Influence of ⁶⁸Ga-DOTATOC on sparing of normal tissue for radiation therapy of skull base meningioma: differential impact of photon and proton radiotherapy

From the institutional database a group of 10 patients with skull base meningiomas treated with RT was chosen randomly from a group of 507 patients treated with high-precision RT [3]. Nine patients were female, one patient was male. The median age was 58 years (range 42–70 years). In 8 out of 10 patients histologically confirmed diagnosis of WHO Grade I meningioma was present, in two patients diagnosis of low-grade meningioma was imaging based. The median planning tumor volume (PTV) was 50 cm³ (range 19.2 cm³–218.4cm³). All patients had been treated with RT as described previously [10, 15]. For treatment planning all patients had been positioned by an individual mask fixation either made of Scotch Cast™ or mask systems made of thermoplastic material as described previously. All patients had received contrast enhanced CT and MRI, as well as ⁶⁸Ga-DOTATOC-PET imaging for RT treatment planning. The study was approved by the Ethic’s Committee of the Medical Faculty, University of Heidelberg.

Target volumes were re-evaluated from all 10 patients and two sets of gross tumor volumes (GTV) were defined. CT and MRI at 1-3 mm slice slickness were used for treatment planning and therefore for the present analysis. After initial automatic and additional manually fine-tuned image fusion of CT, MRI and ⁶⁸Ga-DOTATOC-PET for each patient, target volumes were drawn manually from experienced radiation oncologists with expertise in the field of radiation oncology and nuclear medicine. One volume was based on contrast-enhanced CT and MRI imaging only; the second volume additionally included ⁶⁸Ga-DOTATOC-PET information. Figure 1 shows all three imaging modalities in a typical patient with a skull base meningioma. We followed our imaging protocols as published previously [6, 10, 14, 16]. We defined the meningioma-SUV for each patient: For that, typical meningioma tissue on MRI/CT was identified on the PET- image and the tracer uptake for that region was documented. Then, we calculated the SUV_max for meningioma tissue in relation to the tracer-uptake in normal tissue. By this procedure we defined a specific individual meningioma-SUV for each patient by referencing the SUV_max to a region of typical meningioma tissue visible in CT and MR. The median patients-specific value was 58% (range 54% – 62%). Additionally a clinical target volume (CTV) was determined adding 1 mm safety margin, as well as a planning target volume as described previously [3]. The PTV was added based on institutional standards.

For all patients, we calculated treatment plans for intensity modulated radiotherapy (IMRT) as well as proton therapy using the active raster scanning method. For IMRT planning the Oncentra Masterplan (Nucletron, Elekta, Stockholm, Sweden) software was used as described previously [3]. A template of 9 beam angles at 40 ° distances was used and modified as needed for optimal target volume coverage and OAR sparing. For proton therapy, the syngo RT Planning System (Siemens, Erlangen, Germany) was used. All plans were calculated using horizontal proton beams. The use of horizontal proton beams was generally used at the time of the analysis to treat most skull base lesions at the Heidelberg Ion beam Therapy Center and thus used for this analysis, which was performed also for internal treatment optimization [15].

All plans were optimized to a target dose of 54 Gy in 1.8 Gy single fractions as well as plans for 57.6 Gy in 1.8 Gy single fractions based on the two main published dosing concepts for skull base meningiomas [2, 3]. The aim was to cover 95% of the treatment volume with at least 90% of the median prescribed dose following ICRU (international commission on radiation units & measurements) guidelines for treatment planning and reporting.

For both modalities, treatment plan optimization and OAR sparing followed the QUANTEC (Quantitative Analyses of Normal Tissue Effects in the Clinic) recommendations to remain below a maximal toxicity rate of 5% at 5 years. For example, for brain stem constraints a maximal dose of 59 Gy at 10 cm³ and/or 54 Gy to the whole brain stem volume was allowed [17]. The maximal dose to the optic nerves and chiasm was set at 55 Gy [18]. Highest priority was dose to the brain stem, followed by the optic system. Treatment planning was optimized multiparametrically until the best compromise between target volume coverage and OAR sparing was achieved. All plans were reviewed and accepted by a team of experienced radiation oncologists. (12). Figure 2 depicts the differences in target volumes and corresponding IMRT treatment plans of a typical skull base meningioma case.

To assess doses to OAR, we calculated D_max and D_median of brain stem, chiasm and left and right optic nerves.

For plans calculated for a total dose of 54 Gy, in 9 out of 10 patients PET-based target volumes lead to a reduction of brain stem D_max which was highly significant at p = 0.0097. In 8 out of 10 patients, a reduction of the brain stem D_median was observed which was also significant at p = 0.037. Results are shown in Table 1.

Table 2 shows dose calculations for plans with 57.6 Gy IMRT; total dose reduction of D_max could be achieved in 8 out of 10 patients (p = 0.013); for D_median the IMRT plans of 6 out of 10 patients showed a reduced dose (p = 0.241).

For the optic chiasm, in treatment plans calculated for total dose of 54 Gy, 9 out of 10 patients had a reduction of D_max to the optic chiasm when treatment planning included 68Ga-DOTATOC-PET (p = 0.007). Moreover, D_median was reduced in seven out of 10 patients however not statistically significant (p = 0.23). When the total dose was increased to 57.6 Gy, 8 out of 10 patients had a reduced D_max to the optic chiasm based on PET-planning (p = 0.032) and the D_median was reduced in 9 out of 10 patients (p = 0.007) which was significant in both cases.

For both right and left optic nerve, reduction of dose by addition of ⁶⁸Ga-DOTATOC-PET is minimal compared to the impact observed from the brain stem and optic chiasm. However, the impact of PET depends clearly on the anatomical location of the meningioma. For large skull base lesions, one (or both) optic nerves are often within or very close to the target volume, thus the impact observed is only minimal. However, for both optic nerves, dose reduction is significant with addition of PET, for 54 Gy plans as well as for 57.6 Gy plans. When comparing both dosing regimens the margin of benefit is larger in the 57.6 Gy dataset. Data are shown in Table 1 for 54 Gy plans, and in Table 2 for 57.6 Gy plans.

Tables 3 and 4 summarize the data for D_max and D_medianin proton treatment plans. Both for 54 Gy and for 57.6 Gy the impact of target volume modification by ⁶⁸Ga-DOTATOC PET information is minimal compared to IMRT plans. Generally, compared to the IMRT values, it can be seen that the dose reduction is less with protons than with IMRT. Generally, only the median dose was significantly lower with PET-planning. This was true for all OAR evaluated.