Brachytherapy is better than external beam therapy for partial breast irradiation (2013)

Arguing against the Proposition is Stewart Becker, Ph.D. Dr. Becker obtained his M.S. and Ph.D. degrees in Medical Physics from the University of Wisconsin, Madison after which he moved to the Department of Radiation Oncology, New York University Langone Medical Center, where he is currently a Senior Physicist and an Assistant Professor. He is certified in Therapeutic Radiological Physics by the American Board of Radiology. His major research interests include image-guided radiotherapy, and whole and accelerated partial breast radiotherapy. He currently serves as a member of the AAPM Radiation Oncology Medical Physics Education Subcommittee. The number of techniques and devices used to deliver breast radiotherapy has increased dramatically in recent years in an attempt to create more conformal, homogenous, and reproducible dose distributions as well as to provide shorter, more convenient treatment schedules. Brachytherapy and external beam radiotherapy for PBI offer equal convenience, but differ substantially in dose distribution and treatment delivery. Brachytherapy offers several advantages over EB-PBI. First, brachytherapy techniques are associated with smaller treatment volumes and integral doses as well as smaller normal tissue fraction doses, all of which contribute to a lower normal tissue toxicity. Next, the dosimetric parameters which affect toxicity have been thoroughly investigated for brachytherapy techniques.1 In particular, the use of interstitial brachytherapy is supported by over ten years of follow-up data demonstrating excellent local control and minimal long-term toxicity when established dosimetric guidelines are used for planning.2 Conversely, EB-PBI is the modality associated with the least available follow-up data, and no standardized, evidence-based treatment planning guidelines currently exist for this technique. The experience accumulated in accelerated partial breast irradiation (APBI) suggests a strong volume effect for late normal tissue toxicity.3 There is compelling evidence for a steep dose response with external beam treatment, suggesting that 40 Gy/10 fractions/5 days may represent the maximum tolerance for EB-PBI.4 Given that the current guidelines for the most widely used fractionation for photon EB-PBI (38.5 Gy/10 fractions/5 days) allows for inhomogeneity of up to 120% of the prescribed dose, depending on planning style and physicians’ choice of prescription (from V90 ≥ 90% to V100 = 100%), a significant volume of tissue may receive upwards of 40 Gy in a typical plan. Schedules that may be safe when delivered with brachytherapy to small partial volumes with tightly controlled parameters cannot be assumed safe if delivered to larger partial volumes with external beam. In fact, the most recent evidence shows that APBI using 3D EBRT can increase the risk of moderate radiation side effects leading to poor cosmetic outcome for some patients.5 Finally, a recent analysis showed that incremental cost-effectiveness ratios for balloon-based brachytherapy compared with 3D-CRT were $519/$850 per percent improved excellent/good cosmesis based on reimbursement and $301/$647 based on facility costs, thus making brachytherapy a more cost-effective modality.6 Despite the differences in techniques, evidence currently suggests that treatment with both brachytherapy and EB-PBI have the potential for excellent clinical outcomes for patients. The sometimes conflicting results published by different institutions can likely be explained by differences in planning styles, a lack of proper radiobiological models allowing understanding of toxicity, and the lack of standardized dosimetric parameters.7,8 Debating the relative merits and drawbacks of the various PBI techniques encourages unnecessary partisanship and conflict, and distracts us from our real goal: achieving a better understanding of both techniques, optimizing patient selection and resource allocation, and customizing treatment for each individual patient. This goal will not be achieved until quality indicators for each modality can be established based on clinical data derived from an APBI registry rather than on inherent technical limitations of a method or device. While cost is increasingly important, the ideal choice is not for all patients to get the least expensive treatment but for each patient to get the optimal treatment while minimizing costs at the population level. There are two main priorities in breast cancer treatment: survival and cosmetic outcomes. Partial breast irradiation has been established as a valid alternative to whole breast irradiation for a subset of early stage breast cancer patients based on 5–10 year data.9 This is true whether PBI is administrated via brachytherapy or external beam x-ray therapy (XRT). While both techniques have been studied individually,10–13 no definitive randomized study has been conducted to compare them. These studies have shown similar results in terms of survival outcomes for each technique. Cosmetic outcomes of PBI were discussed at a plenary session of the 2012 ASTRO Annual Meeting. The results varied widely between and among techniques. Because cosmetic outcome studies have not produced definitive answers, we must rely on other measures to determine the most suitable treatment method. Every clinic has a linac, but not every clinic has a HDR unit or facilities to support LDR sources (i.e., free standing clinics). The success of brachytherapy is dependent on the skill and training of the radiation oncologist to achieve high quality implants. Brachytherapy treatments are invasive, whereas XRT is noninvasive and does not subject the patient to additional surgery or anesthesia. A brachytherapy program requires greater effort to commission and maintain due to training, equipment, and personnel coverage required. Brachytherapy is performed BID, which can be more difficult for patients than the once a day treatment schedules that XRT can offer. Some patients cannot be treated with brachytherapy due to their cavity shape or breast size, while these factors have no bearing on XRT. Brachytherapy can result in unnecessary procedures on patients with contraindicative pathology reports. This is not an issue for XRT patients since the pathology reports are available before treatment begins. Brachytherapy requires additional professional time to plan and image compared to XRT. While none of these are as important as outcomes, they are real issues that clinics must assess and patients must endure. My opponent offers a list of reasons for which 3D-CRT PBI is easier and maybe more convenient, but not necessarily better. He opens the list with the argument that “every clinic has a linac.” Just as the availability of fast food does not make a frozen hamburger objectively better or healthier than a gourmet meal, the fact that all clinics theoretically possess the ability to deliver 3D-CRT PBI does not make this treatment better than brachytherapy. Although he appropriately indicates that none of his points “are as important as outcomes,” he fails to acknowledge the paucity of long-term data on local control or the emerging reports describing unacceptable toxicity and cosmesis after 3D-CRT.5 Some arguments are misleading: balloon or catheter placement do not require systemic anesthesia, 3D-CRT PBI is not more convenient as it is commonly delivered with exactly the same schedule as brachytherapy, and neither 3D-CRT nor brachytherapy treatments begin prior to final pathologic review. What is not debatable, however, is that the integral dose to the nontarget aspect of the breast is higher with 3D-CRT compared to brachytherapy. Larger volumes of nontarget breast tissue irradiated with current PBI fractionation schemes may lead to increased toxicity. The “triple-trouble” (high dose, dose/fraction, and volume) phenomenon associated with hot spots in hypofractionated treatment suggests a marked volume response for late effects such as breast size reduction, breast induration, and fat necrosis resulting from hot spots >110%. For these reasons, plan optimization for 3D-CRT might not be a trivial exercise and better plan evaluation guidelines might also be needed. Brachytherapy is a more conformal, better understood technique, which will continue to be a reliable and economical modality for APBI. I agree with my opponent that currently brachytherapy and external beam both offer convenient treatments with comparable survival outcomes. However, we disagree when it comes to the importance of dosimetric differences such as integral dose, the interpretation of early XRT results, normal tissue toxicity outcomes, and the inherent costs of both procedures. First, I want to address the issue of integral dose as a cause of normal tissue complications for XRT. There are many dosimetric issues that are not very well understood. Integral dose is one of them; very high dose regions close to the catheters in HDR is another. While both of these are academically interesting, neither is fully understood nor can they be blamed for toxicities… yet. Interstitial brachytherapy now has ten-year follow-up data, but my opponent fails to mention the difficult start that the procedure had and how they adapted based on their own early data. Breast necrosis and infection were addressed for interstitial and skin toxicity was addressed for balloon systems. XRT-PBI may only have five-year follow-up data but has had a much smoother beginning. XRT will definitely benefit as standards are tightened for volumes and prescriptions based on these five-year studies, just as brachytherapy did. The RTOG and other groups are also helping to standardize planning techniques (i.e., prescriptions, dose constraints, and volumes treated). Our own five-year follow-up experience at New York University, shows a 1% recurrence rate with 11% fair-to-poor cosmesis,10 which is in line with many studies.14,15 My opponent pointed out that the lack of defined prescription standards can result in large high dose regions which affect cosmesis.4 This is the exact type of issue that is currently being studied and will eventually be solved. Finally, my opponent points out that incremental cost-effectiveness ratios favor brachytherapy.6 However, the initial startup and maintenance costs can be prohibitive. Larger clinics may have the patient numbers and staffing to fully schedule a HDR remote afterloader, but a smaller clinic may not be able to justify a new machine and the extra staff required. In addition, reimbursements are constantly being adjusted and clinics always have at least one linac. Finally, the study did not include IMRT, which would increase the reimbursement for XRT. I want to share Dr. Todor's sentiment that both of these methods have shown promising results for PBI. He correctly states that no technique is perfect for all patients and these methods complement each other. My hope is that this debate stimulates thought and generates new and broader perspectives to trigger innovation in the field of PBI.