Late chest wall toxicity after MammoSite breast brachytherapy

Accelerated partial breast irradiation (APBI) with the MammoSite breast brachytherapy (MBB) system is being investigated as an alternative to whole breast radiation in breast conservation therapy (BCT) at multiple centers worldwide. The newness of MBB means a complete understanding of long-term toxicity, particularly involving the chest wall, has yet to be completely articulated. We report the first pathologic rib fractures associated with MBB and dosimetric analysis of the original treatment plans.

As part of ongoing quality assurance, we reviewed the records of 129 sequential patients who underwent MBB for breast cancer and identified those who subsequently had clinically significant and radiographically documented rib fracture(s) involving the ipsilateral chest wall. Equivalent tolerance doses yielding a 5% and 50% risk of rib toxicity within 5 years from treatment with 10 fractions (as with MBB) were previously calculated using the linear quadratic equation based on 2Gy per fraction treatments delivered to one-third of the rib volume (TD5/5=37Gy; TD50/5=44Gy). The original radiation therapy plans were evaluated vis-à-vis the plane films or PET/CT images documenting the osseous abnormalities and presenting complaints to find the specific fractured ribs. The specific effected ribs were contoured on the planning CT in "bone windows" using the Nucletron MicroSelectron-classic V2 (Nucletron B.V., Veenendaal, The Netherlands) for this analysis and the original patient treatments. With these datasets, we determined the dose-volume characteristics of the effected ribs including maximal dose encompassing the entire rib on one CT slice, V(20Gy), V(30Gy), V(37Gy), V(44Gy), D(50), D(25), and D(5) (the mean dose to 50%, 25%, and 5% of the rib).

Between May 2002 and August 2007, three of 105 patients with a minimum of 6-months follow-up who underwent adjuvant APBI by MBB were found to have a total of five treatment-related rib fractures. The average dose-volume characteristics from the original plans were as follows: D(50)=22.1Gy, D(25)=32.2Gy, D(5)=41.6Gy, max dose to 1cc=34.8, D(max) (to 0.1cc)=45.6Gy, V(20)Gy=57.4%, V(30)Gy=30.8%, V(37)Gy=15.9%, V(44)Gy=6.6%, and max dose through rib=35.8Gy. Two patients sustained two rib fractures and 1 patient had a single rib fracture. Four of five fractures occurred in postmenopausal patients and two of five fractures occurred in a patient with a history of osteoporosis and exposure to adjuvant chemotherapy.

Fractures occurred in ribs with V(37)Gy and V(44)Gy each well below 33%. As long-term toxicity data accrue from APBI series, the traditional models for estimating the biologic equivalent dose may benefit from refinements that specifically address the unique radiobiologic and physical properties intrinsic to high-dose-rate brachytherapy for breast conservation therapy.