considered in this decision-making process. Perhaps a higher energy may deliver a plan that is dosimetrically better, but is the plan better for the patient, especially a young patient with a long life expectancy? For some patients, the risk of a secondary malignancy is irrelevant but, for young patients, the risk may clearly outweigh any dosimetry benefit derived from using higher energies. The neutrons generated by the higher energies and their associated RBEs clearly do not benefit the younger patients. The differences between high and low energy IMRT are small and typically do not affect the outcome of the therapy. The vast majority of radiation oncology centers continue to deliver IMRT with as their standard of care. The use of higher energies for IMRT may just simply introduce another risk while not significantly improving the patient's treatment. Selection of the beam energy for an IMRT treatment is only one of many factors that must be considered when making treatment decisions and should not be the overriding factor in the decision making process. Dr. Followill stresses just a single argument, viz. the neutron contamination at higher energies and its impact on secondary malignancies. Therefore, I conclude that we both agree about the many favorable features of IMRT-treatment plans at higher energies (i.e., typically , not or more). So what is in the neutron contamination argument? I agree with the statement that above the neutron production rate increases with photon energy. However, I disagree with nearly all the speculative conclusions Dr. Followill presented and those in his Refs. 5, 7, and 8. Is it scientifically valid to apply the new radiation-weighting factor from the NCRP Report 116 for risk assessment of developing fatal secondary malignancies despite the warnings not to apply the data of the report to certain populations such as cancer patients? Dr. Followill is aware of the large uncertainties of the risk assessments, but he and his colleagues in his Ref. 7 state "until there have been decades of evaluation time for patients treated with IMRT, the best estimate of the risk from IMRT treatments is one calculated with these risk coefficients." One can hardly believe in any significant impact on energy selection in the limited range of 6 and when a slightly less than 0.3% difference in the calculated maximal absolute risk of fatal secondary malignancies between 6 and , for the same linac, has been calculated.7 The statement of a risk of fatal secondary malignancies in the range of 2%–5% associated with leakage in an IMRT treatment is not supported by facts and data from radiation biology and radiation epidemiology. Just one out of many arguments omitted: about only 10% of all secondary malignancies following curative radiotherapy are radiation induced, the remaining 80–90% are due to the increased life expectancy. Nevertheless, we are always challenged to minimize the radiation load to the normal tissue when treating a patient. However, we have to set the priorities appropriately, i.e., increased tumor control and lower complication probabilities, which clearly relate to the dose distribution, rank higher than the speculative and quantitatively overestimated risks for secondary cancers. Certainly manufacturers are challenged to carefully design their equipment before launching new products with significantly higher leakage than well-established alternatives. I am referring to the reported 4–5 times higher leakage of the CyberKnife in comparison to both the Leksell Gamma Knife and linac-based IMRT systems without a proven gain in therapeutic efficiency.13 Data provided by Markus Alber (head and neck study), Oliver Dohm (dosimetry), and Rainer Schmidt (leakage radiation) is gratefully acknowledged.