Chirag Shah, MD

While salvage mastectomy remains the standard of care for addressing a subsequent breast cancer, repeat breast conservation therapy (BCT) with accelerated partial breast irradiation (APBI) is increasingly seen as a viable option for women who wish to preserve their breast. Available data is limited yet promising, demonstrating excellent local control and low rates of toxicities, and a forthcoming Phase II trial will provide important prospective data regarding re-irradiation with APBI.

Radiation oncologist Chirag Shah, MD, reviews the current data and discusses his experience with re-irradiation, including how SAVI may enable more women to choose repeat BCT.

What are the benefits of repeat BCT with APBI (either for a local recurrence or new primary) compared to salvage mastectomy?

I believe the primary benefit is to provide women who desire to preserve their breast an option that allows this. While the standard remains salvage mastectomy in women who received BCT with whole breast irradiation, I have increasingly seen patients who are willing to forgo this option to preserve their breast. In the same way that primary BCT has been shown to lead to more favorable body image compared with mastectomy (Irwiq et al, Aust N Z J Surg, 1997), I believe repeat BCT potentially offers the same benefits.

What are the major concerns over retreatment?

The major concern is that there is limited data on repeat breast conserving therapy and further concerns about higher rates of toxicities in the re-irradiation setting. Initial studies attempted to address the problem by offering patients repeat breast conserving surgery alone without re-irradiation; however, data shows that just as with primary BCT, omission of radiation therapy (RT) significantly increased rates of local recurrence and made it an inferior option to salvage mastectomy.

However, with the advent of partial breast irradiation, re-irradiation has emerged as a technique capable of minimizing toxicities and increasing rates of local control following a second breast conserving surgery. More recent data using a variety of techniques have demonstrated that this technique leads to excellent local control, low rates of toxicities, and high rates of breast conservation. The Radiation Therapy Oncology Group 1014 trial is a recently closed Phase II trial examining the role of re-irradiation using 3D conformal partial breast irradiation following BCT and should provide valuable prospective data regarding local control and toxicities with this approach. Ideally, future studies will utilize brachytherapy as this would potentially offer a reduction in toxicities compared with an external beam approach.

What does the current data show regarding the success/feasibility of retreatment with APBI?

At this time, data is promising but limited to small single institutional series. One of the largest series from the University of Nice included 42 patients who received APBI via an interstitial technique; with a median follow up of 21 months, the local control was 97% (Hannoun-Levi et al, Radiother Oncol 2010). A series from Drexel University of 36 patients (11 of whom received applicator-based APBI) had a median follow up of 37 months with 35 patients remained free from disease (Trombetta et al, Brachytherapy, 2011). These data have been confirmed by data from the University of Pittsburgh (Deutsch M, Int J Radiat Oncol Biol Phys, 2002), Beth Israel (Chadha M et al, Oncology, 2009), and several other institutions. More recently, a large series from the University of Nice was published, evaluating 217 cases treated over a 10-year period. The 10-year rate of second local recurrence was low at 7 percent, with 85 percent excellent/good cosmesis and an 11 percent rate of Grade 3-4 toxicity (Hannoun-Levi et al, Radiother Oncol 2013), which further validates the concept.

How do you determine patient suitability for retreatment?

The first part of the discussion is an explanation that off-protocol, the standard of care remains salvage mastectomy. Once a patient understands that and still wishes to proceed, several factors are involved in my assessment of suitability. These include the time interval between the initial course of RT and the recurrence, the relationship of the new tumor to the original treatment site (new primary v. local recurrence), the toxicities the patient experienced with their initial course of therapy, the breast volume remaining following initial BCT, and the patient’s comorbidities.

Does brachytherapy with SAVI overcome any of the major concerns regarding retreatment? Does the availability of SAVI enable some women to choose retreatment who would have otherwise needed a salvage mastectomy?

I think that SAVI provides the ability to offer more women the chance at repeat BCT based on the ability to shape dose away from the skin and chest wall. Traditional single lumen applicators are unable to differentially shape dose whereas SAVI allows for the ability to differentially shape dose in relation to previous treatment fields, as well as organs at risk. Further, the applicator options allow for me to offer APBI in locations and cavity sizes and shapes that I am not able to with other devices.

Hannoun-Levi et al. (2011) suggest the low rates of IBCR would make it difficult to achieve a Phase III randomized trial comparing retreatment vs. a salvage radical mastectomy. Do you agree with this? If so, do you think the current published literature on the topic is sufficient to justify a change in medical practice?

I think that such a trial would be difficult to achieve as well. With long-term local recurrence rates of 10% at 10 years, it would take a large coordinated effort to get the number of patients needed to power such a study appropriately. One potential option is to tie-in such a trial to several NRG breast trials such that patients that develop an IBTR on those trials would be referred for enrollment to a Phase III addressing repeat BCT v. mastectomy). In the interim, until the publication of RTOG 1014, I think the current literature is insufficient to justify a change in medical practice. While I counsel patients on this, it has been my experience that the shifting paradigm is in large part patient-driven, meaning that even though it may not change primary medical practice, it is something that physicians need to be cognizant about based on patient preferences.

Hannoun-Levi et al. also reference a 10% rate of second locoregional recurrence after mastectomy. How does this challenge the perception that mastectomy is most effective for preventing a recurrence?

I think it is important for patients and physicians to realize that the rate of local recurrence following salvage mastectomy is not 0% and ranges from 3% (Salvadori et al, Br J Surg 1999) to greater than 20% (Voogd et al, Cancer, 1999). Further, despite the thought that salvage mastectomy represents “the cure” for an IBTR, the data is not consistent with this as survival rates are 60-80% following mastectomy (Ofuchi et al, Nippon Rinsho, 2007; Chen et al, Am J Surg, 2008). I think that this data needs to be examined further and compared with data for repeat BCT on a larger scale to better understand if there is a difference in locoregional recurrence or more importantly in survival between the two salvage techniques.

Studies show equivalent recurrence rates for APBI and WBI.  Does treating initially with APBI allow for more options for the patient should a recurrence or second primary develop?

With increasing data supporting equivalence in local recurrence rates between APBI and WBI including 10 year outcomes from the randomized Hungarian trial (Polgar et al., Radiother Oncol 2013), I think that treating initially with APBI does offer patients more options should they develop a local recurrence or second primary while not compromising primary local control. However, at this time, there is limited data looking at repeat BCT in patients who underwent APBI and remains an area of study. It should be noted that options for management of a local recurrence should not be a primary factor in deciding which treatment option patients decide on for primary therapy.

Dr. Shah is a clinical physician in the Department of Radiation Oncology 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.