The effect of tumor volume changes on the boost-volume coverage in glioblastoma patients

Purpose/Objective: Radiotherapy is one of the main treatment modalities in the multimodal therapy of glioblastoma patients. The ongoing NRG-BN001 trial (NCT02179086) is evaluating whether boosting a sub-volume with photons or protons improves overall survival as compared to standard-dose photon irradiation. We hypothesize that anatomical changes during irradiation may affect the dose coverage and that these changes may have a greater impact on proton treatment plans compared to photon treatment plans.
Material & Methods: For 24 glioblastoma patients, the MRI was repeated half way during radiation treatment. Three patients had a gross total resection (GTR), four patients underwent a biopsy and 17 patients had a subtotal resection (STR). These patients were treated according to the EORTC-ACROP guideline. A simulated photon and proton treatment plan (intensity modulated proton therapy; IMPT) according to the NRG-BN001 trial were made retrospectively. In this trial, patients in the experimental arm receive a dose of 46Gy/30fr on the T2w/FLAIR abnormalities and 75Gy/30fr on the planning target boost volume (PTV-7500). The PTV-7500 was defined as the resection cavity and/or contrast enhancing lesion on the T1w post gadolinium sequence of the MRI plus a margin of 5 mm (CTV) plus a 4 mm expansion in all dimensions. The trial constraints states that at least 95% of the PTV-7500 should receive 75Gy. To analyze the effect of anatomical changes during treatment on the dose coverage, we evaluated the planned dose distribution (based on the planning MRI) on the delineated PTV-7500 of the repeated MRI.
Results: The median time interval between the two MRIs was 25.5 days (range 15 – 36 days). Between the two scans, the PTV-7500 volume changed with a median of -0.1cc. However, we observed a wide range of -52.8 to +52.2cc. For the photon treatment plans we observed that 83% (n=20) of the patients showed a decline in PTV-7500 coverage (corresponding with a median decline of 6.5% and 8.3cc). The quartile of patients (n=6) with the largest PTV-7500 increase showed a 10% reduction in dose coverage (corresponding with a median volume of 33.2cc). There was no significant difference in coverage changes of the boost volume between the GTR, biopsy only and STR patients (p=0.632). The evaluation of the IMPT plans is ongoing and will be presented during the conference.
Conclusion: During fractionated radiation treatment for glioblastoma patients we observed large target volumetric changes in the boost volume half way during treatment. These target volume changes may lead to substantial declines in dose coverage when patients are treated according to dose-escalation protocol boosting specific sub-volumes. Thus, an important subset of glioblastoma patients may benefit from an MRI guided dose escalation strategy.