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Black, White, or Shades of Gray?
Int. J. Radiation Oncology Biol. Phys., Vol. 72, No. 5, pp. 1307–1310, 2008 Copyright Ó 2008 Elsevier Inc. Printed in the USA. All rights reserved 0360-3016/08/$–see front matter
CONTROVERSY
expressly to obtain superior dose distributions (skin sparing, reduced dose to bone, and higher dose rates not withstanding). Therefore, they would have us accept that because of its unique dose distributions, and for this reason alone, it is now the turn of PBT to replace high-energy x-ray therapy. On theoretical grounds, their argument is sound. The reduction of dose to surrounding normal tissues by comparison to that to the tumor has long been a tenet central to the practice of radiation oncology, and there is no questioning that protons produce more desirable dose distributions than x-rays. However, the down-to-earth realities of PBT are that despite unique dose distributions, its clinical track record is unremarkable, and it is very expensive. Suit et al. (1) argue that it would be inappropriate to await results of randomized clinical trials (RCTs) before PBT is more widely adopted because such trials could take a number of years, thereby denying many patients the purported benefits of this technology. There is some truth to this argument. When the difference in outcomes of the control and experimental arms of an RCT are expected to be small, such trials require the accrual of many hundreds of patients and, depending on the end point, could take many years of follow-up and posttreatment patient management before conclusions could be reached. Such would be the case for a comparison of PBT with intensity-modulated radiation therapy (IMRT) for the treatment of patients with prostate cancer, for whom 10-year cause-specific survival rates for early-stage disease now exceed 90% (3). Although we accept that the difficulties attendant upon such a trial make it unlikely that one will be undertaken, we find the Goitein and Cox (2) claim that ‘‘practitioners of proton beam therapy have found it ethically unacceptable to conduct RCT’s’’ as showing a faith in PBT that casts doubt on their ability to provide objective clinical evaluations. Are we to accept that PBT is not subject to the constraints of evidence-based medicine?
BLACK, WHITE, OR SHADES OF GRAY? Certain topics are perceived by some as all black or all white. In reality, most are some shade or shades of gray. The topic may have incredible theoretical appeal or its expense might be so great that a ‘‘break-the-bank’’ aura or connotation is associated with it. Often this is the case with new technologies or new drugs (although the pricing of new drugs in particular remains very enigmatic to me, similar to the charges the airlines announce). The truth is that when a new device or drug is approved by the Food and Drug Administration, a stampede ensues to acquire and use such technologies or agents, because they attract patients like a magnet and often a new and more generous reimbursement code is provided. The ‘‘bandwagon,’’ of course, will generally precede the accumulation of real human data, which is what is really needed. Often the preliminary reports are glowing, with results that are called ‘‘promising’’ or ‘‘of great potential.’’ (Shades of Charlie Brown.) Once complications have been reported (and in oncology, it is not possible to ‘‘get something for nothing,’’ no matter who is reporting), the pendulum may swing in the opposite direction. In the end, it usually turns out that specific circumstances exist under which some patients may benefit. Thus, the problem is typically about defining the patient groups and determining whether we are overtreating some patients. I know that I overtreat some patients, but I do not know which ones. The editors of the Journal are recognizing that some of these topics, such as proton therapy, are highly controversial, and people are lining up on both sides. We will try to crystallize the issues in this ‘‘Controversies’’ section. In this Issue, the topic is proton beam therapy. Perhaps the next might be stereotactic therapy, either intra- or extracranial, or perhaps the pros and cons of dose escalation. If we can get past the emotional elements of any controversy, it should come down to interpreting all the data—successes, failures, complications, and economic costs. However, we need the data to evaluate first.
Clinical results Although much in the news these days, PBT is hardly a technologic breakthrough. Since the first treatments were administered in 1954, more than 50,000 patients have received PBT, 65% of them since 1995. With this vast clinical experience supplemented by more than 500 applicable publications, a considerable body of evidence has accumulated about this highly complex and expensive technology, enough one would think to provide support for its wider adoption. Conversely, during the past 2 years, there have been three systematic reviews of the clinical efficacy of PBT applied to a range of cancer sites, and the conclusions reached by each of them are remarkably similar: Brada et al. (4) conclude that ‘‘An uncontrolled expansion of clinical units offering as yet unproven and expensive proton therapy is unlikely to
ELI GLATSTEIN, SENIOR EDITOR doi:10.1016/j.ijrobp.2008.09.001
SHOULD PROTON-BEAM THERAPY BE WIDELY ADOPTED? INTRODUCTION In their recent communications, Suit et al. (1) and Goitein and Cox (2) argue that positive Phase III trials should not be required before proton-beam therapy (PBT) is widely adopted. Their argument is that orthovoltage was replaced by 60Co, and 60Co subsequently was replaced by the linear accelerator, 1307
CONTROVERSY
expressly to obtain superior dose distributions (skin sparing, reduced dose to bone, and higher dose rates not withstanding). Therefore, they would have us accept that because of its unique dose distributions, and for this reason alone, it is now the turn of PBT to replace high-energy x-ray therapy. On theoretical grounds, their argument is sound. The reduction of dose to surrounding normal tissues by comparison to that to the tumor has long been a tenet central to the practice of radiation oncology, and there is no questioning that protons produce more desirable dose distributions than x-rays. However, the down-to-earth realities of PBT are that despite unique dose distributions, its clinical track record is unremarkable, and it is very expensive. Suit et al. (1) argue that it would be inappropriate to await results of randomized clinical trials (RCTs) before PBT is more widely adopted because such trials could take a number of years, thereby denying many patients the purported benefits of this technology. There is some truth to this argument. When the difference in outcomes of the control and experimental arms of an RCT are expected to be small, such trials require the accrual of many hundreds of patients and, depending on the end point, could take many years of follow-up and posttreatment patient management before conclusions could be reached. Such would be the case for a comparison of PBT with intensity-modulated radiation therapy (IMRT) for the treatment of patients with prostate cancer, for whom 10-year cause-specific survival rates for early-stage disease now exceed 90% (3). Although we accept that the difficulties attendant upon such a trial make it unlikely that one will be undertaken, we find the Goitein and Cox (2) claim that ‘‘practitioners of proton beam therapy have found it ethically unacceptable to conduct RCT’s’’ as showing a faith in PBT that casts doubt on their ability to provide objective clinical evaluations. Are we to accept that PBT is not subject to the constraints of evidence-based medicine?
BLACK, WHITE, OR SHADES OF GRAY? Certain topics are perceived by some as all black or all white. In reality, most are some shade or shades of gray. The topic may have incredible theoretical appeal or its expense might be so great that a ‘‘break-the-bank’’ aura or connotation is associated with it. Often this is the case with new technologies or new drugs (although the pricing of new drugs in particular remains very enigmatic to me, similar to the charges the airlines announce). The truth is that when a new device or drug is approved by the Food and Drug Administration, a stampede ensues to acquire and use such technologies or agents, because they attract patients like a magnet and often a new and more generous reimbursement code is provided. The ‘‘bandwagon,’’ of course, will generally precede the accumulation of real human data, which is what is really needed. Often the preliminary reports are glowing, with results that are called ‘‘promising’’ or ‘‘of great potential.’’ (Shades of Charlie Brown.) Once complications have been reported (and in oncology, it is not possible to ‘‘get something for nothing,’’ no matter who is reporting), the pendulum may swing in the opposite direction. In the end, it usually turns out that specific circumstances exist under which some patients may benefit. Thus, the problem is typically about defining the patient groups and determining whether we are overtreating some patients. I know that I overtreat some patients, but I do not know which ones. The editors of the Journal are recognizing that some of these topics, such as proton therapy, are highly controversial, and people are lining up on both sides. We will try to crystallize the issues in this ‘‘Controversies’’ section. In this Issue, the topic is proton beam therapy. Perhaps the next might be stereotactic therapy, either intra- or extracranial, or perhaps the pros and cons of dose escalation. If we can get past the emotional elements of any controversy, it should come down to interpreting all the data—successes, failures, complications, and economic costs. However, we need the data to evaluate first.
Clinical results Although much in the news these days, PBT is hardly a technologic breakthrough. Since the first treatments were administered in 1954, more than 50,000 patients have received PBT, 65% of them since 1995. With this vast clinical experience supplemented by more than 500 applicable publications, a considerable body of evidence has accumulated about this highly complex and expensive technology, enough one would think to provide support for its wider adoption. Conversely, during the past 2 years, there have been three systematic reviews of the clinical efficacy of PBT applied to a range of cancer sites, and the conclusions reached by each of them are remarkably similar: Brada et al. (4) conclude that ‘‘An uncontrolled expansion of clinical units offering as yet unproven and expensive proton therapy is unlikely to
ELI GLATSTEIN, SENIOR EDITOR doi:10.1016/j.ijrobp.2008.09.001
SHOULD PROTON-BEAM THERAPY BE WIDELY ADOPTED? INTRODUCTION In their recent communications, Suit et al. (1) and Goitein and Cox (2) argue that positive Phase III trials should not be required before proton-beam therapy (PBT) is widely adopted. Their argument is that orthovoltage was replaced by 60Co, and 60Co subsequently was replaced by the linear accelerator, 1307