Christy Kesslering, MD & Chirag Shah, MD

In the past several years, randomized clinical trials in Canada and the United Kingdom have compared outcomes of hypofractionated whole breast irradiation (WBI) to conventional WBI. While the data show little difference in local control and survival, there is still disagreement as to whether more evidence is needed before the results can be applied to all patient subgroups.

Radiation oncologists Christy Kesslering, MD, Central DuPage Hospital, Warrenville, Ill., and Chirag Shah, MD, Summa Health System, Akron, Oh., share their views on the current data, how hypofractionated WBI fits into their treatment options, and why patients tend to prefer brachytherapy.

What are your thoughts on the current data available for hypofractionated WBI? Are there areas that require further evaluation?

Chirag Shah, MD: There is increasing data supporting the safety and efficacy of hypofractionated WBI. Multiple Phase III trials, including the Ontario Clinical Oncology Group Trial and the United Kingdom Standardisation of Breast Radiotherapy Trials, have confirmed these findings with long-term follow up; however, further study is required based on the limitations of these trials, including the role of boost radiotherapy and the suitability of hypofractionated WBI for young women, high grade disease, close/positive margins, large breasts, or those receiving chemotherapy.

Christy Kesslering, MD:  Years ago, I began offering hypofractionated WBI to older patients (those we typically offer observation to now), but with the longer follow up on the Canadian and UK trials, I now offer it to any patient who requires adjuvant whole breast radiation. In the START trials, there were about 25% of patients that were under the age of 50, had grade 3 cancer or had chemotherapy (equally distributed between treatment arms). In addition, 60% had boosts in the START A trial and 42% had boosts in the START B. Although I think one situation in which more research is still required is the treatment of nodal regions so I still treat any patient requiring nodal radiation with the standard fractionation.

Where does this option fit into your line-up of treatment options for your patients who opt for breast conservation therapy (BCT)? What patient selection factors do you consider?

Dr. Kesslering: When I have my standard consultation with a patient whom I consider to be a candidate for BCT, I discuss all currently acceptable radiation regimens including what I call the “old-fashioned” whole breast fractionation schedule of six and a half weeks, as well as hypofractionation WBI and, if a patient fits the ASBS selection criteria, then APBI.  I consider every whole breast radiation patient – regardless of age, breast size, left-sided lesions or histology – to be candidates for hypofractionation.

Dr. Shah: I consider hypofractionated WBI an integral part of the treatment paradigm, just as I consider WBI and APBI in all early stage breast cancers requiring adjuvant radiation as part of BCT. The key is patient selection and identifying the right patients for hypofractionated treatment. I limit my recommendations to those justified by the clinical data available.

I do not offer hypofractionated WBI to patients under age 50, consistent with ASTRO guidelines, or to women with large breasts (separation greater than 25 cm). I also do not offer it to those patients requiring a boost (young age, close/positive margins); while boost can be given with hypofractionated WBI, this was not done on the Ontario study and inconsistently in the UK trials. Due to limited data and sub-set analyses showing higher rates of local recurrence, I avoid offering hypofractionated WBI to patients receiving chemotherapy or those with high grade disease.

How do patients respond when given the choice between hypofractionated WBI and APBI?

Dr. Shah: I think patients look at both favorably compared with conventional WBI. In general, patients are more concerned about the length of treatment and if eligible, favor APBI over hypofractionated WBI. Patients also like the idea of reducing dose to the rest of their breast and to the heart and lungs with APBI compared to hypofractionated WBI.

Dr. Kesslering:  When given the option, more than 90% of my patients choose brachytherapy. I consider hypofractionated WBI and APBI to be roughly equivalent for low risk patients as far as tumor control.  Although some women still like the idea of the one week treatment option, most patients choose it because of the volume of tissue being radiated and a perceived difference in anticipated long term side effects. That’s the primary concern for a majority of my patients, so if we can radiate a smaller area, that’s what they want.

What is your opinion about a tumor bed radiation boost as part of hypofractionated WBI? 

Dr. Kesslering:  I add a boost in a majority of cases, except for low-risk patients. I think that boosts were not done very well initially (i.e. 2 cm margin on a scar) but now with CT planning, we’re able to get a higher dose to the area that has the greatest risk for recurrence, and there is data showing a benefit to higher risk patients. Since the START trials both had a substantial number of patients that received boosts, so I feel that this is supported.  I use the Canadian fractionation for the whole breast, so it’s 16 fractions, and then follow it with a 4 day boost.

Dr. Shah: I consider tumor bed boost to be essential for young patients and those with close/positive surgical margins. However, it should be noted that randomized trials have found that while the absolute benefit of tumor bed boost decreases with age, the relative benefit remains the same, which is why I consider tumor bed boost in all patients receiving conventional WBI. With hypofractionated WBI, I consider the same factors; however, limited data exists on the role of boost in the setting of hypofractionated WBI. One of the advantages of APBI is that patients do not require a boost with the high dose region surrounding the lumpectomy cavity already.

What are your thoughts on cardiac dose in left-sided breast cancer patients treated with hypofractionated WBI?  Is there a risk of late cardiac toxicity?

Dr. Shah: There is a concern regarding cardiac dose and potential long-term cardiac complications in patients with left sided breast cancers treated with WBI, both conventional and hypofractionated. To date, there is no data supporting increased cardiac events for hypofractionated WBI compared with conventional WBI based on the START trials but follow up is limited to 5 years.  However, further study is required to elucidate the long term cardiac risk with hypofractionated schedules. APBI, on the other hand, delivers limited to no dose to the heart and would be expected to provide lower rates of cardiac complications compared with conventional or hypofractionated WBI.

Dr. Kesslering: Although there is a risk of late cardiac toxicity with any type of radiation to the heart, I think with today’s three-dimensional treatment planning systems we are able to minimize dose the heart. Appelt, et al. examined the equivalent doses to the heart with different regimens using the linear quadratic model and concluded that “most of the examined hypofractionation schedules are estimated to spare the heart when compared with normofractionation.”

That being said, I certainly think one of the advantages of brachytherapy is that it can deliver the lowest amount of radiation to the heart compared to other modalities, depending on the cavity location.

Dr. Kesslering is a board-certified radiation oncologist at Central DuPage Hospital Cancer Center in Warrenville, Illinois. Her clinical interests include breast and gynecologic malignancies with a special interest in brachytherapy.

Dr. Shah is a board-certified radiation oncologist at Summa Health System in Akron, Ohio. His clinical and research interests include breast and genitourinary malignancies along with lymphoma. He has a particular focus on brachytherapy in the management of breast and prostate cancer.