Postlumpectomy focal brachytherapy for simultaneous treatment of surgical cavity and draining lymph nodes

Abstract

Purpose: The primary objective was to investigate a novel focal brachytherapy technique using lipid nanoparticle (liposome)-carried β-emitting radionuclides (rhenium-186 [(186)Re]/rhenium-188 [(188)Re]) to simultaneously treat the postlumpectomy surgical cavity and draining lymph nodes.

Methods and materials: Cumulative activity distributions in the lumpectomy cavity and lymph nodes were extrapolated from small animal imaging and human lymphoscintigraphy data. Absorbed dose calculations were performed for lumpectomy cavities with spherical and ellipsoidal shapes and lymph nodes within human subjects by use of the dose point kernel convolution method.

Results: Dose calculations showed that therapeutic dose levels within the lumpectomy cavity wall can cover 2- and 5-mm depths for (186)Re and (188)Re liposomes, respectively. The absorbed doses at 1 cm sharply decreased to only 1.3% to 3.7% of the doses at 2 mm for (186)Re liposomes and 5 mm for (188)Re liposomes. Concurrently, the draining sentinel lymph nodes would receive a high focal therapeutic absorbed dose, whereas the average dose to 1 cm of surrounding tissue received less than 1% of that within the nodes.

Conclusions: Focal brachytherapy by use of (186)Re/(188)Re liposomes was theoretically shown to be capable of simultaneously treating the lumpectomy cavity wall and draining sentinel lymph nodes with high absorbed doses while significantly lowering dose to surrounding healthy tissue. In turn, this allows for dose escalation to regions of higher probability of containing residual tumor cells after lumpectomy while reducing normal tissue complications.

Fig. 1

Schematic diagram outlining the treatment design. Radionuclides encapsulated within liposomes are injected into lumpectomy cavity in breast. Sustained retention of liposomal radionuclides in the cavity, as well as the gradual clearance and retention in draining lymphatics provide focal brachytherapy to areas where cancer recurrence will most likely occur.

Fig. 2

Fluorescent image of the distribution of rhodamine B-liposomes in rat lymphatics following intracavitary injection. Arrow points to a draining lymph node.

Fig. 3

Calculated dose point kernels for materials which may represent breast tissue.

Fig. 4

Percent differences versus distance with respect to water between dose point kernels for tissues representing breast tissue for ¹⁸⁶Re-liposomes (A) and ¹⁸⁸Re-liposomes (B).

Fig. 5

Dose profile (A) across center slice of lymph node and dose volume histogram (B) of lymph node and surrounding 1 cm of healthy tissue.

Fig. 6

Dose profiles across center slice of spherical lumpectomy cavities with uniform or targeted liposome distribution.