Impact of Dosimetric Compromises on Early Outcomes of Chordomas and Chondrosarcomas Treated With Image-guided Pencil Beam Scanning Proton Beam Therapy

Purpose

To critically review the clinical factors, dosimetry, and their correlation with early outcomes in patients with chordomas and chondrosarcomas treated with pencil beam scanning (PBS) proton beam therapy (PBT).

Methods and Materials

Consecutive 64 patients diagnosed with chordoma or chondrosarcoma treated at our center were studied. Patient, tumor, and treatment-related factors including dosimetry were captured. Early and late toxicities and early outcomes were evaluated and correlated with clinical and dosimetric factors using standard statistical tools.

Results

The median age of patients was 39 years (range, 4-74 years), and most common site was skull base (47%), followed by sacrum (31%) and mobile spine (22%). The median prescription dose to the high-risk clinical target volumes for chordoma and chondrosarcoma was 70.4 cobalt gray equivalent (CGE) and 66 CGE at 2.2 CGE per fraction, respectively. At presentation, 55% presented after a recurrence/progression of which 17% had received previous radiation and 32% had a significant neural compression. At the time of PBT, 25% of patients had suboptimal neural separation. Three-fourths of patients had at least an acceptable target coverage. Although 11% had a tier 1 compromise (gross tumor volume [GTV] D98 < 90%), 14% had a tier 2 compromise (GTVD98 < 59 CGE). With a median follow-up of 27.5 months, 2-year local control and progression-free survival was 86.7% and 81.8% for chordomas and 87.5% and 77.1% for chondrosarcomas, respectively. Residual GTV of >25 cm³ and a tier 2 compromise were associated with inferior local control (hazard ratio [HR], 0.19; P = .019; HR, 0.061; P = .022, respectively) and progression-free survival (HR, 0.128; P = 0.014; HR, 0.194; P =.025, respectively) on multivariate analysis. Despite multiple surgeries, a majority presented with recurrent disease and previous radiations and grade 3 acute and late toxicities were limited and comparable with others in the literature.

Conclusions

Despite multiple surgeries, adequate neural separation was challenging to achieve. Severe dosimetric compromise (GTV D98 < 59 CGE) led to inferior early outcomes. Adequate neural separation is key to avoiding dosimetric compromise and achieving optimal local control.