Study of linear energy transfer effect on rib fracture in breast patients receiving pencil-beam-scanning proton therapy

TL;DR

This study investigates how the linear energy transfer (LET) of proton therapy affects rib fracture risk in breast cancer patients, using a novel dose-LET volume histogram analysis to identify potential correlations.

Contribution

It introduces a new dose-LET volume histogram (DLVH) method to analyze the relationship between LET and rib fracture risk in proton therapy patients.

Findings

Larger volume receiving moderate dose and high LET correlates with increased rib fracture risk.

Rib fractures occurred on average 12 months post-treatment.

Higher V(0-36 Gy, 4.0-5.0 keV/um) is associated with fractures.

Abstract

Purpose: To study the effect of proton linear energy transfer (LET) on rib fracture in breast cancer patients treated with pencil-beam scanning proton therapy (PBS) using a novel tool of dose-LET volume histogram (DLVH). Methods: From a prospective registry of patients treated with post-mastectomy proton therapy to the chest wall and regional lymph nodes for breast cancer between 2015 and 2020, we retrospectively identified rib fracture cases detected after completing treatment. Contemporaneously treated control patients that did not develop rib fracture were matched to patients 2:1 considering prescription dose, boost location, reconstruction status, laterality, chest wall thickness, and treatment year. The DLVH index, V(d, l), defined as volume(V) of the structure with at least dose(d) and LET(l), was calculated. DLVH plots between the fracture and control group were compared. Conditional logistic regression (CLR) model was used to establish the relation of V(d, l) and the observed fracture at each combination of d and l. The p-value derived from CLR model shows the statistical difference between fracture patients and the matched control group. Using the 2D p-value map, the DLVH features associated with the patient outcomes were extracted. Results: Seven rib fracture patients were identified, and fourteen matched patients were selected for the control group. The median time from the completion of proton therapy to rib fracture diagnosis was 12 months (range 5 to 14 months). Two patients had grade 2 symptomatic rib fracture while the remaining 5 were grade 1 incidentally detected on imaging. The derived p-value map demonstrated larger V(0-36 Gy[RBE], 4.0-5.0 keV/um) in patients experiencing fracture (p<0.1). Conclusions: In breast cancer patients receiving PBS, a larger volume of chest wall receiving moderate dose and high LET may result in increased risk of rib fracture.