Radiosurgery of functioning pituitary adenomas: Comparison of different treatment techniques including dynamic and conformal arcs, shaped beams, and IMRT

Abstract

Purpose: Evaluation of different techniques including intensity-modulated radiotherapy (IMRT) for stereotactic radiosurgery (SRS) of pituitary adenoma (PA).Methods and Materials: Between January 2003 and February 2005, 152 SRS procedures were performed. Ten patients with PA were compared: conformal vs. dynamic arc treatment with micromultileaf collimator (mMLC) vs. circular collimators vs. 8–10 conformal static mMLC beams with and without IMRT. Prescribed total dose: 18 Gy (90%). Constraints: Dmax optic chiasm <8 Gy, Vol10Gy temporal lobe <10 mL. End points: coverage, conformity index, homogeneity index (HI), Vol10Gy temporal lobe.Results: For the end point “improvement in coverage,” an advantage with IMRT was noted for 5 of 10 patients as compared with the dynamic arc approach. Volume treated >18 Gy outside the planning target volume was lowest in 9 of 10 patients after IMRT; 1 patient achieved better conformity with circular collimators. As for Vol10Gy temporal lobe, an advantage was depicted for 1 of 10 patients with IMRT, the other techniques appearing equally effective in shielding the temporal lobe. With all techniques Vol10 Gy temporal lobe was <10 mL and Dmax optic chiasm <8 Gy. However, using circular collimators yielded the highest maximum dose with 39.8 Gy (HI, 2.2) as compared with 20.46–21.74 Gy (HI, 1.13–1.2) for other approaches.Conclusions: Novalis-based radiosurgery using dynamic arc treatment with mMLC is considered a safe and appropriate approach for SRS of PA. Purpose: Evaluation of different techniques including intensity-modulated radiotherapy (IMRT) for stereotactic radiosurgery (SRS) of pituitary adenoma (PA). Methods and Materials: Between January 2003 and February 2005, 152 SRS procedures were performed. Ten patients with PA were compared: conformal vs. dynamic arc treatment with micromultileaf collimator (mMLC) vs. circular collimators vs. 8–10 conformal static mMLC beams with and without IMRT. Prescribed total dose: 18 Gy (90%). Constraints: Dmax optic chiasm <8 Gy, Vol10Gy temporal lobe <10 mL. End points: coverage, conformity index, homogeneity index (HI), Vol10Gy temporal lobe. Results: For the end point “improvement in coverage,” an advantage with IMRT was noted for 5 of 10 patients as compared with the dynamic arc approach. Volume treated >18 Gy outside the planning target volume was lowest in 9 of 10 patients after IMRT; 1 patient achieved better conformity with circular collimators. As for Vol10Gy temporal lobe, an advantage was depicted for 1 of 10 patients with IMRT, the other techniques appearing equally effective in shielding the temporal lobe. With all techniques Vol10 Gy temporal lobe was <10 mL and Dmax optic chiasm <8 Gy. However, using circular collimators yielded the highest maximum dose with 39.8 Gy (HI, 2.2) as compared with 20.46–21.74 Gy (HI, 1.13–1.2) for other approaches. Conclusions: Novalis-based radiosurgery using dynamic arc treatment with mMLC is considered a safe and appropriate approach for SRS of PA. IntroductionPituitary adenomas are very common lesions and represent between 10% and 20% of all primary intracranial tumors. Epidemiologic studies have demonstrated that nearly 20% of the general population has a pituitary adenoma. Among these, two major categories may be distinguished: the more common functioning adenoma producing excess amounts of normal pituitary hormones representing prolactinoma, acromegaly, Cushing’s disease, and Nelson’s syndrome. Approximately 30% of all pituitary tumors are nonfunctioning adenoma, which may clinically appear with symptoms related to compression of optic nerves and chiasm as well as signs of hypopituitarism (1Laws E.R. Ebersold M.J. Piepgras D.G. et al.The results of transsphenoidal surgery in specific clinical entities.in: Laws E.R. Randall R.V. Kern E.B. Management of pituitary adenomas and related lesions with emphasis on transsphenoidal microsurgery. Appleton-Century-Crofts, New York1982: 277-305Google Scholar, 2Radhakrishnan K. Mokri B. Parisi J.E. et al.The trends in incidence of primary brain tumors in the population of Rochester, Minnesota.Ann Neurol. 1995; 37: 67-73Crossref PubMed Scopus (196) Google Scholar, 3Annegers J.F. Schoenberg B.S. Okazaki H. et al.Epidemiologic study of primary intracranial neoplasms.Arch Neurol. 1981; 38: 217-219Crossref PubMed Scopus (111) Google Scholar).Surgical resection using the trans-sphenoidal approach is the gold standard for treatment of sellar lesions. It offers the advantages of pathologic confirmation, immediate decompression of the optic apparatus, and rapid reduction of hormonal oversecretion. For both types of pituitary adenomas, recurrence with rates between 8% and 40% as a result of tumor invasion into adjacent structures and incomplete tumor resection is quite common. Long-term tumor control rates after transsphenoidal microsurgery alone vary from 50% to 80%. Rates of endocrinologic normalization of functioning adenomas after surgical resection alone vary as follows: 56–91% for patients with Cushing’s disease (4Sheehan J.M. Lopes M.B. Sheehan J.P. et al.Results of transsphenoidal surgery for Cushing’s disease in patients with no histologically confirmed tumor.Neurosurgery. 2000; 47: 33-36PubMed Google Scholar, 5Chandler W.F. Schteingard D.E. Lloyd R.V. et al.Surgical treatment of Cushing’s disease.J Neurosurg. 1987; 66: 204-212Crossref PubMed Scopus (100) Google Scholar, 6Friedman R.B. Oldfield E.H. Nieman L.K. et al.Repeat transsphenoidal surgery for Cushing’s disease.J Neurosurg. 1989; 71: 520-527Crossref PubMed Scopus (157) Google Scholar, 7Mampalam T.J. Tyrrell J.B. Wilson C.B. Transsphenoidal microsurgery for Cushing disease.Ann Intern Med. 1988; 109: 487-493Crossref PubMed Scopus (344) Google Scholar), 42–84% for acromegaly (8Buchfelder M. Fahlbusch R. Schott W. et al.Longterm follow-up results in hormonally active pituitary adenomas after primary successful transsphenoidal surgery.Acta Neurochir Suppl (Wien). 1991; 53: 72-76Crossref PubMed Scopus (26) Google Scholar, 9Thapar K. Laws Jr., E.R. Pituitary tumors.in: Kaye A.H. Laws Jr, E.R. Brain tumors. 2nd ed. Churchill Livingstone, London2001: 803-854Google Scholar, 10Kreutzer J. Vance M.L. Lopes M.B. et al.Surgical management of GH-secreting pituitary adenomas: An outcome study using modern remission criteria.J Clin Endocrinol Metab. 2001; 86: 4072-4077Crossref PubMed Scopus (231) Google Scholar, 11Freda P.U. Wardlaw S.L. Post K.D. Long-term endocrinological follow-up evaluation in 115 patients who underwent transsphenoidal surgery for acromegaly.J Neurosurg. 1998; 89: 353-358Crossref PubMed Scopus (248) Google Scholar), 28–87% for prolactinomas (12Randall R.V. Scheithauer B.W. Laws Jr, E.R. et al.Pituitary adenomas associated with hyperprolactinemia: A clinical and immunohistochemical study of 97 patients operated on transsphenoidally.Mayo Clin Proc. 1985; 53: 24-28Google Scholar, 13Molitch M.E. Pathologic hyperprolactinemia.Endocrinol Metab Clin North Am. 1992; 21: 877-901PubMed Google Scholar), and 27–70% for Nelson’s syndrome (9Thapar K. Laws Jr., E.R. Pituitary tumors.in: Kaye A.H. Laws Jr, E.R. Brain tumors. 2nd ed. Churchill Livingstone, London2001: 803-854Google Scholar).Radiation therapy or radiosurgery may be indicated postoperatively as an adjuvant treatment to avoid recurrent growth, or later when clinical symptoms, imaging, or biochemical studies indicate recurrence. They may also be contemplated postoperatively to treat known residual tumor after incomplete resection (14Zierhut D. Flentje M. Adolph J. et al.External radiotherapy of pituitary adenomas.Int J Radiat Oncol Biol Phys. 1995; 33: 307-314Abstract Full Text PDF PubMed Scopus (135) Google Scholar, 15Becker G. Kocher M. Kortmann R.D. et al.Radiation therapy in the multimodal treatment approach of pituitary adenoma.Strahlenther Onkol. 2002; 178: 173-186Crossref PubMed Scopus (115) Google Scholar, 16Kokubo M. Sasai K. Shibamoto Y. et al.Long-term results of radiation therapy for pituitary adenoma.J Neurooncol. 2000; 47: 79-84Crossref PubMed Scopus (23) Google Scholar, 17Yildiz F. Zorlu F. Erbas T. et al.Radiotherapy in the management of giant pituitary adenomas.Radiother Oncol. 1999; 52: 233-237Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar, 18McCord M.W. Buatti J.M. Fennell E.M. et al.Radiotherapy for pituitary adenoma: Long-term outcome and sequelae.Int J Radiat Oncol Biol Phys. 1997; 39: 437-444Abstract Full Text PDF PubMed Scopus (148) Google Scholar, 19Cozzi R. Barausse M. Asnaghi D. et al.Failure of radiotherapy in acromegaly.Eur J Endocrinol. 2001; 145: 717-726Crossref PubMed Scopus (66) Google Scholar, 20Brada M. Burchell L. Ashley S. et al.The incidence of cerebrovascular accidents in patients with pituitary adenoma.Int J Radiat Oncol Biol Phys. 1999; 45: 693-698Abstract Full Text Full Text PDF PubMed Scopus (165) Google Scholar, 21Landolt A.M. Haller D. Lomax N. et al.Stereotactic radiosurgery for recurrent surgically treated acromegaly: Comparison with fractionated radiotherapy.J Neurosurg. 1998; 88: 1002-1008Crossref PubMed Scopus (235) Google Scholar).During the past decades, stereotactic radiosurgery has been used to control tumor growth and to normalize hormonal production from pituitary adenoma mainly by means of the Leksell Gamma Knife. However, almost invariably, single-institutional series, being retrospective in nature without indicating clear radiosurgery quality criteria, have been reported. Linear accelerator (LINAC)-based radiosurgery represents a more recent promising development that is able to incorporate numerous techniques developed to enhance conformity and homogeneity of dose planning and delivery. These include beam shaping and intensity modulation with the introduction of jaws, noncircular, and dynamic minimicroleaf and microleaf collimators.Functioning pituitary adenoma represents a major challenge for radiosurgery because a relatively high minimum dose of 1,800–2,000 cGy must be delivered to a target that is in very close proximity to highly sensitive critical structures such as optic chiasm, optic nerves, and the temporal lobe. It has been our goal to evaluate the usefulness of different treatment techniques (including intensity-modulated radiotherapy [IMRT]) using the Novalis multileaf collimator (MLC) for radiosurgery of this relatively homogeneous group of patients.Materials and methodsPatientsBetween January 2003 and February 2005, 152 radiosurgery procedures were performed in 125 patients at the Novalis Shaped Beam Surgery Center of the University Hospital of Erlangen. Among these, 10 consecutive patients with functioning pituitary adenoma and a planning target volume (PTV) between 0.45 and 4.45 mL (median 1.5 mL) served for comparison of the following treatment techniques: conformal vs. dynamic arc treatment with micro MLC (mMLC) vs. circular collimators (as a surrogate for Gamma Knife treatment) vs. 8–10 conformal static beams using mMLC with and without IMRT. Patient, tumor, and treatment characteristics are given in Table 1. The PTV was defined as the gross tumor volume with a safety margin of 1 mm in all directions. All lesions studied were very small intra- and perisellar objects with or without uni- or bilateral involvement of the cavernous sinus.Table 1Patients, tumor, and treatment characteristicsInitialsTumor typeAge (y)GenderPrescribed dosePTV (mL)IGCushing’s disease31F18.0 Gy (90%)1.70UVAcromegaly40F18.0 Gy (90%)1.50THCushing’s disease32F18.0 Gy (90%)1.86LM-TCushing’s disease42F18.0 Gy (90%)0.45AMAcromegaly35F18.0 Gy (90%)0.76DrBCushing’s disease48F18.0 Gy (90%)1.66HENelson’s syndrome51F18.0 Gy (90%)1.36HSAcromegaly48M18.0 Gy (90%)1.11JWAcromegaly54F18.0 Gy (90%)1.58RWAcromegaly54F18.0 Gy (90%)4.45Abbreviations: M = male; F = female; PTV = planning target volume; y = years. Open table in a new tab Treatment planning and deliveryAll patients were immobilized in a stereotactic frame (BrainLAB AG, Heimstetten, Germany) under local anesthesia. Shortly thereafter, helical computed tomography images of 1-mm slice thickness (Somatom VZ, Siemens, Erlangen, Germany) were obtained with the localizer box attached to the frame; these were coregistered with the previously generated MR images using a magnetization prepared rapid acquisition gradient echo sequence with the following parameters: repetition time/echo time 2020/4.38 ms, 25 × 25 cm field of view, 1-mm isotropic, and 160 slices (1.5 Tesla Magnetom Sonata, Siemens Medical Solutions, Erlangen, Germany). This automated registration process is part of the BrainLAB software and uses a rigid registration algorithm applying an intensity-based pyramidal approach using mutual information.The tumors were planned for routine stereotactic radiosurgery using the Novalis Brain Scan treatment Planning System (Version 5.21, BrainLAB AG). The treatment delivery system consisted of a 6-MeV linear accelerator coupled to an mMLC with 26 pairs of leafs mounted permanently to the LINAC: from the inner to the outer side of the collimator, 14 pairs with 3-mm pitch, 6 pairs with 4.5-mm pitch, and 6 pairs with 5.5-mm pitch (22Cosgrove V.P. Jahn U. Pfaender M. et al.Commissioning of a micro multi-leaf collimator and planning system for stereotactic radiosurgery.Radiother Oncol. 1999; 50: 325-336Abstract Full Text Full Text PDF PubMed Scopus (151) Google Scholar). The dose rate of the LINAC ranged between 0.3 cGy/degree and 20 cGy/degree for arc mode and 800 monitor units/min for fixed mode. In dynamic conformal arc (DCA) technique, the gantry is rotating during irradiation while the leaves of the mMLC are moved according to beam’s-eye view. Thus best fit to the shape of the PTV is allowed by sparing organs at risk.Dose calculationDose calculation was performed for the shaped techniques by the Pencil Beam algorithm, whereas circular arc dose distribution was calculated by the Clarkson dose algorithm. Both algorithms can take inhomogeneities into account by correcting the radiologic pathway by an electron density depending factor gathered from computed tomography Hounsfield units. This pathway correction acts on the surface to point of first collision distance as well as scaling the precalculated differential pencil beam. The differential pencil beam itself is not recalculated for varied inhomogeneities. The Pencil Beam algorithm is characterized by a fast and accurate dose calculation for large and irregular fields and for IMRT, although secondary dose distribution will not be density-corrected and large cavities can still give errors (23Mohan R. Chui C. Lidofsky L. Differential pencil beam dose computation model for photon.Med Phys. 1986; 13: 64-73Crossref PubMed Scopus (266) Google Scholar).Quality criteria and evaluationAccording to the Radiation Therapy Oncology Group guidelines, “dose homogeneity” within the target volume is defined by the ratio between maximum dose and prescription dose ratio (24Shaw E. Kline R. Gillin M. et al.Radiation Therapy Oncology Group: Radiosurgery quality assurance guidelines.Int J Radiat Oncol Biol Phys. 1993; 27: 1231-1239Abstract Full Text PDF PubMed Scopus (478) Google Scholar). This ratio should be ≤2.0. The conformation of the prescription dose to the target is defined by the ratio of the prescription isodose surface volume to the target volume ratio. This value is to be obtained from the dose–volume histogram. The dose gradient achieved outside the target defined as the ratio of the target volume to the volume encompassed by the 90% isodose volume (target volume/V90) is of further use and usually referred to as “coverage.”We compared the originally applied treatment by dynamic arcs with four additionally available approaches (i.e., treatment by conformal arcs vs. 8–10 conformal static beams with and without IMRT vs. treatment using circular collimators [as a surrogate for Gamma Knife treatment]). Details of treatment techniques are displayed in Table 2. All gantry and table positions were checked under realistic conditions. Figure 1 gives an example of a patient with Cushing’s disease displaying the dose distribution of the five different treatment approaches. Prescribed total dose was 18 Gy to the 90%-isodose surface. Dose constraints for organs at risk (OAR) were defined as follows: Dmax optic apparatus <8 Gy, Vol10Gy temporal lobe <10 mL. The following endpoints served for comparison of treatment plans: Conformity, homogeneity index (HI), coverage, Vol10 Gy of the temporal lobe, maximum and median dose to pituitary stalk, and optic apparatus.Table 2Description of treatment techniquesRadiosurgery techniqueConformal beamsConformal arcsDynamic conformal arcsCircular arcsIMRTDescription8–10 static fields with beam shaping by mMLC, monoisocentric5–10 (non)-coplanar rotations with static mMLC positions, monoisocentric5–10 (non)-coplanar rotations, dynamic mMLC positions (at 10°) according to shape of PTV and OARs, monoisocentric5–9 (non)-coplanar rotations with circular collimators of appropriate size, multiple isocenters (2–7)8–10 static fields with beam shaping by mMLC, 10 fluence-modulated steps per field, monoisocentricAbbreviations: IMRT = intensity-modulated radiation therapy; mMLC = micromultileaf collimator; PTV = planning target volume; OAR = organs at risk. Open table in a new tab ResultsResults for the primary endpoints “coverage” and “conformity” are displayed as mean values taking into account all 10 patients in Table 3 and Fig. 2a and 2b. For the end point “improvement in coverage,” the lowest value was noted for conformal arc treatment (−0.55%) and the best coverage was associated with the IMRT approach. Consequently, the volume that was included inside the 90% isodose without belonging to the PTV was lowest with IMRT (1 × VPTV), identical to dynamic arc treatment, and being highest after application of conformal arcs (2.33 × VPTV) as well as conformal static beams (2.25 × VPTV).Table 3Mean values for the primary endpoints (improvement in coverage (%), unnecessarily treated volume (× *VPTV), dose to organs at risk, maximum dose within the PTV) comparing the originally applied dynamic arc treatment to conformal arc, conformal beam, IMRT, and circular collimator treatmentDynamic arcConformal arcConformal beamIMRTCircular arcGain in coverage (%)0.00−0.550.410.720.52Unnecessarily treated volume (× *VPTV)2.172.332.251.001.71Volume of temporal lobe >10 Gy (mL)2.873.012.831.482.04Maximum dose pituitary stalk (Gy)15.7215.8417.2014.0616.00Maximum dose optic chiasm (Gy)7.307.486.806.286.50Median dose optic chiasm (Gy)2.963.202.562.482.79Median dose optic nerve (Gy)1.341.321.020.801.20Abbreviations: PTV = planning target volume; IMRT = intensity-modulated radiation therapy; VPTV = volume of planning target volume. Open table in a new tab Fig. 2(a, b) Results for gain in coverage (%) and unnecessarily treated volume (×⁎ VPTV) displayed as mean values (±SE) for all 10 patients.View Large Image Figure ViewerDownload (PPT)As for critical volumes to neighboring organs at risk, the mean volume of the mediobasal temporal lobe receiving more than 10 Gy turned out to be the lowest with IMRT (1.48 mL) and the highest after conformal arc treatment (3.01 mL). Maximum and median dose to other OARs including the pituitary stalk and optic apparatus did not appear to significantly differ when comparing the five different treatment techniques. Contemplating homogeneity within the PTV, however, it was noted that treatment by circular collimators (comparable to Gamma Knife surgery) yielded the highest mean value for maximum dose with 39.8 Gy (HI, 2.2) as compared with maximum doses between 20.46 and 21.74 Gy (HI, 1.13–1.2) for the other approaches.For the end point “improvement in coverage,” an advantage with IMRT was noted for 5 of 10 patients as compared with the dynamic arc approach. The volume treated with >18 Gy without belonging to the PTV (unnecessarily treated volume) was lowest in 9 of 10 patients after IMRT; only 1 patient achieved better conformity with circular collimators.Figure 3 gives details for all studied patients on Vol10Gy of the temporal lobe. A clear advantage in terms of Vol10Gy may only be depicted for 1 of 10 patients with IMRT, with two other techniques (dynamic arcs, circular collimators) appearing equally effective in shielding the temporal lobe. Noteworthy seems a relatively high dose to the pituitary stalk with circular collimators in 2 of 10 patients. With all techniques Vol10Gy of the temporal lobe was <10 mL and Dmax of the optic chiasm <8 Gy.Fig. 3Vol10Gy of the temporal lobe (mL) displayed individually for all 10 patients.View Large Image Figure ViewerDownload (PPT)Because this article was intended to provide initial data on dose distribution and differences in quality indices of radiosurgery of functioning pituitary adenoma, follow-up times of the treated 10 patients are not sufficiently long enough to give meaningful results on endocrinologic normalization. Follow-up times vary between 10 and 38 months, and only 2 of 10 patients have so far reached an endocrinologic normalization.DiscussionStereotactic radiosurgery has been demonstrated to be a safe and highly effective treatment for patients with recurrent or residual pituitary adenomas. Radiosurgery affords effective growth control and hormonal normalization for patients with a generally shorter latency period than that of fractionated radiotherapy. This shorter latency period with radiosurgery can typically be managed with suppressive medications. Furthermore, the complications (e.g., radiation induced neoplasia, cerebral vasculopathy) associated with radiosurgery appear to be less frequent than those of radiotherapy. Radiosurgery may even serve as a primary treatment for those patients deemed unfit for surgical resection as a result of other comorbidities or with demonstrable tumors in a surgically inaccessible location. Radiosurgery can frequently preserve and, at times, even restore neurologic and hormonal function (25Zhang N. Pan L. Wang E.M. et al.Radiosurgery for growth hormone-producing pituitary adenomas.J Neurosurg. 2000; 93: 6-9PubMed Google Scholar, 26Pan L. Zhang N. Wang E. et al.Pituitary adenomas: The effect of gamma knife radiosurgery on tumor growth and endocrinopathies.Stereotact Funct Neurosurg. 1998; 70: 119-126Crossref PubMed Scopus (52) Google Scholar, 27Sheehan J.M. Lopes M.B. Sheehan J.P. et al.Results of transsphenoidal surgery for Cushing’s disease in patients with no histologically confirmed tumor.Neurosurgery. 2000; 47: 33-36PubMed Google Scholar, 28Sheehan J.M. Vance M.L. Sheehan J.P. et al.Radiosurgery for Cushing’s disease after failed transsphenoidal surgery.J Neurosurg. 2000; 93: 738-742Crossref PubMed Scopus (186) Google Scholar, 29Laws E.R. Vance M.L. Radiosurgery for pituitary tumors and craniopharyngiomas.Neurosurg Clin North Am. 1999; 10: 327-336PubMed Google Scholar).Evolution of radiosurgery techniquesLINAC-based radiosurgery can be performed by different techniques such as the initial arc-based approach with circular collimators (30Colombo F. Benedetti A. Pozza F. et al.Stereotactic radiosurgery utilizing a linear accelerator.Appl Neurophysiol. 1985; 48: 133-145PubMed Google Scholar, 31Lutz W. Winston K.R. Maleki N. A system for stereotactic radiosurgery with a linear accelerator.Int J Radiat Oncol Biol Phys. 1988; 14: 373-381Abstract Full Text PDF PubMed Scopus (573) Google Scholar), static beams (32Bourland J.D. McCollough K.P. Static field conformal stereotactic radiosurgery: Physical techniques.Int J Radiat Oncol Biol Phys. 1994; 28: 471-479Abstract Full Text PDF PubMed Scopus (74) Google Scholar, 33Clark B.G. Robar J.L. Nichol A.M. Analysis of treatment parameters for conformal shaped field stereotactic irradiation: Comparison with non-coplanar arcs.Phys Med Biol. 2001; 46: 3089-3103Crossref PubMed Scopus (8) Google Scholar, 34Hamilton R.J. Kuchnir F.T. Sweeney P. et al.Comparison of static conformal field with multiple noncoplanar arc techniques for stereotactic radiosurgery or stereotactic radiotherapy.Int J Radiat Oncol Biol Phys. 1995; 33: 1221-1228Abstract Full Text PDF PubMed Scopus (59) Google Scholar, 35Shiu A.S. Kooy H.M. Ewton J.R. et al.Comparison of miniature multileaf collimation (MMLC) with circular collimation for stereotactic irradiation.Int J Radiat Oncol Biol Phys. 1997; 37: 679-688Abstract Full Text PDF PubMed Scopus (82) Google Scholar), conformal arc technique, DCA (36Perks J.R. Jalali R. Cosgrove V.P. et al.Optimization of stereotactically guided conformal treatment planning of sellar and parasellar tumors, based on normal brain dose volume histograms.Int J Radiat Oncol Biol Phys. 1999; 45: 507-513Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar, 37Yu C.X. Li X.A. Ma L.M. et al.Clinical implementation of intensity-modulated arc therapy.Int J Radiat Oncol Biol Phys. 2002; 53: 453-463Abstract Full Text Full Text PDF PubMed Scopus (150) Google Scholar), and IMRT (38Baumert B.G. Norton I. Davis B. Intensity-modulated stereotactic radiotherapy vs. stereotactic conformal radiotherapy for the treatment of meningioma located predominantly in the skull base.Int J Radiat Oncol Biol Phys. 2003; 57: 580-592Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar, 39Cardinale R.M. Benedict S.H. Qiuwen W. et al.A comparison of three stereotactic radiotherapy techniques; arcs vs. noncoplanar fixed fields vs. intensity modulation.Int J Radiat Oncol Biol Phys. 1998; 42: 431-436Abstract Full Text Full Text PDF PubMed Scopus (145) Google Scholar, 40Pirzkall A. Debus J. Haering P. et al.Intensity modulated radiotherapy (IMRT) for recurrent, residual, or untreated skull-base meningiomas: Preliminary clinical experience.Int J Radiat Oncol Biol Phys. 2003; 55: 362-372Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar). In the case of circular collimators, as in Gamma Knife treatment, multiple isocenters and a varying collimation of the circular beams can give good conformation to irregular targets with inhomogeneous dose distribution within the target (41Perks J.R. George E.J. El Hamri K. et al.Stereotactic radiosurgery XVI: Isodosimetric comparison of photon stereotactic radiosurgery techniques (gamma knife versus micromultileaf collimator linear accelerator) for acoustic neuroma—and potential clinical importance.Int J Radiat Oncol Biol Phys. 2003; 57: 1450-1459Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar, 42Yu C. Luxton G. Jozsef G. et al.Dosimetric comparison of three photon radiosurgery techniques for an elongated ellipsoid target.Int J Radiat Oncol Biol Phys. 1999; 45: 817-826Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar). Overlapping “shots” create a high internal dose gradient resulting in a potential damage to OARs within the target volume, such as the internal carotid artery, pituitary stalk, and oculomotor nerves (40Pirzkall A. Debus J. Haering P. et al.Intensity modulated radiotherapy (IMRT) for recurrent, residual, or untreated skull-base meningiomas: Preliminary clinical experience.Int J Radiat Oncol Biol Phys. 2003; 55: 362-372Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar). Since MLC technology was implemented in LINAC radiosurgery, conformity and dose homogeneity were improved (41Perks J.R. George E.J. El Hamri K. et al.Stereotactic radiosurgery XVI: Isodosimetric comparison of photon stereotactic radiosurgery techniques (gamma knife versus micromultileaf collimator linear accelerator) for acoustic neuroma—and potential clinical importance.Int J Radiat Oncol Biol Phys. 2003; 57: 1450-1459Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar). During this progress each new planning and delivery advice was compared with the formerly best established one in terms of the Radiation Therapy Oncology Group quality criteria that are acceptable in current radiotherapy practice. Over the last 10 years, there have been many published studies on this issue. The first studies concerning field shaping in LINAC radiosurgery have shown static conformal fields to be superior to arc treatment with circular collimator techniques in terms of conformity (42Yu C. Luxton G. Jozsef G. et al.Dosimetric comparison of three photon radiosurgery techniques for an elongated ellipsoid target.Int J Radiat Oncol Biol Phys. 1999; 45: 817-826Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar). For stereotactically guided conformal radiotherapy to volumes above 13 mL, four to six noncoplanar fixed fields are clearly superior to coplanar field arrangements, whereas even techniques approaching dynamic conformal radiotherapy such as a 30-field approach reveal no further sparing of normal brain irradiated (36Perks J.R. Jalali R. Cosgrove V.P. et al.Optimization of stereotactically guided conformal treatment planning of sellar and parasellar tumors, based on normal brain dose volume histograms.Int J Radiat Oncol Biol Phys. 1999; 45: 507-513Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar). Later dynamic arcing was initiated where the gantry rotates during dose delivery and the dynamic mMLC changes continuously the field shape (43Leavitt D.D. Gibbs F.A. Heilbrun M.P. et al.Dynamic field shaping to optimize stereotactic radiosurgery.Int J Radiat Oncol Biol Phys. 1991; 21: 1247-1255Abstract Full Text PDF PubMed Scopus (84) Google Scholar, 44Leavitt D.D. Tobler M. Gaffney D. et al.Comparison of interpolated vs. calculated micro-multileaf settings in dynamic conformal arc treatment.Med Dosim. 2000; 25: 17-21Abstract Full Text F