Low dose‐rate brachytherapy for the treatment of cervix cancer is outdated and should be discontinued

Arguing against the Proposition is Tewfik J. Bichay, Ph.D. Dr. Bichay obtained his B.Sc. degree in Human Physiology from McGill University, Montreal, his M.Sc. in Radiation Biology from Concordia University, Montreal, and his Ph.D. in Medical Biophysics from the University of Western Ontario, London, Canada. He is currently Director of Medical Physics, Radiation Oncology, The Lacks Cancer Center at Mercy Health, St. Mary's, Grand Rapids, MI. He started his career as a radiation biologist before transitioning into medical physicist with a residency at the Ottawa Regional Cancer Center. He is an accreditation surveyor for the ACR, served for a number of years as an ABR MOC examination committee member, and is the previous President of the Great Lakes Chapter of the AAPM, and holds a patent on a compact doorless radiation vault design. He is certified in Radiation Oncology Physics by the ABMP and his present research interests include SRS and SBRT. Over the past several decades, our profession has seen many changes which have greatly benefited patients. These new technologies allow us to deliver higher doses with increased probability of cure than would have been possible several years ago. We not only deliver higher doses to the disease but also improved spatial accuracy using modern image guidance technology. Continuing to use LDR brachytherapy to treat cervical cancer disparages our technical advancements and is a dis-service to our patients. One of the hallmark attributes of LDR is the fixed geometry of the prescription point (“Point A”)1 relative to the applicator, where Point A is thought to be related to the internal anatomy. However, MRI has shown no correlation between the ICRU point doses and doses to organs at risk (OARs),2 and it has been shown that in patients with large tumors, specifying the dose to Point A can result in decreased local control.3 Today, image guidance is commonly used in HDR, which grants us the benefit of visualizing where the dose is delivered. One of the limitations of LDR brachytherapy is its inherent inability to adapt to the environment of image guidance. Most LDR applicators are limited to 2D imaging due to their design. When we are forced to use 2D imaging, it is assumed that the points (e.g., Point A, rectum and bladder) being used for planning have specific patient anatomical significance. However, the DVH-evaluated bladder and rectal doses are often not consistent with the doses to ICRU points predicted from radiographs.2 Continuing to use LDR results in treating the applicator instead of the patient, and it denies the clinician the benefit of using 3D imaging and planning. The LDR imaging limitation is further exemplified due to its incompatibility with multimodality imaging such as MRI and PET. Since MRI imaging has been shown to be advantageous in defining the extent of cervical cancer, it is important to use this capability for the patient's benefit.4 Dose optimization is also a weakness of LDR brachytherapy. The ability to optimize an LDR applicator is limited to only a few choices for distributing the source activity. Conversely, HDR brachytherapy has a wide range of choices achieved by changing dwell-time pattern, which allows the distribution of source activity to be almost limitless.5 Even though poor implant geometry cannot be overcome entirely by optimization, HDR has the advantage of using inverse volumetric optimization rather than the trial and error approach for source activity used with LDR.6 Inverse optimization allows for simultaneous consideration of tumor and OAR doses. This level of sophistication is impossible when using LDR-based brachytherapy. Another limitation of LDR is applicator motion during the 24–72-h delivery time.7 This problem can be exemplified even over the short time period between OR and simulation, where applicator motion is common. Conversely, the HDR applicator is amenable to stabilization since the delivery and planning can occur in a much shorter time frame compared to LDR. This should result in the more accurate HDR dose delivery compared to LDR. In North America and much of the developed world, the treatment of cervical carcinoma is typically managed by a combination of chemotherapy, external beam irradiation, and intracavitary brachytherapy8 by either LDR or HDR. At this point in time there is certainly sufficient clinical experience to be able to review the merits of both LDR, with about 100 yr of experience, and HDR, with about 30 yr. The questions that may be asked in comparing these two common modalities relate to clinical efficacy, safety, cost, and access to care. Studies comparing treatment outcomes of LDR versus HDR have shown conflicting results, some indicating that LDR is superior,3 some that HDR is superior,9 and some, at least for nonbulky disease, that they are equivalent.5 It appears reasonable to accept that there is no proven difference in clinical outcomes. Remote application of sources in HDR therapy is sometimes presented as the safer modality since the exposure to medical staff is lower than that for sources placed manually in LDR.10 This brings up two important points: first is that remote afterloading is available for LDR and, second, that serious overexposures to patients and personnel have occurred with HDR, despite the perceived improved safety.11 Various analyses have compared the cost of LDR versus HDR. In the case of LDR, the argument is that the cost of patient's overnight stay in a hospital is significant and can be eliminated by having HDR outpatient treatments.12 Although this is certainly true, it is also important to note that HDR involves substantial capital costs; which include not only the HDR unit itself at about $300 K but also the cost of various sized applicators at about $50 K or more. There are also the recurring costs of sources and service that total about $75 K per year. These are real dollars that may be a challenge for smaller centers only treating a small number of patients. For the approximately 15% of radiation therapy centers in the United States that do not have access to HDR equipment,8 the startup cost for such a program may be prohibitive. This will be even more of a challenge for developing countries with considerably lower healthcare budgets than developed countries. Being able to maintain an HDR program in an environment with limited funds would be difficult, while LDR would represent a much less expensive alternative. I agree with Dr. Bichay's statement concerning LDR versus HDR: “It appears reasonable to accept that there is no proven difference in clinical outcomes.” However, recent advances in image guidance with HDR, which allows volume optimization of the dose rather than using a fixed point dose (Point A) prescription, should allow higher doses to be delivered to more bulky tumors, while sparing organs at risk, with an expected improvement in clinical results. This potential benefit could be further enhanced as the adoption of HDR brachytherapy becomes more commonplace and the expertise is shared throughout the brachytherapy community. Dr. Bichay asserts two other points: “remote afterloading is available for LDR” and “serious overexposures… have occurred with HDR.” I agree that LDR afterloading “is available,” but it is far from being commonplace. In my several decades of working in different departments, I have only encountered this technology once; this in a program well known for its brachytherapy expertise. Most institutions still utilizing LDR are doing so by manually loading sources, exposing medical staff, visitors, and patients in adjoining inpatient rooms. His second point refers to a higher likelihood of overexposures with HDR versus LDR. Granted, the consequences of a malpositioned source are much more severe for HDR treatments. But I would also argue that this is the reason for emergency procedure training for all personnel involved in HDR. Mistakes can happen with LDR as well as HDR and we should not be reluctant to use new technology based singularly on this premise. Finally, I agree that HDR technology is more expensive. However, the superior attributes of HDR (radiation safety, planning optimization) make it the best way to treat cervix cancer patients. To continue using LDR when a superior modality is available is unfair to patients. I agree that we are in an age of image guidance and whenever possible the old “close enough” approach of dose placement should move into era of IGRT. However, I do not agree with the claim that LDR cannot adapt to image guidance. Several years ago we moved to a Henschke LDR applicator that is CT/MRI compatible. We did not invent it; it was purchased from a well-known brachytherapy supplier. The cost was less than one month of our service contract for our HDR unit. Interestingly, the ability to use MRI volumetric targeting does not seem to have caught on for either LDR or HDR. According to a recent poll of centers carrying out HDR, the vast majority relies on CT imaging, only about 3% on MRI, and the majority still used Points A for dose prescription.13 Nevertheless, I would strongly agree that a move to volumetric imaging for brachytherapy should take place whether using HDR or LDR. I agree that dose optimization is limited with traditional LDR using cesium pellets that are manually loaded into the applicator. There are cesium afterloader units, which allow for variable source positions and variable dwell times, essentially meeting distributions similar to those of HDR.14 But cesium afterloaders are disappearing from use. The newer focus of pulsed dose rate (PDR) is perhaps a reasonable compromise, where pulsing can achieve dose distributions tailored to an individual patient's needs.14–17 The potential for applicator movement after LDR imaging is of real concern. Of course it is also a concern in the case of HDR. Any movement would negate the plan optimized for the patient. For guidance on this issue, we can look at the outcome data for both toxicity and cure rates. The data show no evidence that either approach results in increased toxicity or decreased cure.10,18 In fact the reference given by my colleague on this topic also agrees that the outcome is the same for both techniques.6 In general, the assumed advantages of HDR presented by my colleague can be matched by using the latest LDR technology. Given the significant program cost for HDR, and similar clinical outcomes, it would be premature to completely discontinue LDR.

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