In 2011, ASTRO published a clinical practice guideline on fractionation for whole breast irradiation. The primary purpose of this guideline was to synthesize the evidence regarding dose-fractionation from the available randomized clinical trials and thus to provide practical advice to radiation oncologists. At this time, the 10-year data from the NCIC (Canadian) trial had just been published, and the data from the START B trial had been published but with only six years follow-up.
The NCIC trial, though an excellent study, did not include a tumor bed boost nor did it include patients treated with more modern chemotherapy regimens, including anthracyclines, taxanes or trastuzumab. These issues, at the time, were considered to limit the external validity of this trial when applied to practice in the United States. Further, while the START B trial addressed these limitations, the lack of long-term follow-up from this trial was still a bit of a concern.
In light of the totality of the evidence at that time, the writing panel opted to define a group of patients for whom there was high confidence that hypofractionated whole breast irradiation and conventionally fractionated whole breast irradiation were equivalent. This group was considered women age 50 and older with pT1/2 N0 breast cancer, not receiving chemotherapy, for whom dose homogeneity goals could be achieved and in whom the heart could generally be excluded from the high-dose region.
These recommendations, while well-intended, now in retrospect seem conservative. In 2013, the long-term results of the START A and B trial were published. They demonstrated no evidence of an effect of chemotherapy, tumor bed boost or patient age on choice of dose-fractionation. There was also no evidence of a deleterious effect of hypofractionation on cardiac mortality. Armed with the long-term START A and B data, many practitioners, including myself, chose to more fully embrace hypofractionation as the preferred standard of care in patients receiving whole breast irradiation.
The patient mentioned in the recent NPR piece published by Liz Szabo had received chemotherapy. While in my personal opinion chemotherapy should not preclude use of hypofractionation, it should be remembered that the currently valid ASTRO guideline does not endorse a preferred dose-fractionation scheme in patients treated with chemotherapy. In essence, the current guideline suggests that either choice may be valid, and the panel deferred making a strong recommendation. Within this context, the patient’s physician is on stable ground to recommend conventional fractionation. However, I would encourage all physicians to engage patients in a process of shared decision-making, particularly in the setting of evolving treatment guidelines, to ensure the decisions are adequately personalized.
Within this setting, I think a couple points should be made. First, I believe in my heart that radiation oncologists who are treating patients with conventionally fractionated whole breast irradiation are not motivated by financial considerations. Rather, I believe these physicians are recommending the treatment they feel is best for their patient—best with regard to long-term toxicity and local-regional control. Practicing radiation oncologists are very cognizant of the fact that radiation delivery is irreversible, and we are very attuned to the potential effects of higher doses in shorter time frames, particularly late effects.
Thus, if a new treatment arises that provokes concern regarding late effects, it is understandable that a radiation oncologist may be reluctant to quickly adopt it. Second, while the reluctance to adopt hypofractionated whole breast irradiation may be very well-intended, what may be forgotten in this calculus is the harm of conventional fractionation. Two to three extra weeks of radiation may be very problematic to a patient—in terms of lost work, lost wages, lost time in caregiving roles and higher health care spending. In addition, research conducted at MD Anderson, my employer, showed that patients treated with conventional fractionation suffer a higher burden of acute toxicity, and they still have more fatigue six months post-radiation than patients treated with hypofractionation. These findings strongly underscore the relative harm of conventional fractionation relative to hypofractionation and, correspondingly, the value of hypofractionated whole breast irradiation.
To respond to the new literature, ASTRO has nearly completed an updated guideline on whole breast irradiation that will supersede the prior guideline. I hope that this new guideline will offer pragmatic assistance to well-intended clinicians, helping to synthesize the existing evidence and frame the literature to facilitate high quality shared decision-making.
What's your take on conventionally fractionated versus hypofractionated radiation therapy for breast cancer? Tell us in the comments.