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[68Ga]-DOTATOC-PET/CT for meningioma IMRT treatment planning

[68Ga]-DOTATOC-PET/CT for meningioma IMRT treatment planning Purpose: The observation that human meningioma cells strongly express somatostatin receptor (SSTR 2) was the rationale to analyze retrospectively in how far DOTATOC PET/CT is helpful to improve target volume delineation for intensity modulated radiotherapy (IMRT). Patients and Methods: In 26 consecutive patients with preferentially skull base meningioma, diagnostic magnetic resonance imaging (MRI) and planning-computed tomography (CT) was 68 1 3 complemented with data from [ Ga]-DOTA-D Phe -Tyr -Octreotide (DOTATOC)-PET/CT. Image fusion of PET/CT, diagnostic computed tomography, MRI and radiotherapy planning CT as well as target volume delineation was performed with OTP-Masterplan . Initial gross tumor volume (GTV) definition was based on MRI data only and was secondarily complemented with DOTATOC-PET information. Irradiation was performed as EUD based IMRT, using the Hyperion Software package. Results: The integration of the DOTATOC data led to additional information concerning tumor extension in 17 of 26 patients (65%). There were major changes of the clinical target volume (CTV) which modify the PTV in 14 patients, minor changes were realized in 3 patients. Overall the GTV- MRI/CT was larger than the GTV-PET in 10 patients (38%), smaller in 13 patients (50%) and almost the same in 3 patients (12%). Most of the adaptations were performed in close vicinity to bony skull base structures or after complex surgery. Median GTV based on MRI was 18.1 cc, based on PET 25.3 cc and subsequently the CTV was 37.4 cc. Radiation planning and treatment of the DOTATOC-adapted volumes was feasible. Page 1 of 8 (page number not for citation purposes) Radiation Oncology 2009, 4:56 http://www.ro-journal.com/content/4/1/56 Conclusion: DOTATOC-PET/CT information may strongly complement patho-anatomical data from MRI and CT in cases with complex meningioma and is thus helpful for improved target volume delineation especially for skull base manifestations and recurrent disease after surgery. after repetitive surgery and in case of an infiltrative growth Introduction Meningiomas represent about 20% of all intracranial pattern these imaging modalities have their limitations. brain tumors and are therefore the most frequent nonglial brain tumors in adults with a clear predomination in Meningioma cells strongly express somatostatin receptor women (f/m 2:1) [1]. More than 90% are histological subtype 2 (SSTR 2) which offers an additional positron benign of mesodermal origin arising from the arachnoid emission tomography (PET) based imaging for tumor meninges of the brain and are slow-growing with a low delineation with the somatostatin-receptor ligand [ Ga]- 1 3 proliferation index. Atypical or malignant histology is rare DOTA-D Phe -Tyr -Octreotide (DOTATOC) [27]. DOTA- and often requires multimodal treatment caused by TOC-PET/CT shows a high meningioma to background increased local relapse. ratio which can be used to improve target volume defini- tion prior to IMRT [28,29]. Particularly meningiomas of the skull base are difficult to treat due to their close relation to critical structures like To document the value of [ Ga]-DOTATOC-PET/CT for brainstem, major vessels and cranial nerves. treatment planning of complex meningiomas preferen- tially of the skull base we retrospectively analyzed a series Although surgical resection of meningioma is the pre- of patients in whom CT/MRI based treatment planning ferred treatment approach, ionizing radiation is a highly was complemented by [ Ga]-DOTATOC-PET/CT. effective treatment modality. After complete surgical resection long-term recurrence-free survival can be Patients and Methods achieved up to 93 and 80% after 5 and 10 years, respec- Patients tively. Without total removal the recurrence-free survival 26 consecutive patients with preferentially skull base is inferior, up to 65 and 45% or worse after 5 and 10 years, meningiomas received diagnostic MRI, RT planning CT respectively [1-4]. Adjuvant radiotherapy (RT) can and additional [ Ga]-DOTATOC-PET/CT prior to frac- improve local tumor control and overall survival after tionated stereotactic IMRT between 2007 and 2008 in our incomplete surgical resection [5-8]. Similar to resection, institution. 20 meningiomas were located at the skull radiotherapy alone offers 5-year local control above 90% base, one was an optic nerve sheath meningioma. Median [9,10]. However, the surrounding tissue and the benign age at treatment was 59.5 years (range 28-82 years). The histology mandate extreme precision during treatment male/female ratio was 3/23, median Karnofsky perform- planning in order to minimize the risk of side effects. ance score was 90% (range 70-100%). 19 of the 26 Therefore stereotactic fractionated treatment protocols patients underwent surgical treatment or extended biopsy, comprise the standard radiotherapy approach. Similar to 13 once, five twice and one woman for three times before numerous different malignancies treated with intensity- start of RT. The pathological examination revealed a modulated RT [11-13], recently several IMRT based proto- World Health Organization (WHO) grade I meningioma cols for meningiomas have been issued offering even in 14 and a WHO grade II tumor in four patients. One higher target volume conformity and improved normal young patient with a WHO grade II meningioma received tissue protection [14-19]. With increasing conformity the a prior prophylactic radiation of the brain with a cumula- need for accurate target volume delineation is of outmost tive dose of 18 Gy due to the therapy regime of a hemato- importance. Of special importance is the fact that target logical disorder 26 years before. Seven patients received volume definition after single or repeated surgical inter- IMRT as primary treatment without proven histology vention is frequently hampered by artifacts. In general the because biopsy was concluded to be infeasible. In these use of highly conformal treatment techniques mandates cases diagnosis of meningioma was based on CT and MRI improved pretherapeutic imaging. In this regard, positron offering typical radiologic characteristics of a benign men- emission tomography (PET) based techniques as well as ingioma. Characteristics of the patients are listed in Table other functional imaging modalities including SPECT-CT 1. or also MRI enter the routine in radiation oncology [20- 26]. [ Ga]-DOTATOC-PET/CT Imaging was performed using a dedicated PET/CT scanner Up to now treatment planning was mainly based on com- (Biograph 16 HiRez; Siemens Medical Solutions, Erlan- binations of contrast enhanced CT and MRI. Especially gen, Germany). Page 2 of 8 (page number not for citation purposes) Radiation Oncology 2009, 4:56 http://www.ro-journal.com/content/4/1/56 Table 1: Patients characteristics Patients treated with IMRT n = 26 Patients (female/male) 23;3 Karnofsky Performance Scale (median/range) [%] 95 (70-100) Age (median/range) [years] 60 (28-82) Tumor site Olfactorius nerve 5 Optic nerve sheath 1 Sphenoidal 4 Cavernous sinus 2 Petroclival/clival 5 Frontoparietal/-basal 2 Sphenoorbital 2 Parasagittal/falx 3 Infratentoriell 1 Convexity 1 Surgery/biopsy 19 resection for 1/2/3 times 13;5;1 Histology/WHO grading WHO I 14 WHO II (atypical meningioma) 4 Tissue lost 1 Unknown (diagnosis based on MRI, CT) 7 Postoperative period until initiation of radiation (median/range) [months] 56.1 (3-249) Forty minutes after intravenous injection of 150 MBq the information from [ Ga]-DOTATOC-PET. Addition- [ Ga]-DOTATOC the combined examination com- ally all patients routinely had a neuroophthalmological menced with a topogram to define the PET/CT examina- and endocrinological examination and an audiometry. RT tion range (2 fields of view (FOV)). Non-contrast CT scans planning was performed on a 3D-data set generated from were performed firstly for attenuation correction of PET 3 mm CT scans in treatment position. For immobilization data and for anatomic correlation. Subsequently the PET of the head an individual thermoplastic head mask fixa- scan was done acquiring static emission data for 4 min- tion was used. Image fusion of diagnostic MRI, RT plan- utes per FOV. ning CT and PET/CT as well as target volume delineation was done with OTP-Masterplan package (Theranostic PET images were reconstructed by using an iterative algo- GmbH, Solingen, D). The CT planning images in mask rithm (ordered-subset expectation maximization: 4 itera- fixation were fused with the CT images derived from PET/ tions, 8 subsets). Non-enhanced CT data were CT (CT to CT, additionally CT to diagnostic MRI) using reconstructed with a slice thickness of 5 mm (axial) and the automatic matching algorithm stored in the OTP-Mas- an increment of 5 mm. terplan system. As being initially linked to the combined PET/CT images the raw PET data did not require a separate The reconstructed PET, CT and fused images were dis- image fusion. played on the manufacturer's workstation (e-soft, Sie- mens Medical Solutions) in axial, coronal and sagittal For gross tumor volume (GTV) delineation the initial planes with a resolution of 128 × 128 pixels for the PET macroscopic tumor volume definition was based on MRI and 512 × 512 pixels for the CT images. findings and RT planning CT information only (GTV- MRI/CT). Subsequently the PET positive tumor lesions The fused PET/CT images were evaluated by two experi- were defined by the same therapist (GTV-PET). The GTV- enced nuclear medicine experts and two experienced radi- MRI/CT as well as the GTV-PET was counterchecked by an ologists in consensus. For all detected meningiomas the advanced neuroradiologist or rather nuclear medicine standardized uptake value (SUV) was calculated using the physician. MRI data were complemented by DOTATOC- region of interest (ROI, 50% isocontour) method and was PET findings and additional clinical information (particu- corrected for weight. larly including potential areas of microscopic tumor growth) with a resulting CTV. Finally the CTV was Treatment planning and target volume definition expanded with an overall safety margin of 4 mm to the IMRT treatment planning was primarily based on diag- PTV. nostic MRI data and was secondarily complemented by Page 3 of 8 (page number not for citation purposes) Radiation Oncology 2009, 4:56 http://www.ro-journal.com/content/4/1/56 For IMRT treatment planning organs at risk (brainstem, Target volume definition based on [ Ga]-DOTATOC-PET optical nerves, chiasm, lens, internal ear and hippocam- (GTV-PET) included the tumor volume with an intense pus) were outlined. Irradiation was performed as EUD tracer uptake, all 26 meningiomas showed a high tumor- (equivalent uniform dose)-based IMRT, using the Hyper- to-background contrast. For the target volume definition ion software package. Three-dimensional dose distribu- the windowing of the DOTATOC-PET was determined by tions were calculated and optimized via Monte Carlo dose the optimal matching between the PET-positive areas and calculation using a multileaf collimator (leaf width: 4 mm the viewable tumor margins determined by CT/MRI. The at isocenter). The purpose of treatment planning was to physiological signal of the bony skull and the air-filled cover the 95% isoline by the PTV. The dose prescription nasal cavity was masked out via windowing; neither a SUV was 54 Gy in total with a daily fraction dose of 1.8 Gy, 5 cut-off nor a safety margin was defined. In general, the dif- times a week. Patient positioning was verified by cone ferentiation between the pituitary gland and adjacent beam CT imaging every day in the first week of irradiation located tumor manifestations is mostly sophisticated and afterwards twice a week. caused by the SSTR 2 expression of the gland itself. In cases with PET positive tumor manifestations nearby the Quantitative analysis of tumor volumes pituitary gland, they were included completely if it was For quantification of target volume changes based on the not possible to distinguish gland from tumor manifesta- PET findings we evaluated both the tumor volumes (GTV- tion. The median GTV-PET was 25.3 cc (mean: 33.5 cc; MRI/CT and GTV-PET) and intersection areas between the range 0.6-106.1 cc). GTV-MRI/CT and GTV-PET (Intersection-GTV-MRI/CT/ PET). For both modalities we computed the increase in Correlation of GTV-PET and GTV-MRI/CT - Multimodal [cc] with respect to the intersection area (Increase-MRI/CT target volume definition vs. Intersection, respectively Increase-PET vs. Intersec- In 17 of 26 patients DOTATOC-PET data led to additional tion). These areas are those, which are visible in one target information concerning the tumor extension (examples volume only. Finally the ratios between the increased vol- Figures 1, 2). Overall the GTV-MRI/CT was larger than the umes with respect to the GTV-MRI/CT were assessed. In GTV-PET in 10 patients, smaller in 13 patients and almost order to report these volume values for the whole patient the same in three patients (< = 0.7 cc deviation). Among collective pure descriptive statistics (mean, standard devi- the 13 patients with a larger GTV-PET than GTV-MRI/CT ation, median, maximum, minimum) were used. there were three patients with an inclusion of the pituitary gland region caused by difficult discrimination gland Results from tumor manifestation. IMRT A median treatment dose of 53 Gy (range 51.2-57 Gy) In 14 cases there were major changes of the clinical target could be achieved. IMRT was submitted with a 6/15 MV volume (CTV) based on PET findings (10 enlargements, linear accelerator (Elekta Synergy SBM XVI) and was car- two reductions and in two cases areas of target volume ried out on average with 8 beams (range 6-10) and 41 seg- enlargement as well as reduction). Minor changes (only ments (range 17-70). changes at the borders of the target volume without affec- tion of a new anatomical area) were seen in three patients Target volume definition by MRI/CT (three enlargements). Three cases showed a pronounced The GTV-MRI/CT included the macroscopic tumor visible enlargement of the CTV in the postoperative situation in the planning CT and contrast-enhanced T1-weighted based on enclosure of the PET positive resection hole. MRI. All meningiomas could be delineated on MRI and Exemplarily, in one patient the conventional MRI imaging CT. For the GTV-MRI/CT no safety margin was defined. showed no residual tumor growth after resection of an Median GTV-MRI/CT was 18.1 cc (mean: 27.5; range 1.2- olfactory's meningioma, whereas the additional PET data 79.5 cc). revealed active tumor mass in the nasal cavity and in the ethmoidal sinus. Therefore a clear enlargement of the CTV Target volume definition by [ Ga]-DOTATOC-PET (GTV-MRI/CT 13.6 cc; GTV-PET 18.2 cc; CTV 19.6 cc) All 26 patients displayed a pronounced SSTR 2 tracer resulted. In one case there was a remarkable enlargement retention within the meningioma. In addition to a strong of the CTV caused by a PET positive osseous lesion which signal in three patients there were distant small spots could not clearly be seen on MRI and CT imaging (GTV- without a morphologic correlate in the cranial MRI, which MRI/CT 69.3 cc; GTV-PET 94 cc; CTV 99 cc). In 9 of 26 were not included in the GTV-PET. patients DOTATOC-PET delivered no supplementary information regarding tumor extension known from MRI There were several DOTATOC-PET positive lesions and CT. The median CTV as a summation of the GTV- beyond the cranium without any further suspicious tumor MRI/CT and the GTV-PET without a safety margin was detection in an additional CT or MRI examination. 37.4 cc (mean 42.2 cc; range 1.3-143.2 cc). With the Page 4 of 8 (page number not for citation purposes) Radiation Oncology 2009, 4:56 http://www.ro-journal.com/content/4/1/56 Larg left) Figure 1 /e CT image fusion (top right) skull base meningioma with orbital invasion and close relation to the sella turcica region, [68Ga]-DOTATOC-PET (top Large skull base meningioma with orbital invasion and close relation to the sella turcica region, [68Ga]- DOTATOC-PET (top left)/CT image fusion (top right). Physiological tracer uptake of the pituitary gland. CTV/GTV contours (below left): red = GTV-PET; green = GTV-MRI/CT; yellow = CTV, CTV enlargement by GTV-PET. Dose distribu- tion with enclosing 90% PTV isoline. exception of three patients in the group of patients with Discussion additional information from the DOTATOC-PET the CTV A wide range of publications has documented the value of was always larger than each single of the correlating GTV external beam radiation for the treatment of meningioma. (PET and MRI/CT). The PTV was created from the CTV However clinical practice is more likely to show that only with an overall safety margin of 4 mm. Median PTV was those cases suffering from complex meningioma are 78.3 cc (mean: 92.3 cc; range 6.8-227.7 cc). referred to radiotherapy. This included patients with relapse after surgery, large tumors or complexly growing The median intersection volume of the GTV-MRI/CT and tumor. Thus the treating physician is frequently faced with the GTV-PET was 13.4 cc (mean 21.3 cc). The median vol- the dilemma to spare as much of critical normal tissue ume increase based on the PET findings compared to the without missing gross tumor. The use of highly conformal intersection was 6.1 cc (mean 12.2 cc ± 13.3 cc), based on treatments including IMRT even increases the need for the MRI and planning-CT data 5.7 cc (mean 6.2 cc ± 4.6 optimal target volume delineation. cc). Hence the increase is approximately the same for both defined GTVs. The median ratio of the overall MRI-posi- In the present study we evaluated the value of the [ Ga]- tive but PET-negative volume to the GTV-MRI/CT was DOTATOC-PET for treatment planning of intracranial 0.28 (mean 0.33 ± 0.21; range 0.02-0.75). The percentage complexly shaped meningiomas. Up to now the follow up of enlargement over the GTV-MRI/CT based on DOTA- time in our cohort is all too short to give some informa- TOC-PET was 0.31 (mean 1.03 ± 2.8; range 0-14.36, after tion about local control after IMRT treatment. However, removing one patient with a PET-tracer uptake in the our data show clearly that the use of [ Ga]-DOTATOC- resection hole without a visible tumor growth in the MRI, PET improved target volume delineation in a larger pro- the median ratio was 0.3 (mean 0.49 ± 0.68; range 0-3.1) portion of our patients schedule for an IMRT based radia- (Table 2). We conclude that about 30% of the GTV-MRI/ tion approach when compared to MRI based planning CT display no PET-tracer uptake and vice versa the volume alone. Particularly bony lesions or direct bone infiltration outside the GTV-MRI/CT with PET-tracer uptake not being by adjacent meningioma tissue were more likely to be visible in the MRI/CT images has a volume approximately detected with PET. Basically we found a geographical miss of 30% of the GTV-MRI/CT. in 50% of the patients and - on the other hand - were able Page 5 of 8 (page number not for citation purposes) Radiation Oncology 2009, 4:56 http://www.ro-journal.com/content/4/1/56 Recurrence of Figure 2 olfactory's meningioma (MRI left) Recurrence of olfactory's meningioma (MRI left). [68Ga]-DOTATOC-PET/CT image fusion with small distant lesion at the left dorsal orbital bone and physiological tracer uptake of the pituitary gland. Dose distribution (right) with inclusion of the small distant lesion and enclosing 90% PTV isoline. to reduce the CTV in 38% of the patients. When compared are responsible for the differences in target volume 68 11 to other observations using [ Ga]-DOTATOC-PET, C- changes. Methionine [30,31] or F-Tyrosine [32], similar ranges were reported in the term of PET scanning offering addi- An important consideration in this context is the open tional information. In this regard Milker-Zabel reported question if there is s SUV-threshold to define the GTV- relevant information in 19 out of 26 patients using PET. In our study for the target volume definition the win- DOTATOC [33], Astner reported additional information dowing of the DOTATOC-PET was determined by the in 29 out of 32 patients [30] and Rutten reported changes matching between the PET-positive areas and the viewa- in 6 out of 13 lesions in 11 patients using F-Tyrosine ble tumor margins determined by CT/MRI. The physio- [32]. In our series in 17 out of 26 patients PET scanning logical signal of the bony skull and the air-filled nasal offered relevant complementary information. cavity was masked out via windowing. Although a SUV- threshold would be helpful for the GTV-DOTATOC-PET When one analyzes the pattern of changes in more detail, delineation in meningiomas, up to know clear evidence Milker-Zabel and Rutten reported larger proportions of for a SUV cut-off is missing. Astner et al. [34] reported an potential geographical misses avoided by PET scanning interesting phantom study in 11 patients with glomus (38% in both studies) [32,33]. This is in accordance with tumors and revealed that a value of 32% of the maximum our findings where the CTV was increased after inclusion standardized uptake was an appropriate threshold for of the PET data (50%). In contrast, the study by Astner tumor delineation. At the moment we do not have this reported a larger proportion of GTV/PTV reductions after information for meningiomas in DOTATOC-PET imag- inclusion of C-Methionine-PET data when compared to ing. However, in regard to IMRT planning for meningi- MRI scanning alone (75%) [30]. omas special biological characteristics of microscopic tumor growth have to be taken into account especially for The reasons for these differences are not readily deducible CTV delineation. Hence in our opinion we have to be cau- from the reported data. However, it may be speculated tious in reducing target volumes along an experimental that the inherent bias of patient selection and strategies SUV-threshold alone. employed for MRI-GTV definition may be the underlying reason. This assumption is supported by the fact that at From the data currently available it seems that either 68 11 18 least comparable volumes were treated in all three studies [ Ga]-DOTATOC, C-Methionine or F-Tyrosine are excluding the possibility that differences in tumor volume useful tracers for target volume definition in patients with Table 2: Treatment characteristics, target volumes Median Maximum Minimum SD Mean GTV-MRI/CT [cc] 18,1 79,5 1,2 23,5 27,5 GTV-PET [cc] 25,3 106,1 0,6 29,1 33,5 CTV [cc] 37,4 143,2 1,3 34,7 42,2 Intersection-GTV-MRI/CT/PET [cc] 13,4 78,2 0,3 21,5 21,3 Increase-MRI/CT vs Intersection [cc] 5,7 15,5 0,8 4,6 6,2 Increase-PET vs Intersection [cc] 6,1 48,8 0 13,2 12,2 Ratio Increase-MRI/CT to GTV-MRI/CT 0,28 0,75 0,02 0,21 0,33 Ratio Increase-PET to GTV-MRI/CT 0,31 14,36 0,00 2,80 1,03 Page 6 of 8 (page number not for citation purposes) Radiation Oncology 2009, 4:56 http://www.ro-journal.com/content/4/1/56 meningioma. Up to now there is no clear evidence availa- radiotherapy; SPECT: single photon emission computed ble supporting the superiority of any of the given tracers. tomography; SSTR: somatostatin receptor; SUV: standard- ized uptake value. As stated above, meningiomas particularly show high lev- els of somatostatin receptor expression (SSTR2) resulting Competing interests in a high tracer uptake. The usefulness of [ Ga]-DOTA- The authors declare that they have no competing interests. TOC-PET for a distinction of meningioma from other brain tumors has been well documented [35-37]. In sev- Authors' contributions eral disorders including metastasis or glioma Methionine CB & UG planned, coordinated and conducted the study. or Tyrosine may produce false positive results. However, MÖ, SE, RB & CP performed PET imaging. BG, T-KH & amino acid tracers like Methionine or Tyrosine are mark- MÖ analyzed the PET and MRI imaging data. BG, UG, CB ers of amino acid transport and give some more informa- & FP analyzed the treatment planning data. BG, CB, PB & tion in regard to metabolic activity of several tumor UG prepared the manuscript. Medical care was covered by tissues. At least Methionine-PET may help to judge the BG, UG, CB, FP & MB. All authors read and approved the aggressiveness of meningioma since the uptake has been final manuscript. reported to correlate with the proliferative activity meas- ured by the KI-67 index [38-40]. In our opinion for IMRT References 1. Mirimanoff RO, Dosoretz DE, Linggood RM, Ojemann RG, Martuza planning it seems reasonable to use the tracer with the RL: Meningioma: analysis of recurrence and progression fol- highest inherent specificity which - by means of its mech- lowing neurosurgical resection. J Neurosurg 1985, 62(1):18-24. anism of action - is [ Ga]-DOTATOC-PET. 2. McCutcheon IE: The biology of meningiomas. J Neurooncol 1996, 29(3):207-216. 3. Stafford SL, Perry A, Suman VJ, Meyer FB, Scheithauer BW, Lohse A given disadvantage of DOTATOC is the fact that the CM, Shaw EG: Primarily resected meningiomas: outcome and prognostic factors in 581 Mayo Clinic patients, 1978 through pituitary gland is generally highly positive and limits the 1988. Mayo Clin Proc 1998, 73(10):936-942. precision of target volume definition in this area. 4. Mathiesen T, Lindquist C, Kihlstrom L, Karlsson B: Recurrence of cranial base meningiomas. Neurosurgery 1996, 39(1):2-7. discus- sion 8-9 Although PET/CT images have reached a considerable 5. Barbaro NM, Gutin PH, Wilson CB, Sheline GE, Boldrey EB, Wara level of spatial discrimination the current technology does WM: Radiation therapy in the treatment of partially resected not allow for the visualization of microscopic tumor meningiomas. Neurosurgery 1987, 20(4):525-528. 6. Goldsmith BJ, Wara WM, Wilson CB, Larson DA: Postoperative growth along the dural membranes. Thus it will be still irradiation for subtotally resected meningiomas. A retro- necessary to add empirical margins to cover all areas. spective analysis of 140 patients treated from 1967 to 1990. J Neurosurg 1994, 80(2):195-201. 7. Mesic JB, Hanks GE, Doggett RL: The value of radiation therapy Conclusion as an adjuvant to surgery in intracranial meningiomas. Am J [ Ga]-DOTATOC-PET/CT information strongly comple- Clin Oncol 1986, 9(4):337-340. 8. Taylor BW Jr, Marcus RB Jr, Friedman WA, Ballinger WE Jr, Million ments image data from MRI and CT in cases with complex RR: The meningioma controversy: postoperative radiation meningiomas of the skull base. In all meningioma therapy. Int J Radiat Oncol Biol Phys 1988, 15(2):299-304. patients a tracer uptake of the [ Ga]-DOTATOC was seen. 9. Debus J, Wuendrich M, Pirzkall A, Hoess A, Schlegel W, Zuna I, Engenhart-Cabillic R, Wannenmacher M: High efficacy of fraction- Especially in patients with complex skull base meningi- ated stereotactic radiotherapy of large base-of-skull menin- oma or recurrent disease [ Ga]-DOTATOC offers impor- giomas: long-term results. J Clin Oncol 2001, 19(15):3547-3553. 10. Milker-Zabel S, Zabel A, Schulz-Ertner D, Schlegel W, Wannen- tant additional information. Therefore we would macher M, Debus J: Fractionated stereotactic radiotherapy in recommend the use of the [ Ga]-DOTATOC for GTV def- patients with benign or atypical intracranial meningioma: inition in all cases with complex meningioma. long-term experience and prognostic factors. Int J Radiat Oncol Biol Phys 2005, 61(3):809-816. 11. van Rij CM, Oughlane-Heemsbergen WD, Ackerstaff AH, Lamers EA, Further evaluation with a larger number of patients seems Balm AJ, Rasch CR: Parotid gland sparing IMRT for head and to be justified and long-term follow-up is needed to eval- neck cancer improves xerostomia related quality of life. Radiat Oncol 2008, 3:41. uate the clinical impact. 12. Lips IM, Dehnad H, van Gils CH, Boeken Kruger AE, Heide UA van der, van Vulpen M: High-dose intensity-modulated radiother- apy for prostate cancer using daily fiducial marker-based Abbreviations position verification: acute and late toxicity in 331 patients. cc: cubic centimetre; CT: computed tomography; CTV: Radiat Oncol 2008, 3:15. clinical target volume; 3-D: three-dimensional; DOTA- 13. Menkarios C, Azria D, Laliberte B, Moscardo CL, Gourgou S, Leman- 68 1 3 ski C, Dubois JB, Ailleres N, Fenoglietto P: Optimal organ-sparing TOC: [ Ga]-DOTA-D Phe -Tyr -Octreotide; EUD: equiv- intensity-modulated radiation therapy (IMRT) regimen for alent uniform dose; f: female; FOV: field of view; GTV: the treatment of locally advanced anal canal carcinoma: a comparison of conventional and IMRT plans. Radiat Oncol gross tumor volume; IMRT: intensity modulated radio- 2007, 2:41. therapy; m: male; MBq: megaBecquerel; MRI: magnetic 14. Baumert BG, Norton IA, Davis JB: Intensity-modulated stereo- resonance imaging; PET: positron emission tomography; tactic radiotherapy vs. stereotactic conformal radiotherapy for the treatment of meningioma located predominantly in PTV: planning target volume; ROI: region of interest; RT: the skull base. Int J Radiat Oncol Biol Phys 2003, 57(2):580-592. Page 7 of 8 (page number not for citation purposes) Radiation Oncology 2009, 4:56 http://www.ro-journal.com/content/4/1/56 15. Milker-Zabel S, Zabel-du Bois A, Huber P, Schlegel W, Debus J: 32. Rutten I, Cabay JE, Withofs N, Lemaire C, Aerts J, Baart V, Hustinx Intensity-modulated radiotherapy for complex-shaped men- R: PET/CT of skull base meningiomas using 2-18F-fluoro-L- ingioma of the skull base: long-term experience of a single tyrosine: initial report. J Nucl Med 2007, 48(5):720-725. institution. Int J Radiat Oncol Biol Phys 2007, 68(3):858-863. 33. Milker-Zabel S, Zabel-du Bois A, Henze M, Huber P, Schulz-Ertner D, 16. Uy NW, Woo SY, Teh BS, Mai WY, Carpenter LS, Chiu JK, Lu HH, Hoess A, Haberkorn U, Debus J: Improved target volume defini- Gildenberg P, Trask T, Grant WH, et al.: Intensity-modulated tion for fractionated stereotactic radiotherapy in patients radiation therapy (IMRT) for meningioma. Int J Radiat Oncol Biol with intracranial meningiomas by correlation of CT, MRI, Phys 2002, 53(5):1265-1270. and [68Ga]-DOTATOC-PET. Int J Radiat Oncol Biol Phys 2006, 17. Pirzkall A, Debus J, Haering P, Rhein B, Grosser KH, Hoss A, Wan- 65(1):222-227. nenmacher M: Intensity modulated radiotherapy (IMRT) for 34. Astner ST, Bundschuh RA, Beer AJ, Ziegler SI, Krause BJ, Schwaiger recurrent, residual, or untreated skull-base meningiomas: M, Molls M, Grosu AL, Essler M: Assessment of tumor volumes preliminary clinical experience. Int J Radiat Oncol Biol Phys 2003, in skull base glomus tumors using Gluc-Lys[(18)F]-TOCA 55(2):362-372. positron emission tomography. Int J Radiat Oncol Biol Phys 2009, 18. Clark BG, Candish C, Vollans E, Gete E, Lee R, Martin M, Ma R, 73(4):1135-1140. McKenzie M: Optimization of stereotactic radiotherapy treat- 35. Schulz S, Pauli SU, Handel M, Dietzmann K, Firsching R, Hollt V: ment delivery technique for base-of-skull meningiomas. Med Immunohistochemical determination of five somatostatin Dosim 2008, 33(3):239-247. receptors in meningioma reveals frequent overexpression of 19. Sajja R, Barnett GH, Lee SY, Harnisch G, Stevens GH, Lee J, Suh JH: somatostatin receptor subtype sst2A. Clin Cancer Res 2000, Intensity-modulated radiation therapy (IMRT) for newly 6(5):1865-1874. diagnosed and recurrent intracranial meningiomas: prelimi- 36. Hildebrandt G, Scheidhauer K, Luyken C, Schicha H, Klug N, Dahms nary results. Technol Cancer Res Treat 2005, 4(6):675-682. P, Krisch B: High sensitivity of the in vivo detection of soma- 20. Ganswindt U, Paulsen F, Corvin S, Eichhorn K, Glocker S, Hundt I, tostatin receptors by 111 indium (DTPA-octreotide)-scintig- Birkner M, Alber M, Anastasiadis A, Stenzl A, et al.: Intensity mod- raphy in meningioma patients. Acta Neurochir (Wien) 1994, ulated radiotherapy for high risk prostate cancer based on 126(2-4):63-71. sentinel node SPECT imaging for target volume definition. 37. Barth A, Haldemann AR, Reubi JC, Godoy N, Rosler H, Kinser JA, BMC Cancer 2005, 5:91. Seiler RW: Noninvasive differentiation of meningiomas from 21. Ganswindt U, Paulsen F, Corvin S, Hundt I, Alber M, Frey B, Stenzl A, other brain tumours using combined 111 Indium-octreotide/ Bares R, Bamberg M, Belka C: Optimized coverage of high-risk 99 mtechnetium-DTPA brain scintigraphy. Acta Neurochir adjuvant lymph node areas in prostate cancer using a senti- (Wien) 1996, 138(10):1179-1185. nel node-based, intensity-modulated radiation therapy tech- 38. Nyberg G, Bergstrom M, Enblad P, Lilja A, Muhr C, Langstrom B: nique. Int J Radiat Oncol Biol Phys 2007, 67(2):347-355. PET-methionine of skull base neuromas and meningiomas. 22. Deantonio L, Beldi D, Gambaro G, Loi G, Brambilla M, Inglese E, Acta Otolaryngol 1997, 117(4):482-489. Krengli M: FDG-PET/CT imaging for staging and radiotherapy 39. Ericson K, Lilja A, Bergstrom M, Collins VP, Eriksson L, Ehrin E, von treatment planning of head and neck carcinoma. Radiat Oncol Holst H, Lundqvist H, Langsrom BB, Mosskin M: Positron emission 2008, 3:29. tomography with ([11C]methyl)-L-methionine, [11C]D-glu- 23. Rothschild S, Studer G, Seifert B, Huguenin P, Glanzmann C, Davis JB, cose, and [68Ga]EDTA in supratentorial tumors. J Comput Lutolf UM, Hany TF, Ciernik IF: PET/CT staging followed by Assist Tomogr 1985, 9(4):683-689. Intensity-Modulated Radiotherapy (IMRT) improves treat- 40. Iuchi T, Iwadate Y, Namba H, Osato K, Saeki N, Yamaura A, Uchida ment outcome of locally advanced pharyngeal carcinoma: a Y: Glucose and methionine uptake and proliferative activity matched-pair comparison. Radiat Oncol 2007, 2:22. in meningiomas. Neurol Res 1999, 21(7):640-644. 24. Weber DC, Zilli T, Buchegger F, Casanova N, Haller G, Rouzaud M, Nouet P, Dipasquale G, Ratib O, Zaidi H, et al.: [(18)F]Fluoroethyl- tyrosine- positron emission tomography-guided radiother- apy for high-grade glioma. Radiat Oncol 2008, 3:44. 25. Singh AK, Guion P, Sears-Crouse N, Ullman K, Smith S, Albert PS, Fichtinger G, Choyke PL, Xu S, Kruecker J, et al.: Simultaneous integrated boost of biopsy proven, MRI defined dominant intra-prostatic lesions to 95 Gray with IMRT: early results of a phase I NCI study. Radiat Oncol 2007, 2:36. 26. Sharma N, Neumann D, Macklis R: The impact of functional imaging on radiation medicine. Radiat Oncol 2008, 3:25. 27. Dutour A, Kumar U, Panetta R, Ouafik L, Fina F, Sasi R, Patel YC: Expression of somatostatin receptor subtypes in human brain tumors. Int J Cancer 1998, 76(5):620-627. 28. Henze M, Schuhmacher J, Hipp P, Kowalski J, Becker DW, Doll J, Macke HR, Hofmann M, Debus J, Haberkorn U: PET imaging of somatostatin receptors using [68Ga]DOTA-D-Phe1-Tyr3- octreotide: first results in patients with meningiomas. J Nucl Med 2001, 42(7):1053-1056. 29. Henze M, Dimitrakopoulou-Strauss A, Milker-Zabel S, Schuhmacher J, Strauss LG, Doll J, Macke HR, Eisenhut M, Debus J, Haberkorn U: Publish with Bio Med Central and every Characterization of 68Ga-DOTA-D-Phe1-Tyr3-octreotide scientist can read your work free of charge kinetics in patients with meningiomas. J Nucl Med 2005, 46(5):763-769. "BioMed Central will be the most significant development for 30. Astner ST, Dobrei-Ciuchendea M, Essler M, Bundschuh RA, Sai H, disseminating the results of biomedical researc h in our lifetime." Schwaiger M, Molls M, Weber WA, Grosu AL: Effect of 11C- Sir Paul Nurse, Cancer Research UK methionine-positron emission tomography on gross tumor volume delineation in stereotactic radiotherapy of skull base Your research papers will be: meningiomas. Int J Radiat Oncol Biol Phys 2008, 72(4):1161-1167. available free of charge to the entire biomedical community 31. Grosu AL, Weber WA, Astner ST, Adam M, Krause BJ, Schwaiger M, Molls M, Nieder C: 11C-methionine PET improves the target peer reviewed and published immediately upon acceptance volume delineation of meningiomas treated with stereotac- cited in PubMed and archived on PubMed Central tic fractionated radiotherapy. 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Medicine & Public Health; Oncology; Radiotherapy
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Abstract

Purpose: The observation that human meningioma cells strongly express somatostatin receptor (SSTR 2) was the rationale to analyze retrospectively in how far DOTATOC PET/CT is helpful to improve target volume delineation for intensity modulated radiotherapy (IMRT). Patients and Methods: In 26 consecutive patients with preferentially skull base meningioma, diagnostic magnetic resonance imaging (MRI) and planning-computed tomography (CT) was 68 1 3 complemented with data from [ Ga]-DOTA-D Phe -Tyr -Octreotide (DOTATOC)-PET/CT. Image fusion of PET/CT, diagnostic computed tomography, MRI and radiotherapy planning CT as well as target volume delineation was performed with OTP-Masterplan . Initial gross tumor volume (GTV) definition was based on MRI data only and was secondarily complemented with DOTATOC-PET information. Irradiation was performed as EUD based IMRT, using the Hyperion Software package. Results: The integration of the DOTATOC data led to additional information concerning tumor extension in 17 of 26 patients (65%). There were major changes of the clinical target volume (CTV) which modify the PTV in 14 patients, minor changes were realized in 3 patients. Overall the GTV- MRI/CT was larger than the GTV-PET in 10 patients (38%), smaller in 13 patients (50%) and almost the same in 3 patients (12%). Most of the adaptations were performed in close vicinity to bony skull base structures or after complex surgery. Median GTV based on MRI was 18.1 cc, based on PET 25.3 cc and subsequently the CTV was 37.4 cc. Radiation planning and treatment of the DOTATOC-adapted volumes was feasible. Page 1 of 8 (page number not for citation purposes) Radiation Oncology 2009, 4:56 http://www.ro-journal.com/content/4/1/56 Conclusion: DOTATOC-PET/CT information may strongly complement patho-anatomical data from MRI and CT in cases with complex meningioma and is thus helpful for improved target volume delineation especially for skull base manifestations and recurrent disease after surgery. after repetitive surgery and in case of an infiltrative growth Introduction Meningiomas represent about 20% of all intracranial pattern these imaging modalities have their limitations. brain tumors and are therefore the most frequent nonglial brain tumors in adults with a clear predomination in Meningioma cells strongly express somatostatin receptor women (f/m 2:1) [1]. More than 90% are histological subtype 2 (SSTR 2) which offers an additional positron benign of mesodermal origin arising from the arachnoid emission tomography (PET) based imaging for tumor meninges of the brain and are slow-growing with a low delineation with the somatostatin-receptor ligand [ Ga]- 1 3 proliferation index. Atypical or malignant histology is rare DOTA-D Phe -Tyr -Octreotide (DOTATOC) [27]. DOTA- and often requires multimodal treatment caused by TOC-PET/CT shows a high meningioma to background increased local relapse. ratio which can be used to improve target volume defini- tion prior to IMRT [28,29]. Particularly meningiomas of the skull base are difficult to treat due to their close relation to critical structures like To document the value of [ Ga]-DOTATOC-PET/CT for brainstem, major vessels and cranial nerves. treatment planning of complex meningiomas preferen- tially of the skull base we retrospectively analyzed a series Although surgical resection of meningioma is the pre- of patients in whom CT/MRI based treatment planning ferred treatment approach, ionizing radiation is a highly was complemented by [ Ga]-DOTATOC-PET/CT. effective treatment modality. After complete surgical resection long-term recurrence-free survival can be Patients and Methods achieved up to 93 and 80% after 5 and 10 years, respec- Patients tively. Without total removal the recurrence-free survival 26 consecutive patients with preferentially skull base is inferior, up to 65 and 45% or worse after 5 and 10 years, meningiomas received diagnostic MRI, RT planning CT respectively [1-4]. Adjuvant radiotherapy (RT) can and additional [ Ga]-DOTATOC-PET/CT prior to frac- improve local tumor control and overall survival after tionated stereotactic IMRT between 2007 and 2008 in our incomplete surgical resection [5-8]. Similar to resection, institution. 20 meningiomas were located at the skull radiotherapy alone offers 5-year local control above 90% base, one was an optic nerve sheath meningioma. Median [9,10]. However, the surrounding tissue and the benign age at treatment was 59.5 years (range 28-82 years). The histology mandate extreme precision during treatment male/female ratio was 3/23, median Karnofsky perform- planning in order to minimize the risk of side effects. ance score was 90% (range 70-100%). 19 of the 26 Therefore stereotactic fractionated treatment protocols patients underwent surgical treatment or extended biopsy, comprise the standard radiotherapy approach. Similar to 13 once, five twice and one woman for three times before numerous different malignancies treated with intensity- start of RT. The pathological examination revealed a modulated RT [11-13], recently several IMRT based proto- World Health Organization (WHO) grade I meningioma cols for meningiomas have been issued offering even in 14 and a WHO grade II tumor in four patients. One higher target volume conformity and improved normal young patient with a WHO grade II meningioma received tissue protection [14-19]. With increasing conformity the a prior prophylactic radiation of the brain with a cumula- need for accurate target volume delineation is of outmost tive dose of 18 Gy due to the therapy regime of a hemato- importance. Of special importance is the fact that target logical disorder 26 years before. Seven patients received volume definition after single or repeated surgical inter- IMRT as primary treatment without proven histology vention is frequently hampered by artifacts. In general the because biopsy was concluded to be infeasible. In these use of highly conformal treatment techniques mandates cases diagnosis of meningioma was based on CT and MRI improved pretherapeutic imaging. In this regard, positron offering typical radiologic characteristics of a benign men- emission tomography (PET) based techniques as well as ingioma. Characteristics of the patients are listed in Table other functional imaging modalities including SPECT-CT 1. or also MRI enter the routine in radiation oncology [20- 26]. [ Ga]-DOTATOC-PET/CT Imaging was performed using a dedicated PET/CT scanner Up to now treatment planning was mainly based on com- (Biograph 16 HiRez; Siemens Medical Solutions, Erlan- binations of contrast enhanced CT and MRI. Especially gen, Germany). Page 2 of 8 (page number not for citation purposes) Radiation Oncology 2009, 4:56 http://www.ro-journal.com/content/4/1/56 Table 1: Patients characteristics Patients treated with IMRT n = 26 Patients (female/male) 23;3 Karnofsky Performance Scale (median/range) [%] 95 (70-100) Age (median/range) [years] 60 (28-82) Tumor site Olfactorius nerve 5 Optic nerve sheath 1 Sphenoidal 4 Cavernous sinus 2 Petroclival/clival 5 Frontoparietal/-basal 2 Sphenoorbital 2 Parasagittal/falx 3 Infratentoriell 1 Convexity 1 Surgery/biopsy 19 resection for 1/2/3 times 13;5;1 Histology/WHO grading WHO I 14 WHO II (atypical meningioma) 4 Tissue lost 1 Unknown (diagnosis based on MRI, CT) 7 Postoperative period until initiation of radiation (median/range) [months] 56.1 (3-249) Forty minutes after intravenous injection of 150 MBq the information from [ Ga]-DOTATOC-PET. Addition- [ Ga]-DOTATOC the combined examination com- ally all patients routinely had a neuroophthalmological menced with a topogram to define the PET/CT examina- and endocrinological examination and an audiometry. RT tion range (2 fields of view (FOV)). Non-contrast CT scans planning was performed on a 3D-data set generated from were performed firstly for attenuation correction of PET 3 mm CT scans in treatment position. For immobilization data and for anatomic correlation. Subsequently the PET of the head an individual thermoplastic head mask fixa- scan was done acquiring static emission data for 4 min- tion was used. Image fusion of diagnostic MRI, RT plan- utes per FOV. ning CT and PET/CT as well as target volume delineation was done with OTP-Masterplan package (Theranostic PET images were reconstructed by using an iterative algo- GmbH, Solingen, D). The CT planning images in mask rithm (ordered-subset expectation maximization: 4 itera- fixation were fused with the CT images derived from PET/ tions, 8 subsets). Non-enhanced CT data were CT (CT to CT, additionally CT to diagnostic MRI) using reconstructed with a slice thickness of 5 mm (axial) and the automatic matching algorithm stored in the OTP-Mas- an increment of 5 mm. terplan system. As being initially linked to the combined PET/CT images the raw PET data did not require a separate The reconstructed PET, CT and fused images were dis- image fusion. played on the manufacturer's workstation (e-soft, Sie- mens Medical Solutions) in axial, coronal and sagittal For gross tumor volume (GTV) delineation the initial planes with a resolution of 128 × 128 pixels for the PET macroscopic tumor volume definition was based on MRI and 512 × 512 pixels for the CT images. findings and RT planning CT information only (GTV- MRI/CT). Subsequently the PET positive tumor lesions The fused PET/CT images were evaluated by two experi- were defined by the same therapist (GTV-PET). The GTV- enced nuclear medicine experts and two experienced radi- MRI/CT as well as the GTV-PET was counterchecked by an ologists in consensus. For all detected meningiomas the advanced neuroradiologist or rather nuclear medicine standardized uptake value (SUV) was calculated using the physician. MRI data were complemented by DOTATOC- region of interest (ROI, 50% isocontour) method and was PET findings and additional clinical information (particu- corrected for weight. larly including potential areas of microscopic tumor growth) with a resulting CTV. Finally the CTV was Treatment planning and target volume definition expanded with an overall safety margin of 4 mm to the IMRT treatment planning was primarily based on diag- PTV. nostic MRI data and was secondarily complemented by Page 3 of 8 (page number not for citation purposes) Radiation Oncology 2009, 4:56 http://www.ro-journal.com/content/4/1/56 For IMRT treatment planning organs at risk (brainstem, Target volume definition based on [ Ga]-DOTATOC-PET optical nerves, chiasm, lens, internal ear and hippocam- (GTV-PET) included the tumor volume with an intense pus) were outlined. Irradiation was performed as EUD tracer uptake, all 26 meningiomas showed a high tumor- (equivalent uniform dose)-based IMRT, using the Hyper- to-background contrast. For the target volume definition ion software package. Three-dimensional dose distribu- the windowing of the DOTATOC-PET was determined by tions were calculated and optimized via Monte Carlo dose the optimal matching between the PET-positive areas and calculation using a multileaf collimator (leaf width: 4 mm the viewable tumor margins determined by CT/MRI. The at isocenter). The purpose of treatment planning was to physiological signal of the bony skull and the air-filled cover the 95% isoline by the PTV. The dose prescription nasal cavity was masked out via windowing; neither a SUV was 54 Gy in total with a daily fraction dose of 1.8 Gy, 5 cut-off nor a safety margin was defined. In general, the dif- times a week. Patient positioning was verified by cone ferentiation between the pituitary gland and adjacent beam CT imaging every day in the first week of irradiation located tumor manifestations is mostly sophisticated and afterwards twice a week. caused by the SSTR 2 expression of the gland itself. In cases with PET positive tumor manifestations nearby the Quantitative analysis of tumor volumes pituitary gland, they were included completely if it was For quantification of target volume changes based on the not possible to distinguish gland from tumor manifesta- PET findings we evaluated both the tumor volumes (GTV- tion. The median GTV-PET was 25.3 cc (mean: 33.5 cc; MRI/CT and GTV-PET) and intersection areas between the range 0.6-106.1 cc). GTV-MRI/CT and GTV-PET (Intersection-GTV-MRI/CT/ PET). For both modalities we computed the increase in Correlation of GTV-PET and GTV-MRI/CT - Multimodal [cc] with respect to the intersection area (Increase-MRI/CT target volume definition vs. Intersection, respectively Increase-PET vs. Intersec- In 17 of 26 patients DOTATOC-PET data led to additional tion). These areas are those, which are visible in one target information concerning the tumor extension (examples volume only. Finally the ratios between the increased vol- Figures 1, 2). Overall the GTV-MRI/CT was larger than the umes with respect to the GTV-MRI/CT were assessed. In GTV-PET in 10 patients, smaller in 13 patients and almost order to report these volume values for the whole patient the same in three patients (< = 0.7 cc deviation). Among collective pure descriptive statistics (mean, standard devi- the 13 patients with a larger GTV-PET than GTV-MRI/CT ation, median, maximum, minimum) were used. there were three patients with an inclusion of the pituitary gland region caused by difficult discrimination gland Results from tumor manifestation. IMRT A median treatment dose of 53 Gy (range 51.2-57 Gy) In 14 cases there were major changes of the clinical target could be achieved. IMRT was submitted with a 6/15 MV volume (CTV) based on PET findings (10 enlargements, linear accelerator (Elekta Synergy SBM XVI) and was car- two reductions and in two cases areas of target volume ried out on average with 8 beams (range 6-10) and 41 seg- enlargement as well as reduction). Minor changes (only ments (range 17-70). changes at the borders of the target volume without affec- tion of a new anatomical area) were seen in three patients Target volume definition by MRI/CT (three enlargements). Three cases showed a pronounced The GTV-MRI/CT included the macroscopic tumor visible enlargement of the CTV in the postoperative situation in the planning CT and contrast-enhanced T1-weighted based on enclosure of the PET positive resection hole. MRI. All meningiomas could be delineated on MRI and Exemplarily, in one patient the conventional MRI imaging CT. For the GTV-MRI/CT no safety margin was defined. showed no residual tumor growth after resection of an Median GTV-MRI/CT was 18.1 cc (mean: 27.5; range 1.2- olfactory's meningioma, whereas the additional PET data 79.5 cc). revealed active tumor mass in the nasal cavity and in the ethmoidal sinus. Therefore a clear enlargement of the CTV Target volume definition by [ Ga]-DOTATOC-PET (GTV-MRI/CT 13.6 cc; GTV-PET 18.2 cc; CTV 19.6 cc) All 26 patients displayed a pronounced SSTR 2 tracer resulted. In one case there was a remarkable enlargement retention within the meningioma. In addition to a strong of the CTV caused by a PET positive osseous lesion which signal in three patients there were distant small spots could not clearly be seen on MRI and CT imaging (GTV- without a morphologic correlate in the cranial MRI, which MRI/CT 69.3 cc; GTV-PET 94 cc; CTV 99 cc). In 9 of 26 were not included in the GTV-PET. patients DOTATOC-PET delivered no supplementary information regarding tumor extension known from MRI There were several DOTATOC-PET positive lesions and CT. The median CTV as a summation of the GTV- beyond the cranium without any further suspicious tumor MRI/CT and the GTV-PET without a safety margin was detection in an additional CT or MRI examination. 37.4 cc (mean 42.2 cc; range 1.3-143.2 cc). With the Page 4 of 8 (page number not for citation purposes) Radiation Oncology 2009, 4:56 http://www.ro-journal.com/content/4/1/56 Larg left) Figure 1 /e CT image fusion (top right) skull base meningioma with orbital invasion and close relation to the sella turcica region, [68Ga]-DOTATOC-PET (top Large skull base meningioma with orbital invasion and close relation to the sella turcica region, [68Ga]- DOTATOC-PET (top left)/CT image fusion (top right). Physiological tracer uptake of the pituitary gland. CTV/GTV contours (below left): red = GTV-PET; green = GTV-MRI/CT; yellow = CTV, CTV enlargement by GTV-PET. Dose distribu- tion with enclosing 90% PTV isoline. exception of three patients in the group of patients with Discussion additional information from the DOTATOC-PET the CTV A wide range of publications has documented the value of was always larger than each single of the correlating GTV external beam radiation for the treatment of meningioma. (PET and MRI/CT). The PTV was created from the CTV However clinical practice is more likely to show that only with an overall safety margin of 4 mm. Median PTV was those cases suffering from complex meningioma are 78.3 cc (mean: 92.3 cc; range 6.8-227.7 cc). referred to radiotherapy. This included patients with relapse after surgery, large tumors or complexly growing The median intersection volume of the GTV-MRI/CT and tumor. Thus the treating physician is frequently faced with the GTV-PET was 13.4 cc (mean 21.3 cc). The median vol- the dilemma to spare as much of critical normal tissue ume increase based on the PET findings compared to the without missing gross tumor. The use of highly conformal intersection was 6.1 cc (mean 12.2 cc ± 13.3 cc), based on treatments including IMRT even increases the need for the MRI and planning-CT data 5.7 cc (mean 6.2 cc ± 4.6 optimal target volume delineation. cc). Hence the increase is approximately the same for both defined GTVs. The median ratio of the overall MRI-posi- In the present study we evaluated the value of the [ Ga]- tive but PET-negative volume to the GTV-MRI/CT was DOTATOC-PET for treatment planning of intracranial 0.28 (mean 0.33 ± 0.21; range 0.02-0.75). The percentage complexly shaped meningiomas. Up to now the follow up of enlargement over the GTV-MRI/CT based on DOTA- time in our cohort is all too short to give some informa- TOC-PET was 0.31 (mean 1.03 ± 2.8; range 0-14.36, after tion about local control after IMRT treatment. However, removing one patient with a PET-tracer uptake in the our data show clearly that the use of [ Ga]-DOTATOC- resection hole without a visible tumor growth in the MRI, PET improved target volume delineation in a larger pro- the median ratio was 0.3 (mean 0.49 ± 0.68; range 0-3.1) portion of our patients schedule for an IMRT based radia- (Table 2). We conclude that about 30% of the GTV-MRI/ tion approach when compared to MRI based planning CT display no PET-tracer uptake and vice versa the volume alone. Particularly bony lesions or direct bone infiltration outside the GTV-MRI/CT with PET-tracer uptake not being by adjacent meningioma tissue were more likely to be visible in the MRI/CT images has a volume approximately detected with PET. Basically we found a geographical miss of 30% of the GTV-MRI/CT. in 50% of the patients and - on the other hand - were able Page 5 of 8 (page number not for citation purposes) Radiation Oncology 2009, 4:56 http://www.ro-journal.com/content/4/1/56 Recurrence of Figure 2 olfactory's meningioma (MRI left) Recurrence of olfactory's meningioma (MRI left). [68Ga]-DOTATOC-PET/CT image fusion with small distant lesion at the left dorsal orbital bone and physiological tracer uptake of the pituitary gland. Dose distribution (right) with inclusion of the small distant lesion and enclosing 90% PTV isoline. to reduce the CTV in 38% of the patients. When compared are responsible for the differences in target volume 68 11 to other observations using [ Ga]-DOTATOC-PET, C- changes. Methionine [30,31] or F-Tyrosine [32], similar ranges were reported in the term of PET scanning offering addi- An important consideration in this context is the open tional information. In this regard Milker-Zabel reported question if there is s SUV-threshold to define the GTV- relevant information in 19 out of 26 patients using PET. In our study for the target volume definition the win- DOTATOC [33], Astner reported additional information dowing of the DOTATOC-PET was determined by the in 29 out of 32 patients [30] and Rutten reported changes matching between the PET-positive areas and the viewa- in 6 out of 13 lesions in 11 patients using F-Tyrosine ble tumor margins determined by CT/MRI. The physio- [32]. In our series in 17 out of 26 patients PET scanning logical signal of the bony skull and the air-filled nasal offered relevant complementary information. cavity was masked out via windowing. Although a SUV- threshold would be helpful for the GTV-DOTATOC-PET When one analyzes the pattern of changes in more detail, delineation in meningiomas, up to know clear evidence Milker-Zabel and Rutten reported larger proportions of for a SUV cut-off is missing. Astner et al. [34] reported an potential geographical misses avoided by PET scanning interesting phantom study in 11 patients with glomus (38% in both studies) [32,33]. This is in accordance with tumors and revealed that a value of 32% of the maximum our findings where the CTV was increased after inclusion standardized uptake was an appropriate threshold for of the PET data (50%). In contrast, the study by Astner tumor delineation. At the moment we do not have this reported a larger proportion of GTV/PTV reductions after information for meningiomas in DOTATOC-PET imag- inclusion of C-Methionine-PET data when compared to ing. However, in regard to IMRT planning for meningi- MRI scanning alone (75%) [30]. omas special biological characteristics of microscopic tumor growth have to be taken into account especially for The reasons for these differences are not readily deducible CTV delineation. Hence in our opinion we have to be cau- from the reported data. However, it may be speculated tious in reducing target volumes along an experimental that the inherent bias of patient selection and strategies SUV-threshold alone. employed for MRI-GTV definition may be the underlying reason. This assumption is supported by the fact that at From the data currently available it seems that either 68 11 18 least comparable volumes were treated in all three studies [ Ga]-DOTATOC, C-Methionine or F-Tyrosine are excluding the possibility that differences in tumor volume useful tracers for target volume definition in patients with Table 2: Treatment characteristics, target volumes Median Maximum Minimum SD Mean GTV-MRI/CT [cc] 18,1 79,5 1,2 23,5 27,5 GTV-PET [cc] 25,3 106,1 0,6 29,1 33,5 CTV [cc] 37,4 143,2 1,3 34,7 42,2 Intersection-GTV-MRI/CT/PET [cc] 13,4 78,2 0,3 21,5 21,3 Increase-MRI/CT vs Intersection [cc] 5,7 15,5 0,8 4,6 6,2 Increase-PET vs Intersection [cc] 6,1 48,8 0 13,2 12,2 Ratio Increase-MRI/CT to GTV-MRI/CT 0,28 0,75 0,02 0,21 0,33 Ratio Increase-PET to GTV-MRI/CT 0,31 14,36 0,00 2,80 1,03 Page 6 of 8 (page number not for citation purposes) Radiation Oncology 2009, 4:56 http://www.ro-journal.com/content/4/1/56 meningioma. Up to now there is no clear evidence availa- radiotherapy; SPECT: single photon emission computed ble supporting the superiority of any of the given tracers. tomography; SSTR: somatostatin receptor; SUV: standard- ized uptake value. As stated above, meningiomas particularly show high lev- els of somatostatin receptor expression (SSTR2) resulting Competing interests in a high tracer uptake. The usefulness of [ Ga]-DOTA- The authors declare that they have no competing interests. TOC-PET for a distinction of meningioma from other brain tumors has been well documented [35-37]. In sev- Authors' contributions eral disorders including metastasis or glioma Methionine CB & UG planned, coordinated and conducted the study. or Tyrosine may produce false positive results. However, MÖ, SE, RB & CP performed PET imaging. BG, T-KH & amino acid tracers like Methionine or Tyrosine are mark- MÖ analyzed the PET and MRI imaging data. BG, UG, CB ers of amino acid transport and give some more informa- & FP analyzed the treatment planning data. BG, CB, PB & tion in regard to metabolic activity of several tumor UG prepared the manuscript. Medical care was covered by tissues. At least Methionine-PET may help to judge the BG, UG, CB, FP & MB. All authors read and approved the aggressiveness of meningioma since the uptake has been final manuscript. reported to correlate with the proliferative activity meas- ured by the KI-67 index [38-40]. In our opinion for IMRT References 1. Mirimanoff RO, Dosoretz DE, Linggood RM, Ojemann RG, Martuza planning it seems reasonable to use the tracer with the RL: Meningioma: analysis of recurrence and progression fol- highest inherent specificity which - by means of its mech- lowing neurosurgical resection. J Neurosurg 1985, 62(1):18-24. anism of action - is [ Ga]-DOTATOC-PET. 2. McCutcheon IE: The biology of meningiomas. J Neurooncol 1996, 29(3):207-216. 3. Stafford SL, Perry A, Suman VJ, Meyer FB, Scheithauer BW, Lohse A given disadvantage of DOTATOC is the fact that the CM, Shaw EG: Primarily resected meningiomas: outcome and prognostic factors in 581 Mayo Clinic patients, 1978 through pituitary gland is generally highly positive and limits the 1988. Mayo Clin Proc 1998, 73(10):936-942. precision of target volume definition in this area. 4. Mathiesen T, Lindquist C, Kihlstrom L, Karlsson B: Recurrence of cranial base meningiomas. Neurosurgery 1996, 39(1):2-7. discus- sion 8-9 Although PET/CT images have reached a considerable 5. Barbaro NM, Gutin PH, Wilson CB, Sheline GE, Boldrey EB, Wara level of spatial discrimination the current technology does WM: Radiation therapy in the treatment of partially resected not allow for the visualization of microscopic tumor meningiomas. Neurosurgery 1987, 20(4):525-528. 6. Goldsmith BJ, Wara WM, Wilson CB, Larson DA: Postoperative growth along the dural membranes. Thus it will be still irradiation for subtotally resected meningiomas. A retro- necessary to add empirical margins to cover all areas. spective analysis of 140 patients treated from 1967 to 1990. J Neurosurg 1994, 80(2):195-201. 7. Mesic JB, Hanks GE, Doggett RL: The value of radiation therapy Conclusion as an adjuvant to surgery in intracranial meningiomas. Am J [ Ga]-DOTATOC-PET/CT information strongly comple- Clin Oncol 1986, 9(4):337-340. 8. Taylor BW Jr, Marcus RB Jr, Friedman WA, Ballinger WE Jr, Million ments image data from MRI and CT in cases with complex RR: The meningioma controversy: postoperative radiation meningiomas of the skull base. In all meningioma therapy. Int J Radiat Oncol Biol Phys 1988, 15(2):299-304. patients a tracer uptake of the [ Ga]-DOTATOC was seen. 9. Debus J, Wuendrich M, Pirzkall A, Hoess A, Schlegel W, Zuna I, Engenhart-Cabillic R, Wannenmacher M: High efficacy of fraction- Especially in patients with complex skull base meningi- ated stereotactic radiotherapy of large base-of-skull menin- oma or recurrent disease [ Ga]-DOTATOC offers impor- giomas: long-term results. J Clin Oncol 2001, 19(15):3547-3553. 10. Milker-Zabel S, Zabel A, Schulz-Ertner D, Schlegel W, Wannen- tant additional information. Therefore we would macher M, Debus J: Fractionated stereotactic radiotherapy in recommend the use of the [ Ga]-DOTATOC for GTV def- patients with benign or atypical intracranial meningioma: inition in all cases with complex meningioma. long-term experience and prognostic factors. Int J Radiat Oncol Biol Phys 2005, 61(3):809-816. 11. van Rij CM, Oughlane-Heemsbergen WD, Ackerstaff AH, Lamers EA, Further evaluation with a larger number of patients seems Balm AJ, Rasch CR: Parotid gland sparing IMRT for head and to be justified and long-term follow-up is needed to eval- neck cancer improves xerostomia related quality of life. Radiat Oncol 2008, 3:41. uate the clinical impact. 12. Lips IM, Dehnad H, van Gils CH, Boeken Kruger AE, Heide UA van der, van Vulpen M: High-dose intensity-modulated radiother- apy for prostate cancer using daily fiducial marker-based Abbreviations position verification: acute and late toxicity in 331 patients. cc: cubic centimetre; CT: computed tomography; CTV: Radiat Oncol 2008, 3:15. clinical target volume; 3-D: three-dimensional; DOTA- 13. Menkarios C, Azria D, Laliberte B, Moscardo CL, Gourgou S, Leman- 68 1 3 ski C, Dubois JB, Ailleres N, Fenoglietto P: Optimal organ-sparing TOC: [ Ga]-DOTA-D Phe -Tyr -Octreotide; EUD: equiv- intensity-modulated radiation therapy (IMRT) regimen for alent uniform dose; f: female; FOV: field of view; GTV: the treatment of locally advanced anal canal carcinoma: a comparison of conventional and IMRT plans. Radiat Oncol gross tumor volume; IMRT: intensity modulated radio- 2007, 2:41. therapy; m: male; MBq: megaBecquerel; MRI: magnetic 14. Baumert BG, Norton IA, Davis JB: Intensity-modulated stereo- resonance imaging; PET: positron emission tomography; tactic radiotherapy vs. stereotactic conformal radiotherapy for the treatment of meningioma located predominantly in PTV: planning target volume; ROI: region of interest; RT: the skull base. Int J Radiat Oncol Biol Phys 2003, 57(2):580-592. Page 7 of 8 (page number not for citation purposes) Radiation Oncology 2009, 4:56 http://www.ro-journal.com/content/4/1/56 15. Milker-Zabel S, Zabel-du Bois A, Huber P, Schlegel W, Debus J: 32. Rutten I, Cabay JE, Withofs N, Lemaire C, Aerts J, Baart V, Hustinx Intensity-modulated radiotherapy for complex-shaped men- R: PET/CT of skull base meningiomas using 2-18F-fluoro-L- ingioma of the skull base: long-term experience of a single tyrosine: initial report. J Nucl Med 2007, 48(5):720-725. institution. Int J Radiat Oncol Biol Phys 2007, 68(3):858-863. 33. Milker-Zabel S, Zabel-du Bois A, Henze M, Huber P, Schulz-Ertner D, 16. Uy NW, Woo SY, Teh BS, Mai WY, Carpenter LS, Chiu JK, Lu HH, Hoess A, Haberkorn U, Debus J: Improved target volume defini- Gildenberg P, Trask T, Grant WH, et al.: Intensity-modulated tion for fractionated stereotactic radiotherapy in patients radiation therapy (IMRT) for meningioma. Int J Radiat Oncol Biol with intracranial meningiomas by correlation of CT, MRI, Phys 2002, 53(5):1265-1270. and [68Ga]-DOTATOC-PET. Int J Radiat Oncol Biol Phys 2006, 17. Pirzkall A, Debus J, Haering P, Rhein B, Grosser KH, Hoss A, Wan- 65(1):222-227. nenmacher M: Intensity modulated radiotherapy (IMRT) for 34. Astner ST, Bundschuh RA, Beer AJ, Ziegler SI, Krause BJ, Schwaiger recurrent, residual, or untreated skull-base meningiomas: M, Molls M, Grosu AL, Essler M: Assessment of tumor volumes preliminary clinical experience. Int J Radiat Oncol Biol Phys 2003, in skull base glomus tumors using Gluc-Lys[(18)F]-TOCA 55(2):362-372. positron emission tomography. Int J Radiat Oncol Biol Phys 2009, 18. Clark BG, Candish C, Vollans E, Gete E, Lee R, Martin M, Ma R, 73(4):1135-1140. McKenzie M: Optimization of stereotactic radiotherapy treat- 35. Schulz S, Pauli SU, Handel M, Dietzmann K, Firsching R, Hollt V: ment delivery technique for base-of-skull meningiomas. Med Immunohistochemical determination of five somatostatin Dosim 2008, 33(3):239-247. receptors in meningioma reveals frequent overexpression of 19. Sajja R, Barnett GH, Lee SY, Harnisch G, Stevens GH, Lee J, Suh JH: somatostatin receptor subtype sst2A. Clin Cancer Res 2000, Intensity-modulated radiation therapy (IMRT) for newly 6(5):1865-1874. diagnosed and recurrent intracranial meningiomas: prelimi- 36. Hildebrandt G, Scheidhauer K, Luyken C, Schicha H, Klug N, Dahms nary results. Technol Cancer Res Treat 2005, 4(6):675-682. P, Krisch B: High sensitivity of the in vivo detection of soma- 20. Ganswindt U, Paulsen F, Corvin S, Eichhorn K, Glocker S, Hundt I, tostatin receptors by 111 indium (DTPA-octreotide)-scintig- Birkner M, Alber M, Anastasiadis A, Stenzl A, et al.: Intensity mod- raphy in meningioma patients. Acta Neurochir (Wien) 1994, ulated radiotherapy for high risk prostate cancer based on 126(2-4):63-71. sentinel node SPECT imaging for target volume definition. 37. Barth A, Haldemann AR, Reubi JC, Godoy N, Rosler H, Kinser JA, BMC Cancer 2005, 5:91. Seiler RW: Noninvasive differentiation of meningiomas from 21. Ganswindt U, Paulsen F, Corvin S, Hundt I, Alber M, Frey B, Stenzl A, other brain tumours using combined 111 Indium-octreotide/ Bares R, Bamberg M, Belka C: Optimized coverage of high-risk 99 mtechnetium-DTPA brain scintigraphy. Acta Neurochir adjuvant lymph node areas in prostate cancer using a senti- (Wien) 1996, 138(10):1179-1185. nel node-based, intensity-modulated radiation therapy tech- 38. Nyberg G, Bergstrom M, Enblad P, Lilja A, Muhr C, Langstrom B: nique. Int J Radiat Oncol Biol Phys 2007, 67(2):347-355. PET-methionine of skull base neuromas and meningiomas. 22. Deantonio L, Beldi D, Gambaro G, Loi G, Brambilla M, Inglese E, Acta Otolaryngol 1997, 117(4):482-489. Krengli M: FDG-PET/CT imaging for staging and radiotherapy 39. Ericson K, Lilja A, Bergstrom M, Collins VP, Eriksson L, Ehrin E, von treatment planning of head and neck carcinoma. Radiat Oncol Holst H, Lundqvist H, Langsrom BB, Mosskin M: Positron emission 2008, 3:29. tomography with ([11C]methyl)-L-methionine, [11C]D-glu- 23. Rothschild S, Studer G, Seifert B, Huguenin P, Glanzmann C, Davis JB, cose, and [68Ga]EDTA in supratentorial tumors. J Comput Lutolf UM, Hany TF, Ciernik IF: PET/CT staging followed by Assist Tomogr 1985, 9(4):683-689. Intensity-Modulated Radiotherapy (IMRT) improves treat- 40. Iuchi T, Iwadate Y, Namba H, Osato K, Saeki N, Yamaura A, Uchida ment outcome of locally advanced pharyngeal carcinoma: a Y: Glucose and methionine uptake and proliferative activity matched-pair comparison. Radiat Oncol 2007, 2:22. in meningiomas. Neurol Res 1999, 21(7):640-644. 24. Weber DC, Zilli T, Buchegger F, Casanova N, Haller G, Rouzaud M, Nouet P, Dipasquale G, Ratib O, Zaidi H, et al.: [(18)F]Fluoroethyl- tyrosine- positron emission tomography-guided radiother- apy for high-grade glioma. Radiat Oncol 2008, 3:44. 25. Singh AK, Guion P, Sears-Crouse N, Ullman K, Smith S, Albert PS, Fichtinger G, Choyke PL, Xu S, Kruecker J, et al.: Simultaneous integrated boost of biopsy proven, MRI defined dominant intra-prostatic lesions to 95 Gray with IMRT: early results of a phase I NCI study. Radiat Oncol 2007, 2:36. 26. Sharma N, Neumann D, Macklis R: The impact of functional imaging on radiation medicine. Radiat Oncol 2008, 3:25. 27. Dutour A, Kumar U, Panetta R, Ouafik L, Fina F, Sasi R, Patel YC: Expression of somatostatin receptor subtypes in human brain tumors. Int J Cancer 1998, 76(5):620-627. 28. Henze M, Schuhmacher J, Hipp P, Kowalski J, Becker DW, Doll J, Macke HR, Hofmann M, Debus J, Haberkorn U: PET imaging of somatostatin receptors using [68Ga]DOTA-D-Phe1-Tyr3- octreotide: first results in patients with meningiomas. J Nucl Med 2001, 42(7):1053-1056. 29. Henze M, Dimitrakopoulou-Strauss A, Milker-Zabel S, Schuhmacher J, Strauss LG, Doll J, Macke HR, Eisenhut M, Debus J, Haberkorn U: Publish with Bio Med Central and every Characterization of 68Ga-DOTA-D-Phe1-Tyr3-octreotide scientist can read your work free of charge kinetics in patients with meningiomas. J Nucl Med 2005, 46(5):763-769. "BioMed Central will be the most significant development for 30. Astner ST, Dobrei-Ciuchendea M, Essler M, Bundschuh RA, Sai H, disseminating the results of biomedical researc h in our lifetime." Schwaiger M, Molls M, Weber WA, Grosu AL: Effect of 11C- Sir Paul Nurse, Cancer Research UK methionine-positron emission tomography on gross tumor volume delineation in stereotactic radiotherapy of skull base Your research papers will be: meningiomas. Int J Radiat Oncol Biol Phys 2008, 72(4):1161-1167. available free of charge to the entire biomedical community 31. Grosu AL, Weber WA, Astner ST, Adam M, Krause BJ, Schwaiger M, Molls M, Nieder C: 11C-methionine PET improves the target peer reviewed and published immediately upon acceptance volume delineation of meningiomas treated with stereotac- cited in PubMed and archived on PubMed Central tic fractionated radiotherapy. Int J Radiat Oncol Biol Phys 2006, 66(2):339-344. yours — you keep the copyright BioMedcentral Submit your manuscript here: http://www.biomedcentral.com/info/publishing_adv.asp Page 8 of 8 (page number not for citation purposes)

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Radiation OncologySpringer Journals

Published: Nov 18, 2009

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